Exhibit 10.30

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

 

Work Order 1

 

INS-212

 

Insmed Incorporated  -  SynteractHCR, Inc.

 

Work Order 1

 

Comprehensive Services for:

 

Protocol INS-212: A Randomized, Open-Label, Multicenter Study of Liposomal
Amikacin for Inhalation (LAI) in Adult Patients with Nontuberculous
Mycobacterial (NTM) lung infections caused by Mycobacterium avium complex (MAC)
that are refractory to treatment

 

Table of Contents

 

1

Incorporation

2

2

Statement of Services

2

3

Project Specifications

8

4

Miscellaneous

19

4.1

Backup and Security

19

4.2

Language

19

5

Project Costs

20

5.1

Assumptions

20

5.2

Summary Cost Estimates

27

5.3

Pass-Through Costs

28

5.4

Payment Terms

29

5.5

Change in Scope

30

5.6

Invoices and Payment Correspondence

30

Attachment 1: Detailed Budget

32

 

1

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

 

Work Order 1

 

INS-212

 

INSMED INCORPORATED — SYNTERACTHCR

 

WORK ORDER 1

 

COMPREHENSIVE SERVICES

 

1                      Incorporation

 

This Work Order 1 is made and entered on 24 December 2014 (“Effective Date”)
between Insmed Incorporated (“Sponsor”) and SynteractHCR, Inc. (“SynteractHCR”).
Unless specifically stated otherwise in this Work Order 1, the Master Agreement
for Services, signed on 27 August 2014 between Sponsor and SynteractHCR shall
govern the provision of services set forth in this Work Order 1 for
comprehensive clinical trial services in support of Sponsor’s protocol INS-212.

 

2                      Statement of Services

 

The table below describes the activities (“Services”) that would be performed
for this study as detailed in this Work Order 1. This Work Order 1 with any
incorporated Work Order Amendments will collectively hereinafter be referred to
as the “Project”.

 

Sponsor: Insmed

 

Study ID:  INS-212

 

Services Checklist & Transfer of Obligations

X=Responsibility (Primary); (X)=Responsibility (Secondary); A=Approve; R=Review;
NA=Not Applicable

 

Activity

 

Sponsor

 

SynteractHCR

 

Comments

REGULATORY ***

 

 

 

 

 

 

Investigational New Drug (IND) Preparation/ Submission (***)

 

X

 

 

 

 

IND Ongoing Maintenance (***)

 

X

 

 

 

 

Annual Update/Report to the IND (***)

 

X

 

 

 

 

Annual Update/Report to the IND — Preparation of the T/L/Fs  (***)

 

 

 

X

 

 

New Drug Application (NDA) or Biologics License Application (BLA)
Preparation/Submission (***)

 

NA

 

NA

 

 

Drug Submission Application (***)

 

NA

 

NA

 

 

Document Submission to Regulatory Authority (***)

 

 

 

X

 

CTA and Clinical Trial Site Information Form (CTSIF) which includes REB approval

REGULATORY ***

 

 

 

 

 

 

Obtain a *** Clinical Trials (*** Database Number

 

 

 

X

 

 

Application for Clinical Trial Authorization (CTA) Preparation/Submission

 

 

 

X

 

 

 

2

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

 

Work Order 1

 

INS-212

 

 

Sponsor: Insmed

 

Study ID:  INS-212

 

Services Checklist & Transfer of Obligations

X=Responsibility (Primary); (X)=Responsibility (Secondary); A=Approve; R=Review;
NA=Not Applicable

 

Activity

 

Sponsor

 

SynteractHCR

 

Comments

Investigational Medicinal Product Dossier (IMPD) Preparation/Submission

 

X

 

X

 

CRO will review and submit

Application for Ethics Committee (EC) Approval Preparation/Submission

 

 

 

X

 

 

Qualified Person (QP) Release

 

X

 

 

 

 

Investigational Drug Import Licensure

 

X

 

 

 

 

Investigational Drug Export Licensure

 

X

 

 

 

 

Local Warehouse(s)

 

X

 

 

 

 

Clinical Trial Insurance (Provide/Arrange For)

 

 

 

X

 

 

REGULATORY (for ***)

 

 

 

 

 

 

Ethics Committee Submission

 

A

 

X

 

 

Regulatory Authority Notification (TGA)

 

A

 

X

 

 

PROJECT START-UP/INITIATION: Assume CRO SOPs to be used

 

 

 

 

 

 

Protocol Development

 

X

 

 

 

 

Protocol Amendment(s) Development

 

A

 

X

 

To be costed if applicable

Protocol Review

 

X

 

R

 

 

Protocol Amendment(s) Review & Approval

 

A

 

 

 

 

Protocol/Protocol Amendment(s) Printing/Distribution

 

 

 

X

 

To be costed if applicable

Investigator Drug Brochure (IDB) Development

 

X

 

R

 

 

IDB Printing/Distribution

 

 

 

X

 

 

Model Informed Consent Form (ICF) Development

 

A

 

X

 

 

Model ICF Review

 

A

 

X

 

 

Model ICF Distribution

 

 

 

X

 

 

Country-Specific ICF (***)

 

A

 

X

 

 

Country-Specific ICF Distribution (***

 

 

 

X

 

 

Case Report Form (CRF) Screens Development

 

A

 

X

 

 

CRF Printing/Shipping

 

 

 

NA

 

 

CRF Review

 

A

 

X

 

 

CRF Completion Guidelines

 

A

 

X

 

 

Translation of Study Documents

 

 

 

X

 

SynteractHCR will manage translation vendor

Site Feasibility/Report

 

R

 

X

 

 

Site Identification/Selection

 

A

 

X

 

 

Document Submission to Appropriate Review Committee (i.e., IRB/EC)

 

 

 

X

 

 

Regulatory/Essential Document Collection/Review

 

 

 

X

 

 

 

3

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

 

Work Order 1

 

INS-212

 

 

Sponsor: Insmed

 

Study ID:  INS-212

 

Services Checklist & Transfer of Obligations

X=Responsibility (Primary); (X)=Responsibility (Secondary); A=Approve; R=Review;
NA=Not Applicable

 

Activity

 

Sponsor

 

SynteractHCR

 

Comments

Regulatory/Essential Document Maintenance (Ongoing Collection/Review)

 

 

 

X

 

 

Trial Master File (TMF) Set-up/Maintenance

 

A

 

X

 

 

Site Regulatory Binder/Study Procedures Manual

 

A

 

X

 

 

Other Study Documents/Tools

 

R

 

X

 

 

Investigator (Site) Agreements/Contracts

 

A

 

X

 

SynteractHCR will sign site contracts after Sponsor review/approval

Investigator Fee Negotiation

 

A

 

X

 

 

Investigator Fee Payment/Tracking

 

A

 

X

 

 

Investigator’s Meeting (Organization/Conduct)

 

 

 

X

 

3 IMs, SynteractHCR will manage meeting planning vendor

Prepare Investigator’s Meeting Binders

 

R

 

X

 

 

Investigator’s Meeting (Attend/Participate)

 

X

 

X

 

 

Aggregate spend/Sunshine Data Reporting

 

A

 

X

 

 

CLINICAL MONITORING Assume CRO SOPs to be used

 

 

 

 

 

 

Monitoring Plan

 

A

 

X

 

 

Pre-Study Qualification Visits

 

 

 

X

 

On site or via telephone

Site Initiation Visits

 

 

 

X

 

 

Interim Monitoring Visits

 

 

 

X

 

 

Site Close-out Visits

 

 

 

X

 

 

Monitoring Visit Reports/Follow-up Letters

 

R

 

X

 

 

Site Management/Contact

 

 

 

X

 

 

Query Resolution

 

 

 

X

 

 

Study Drug Management (Storage/Distribution/Destruction)

 

 

 

X

 

Site level

Nebulizer and cleaning supplies Management
(Storage/Distribution/Return/Destruction)

 

 

 

X

 

Site level

MEDICAL MONITORING

 

 

 

 

 

 

Medical Monitoring/Support to Project Team/Sites

 

X

 

 

 

 

After-Hours Medical Coverage

 

X

 

 

 

 

Review of AE Coding

 

A

 

 

 

 

Review of SAE Coding

 

X

 

 

 

 

Medical Review of Routine Laboratory Reports

 

X

 

 

 

 

Review (Medical) of Data Listings

 

X

 

 

 

 

Review (Medical) of CRFs

 

X

 

 

 

 

Review (Medical) of Routine ECG Reports

 

NA

 

 

 

 

 

4

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

 

Work Order 1

 

INS-212

 

Sponsor: Insmed

 

Study ID:  INS-212

 

Services Checklist & Transfer of Obligations

X=Responsibility (Primary); (X)=Responsibility (Secondary); A=Approve; R=Review;
NA=Not Applicable

 

Activity

 

Sponsor

 

SynteractHCR

 

Comments

Safety Management Plan

 

X

 

 

 

3rd party vendor

SAE Receipt/Review

 

X

 

 

 

3rd party vendor

SAE Documentation (SAE Narrative Form)

 

X

 

 

 

 

Collection of Safety Data (SAE Data)

 

X

 

X

 

Work with 3rd party vendor to obtain information from sites

Preparation of *** Form (Safety Reports) North America

 

X

 

 

 

3rd party vendor

Preparation of *** Form (Suspected Unexpected Serious Adverse Reactions [SUSARs]
Reports) (***)

 

X

 

 

 

3rd party vendor

Safety Reporting to Health/Regulatory Authorities

 

X

 

 

 

3rd party vendor

SUSARs Reporting to Competent Authorities (***)

 

X

 

 

 

3rd party vendor

Electronic Reporting of SUSARs to (***) (***)

 

X

 

 

 

3rd party vendor

Preparation/Submission of Registration Package for Electronic Reporting of
SUSARs (***)

 

X

 

 

 

3rd party vendor

Notify Sites of SAEs/Distribute Safety Reports

 

X

 

 

 

3rd party vendor will provide notifications, per ***

Notify Sites and ECs of SAEs and SUSARs/ Distribute Safety Reports (***)

 

X

 

 

 

3rd party vendor will provide notifications, per ***

SAE Reconciliation

 

 

 

(X)

 

CRO to assume collaboration with 3rd party vendor for SAE reconciliation

DATA MANAGEMENT: Assume CRO SOPs to be used

 

 

 

 

 

 

Data Management Plan

 

A

 

X

 

 

Data Edit Specifications

 

A

 

X

 

 

Data Listings

 

A

 

X

 

 

Annotated CRF

 

A

 

X

 

 

Database Development/Set-up/Programming

 

A

 

X

 

***

Electronic Data Capture (EDC)

 

A

 

X

 

 

Electronic Data Capture (EDC) Training

 

A

 

X

 

 

EDC Helpdesk

 

 

 

X

 

 

CRF Processing, Tracking, and Receipting

 

NA

 

NA

 

 

Data Entry/Verification

 

NA

 

NA

 

 

Queries Generation/Resolution

 

A

 

X

 

 

Coding Dictionaries (***)

 

X

 

X

 

 

 

5

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

 

Work Order 1

 

INS-212

 

Sponsor: Insmed

 

Study ID:  INS-212

 

Services Checklist & Transfer of Obligations

X=Responsibility (Primary); (X)=Responsibility (Secondary); A=Approve; R=Review;
NA=Not Applicable

 

Activity

 

Sponsor

 

SynteractHCR

 

Comments

Medical Coding (AEs; medical histories; concomitant drugs)

 

A

 

X

 

 

SAE Reconciliation

 

A

 

X

 

 

Receipt of Local Lab Data (Paper)

 

NA

 

NA

 

 

Receipt of Vendor Electronic Data (Central Laboratory, Electrocardiogram, etc.)

