CLINICAL DEVELOPMENT MASTER SERVICE AGREEMENT
Exhibit 10.2
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
This
Agreement is between Miravant Pharmaceuticals, Inc., a wholly owned subsidiary
of Miravant Medical Technologies, a Delaware corporation, with offices at
000
Xxxxxx Xxxxx, Xxxxx Xxxxxxx, Xxxxxxxxxx 00000 (hereinafter “Sponsor”) and Xxxxxx
International Inc., having its principal place of business at 0000 Xxxxx
Xxxxx,
000 Xxxx Xxxxxx, Xxxxxxxxxx, Xxxx 00000 (hereinafter “CRO”) and is effective as
of the 27th
day
of
April, 2005.
WITNESSETH:
WHEREAS,
Sponsor is in the business of discovering, developing and marketing photodynamic
therapy pharmaceutical products; and,
WHEREAS,
CRO is engaged in the business of providing clinical trials management and
related clinical development services to the pharmaceutical industry;
and,
WHEREAS,
both Sponsor and CRO desire to enter into a Clinical Development Master Service
Agreement for the purpose of delineating in advance the terms and conditions
which will govern the relationship between the parties and define the conditions
under which Sponsor would award to CRO and CRO would accept from and perform
for
Sponsor, certain services.
NOW,
THEREFORE, the parties hereto agree as follows:
I.
DEFINITIONS
1.1
“Act"
shall mean the Food and Drug and Cosmetic Act.
1.2 “Agreement”
shall mean this Clinical Development Master Service Agreement as agreed between
the parties.
1.3 “EMEA”
means the European Medicines Evaluation Agency.
1.4 “FDA”
means the United States Food and Drug Administration or any successor entity
thereto.
1.5 “Investigator”
means a licensed physician engaged by Sponsor to conduct the Study.
1.6 “IRB”
means the Institutional Review Board(s) organized in accordance with the
US
Food, Drug and Cosmetic Act.
1.7 “Proposal”
shall mean written descriptions of services (and costs) offered by CRO in
response to a Request for Proposal from Sponsor.
1.8 “Protocol”
shall refer to the particular Protocol prepared for the study and under which
the Services described in the Task Order are to be performed.
1.9 “Regulatory
Authority” shall mean: (a) any and all national, multi-national (as used in this
Agreement including without limitation the European Union), or other
governmental or industry agency or body with authority over the manner in
which
a Study is conducted in a country; and/or (b) any and all national or
multi-national authority responsible for granting regulatory approval in
a
particular country or multi-national group or union of countries.
1.10 “Services”
shall mean the particular tasks to be performed by CRO as set out in any
Task
Order or document attached thereto including, but not limited to, the
Proposal.
1.11 “Site”
means the physical location at which a particular Investigator conducts the
Study.
1.12 “Study”
shall mean the clinical trial of the pharmaceutical identified in the Task
Order
(by study drug name or protocol number).
1.13 “Task
Order” shall mean the written agreement between Sponsor and CRO which sets out
with specificity the Services to be performed, the obligations transferred
pursuant to any federal or local law, the timeline for the performance of
the
Services, the costs associated with the Services, the schedule of payments
for
the performance of the Services and specifically incorporates by reference
the
terms and conditions of this Agreement. No Task Order shall be effective
until
it is accepted in writing by both Sponsor and CRO. The terms and conditions
of
this Agreement shall be made a part of and incorporated by reference into
each
Task Order. The template Task Order to be used by the parties is attached
hereto
as Exhibit A.
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The
existence of this Agreement shall not preclude or limit the ability
of the
parties to enter into independent contracts outside of this Agreement
when
the nature of the work and particular program requirements make
the entry
of an independent and free standing contract both necessary and
reasonable. The existence of any contractual relationship outside
of this
Agreement shall have no effect on the validity of this Agreement
or any
Task Order entered in accordance with its
terms.
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II.
SCOPE OF WORK
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2.1
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There
shall be no limit to the number of Task Orders that may be entered
into
and regulated by the terms and conditions of this Agreement. Each
Task
Order shall constitute a unique agreement and shall stand alone
with
respect to any other Task Order entered under this Agreement. The
performance of obligations under any one Task Order shall not effect,
and
shall at all times be unrelated to, the performance of any other
Task
Order entered under this Agreement.
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2.2
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CRO
will perform the Services and all of its other obligations set
forth
herein in strict accordance with:
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(a) all
applicable statutes, rules and regulations including, without limitation,
the
Act, the Declaration of Helsinki, the EMEA and any proposed FDA regulations
provided by Sponsor;
(b) the
Protocol;
(c) the
mandates of the IRB approving the Study;
(d) the
CRO’s
standard operating procedures; and
(e) any
other
written instructions from Sponsor.
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Further,
CRO will perform the Services in a competent and professional manner,
consistent with the current state of clinical research and good
clinical
practices acceptable to the FDA and applicable Regulatory
Authority.
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2.3 In
the
event there is any material change totaling more than $100,000 in the scope
of
Services set forth in a Task Order, the parties will agree in writing to
such
change and shall cooperate with each other in reaching agreement with respect
to
any corresponding increase or decrease in the Task Order budget. Any changes
in
scope less than $100,000 will not require an Amendment. Miravant agrees to
pay
for these additional services.
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2.4
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If
the assumptions under which the parties create a Task Order budget
and
timeline prove to be materially inaccurate, in whole or in part,
then the
parties will review both the Task Order budget and the timeline
and make
all reasonable revisions to ensure that the Study is sufficiently
funded
and to promote the best interests of the
Study.
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2.5
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Unless
otherwise stated and agreed to by the parties, in the event of
a conflict
between the terms of this Agreement, a Task Order, or the Proposal,
the
terms of this Agreement shall govern first followed by the individual
Task
Order and, lastly, the
Proposal.
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III.
TERM OF AGREEMENT
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3.1
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The
term of this Agreement shall commence on the date set forth above
and
shall remain in effect until terminated by either party as provided
herein.
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3.2
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During
times in which there are no Task Orders in effect, this Agreement
may be
terminated by either party immediately upon written notice. Sponsor
or CRO
may terminate any individual Task Order immediately upon written
notice in
the event of medical risk to Study participants or upon regulatory
action
by the FDA or any other Regulatory Authority in the country in
which the
Services are performed. Both parties agree that termination of
a Task
Order shall not constitute termination of this
Agreement.
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3.3
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Either
party may terminate this Agreement or any individual Task Order
as
follows:
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| (a) |
on
written notice effective immediately if the other party commits
a material
breach of this Agreement or a Task Order which is not cured within
thirty
(30) days of receipt of written notice from the other party;
or
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| (b) |
on
written notice effective immediately if the other party becomes
insolvent,
is dissolved or liquidated, makes a general assignment for the
benefit of
its creditors, files or has filed against it, a petition in bankruptcy,
or
has a receiver appointed for a substantial part of its assets;
or
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| (c) |
on
sixty (60) days prior written
notice.
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3.4
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Upon
early termination of any Task Order, Sponsor shall pay to CRO (i)
a
pro-rata portion of the fees owing to CRO based on the degree of
completion of the Services as of the time of termination (ii) all
pass
through expenses incurred or accrued at the time of termination;
and (iii)
all non-cancelable expenses;. Upon notice of termination, the parties
shall negotiate in good faith the tasks to be undertaken and the
costs
associated with the winding down and closing out of the Study or
applicable Task Order.
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3.5
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In
the event a study is delayed, the parties agree to adjust the time
and
costs estimates in the form of a change order. If the delay extends
for
greater than one (1) month, or if the parties are unable to agree
to a
change order, then either party may terminate this Agreement. In
the event
this Agreement is terminated pursuant to the foregoing, then Sponsor
shall
pay CRO an amount equal to (i) a pro-rata portion of the compensation
as
provided under Article 9 based on the degree of completion of the
services
of the date of termination; (ii) all pass-through expenses incurred
up to
and including the date of termination; and (iii) all non-cancelable
expenses.
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3.6
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This
Agreement may survive its termination but only as necessary to
allow
completion of any particular Task Order and for the limited purpose
of
regulating the obligations and duties of the parties with respect
to
particular Task Order obligations that extend beyond contract
termination.
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IV.
REGULATORY
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4.1
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Both
parties shall promptly notify the other party of any regulatory
inspections of investigator sites of which it becomes aware. Where
appropriate and permitted by the Regulatory Authority, Sponsor
will have
the right to be present at any such inspections and will have primary
responsibility for preparing any responses which may be required.
In the
event CRO’s participation in any regulatory review is material in terms of
personnel time and expense, the parties shall review costs associated
with
participation and shall agree to a reasonable rate of compensation
in
advance of the performance of any regulatory services. CRO shall
reasonably act to secure the cooperation of investigators with
respect to
regulatory review.
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4.2
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As
set forth in the individual Task Orders, CRO’s personnel will make
periodic site visits to the Study sites. CRO will provide Sponsor
with
visit schedules and it is agreed that Sponsor personnel may, upon
reasonable notice and in its discretion, accompany CRO’s personnel on such
site visits.
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4.3
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Designated
representatives of Sponsor shall, upon reasonable notice to CRO,
have
access to and shall be permitted to review all documents, information,
data and materials in the possession of CRO directly relating to
the work
performed hereunder with the exception of any such documents, information,
data and/or materials that contain information deemed, in good
faith by
CRO, to be confidential, privileged, proprietary, or not directly
related
to the performance of this Agreement or any Task Order. Sponsor,
its
agents and its consultants shall keep strictly confidential any
documents,
information, data or materials belonging to CRO that are confidential
to
CRO.
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4.4
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The
transfer of obligations from Sponsor to CRO pursuant to 21 CFR
312.52 or
any other federal or local law will be agreed to and set forth
in each
individual Task Order.
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V.
OWNERSHIP OF DATA
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5.1
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Except
as otherwise provided herein, all data, documents and information
provided
by Sponsor to CRO together with all data or reports generated or
prepared
by CRO in connection with the Study shall be the sole and exclusive
property of Sponsor. Sponsor will pay all costs associated with
the
shipping and storage of documents and records and will provide
CRO with
written instructions regarding the shipping, storage and/or disposal
of
all such documents.
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5.2
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Notwithstanding
the foregoing, CRO data, documents, and all information of a privileged
and/or proprietary nature, including without limitation all CRO-developed
computer software, processes, procedures and related manuals, are
the sole
and exclusive property of CRO.
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5.3
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At
the completion of the Services by CRO, all Sponsor property and
Confidential Information, regardless of the method of storage or
retrieval, shall be delivered to Sponsor in such form as is then
currently
in the possession of CRO. Alternatively, at Sponsor’s written request,
such Sponsor property and Confidential Information may be retained
by CRO
for Sponsor for a period of two (2) years, or disposed of pursuant
to the
written directions of Sponsor. Sponsor shall pay the costs associated
with
any of the above options. CRO, however, reserves the right to retain,
at
its own cost and subject to the confidentiality provisions herein,
one
copy of all Sponsor property and Confidential Information provided
to
Sponsor as the result of the Services to be used to satisfy regulatory
requirements or to resolve disputes regarding the Services. Nothing
in
this Master Agreement shall be construed to transfer from Sponsor
to CRO
any FDA or regulatory record-keeping requirements unless such transfer
is
specifically provided for in the applicable Transfer of
Obligations.
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5.4
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Sponsor
may, at its own discretion, file and prosecute in its own name
and at its
own expense, applications for foreign and United States letters
patent or
any patentable information derived from the Services in accordance
with
this Article V. Upon the request and at the sole expense of Sponsor,
CRO
shall assist in prosecuting such applications and shall execute
and
deliver any and all instruments necessary to make, file, and prosecute
all
such applications, divisions, continuations, continuations-in-part,
or
reissue thereof. CRO will be reimbursed for reasonable expenses
and
personnel charges incurred in complying with Sponsor’s
request.
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VI.
CONFIDENTIALITY
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6.1
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During
the term of this Agreement and for a period of two (2) years thereafter,
CRO and its employees, agents and contractors will keep strictly
confidential and will not use for any purpose other than as described
herein all information transmitted to it by Sponsor, developed
by CRO or
generated by investigators hereunder. For purposes hereof, confidential
information shall not include, and the obligations of confidentiality
and
use shall not apply to, information
that:
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| (a) |
is
or becomes publicly available through no fault of
CRO;
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| (b) |
is
received from a third party which CRO believes in good faith has
a right
to disclose it;
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| (c) |
is
already known to CRO as shown by its prior written records;
or
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| (d) |
is
required by law, rule or regulation to be
disclosed.
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6.2
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Notwithstanding
the foregoing, CRO may disclose the confidential information to
employees,
consultants and/or subcontractors who have a need to know such
confidential information for purposes of performing CRO’s obligations
under this Agreement or any individual Task Order. CRO will use
its best
efforts to require any third party to whom it discloses such information
to maintain its confidentiality to the same extent as
CRO.
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| 6.3 |
It
may become necessary for CRO to disclose to Sponsor information
which CRO
considers proprietary, privileged and confidential. If disclosure
occurs,
then Sponsor agrees to protect the information as confidential
with same
degree of care as Sponsor would protect its own confidential information
and will not use such information for any purpose other than in
connection
with the performance of obligations
hereunder.
