Document:

exhibit_4-26.htm

Exhibit 4.26

 

 

WORK ORDER

INC Research Project # 1000504

Protocol # PBT2-203

 

This Work Order (hereinafter “Work Order”) is between Prana Biotechnology Limited (hereinafter “Sponsor”) with principal offices located at Level 2, 369 Royal Parade, Parkville VIC 3052 Australia and INCResearch Australia Pty Limited, together with its parent company, subsidiaries and legal affiliates (hereinafter “INC Research”) with offices located at 124 Lipson Street, Port Adelaide SA 5015 Australia and relates to the Master Services Agreement effectively dated 22nd September 2011 which expressly incorporates this Work Order hereto by reference into the Master Services Agreement. Pursuant to the Master Services Agreement, INC Research has agreed to perform certain services in accordance with written work orders, such as this one, entered into from time to time describing such services.

 

This document constitutes a Work Order under the Master Services Agreement and this Work Order and the Services contemplated herein are subject to the terms and provisions of the Master Services Agreement.

 

	
1.

	
SERVICES: INC Research will render such services (hereinafter “Services”) as may be necessary to complete in a professional manner the project described below:

	  	  
	  	
A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Tolerability, and Efficacy of PBT2 in Patients with Early to Mid-stage Huntington Disease (#PBT2-203)

	  	  
	  	
INC Research will perform the Services as specified in Attachment A to this Work Order.

	  	  
	
2.

	
PROJECT SCHEDULE: The major project milestones and target dates are described in Attachment B to this Work Order. Both parties agree that the Project Schedule is a reasonable schedule for the Services to be performed and will put forth all reasonable efforts to comply with these dates.

	  	  
	
3.

	
COMPENSATION AND EXPENSES: Sponsor shall pay the fees for INC Research’s Services in accordance with the Project Budget and Payment Schedule provided in Attachment C of this Work Order. INC Research shall invoice Sponsor for taxes or duties actually incurred by INC Research which are imposed upon INC Research by any governmental agency, including, but not limited to Value Added Tax, Stamp Tax, and/or General Sales Tax, as a result of this Agreement with the exception of taxes based on INC Research’s income.

 

	
INCResearch Australia Pty Limited

	
Prana Work Order 1000504 v4 3rd August 2012

 

  

  

  

 

 

	
4.

	
NOTICES AND PAYMENTS: All communications, notices and payments required under this Work Order shall be mailed by first class mail, postage prepaid, or by overnight carriers, to the respective parties at the addresses set forth below, or to such other addresses as the parties may from time to time specify in writing.

 

	 	
If to Sponsor:

	  
	 	  	
Caroline Herd

Chief Development Consultant 

Prana Biotechnology Limited 

Level 2

369 Royal Parade

Parkville VIC 3052 Australia

Phone: +61 (0) 3 9349 4906

Facsimile: +61 (0) 3 9348 0377

	 	
If to INC Research:

	  
	 	  	  
	 	
For Communications:

	
Contracts Management

INCResearch Australia Pty Limited 

124 Lipson Street

Port Adelaide SA 5015 Australia

Phone: +61 (0) 8 8447 3500

Facsimile: +61 (0) 8 8447 3511

	 	
For Payments (Via Wire):

	  
	 	 	 
	 	
Beneficiary Bank:

	
Bank of South Australia (A Division of 

St George Bank Limited)

	 	
Account Name:

	
INCResearch Australia Pty Limited

	 	
BSB (Routing Number):

	 
	 	
Account Number:

	 
	 	
Swift:

	 

 

	
5.

	
TRANSFER OF OBLIGATIONS: Sponsor assigns the responsibilities pertaining to the Study to INC Research as indicated in Attachment A, Services.

 

	
INCResearch Australia Pty Limited

	
Prana Work Order 1000504 v4 3rd August 2012

 

  

  

  

 

 

IN WITNESS WHEREOF, the undersigned have caused this Work Order to be executed by a duly authorized individual on behalf of each requisite party effective as of the day and year last written below. In the event that the parties execute this Work Order by exchange of electronically signed copies or facsimile signed copies, the parties agree that, upon being signed by both parties, this Work Order shall become effective and binding and that facsimile copies and/or electronic signatures will constitute evidence of the existence of this Work Order with the expectation that original documents may later be exchanged in good faith. Thereafter, the parties agree that in connection with request for information that either party may need from the other related to the Services provided hereunder, both parties expressly permit communication via facsimile to the extent allowed by applicable laws and regulations to be disseminated in that manner.

 

Prana Biotechnology Limited

 

	
By:

	       
	  	  
	
Name:

	Dianne Angus
	  	  
	
Title:

	
Chief Operating Officer

	  	  
	
Date:

	
6th August 2012

 

INCResearch Australia Pty Limited

 

	
By:

	      
	  	  
	
Name:

	
Garth Tierney

	  	  
	
Title:

	
Regional General Manager, Australia and South East Asia

	  	  
	
Date:

	
14th August 2012.

