Work Order #1 Dated November 9, 2007
Work
Order #1
Dated
November 9, 2007
The
services described herein will be provided in accordance with the terms and
conditions of the Master Services Agreement, dated August 24, 2007, between
AAIPharma Inc., on behalf of itself and its subsidiaries (collectively,
‘AAIPharma’) and YM Biosciences USA Inc. (hereinafter referred to as “YMB
USA”).
The
following documents are attached to this Work Order and shall be incorporated
herein:
|
Attachment I
|
Final
Scope of Work, including the description of Services to be provided
and
timeline
|
|
Attachment II
|
Budget
and Payment Terms for the Final Scope of
Work
|
All
terms
and conditions provided in the Master Services Agreement executed by the parties
with an Effective Date of August 24, 2007 remain unmodified and in full force
and effect.
ACKNOWLEDGED,
ACCEPTED AND AGREED TO:
AAIPharma
Inc.
|
Signature
|
Date
|
|
|
Name
|
||
|
Title
|
YM
Biosciences USA Inc.
|
/s/
Xxxxx X.X. Xxxxx
|
[ILLEGIBLE]
|
|
|
Signature
|
Date
|
|
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Xxxxx
X.X. Xxxxx
|
||
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Name
|
||
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CHAIR
& CEO
|
||
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Title
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ATTACHMENT
I to Work Order #1
Final
Scope of Work
Protocol
No. YMB USA1000/009
entitled
“Phase II Study of Safety and Efficacy of Nimotuzumab
(TheraCIM®) In Pediatric Patients with Recurrent Diffuse Intrinsic Pontine
Glioma”
SCOPE
OF WORK:
|
·
|
Project
Management (USA)
|
·
|
Medical
Monitoring (USA)
|
|
|
·
|
Clinical
Monitoring (USA)
|
·
|
Pharmacovigilance
(inc OC AERS set-up/maintenance)
|
|
|
·
|
Data
Management
|
·
|
Medical
Writing
|
|
|
·
|
Biostatistics
|
·
|
Clinical
Trial Material Distribution (USA)
|
STUDY
PARAMETERS:
| PARAMETERS: | |
|
Number
of Completed Patients:
|
44
|
|
(30
USA patients)
|
|
|
Number
of Investigative Sites:
|
[*]
|
|
(
[*]
USA)
|
|
|
Estimated
Number of Total CRF Pages Per Patient:
|
150
|
|
Estimated
Number of Unique CRF Pages Per Patient:
|
25
|
|
Total
Number of CRF Pages:
|
6,600
|
|
Estimated
Number of Queries:
|
1,320
|
|
Total
Number of Serious Adverse Events:
|
[*]
|
|
Total
Number of Face-to-Face Project Meetings
(alternating
between AAIPharma and YMB USA):
|
4
with PM
2
with Team
|
|
Total
Number of Teleconferences:
|
47
with PM/RA (24 inc. Team)
|
|
USA
SITES
|
|
|
Total
Number of Qualification Site Assessment (QSA)
|
|
|
Visits:
|
To
be performed during Initiation Visit
|
|
Total
Number of Initiation Visits:
|
8
|
|
Total
Number of Interim Visits:
|
Average
5 two-day Visits per site
|
|
Total
Number of Closeout Visits:
|
8
|
|
Total
Number of Tables:
|
30
|
|
Total
Number of Listings:
|
25
|
|
Total
Number of Figures:
|
5
|
|
Total
Number of Outputs:
|
5
|
|
AAIPharma/YMB
USA Work Order #1 R3
|
Page
1 of 5
|
|
Attachment
I
|
|
TIMELINE
| TIME LINE | |
|
Project
Award (LOI executed):
|
August
27, 2007
|
|
Study
Start-up:
|
3
months
|
|
Patient
Enrollment Duration:
|
14
months
|
|
Patient
Treatment Duration:
|
Up
to 4.5 months (18 weeks)
|
|
Follow-up
Duration:
|
Up
to 4 months
|
|
Database
Lock:
|
1
month after last CRF in-house
|
|
Draft
Tables, Listings and Figures1:
|
3
Weeks from Database Lock
|
|
Final
Tables, Listings and Figures1:
|
2
Weeks from Receipt of YMB USA’s
Comments
|
|
Draft
Report1:
|
4
Weeks from Final Tables, Listings and Figures
|
|
Final
Report1:
|
2
Weeks from Receipt of YMB USA’s Comments
|
|
TOTAL
PROJECT DURATION
|
29
months
|
1Assumes
an optimized collaborative process between AAIPharma and YMB USA during
statistical analysis, results reviews, and report planning and
generation.