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| 6.4 |
The
parties are subject to a Confidentiality and Non-Disclosure Agreement
dated October 19, 2004 which shall remain in full force and effect
according to its terms.
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VII.
OBLIGATIONS IN THE EVENT OF POSSIBLITY OF FRAUD; DEBARRED
PERSONS
| 7.1 |
If,
during the course of conducting the Services, CRO becomes aware
of
information which indicates possible fraud at an investigator site,
and
after a reasonable investigation determines that the possibility
of fraud
is real, CRO will promptly inform Sponsor of its findings and it
will be
the Sponsor’s responsibility to conduct a full investigation. If this
investigation confirms fraud then it will be the responsibility
of the
Sponsor to notify the FDA or any other Regulatory Authority. After
completion of its investigation, the Sponsor will provide evidence
to CRO
either (i) that fraud was not committed or, (ii) if fraud was committed,
that confirms the proper reporting of the fraud or misrepresentation
to
the FDA. If the Sponsor does not investigate the possible fraud
within a
reasonable time, or if fraud is confirmed by investigation and
the Sponsor
does not fulfill its obligations to report the fraud within a reasonable
time, then CRO will report its suspicions of possible fraud to
the
appropriate governmental agency and notify the Sponsor of this
action in
writing.
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| 7.2 |
CRO
represents and warrants that CRO has not been nor is
currently:
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| (a) |
an
individual who has been debarred by the FDA pursuant to 21 U.S.C.
§335a
(a) or (b) (a “Debarred
Individual”)
from providing services in any capacity to a person that has an
approved
or pending drug product application, or an employer, employee or
partner
of a Debarred Individual; or
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| (b) |
a
corporation, partnership, or association that has been debarred
by the FDA
pursuant to 21 U.S.C. §335a (a) or (b) (a “Debarred
Entity”)
from submitting or assisting in the submission of an abbreviated
new drug
application, or an employee, partner, shareholder, member, subsidiary
or
affiliate entity of a Debarred
Entity.
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| (c) |
CRO
further represents and warrants that CRO has no knowledge of any
circumstances which may affect the accuracy of the representations
and
warranties set forth in Section
7.2
including, but not limited to, FDA investigations of, or debarment
proceedings against, CRO or any person or entity performing, or
rendering
assistance related to, the Services. CRO will notify Sponsor promptly
upon
becoming aware of any such circumstances during the term of this
Master
Agreement.
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VIII.
INDEMNIFICATION
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8.1
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Sponsor
will indemnify, defend and hold harmless CRO and its employees,
officers,
directors, parent and affiliated companies, agents, subcontractors,
authorized independent contractors (including but not limited to
participating clinical investigators and the providers of laboratory
services) successors and assigns (hereinafter “Indemnitee”) from all
losses, costs, expenses, liabilities and damages of every kind
and nature,
including without limitation interest, penalties, reasonable attorney’s
fees and arbitration and/or litigation costs, arising out of claims
brought against CRO in connection with the Study or CRO’s performance of
this Agreement or any Task Order (collectively the “Claims”) except to the
extent that any such Claim is caused solely by the Indemnitee’s own
negligence or intentional misconduct in the performance of its
obligations
and responsibilities under this Agreement or any Task
Order.
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8.2
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Indemnitee
may tender to Sponsor the defense of any claim by giving Sponsor
timely
written notice after such claim was served upon Indemnitee. Sponsor
shall
defend Indemnitee from any claim so tendered to Sponsor at Sponsor’s sole
cost and expense and Sponsor shall keep Indemnitee informed as
to the
progress of its defense of any such claim. Sponsor shall have the
right to
control the defense and disposition (including, without limitation,
settlement, litigation or appeal) of any such claim. The parties
agree,
however, that no such settlement shall serve to establish liability
on the
part of CRO, its parent, employees or agents without the express
written
consent of CRO. Sponsor shall be obligated to fully indemnify the
Indemnitee as described in this Article
VIII.
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8.3
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CRO
agrees to indemnify, defend and hold harmless Sponsor against any
and all
losses, costs, expenses, liabilities and damage, including without
limitation interest, penalties and reasonable attorney’s fees to the
extent such losses result from CRO’s negligent performance of the
obligations required herein.
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| 8.4 |
Upon
their written request, Sponsor will indemnify each clinical investigator
and the clinical investigator’s institution, directors, officers,
employees and agents pursuant to the terms
hereof.
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| 8.5 |
Neither
party, nor its affiliates, nor any of their respective directors,
officers, employees or agents shall have any liability of any type
(including, but not limited to, contract, negligence, and tort
liability),
for any special, incidental, indirect or consequential damages
,
including, but not limited to the loss of opportunity, loss of
use, or
loss of revenue or profit, in connection with or arising out of
this
Agreement, any Task Order, or the Services contemplated hereunder,
even if
such damages may have been foreseeable to such party. In addition,
in no
event shall the collective, aggregate liability (including, but
not
limited to, contract, negligence and tort liability) of CRO and
its
affiliates and its and their respective directors, officers, employees
and
agents under this Agreement or any Task Order hereunder exceed
the amount
of the Budget for a particular Task Order from which such liability
arose.
Notwithstanding the foregoing, nothing in this Section 8.5 is intended
to
limit or restrict the indemnification rights or obligations of
any party
under this Article 8.
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IX.
PAYMENT AND BUDGET
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9.1
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Each
Task Order will include a budget and payment schedule which will
set forth
CRO’s fee for performance of the Services and the estimated costs and
expenses associated therewith.
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| 9.2 |
In
the event Sponsor makes any material changes totaling over $100,000
to the
Study or the Services to be performed in the Task Order, the parties
will
agree in writing as to any increase or decrease in the fees and
expenses
in accordance with Section 2.3 of this
Agreement.
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| 9.3 |
When
appropriate, a Task Order shall include appropriate currency exchange
rate
fluctuation language to protect both parties from losses due to
such
fluctuations.
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| 9.4 |
Payments
will be made in accordance with the payment plan agreed to for
each
individual Task Order. Except as provided above, Sponsor will pay
CRO
within thirty (30) days of date of invoices. Checks will be made
payable
to Xxxxxx International Inc., and mailed to the address first set
forth
above, “Attention: Controller”.
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9.5
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Within
sixty seventy five (75) after the conclusion of the Services for
each Task
Order, CRO will submit to Sponsor a final invoice which will include
an
accounting reconciling all activities actually performed and associated
fees and costs, all payments made by Sponsor and all amounts invoiced
by
CRO. Any overpayment by Sponsor shall be credited or refunded to
Sponsor
by CRO at the time of submission of such final invoice. Any underpayment
by Sponsor shall be paid to CRO within thirty (30) days after receipt
by
Sponsor of such final invoice.
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9.6
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CRO
shall keep and maintain complete and accurate books and records
in
sufficient detail to determine amounts owed to CRO hereunder. Such
books
and records shall be maintained for at lease one (1) year following
termination of a Task Order and shall be made available for inspection,
copying and audit by Sponsor, upon reasonable notice by Sponsor,
for the
sole purpose of determining the accuracy of amounts invoiced
thereunder.
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9.7
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The
parties agree that, because each Task Order shall constitute a
unique
agreement, payments due under other Task Orders shall not be set
off or
applied to sums due as a result of the performance of other Task
Orders.
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X.
NON-SOLICITATION
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10.1
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Neither
party will solicit or hire employees of the other party while such
employees are providing these Services or for a period of six months
after
the termination thereof without the other party’s prior written consent.
Notwithstanding the foregoing, should either party hire any of
the
employees of the other party with whom that party comes into contact
as a
result of the Study, the hiring party shall pay the other 100%
of such
employee’s annual compensation as a recruitment
fee.
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XI.
LIMITATION OF LIABILITY
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11.1
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CRO’s
entire liability or damages arising out of or related to this Agreement,
regardless of the form of action, whether in contract, equity,
negligence,
intended conduct, tort or otherwise, will be limited to and will
not
exceed, in the aggregate for all claims, actions and causes of
action of
every kind and nature the lesser of, i) the amount paid to CRO
under this
Agreement for the specific item that caused the damage or that
is the
subject matter of, or is directly related to, the cause of action,
or ii)
the amount paid by Sponsor in the 12 month period proceeding such
claim.
In no event will the measure of damages payable by CRO include,
nor will
CRO be liable for, any amounts for loss of income, profit or savings
or
indirect, incidental, consequential, exemplary, punitive or special
damages of any party, including third parties, even if CRO has
been
advised of the possibility of such damages in advance, and all
such
damages are expressly disclaimed. No cause of action which arose
out of an
event or events which occurred more than one year prior to the
filing of a
suit alleging a claim or cause of action may be asserted by
Sponsor.
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XII.
MISCELLANEOUS
12.1
This
Agreement may not be assigned by either party without the other’s prior written
consent which
shall not be unreasonably withheld.
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12.2
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The
relationship between the parties is that of an independent contractor
and
neither party shall have the authority to bind or act on behalf
of the
other party without its prior written consent. This Agreement shall
not
constitute, create, or in any way be interpreted as a joint venture,
partnership or business organization of any
kind.
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12.3
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This
Agreement shall constitute the entire understanding of the parties
and
shall not be changed or modified except in writing and signed by
authorized representatives of the parties. All prior Agreements,
whether
written or oral between the parties relating to the subject matter
hereof
are superseded by this Agreement and are of no further force or
effect.
Notwithstanding the foregoing, the following agreements, in existence
on
the date hereof, will remain in full force and effect and are considered
to be independent and separate from this Agreement: (Insert
details of other agreements here).
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12.4
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The
convenants and conditions contained herein will apply to and bind
the
successors, representatives and assigns of all parties
hereto.
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12.5
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If
any provision of this Agreement shall be deemed void in whole or
in part
for any reason whatsoever, the remaining provisions shall remain
in full
force and effect.
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12.6
This
Agreement shall be governed by and interpreted in accordance with the laws
of
the State of Ohio.
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12.7
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Waiver
by either party or the failure by either party to claim a breach
of any
provision of this Agreement shall not be deemed to constitute a
waiver or
estoppel with respect to any subsequent breach of any provision
hereof.
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12.8
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Each
party, on behalf of itself, its agents, employees, subcontractors
and
representatives agree not to use the name of the other party or
its
agents, employees, subcontractors and representatives in any publication,
promotional material or other writing or oral statement for public
distribution, relative to the subject matter or existence of this
Agreement, except as otherwise required by law or SEC regulations
or
previously consented to in writing by the other party. Notwithstanding
the
foregoing, Sponsor consents to CRO advising prospective clients
that CRO
has performed clinical research services for
Sponsor.
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12.9
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Either
party’s failure to perform its obligations hereunder shall be excused
to
the extent and for a period of time such nonperformance is caused
by an
event of force
majeure,
including but not limited to, the occurrence of war, invasion,
acts of
terrorism, fire, explosion, flood, riot, strikes, acts of God,
acts of
government or governmental agencies or instrumentalities or contingencies
or causes beyond such party’s reasonable
control.
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12.10
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Any
notices which either party may require or shall desire to give
hereunder
will be deemed to be duly given when delivered personally or received
by
the addressee through mail (electronic or postage prepaid), telefax
or
telex at the address first provided above, “Attention: General Counsel”,
or to other address(es) of which such party shall have given written
notice. Notices given other than through postage prepaid mail shall
be
confirmed by postage prepaid mail.
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12.11
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This
Agreement is designed, where appropriate and where required under
any
individual Task Order, to accommodate the provision of services
on a
global basis. Under such circumstances, Sponsor acknowledges that
all or
part of the Services may be performed by CRO, its subsidiaries
or
affiliates and that such performance will constitute performance
by the
CRO for purposes of this Agreement and the individual Task
Order.
|
|
12.12
|
Articles,
5, 6, 8, 11.1, 12.5, 12.6, 12.7, 12.8, 12.10 and this Section 12.12
shall
survive termination of this Agreement and shall be binding to the
respective successors, assigns, subsidiaries or
affiliates.
|
|
12.13
|
CRO shall
maintain adequate levels and types of insurance coverage appropriate
to
its business, including without limitation workers’ compensation,
comprehensive general liability, and errors and omissions
coverage.
|
|
12.14
|
No
printed standard terms appearing on any purchase order, invoice
or
despatch order relating to the Services will be effective in adding
or
changing the terms of this Agreement (or any Task
Order).
|
AS
TO
SPONSOR:
AS TO CRO:
By:
/s/ Xxxxx
X. Xxxxxx By:
/s/ Xxxx Xxxxxxxx
Name: Xxxxx
X. Xxxxxx
Name:
Xxxx Xxxxxxxx
Title: Sr.
Vice President Pharmaceuticals Title:
Sr. Vice President & CFO
Date: May
2, 2005
Date:
April 28, 2005
By:
/s/
Xxxx X. Xxxxxxxx
Name:
Xxxx
X. Xxxxxxxx
Title:
Chief
Financial Officer
Date: May
2, 2005
EXHIBIT
A
FORM
OF TASK ORDER
Miravant
Pharmaceuticals, Inc. (“Sponsor”) and Xxxxxx International Inc. (“Xxxxxx”) have
entered into a Clinical Development Master Services Agreement dated
_______________(“Master Agreement”) which provides that a Task Order be entered
into to set out with specificity the details of a particular Study. The terms
contained herein are pursuant to and governed by such Master
Agreement.