 

	
INCResearch Australia Pty Limited

	
Prana Work Order 1000504 v4 3rd August 2012

 

  

  

  

 

 

ATTACHMENT A

Services

 

	
DETAILED ASSUMPTIONS

	  	  	  
	
GENERAL

	  	  
	
DRUG NAME

	  	
PBT2

	
INDICATION

	  	
Huntington Disease

	
PHASE

	  	
2a

	
SITES

	  	  
	
NUMBER OF COUNTRIES

	  	
1 - Australia

	
NUMBER OF SITES

	  	
5

	
NUMBER OF APPLICABLE LANGUAGES

	  	
1 - English

	
CASE REPORT FORM (CRF)

	  	  
	
PAPER OR ELECTRONIC CRF

	  	
eCRF

	
NUMBER OF PAGES PER ENROLLED PATIENT

	  	
70

	
TOTAL PAGES

	  	
2,100

	
INVESTIGATOR MEETING

	  	  
	
NUMBER OF MEETING(S)

	  	
1 - Melbourne

	
DURATION OF MEETING(S)

	  	
1.5 days

	  	
•

	
NUMBER OF SITE ATTENDEES

	  	
3 attendees per site (15 total site attendees)

	  	
•

	
NUMBER OF CUSTOMER ATTENDEES

	  	
5

	  	
•

	
NUMBER OF INC RESEARCH ATTENDEES

	  	
2 CRAs + 1 PM

	
SITE MONITORING

	  	  
	
NUMBER OF CRAs

	  	
3 - based in Sydney, Melbourne and Perth

	
NUMBER OF INITIATION VISITS

	  	
5

	
NUMBER OF MONITORING VISITS

	  	
25 one-day visits - 5 visits/site

	
NUMBER OF CLOSEOUT VISITS

	  	
5

	
PHARMACOVIGILANCE (SAFETY)

	  	  
	
NUMBER OF SERIOUS ADVERSE EVENTS (SAEs)

	  	
Assume 1

	
NUMBER OF REPORTABLE SAEs

	  	
Assume 1

	
NUMBER OF SUSPECTED UNEXPECTED SERIOUS ADVERSE REACTIONS

	  	
1

	
NUMBER OF SAEs REPORTING TO LOCAL REGULATORY AUTHORITY

	  	
1

	
PROJECT MANAGEMENT

	  	  
	
NUMBER OF CUSTOMER TELECONFERENCES

	  	
21

	  	
•

	
FREQUENCY OF TELECONFERENCES

	  	
Monthly

	
INCResearch Australia Pty Limited

	
Prana Work Order 1000504 v4 3rd August 2012

 

  

  

  

 

 

	
DETAILED ASSUMPTIONS

	  	
•

	
DURATION OF TELECONFERENCES

	  	
1 hour

	  	
•

	
TELECONFERENCE ATTENDEES

	  	
Project Manager

 

	
ACTIVITY

	 	
Prana

	 	
INCResearch

	
Study Start-up Activities

	 	  	 	  
	
Study Sponsorship - Australia

	 	
ü

	 	  
	
Protocol Development

	 	
ü

	 	  
	
Approval and Authorisation of Final Protocol

	 	
ü

	 	  
	
Patient Information Sheet & Consent Template Development

	 	
ü

	 	  
	
Creation of Study Manual/Monitoring Guidelines

	 	
ü

	 	  
	
List Trial on Public Register e.g. ANZCTR, Clinicaltrials.gov

	 	
ü

	 	  
	
Conduct Internal Team Kick-Off Meeting

	 	  	 	
ü

	
Investigator/Site Identification

	 	
ü

	 	  
	
Approval of Final Investigator’s/Sites

	 	
ü

	 	  
	
Finalise Clinical Trial Agreements

	 	
ü

	 	  
	
Creation and Collection of Essential Documents

	 	  	 	
ü

	
Conduct Pre-study/Site Qualification Visits

	 	
ü

	 	  
	
Complete Ethics Submissions and Follow-up

	 	
ü

	 	  
	
Respond to Issues Raised by the Ethics Committee

	 	
ü

	 	  
	
Regulatory Submissions

	 	
ü

	 	  
	
Import/Export Permit Handling

	 	
ü

	 	  
	
Customer Project Team Meetings

	 	  	 	  
	
Attend Project Team Meeting

	 	
ü

	 	
ü

	
Organise Project Team Meeting

	 	
ü

	 	  
	
Investigator’s Meeting

	 	 	 	  
	
Attend Investigator’s Meeting

	 	
ü

	 	
ü

	
Present at Investigator’s Meeting

	 	
ü

	 	  
	