TASK
OWNERSHIP
Study
Setup (services to achieve the “First Patient Enrolled”
milestone)
|
Service
|
YMB
USA
Responsibility
|
AAIPharma
Responsibility
|
||
|
Kickoff
Meeting
|
ü
|
ü
|
||
|
Prepare
Project Operational Plan (POP)
|
ü
|
|||
|
CRF
Design
|
ü
|
|||
|
CRF
Printing and Shipping
|
ü
|
|||
|
Develop
Model Informed Consent Form
|
ü
|
|||
|
Investigator
Selection
|
ü
|
|||
|
Conduct
Qualifying Site Assessment Visits (USA Sites)
|
Performed
at
Initiation
Visit
|
|||
|
Collect/Review
Regulatory Documents (USA Sites)
|
ü
|
|
AAIPharma/YMB
USA Work Order #1 R3
|
Page
2 of 5
|
|
Attachment
I
|
| Service |
YMB
USA
Responsibility
|
AAIPharma
Responsibility
|
||
|
Maintain
Trial Master File (USA Sites)
|
ü
|
|||
|
File
Regulatory Documents with FDA
|
ü
|
|||
|
Coordinate
Investigational Product Packaging/Shipping
|
ü
|
US
Sites
|
||
|
· Client
will provide ready-to distribute clinical supplies
|
||||
|
· storage
at
2-8C
|
||||
|
· Distribution
performed at 2-8C w/ temperature monitoring required
|
||||
|
· Drug
return
activities and destruction not required
|
||||
|
Assist
sites with IRB requirements
|
ü
|
|||
|
Negotiate
Site Agreements
|
ü
|
|||
|
Execute
Site Agreements
|
ü
|
|||
|
Plan
and Coordinate Investigators’ Meeting
|
ü
|
|||
|
Attend
Investigators’ Meeting
|
ü
|
ü
|
||
|
5
attendees
|
||||
|
Attend
Training Meeting
|
ü
|
ü
|
||
|
Conduct
Initiation Visits with Medical Monitor
|
US
Sites
|
|||
|
Develop
Monitor Guidelines and Source Document Verification Plan
(SDVP)
|
ü
|
|||
|
Database
Design
|
ü
|
|||
|
Data
Management Operational Plan (DMOP)
|
ü
|
|||
|
Generate
Statistical Analysis Plan
|
ü
|
Ongoing
Study Management (Services from First Patient Enrolled through Database
Lock)
| Service |
YMB
USA
Responsibility
|
AAIPharma
Responsibility
|
||
|
Provide
Interim Monitoring Visits (USA Sites)
|
ü
|
|||
|
Provide
Ongoing Site Management Services (USA
|
ü
|
|||
|
Sites)
|
||||
|
Administer
Payments of Investigator Grants
|
ü
|
|||
|
Provide
Status Reports to YMB USA
|
ü
|
|||
|
Provide
Medical Management (USA)
|
ü
|
|||
|
Set-up
and Maintain Oracle AERS Database
|
ü
|
|||
|
Provide
SAE Management
|
ü
|
|||
|
Preparation
of SAE narratives
|
ü
|
|
AAIPharma/YMB
USA Work Order #1 R3
Attachment
I
|
Page
3 of 5
|
| Service |
YMB
USA
Responsibility
|
AAIPharma
Responsibility
|
||
|
Filing
of SAE Reports with the FDA
|
ü
|
|||
|
Participate
in Project Team Meetings
|
ü
|
ü
|
||
|
Participate
in Teleconferences
|
ü
|
ü
|
||
|
Provide
Quality Assurance Site Audits
|
ü
|
|||
|
CRF
and Query Scanning, Tracking, and Storage
|
ü
|
|||
|
Data
Entry
|
ü
|
|||
|
Data
Verification
|
ü
|
|||
|
Integration
of External Electronic Data
|
ü
|
|||
|
Data
Validation
|
ü
|
|||
|
Data
Coding
|
ü
|
|||
|
SAE
Report Reconciliation against CRF Data