 

 

 

X

 

Needs to be reconciliation of this data too.

Define Critical Variables

 

NA

 

NA

 

 

Critical Variable Audit

 

NA

 

NA

 

 

Final Database QC Audit

 

NA

 

NA

 

 

Interim Data Transfer(s)

 

A

 

X

 

 

Final Database Closure/Transfer

 

A

 

X

 

 

Archive CRFs and Database of Record

 

A

 

X

 

 

Planning & Coordination

 

 

 

X

 

 

Routine Status Reports

 

A

 

X

 

 

Create and transfer CDISC compliant datasets (SDTM)

 

A

 

X

 

Quarterly SDTM transfers to sponsor, SDTM reviewers guide at end of study

BIOSTATISTICAL SERVICES Assume CRO SOPs to be used

 

 

 

 

 

 

Develop Randomization Code

 

A

 

X

 

 

Statistical Analysis Plan (SAP)

 

A

 

X

 

 

T/L/Fs

 

A

 

X

 

 

Dry Runs

 

 

 

X

 

*** dry runs prior to first interim analysis

Interim Statistical Analysis/Summary

 

A

 

X

 

 

Statistical Analysis

 

A

 

X

 

 

Final Summary T/L/Fs

 

A

 

X

 

 

Final Statistical Report

 

NA

 

NA

 

 

Analysis Datasets Transfers (ADaM)

 

A

 

X

 

ADaM reviewers guide at end of study

DSMB TLFs

 

 

 

X

 

SynteractHCR statistician attendance (via teleconference) at DSMB meetings

DSMB Plan

 

 

 

X

 

Analysis plan for DSMB

Population PK Analysis

 

X

 

 

 

 

MEDICAL WRITING Assume CRO SOPs to be used

 

 

 

 

 

 

Patient Narratives (for Study Report)

 

X

 

 

 

Provided by ***

CSR with appendices

 

A

 

X

 

 

Activation of Hyperlinks

 

 

 

X

 

Assumes *** links per TLF, section cross-references, external links

 

6

--------------------------------------------------------------------------------

 

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

 

Work Order 1

 

INS-212

 

Sponsor: Insmed

 

Study ID:  INS-212

 

Services Checklist & Transfer of Obligations

X=Responsibility (Primary); (X)=Responsibility (Secondary); A=Approve; R=Review;
NA=Not Applicable

 

Activity

 

Sponsor

 

SynteractHCR

 

Comments

Final Integrated Study Report

 

A

 

X

 

 

Subject Profiles

 

A

 

X

 

SynteractHCR will provide patient profiles via ***.

Manuscript

 

NA

 

NA

 

 

Preparation of Periodic and Annual Safety ***

 

X

 

 

 

 

Submission of Periodic and Annual Safety Reports to the Health/Competent
Authorities and Ethics Committees (ECs) (***)

 

A

 

X

 

 

IWRS

 

 

 

 

 

 

IWRS for randomization, tracking enrollment and drug supplies, nebulizers and
cleaning supplies

 

 

 

 

 

TBD

Drug Supply, Nebulizer and Cleaning Supplies Management — tracking through IWRS

 

 

 

 

 

TBD

QUALITY ASSURANCE (QA)

 

 

 

 

 

 

GCP/ICH Site Audits

 

X

 

X

 

Assumes ***% of sites may require a GCP audit

Vendor Audits

 

X

 

X

 

Vendor audits may occur for those sponsor designated vendors that SynteractHCR
will hold the contract for

PROJECT MANAGEMENT Assume CRO SOPs to be used

 

 

 

 

 

 

Project Management

 

 

 

X

 

 

Project Management Plan

 

A

 

X

 

 

Project Set-up/Maintenance

 

 

 

X

 

 

Face-to-Face Meeting(s)

 

X

 

X

 

*** per year, per sponsor, Global PM, Global CL, regional PMs

Team Teleconference(s) (Frequency: weekly)

 

X

 

X

 

 

Enrollment Updates/Project Status Reports

 

A

 

X

 

Posted on project website

Project Newsletters

 

NA

 

NA

 

Regular, frequent eBlasts

Trial Master File (TMF) Reconciliation

 

A

 

X

 

 

Training of Project Team

 

X

 

X

 

 

Vendor Management

 

 

 

X

 

 

SUB-CONTRACTING SERVICES

 

 

 

 

 

 

Central IRB Selection

 

 

 

X

 

 

Drug Packaging/Labeling/Depot

 

X

 

 

 

 

Central Laboratory (Select/Contract)

 

 

 

X

 

 

Vendor Management

 

A

 

X

 

Includes contracting and payment administration

 

7

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

 

Work Order 1

 

INS-212

 

3                      Project Specifications

 

Global Project Management

 

SynteractHCR manages all projects according to a Project Team approach. The
SynteractHCR Global Program Manager will have the primary responsibility of
communication with Sponsor for overall project information for the duration of
the project. However, Sponsor is welcome to contact any team members as needed.
This includes daily, weekly and monthly updates to keep core team members
current on all project activities.

 

Project meetings will be conducted on a routine basis. During each meeting,
critical issues, unexpected problems and trends are identified and discussed. In
addition, milestones are set and reviewed and timelines for all departments
working on the project are discussed. Any deviations in project deadlines,
expenses and action items are examined with respect to the impact on all
departments. Additionally, the team members will “trouble-shoot” problems and
solutions before milestones or deadlines are jeopardized. Meeting minutes will
be distributed to all team members.

 

Secure Web-Access

 

SynteractHCR will provide secure, web-based access via browser-enabled computers
for Sponsor and the rest of the project team to project information such as:

 

·                  Enrollment Status Reports

·                  Regulatory Document status

·                  Monitoring Schedule and report status

·                  CRF, data clarification status, and other data management
reports

·                  Project Timelines

 

Specific information to be provided on the website would be determined in
conjunction with Sponsor.

 

Vendor Contracts and Management

 

On behalf of Sponsor, SynteractHCR will execute contracts with
Sponsor-designated vendors. These vendors may also require audits by
SynteractHCR to be compliant with SOPs. SynteractHCR will administer vendor
payments for Sponsor.

 

Regulatory Submissions Across Regions

 

SynteractHCR will provide Sponsor with list(s) of required documentation in
order to submit to appropriate regulatory authorities in the regions selected
for this study.

 

IMPD Review/CTA Submission to Regulatory Authorities

 

SynteractHCR will provide review of IMPD for CTA submission ***. Submissions to
Central Regulatory Authorities, as well as to the local authorities and ECs,
have been included. Costs associated with amendments are not included in this
work order.

 

CTA submission *** to Health Authorities

 

SynteractHCR will prepare the CTA for submission ***. Sponsor will provide the
the Quality Overall Summary (QOS). After approval of the CTA by ***,
SynteractHCR will prepare the Clinical Trial Site Information Form (CTSIF) for
each participating site. Costs have not been included for CTA amendments.

 

8

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

Submissions in Australia

 

SynteractHCR will submit to the Ethics Committee. Therapeutics Goods
Administration (TGA) will be notified once approval has been provided.

 

Project Start-Up Activities

 

Protocol and Investigators Brochure Development

 

Sponsor will prepare the protocol and Investigators Brochure (IB) and
incorporate any revisions to the protocol and IB which may occur during the
project. SynteractHCR in conjunction with Sponsor will ensure that all revisions
of the IB have been submitted to the site and are in the Investigator files.

 

Investigator Selection

 

SynteractHCR will perform site identification and will obtain a Non-Disclosure
Agreement in a form approved by sponsor, complete a phone questionnaire (if
needed) for the site. SynteractHCR will perform a Site Qualification Visit at
the site and document the visit in a Site Qualification Visit report. Sponsor
will make the final decision on site selection for the project.

 

Negotiation of Clinical Trial Agreements and Site Budgets

 

A Clinical Trial Agreement is defined as any agreement between SynteractHCR or
Sponsor and a clinical site, site personnel, Investigator, or site ancillary
service provider, in order to perform clinical research for the study. Sponsor
will review and approve the SynteractHCR clinical trial agreement, site budget
and letter of indemnification templates. SynteractHCR will negotiate the
clinical trial agreement and budget to reach mutually agreeable final and fully
executed Clinical Trial Agreements and site budgets. Sponsor will provide to
SynteractHCR the site budget negotiation parameters for study budget items, such
as start-up, scheduled visits, unscheduled visits, screen failure and
pass-through fees. After execution of this Work Order, Sponsor and SynteractHCR
will develop a mutually agreed upon “Contracts Program Plan” that sets forth the
escalation, communication, and approval processes for all Clinical Trial
Agreements and their respective components.

 

In addition, SynteractHCR will facilitate the negotiation of the site letter of
indemnification, which will be executed by the Sponsor and site. The negotiation
and execution shall follow the process as specifically set forth in the
Contracts Program Plan for the site letter of indemnification.

 

SynteractHCR will administer site payments on behalf of Sponsor as a
pass-through expense. SynteractHCR will invoice Sponsor for the site payment
amount (and any applicable bank wire transfer fees) on a monthly basis and will
be due upon receipt. Once the site payment amount is received and processed,
SynteractHCR will remit payment on behalf of Sponsor to the sites. SynteractHCR
will track the site payments administered by SynteractHCR on behalf of Sponsor.

 

Project Meetings

 

Project Kick-off Meeting

 

SynteractHCR will attend a Project Kick-off Meeting with Sponsor. The agenda for
the Kick-off Meeting will be planned jointly by SynteractHCR and Sponsor.
SynteractHCR will determine with Sponsor the required project team members for
attendance.

 

Investigators Meetings

 

SynteractHCR will plan and conduct regional Investigators Meetings in
conjunction with Sponsor. SynteractHCR will be responsible for planning meeting
logistics. Each Investigators Meeting will include a CRA training meeting. The
agenda for the Investigators Meetings will be planned jointly by SynteractHCR
and Sponsor.

 

9

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

Teleconferences

 

SynteractHCR will conduct regular team teleconferences, both internally and with
Sponsor. Minutes for Sponsor teleconferences will be provided by SynteractHCR.