The
Master Agreement effective as of __________ is hereby incorporated by reference.
This
Task
Order is effective as of the _____ day of February, 2005 and shall terminate
at
the conclusion of the work to be performed by Xxxxxx.
A.
Description
of Services
| 1. |
Protocol
Name and Number
|
| 2. |
Project
Assumptions
|
| 3. |
Responsibilities
Overview
|
B.
Timeline
for Performance of Services
[Xxxxxx
and Sponsor shall cooperate to meet the timelines set forth below.]
C
Description
of Transferred Obligations
D.
Budget
which
shall include the following information:
| 1. |
Total
amount of Work Order;
|
| 2. |
Identification
of pass-through expenses, if any, as fixed or pass-throughs;
and
|
| 3. |
Amount
of expenses allocated to travel, investigator payments, and
other.
|
E.
Schedule
of Payment
which
shall include the following information:
| 1. |
Sponsor
billing address and billing contact person
information;
|
| 2. |
Third
party Federal Express billing number, if
appropriate;
|
| 3. |
Type
of invoice, i.e. time and materials, milestone, unit or otherwise;
and
|
| 4. |
Currency
exchange rate fluctuation language as follows (IF
APPLICABLE):
|
1.
Since
pricing and subsequent invoicing are denominated in [U.S. dollars] while
at
least a portion of expenditure on the services provided will arise in (one
or
more different currencies), and the contract pricing totals do not include
a
margin to cover currency exchange rate fluctuations (“CERF”), the parties agree
to review CERF’s every three months throughout the term of this Task Order in
accordance with this Section ___.
2.
The
contract pricing is based on the following exchange rates : 1 US dollar =
_________ Pounds Sterling = _______ Euro (etc.). Provided no currency in
which
expenditure occurs increases or decreases by more than 3% with respect to
the
(original pricing currency, same as in 1 above), the review will conclude
that
no adjustment to the original pricing is required in relation to the services
provided to that date.
3.
Where
a CERF between the [U.S. dollar] and any other currency of expenditure exceeds
3%, one party will have the potential for gain and the other will have the
potential for unacceptable and unintentional loss. Both parties agree that
where
this occurs it will be necessary to adjust the pricing of the services to
eliminate any loss which would otherwise be incurred by the CRO or Sponsor
through no fault of either party.
4.
Sponsor agrees that if a CERF produces an unscheduled loss not specifically
included in the contract price, Sponsor will agree to a positive price
adjustment (i.e. a payment to the CRO) in relation to the services affected,
with the effect of offsetting this loss in its entirety.
| 5. |
The
CRO agrees that if a CERF produces an unscheduled gain not included
in the
contract price, the CRO will agree to a negative price adjustment
(i.e. a
reduction in price) in relation to the services affected, with
the effect
of offsetting this gain in its entirety. In the calculation of
the
adjustments referred to above, the % CERF will be multiplied by
the
proportion of service pricing that is denominated in the currencies
that
have been subject to the CERF, and these services will then be
invoiced at
the adjusted prices until reviewed by the parties.
|
AGREED
TO
AND ACCEPTED BY
XXXXXX
INTERNATIONAL INC. MIRAVANT
PHARMACEUTICALS, INC.
_______________________________ ____________________________
Name: Name:
Xxxxx X. Xxxxxx
Title: Title: Sr.
VP,
Pharmaceuticals
Date: Date:
____________________
_______
Name: Xxxx
X.
Xxxxxxxx
Title:
Chief Financial Officer
Date:
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
TASK
ORDER
For
Study 31293
Miravant
Pharmaceuticals, Inc. and Xxxxxx International Inc. have entered into a Clinical
Development Master Services Agreement dated April 27, 2005 (“Master Agreement”)
which provides that a Task Order be entered into to set out with specificity
the
details of a particular Study. The terms contained herein are pursuant to
and
governed by such Master Agreement.
The
Master Agreement effective as of April
27,
2005
is
hereby incorporated by reference.
This
Task
Order is effective as of the 14th day of June, 2005 and shall terminate as
of
the 1st day of July, 2008.
| I. |
Description
of Services
|
A.
Protocol
:
“MRVT-920101-OPH005, A Phase III Randomized multicentre, multinational,
double-masked placebo controlled study of Photrex™ (Rostaporfin) Photodynamic
Therapy in the treatment of classic and occult subfoveal choroidal
neovascularization associated with age-related macular
degeneration.”
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
B.
Project
Assumptions:
The
table
below and the endnotes which follow summarize the assumptions used for the
key
cost drivers for Miravant’s
project. Certain assumption changes may result in a revision in costs. If
this
situation appears likely, it will be discussed fully with Miravant.
|
Service
|
Category
|
Description
|
Assumption
|
|
General
Study Parameters
|
|||
|
Site
and Patient Information
|
|||
|
Number
of sites
|
[***]
|
||
|
Number
of participating countries
|
[***]
|
||
|
Participating
countries and number of sites per country
|
[***]
|
||
|
Participating
countries and number of enrolled patients per country
|
[***]
|
||
|
Number
of screened patients
|
[***]
|
||
|
Number
of enrolled patients
|
[***]
|
||
|
Number
of completed patients
|
[***]
|
||
|
Screen
failure rate
|
15
%
|
||
|
Drop
out rate
|
10.9
%
|
||
|
SAE
rate
|
2.3
%
|
||
|
Number
of SAEs
|
[***]
|
||
|
Project
Period
|
|||
|
Implementation
|
[***]
|
||
|
Enrollment
duration
|
[***]
|
||
|
Treatment
duration
|
[***]
|
||
|
Study
close out (treatment end through submission of final clinical study
report
to sponsor)
|
[***]
|
||
|
Total
project duration
|
[***]
|
||
|
CRF
Pages
|
|||
|
e-CRF
pages per completed patient (Miravant Assumption)
|
82
|
||
|
Unique
e-CRF pages (Miravant Assumption)
|
14
|
||
|
Total
number of CRF pages
|
60,762
|
||
|
Miscellaneous
|
|||
|
Number
of Central Labs
|
1
|
||
|
Number
of Associate CROs
|
2
|
||
|
Study
Documents
|
|||
|
CRFs
|
|||
|
Develop
CRF
|
Included
in EDC set up Costs
|
||
|
Review
CRF
|
Yes
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Ship
CRFs
|
No
|
||
|
Print
CRFs
|
N/A
EDC
|
||
|
Protocol
and Informed Consent
|
|||
|
Develop
and write Informed Consent (does not include revisions)
|
Yes
|
||
|
Use
sponsor provided template to write consent
|
Yes
|
||
|
Miscellaneous
|
|||
|
Translate
study documents
|
Yes
|
||
|
Ship
final study documents to sponsor
|
Yes
|
||
|
Drug
and Clinical Trial Materials Management
|
|||
|
Drug
Management
|
|||
|
Drug
Management provided by 3rd party vendor
|
Yes
(fees included in pass through costs)
|
||
|
Ship
drug
|
Yes
|
||
|
Number
of drug shipments per site
|
7
|
||
|
Site
Identification / Essential Document Collection
|
|||
|
Site
Identification
|
|||
|
Conduct
feasibility analysis
|
No
- Already Paid for Under Separate Contract
|
||
|
Identify
sites
|
Yes
|
||
|
Xxxxxx
responsible for confidentiality agreements
|
Yes
|
||
|
Number
of sites identified by Xxxxxx
|
[***]
|
||
|
Number
of sites contacted by Xxxxxx to identify requested number of
sites
|
[***]
|
||
|
Essential
Document Collection
|
|||
|
Collect
essential documents
|
Yes
|
||
|
Number
of sites requiring document collection
|
[***]
|
||
|
IRB
and Ethics Committee Submissions
|
|||
|
IRB
/ Ethics Committee Submissions
|
|||
|
Obtain
IRB/Ethics Committee approvals
|
Yes
|
||
|
Number
of local Ethics Committee submissions (Note: some countries require
one
submission per site)
|
[***]
|
||
|
Clinical
Regulatory
|
|||
|
General
|
|||
|
Submit
Clinical Trial Application to Regulatory Authorities (includes
preparation
of IMPD in Europe)
|
Yes
(Costs
reflected in fee estimate are based on detailed assumptions outlined
in
proposal text)
|
||
|
Number
of countries submitting to Regulatory Authorities (Note: some countries
require one submission per site)
|
[***]
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Biotech
product
|
No
|
||
|
Registered
product
|
Yes
|
||
|
Ensure
drug label text complies with regulatory requirements (includes
translation into local language)
|
Yes
(Europe only)
|
||
|
Submit
protocol amendments to Regulatory Authorities
|
Yes
|
||
|
Number
of protocol amendments (additional amendments will be billed at
the cost
outlined in the fee estimate)
|
1
Europe
|
||
|
Notify
Regulatory Authorities of end of trial
|
Yes
(Europe only)
|
||
|
Submit
summary of study outcome to Regulatory Authorities (1 year after
LPO)
|
Yes
(Europe only)
(Costs
reflected in fee estimate are based on assumption that final study
report
is available)
|
||
|
Close-out
study with Regulatory Authorities
|
No
(N/A in Europe)
|
||
|
Administration
of Contracts and Payments
|
|||
|
Contracts
and Budget
|
|||
|
Negotiate
Investigator contracts and budgets
|
Yes
|
||
|
Number
of sites requiring contract and budget negotiation
|
[***]
|
||
|
Investigator
Payments
|
|||
|
Administer
investigator payments
|
Yes
|
||
|
Number
of sites requiring investigator payment processing
|
[***]
|
||
|
Number
of investigator payments - Europe
|
[***]
|
||
|
Frequency
of payments - Europe
|
[***]
|
||
|
Other
Payments
|
|||
|
Administer
Central Lab payments
|
Yes
|
||
|
Number
of Central Lab payments
|
18
|
||
|
Combined
Investigator / Kick-off Meeting
|
|||
|
Location
and Duration
|
|||
|
Number
of combined meetings
|
2
|
||
|
Location
of combined meetings
|
Bucharest,
Prague
|
||
|
Duration
of each meeting
|
2
days/ 2 nights Investigator Meeting, 1 day Kick-off
Meeting
|
||
|
Combined
Investigator/Kick-off Meeting Location A -
Bucharest
|
|||
|
Total
number of Xxxxxx attendees
|
[***]
|
||
|
Project
Leader
|
[***]
|
||
|
Lead
CRA
|
[***]
|
||
|
CRAs
|
[***]
|
||
|
Clinical
Data Manager
|
[***]
|
||
|
IT
|
[***]
|
||
|
IVRS
Manager
|
[***]
|
||
|
Combined
Investigator/Kick-off Meeting Location B -
Prague
|
|||
|
Total
number of Xxxxxx attendees
|
[***]
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Project
Leader
|
[***]
|
||
|
Lead
CRA
|
[***]
|
||
|
CRAs
|
[***]
|
||
|
Clinical
Data Manager
|
[***]
|
||
|
IT
|
[***]
|
||
|
IVRS
Manager
|
[***]
|
||
|
Investigator
Meeting Planning
|
|||
|
Management
|
|||
|
Plan
investigator meeting location A - Bucharest
|
Yes
|
||
|
Plan
investigator meeting location B - Prague
|
Yes
|
||
|
Duration
of EACH investigator meeting
|
2
days/ 2 nights
|
||
|
Provide
web-based registration (including hotel and air
reservations)
|
Yes
|
||
|
Invitations
|
|||
|
Develop
and mail invitations
|
Yes
|
||
|
Ground
and Air Transportation
|
|||
|
Provide
airfare, hotel accommodations (at moderate hotel) and ground
transportation to/from the airport and hotel (does not include
reimbursement for physician expenses such as airport parking and
mileage
to/from airport in their home city).