|
ü
|
|||
|
Database
Quality Control Audit
|
ü
|
|||
|
Provide
Clean, Locked Database to YMB USA
|
ü
|
|||
|
Quality
Assurance Site Audits
|
ü
|
|||
|
Optional
|
||||
|
Advance
Planning for Study Report
|
ü
|
ü
|
|
AAIPharma/YMB
USA Work Order #1 R3
|
Page
4 of 5
|
|
Attachment
I
|
Study
Closeout Services (Services from Database Lock to final
Deliverable)
| Service |
YMB
USA
Responsibility
|
AAIPharma
Responsibility
|
||
|
Conduct
Study Closeout Visits (USA Sites)
|
ü
|
|||
|
Generate
Statistical Tables, Listings, and Figures
|
ü
|
|||
|
Attend
Results Review Meeting
|
ü
|
ü
|
||
|
Generate
Draft Clinical Study Report (CSR)
|
ü
|
|||
|
Comment
on Draft CSR
|
ü
|
|||
|
Finalize
Clinical Study Report
|
ü
|
|||
|
Prepare
and Transfer SAS Code
|
ü
|
|||
|
Study
Closeout Meeting
|
ü
|
ü
|
|
AAIPharma/YMB
USA Work Order #1 R3
Attachment
I
|
Page
5 of 5
|
ATTACHMENT
II to Work Order #1
Budget
and Payment Terms for the Final Scope of Work
ESTIMATED
BUDGET
[Intentionally
Left Blank]
|
AAIPharma/YMB
USA Work Order #1 R2
|
|
|
Attachment
II
|
ESTIMATED
BUDGET
YM
Biosciences - 07-138.R3 dated November 8, 2007
#Sites
#CRFs
|
44
|
Total
Enrolled Patients
|
|
|
30
|
Total
US Patients
|
|
|
8
|
US
Sites
|
|
|
6,600
|
Total
CRF Pages
|
|
|
29
|
Months
Study Duration
|
|
ESTIMATED
BUDGET
|
|||||||
|
PROJECT
MANAGEMENT
|
[*]
|
||||||
|
PROJECT
COORDINATION (29 months)
|
[*]
|
||||||
|
PROJECT
MEETINGS AND CONFERENCE CALLS
|
[*]
|
||||||
|
STUDY
SETUP
|
[*]
|
||||||
|
REGULATORY
DOCUMENT COLLECTION AND PROCESSING
|
[*]
|
||||||
|
PROJECT
TEAM TRAINING AND KICK-OFF MEETING
|
[*]
|
||||||
|
INVESTIGATORS
MEETINGS (US Sites Face-to-Face)
|
|||||||
|
ATTENDANCE
& PARTICIPATION
|
[*]
|
||||||
|
COORDINATION
FEE
|
[*]
|
||||||
|
CRF
DESIGNS AND INSTRUCTIONS
|
[*]
|
||||||
|
ADMINISTRATION
& PAYMENT OF LABORATORY
|
[*]
|
||||||
|
ADMINISTRATION
OF INVESTIGATOR GRANTS
|
[*]
|
||||||
|
CLINCAL/MEDICAL
AFFAIRS
|
[*]
|
||||||
|
QSA/INITIATION
VISITS (8)
|
[*]
|
||||||
|
MEDICAL
MONITOR TO ATTEND QSA/INITIATION VISITS
|
[*]
|
||||||
|
INTERIM
MONITORING VISITS (Average 5 two-day visits per site)
|
[*]
|
||||||
|
CLOSEOUT
VISITS (8)
|
[*]
|
||||||
|
STATUS
REPORTS
|
[*]
|
||||||
|
MEDICAL
MANAGEMENT
|
[*]
|
||||||
|
SAE
MANAGEMENT SET-UP AND MAINTENANCE (Oracle AERS)
|
[*]
|
||||||
|
SAE
MANAGEMENT
|
[*]
|
||||||
|
SAE
NARRATIVES (Includes MedWatch/CIOMS reports)
|
[*]
|
||||||
|
SITE
MANAGEMENT
|
[*]
|
||||||
|
CLINICAL
REGULATORY SITE SUPPORT
|
[*]
|
||||||
|
CLINICAL
PROJECT COORDINATION
|
[*]
|
||||||
|
DATA
MANAGEMENT & CLINICAL DATA SYSTEMS
|
[*]
|
||||||
|
DATA
MANAGEMENT OPERATIONAL PLAN
|
[*]
|
||||||
|
DATABASE
DESIGN, PROGRAMMING AND TESTING
|
[*]
|
||||||
|
DATA
ENTRY AND VERIFICATION
|
[*]
|
||||||
|
DICTIONARY
CODING
|
[*]
|
||||||