Organise Investigator’s Meeting

	 	
ü 

	 	  
	
Investigational Product (IP)

	 	
 

	 	  
	
IP Packaging and Labelling

	 	
ü

	 	  
	
IP Storage

	 	
ü

	 	  
	
IP Distribution

	 	
ü 

	 	  

 

	
INCResearch Australia Pty Limited

	
Prana Work Order 1000504 v4 3rd August 2012

 

  

  

  

 

 

	
ACTIVITY

	 	
Prana

	 	
INCResearch

	
IP Accountability

	 	  	 	
ü

	
IP Destruction

	 	
ü

	 	  
	
Site Visits

	 	  	 	  
	
Site Initiation Visits

	 	  	 	
ü

	
Monitoring Visits

	 	  	 	
ü

	
Close-out Visits

	 	  	 	
ü

	
Completion of Visit Reports

	 	  	 	
ü

	
Site Management

	 	  	 	  
	
Site Management

	 	  	 	
ü

	
Project Management

	 	  	 	  
	
Project Management (Local)

	 	  	 	
ü

	
Project Tool Development

	 	  	 	
ü

	
Create Master Study Files

	 	
ü

	 	  
	
Maintenance of Master Study Files During Study

	 	
ü

	 	  
	
Create Investigator In-house and Site Study Files

	 	  	 	
ü

	
Maintain In-house Investigator Study Files During Study

	 	  	 	
ü

	
Manage and Make Payments to Investigators/Sites

	 	
ü

	 	  
	
Archiving of Study Files Post-study

	 	
ü

	 	  
	
Safety Reporting & Medical Monitoring

	 	  	 	  
	
Handling of SAEs (notification)

	 	  	 	
ü

	
Medical Review of SAEs & Narrative Creation

	 	  	 	
ü

	
Reporting to Local Regulatory Authority

	 	  	 	
ü

	
Follow-up of SAEs

	 	
ü

	 	  
	
Creation and Distribution of Investigator Notification Letters

	 	
ü

	 	  
	
Medical Monitoring

	 	
ü

	 	  
	
Safety Management Plan (review)

	 	  	 	
ü

 

	
INCResearch Australia Pty Limited

	
Prana Work Order 1000504 v4 3rd August 2012

 

  

  

  

 

ATTACHMENT B

Project Schedule

 

	
Project Timeline/Activities

	
Project Milestones

	 	
Duration

	 	
Start Date

	 	
End Date

	
Pre-Study Period

	 	
3 Months

	 	
1-Mar-12

	 	
31-May-12

	
Enrolment Period

	 	
8 Months

	 	
1-Jun-12

	 	
31-Dec-12

	
Treatment Period

	 	
8 Months

	 	
1-Jan-13

	 	
30-Sep-13

	
Close-out Period

	 	
2 Months

	 	
1-Oct-13

	 	
30-Nov-13

	
Total Study Duration

	 	
21 Months

 

	
INCResearch Australia Pty Limited

	
Prana Work Order 1000504 v4 3rd August 2012

 

  

  

  

 

 

ATTACHMENT C

Project Budget and Payment Schedule

 

Goods and Services Tax (GST)

 

In Australia all goods and services are subject to GST of 10%. Unless otherwise specified, fees are expressed as exclusive of Goods and Services Tax (GST). Where fees are GST exclusive and INC Research is liable to pay GST in respect of any Services provided pursuant to this Agreement, INC Research may add the GST amount to invoices provide to Sponsor for the Services. Provided that the relevant invoice complies with the requirements of a tax invoice to enable Sponsor to claim a credit or refund of GST, Sponsor shall pay the GST amount at the same time and in the same manner as other amounts invoiced under this Agreement.

 

Where the services are directly contracted by an overseas Sponsor GST will not be applicable.

 

Project Costs and Payment Schedule

 

The project budget has been provided in AUD. This will also be the prime currency for invoicing and payment on this project.

 

All clinical services will be invoiced on a unit basis as per the proposed direct cost estimate budget.

 

Upon execution of this Work Order, Sponsor shall make a payment of $58,338.40 (20% of the total direct costs). Thereafter, INC Research will invoice Sponsor on a monthly basis for actual units completed and reconciled at the end of the study.

 

If services requirement exceeding those specified in the cost estimate are required then written approval will be obtained from the Sponsor before conducting the additional services.

 

All professional services have been adjusted to take into account standard fee reviews that would occur over the period of the trial. If the timelines extend beyond the period estimated then INC Research may increase fees beyond the period stated.

 

Indirect costs will be invoiced separately on a monthly basis.

 

INC Research shall provide Sponsor with itemized invoicing of all expenses and fees. Undisputed invoices are payable within 30 days of date of Sponsor’s receipt of invoice as per MSA clause 12.