|
Yes
|
||
|
On-site
Logistics
|
|||
|
Provide
food and beverages
|
Yes
|
||
|
Provide
audio-visual, signage and welcome materials
|
Yes
|
||
|
Provide
binders
|
Yes
|
||
|
Provide
shipping and drayage
|
Yes
|
||
|
Sites
and Attendees
|
|||
|
Number
of sites
|
[***]
|
||
|
Number
of attendees per site
|
Costs
reflect three attendees per site (Investigator, Study Coordinator
and
Photographer)
|
||
|
Number
of Xxxxxx attendees Location A - Europe
|
[***]
|
||
|
Number
of Xxxxxx attendees Location B - Europe
|
[***]
|
||
|
Number
of sponsor attendees per meeting
|
Assumes
one sponsor attendee for each Xxxxxx attendee
|
||
|
Number
of Xxxxxx Program Managers
|
Assumes
one Program Manager will be attending each meeting
|
||
|
Clinical
Monitoring
|
|||
|
General
|
|||
|
Number
of sites
|
[***]
|
||
|
Number
of CRAs assigned
|
[***]
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Number
of unblinded CRAs assigned
|
[***]
|
||
|
Number
of Lead CRAs assigned
|
[***]
|
||
|
Travel
hours per site visit
|
[***]
|
||
|
Pre-study
visits
|
|||
|
Number
of visits
|
[***]
|
||
|
Number
of hours on site
|
[***]
|
||
|
Number
of hours prep & follow up
|
[***]
|
||
|
Initiation
visits
|
|||
|
Number
of visits
|
[***]
|
||
|
Number
of hours on site
|
[***]
|
||
|
Number
of hours prep & follow up
|
[***]
|
||
|
Monitoring
visits
|
|||
|
Number
of visits
|
[***]
|
||
|
Number
of hours on site
|
[***]
|
||
|
Number
of hours on site (unblended visits)
|
[***]
|
||
|
Number
of hours prep & follow up
|
[***]
|
||
|
Site
close-out visits
|
|||
|
Number
of visits
|
[***]
|
||
|
Number
of hours on site
|
[***]
|
||
|
Number
of hours prep & follow up
|
[***]
|
||
|
Investigative
Site Interaction
|
|||
|
Handle
miscellaneous phone calls to and from investigative sites
|
Yes
|
||
|
Number
of site contacts
|
[***]
|
||
|
Number
of hours per site contact
|
0.3
Europe
|
||
|
Number
of site contacts per site/per week during enrollment
period
|
1
Europe
|
||
|
Number
of site contacts per site/per week during treatment period
|
1
Europe
|
||
|
Collect
SAE information
|
Yes
|
||
|
Site
Management
|
|||
|
Prepare
and attend monitoring team meetings
|
Yes
|
||
|
Review
all monitoring reports - LCRA
|
Yes
|
||
|
Review
and analyze tracking reports regarding patient and site recruitment
-
LCRA
|
Yes
|
||
|
Manage
timelines and deliverables - LCRA
|
Yes
|
||
|
Communicate
with project team (outside of monitoring team meetings) -
LCRA
|
Yes
|
||
|
Oversee
workload and team assignments - LCRA
|
Yes
|
||
|
Design
and implement contingency plans - LCRA
|
Yes
|
||
|
Track
reports, compile progress reports and study updates -
CSSPEC
|
Yes
|
||
|
Administer
site faxes, site enrollment and site patient log - CSSPEC
|
Yes
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Merge
investigator files into central file - CRA
|
Yes
|
||
|
Sponsor
Meetings and Teleconferences
|
|||
|
LCRA
attending sponsor meetings
|
Yes
|
||
|
Number
of sponsor meetings
|
4
|
||
|
Number
of sponsor meetings with travel
|
2
|
||
|
Duration
of sponsor meetings
|
8
hours
|
||
|
LCRA
attending sponsor teleconferences
|
Yes
|
||
|
Number
of sponsor teleconferences
|
60
|
||
|
Duration
of sponsor teleconferences
|
1
hour
|
||
|
Project
Management
|
|||
|
Project
Management - Project Leader
|
|||
|
Average
Project Leader hours per week - implementation phase
|
[***]
|
||
|
Average
Project Leader hours per week - enrollment - study close out
phase
|
[***]
|
||
|
Average
Project Leader hours per week - clinical report phase
|
[***]
|
||
|
Project
Management - Project Assistant
|
|||
|
Average
Project Assistant hours per week - implementation phase
|
[***]
|
||
|
Average
Project Assistant hours per week - enrollment - study close out
phase
|
[***]
|
||
|
Average
Project Assistant hours per week - clinical report phase
|
[***]
|
||
|
Sponsor
Meeting and Teleconferences
|
|||
|
Project
Leaders attending sponsor meetings
|
Yes
(1 Europe)
|
||
|
Project
Director attending sponsor meetings
|
No
|
||
|
Number
of sponsor meetings
|
4
|
||
|
Number
of sponsor meetings with travel
|
2
|
||
|
Duration
of sponsor meetings
|
8
hours
|
||
|
Project
Leader attending sponsor teleconferences
|
Yes
|
||
|
Project
Assistant attending sponsor teleconferences
|
Yes
|
||
|
Number
of sponsor teleconferences
|
62
|
||
|
Duration
of sponsor teleconferences (does not include prep and f/u)
|
1
hour
|
||
|
Miscellaneous
|
|||
|
Frequency
of newsletters
|
[***]
|
||
|
Number
of newsletters
|
[***]
|
||
|
Global
Project Leader Location
|
1
Europe
|
||
|
Clinical
Data Management
|
|||
|
General
|
|||
|
Number
of sites
|
[***]
|
||
|
Number
screened patients (not to be cleaned)
|
[***]
|
||
|
Number
of enrolled patients
|
[***]
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Number
of completed patients
|
[***]
|
||
|
Number
of dropped patients
|
[***]
|
||
|
Number
e-CRFs per completed patient (Miravant Assumption)
|
[***]
|
||
|
Number
of unique e-CRF pages (Miravant Assumption)
|
[***]
|
||
|
Frequency
of CDM status reports
|
Not
Requested
|
||
|
Data
Handling
|
|||
|
Number
of e-CRF pages (does not include screening data)
|
[***]
|
||
|
Process
working copies
|
No
|
||
|
Reconcile
SAEs
|
Yes
|
||
|
Number
of edit checks (Miravant Assumption)
|
150
|
||
|
Data
Coding
|
|||
|
Number
of codes - AEs (Miravant Assumption)
|
11,050
|
||
|
Number
of codes - medication/drugs (Miravant Assumption)
|
13,000
|
||
|
Number
of codes - medical history
|
2,600
|
||
|
Number
of codes - diagnosis
|
1,300
|
||
|
Data
Cleaning and Query Processing
|
|||
|
Manual
Query rate
|
5%
|
||
|
Number
of manual queries
|
3,038
|
||
|
Number
of e-queries (Miravant Assumption)
|
9,100
|
||
|
Quality
Control
|
|||
|
Verify
100% of data for 10% of subjects against e-CRF
|
Yes
|
||
|
Verify
100.0%of key variables (safety and efficacy)
|
Yes
|
||
|
External
Data Loads
|
|||
|
Process
local labs
|
No
|
||
|
Number
of central lab loads
|
34
|
||
|
Number
of IVRS data loads
|
34
|
||
|
External
data sources
|
2
(IVRS and Lab format)
|
||
|
Number
of Fundus data loads
|
68
|
||
|
Data
Transfers (mapping)
|
|||
|
Number
of data transfers
|
2
|
||
|
Number
of final data transfers
|
1
|
||
|
Sponsor
Meeting and Teleconferences
|
|||
|
Clinical
Data Manager attending sponsor meetings
|
Yes
|
||
|
Number
of sponsor meetings
|
4
|
||
|
Number
of sponsor meetings with travel
|
2
|
||
|
Duration
of sponsor meetings
|
8
hours
|
||
|
Clinical
Data Manager attending sponsor teleconferences
|
Yes
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Number
of sponsor teleconferences
|
56
|
||
|
Duration
of sponsor teleconferences
|
0.5
hour
|
||
|
Safety
/ Medical Monitoring
|
|||
|
General
|
|||
|
Connect
to sponsor's safety database
|
No
|
||
|
Use
Xxxxxx'x database as study safety database
|
Yes
|
||
|
Prepare
SAE reporting plan
|
Yes
|
||
|
SAE
Handling/Reporting
|
|||
|
Number
of SAEs processed by Xxxxxx (includes site contact)
|
17
Europe (17 total)
|
||
|
Reconcile
SAEs
|
Yes
|
||
|
SAE
Narratives
|
|||
|
Write
SAE narratives for reporting to Regulatory Authorities
|
Yes
|
||
|
Safety
Alert Letters
|
|||
|
Compose
safety alert letters to Investigators
|
Yes
|
||
|
Distribute
safety alert letters to Investigators
|
Yes
|
||
|
Single
Case Reporting
|
|||
|
Number
of expected single case reports
|
1
Europe (1 total)
|
||
|
Submit
single case reports to FDA - USA
|
No
|
||
|
Submit
single case reports to Regulatory Authorities and Ethics Committees
-
ROW
|
Yes
(Fees reflect estimate. Additional units will be billed
accordingly.)
|
||
|
Number
of countries in European Union (assumes 1 SUSAR submitted for all
countries in union)
|
3
|
||
|
Number
of countries in ROW (assumes one submission per single case report
per
country)
|
4
|
||
|
Submit
single case reports to sponsor affiliates
|
Yes
|
||
|
Periodic
or Annual Reporting
|
|||
|
Periodic
reporting to FDA - USA
|
No
|
||
|
Prepare
SAR listing for annual safety report according to Directive
2001/20/EC
|
Yes
|
||
|
Review
sponsor provided annual safety report
|
Yes
|
||
|
Submit
annual safety reports
|
Yes
|
||
|
DSMB/CEC
Reporting
|
|||
|
Report
to DSMB/CEC
|
Yes
|
||
|
Number
of reports to DSMB/CEC
|
10
|
||
|
Safety
Reviews
|
|||
|
Conduct
safety reviews
|
No
|
||
|
Medical
Monitoring
|
|||
|
Provide
Medical Monitoring 24/7
|
Yes
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Medical
Monitoring in Europe provided by
|
GER
|
||
|
Sponsor
Meetings and Teleconferences
|
|||
|
Safety
Specialist attending technical meetings
|
No
|
||
|
Safety
Specialist attending sponsor teleconferences
|
No
|
||
|
Medical
Officer attending sponsor teleconferences
|
No
|
||
|
Biostatistics
|
|||
|
General
|
|||
|
Provide
statistical input to protocol development
|
No
|
||
|
Determine
sample size
|
No
|
||
|
Develop
randomization code
|
No
|
||
|
Validate
randomization code
|
No
|
||
|
Dynamic
randomization
|
No
|
||
|
Tabulate
CRFs
|
No
|
||
|
Tables,
Listings, Figures
|
|||
|
Generate
and review TLFs
|
Yes
|
||
|
Number
of analysis datasets
|
1
|
||
|
Number
of unique efficacy tables
|
21
|
||
|
Number
of unique figures
|
2
|
||
|
Number
of non-unique efficacy tables
|
20
|
||
|
Number
of summary tables -standard/safety
|
26
|
||
|
Number
of non-unique figures
|
20
|
||
|
Number
of data listings
|
30
|
||
|
Statistical
Analysis Plan
|
|||
|
Statistical
analysis plan - prepare statistical text
|
No
|
||
|
Statistical
analysis plan - unique efficacy tables/figures
|
Yes
|
||
|
Statistical
analysis plan - non-unique efficacy tables/figures/summary
tables/listings
|
Yes
|
||
|
Analysis
|
|||
|
[***]
|
[***]
|
||
|
[***]
|
[***]
|
||
|
[***]
|
[***]
|
||
|
[***]
|
[***]
|
||
|
[***]
|
[***]
|
||
|
Quality
Control and Validation
|
|||
|
Quality
control of TLFs only
|
Yes
|
||
|
Statistical
Report/Manuscript
|
|||
|
Provide
independent statistical report
|
No
|
||
|
Provide
statistical input and review final study report
|
Yes
|
||
|
Provide
statistical input and review manuscript for publication
|
No
|
||
|
DSMB/CEC
Reporting
|
|||
|
Report
to DSMB/CEC
|
Yes
|
||
|
Number
of reports to DSMB/CEC
|
10
|
||
|
Number
of DSMB TLFs
|
10
|
||
|
Data
Transfer
|
|||
|
Transfer
analysis data and programming documents
|
Yes
|
||
|
Number
transfers
|
1
|
||
|
Sponsor
Meetings and Teleconferences
|
|||
|
Statistician
attending DSMB meetings
|
Yes
|
||
|
Number
of DSMB meetings
|
5
(2 attendees per meeting)
|
||
|
Number
of DSMB meetings with travel
|
5
(2 attendees per meeting)
|
||
|
Statistician
attending sponsor teleconferences
|
Yes
|
||
|
Programmer
attending sponsor teleconferences
|
Yes
|
||
|
Number
of sponsor teleconferences
|
10
|
||
|
Duration
of teleconferences
|
1
hour
|
||
|
IVRS
- TriaLine®
|
|||
|
General
|
|||
|
Number
of sites
|
[***]
|
||
|
Number
of patients
|
[***]
|
||
|
Interactive
voice response (IVR)
|
Yes
|
||
|
Interactive
web response (IWR)
|
No
|
||
|
Call
Types
|
|||
|
Enrollment/Screening
(includes enrollment/screening report for site and enrollment summary
report for sponsor)
|
Yes
|
||
|
Randomization
(includes randomization report for site and randomization summary
for
sponsor)
|
Yes
|
||
|
Drug
Management (includes drug re-supply request report, drug shipment
listings
report and drug inventory report for sponsor)
|
Yes
|
||
|
Acknowledge
receipt of drug (includes acknowledge receipt of drug report, pending
drug
acknowledgement report and drug shipment overdue for acknowledgement
report for site, and site summary/listing report for
sponsor)
|
Yes
|
||
|
Drug
dispensing (includes drug dispensing report for site and dispensing
summary for sponsor)
|
Yes
|
||
|
#
of shipments per site
|
4
|
||
|
Study
Bulk Supplies (includes dispatch order form for site and drug shipment
summary report for sponsor)
|
Yes
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Patient
Tracking (includes tracking report and patient overdue for visit
notice
report for site and patient activity summary report for
sponsor)
|
No
|
||
|
Withdrawals/Discontinuation
(includes withdrawal/discontinued report for site and
withdrawal/discontinued summary for sponsor)
|
No
|
||
|
Unblinding
(includes unblinding confirmation for site and patient unblinding
report
for sponsor)
|
No
|
||
|
Treatment
re-allocation (includes treatment re-allocation confirmation for
site and
treatment re-allocation summary report for sponsor)
|
No
|
||
|
Patient
diary (includes patient missed diary call notice report, patient
diary
completion call report and patient diary alert report for site
and patient
diary compliance status report for sponsor)
|
No
|
||
|
Medical
Survey (includes medical survey completion confirmation for site
and
survey results summary report for sponsor)
|
No
|
||
|
Score/Index
Calculations (includes subject score/index completion confirmation