|
CRF
AND QUERY TRACKING & INVENTORY VIA SCANNING
|
[*]
|
||||||
|
DATA
VALIDATION INCLUDING QUERY GENERATION & RESOLUTION
|
[*]
|
||||||
|
MEDICAL
REVIEW OF CRFs
|
[*]
|
||||||
|
DATABASE
QUALITY CONTROL AUDIT
|
[*]
|
||||||
|
EXTERNAL
DATA INTEGRATION
|
[*]
|
||||||
|
DATA
MANAGEMENT PROJECT COORDINATION
|
[*]
|
||||||
|
ADMINISTRATIVE
|
[*]
|
||||||
|
BIOSTATISTICAL/REPORT
PREPARATION SERVICES
|
[*]
|
||||||
|
STATISTICAL
ANALYSIS PLAN
|
|
|
[*]
|
|
|
|
|
|
STATISTICAL
TABLES, LISTINGS & PROGRAMMING
|
|
|
[*]
|
|
|
|
|
|
ANALYSIS
PRODUCTION
|
|
|
[*]
|
|
|
|
|
|
INTEGRATED
CLINICAL/STATISTICAL REPORT
|
|
|
[*]
|
|
|
|
|
|
RESULTS
REVIEW MEETING
|
|
|
[*]
|
|
|
|
|
|
BIOSTATISTICAL/REPORT
PROJECT COORDINATION
|
|
[*]
|
|||||
|
TOTAL
ESTIMATED BUDGET
|
[*]
|
||||||
|
ADDITIONAL
SERVICES
|
|||||||
|
CLINICAL
TRIAL MATERIAL DISTRIBUTION TO US SITES
|
[*]
|
||||||
|
TOTAL
ESTIMATED BUDGET EXCLUSIVE OF PASS THROUGH
EXPENSES
|
[*]
|
||||||
|
ESTIMATED
PASS THROUGH EXPENSES
|
|
|
|
|
|
[*]
|
|
|
INVESTIGATOR
MEETING (incidentals @$100/attendee)
|
|
|
[*]
|
|
|
|
|
|
MONITOR
TRAVEL
|
|
|
[*]
|
|
|
|
|
|
MEDICAL
MONITOR TRAVEL (8 VISITs)
|
|
|
[*]
|
|
|
|
|
|
CRF
PRINTING AND SHIPPING
|
|
|
[*]
|
|
|
|
|
|
PROJECT
MEETING EXPENSES
|
|
|
[*]
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
TOTAL
ESTIMATED BUDGET
|
|
|
[*]
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
OPTIONAL
COSTS
|
|
|
|
|
|
|
|
|
CLINICAL
INTERIM MONITORING
|
|
|
|
|
|
|
|
|
ADDITIONAL
VISIT PER PATIENT (From 1 to 2 Visits per Patient)
|
|
|
[*]
|
|
|
|
|
|
SITE
VISIT TRAVEL
|
|
|
[*]
|
|
|
|
|
|
QUALITY
ASSURANCE
|
|
|
|
|
|
|
|
|
INVESTIGATOR
SITE VISITS
|
|
|
[*]
|
|
|
|
|
|
SITE
VISIT TRAVEL
|
|
|
[*]
|
|
|
||
AAIPharma/YMB
USA Work Order #1 R2
Attachment
II
Payment
Schedule
YM
Biosciences
YMB1000/009
|
First
Budget
|
||||
|
Direct
Costs:
|
USD
|
|||
|
Execution
of WorkOrder
|
$ |
[*]
|
||
|
Milestones:
|
||||
|
Monthly
Maintence Fee (Project Management, Site Management, PVG, QA and Medical
Overview)
|
||||
|
$[*]month
for [*]
months (Sept-07-Jan-07)
|
$ |
[*]
|
||
|
Clinical:
|
||||
|
Completion
of Base Documents
|
$
|
[*]
|
||
|
First
Site Initiated
|
$
|
[*]
|
||
|
100%
Sites Initiated
|
$
|
[*]
|
||
|
First
Patient Enrolled
|
$
|
[*]
|
||
|
20%
Monitoring Visits Completed
|
$
|
[*]
|
||
|
40%
Monitoring Visits Completed
|
$
|
[*]
|
||
|
60%
Monitoring Visits Completed
|
$
|
[*]
|
||
|
80%
Monitoring Visits Completed
|
$
|
[*]
|
||
|
100%
Monitoring Visits Completed
|
$
|
[*]
|
||
|
All
Sites Closed-out
|
$
|
[*]
|
||
|
Database
Set-Up
|
$
|
[*]
|
||
|
50%
CRFs Completed
|
$
|
[*]
|
||
|
100%
CRFs Completed
|
$
|
[*]
|
||
|
Database
Lock
|
$
|
[*]
|
||
|
Clinical
Study Report
|
$
|
[*]
|
||
|
Total
Direct Costs
|
$
|
[*]
|
||
Attachment
II