 

Face-to-Face Meetings

 

Per Sponsor request, SynteractHCR will attend face-to-face status update
meetings at Sponsor offices in New Jersey, US. The Global Project Manager,
Global Clinical Lead, and regional Project Managers will attend in person.
Additional team attendees may participate via teleconference.

 

Regulatory Documents

 

SynteractHCR will prepare the template patient Informed Consent Form (ICF).
SynteractHCR will ensure that the ICF meets the minimum requirements as outlined
by the US Code of Federal Regulations and ICH guidelines where applicable.
SynteractHCR will develop draft Protected Health Information (PHI) language to
be incorporated into the ICF, or as a standalone authorization form for use with
this project.

 

SynteractHCR will be responsible for the initial collection and review of all
regulatory documents, such as IRB approvals, Informed Consent Documents, and
financial disclosure statements, from the site to ensure compliance with
appropriate regulations and ICH/ GCP Guidelines. SynteractHCR will assist the
sites with obtaining IRB approval. Regulatory documents will be sent to Sponsor
for full approval. Sponsor will forward all fully approved regulatory packages
to SynteractHCR for Central files. SynteractHCR will maintain the Central files
for the project and the project sites. SynteractHCR will track and collect
regulatory documents after the receipt of the initial regulatory package.

 

Set up Project Tracking System

 

SynteractHCR will track regulatory documents, site visits and reports as well as
project team contact information within its Clinical Trials Management system.

 

Study Reference Manual

 

SynteractHCR will prepare a Study Reference Manual. The Study Reference Manual
will consist of key project instructions for project specific procedures, and
items such as, adverse experience reporting, key contacts and project supply
ordering. SynteractHCR will prepare the CRF completion instructions in
conjunction with Sponsor. Sponsor will provide review and feedback prior to
finalization.

 

Site Qualification & Initiation Visits

 

Site Qualification Visit

 

SynteractHCR will qualify the investigational sites and project investigators.
The Site Qualification Visit may be performed in conjunction with Sponsor at
Sponsor’s option. SynteractHCR may qualify sites via telephone if they have been
previously qualified and/or participated in a trial with Sponsor or SynteractHCR
within the past 12 months. SynteractHCR will communicate to Sponsor any concerns
regarding the site’s ability to conduct the project. Sponsor will make the final
decision on site selection.

 

Site Initiation Visit

 

SynteractHCR will conduct Site Initiation Visits (SIV) at the sites. The SIVs
may be performed in conjunction with Sponsor at Sponsor’s option. The SIV will
include a review of the protocol and project procedures, case report form (CRF)
completion, investigator obligations, laboratory specimen collection and
handling. SynteractHCR will confirm that proper source documentation is in place
in addition to receipt/storage of project drug if available during the scheduled
visit.

 

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COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

The Site Initiation Visits will be documented in a monitoring visit report and
follow-up letter to the site. The visit report will be drafted within ***
working days from the last day of the visit.

 

On-Site Monitoring

 

Monitoring Plan

 

SynteractHCR will develop a monitoring plan for review and approval by Sponsor.
The monitoring plan will address the proposed monitoring schedule for each
region. The monitoring plan will also describe source document verification
(SDV) and any other monitoring conventions. SynteractHCR will provide Curricula
Vitae (CVs) of prospective project monitors to Sponsor for review prior to
project assignment. Every effort will be made to assign project monitor(s) in
close proximity to the selected project sites to reduce travel time and cost.

 

Site Monitoring Visits

 

Monitoring frequency may be adjusted as necessary on a site-by-site basis, based
on patient enrollment, monitoring requirements prior to the interim database
lock, or specific site issues. Sponsor would be involved in monitoring frequency
discussions, if any adjustments are necessary.

 

During on-site monitoring visits SynteractHCR will perform the following tasks
to monitor compliance with GCP and appropriate federal regulations and Sponsor
requirements as stated in the monitoring plan:

 

·                  Perform ***% review of all signed ICFs and PHI authorizations
or local privacy laws;

·                  Review and verify ***% of available source documentation on
all CRFs;

·                  Review all clinical data at the site for legibility,
completeness, and consistency within the CRF set;

·                  Instruct clinical site staff to supply missing data, complete
data corrections, and clarify CRF information;

·                  Check data clarifications against source documents to confirm
that all clarifications accurately reflect the source documents;

·                  Monitor IP and nebulizer accountability, including the
reconciliation of inventory;

·                  Review required clinical site regulatory documentation, and
provide updates to Sponsor;

·                  Document deficiencies and follow-up until they are corrected
by the clinical site staff;

·                  Train site personnel as required.

 

SynteractHCR will monitor to verify that the clinical site staff perform the
following tasks:

 

·                  CRF completion and Data Corrections;

·                  Provision of source documents at each site visit;

·                  CRF corrections as necessary during each monitoring visit or
prior to the next scheduled monitoring visit.

 

The monitoring visits will be documented in a monitoring visit report and
follow-up letter to the sites.

 

Close-Out Visits

 

SynteractHCR will conduct one project closeout visit at each of the clinical
sites. While conducting this visit, SynteractHCR will perform the following
tasks:

 

·                  Final IP, nebulizer, and supply accountability review and
authorize final project supply returns to Sponsor;

·                  Reconcile the site regulatory binder including the IRB final
report;

 

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COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

·                  Required data reconciliation;

·                  Review investigator’s adherence to record retention
responsibilities and preparation of project records; and

·                  Collect and dispose of unused project supplies in a manner
agreed upon with Sponsor.

 

Site Visit Reports

 

Site visit reports will be drafted within the time frame agreed upon in the
monitoring plan. Upon completion of a draft visit report, the report will be
forwarded to SynteractHCR and Sponsor for review and comment. Revisions and
comments will be returned to the appropriate monitor for incorporation into the
final report. The final report will be forwarded to Sponsor within *** of
finalization. Any urgent project issues will be communicated to Sponsor
immediately.

 

Clinical Lead

 

SynteractHCR will utilize a Global Clinical Lead, approved by Sponsor, to
oversee the clinical aspects of the entire project. Additionally, there will be
regional Clinical Lead(s) in Europe and regional Clinical Lead(s) in the US, all
approved by Sponsor. SynteractHCR will require any non-employee Global Clinical
Lead and regional Clinical Leads agree to execute an agreement to comply with
the terms of the MSA prior to commencing services, and will ensure their
compliance with the Sponsor-SynteractHCR MSA terms. SynteractHCR will remain
responsible for their performance.

 

The SynteractHCR Clinical Lead assumes responsibility for the coordination of
the CRA team and monitoring of daily activities to ensure the successful
completion of clinical trials. The Clinical Lead participates in the planning,
implementation, and management of clinical trials in compliance with federal
regulations, ICH Guidelines, Good Clinical Practices (GCPs) and standard
operating procedures (SOPs). Specific lead activities include designating site
assignments and ensuring CRA resources are continuously adequate; tracking and
reviewing monitoring visit reports and ensuring standards for monitoring and
reporting are met; facilitating communication and standardization of monitoring
procedures by providing a leadership role at CRA teleconferences; preparing
materials and minutes for CRA teleconferences, meetings, and training seminars;
and coordination of project specific training and other requirements for
internal and external staff. The clinical lead develops and/or contributes to
the development of clinical documents such as Study Manuals, CRF Completion
Guidelines, Monitoring Plans and other project specific tools as required and
may perform the on-site monitoring of clinical studies.

 

Site Management and Communication

 

The SynteractHCR project monitor will be the primary point of contact with the
sites, and will be in contact with the site on a regular basis. SynteractHCR
will document relevant correspondence with clinical site and Sponsor.
SynteractHCR will keep Sponsor informed of all project issues on an ongoing
basis throughout the project. Original copies of telephone reports and other
written clinical site correspondence will be provided to Sponsor at the
conclusion of the project as part of the central file transfer. Proper
documentation within the regulatory files and IRB of all serious adverse events
(SAEs) will be confirmed during the monitoring visits.

 

Site Audits

 

SynteractHCR and/or Sponsor may conduct clinical site audits at selected
clinical sites according to their respective SOPs. Sponsor may accompany
SynteractHCR during their audits. Sponsor will work with SynteractHCR to
determine the sites to be audited. SynteractHCR will provide an audit report to
Sponsor within *** business days.

 

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COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

Vendor Audits

 

SynteractHCR and/or Sponsor may conduct audits for selected vendors (e.g.,
sponsor-designated vendors) according to their respective SOPs. Sponsor may
accompany SynteractHCR during their audits. These audits may be conducted on
site at a vendor location or via the internet. SynteractHCR will provide an
audit report to Sponsor within *** business days.

 

Investigational Product (IP) Management

 

IP Shipments

 

Sponsor will be responsible for supplying, packaging, labeling, and distributing
the IP to the project sites. During the course of routine site management,
SynteractHCR will be responsible for requesting additional IP shipments as
necessary and returning any unused IP at the project conclusion to Sponsor.
Project supplies that remain on site at the conclusion of the project will
either be destroyed or returned to Sponsor as requested. SynteractHCR will
ensure that all proper documentation is filed appropriately in the
investigator’s project files. This includes IP receipt, inventory,
accountability and return.

 

Nebulizer and Cleaning Supply Management

 

Nebulizer and Cleaning Supply Shipments

 

Sponsor will be responsible for supplying, packaging, labeling, and distributing
the nebulizers and cleaning supplies to the project sites.  During the course of
routine site management, SynteractHCR will be responsible for requesting
additional nebulizers and cleaning supply shipments as necessary and returning
all used and any unused nebulizers and cleaning supplies at the project
conclusion to Sponsor. SynteractHCR will ensure that all proper documentation is
filed appropriately in the investigator’s project files. This includes nebulizer
and cleaning supply receipt, inventory, accountability and return.

 

Interactive Web-Response System (IWRS)

 

Specific transfer of obligations for IWRS services are to be determined; costs
for IWRS support will be included in a Change in Scope.

 

Data Management

 

Accuracy and timeliness are of the highest priority in SynteractHCR’s management
of clinical data. Once entered, data are stored in a SAS database from which all
reporting and data analyses are done. Quality control checks are built in every
step of the way to ensure complete accuracy. An experienced data manager will be
assigned to the project and will be responsible for all activities leading to a
clean database.

 

Data Management Plan

 

The SynteractHCR data manager will develop a data management plan, incorporating
input from Sponsor, addressing the following:

 

·                  Overview of the data entry and data management process for
the project

·                  Special handling procedures

·                  Edit check plan

·                  Database close procedures

·                  Data back-up processes

·                  Any other project-specific processes or issues.

 

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COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

This data management plan will be sent to Sponsor for review and approval prior
to implementation.

 

***

 

Electronic Case Report Forms

 

SynteractHCR will develop the Pre-build worksheet. The design will be reviewed
from a data management perspective and suggestions will be made regarding
consistency and the ability to collect the data accurately and in a manner that
will facilitate analysis.