for
site and calculated score/index summary report for
sponsor)
|
No
|
||
|
Site
Management (includes site activation/deactivation confirmation
and site
status confirmation for site and site status summary report for
sponsor)
|
No
|
||
|
Target
enrollment tracking (includes target enrollment summary report
for site
and target enrollment summary report for sponsor)
|
No
|
||
|
Customized
reports (includes completions, confirmations, calculations and
tracking
for site and summary reports by site, country and study for
sponsor)
|
No
|
||
|
Call
Parameters
|
|||
|
Number
of languages required (excluding English)
|
6
|
||
|
English
required
|
Yes
|
||
|
Number
of dedicated T1 phone lines
|
1
|
||
|
Number
of months for T1 line
|
[***]
|
||
|
Call
Center Support
|
|||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Provide
24/7 Call Center Support
|
Yes
|
||
|
Number
of expected calls
|
65
|
||
|
Password
Mailings
|
|||
|
Number
of investigator letters per site
|
1
|
||
|
Number
of study coordinator letters per site
|
1
|
||
|
Number
of pharmacist letters per site
|
1
|
||
|
Timelines
|
|||
|
IVRS
project duration
|
[***]
|
||
|
Medical
Writing
|
|||
|
General
|
|||
|
Write
full protocol
|
No
|
||
|
Clinical
Study Report
|
|||
|
Write
patient narratives
|
Assume
use Narratives provided by Safety
|
||
|
Write
clinical study report
|
Yes
|
||
|
Number
of clinical study reports
|
2
|
||
|
Attend
one sponsor teleconference
|
Yes
|
||
|
Prepare
and QC submission ready PDF
|
No
|
||
|
Generate
and compile appendices
|
Yes
|
||
|
Manuscript
|
|||
|
Write
Manuscript for publication
|
No
|
||
|
Timelines
and Meetings
|
|||
|
Attend
technical meetings
|
No
|
||
|
Attend
sponsor teleconferences
|
No
|
||
|
Quality
Assurance Audits
|
|||
|
Site
Audits
|
|||
|
Conduct
site audits
|
Yes
|
||
|
Number
of sites to audit
|
[***]
|
||
|
Number
hours on site
|
16
hours
|
||
|
Number
hours to prepare draft audit report and final editing
|
20
hours
|
||
|
Number
of hrs to travel to sites - US
|
0
hours
|
||
|
Number
of hrs to travel to sites - Europe
|
6
hours
|
||
|
Number
of hrs to travel to sites - USA to AUS
|
0
hours
|
||
|
Other
Audits
|
|||
|
Database
audit
|
Yes
|
||
|
%
of enrolled patients audited Safety & Efficacy
|
1%
|
||
|
IVRS
audit
|
No
|
||
|
Statistical
report audit
|
No
|
||
|
Master
file audit (not part of site audit)
|
No
|
||
|
Protocol
audit
|
No
|
||
|
Central
laboratory audit
|
Yes
|
||
|
Number
of central labs audited
|
1
|
||
|
Clinical
report audit
|
Yes
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Drug
compliance audit
|
Yes
|
||
|
Vendor
facility audit
|
No
|
|
CRF
audit
|
No
|
||
|
Informed
consent audit
|
No
|
||
|
Diary
card audit
|
No
|
||
|
Clinical
Support Center
|
Service
not requested
|
||
|
Therapeutic
Services
|
Service
not requested
|
||
|
Document
Management
|
|||
|
Document
Management & Storage
|
|||
|
Number
of sites
|
[***]
|
||
|
TrialWeb
|
|||
|
TrialWeb
|
|||
|
Configure
TrialWeb study project and access rights
|
Yes
|
||
|
Number
of sponsor users included in standard TrialWeb
configuration
|
25
|
||
|
Access
right for additional sponsor or non-site users (after initial
25)
|
[***]
|
||
|
Set
up retrieval system with images of annotated CRFs or other
images
|
No
|
||
|
Offer
sites access to study progress areas for newsletters, study status
etc.
|
[***]
|
||
|
Automate
process to post TriaLine reports to TrialWeb
|
[***]
|
||
|
Configure
custom home page (some restrictions apply)
|
[***]
|
||
|
Patient
Recruitment
|
Service
not requested
|
||
|
Pass
Through Estimates
|
|||
|
Estimated
Patient Grant Fees
|
|||
|
Grant
fees per completed patient - [***]
|
[***]
|
||
|
Grant
fees per screen failure - [***]
|
[***]
|
||
|
Grant
fees per dropped patient - [***]
|
[***]
|
||
|
Grant
fees per completed patient - [***]
|
[***]
|
||
|
Grant
fees per screen failure - [***]
|
[***]
|
||
|
Grant
fees per dropped patient - [***]
|
[***]
|
||
|
Grant
fees per completed patient - [***]
|
[***]
|
||
|
Grant
fees per screen failure - [***]
|
[***]
|
||
|
Grant
fees per dropped patient - [***]
|
[***]
|
||
|
Grant
fees per completed patient - [***]
|
[***]
|
||
|
Grant
fees per screen failure - [***]
|
[***]
|
||
|
Grant
fees per dropped patient - [***]
|
[***]
|
||
|
Grant
fees per completed patient - [***]
|
[***]
|
||
|
Grant
fees per screen failure - [***]
|
[***]
|
||
|
Grant
fees per dropped patient - [***]
|
[***]
|
||
|
Grant
fees per completed patient - [***]
|
[***]
|
||
|
Grant
fees per screen failure - [***]
|
[***]
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Grant
fees per dropped patient - [***]
|
[***]
|
||
|
Grant
fees per completed patient - [***]
|
[***]
|
||
|
Grant
fees per screen failure - [***]
|
[***]
|
||
|
Grant
fees per dropped patient - [***]
|
[***]
|
Endnotes
for Project Assumptions
GENERAL:
Travel
expenses (airfare, etc.) for meetings will be billed as pass-through expenses.
Time and travel expenses for other face-to-face meetings required by
Miravant
or
within-Xxxxxx travel which is needed to produce deliverables will be billed
in
addition to the monetary amount
cited in
the bid.
Costs
for
shipping will be billed as pass-through expenses.
PROJECT
MANAGEMENT:
If
Miravant’s
SOPs
are to be used, additional time will need to be added for training.
Cost
assumes study status reports are provided in Xxxxxx’x standard format. In
addition to providing details on the status of the study/sites, these reports
will also identify any potential issues requiring referral to Miravant
ESSENTIAL
DOCUMENT COLLECTION:
Includes
all regulatory and administrative documents agreed to by Xxxxxx and Miravant.
Also
includes the INITIAL collection of Financial Disclosure Form from the principal
investigator and all sub-investigators listed on the FDA Form 1572 (additional
iterations of these forms are considered out of scope.)
DOCUMENT
MANAGEMENT:
At
Miravant’s
request, continued storage of original study documents can be provided by
Xxxxxx
through a 3rd
party
for up to 15 years for an additional cost. Fees for this service will be
determined at the time of the request and will depend upon the
anticipated length of storage time needed as well as the number of documents
to
be stored.
There
will be a per site charge for each protocol amendment or administrative
change.
INTERACTIVE
VOICE RESPONSE SYSTEM (IVRS) - TRIALINE®:
After
the
requirement document sign-off, changes to the requirements will be considered
changes-in-scope and require additional costs and time for
completion.
After
the
requirement document sign-off, additional languages and prompts will take
approximately 4 weeks before being placed into production. These languages
will
be priced at our standard language cost.
Amendments
to the project which affect the database design (e.g. modifications to drug
shipment process, etc.) will result in additional costs.
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
MONITORING:
Assumes
that source document verification will be handled according to Xxxxxx
SOPs.
SAFETY:
SAE(s)
Processing and SUSAR(s) reporting to Authorities and EC concerned will be
charged by unit price as they occur.
BIOMETRICS
- Clinical Data Management:
After sign-off,
changes to the Data Validation Plan or CDM status reports will be considered
changes-in-scope.
Amendments
to the project which affect the database design (e.g. modifications to CRFs,
edits, etc.) will result in additional costs.
Contents
of SAS data sets are based on Xxxxxx’x definitions of logical data groupings and
logical field names, descriptions and formats. When Miravant
provides
data transfer specifications, Xxxxxx will review them and determine if
additional resources and fees are necessary.
Additional
transfers of data will result in additional costs.
If
requested, costs for additional QC of key efficacy and safety variables will
be
determined when these variables are defined.
Amendments
to the project which affect the data processing, validation and handling
(e.g.
modifications to the data validation plan, data handling procedure), data
flow,
status reporting, etc. will result in additional costs.
Assumes
that processing of ancillary pages is limited to reviewing and reconciling
patient identifiers with CRF data, and that NO data entry from these pages
is
required.
Xxxxxx
uses standard shipping boxes via Federal Express to return CDM study materials.
FedEx insures contents of boxes up to €100.00 Additional weight boxes or
additional insurance can be coordinated by Xxxxxx for additional cost if
desired
by Miravant.
All
archiving costs (both professional fees and associated pass-through fees)
incurred on behalf of Miravant
will
be
billed separately and are not included in this bid.
External
data loads are currently costed for monthly transfers of data from IVRS and
Lab
and twice a month from the Fundus Reading Centre.
BIOMETRICS
- Statistics:
While
the
fee for biostatistician services is quoted as a “fixed cost” fee, it is
important to note that this is based on several assumptions as to the magnitude
of the work and comprises of both fixed and variable cost components. The
variable cost component relates mostly to the statistical programming needed
for
generating the report output items (tables, listings, and figures) - the
number
needed and their complexity. It should also be noted that additional work
resulting from changes to an approved statistical analysis plan (e.g., changes
to formats of tables, additional tables, data driven exploratory analyses,
etc.)
will be treated as “out of scope and will be billed separately.
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
MEDICAL
WRITING - Europe
[***]
If
Miravant
would
like to manage reporting in this study differently, Xxxxxx would be happy
to
revise the bid according to Miravant
needs.
The
price
for report writing is preliminary because the parameters and analyses to
be
described are not specified yet. The variable cost component relates to the
number of parameters and analyses to be described and the complexity of the
results. Thus, the price may be revised once the statistical analysis plan
is
available.
[***]
Additional drafts of the CSR will be considered out of scope. Allocation
of
additional resources due to sponsor required abbreviated writing timelines
will
be considered out of scope.
The
bid
assumes that Xxxxxx will not be required to search through subject data listings
to identify protocol violators/deviators, or compile and classify protocol
violations/deviations from a deviation log. If Xxxxxx is required to do this
task, it will be considered out of scope, and the hours spent will be billed
at
the current billing rate of the Xxxxxx associate performing the work.
It
is
assumed that SAE narratives would be written by Xxxxxx’x safety department. If
there are any narratives, i.e., withdrawals due to AEs, AEs of special interest,
that Xxxxxx is required to write, they will be billed at 1.5 hrs (one and
a half
hours)/narrative at current medical writer billing rate.
The
bid
price includes
60
hours
for generation/compilation of report appendices. Additional hours (if any)
will
be billed at the current billing rate of the Xxxxxx associate performing
the
task. This will apply especially for appendix work for preparation of electronic
appendices, e.g. scanning from hardcopy or conversion of documents to PDF
format.
The
sponsor will provide the individual parts of the appendices which are outside
Xxxxxx'x control, e.g., required regulatory documents, test article information,
references, etc., in a timely manner and in a format suitable for inclusion
into
the final CSR. Xxxxxx is responsible for the following documents: CVs, IRB
information (local submissions made by Xxxxxx), audit certificates
(3rd
party
vendors that Xxxxxx will audit).
The
following may incur out-of-scope charges:
| - |
Major
delays and restart time
|
| - |
Face
to face meetings required by Miravant.
|
| - |
Major
changes to the report after the shell has been
approved
|
| - |
Major
template issues
|
| - |
Not
receiving the final protocol, amendment(s), administrative change(s)
and/or final SAP as MS Word documents (e.g., if they are received
as PDF
files)
|
| - |
Not
receiving one set of reconciled, consolidated review comments from
Miravant.
|
| - |
Writing
patient narratives from CRFs (rather than CIOMS or similar documents)
|
| - |
Finding
and obtaining required documents for the
appendices
|
EUROPEAN
COMPETENT AUTHORITIES BID:
The
scope
of work covers preparation of one Competent Authority application for Clinical
Trial Approval per country and submission of the finalized Competent Authority
Application on one occasion only, unless otherwise stated.
