CHANGE ORDER FORM
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PHARM-OLAM
International
Ltd
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CO#1
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CHANGE
ORDER FORM
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This
Change Order 1 “CO1” is hereby incorporated into the terms and conditions of the
Clinical Research Services Agreement dated 04 December 2005 (hereinafter
referred to as the “Agreement”) by and between Pharm-Olam International (UK)
Limited, (hereinafter referred to as “POI”) and Advaxis, Inc, (hereinafter
referred to as “Client”).
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Date:
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13
December 2006
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Change
Requested by:
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Xxxxxx
Xxxxx
(POI
Project Manager)
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Customer
Name:
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Customer
Address:
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000
Xxxxxxxx Xxxxxx
Xxxxx
000 Xxxxxxxx
Xxx
Xxxxxx 00000
XXX
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Protocol
Title:
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A
Phase 1 Open Dose Escalation Study to Determine the Safety and
Immunogenicity of Vaccination with Listeria
monocytogenes
expressing Human Papilloma Virus type 16 E7 (Lovaxin-C) for the
Treatment
of Progressive, Recurrent and Advanced Squamous Cell Cancer of
the
Cervix
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Protocol
Number:
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Lm-LLO-E7-01
(POI Study# 319)
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Description
of Change Order
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The
original contract was for 2 sites in Serbia and 1 in Mexico. The
actual
sites POI has are 1 site in Serbia and 2 in sites Mexico. In addition,
there have been 5 protocol amendments and one Investigator Brochure
update. In addition, the timelines have been extended by 4.5 months
with
the estimated completion date revised to 15 October 2006. The out
of scope
services associated with this change are described below:
1. Identification
of 2 additional sites in Mexico
2. Protocol
Review for additional site in Mexico
3. Translations
of submission and approval documents and additional PIL
4. Preparation
of Investigator Source Document Notebook
5. Review
of AML lab manual (for the Israeli central lab)
6. Listeria
quantification procedure - preparation (review and amending of
procedure, TC with microbiologists from Serbia and
Israel)
7. HPV
and Flow cytometry procedure - preparation
8. PM
time for original SEVs reduced from 3 days to 2 days
9. 2
SEVs for additional sites in Mexico
10. Reduction
in cost for initial SEVs due to change in responsibility
assumptions
11. Reduction
in costs for initial EC and MoH submissions due to change in
assumptions
12. Translations
and back translation of additional PIF
13. Regulatory
submission of 5 protocol amendments in 2 countries
14. EC
submissions of 5 protocol amendments at 3 study sites
15. Translations
of approvals for 5 amendments
16. Initial
EC submissions for additional sites
17. MoH
submission for additional sites
18. Import
licenses for additional sites
19. Monitoring
guidelines writing
20. Reduction
in Investigator/Hospital contracts due to a change in
assumptions
21. Insurance
negotiation and agreement
22. First
drug re-labeling at all sites
23. Second
drug re-labeling at all sites
24. CRA
and CTA time included for attendance at weekly teleconferences
with
Sponsor for 11 months
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Effective
01 February 2006
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PHARM-OLAM
International
Ltd
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CO#1
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CHANGE
ORDER FORM
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25. SAE
narrative preparation and CIOMS form preparation for 10 SAEs
26. Project
management time increased from 1 to 1.5 days per week for the
first 48
weeks and the additional 6 months extended study duration
27. Medical
Writing - five amendments to the protocol
28. Medical
Writing - one IB update
29. Writing
of drug re-allocation
procedure
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Study
Timelines:
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Event
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Date
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POI
Study Start Date
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Completed
Aug 2005
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Protocol
Completion and Investigator Brochure
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Completed
Oct 2005
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Submitting
Request for Special Protocol Assessment Meeting with FDA
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Completed
Aug 2006
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Special
Protocol Assessment Meeting with FDA
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Completed
Aug 2006
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Submit
to Ethics Committee and Regulatory Authority, Mexico and
Serbia
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Completed
Dec 2005
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Approval
Serbia
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Completed
Feb 2006
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Approval
Mexico
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Completed
Feb 2006
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First
Patient into Study, Serbia
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Completed
16 March 2006
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Last
Patient into Study
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01
May 2007
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Last
Patient out of Study
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01
September 2007
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Close
Database
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15
September 2007
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Statistical
Analysis Complete
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30
September 2007
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Study
Draft Final Report
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15
October 2007
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Estimated
Costs:
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Contract
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Original
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CO1
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Revised
Total
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Price
(US$)
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$430,000
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$92,000
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$522,000
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Effective
01 February 2006
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PHARM-OLAM
International
Ltd
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CO#1
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CHANGE
ORDER FORM
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Payment
Schedule:
Reimbursement
for the POI services outlined in this Project Change Order will be paid to
POI
according to the following schedule:
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Item
#
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Milestone
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%
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Amount
in USD ($)
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1
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At
execution of Clinical Research Services Agreement
(Already
Invoiced)
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8.24
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43,000
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2
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Upon
Protocol and IB Completion
(Already
Invoiced)
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8.24
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43,000
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3
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Upon
Minister of Health Approval in Both Countries
(Already
Invoiced)
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12.36
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64,500
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4
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10
patients in
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20.00
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104,400
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5
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Last
patient in
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20.00
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104,400
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6
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Last
patient out
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15.58
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81,350
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7
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Signed
final report
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15.58
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81,350
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Total
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100
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522,000
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POI
shall
submit invoices to the sponsor for each payment in accordance with the payment
schedule outlined above. Pass-through expenses will be invoiced to the sponsor
as made by POI. All other terms and conditions according to the Agreement
shall
remain in full force and effect.
Sponsor
hereby authorises commencement of the tasks set forth above according to
the
estimated costs and payment schedule stated above.
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Pharm-Olam
International Ltd
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Sponsor
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Accepted
by:
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Accepted
by:
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Name:
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Name:
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Title:
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Title:
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Date:
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Date:
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Effective
01 February 2006
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