 

eCRF Completion Guidelines

 

SynteractHCR Data Manager will prepare eCRF Completion Guidelines. This document
contains a general overview of the database, data entry guidelines, general site
requirements and expectations, completion instructions for all of the eCRFs, and
any specific instructions.

 

Start-up Activities

 

SynteractHCR will set up a database for this project using the ***. (“***”) ***
system for electronic data capture at the project sites. The SynteractHCR team
will work with the team at Sponsor to determine goals and project requirements.

 

Start-up activities include (in conjunction with Sponsor as appropriate):

 

·                  Design project workflow and training documentation.

·                  Design roles and responsibilities matrix.

·                  Prepare appropriate materials necessary to train Sponsor and
project site personnel at the start-up meetings.

·                  Implementation of automated data edit checks (browser-side
and server-side).

·                  Validate configured system.

·                  Devise system management and database strategy, which
includes security, storage, back-ups, recovery, and server connectivity.

 

Database Creation

 

SynteractHCR will provide the *** database build. A new Sponsor -SynteractHCR
URL hosted securely by *** will be created for Sponsor for the performance of
studies performed in collaboration with SynteractHCR. SynteractHCR will provide
a Core Configuration model from which Sponsor may customize for their unique
project requirements. In order to identify potential errors in data entry,
SynteractHCR will provide a list of validation checks. Upon approval of the Edit
Check Document, the edit checks and custom functions will be programmed to help
identify any errors in data entry.

 

*** ***. *** was developed with ease-of-use as a fundamental design principal
providing ‘point and click’ functionality to end users. All modules and tools
within *** are deployed securely over the Internet and require no special skills
to operate the system.

 

License Grant and Use

 

Subject to this Agreement and Sponsor’s payment of the applicable Applications
Services Fees (including License Fees), SynteractHCR (“SynteractHCR”) hereby
grants Sponsor, during the term set forth in the applicable Statement of
Work/Sales Order, a non-exclusive, limited, non-transferable license to remotely
access and use the object code version of the *** software applications and
documentation (collectively, the *** Applications) only for Sponsor’s internal
business purposes for conducting the clinical trial project identified in the
applicable Statement of Work. Only Sponsor’s employees and contractors
conducting the clinical trial project (the “Authorized Users”) may access the
*** Applications on behalf of Sponsor. Sponsor shall use the *** Applications
only for lawful

 

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COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

purposes and in accordance with this Agreement. All rights not expressly granted
under this Agreement are reserved to *** (“***”).

 

Restrictions Applicable to *** Applications:

 

Sponsor acknowledges that the *** Applications that will be made available to
Sponsor by SynteractHCR on a hosted basis is proprietary to *** and that ***
owns all right, title and interest in the *** Applications, including, but not
limited to, any derivative works, modifications, updates and enhancements. The
*** Applications and all materials relating thereto are confidential and
proprietary to *** and Sponsor and its Authorized Users shall protect and treat
such as confidential using the same care as required under the Agreement with
respect to SynteractHCR’s confidential information, but no less than reasonable
care. Sponsor understands and agrees that the *** Applications may only be used
by Sponsor and its Authorized Users in accordance with the license grant set
forth above and that Sponsor will not (1) modify, copy, reverse engineer or
create derivative works of the *** Applications; (2) use the *** Applications to
provide hosting, service bureau, time sharing, outsourcing or other services to
third parties; (3) resell, lease, license, sublicense or time-share the ***
Applications to third parties or otherwise permit the use of or access to the
*** Applications by any third party, (4) transfer an existing clinical trial to
a third party that is either a competitor of *** or doesn’t implement the ***
Applications to support the balance of such clinical trial; (5) remove or alter
any proprietary rights notices affixed to or contained within the ***
Applications; or (6) use the *** Applications to build a competitive product or
service or to perform clinical trial studies for any third party(ies) or input
data from any clinical trial project of any third party(ies). Sponsor shall not
disclose the *** Applications to third-parties or use such *** Applications for
any purposes whatsoever other than in accordance with this Agreement and agrees
that it will not engage in, and may be held liable for any unauthorized use,
copying or disclosure of the *** Applications. The parties agree that *** is a
direct and intended third party beneficiary to this Agreement and shall have the
right to enforce the license restrictions and confidentiality obligations
contained herein.

 

Access from Any Browser on Any Computer

 

*** is designed to enhance the role of the entire project team, anywhere in the
world, on any computer, through any browser. The *** system user interface
requires only an HTML 4.01 Transitional compliant browser such as Internet
Explorer, Netscape, or Safari to be accessed. This standard is now adopted by
virtually all current browsers (and is overseen by the W3C consortium). All
platforms and browsers that fulfill this requirement can be used to access any
*** module. This architectural feature ensures the maximum amount of flexibility
for user adoption at all levels, as well as eliminating reliance on any current
Sponsor technology which may be superseded or amended (e.g. Windows XP
SP2, Internet Explorer 8, etc.). All data processing, including edit checks and
derivations, are conducted on the server side. The zero Sponsor approach applies
equally to the project build tools as well as the data entry and cleaning
functions. At no time is any data being processed or stored on the Sponsor
platform. Similarly, any identifiers such as standard cookies or session cookies
(which may be hijacked or decrypted) are not used. This eliminates any
concerning factors surrounding validation and firewall issues in the deployment
of ***.

 

One login, One password, One URL

 

While many systems have been designed as an EDC front-end to the CDMS (Clinical
Data Management System) back-end database, *** ***. The *** system uses a single
integrated database to manage one or more project environments. The development,
production and a virtually unlimited number of test and or training environments
can be managed centrally within the application, with ***, eliminating the need
for the definition and maintenance of complex multi-database, multi application
configurations.

 

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COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

Lab Administrative Module

 

*** provides robust lab data management which includes multivariable dependent
reference ranges (e.g. gender, age, fasting status, analyte effective dates),
central lab data import, and site maintenance of local lab ranges. Some
additional lab management features include two-way unit conversions that
accommodate percent to absolute and absolute to percent, auto prompting for
clinical significance when required, on CRF display of appropriate lab ranges,
and auto fill/automatic updates to all lab values upon lab configuration
changes.

 

Local Lab Capabilities: *** includes the ability to manage multiple local labs
for each investigational site. Local lab ranges can be administered by the site
or centrally by a user with the appropriate level of permissions. Local lab
ranges can be dependent upon parameters based on any data point entered on the
eCRF (i.e. gender, fasting status), as well as, effective dates. Non-numeric
data including code lists and out of limits of detection results (e.g. < .001%),
can still be interpreted by ***and have range checks applied against them. In
situations where sites may not have access to local lab ranges, they can enter
their data and substitute reference or text book ranges. Labs and local ranges
that are entered for one project can be leveraged in subsequent studies
eliminating the need for redundant efforts in lab setup.

 

Site Training

 

Prior to receiving access to ***, each site user must complete the required
training provided by *** and also by SynteractHCR. *** training will be
completed using their on-line eLearning tool. The SynteractHCR data manager will
set up each user so that the eLearning module can be completed. Additionally,
SynteractHCR will provide project-specific training to site personnel by WebEx,
if requested by Sponsor. All training will be documented and retained in the
project files.

 

Data Processing

 

Sites will enter data, which will be followed by CRA source document
verification and review of the data. A data management review of the data will
also be performed, which will include the execution of some post-entry logical
edit checks.

 

Data Management Review

 

SynteractHCR’s data management personnel will run crosschecks and review data as
needed. Queries will be provided to the sites. This process will be performed as
needed, providing there is new data to be processed.

 

Adverse Event and Medications Coding

 

SynteractHCR will use ***’s *** *** for all coding activities. SynteractHCR will
code adverse events and medical history terms using ***. Concomitant medications
will be coded using WHO-Drug. Appropriate codes will be agreed upon with Sponsor
and SynteractHCR will generate coding reports for review and approval by the
Sponsor designee. Sponsor will be provided with all current mappings and
provided adjustments, as necessary. SynteractHCR and Sponsor will agree on the
frequency that these mappings will be generated and reviewed.

 

Sponsor and SynteractHCR hold current *** licenses. Validation of licenses may
be requested by the MSSO (Maintenance and Support Services Organization) for ***
and by the UMC (Uppsala Monitoring Centre) for ***.

 

Integrated Review (***)

 

SynteractHCR will provide *** whereby Sponsor personnel can review data over the
private website. *** is a clinical data review, reporting, multi-dimensional
analysis, graphical and statistical modeling tool. It facilitates the creation
of graphical profiles, tabular profiles, as well as data browsing without

 

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COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

the need for custom programming. The following reports are standard *** reports
and will be provided in MS Excel format:

 

·                  Graphic patient profile containing AE, CM, vitals, demography
and lab

·                  AE listing

·                  CM listing

·                  DM listing

·                  Term listing

·                  Vitals listing

·                  Labs listing

·                  Patient profile containing all patient data

 

Biostatistics

 

Programming and statistical analysis are done using *** software (currently
version ***). As with data management, quality control checks are built into the
programming and data analysis process to ensure the accurate reporting of data.

 

Analysis Plan

 

SynteractHCR will prepare an analysis plan including definition of endpoints to
be analyzed, statistical methodology, rules for data handling, requirements for
dry runs, and design of tables, figures, and listings (TFLs) for all data
displays. The analysis plan will also incorporate the DSMB analyses. Sponsor
will review the analysis plan and provide consolidated comments prior to
finalization by SynteractHCR.

 

Patient Randomization

 

A randomization schedule will be developed by SynteractHCR using *** (currently
version ***) *** and will be incorporated into the randomization IWR system. The
randomization code will be developed by the project Statistician and finalized
and QC’d by an independent unblinded statistician.

 

Statistical Analysis

 

A Statistician will perform the statistical analysis. Statistical analysis
includes time for review of relevant project documentation including the SAP,
programming of primary and secondary efficacy analyses, statistical oversight of
the project (where applicable), and Senior Level Review of deliverables.

 

Programming/Validation

 

After approval of the analysis plan, programmers will develop the programs to
generate the TFLs using SAS according to the agreed analysis plan.

 

The programmer will verify the accuracy of his/her own work, but all outputs
will be independently verified for accuracy and consistency by a second
individual. This validation will be carried out by a combination of independent
programming, cross-checking, and verification against CRFs. Quality assurance
documentation will be maintained, including samples of each output, the ***
program used to produce it, and the quality assurance checks performed.

 

Dry Runs

 

Draft TLFs (dry runs) will be generated by SynteractHCR prior to the interim
database lock for Sponsor’s review and query of data as appropriate. Each set of
draft TLFs will be QC’d by SynteractHCR before sending to Sponsor for review.

 

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COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

*** Programming

 

SynteractHCR will create *** datasets per SynteractHCR’s standard processes for
creating *** datasets. SynteractHCR will provide *** format.