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
Ongoing
maintenance of the Clinical Trial approval such as protocol amendments and
routine updates will be charged on a fee for service basis as it is not possible
to predict the work volume in advance.
This
estimate does not include a fixed cost for importation/re-testing/QP release
of
drug product into the Europe from a third country as Xxxxxx do not currently
hold the required manufacturer's authorization and are therefore required
to
subcontract this work. Precise estimates can be obtained from sub-contractors
when further product details are available.
Competent
Authority fees will be treated as pass- through.
This
estimate assumes that appropriate local insurance cover will be arranged
by the
Sponsor and that a copy of the local insurance policy is provided to Xxxxxx
for
those countries where there are specific local insurance
requirements.
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
This
estimate assumes the product is an unregistered small molecule
pharmaceutical.
This
estimate assumes the Sponsor will provide an updated Investigator Brochure
for
each competent authority submission.
As
it is
not possible to guarantee Competent Authority approval, subsequent contact
with
the authorities post filing of the application will be made on a ‘fee for
service’ basis at the appropriate hourly consultancy rates.
This
estimate assumes all required data for the preparation of the investigational
medicinal product dossier (IMPD) will be provided by the Sponsor in summary
form. As this estimate is based on unseen data, costs are subject to
confirmation on review of the available data. It should be noted that
approximately 4-6 weeks of elapsed time is required for Xxxxxx Regulatory
to
prepare the IMPD after receipt of all required technical documentation from
the
Sponsor. Where the Sponsor wishes to prepare the IMPD, this estimate will
be
revised accordingly. Xxxxxx can review the IMPD prepared by the Sponsor but
this
consultancy activity will be charged on a ‘fee for service’ basis.
This
estimate assumes that Xxxxxx will serve as local representative of the Sponsor
in the Europe; legal representation can be arranged but is charged on a separate
'fee for service' basis.
This
estimate does not include regulatory consultancy with respect to the development
of a Regulatory submissions strategy for marketing authorization applications;
this service can be provided but will be charged on a 'fee for service' basis.
Out
of
scope consultancy is available but will be charged on a separate ‘fee for
service’ basis.
IT
OC RDC
Helpdesk:
The
First
Line Clinical & Helpdesk Support (monthly fee) is based on single language
support with 8am to 8pm coverage. The additional charge for weekend coverage
would increase the monthly fee. If Multi Lingual support in required the
Xxxxxx
can provide either a unit based cost per call of a fixed price for unlimited
calls.
CENTRAL
LABORATORY BID:
The
third
party central laboratory bid includes laboratory testing, supplies, starter
packs and resupplies and an estimation of transportation costs.
DRUG
DISTRIBUTION/MANAGEMENT BID:
The
third
party Drug distribution/management bid includes packaging, labeling,
procurement. distribution, storage, returns, destruction and an estimation
of
average courier fees. Any changes in specification or study stated assumptions
may result in changes to this quotation.
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
C.
Retinal Photography Process
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
Timeline
for Performance of Services
Xxxxxx
and Miravant shall cooperate to meet the timelines set forth below.
|
Critical
Milestones
|
Estimated
Date
|
|
Project
commencement
|
[***]
|
|
First
Investigator Meeting
|
[***]
|
|
First
subject First Treatment
|
[***]
|
|
Last
subject First Treatment
|
[***]
|
|
Last
subject completed at one year
|
[***]
|
|
Database
locked at one year
|
[***]
|
|
First
year statistical analysis complete
|
[***]
|
|
First
draft integrated clinical study report complete
|
[***]
|
|
Final
draft integrated clinical study report
|
[***]
|
|
Last
subject completed second year
|
[***]
|
|
Last
close-out visit
|
[***]
|
|
Database
locked at second year
|
[***]
|
|
Second
year statistical analysis complete
|
[***]
|
|
First
draft integrated clinical study report complete
|
[***]
|
|
Final
draft integrated clinical study report
|
[***]
|
The
milestones are dependent upon factors which may be outside Xxxxxx’x control, for
example: provision of final protocol, final CRF, treatment supplies, regulatory
approvals and EC/IRB approvals. Should any of these be delayed, there may
be
resulting effects upon subsequent time points and costs.
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
| II. |
Description
of Transferred
Obligations
|
|
Sponsor:
|
Project
Code/
Work
Order Number:
|
31293R4
|
|
|
Study
Title:
|
A
PHASE III RANDOMIZED, MULTICENTER, MULTINATIONAL, DOUBLE-MASKED,
PLACEBO-CONTROLLED STUDY OF PHOTREX™ (ROSTAPORFIN) PHOTODYNAMIC THERAPY IN
THE TREATMENT OF CLASSIC AND OCCULT SUBFOVEAL CHOROIDAL NEOVASCULARIZATION
ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION
|
IND
Number:
|
49,648
|
|
Indication:
|
SUBFOVEAL
CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH AGE-RELATED MACULAR
DEGENERATION
|
Protocol
Number:
|
MRVT-920101-OPH005
|
|
Obligation
Assigned to:
|
|||||
|
Regulatory
Obligation
|
Reference
|
Miravant
|
Xxxxxx
|
Xxxxxxxx
|
|
|
A.
|
1. Preparation
of all or part of an initial IND application
|
21
CFR 312.23
|
|||
|
a) Content
|
x | ||||
|
b) Format
|
x | ||||
|
2. Delivery
of initial IND application to FDA
|
x | ||||
|
3. Act
as authorized representative (agent for foreign applicant)
|
21
CFR 312.23 (a)(1)(ix)
|
x | |||
|
B.
|
Maintain
all or part of an IND with the following amendments, as necessary:
|
||||
|
1. Protocol
amendments (includes new protocols, changes in protocols, adding
new
investigators)
|
21
CFR 312.30
|
||||
|
a) Content
|
x | ||||
|
b) Format
|
x | ||||
|
c) Delivery
to FDA
|
x | ||||
|
2. Information
Amendments:
|
|||||
|
Chemistry,
Manufacturing, and Control amendments
|
21
CFR 312.31
|
||||
|
a) Content
|
x | ||||
|
b) Format
|
x | ||||
|
c) Delivery
to FDA
|
x | ||||
|
Pharmacology
and Toxicology amendments
|
21
CFR 312.31
|
||||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
a) Content
|
x | ||||
|
b) Format
|
x | ||||
|
c) Delivery
to FDA
|
x | ||||
|
Clinical
amendments
|
21
CFR 312.31
|
||||
|
a) Content
|
x | ||||
|
b) Format
|
x | ||||
|
c) Delivery
to FDA
|
x | ||||
|
3. IND
Safety Reports
a) Preparation
of safety report (s) (Update Reports Only)
b) Notifications
to FDA (phone/fax or written)
|
21
CFR 312.32
|
x
|
x | ||
|
4. Annual
Reports
|
21
CFR 312.33
|
||||
|
a) Content
|
x | ||||
|
b) Format
|
x | ||||
|
c) Delivery
to FDA
|
x | ||||
|
5. Response
to request for information or clinical hold
|
21
CFR 312.41, 312.42
|
||||
|
a) Content
|
x | ||||
|
b) Format
|
x | ||||
|
c) Delivery
to FDA
|
x | ||||
|
6. Letter
to withdraw an IND
|
21
CFR 312.38
|
||||
|
a) Content
|
x | ||||
|
b) Format
|
x | ||||
|
c) Delivery
to FDA
|
x | ||||
|
7. General
Correspondence / Other
|
Form
FDA-1571
|
||||
|
a) Content
|
x | ||||
|
b) Format
|
x | ||||
|
c) Delivery
to FDA
|
x | ||||
|
C.
|
Investigator
Brochure
|
21
CFR 312.55 (a); ICH E6 5.12, 7.3
|
|||
|
a) Content
|
x |
xUpdates
only
|
|||
|
b) Format
|
xUpdates
Only
|
||||
|
D.
|
Selecting
investigators and monitors
|
21
CFR 312.53
|
|||
|
1. Select
qualified investigators
|
21
CFR 312.53 (a); ICH E6 5.6.1
|
||||
|
a) Identify
qualified investigators/sites
|
x | ||||
|
b) Approve
investigators/sites for participation
|
x | ||||
|
2. Control
of drug
|
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
a) Obtain
required information from investigator (including signed Form
FDA 1572,
CV)
|
21
CFR 312.53 (c); ICH E6 5.14.2, 8.2
|
x | |||
|
b) Approve
investigators for receipt of drug shipment
|
21
CFR 312.53 (b); ICH E6 5.14.2
|
x | |||
|
c) Ship
drug to approved investigators
|
21
CFR 312.53 (b); ICH E6 5.14.1, 5.14.4(a)
|
x
|
|||
|
d) Maintain
shipment records
|
21
CFR 312.57(a); ICH E6 5.14.4(b)
|
x
|
|||
|
3. Provide
qualified monitors
|
21
CFR 312.53 (d); ICH E6 5.18.2
|
x | |||
|
4. Informing
investigators
|
|||||
|
a) Review
with investigators their regulatory responsibilities
|
Guideline
for the Monitoring of Clinical Investigations; ICH E6
5.18.4(f)(g)
|
x | |||
|
b) Deliver
investigator’s brochure
|
21
CFR 312.55 (a); ICH E6 5.6.2
|
x | |||
|
c) Inform
participating investigators of new safety information about the
study
drug
|
21
CFR 312.55 (b); ICH E6 5.16.2
|
x | |||
|
d) Notify
participating investigators of all serious, unexpected adverse
drug
reactions
|
21
CFR 312.32 (c); ICH E6 5.17.1
|
x | |||
|
E.
|
Review
of ongoing investigations
|
21
CFR 312.56
|
|||
|
1. Monitoring
the investigation
|
21
CFR 312.56
(a);
ICH E6 5.18.4
|
x | |||
|
2. Discontinue
investigator participation if not compliant
Note:
If the sponsor does not agree with Xxxxxx’x decision to discontinue an
investigator who is believed to be significantly non-compliant,
Xxxxxx
will request a complete transfer of regulatory obligation for
that site
back to the sponsor.
|
21
CFR 312.56 (b); ICH E6 5.20
|
x | x | ||
|
a) Notify
FDA
|
x | ||||
|
b) Assure
disposal or return of investigational drug
|
x | ||||
|
3. Provide
medical expertise to evaluate safety information
|
21
CFR 312.56 (c); ICH E6 5.16.1
|
x | |||
|
4. Upon
premature termination or suspension of a trial:
|
21
CFR 312.56 (d); ICH E6 5.21
|
||||
|
a) Notify
FDA
|
x | ||||
|
b) Notify
IRBs or notify investigators of their responsibility to notify
IRBs
|
x | ||||
|
c) Notify
investigators
|
x | ||||
|
d) Assure
disposition of drug from sites to sponsor
|
x | ||||
|
F.
|
Trial
Data Handling and Reporting
|
||||
|
a) Manage
an independent data monitoring committee
|
ICH
E6 5.5.2
|
x | |||
|
b) Data
management
|
ICH
E6 5.5.1
|
x | |||
|
c) Statistical
plan and/or analysis
|
ICH
E6 5.5.1
|
x | x | ||
|
d) Final
study report
|
ICH
E6 5.5.1
|
x | x | ||
|
G.
|
Recordkeeping
and record retention
|
21
CFR 312.57
|
|||
|
1. Maintain
sponsor records and reports during the course of the
investigation
|
21
CFR 312.57 (b), 312.58 (a); ICH E6 5.5.6, 5.5.7, 8
|
x | |||
|
2. Archive
sponsor records and reports according to applicable regulatory
requirements. (Please refer to the contract for specifics of
the records
for which Xxxxxx is responsible.)
|
21
CFR 312.57 (a)(b)(c), 312.58 (a); ICH E6 5.5.8, 5.5.11, 8
|
x |
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
3. Retain
reserve samples of test articles and reference standards used
in
bioequivalence or bioavailability studies
|
21
CFR 312.57 (d); ICH E6 5.14.5(b)
|
x | |||
|
H.
|
Disposition
of unused supply of investigational drug
|
21
CFR 312.59; ICH E6 5.14.4(c)(d), 5.18.4(c)(iv)(v)
|
|||
| x | |||||
|
1. Assure
return of drug from site to Third Party for Drug
Destruction
|
|||||
|
2. Conduct
final disposition or destruction of drug
|
x | ||||
|
I.
|
Application
for FDA approval to export investigational drug
|
21
CFR 312.110; ICH E6 5.14.2
|
|||
|
a) Content
|
x | ||||
|
b) Format
|
x | ||||
|
J.
|
Obtain
investigator financial disclosure information
|
21
CFR 312.53 (c)(4)
|
|||
|
1. Initial
collection prior to study participation
|
x | ||||
|
2. Responsibility
for the one year follow-up financial disclosure collection shall
remain
with the Sponsor (one year following the completion of the
study)
|
x |
The
sponsor hereby transfers to Xxxxxx International Inc. the responsibilities
indicated above under the column titled:
“Obligation
Assigned to Xxxxxx”.
| III. |
Budget
|
A.