 

Blankcrf.pdf

 

SynteractHCR will create the annotated CRF (blankcrf.pdf) after the modeling of
SDTM begins and will complete these items when the database is closed and all
programming and quality control procedures have been completed.

 

*** Programming

 

SynteractHCR will create *** analysis datasets per SynteractHCR’s standard
processes for creating *** datasets. *** datasets will be used exclusively as
the source data for *** datasets. SynteractHCR will provide *** datasets in ***
format.

 

Define.xmls

 

SynteractHCR will create the Define.xmls after the modeling *** begins and will
complete these deliverables when the database is closed and all programming and
quality control procedures have been completed.

 

CDISC Reviewer’s Guides

 

Per Sponsor’s request, SynteractHCR will prepare a Reviewer’s Guide ***. These
guides will contain a brief summary of notes or unusual issues regarding the
final data that is not included in the define.***. The guides will be delivered
to Sponsor at the end of the study.

 

DSMB Meetings

 

SynteractHCR will prepare the tables and listings for the DSMB data review
meetings. The Project Biostatistician will also attend the meetings via
teleconference.

 

Clinical Study Report

 

A final clinical study report will be developed that includes a complete
description of the clinical and statistical aspects of the trial. The
SynteractHCR medical writer will work with Sponsor to develop a clinical study
report in a format that is compliant with FDA and ICH Guidelines. SynteractHCR
can also provide a standardized ICH compliant CSR template.

 

An initial draft of the report includes a description of all study methodology
and presentation of results based on final tables, listings, and figures. The
draft report will undergo statistical and quality review by SynteractHCR prior
to distribution. A draft clinical study report is typically generated within
four to six weeks after final tables, listings, and graphs are received or
generated and approved by Sponsor. The cost of this report includes up ***
revisions of the report, and inclusion of up to *** narratives of serious
adverse events, deaths, or discontinuations due to adverse events (combined).
Cost estimates assume the CSR conforms to standard metrics detailed in the
assumptions table.

 

For each revision cycle, SynteractHCR will circulate the draft report for review
to Sponsor; consolidated comments/changes will be provided to SynteractHCR, and
the report will be revised by SynteractHCR accordingly for either the next
review or final approval by Sponsor. If requested by Sponsor, SynteractHCR can
perform a *** QC review of the report prior to finalization. Estimates for a ***
QC review are not included in this proposal and can be provided upon request.

 

Compiling the Final Clinical Study Report and Appendices for Regulatory
Submission

 

SynteractHCR will compile (publish or PDF) the final clinical study report and
all supporting documentation referenced in the CSR for regulatory submission.
Required documentation will be

 

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COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

provided by SynteractHCR (if available) and Sponsor. A final project signature
page is also required to begin compiling.

 

The compiled granular CSR consists of the main body (sections 1,3-15), Synopsis
(Section 2), and Appendix 16 (each appendix in 16.1, 16.2 and 16.3 as separate
granules).

 

The main body granule of the CSR will have a bookmarked and hyperlinked Table of
Contents. TFLs and section cross-references will be hyperlinked within the CSR.

 

4                      Miscellaneous

 

4.1            Backup and Security

 

SynteractHCR performs incremental *** backups *** are retained for a *** period.
***, a full backup is written to media and stored off-site for a *** retention
period at ***. All backups are verified and logged by the Global Systems staff.
Quarterly tapes are stored offsite at *** for ***. Offsite data is available
within a few hours of requesting the data from ***.

 

Clinical data is generally stored on SynteractHCR network servers unless
otherwise specified (e.g., third party hosting that is contractually specified).
No clinical data are stored on local workstations. Access to the clinical data
files is restricted based on directory permission levels that are determined by
job function. *** No clinical data will be altered or updated without going
through the proper application interface. Anti-virus scan software programs are
in place to detect and prevent corruption of data due to computer viruses. All
server-side application files are stored in a secured, dedicated network
directory.

 

All connections to SynteractHCR’s secure web site, used for document viewing,
downloading, and Argus are encrypted using ***. Published applications, like ***
and ***, are secured via our ***. A *** is available for uploading files to the
SynteractHCR network. SynteractHCR utilizes *** for securing e-mail
communication if requested by Sponsor.

 

4.2            Language

 

All deliverables will be provided in English for this study.

 

19

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

5                      Project Costs

 

5.1            Assumptions

 

Project Assumptions

 

 

 

General Study Information

 

 

 

Number of Screened Patients

 

***

 

Total Number of Enrolled Patients

 

***

 

Projected Number of Enrolled Patients ***

 

***

 

Projected Number of Enrolled Patients in ***

 

***

 

Projected Number of Enrolled Patients in ***

 

***

 

Total Number of Sites

 

***

 

Number of Sites — ***

 

***

 

Number of Sites — ***

 

***

 

Number of Sites — ***

 

***

 

Number of Sites — ***

 

***

 

Number of Sites — ***

 

***

 

Number of Sites — ***

 

***

 

Number of Sites — ***

 

***

 

Number of Sites — ***

 

***

 

Number of Sites — ***

 

***

 

Number of Sites — ***

 

***

 

Number of Sites — ***

 

***

 

Number of Sites — ***

 

***

 

Project Duration (Months)

 

***

 

Clinical Operations (Months)

 

***

 

Patient Enrollment Duration (Months)

 

***

 

Patient Randomized Open-Label Treatment Duration (Months)

 

***

 

Patient Off-Treatment Duration (Months)

 

***

 

Project Meetings

 

 

 

Kick-Off Meeting at Sponsor office in ***

 

***

 

Investigator Meetings assumes *** in each region (***)

 

***

 

Number of Days per Meeting (Including CRA Training Meeting)

 

***

 

*** Meeting: Global Project Manager, Global Clinical Lead, *** Clinical Lead,
*** Project Manager, *** Project Manager, CRA team, Lead Data Manager, IWRS
Manager

 

 

 

 

20

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

Project Assumptions

 

 

 

*** Meeting: Global Project Manager, Global Clinical Lead, *** Clinical Leads,
***, ***, and ***s Project Manager, CRA team, Lead Data Manager, IWRS Manager

 

 

 

*** Meeting: Global Project Manager, Global Clinical Lead, *** Clinical Lead,
*** and *** Project Manager, CRA team, Lead Data Manager, IWRS Manager

 

 

 

Number of Face-to-Face Meetings *** per year per Sponsor

 

***

 

Number of Team Teleconferences with Sponsor

 

***

 

Data Management

 

 

 

Number of Unique CRF Pages

 

***

 

Number of CRF Pages per Screened Patient per Sponsor

 

***

 

Number of CRF Pages per Completed Patient

 

***

 

Total Number of CRF Pages

 

***

 

Number of Edit Checks

 

***

 

Number of Queries per Patient

 

***

 

Number of Complex BOXI Reports

 

***

 

Number of Non-Complex BOXI Reports

 

***

 

Site Identification

 

 

 

Site ID Duration (Months)

 

***

 

Number of Sites Contacted with Survey/Questionnaire

 

***

 

Number of Sites for Debarment Verification

 

***

 

Number of Countries

 

***

 

Site Contracts

 

 

 

Total Estimated Number of Site Contracts

 

 

 

Number of Contracts per Site — ***

 

***

 

Number of Contracts per Site — ***

 

***

 

Number of Contracts per Site — ***

 

***

 

Number of Contracts per Site — ***

 

***

 

Number of Contracts per Site — ***

 

***

 

Number of Contracts per Site — ***

 

***

 

Number of Contracts per Site — ***

 

***

 

Number of Contracts per Site — ***

 

***

 

Number of Contracts per Site — ***

 

***

 

Number of Contracts per Site — ***

 

***

 

Number of Contracts per Site — ***

 

***

 

Number of Contracts per Site — ***

 

***

 

costs for additional sworn translations are not included

 

 

 

 

21

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

Project Assumptions

 

 

 

Clinical Operations

 

 

 

Total Number of Clinical Leads

 

***

 

Global Clinical Lead

 

***

 

Regional Clinical Leads — ***

 

***

 

Regional Clinical Lead — ***

 

***

 

 

22

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

Project Assumptions

 

 

 

Total Number of Regional CRAs

 

***

 

Number of CRAs — ***

 

***

 

Number of CRAs — ***

 

***

 

Number of CRAs — ***

 

***

 

Number of Qualification Visits — ***

average *** day travel, *** day on site, *** day
preparation/follow-up/report-writing

 

***

 

Number of Qualification Visits — ***

average *** day travel, *** day on site, *** day
preparation/follow-up/report-writing

 

***

 

Number of Qualification Visits — ***

average *** day travel, *** day on site, *** day
preparation/follow-up/report-writing

 

***

 

Number of Telephone Qualification Visits — ***

 

***

 

Number of Initiation Visits — ***

average *** day travel, *** day on site, *** day
preparation/follow-up/report-writing

 

***

 

Number of Initiation Visits — ***

average *** day travel, *** day on site, *** day
preparation/follow-up/report-writing

 

***

 

Number of Initiation Visits — ***

average *** day travel, *** day on site, *** day
preparation/follow-up/report-writing

 

***

 

Number of Monitoring Visits/Site — ***

average *** day travel, *** day on site, *** day
preparation/follow-up/report-writing

 

***

 

Number of Monitoring Visits/Site — ***

average *** day travel, *** day on site, *** day
preparation/follow-up/report-writing

 

***

 

Number of Monitoring Visits/Site — ***

average *** day travel, *** day on site, *** day
preparation/follow-up/report-writing

 

***

 

Total Number of Monitoring Visits — ***

 

***

 

Total Number of Monitoring Visits — ***

 

***

 

 

23

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

Project Assumptions

 

 

 

Total Number of Monitoring Visits — ***

 

***

 

Additional Days on Site — ***

 

***

 

Additional Days on Site — ***

 

***

 

Additional Days on Site — ***

 

***

 

Number of Study Close-out Visits — ***

average *** days travel, *** day on site, *** days
preparation/follow-up/report-writing

 

***

 

Number of Study Close-out Visits — ***

average *** day travel, *** day on site, *** day
preparation/follow-up/report-writing

 

***

 

Number of Study Close-out Visits — ***

average *** day travel, *** day on site, *** day
preparation/follow-up/report-writing

 

***

 

Q.A. Audits

 

 

 

Number of Site Audits — ***

 

***

 

Number of Site Audits — ***

 

***

 

Number of Site Audits — ***

 

***

 

Number of Vendor Audits — ***

 

***

 

Number of Vendor Audits — ***

 

***

 

Number of Vendor Audits — ***

 

***

 

Medical Safety

 

 

 

Number of SAEs

 

***

 

Number of Coded Items per Patient

 

***

 

Biostatistics

 

 

 

Number of Outside Data Vendors

 

***

 

Number of Outside Vendor Data Transfers (Monthly)

 

***

 

Number of Unique Efficacy Tables

 

***

 

Number of Unique Safety Tables

 

***

 

Number of Repeat Tables

 

***

 

Number of DSMB Tables

 

***

 

Number of Annual Report Tables

 

***

 

Number of Unique Graphs

 

***

 

Number of Repeat Graphs

 

***

 

Number of DSMB Graphs

 

***

 

Number of Listings

 

***

 

 

24

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

Project Assumptions

 

 

 

Number of DSMB Listings

 

***

 

Number of Annual Report Listings

 

***

 

Number of *** Datasets

 

***

 

Number of *** Domains

 

***

 

Number of *** Datasets

 

***

 

Number of Interim Analyses

 

***

 

Number of DSMB Meetings

 

***

 

Number of Transfers of SDTMs to Sponsor

 

***

 

Number of Annual Reports

 

***

 

 

The following assumptions have also been made in determining the cost estimates:

 

1.              All assumptions are based on the draft protocol and schedule of
events dated *** and are subject to change based on the final protocol and/or
amendments.

2.              Costs are included for SynteractHCR to perform activities in the
regions and service areas and with the vendors as detailed in this Work Order.
Activities requested by Sponsor not included in this Work Order will be included
in a Change in Scope.

3.              All deliverables and project materials will be in English (this
includes all documents provided to SynteractHCR). If translations are needed,
translation activities will be handled by a third party vendor and SynteractHCR.

4.              All SynteractHCR activities will be conducted according to
SynteractHCR SOPs.

5.              SynteractHCR templates will be used for all appropriate project
documents.

6.              Sponsor will retain responsibility for any other activities that
are not referenced in this proposal.

7.              Estimates assume four rounds of revisions for project documents
requiring review/approval by Sponsor. All Sponsor comments/changes will be
collated and provided to SynteractHCR in one document.

8.              SynteractHCR may perform site and vendor audits; exact
sites/locations will be determined by SynteractHCR and Sponsor and costs may be
adjusted accordingly.

9.              Site CDAs and contracts will be between SynteractHCR and the
sites, after Sponsor has reviewed and approved.

10.       Sponsor and SynteractHCR hold a current *** license and a current ***
license.

11.       Data for screen failure patients will be entered into *** on eCRFs by
site personnel.

12.       *** training will be web-based.

13.       Costs include Sponsor User Acceptance Testing (UAT) of the clinical
database.

14.       Web Access includes access to the reports portion of the project web
page and *** for eight Sponsor personnel. Additional users will incur additional
costs.

15.       All Central Laboratory results will be provided to SynteractHCR as
electronic data transfers.

16.       Costs have been included for central laboratory data to be integrated
into *** via *** Web Services.

17.       Costs do not include database migrations.

18.       SynteractHCR will receive and reconcile PK header information on a
monthly basis for this study.

19.       DM site payment report programming assumes monthly site payments.

20.       For the interim analyses, SynteractHCR will provide a subset of the
final tables, listings and figures.

21.       The database will be locked for the *** of primary endpoints. For the
DSMB analyses and the ***, the tables, listings, and figures will be run on
dirty data (a database soft-lock will not occur prior to the analyses).

 

25

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

22.       SynteractHCR will provide *** datasets, *** datasets, *** and user
guides.

23.       Sponsor (or designee) will provide SynteractHCR with the final patient
SAE narratives for inclusion in the final study report. The SynteractHCR medical
writer will not revise or re-format the patient SAE narratives.

24.       Non-SAE narratives are generally written and included in the CSR for
patients with AEs that lead to discontinuation of the study and/or study drug,
or for AEs of special interest. Depending on the number and complexity of these
narratives, additional time may be required to produce and QC. This is usually
determined during CSR development.

25.       The compiled CSR will have a hyperlinked and bookmarked Table of
Contents. Collection and filing of CSR appendix documents will be completed per
ICH guidelines.

26.       Project Management costs include Sponsor meeting attendance, managing
team meetings and conference calls and providing meeting minutes, vendor
management, and overall project administration tasks.

27.       Project Administration includes the creation and maintenance of the
clinical document database, maintenance of regulatory documents, review and
processing of expense reports, generation of regular reports, and processing of
site and vendor payments.

28.       If reasonably requested by Sponsor, periodic face to face internal
management meetings between SynteractHCR and ***, US SynteractHCR and EU
SynteractHCR, and SynteractHCR and Insmed may occur during the life of the
study. Sponsor will be billed for pass-through travel costs if applicable.

 

26

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

5.2            Summary Cost Estimates

 

With the exception of flat rate/unit items listed in the detailed budget,
SynteractHCR will only charge for actual time spent per task. SynteractHCR will
not exceed the project study maximum without an approved change order. A
detailed budget table is provided in Attachment 1, Detailed Budget.

 

ACTIVITY

 

 

 

***

 

***

 

***

 

Clinical Operations

 

$

***

 

$

***

 

$

***

 

Site/Vendor Audits

 

$

***

 

$

***

 

$

***

 

Regulatory Affairs

 

$

***

 

$

***

 

$

***

 

Interactive Web Response System (IWRS) - Central Randomization/ Inventory
Management

 

 

 

***

 

 

 

Data Management

 

 

 

$

***

 

 

 

Biostatistics

 

 

 

$

***

 

 

 

Medical Writing

 

 

 

$

***

 

 

 

Project Management

 

$

***

 

$

***

 

$

***

 

Sub-Totals

 

$

***

 

$

***

 

$

***

 

Study Total

 

 

 

$

***

 

 

 

***% discount on invoicing

 

 

 

$

***

 

 

 

Estimated Study Total

 

 

 

$

***

 

 

 

 

Rates stated in this Work Order are current through ***. As of *** of each year
starting in ***, SynteractHCR’s activity rates will increase or decrease in
accordance with the most recent ***, and the percent increase or decrease will
not exceed the percent increase or decrease corresponding to the median
compensation rates for the functions listed in the budget for a similarly sized
study in the prior 1-year period. SynteractHCR will notify Sponsor of the
proposed increase at least *** (***) days in advance of such increase. 
SynteractHCR and Sponsor shall negotiate in good faith any disagreement as to
the appropriate percent increase, and Sponsor may terminate this Work Order upon
*** (***) days notice.

 

The costs for services provided by resources in the *** and *** and presented in
this Work Order are based on an identified fixed exchange rate dated *** using
*** between *** and *** and *** and ***, (“Base Rate: *** = ***, *** = ***”). If
the exchange value of the *** rises or falls by ***% or more from the Base Rate
during the course of the project, the costs *** and ***-resourced services shall
be adjusted accordingly.

 

The above-referenced ***% discount on invoicing will be applied only if the ***
project (or a similar study or group of studies with a service value of $***
using SynteractHCR standard rates) is contracted in conjunction (i.e., within
*** months of work order execution) with the INS-212 project. The discount will
be applied to both projects as a bottom line discount on monthly invoices, and
no other additional discounts will apply to these projects.

 

If the *** study (or a similar study or group of studies with a service value of
$*** using SynteractHCR standard rates) is not contracted and initiated with
SynteractHCR, Sponsor will refund the sum total of the ***% applied discount to
SynteractHCR within *** months of INS-212 work order execution.

 

27

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

5.3            Pass-Through Costs

 

Travel-related expenses, mailing/courier costs, translation costs, IRB/EC and
other regulatory submission fees, site fees, patient recruitment/retention
fees, Investigator Meeting planning fees, laboratory fees, and miscellaneous
project expenses (e.g., binders, folders, tabs, labels, packaging materials,
printing)  are considered project-related pass-through costs and are not
included in the above cost estimates. These costs would be invoiced directly to
Sponsor without markup. Additional pass-through expenses that are not listed in
the table below will require pre-approval from Sponsor before incurring and
invoicing.

 

SynteractHCR assumes that Sponsor’s teleconference number(s) will be used for
regular project team calls, otherwise SynteractHCR will pass through conference
call costs directly to Sponsor.

 

International wire fees for site/vendor payments will be passed through to
Sponsor.

 

*** pass-through costs are estimates and subject to change.

 

Prices quoted in the proposal are net and excluding any applicable VAT.

 

Estimated pass-through costs have been provided in the table below; these
estimates will be passed through at no mark-up to Sponsor based on the actual
costs. SynteractHCR will not exceed the estimated pass-through budget maximum
without an approved change order.

 

Item

 

Number

 

Unit

 

Cost Per
Unit

 

Total

Travel

 

 

 

 

 

 

 

 

Travel (*** Visits)

 

***

 

visit

 

***

 

***

Travel (*** Visits)

 

***

 

visit

 

***

 

***

Travel (*** Visits — Air, etc.)

 

***

 

visit

 

***

 

***

Travel (*** Visits — Local)

 

***

 

visit

 

***

 

***

Meeting Travel — ***

 

***

 

meeting

 

***

 

***

Meeting Travel — ***

 

***

 

meeting

 

***

 

***

Meeting Travel — ***

 

***

 

meeting

 

***

 

***

Ad hoc Visit Travel — ***

 

***

 

visit

 

***

 

***

Site Audit Travel - ***

 

***

 

audit

 

***

 

***

Site Audit Travel - ***

 

***

 

audit

 

***

 

***

Site Audit Travel - ***

 

***

 

audit

 

***

 

***

Vendor Audit Travel - ***

 

***

 

audit

 

***

 

***

Vendor Audit Travel - ***

 

***

 

audit

 

***

 

***

Vendor Audit Travel - ***

 

***

 

audit

 

***

 

***

Regulatory/EC/IRB Fees

 

 

 

 

 

 

 

 

Central IRB Fees ***

 

***

 

study

 

***

 

***

Local and Central EC Fees ***

 

***

 

study

 

***

 

***

Fees for Central Authority Notification - ***

 

***

 

country

 

***

 

***

 

28

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

Item

 

Number

 

Unit

 

Cost Per
Unit

 

Total

Regulatory/EC Submission Fees ***

 

***

 

study

 

***

 

***

Regulatory Fees ***

 

 

 

 

 

 

 

***

Other

 

 

 

 

 

 

 

 

Protocol and ICF Printing

 

***

 

*** sites

 

***

 

***

Shipping

 

***

 

month

 

***

 

***

Miscellaneous Project Expenses

 

***

 

month

 

***

 

***

Legal Representation - ***

 

***

 

study

 

 

 

***

Investigator Fees — ***

 

***

 

patient

 

***

 

***

Investigator Fees — ***

 

***

 

patient

 

 

 

***

Investigator Fees — ***

 

***

 

patient

 

 

 

***

Site Start-up Fees — ***

 

***

 

site

 

***

 

***

Site Start-up Fees — ***

 

***

 

site

 

 

 

***

Site Start-up Fees — ***

 

***

 

site

 

 

 

***

Trial Insurance

 

 

 

 

 

 

 

***

Central Laboratory (***)

 

***

 

laboratory

 