Main Project Budget
|
Service
|
Description
|
Unit
Description
|
#Units
|
Average
Unit Cost
|
Total
(USD)
|
|
Study
Documents
|
[***]
|
||||
|
Write
Informed Consent
|
study
start-up
|
1.0
|
[***]
|
[***]
|
|
|
Site
Identification / Essential Document Collection
|
[***]
|
||||
|
Site
Identification
|
#
sites
|
[***]
|
[***]
|
[***]
|
|
|
Collect
and Manage Initial Essential Study Documents (includes QC)
|
#
sites
|
[***]
|
[***]
|
[***]
|
|
|
Collect
and Manage On-going Essential Study Documents (includes
QC)
|
#
site months
|
[***]
|
[***]
|
[***]
|
|
|
IRB
and Ethics Committee Submissions
|
[***]
|
||||
|
Ethics
Committee Submissions
|
#
submissions
|
10.0
|
[***]
|
[***]
|
|
|
Protocol
Amendment
|
#
submissions
|
10.0
|
[***]
|
[***]
|
|
|
End
of Trial Notification
|
#
notifications
|
10.0
|
[***]
|
[***]
|
|
|
Summary
of Study Outcome (1 year after LPO)
|
#
submissions
|
6.0
|
[***]
|
[***]
|
|
|
Clinical
Regulatory
|
[***]
|
||||
|
Regulatory
Submissions
|
#
submissions
|
7.0
|
[***]
|
[***]
|
|
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Drug
label text compliance with local regulatory requirements and translation
into local language
|
#
countries
|
7.0
|
[***]
|
[***]
|
|
|
Protocol
Amendment
|
#
submissions
|
7.0
|
[***]
|
[***]
|
|
|
End
of Trial Notification
|
#
notifications
|
7.0
|
[***]
|
[***]
|
|
|
Summary
of Study Outcome (1 year after LPO)
|
#
submissions
|
7.0
|
[***]
|
[***]
|
|
|
Administration
of Contracts and Payments
|
[***]
|
||||
|
Administer
Investigator Contracts and Budgets
|
#
sites
|
[***]
|
[***]
|
[***]
|
|
|
Administer
Investigator Payments
|
#
payments
|
[***]
|
[***]
|
[***]
|
|
|
Administer
Payments to Central Labs
|
#
payments
|
[***]
|
[***]
|
[***]
|
|
|
Combined
Investigator / Kick-Off Meeting Travel and Attendance
|
[***]
|
||||
|
Investigator
Meeting
|
#
attendees x # meetings
|
22.0
|
[***]
|
[***]
|
|
|
Kick-Off
Meeting
|
#
attendees x # meetings
|
22.0
|
[***]
|
[***]
|
|
|
Investigator
Meeting Planning
|
[***]
|
||||
|
Program
Management Location A - EUR
|
#
meetings
|
1.0
|
[***]
|
[***]
|
|
|
Website
Development and Usage Location A - EUR
|
#
meetings
|
1.0
|
[***]
|
[***]
|
|
|
On-Site
Fees Location A - EUR
|
#
meetings
|
1.0
|
[***]
|
[***]
|
|
|
Program
Management Location B - EUR
|
#
meetings
|
1.0
|
[***]
|
[***]
|
|
|
Website
Development and Usage Location B - EUR
|
#
meetings
|
1.0
|
[***]
|
[***]
|
|
|
On-Site
Fees Location B - EUR
|
#
meetings
|
1.0
|
[***]
|
[***]
|
|
|
Clinical
Monitoring
|
[***]
|
||||
|
Study
Start-Up Activities (includes development of study manual, monitoring
plan
etc. Does not include review of Sponsor SOPs)
|
study
start-up
|
1.0
|
[***]
|
[***]
|
|
|
Pre-study
Site Visit
|
#
visits
|
[***]
|
[***]
|
[***]
|
|
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Initiation
Visit
|
#
visits
|
[***]
|
[***]
|
[***]
|
|
|
Interim
Monitoring Visits (1)
|
#
visits
|
[***]
|
[***]
|
[***]
|
|
|
Unblinded
CRA Visits (2)
|
#
visits
|
[***]
|
[***]
|
[***]
|
|
|
Close-out
Visit
|
#
visits
|
[***]
|
[***]
|
[***]
|
|
|
DRF
Resolution
|
#
DRFs
|
3,039.0
|
[***]
|
[***]
|
|
|
Sponsor
Meetings
|
#
attendees x # meetings
|
8.0
|
[***]
|
[***]
|
|
|
Sponsor
Teleconferences
|
#
attendees x # meetings
|
120.0
|
[***]
|
[***]
|
|
|
Site
Management - LCRA and CSSPEC
|
#
site months
|
1,788.0
|
[***]
|
[***]
|
|
|
Site
Management - CRA
|
#
site months
|
1,786.0
|
[***]
|
[***]
|
|
|
Project
Management
|
[***]
|
||||
|
Project
Management - Project Assistant
|
#
weeks
|
174.0
|
[***]
|
[***]
|
|
|
Project
Management - Project Leader
|
#
weeks
|
174.0
|
[***]
|
[***]
|
|
|
Project
Plan Management
|
#
plans
|
1.0
|
[***]
|
[***]
|
|
|
Newsletters
|
#
letters
|
[***]
|
[***]
|
[***]
|
|
|
Sponsor
Meetings
|
#
attendees x # meetings
|
4.0
|
[***]
|
[***]
|
|
|
Sponsor
Teleconferences
|
#
attendees x # meetings
|
124.0
|
[***]
|
[***]
|
|
|
Clinical
Data Management
|
[***]
|
||||
|
Study
Start-Up Activities (includes defining edit checks, PSOP's and
study
binders)
|
study
start-up
|
1.0
|
[***]
|
[***]
|
|
|
Database
Design (includes programming and mapping)
|
database
|
1.0
|
[***]
|
[***]
|
|
|
Status
Report Repository
|
database(s)
|
2.0
|
[***]
|
[***]
|
|
|
Coding
2 old phase III studies
|
#
codes
|
27,000.0
|
[***]
|
[***]
|
|
|
Data
Coding
|
#
codes
|
27,950.0
|
[***]
|
[***]
|
|
|
Ship
documents to sponsor
|
#
case books
|
741.0
|
[***]
|
[***]
|
|
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Manual
and Electronic Review
|
#
CRF pages
|
60,762.0
|
[***]
|
[***]
|
|
|
Data
Cleaning and Query Processing
|
#
queries
|
3,038.1
|
[***]
|
[***]
|
|
|
Enter
& QC Lab Normal Ranges
|
#
lab normal range(s)
|
1.0
|
[***]
|
[***]
|
|
|
External
Data Loads (includes QC) (Central Labs, IVRS, Fundus )
|
#
loads
|
136.0
|
[***]
|
[***]
|
|
|
Data
Transfer
|
#
transfers
|
3.0
|
[***]
|
[***]
|
|
|
Sponsor
Teleconferences
|
#
attendees x # meetings
|
56.0
|
[***]
|
[***]
|
|
|
Sponsor
Meetings
|
#
attendees x # meetings
|
4.0
|
[***]
|
[***]
|
|
|
Status
Reports
|
#
reports
|
5.0
|
[***]
|
[***]
|
|
|
DSMB
- Prepare, Review and Clean Data
|
#
packets(s)
|
10.0
|
[***]
|
[***]
|
|
|
Data
Archiving to CDROM
|
#
sites
|
[***]
|
[***]
|
[***]
|
|
|
Project
Coordination
|
#
months
|
[***]
|
[***]
|
[***]
|
|
|
Final
QC of key Variables
|
#
CRF pages
|
[***]
|
[***]
|
[***]
|
|
|
Study
Close-Out
|
study
close-out
|
1.0
|
[***]
|
[***]
|
|
|
Imaging
Logistics Tracking
|
#
Faxes
|
8,580.0
|
[***]
|
[***]
|
|
|
Safety
/ Medical Monitoring
|
[***]
|
||||
|
Study
Start-up Activities (includes clinical study orientation, database
set-up,
SAE reporting plan)
|
study
start-up
|
1.0
|
[***]
|
[***]
|
|
|
SAE
Handling/Reporting
|
#
SAEs
|
17.0
|
[***]
|
[***]
|
|
|
Write
SAE Narratives for reporting to Regulatory Authorities
|
#
SAEs
|
17.0
|
[***]
|
[***]
|
|
|
Compose
and distribute Safety Alert Letters
|
#
letters
|
1.0
|
[***]
|
[***]
|
|
|
Prepare
and submit Single Case Safety Report to Regulatory Authorities
and
ECs
|
#
submissions
|
5.0
|
[***]
|
[***]
|
|
|
Prepare
Annual Safety Report according to Directive 2001/20/EC
|
#
reports
|
3.0
|
[***]
|
[***]
|
|
|
Reporting
to DEC / DSMB
|
#
reports
|
[***]
|
[***]
|
[***]
|
|
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Medical
monitoring 24/7
|
#
months
|
32.9
|
[***]
|
[***]
|
||
|
Project
Coordination
|
#
months
|
38.0
|
[***]
|
[***]
|
||
|
Biostatistics
|
[***]
|
|||||
|
Establish
patient compliance and evaluability definitions
|
study
start-up
|
1.0
|
[***]
|
[***]
|
||
|
Program
and QC Analysis (derived) datasets (includes QC of mapped
data)
|
#
datasets
|
1.0
|
[***]
|
[***]
|
||
|
Program
and QC unique/non-unique figures
|
#
figures
|
22.0
|
[***]
|
[***]
|
||
|
Program
and QC unique/non-unique and summary tables
|
#
tables
|
67.0
|
[***]
|
[***]
|
||
|
Program
and QC listings
|
#
listings
|
30.0
|
[***]
|
[***]
|
||
|
Generate
and review TLFs
|
#
reviews
|
3.0
|
[***]
|
[***]
|
||
|
Data
Transfer
|
#
transfers
|
1.0
|
[***]
|
[***]
|
||
|
[***]
|
#
analyses
|
1.0
|
[***]
|
[***]
|
||
|
[***]
|
#
analyses
|
1.0
|
[***]
|
[***]
|
||
|
[***]
|
#
analyses
|
1.0
|
[***]
|
[***]
|
||
|
DSMB
Listings [***]
|
#
reports
|
1.0
|
[***]
|
[***]
|
||
|
Statistical
Input and Review of Final Study Report
|
#
reviews
|
1.0
|
[***]
|
[***]
|
||
|
DSMB
Meetings
|
#
attendees x # meetings
|
10.0
|
[***]
|
[***]
|
||
|
Sponsor
Teleconferences
|
#
attendees x # meetings
|
20.0
|
[***]
|
[***]
|
||
|
Project
Coordination
|
#
months
|
41.0
|
[***]
|
[***]
|
||
|
IT
|
[***]
|
|||||
|
Oracle
Clinical
|
||||||
|
Site
Connectivity
|
#
sites
|
[***]
|
[***]
|
[***]
|
||
|
Site
IT Feasibility
|
#
sites
|
[***]
|
[***]
|
[***]
|
||
|
OC
Setup (Initiation)
|
study
|
1.0
|
[***]
|
[***]
|
||
|
OC
Set-up (Database set up)
|
study
|
1.0
|
[***]
|
[***]
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
OC
Set-up (study configuration)
|
study
|
1.0
|
[***]
|
[***]
|
||
|
IT
Training (Inv meeting)
|
Meetings
|
1.0
|
[***]
|
[***]
|
||
|
First
Line Clinical & Helpdesk Support (set up fee)
|
study
|
1.0
|
[***]
|
[***]
|
||
|
First
Line Clinical & Helpdesk Support (monthly fee)
|
#
site months
|
[***]
|
[***]
|
[***]
|
||
|
Data
Archiving to CDROM
|
#
sites
|
[***]
|
[***]
|
[***]
|
||
|
Logistics
Tracking
|
||||||
|
Setup
Imaging Logistics Support
|
study
|
1.0
|
[***]
|
[***]
|
||
|
Laptop
Build
|
#
laptops
|
[***]
|
[***]
|
[***]
|
||
|
Maintenance/Support
Imaging Logistics
|
#
months
|
[***]
|
[***]
|
[***]
|
||
|
Internet
Hosting
|
#
months
|
[***]
|
[***]
|
[***]
|
||
|
FRC
Data Link
|
||||||
|
FRC
Data Link
|
study
|
1.0
|
[***]
|
[***]
|
||
|
Customised
Study Portal
|
[***]
|
[***]
|
||||
|
Customised
Study Portal (work already performed before service
removed)
|
study
|
1.0
|
[***]
|
[***]
|
||
|
Auto
Generated OC RDC Metrics
|
[***]
|
|||||
|
Auto
Generated OC RDC Metrics
|
project
|
1.0
|
[***]
|
[***]
|
||
|
IVRS
- TriaLine®
|
[***]
|
|||||
|
IT
Development Charges
|
study
start-up
|
1.0
|
[***]
|
[***]
|
||
|
Clinical
Support Center Charges (24/7)
|
#
calls
|
65.0
|
[***]
|
[***]
|
||
|
IT
Support Charges
|
#
months
|
32.9
|
[***]
|
[***]
|
||
|
Password
Mailings
|
study
start-up
|
1.0
|
[***]
|
[***]
|
||
|
IVRS
Technical Manager
|
#
months
|
32.9
|
[***]
|
[***]
|
||
|
IVRS
Non-Labor Costs
|
study
start-up
|
1.0
|
[***]
|
[***]
|
||
|
Medical
Writing
|
[***]
|
|||||
|
Final
study report
|
#
reports
|
1.0
|
[***]
|
[***]
|
||
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Generate
and Compile Appendices (Final report)
|
#
reports
|
1.0
|
[***]
|
[***]
|
|
|
[***]
|
#
reports
|
[***]
|
[***]
|
[***]
|
|
|
[***]
|
#
reports
|
[***]
|
[***]
|
[***]
|
|
|
Quality
Assurance Audits
|
[***]
|
||||
|
Site
Audits
|
#
audits
|
7.0
|
[***]
|
[***]
|
|
|
Data
Management Audit
|
#
audits
|
1.0
|
[***]
|
[***]
|
|
|
Central
Lab Audit
|
#
audits
|
1.0
|
[***]
|
[***]
|
|
|
Clinical
Report Audit
|
#
audits
|
1.0
|
[***]
|