***

 

***

Regional Laboratories (***)

 

***

 

laboratory

 

 

 

***

Investigator Meeting — ***

 

***

 

meeting

 

***

 

***

Investigator Meeting — ***

 

***

 

meeting

 

***

 

***

Investigator Meeting — ***

 

***

 

meeting

 

***

 

***

Translation Vendor (estimate)

 

***

 

language

 

***

 

***

***: Professional Service Fee including New URL

 

***

 

study

 

***

 

***

*** Applications Service Fee (Hosting) for Rave

 

***

 

month

 

***

 

***

Total

 

 

 

 

 

 

 

$

***

 

5.4            Payment Terms

 

An advance of $*** (***% of the Cost Estimate after discount, less the $***
advance from the Letter of Intent) is due (i) *** and (ii) ***. Sponsor will
then be invoiced *** for actual work performed. The total advance provided
($***+$***) of $*** (the “Advance”) will be adjusted on *** basis, beginning ***
from the signing of this Work Order 1 until all payments have been made/credited
under this Work Order 1, such that the Advance will equal ***% of the remaining
Cost Estimate, after discount, that remains following payments made during the
prior year.  The dollar amount of the Advance that exceeds ***% of the remaining
Cost Estimate shall be, at Sponsor’s option, refunded to Sponsor within ***
(***) days or credited against any outstanding invoice(s) and then any
subsequent invoice(s) until expended.  Flat-rate/unit items will be billed upon
completion of the deliverable or *** as indicated in

 

29

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

the detailed cost estimates provided in Attachment 1, Detailed Budget. At the
completion of the project, if payments received by SynteractHCR exceed the cost
of the work completed, SynteractHCR will reimburse Sponsor for the amount
overpaid within *** (***) days.

 

Additionally, prior to the payment of sites, Sponsor and SynteractHCR will agree
upon the site/investigator grant schedule and budget that corresponds with the
schedule and budget in the executed Site Agreement and Sponsor will provide
adequate funds to SynteractHCR in advance for site payments. All payments from
SynteractHCR to investigators will be made from funds provided in advance by
Sponsor. SynteractHCR will make payment to sites upon presentation of an invoice
at the frequency detailed within the site agreement.

 

5.5            Change in Scope

 

If, in the opinion of SynteractHCR, and mutually agreed to by Sponsor, the scope
of the work exceeds, or is reduced from, what is described in this Work Order 1,
the nature, time, and cost of work over or under scope will be documented in a
change order and provided to Sponsor. A Work Order Amendment will be generated
by SynteractHCR to reflect these changes and will be reviewed, mutually agreed
to, and signed by SynteractHCR and Sponsor. If the scope of Services in a Work
Order Amendment causes the total Project cost estimate to increase,
SynteractHCR, at its discretion, reserves the right to request from Sponsor an
additional advance in proportion to that provided for in section 5.4 above to be
payable to SynteractHCR. If the scope of Services in a Work Order Amendment
causes the total Project cost estimate to decrease, Sponsor, at its discretion,
reserves the right to request from SynteractHCR refund of the Advance in
proportion to that provided for in section 5.4 above to be payable to Sponsor.

 

5.6            Invoices and Payment Correspondence

 

SynteractHCR will send invoices via US Mail and email to the following mailing
address and email:

 

Insmed Incorporated

10 Finderne Avenue

Building 10

Bridgewater, NJ 08807-3365

Attn: Accounts Payable

Phone: ***

Email:  ***

With an email copy to:

***

 

Phone or email correspondence in regard to payment inquiries should be addressed
to the following individuals:

 

If to Sponsor:

If to SynteractHCR:

Insmed Incorporated

SynteractHCR, Inc

10 Finderne Avenue

5759 Fleet Street

Building 10

Suite 100

Bridgewater, NJ 08807-3365

Carlsbad, CA 92008

Attn: Accounts Payable

Attn: Accounts Receivable

Phone: ***

Phone: ***

Email: ***

Email: ***

 

30

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

Each Party may change its address and/or contact person for such notices and
communications by written notice to the other party in accordance with this
Section.

 

To pay an invoice via wire transfer, Sponsor will use the following information
to process the payment:

 

Account Name:  SynteractHCR, Inc.

Bank Name:  ***

Account Number:  ***

Routing Number:  ***

 

For invoices paid via wire transfer or ACH, Sponsor will send a remittance of
the payment to Accounts Receivable at *** or fax number ***.

 

IN WITNESS WHEREOF, the parties have caused this Work Order to be executed by
duly authorized representatives as of the Work Order 1 Effective Date.

 

SynteractHCR, Inc.

 

Insmed Incorporated

 

 

 

/s/ Stewart Bieler***

 

/s/ Peggy Berry

 

 

 

Name: ***Stewart Bieler

 

Name: Peggy Berry

 

 

 

Title: ***CAO

 

Title: VP, Regulatory Affairs

 

 

 

 

31

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

ATTACHMENT 1: DETAILED BUDGET

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

ACTIVITY

 

RATE

 

UNIT

 

EST.
REQ.

 

ESTIMATED
CHARGE

 

COMMENTS

Clinical Operations

 

 

 

 

 

 

 

 

 

 

Feasibility ***

 

***

 

day

 

***

 

***

 

 

Feasibility ***

 

***

 

day

 

***

 

***

 

Assumes *** countries

Site Identification — ***

 

***

 

day

 

***

 

***

 

Assumes ID/screening of *** sites

Site Identification - ***

 

***

 

day

 

***

 

***

 

Assumes ID/screening of *** sites

Site Identification - ***

 

***

 

day

 

***

 

***

 

Assumes ID/screening of *** sites

Site Qualification Visits — Telephone — ***

 

***

 

visit

 

***

 

***

 

Telephone qualifications in lieu of a site qualification visit for sites that
have been used (or qualified) within the past *** months, assumes *** sites

Site Qualification Visits - ***

 

***

 

visit

 

***

 

***

 

Visits will be billed upon completed visit unit.

Site Qualification Visits - *** — Telephone

 

 

 

visit

 

 

 

***

 

No telephone qualification visits anticipated in ***

Site Qualification Visits - ***

 

***

 

visit

 

***

 

***

 

Visits will be billed upon completed visit unit.

Site Qualification Visits - *** — Telephone

 

 

 

visit

 

 

 

***

 

No telephone qualification visits anticipated in ***

Site Qualification Visits - ***

 

***

 

visit

 

***

 

***

 

Visits will be billed upon completed visit unit.

Site Initiation Visits — ***

 

***

 

visit

 

***

 

***

 

Visits will be billed upon completed visit unit.

Site Initiation Visits — ***

 

***

 

visit

 

***

 

***

 

Visits will be billed upon completed visit unit.

Site Initiation Visits - ***

 

***

 

visit

 

***

 

***

 

Visits will be billed upon completed visit unit.

 

32

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

ACTIVITY

 

RATE

 

UNIT

 

EST.
REQ.

 

ESTIMATED
CHARGE

 

COMMENTS

Investigators Meeting — *** Attendees

 

***

 

day

 

***

 

***

 

Attendance of CRAs at *** meeting, regional CL at *** and *** meetings, and
global PM, *** PM, Lead DM, and IWRS at three, average *** d per attendee per
meeting

Investigators Meeting - *** Attendees

 

***

 

day

 

***

 

***

 

Attendance of CRAs, regional CLs, regional PM at *** meeting, and global CL at
***

Investigators Meeting - *** Attendees

 

***

 

day

 

***

 

***

 

Attendance of CRAs at *** meeting and *** Project Manager at three

Study Document Development — ***

 

***

 

day

 

***

 

***

 

Includes review of global monitoring plan and other documents

Study Document Development - ***

 

***

 

day

 

***

 

***

 

Includes development of ICF templates, global monitoring plan and other
documents

Study Document Development - ***

 

***

 

day

 

***

 

***

 

Informed consent development

Budgets/Contracts: 3rd Party Vendors

 

***

 

day

 

***

 

***

 

For sponsor-designated third party vendors

Site Budgets/Contracts — ***

 

***

 

day

 

***

 

***

 

*** and *** sites, SynteractHCR will negotiate and will hold contracts directly
with sites on Insmed’s behalf. SynteractHCR will negotiate Indemnification
agreements between sites and Sponsor. SynteractHCR will develop master budgets
for each country listed in this Work Order 1.

Site Budgets/Contracts- ***

 

***

 

day

 

***

 

***

 

*** sites, SynteractHCR will negotiate and will hold contracts directly with
sites on Insmed’s behalf. SynteractHCR will negotiate Indemnification agreements
between sites and Sponsor. SynteractHCR will develop master budgets for each
country listed in this Work Order 1.

 

33

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

ACTIVITY

 

RATE

 

UNIT

 

EST.
REQ.

 

ESTIMATED
CHARGE

 

COMMENTS

Site Budgets/Contracts - ***

 

***

 

day

 

***

 

***

 

*** sites, SynteractHCR will negotiate and will hold contracts directly with
sites on Insmed’s behalf. SynteractHCR will negotiate Indemnification agreements
between sites and Sponsor. SynteractHCR will develop master budgets for each
country listed in this Work Order 1.

Study Start-up- ***

 

***

 

day

 

***

 

***

 

project team familiarization and training for *** team members

Study Start-up - ***

 

***

 

day

 

***

 

***

 

project team familiarization and training for *** team members

Regulatory Document Collection — ***

 

***

 

day

 

***

 

***

 

 

Regulatory Document Collection — ***

 

***

 

day

 

***

 

***

 

 

Regulatory Document Collection — ***

 

***

 

day

 

***

 

***

 

 

TMF Set-up and Maintenance — ***

 

***

 

day

 

***

 

***

 

Regional site files and TMF

TMF Set-up and Maintenance — ***

 

***

 

day

 

***

 

***

 

Regional site files and Master TMF for project

TMF Set-up — ***

 

***

 

day

 

***

 

***

 

Regional TMF (set-up only)

Study Monitoring — Interim Monitoring Visits — ***

 

***

 

visit

 

***

 

***

 

Visits will be billed upon completed visit unit.

Study Monitoring — Additional Days On Site — ***

 

***

 

day

 

***

 

***

 

To be used in conjunction with an existing visit if more time on-site is
required

Study Monitoring — Interim Monitoring Visits - ***

 

***

 

visit

 

***

 

***

 

Visits will be billed upon completed visit unit.

Study Monitoring — Additional Days on Site — ***

 

***

 

day

 

***

 

***

 

To be used in conjunction with an existing visit if more time on-site is
required

Study Monitoring — Interim Monitoring Visits — ***

 

***

 

visit

 

***

 

***

 

Visits will be billed upon completed visit unit.

 

34

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

ACTIVITY

 

RATE

 

UNIT

 

EST.
REQ.

 

ESTIMATED
CHARGE

 

COMMENTS

Study Monitoring — Additional Days On Site — ***

 

***

 

day

 

***

 

***

 

To be used in conjunction with an existing visit if more time on-site is
required

Clinical Operations Lead — Regional (***)

 

***

 

day

 

***

 

***

 

Clinical oversight of *** and ***, approximately *** FTE

Clinical Operations Leads — Regional (***)

 

***

 

day

 

***

 

***

 

Clinical oversight of ***, approximately *** FTE

Clinical Operations Lead — Global (***)

 

***

 

day

 

***

 

***

 

Global clinical oversight, approximately *** FTE

Site Management — ***

 

***

 

day

 

***

 

***

 

Contact with sites, respond to site questions, reminder calls to push
recruitment, reminder calls to get data in the eCRF/answer queries, request
updated study documents, address any issue with supplies, team calls, etc.

Site Management — ***

 

***

 

day

 

***

 

***

 

Contact with sites, respond to site questions, reminder calls to push
recruitment, reminder calls to get data in the eCRF/answer queries, request
updated study documents, address any issue with supplies, team calls, etc.

Site Management - ***

 

***

 

day

 

***

 

***

 

Contact with sites, respond to site questions, reminder calls to push
recruitment, reminder calls to get data in the eCRF/answer queries, request
updated study documents, address any issue with supplies, team calls, etc.

Study Close-Out Visits — ***

 

***

 

visit

 

***

 

***

 

Visits will be billed upon completed visit unit.

Study Close-Out Visits — ***

 

***

 

visit

 

***

 

***

 

Visits will be billed upon completed visit unit.

Study Close-Out visits - ***

 

***

 

visit

 

***

 

***

 

Visits will be billed upon completed visit unit.

Clinical Operations Subtotal

 

 

 

 

 

 

 

***

 

 

Quality Assurance

 

 

 

 

 

 

 

 

 

 

Site Audit — ***

 

***

 

day

 

***

 

***

 

Time includes prep, travel, on-site audit, and report-writing/follow-up for ***
site audits

 

35

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

ACTIVITY

 

RATE

 

UNIT

 

EST.
REQ.

 

ESTIMATED
CHARGE

 

COMMENTS

Site Audit — ***

 

***

 

day

 

***

 

***

 

Time includes prep, travel, on-site audit, and report-writing/follow-up for ***
site audits

Site Audit — ***

 

***

 

day

 

***

 

***

 

Time includes prep, travel, on-site audit, and report-writing/follow-up for ***
site audits

Vendor Audit — ***

 

***

 

day

 

***

 

***

 

Vendor audits (sponsor-designated vendors)

Vendor Audit — ***

 

***

 

day

 

***

 

***

 

Vendor audits (sponsor-designated vendors)

Vendor Audit — ***

 

***

 

day

 

***

 

***

 

Vendor audits (sponsor-designated vendors)

Quality Assurance Subtotal

 

 

 

 

 

 

 

***

 

 

Regulatory Affairs

 

 

 

 

 

 

 

 

 

 

IMPD Review

 

***

 

day

 

***

 

***

 

 

Regulatory Submissions - ***

 

***

 

day

 

***

 

***

 

Submissions to central and local authorities/ECs

Regulatory Submissions - ***

 

***

 

day

 

***

 

***

 

Submissions to EC and TGA

Regulatory Submissions - ***

 

***

 

day

 

***

 

***

 

CTA preparation and publishing for ***, plus Clinical Trial Site Information
Form (CTSIF) submissions

Regulatory Document Management

 

***

 

day

 

***

 

***

 

Handling of insurance, translations, label review

Regulatory Correspondence

 

***

 

day

 

***

 

***

 

Communication with authorities

Regulatory Document Preparation - ***

 

***

 

day

 

***

 

***

 

CTA preparation for ***

Regulatory Consulting - ***

 

***

 

day

 

***

 

***

 

Regulatory Lead for ***

Legal Representation - ***

 

***

 

project

 

***

 

***

 

*** will act as the local sponsor in ***

Regulatory Affairs Subtotal

 

 

 

 

 

 

 

***

 

 

Interactive Web Response System (IWRS) - Central Randomization/Inventory
Management

 

 

 

 

 

 

 

 

 

 

 

36

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

ACTIVITY

 

RATE

 

UNIT

 

EST.
REQ.

 

ESTIMATED
CHARGE

 

COMMENTS

IWRS Development, Testing and Implementation

 

***

 

day

 

 

 

***

 

Randomization and inventory management via IWRS

IWRS Study Maintenance, Site Support, and DCF processing

 

***

 

month

 

 

 

***

 

Enrollment/treatment/follow-up period

24 hour Technical Support

 

***

 

month

 

 

 

***

 

International support

Interactive Web Response System (IWRS) - Central Randomization/Inventory
Management

 

 

 

 

 

 

 

***

 

 

Data Management

 

 

 

 

 

 

 

 

 

 

CRF Completion Guidelines

 

***

 

day

 

***

 

***

 

 

Clinical Database Design

 

***

 

day

 

***

 

***

 

*** database

DM Programming

 

***

 

day

 

***

 

***

 

DM SAS programming for reports outside of *** (e.g. site payment reports, coding
reports), also includes programming to set up patient profiles in ***

Site Training/Documentation

 

***

 

site

 

***

 

***

 

 

Database Management (Reports/Meetings)

 

***

 

month

 

***

 

***

 

 

Data Management Plan

 

***

 

day

 

***

 

***

 

includes defining data handling processes and writing of edit specifications

Data Management

 

***

 

day

 

***

 

***

 

Assumes data management involvement over *** months of study (clinical duration)

Local Lab Reference Ranges

 

***

 

day

 

***

 

***

 

No normal ranges needed for these lab results

*** Set-up & Training

 

***

 

day

 

***

 

***

 

 

Web Access Set-up

 

***

 

user

 

***

 

***

 

Project website

Monthly Web Access

 

***

 

month

 

***

 

***

 

 

User Administration Support

 

***

 

day

 

***

 

***

 

For *** users, including site personnel, CRAs, Sponsor, safety vendor

 

37

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

ACTIVITY

 

RATE

 

UNIT

 

EST.
REQ.

 

ESTIMATED
CHARGE

 

COMMENTS

Medical Terminology Coding

 

***

 

day

 

***

 

***

 

Assumes *** coded terms per patient

Data Management Subtotal

 

 

 

 

 

 

 

***

 

 

Biostatistics

 

 

 

 

 

 

 

 

 

 

Statistical Writing: Protocol Review

 

***

 

day

 

***

 

***

 

 

Analysis Plan

 

***

 

day

 

***

 

***

 

Statistical analysis plan to include appendix for DSMB analysis plan, includes
mock TFLs

Randomization Schedule

 

***

 

day

 

***

 

***

 

 

Programming / Validation

 

***

 

day

 

***

 

***

 

Standard TFL programming, includes programming and QC for DSMBs, annual reports,
interim analyses, and final analysis

Statistical Programming

 

***

 

day

 

***

 

***

 

Efficacy table programming, includes more complicated programming and QC for
DSMBs, annual reports, interim analyses, and final analysis

CDISC Specifications — Reviewer’s Guides

 

***

 

day

 

***

 

***

 

*** Reviewer’s Guide and *** Reviewer’s guide

CDISC-*** Dataset Programming

 

***

 

day

 

***

 

***

 

*** *** datasets

CDISC-*** Dataset Programming

 

***

 

day

 

***

 

***

 

*** *** datasets; includes *** transfers of *** per sponsor request

CDISC-*** Dataset Programming

 

***

 

day

 

***

 

***

 

*** *** datasets

CDISC aCRF: blankcrf.pdf

 

***

 

day

 

***

 

***

 

 

CDISC Define.xml (SDTM and ADaM)

 

***

 

xml

 

***

 

***

 

 

Data Transfers (from 3rd party vendors)

 

***

 

day

 

***

 

***

 

*** transfers from *** data vendors

 

38

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

ACTIVITY

 

RATE

 

UNIT

 

EST.
REQ.

 

ESTIMATED
CHARGE

 

COMMENTS

Statistical Analysis

 

***

 

day

 

***

 

***

 

Includes time for project statistician to attend regular team meetings as
needed, DSMB meetings via teleconference, and ad hoc face-to-face meetings; also
includes interim and final statistical analyses

Statistical Review of the CSR

 

***

 

day

 

***

 

***

 

 

Biostatistics Subtotal

 

 

 

 

 

 

 

***

 

 

Medical Writing

 

 

 

 

 

 

 

 

 

 

Protocol Review/Writing

 

***

 

day

 

***

 

 

 

 

Clinical Study Report (CSR)

 

***

 

day

 

***

 

***

 

Assumes *** major round of reviews, *** minor round

Clinical Writing General — Informed Consent Template Review

 

***

 

day

 

***

 

***

 

Review of ICF template

CSR Compilation and Activation of Hyperlinks

 

***

 

day

 

***

 

***

 

Compilation of appendices to the CSR, activation of hyperlinks (e.g., TFLs)

Medical Writing Subtotal

 

 

 

 

 

 

 

***

 

 

Project Management

 

 

 

 

 

 

 

 

 

 

Project Administration — ***

 

***

 

day

 

***

 

***

 

Includes project support, teleconference/minutes, assistance with status
reports, and payment administration (sites, vendors) for ***

Project Administration- ***

 

***

 

day

 

***

 

***

 

Includes project support, assistance with status reports, and payment
administration (sites, vendors) for ***

Project Administration - ***

 

***

 

day

 

***

 

***

 

Includes project support for Australia

Project Management — ***

 

***

 

day

 

***

 

***

 

*** project management, vendor management

Project Management — ***

 

***

 

day

 

***

 

***

 

*** project management

 

39

--------------------------------------------------------------------------------

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS
DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN
ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.]

 

Insmed Incorporated — SynteractHCR

Work Order 1

INS-212

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

ACTIVITY

 

RATE

 

UNIT

 

EST.
REQ.

 

ESTIMATED
CHARGE

 

COMMENTS

Project Management - ***

 

***

 

day

 

***

 

***

 

*** project management

Global Project Management

 

***

 

day

 

***

 

***

 

Global Project Director to oversee all global aspects of the project

Project Archival

 

***

 

project

 

***

 

***

 

 

Project Meetings — ***

 

***

 

day

 

***

 

***

 

Face-to-face meetings (e.g., kick-off meeting, sponsor meetings, ad hoc site
visits) for *** team members

Project Meetings — ***

 

***

 

day

 

***

 

***

 

Face-to-face meetings for *** Project Manager, assumes attendance at *** F2F
meetings

Project Management Subtotal

 

 

 

 

 

 

 

***

 

 

SynteractHCR Study Total

 

 

 

 

 

 

 

***

 

 

discount on invoicing

 

***

%

 

 

 

 

***

 

 

SynteractHCR Study Total After Discount

 

 

 

 

 

 

 

***

 

 

 

40

--------------------------------------------------------------------------------