[***]
|
|
|
Drug
Compliance Audit
|
#
audits
|
1.0
|
[***]
|
[***]
|
|
|
Document
Management
|
[***]
|
||||
|
Document
Management
|
#
site months
|
1,621.5
|
[***]
|
[***]
|
|
|
TrialWeb
|
[***]
|
||||
|
Provide
TrialWeb
|
study
start-up
|
1.0
|
[***]
|
[***]
|
|
|
Patient
Access Consultancy
|
[***]
|
||||
|
Group
Contacts
|
#
countries
|
7.0
|
[***]
|
[***]
|
|
|
Set-Up
GP Referrals
|
#
countries
|
7.0
|
[***]
|
[***]
|
|
|
Retention
Plan
|
#Countries
x # Telecons
|
20.0
|
[***]
|
[***]
|
|
|
Patient
Recruitment Co-Ordination
|
#
site months
|
[***]
|
[***]
|
[***]
|
|
|
Professional
Fees Total
|
[***]
|
||||
|
Pass-Through
Estimates **
|
[***]
|
||||
|
Investigator
Meeting Costs Location A - Invitations - EUR
|
#
meetings
|
1.0
|
[***]
|
[***]
|
|
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
Investigator
Meeting Costs Location A - Air/Ground Transportation - EUR
|
#
meetings
|
1.0
|
[***]
|
[***]
|
|
|
Investigator
Meeting Costs Location A - On-Site Logistics (hotel accommodations,
meals,
visuals etc.) - EUR
|
#
meetings
|
1.0
|
[***]
|
[***]
|
|
|
Investigator
Meeting Costs Location B - Invitations - EUR
|
#
meetings
|
1.0
|
[***]
|
[***]
|
|
|
Investigator
Meeting Costs Location B - Air/Ground Transportation - EUR
|
#
meetings
|
1.0
|
[***]
|
[***]
|
|
|
Investigator
Meeting Costs Location B - On-Site Logistics (hotel accommodations,
meals,
visuals etc.) - EUR
|
#
meetings
|
1.0
|
[***]
|
[***]
|
|
|
Pre-Study
Site Visit Travel
|
#
trips
|
[***]
|
[***]
|
[***]
|
|
|
Initiation
Visit Travel
|
#
trips
|
[***]
|
[***]
|
[***]
|
|
|
Monitoring
Visit Travel
|
#
trips
|
[***]
|
[***]
|
[***]
|
|
|
Close-out
Visit Travel
|
#
trips
|
[***]
|
[***]
|
[***]
|
|
|
Site
Audit Travel
|
#
trips
|
7.0
|
[***]
|
[***]
|
|
|
Central
Lab Audit Travel
|
#
trips
|
1.0
|
[***]
|
[***]
|
|
|
Sponsor
Meeting Travel
|
#
trips
|
8.0
|
[***]
|
[***]
|
|
|
Technical
Meeting Travel
|
#
trips
|
10.0
|
[***]
|
[***]
|
|
|
Initial
Ethics Committee Approval Fees
|
#
approvals
|
10.0
|
[***]
|
[***]
|
|
|
Regulatory
Approval Fees
|
#
submissions
|
7.0
|
[***]
|
[***]
|
|
|
Central
Lab Fees
|
project
|
1.0
|
[***]
|
[***]
|
|
|
Study
Document Translation
|
#
translations
|
7.0
|
[***]
|
[***]
|
|
|
Regulatory
Document Shipment
|
#
sites
|
[***]
|
[***]
|
[***]
|
|
|
Final
Document Shipment to Sponsor
|
#
shipments
|
1.0
|
[***]
|
[***]
|
|
|
Drug
Management - 3rd party vendor bid
|
study
|
1.0
|
[***]
|
[***]
|
|
|
OC
RDC - Hardware
|
laptops
|
[***]
|
[***]
|
[***]
|
|
|
Local
Insurance (not all countries, some covered by Global Insurance)
Ranges
from [***]
|
#
patients
|
[***]
|
[***]
|
[***]
|
|
|
Device
Importation Tax [***]
Range
of 18-35% VAT and Taxes Of Declared Value
|
#
countries
|
4.0
|
[***]
|
[***]
|
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
[***]
|
#
randomised patients
|
[***]
|
[***]
|
[***]
|
|
|
[***]
|
#
sites
|
[***]
|
[***]
|
[***]
|
|
|
Proposed
average Investigator Grant - screen failures (see project assumptions
for
details)
|
#
screen failures
|
[***]
|
[***]
|
[***]
|
|
|
Slit
lamps
|
#
lamps
|
[***]
|
[***]
|
[***]
|
|
|
Broadband
(3 year contracts)
|
#
sites
|
35.0
|
[***]
|
[***]
|
|
|
ETDRS
|
#
sites
|
24.0
|
[***]
|
[***]
|
|
|
Contact
lenses
|
#
sites
|
[***]
|
[***]
|
[***]
|
|
|
Courier
Costs (Disks and Photographs) based on 0.5KG
|
shipments
|
8,580.0
|
[***]
|
[***]
|
|
|
Proposed
average Investigator Grant - dropped patients (see project assumptions
for
details)
|
#
dropped patients
|
81.0
|
[***]
|
[***]
|
|
|
Proposed
average Investigator Grant - completed patients (see project assumptions
for details)
|
#
completed patients
|
660.0
|
[***]
|
[***]
|
|
|
Grand
Total
|
[***]
|
||||
**
Estimates. Actual expenses will be billed as pass-through.
Additional
work by Xxxxxx, undertaken at the written request of the Sponsor, or the
Sponsor's failure to communicate all relevant policies and procedures on
a
timely basis or modifications of such policies and procedures once work has
begun, will result in charges over and above the stated contract amounts
at
Xxxxxx'x hourly rates.
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
B.
Time and Materials Budget
Biostatistics
and Medical Writing- For the ISE/ISS Miravant will be charged as a time and
material at the current billing rate of the Xxxxxx associate performing the
tasks. If Miravant require a costing for this task then additional information
will have to be obtained.
Regulatory-
For Regulatory consultancy, strategic development plan, FDA submission of
any
protocol amendments, Investigator brochure update, IND supplement, IND report,
ND and PMA applications these will be charged as a time and material at the
current billing rate of the Xxxxxx associate performing the tasks. If Miravant
require a costing for these tasks then additional information will have to
be
obtained from Miravant on your requirements.
Regulatory/Medical
Writing - Update of XX
Xxxxxx
2005 rates based on the current exchange rate are:
[***]
The
Xxxxxx rates referenced are applicable for 2005 only. Activities completed
in
later years will be subject to inflation.
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
| IV. |
Schedule
of Payments
|
| A. |
Main
Budget Payments for Xxxxxx Fees
|
|
Date
|
Milestone
|
Milestone
%
|
Monthly
%
|
Total
%
|
Amount
|
Accumulated
Total $
|
|
[***]
|
[***]
|
[***]
|
0.00%
|
4.66%
|
[***]
|
[***]
|
|
[***]
|
|
|
0.00%
|
0.00%
|
[***]
|
[***]
|
|
[***]
|
|
|
0.00%
|
0.00%
|
[***]
|
[***]
|
|
[***]
|
[***]
|
[***]
|
1.67%
|
7.00%
|
[***]
|
[***]
|
|
[***]
|
[***]
|
[***]
|
1.67%
|
11.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
[***]
|
[***]
|
1.67%
|
9.17%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
[***]
|
[***]
|
1.67%
|
6.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
[***]
|
[***]
|
1.67%
|
6.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
0.00%
|
0.00%
|
[***]
|
[***]
|
|
[***]
|
[***]
|
[***]
|
0.00%
|
2.50%
|
[***]
|
[***]
|
|
|
[***]
|
40.00%
|
60.00%
|
100.00%
|
[***]
|
|
|
These
milestones have been compiled based on a 30 day invoicing term.
Should
invoicing terms exceed 30 days these milestones will be revised
accordingly.
|
||||||
*
[***]
|
Date
|
Milestone
|
Milestone
%
|
Monthly
%
|
Total
%
|
Amount
|
Accumulated
Total $
|
|
[***]
|
[***]
|
0.00%
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
|
|
1.67%
|
1.67%
|
[***]
|
[***]
|
|
[***]
|
[***]
|
[***]
|
1.67%
|
5.17%
|
[***]
|
[***]
|
|
[***]
|
|
|
0.00%
|
0.00%
|
[***]
|
[***]
|
|
[***]
|
[***]
|
[***]
|
0.00%
|
4.00%
|
[***]
|
[***]
|
|
|
TOTAL
|
40.00%
|
60.00%
|
100.00%
|
[***]
|
|
All
other
milestone and monthly payments will remain as per the main budget payments
table.
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
| B. |
Time
and Materials Payments
|
Xxxxxx
will invoice monthly for actual services performed in the previous month
at the
rates in the Time and Materials Budget.
All
Xxxxxx fees invoices will be paid within 30 days of receipt of
invoice.
C.
Estimated Pass Through Expenses
Xxxxxx
will invoice for pass through expenses as incurred, invoices
will be sent to Miravant by email and post with supporting
receipts.
Supplier
invoices and investigators will not be paid by Xxxxxx until funds have been
received from Miravant to cover these costs.
All
pass through expense invoices will be payable immediately upon receipt of
invoice.
D.
Currency Exchange Rate Fluctuation
1.
Since
pricing and subsequent invoicing are denominated in U.S. dollars while at
least
a portion of expenditure on the services provided will arise in (one or more
different currencies), and the contract pricing totals do not include a margin
to cover currency exchange rate fluctuations (“CERF”), the parties agree to
review CERF’s every three months throughout the term of this Task Order in
accordance with this Section V.
2.
The
contract pricing is based on the following exchange rates: 1
US $ to 0.7711
Euro
and 1 US $ to £ 0.5387.
Provided
no currency in which expenditure occurs increases or decreases by more than
3%
with respect to the US Dollar, the review will conclude that no adjustment
to
the original pricing is required in relation to the services provided to
that
date. Exchange
rates are based on average monthly rates taken from the Wallstreet Journal
or
similar source.
3.
Where
a CERF between the U.S. dollar and any other currency of expenditure exceeds
3%,
one party will have the potential for gain and the other will have the potential
for unacceptable and unintentional loss. Both parties agree that where this
occurs it will be necessary to adjust the pricing of the services to eliminate
any loss which would otherwise be incurred by the CRO or Sponsor through
no
fault of either party.
4.
Sponsor agrees that if a CERF produces an unscheduled loss not specifically
included in the contract price, Sponsor will agree to a positive price
adjustment (i.e. a payment to the CRO) in relation to the services affected,
with the effect of offsetting this loss in its entirety.
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
The
CRO
agrees that if a CERF produces an unscheduled gain not included in the contract
price, the CRO will agree to a negative price adjustment (i.e. a reduction
in
price) in relation to the services affected, with the effect of offsetting
this
gain in its entirety. In the calculation of the adjustments referred to above,
the % CERF will be multiplied by the proportion of service pricing that is
denominated in the currencies that have been subject to the CERF, and these
services will then be invoiced at the adjusted prices until reviewed by the
parties.
AGREED
TO AND ACCEPTED BY
Xxxxxx
International Inc. Miravant
Pharmaceuticals, Inc.
By:
/s/ Xxxx Xxxxxxxx By:
/s/ Xxxx X. Xxxxxxxx
Name:
Xxxx Xxxxxxxx Name: Xxxx
X.
Xxxxxxxx
Title:
Sr. Vice President & CFO Title:
Chief Financial Officer
Date: June
14,
2005 Date:
June 14, 2005