 

	
INCResearch Australia Pty Limited

	
Prana Work Order 1000504 v4 3rd August 2012

 

  

  

  

 

 

DIRECT COSTS

 

	
Service/Item

	 	
Comments

	 	
Responsibility

	 	
Unit

	 	
Unit Cost (AUD)

	 	
Number 

of Units

	 	
Item Cost

	 	
AUD$

	
Study Start Up Activities

	 	  	 	  	 	  	 	  	 	  	 	  	 	  
	
Study Training/Internal Kick Off Meeting

	 	
Familiarisation, Protocol, IB

	 	
CRA

	 	
per CRA

	 	
1123

	 	
3.00

	 	
3,370

	 	  
	
Study Training/Internal Kick Off Meeting

	 	
Familiarisation, Protocol, IB

	 	
PM

	 	
per PM

	 	
1290

	 	
1.00

	 	
1,290

	 	  
	
Essential Document Collection

	 	
Creation, Collection and Tracking

	 	
CRA

	 	
per site

	 	
1123

	 	
5.00

	 	
5,616

	 	  
	
Study Files

	 	
Set-up of Study Master Files and Investigator Site Files

	 	
PA

	 	
per study

	 	
749

	 	
1.00

	 	
749

	 	  
	
CRA Administration (March 2012 - May 2012)

	 	
Communications - Customer, Site, Project Manager

	 	
CRA

	 	
per month

	 	
3019

	 	
3.00

	 	
9,056

	 	  
	  	 	  	 	  	 	  	 	  	 	  	 	
Subtotal

	 	
$20,080

	
Customer Project Team Meetings

	 	  	 	  	 	  	 	  	 	  	 	  	 	  
	
Customer Kick-off Meeting

	 	
Teleconference

	 	
PM

	 	
per PM

	 	
322

	 	
1.00

	 	
322

	 	  
	
Sponsor Teleconference Participation

	 	
21 x 1 hour Telecon

	 	
PM

	 	
per telecon

	 	
165

	 	
21.00

	 	
3,456

	 	  
	  	 	  	 	  	 	  	 	  	 	  	 	
Subtotal

	 	
$3,778

	
Investigator’s/Monitor’s meeting

	 	  	 	  	 	  	 	  	 	  	 	  	 	  
	
Travel Time

	 	
4 hours Return

	 	
PM

	 	
per PM

	 	
645

	 	
1.00

	 	
645

	 	  
	
Travel Time

	 	
8 hours Return

	 	
CRA

	 	
per CRA

	 	
1123

	 	
1.00

	 	
1,123

	 	  
	
Attendance

	 	
Assume 1.5 day Meeting, 1 PM

	 	
PM

	 	
per PM

	 	
1934

	 	
1.00

	 	
1,934

	 	  
	
Attendance

	 	
Assume 1.5 day Meeting, 2 CRAs

	 	
CRA

	 	
per CRA

	 	
1685

	 	
2.00

	 	
3,370

	 	  
	  	 	  	 	  	 	  	 	  	 	  	 	
Subtotal

	 	
$7,072

	
Site Visits

	 	  	 	  	 	  	 	  	 	  	 	  	 	  
	
Study Initiation

	 	
Includes Preparation, Travel, Time On-site, Reporting and Follow-up

	 	
CRA

	 	
per visit

	 	
1404

	 	
5.00

	 	
7,020

	 	  
	
Monitoring Visits (1 Day Visits)

	 	
Including Preparation, Travel, 1 day On­-site, Reporting and Follow-up 5 Visits/Site

	 	
CRA

	 	
per visit

	 	
1579

	 	
25.00

	 	
39,478

	 	  
	
Closeout Visits

	 	
Includes Preparation, Travel, Time On-site, Reporting and Follow-up

	 	
CRA

	 	
per visit

	 	
1752

	 	
5.00

	 	
8,761

	 	  
	  	 	  	 	  	 	  	 	  	 	  	 	
Subtotal

	 	
$55,258

	
Site Management

	 	  	 	  	 	  	 	  	 	  	 	  	 	  
	
Site Management (June 2012 • September 2013)

	 	
per Month

	 	
CRA

	 	
per month

	 	
3086

	 	
16.00

	 	
49,383

	 	  
	
Site Management (October 2013 • November 2013)

	 	
per Month

	 	
CRA

	 	
per month

	 	
1460

	 	
2.00

	 	
2,920

	 	  
	  	 	  	 	  	 	  	 	  	 	  	 	
Subtotal

	 	
$52,303

	
Project Management

	 	  	 	  	 	  	 	  	 	  	 	  	 	  
	
Local Coordination/Supervision (March 2012 • May 2012)

	 	
per Month

	 	
PM

	 	
per month

	 	
5158

	 	
3.00

	 	
15,475

	 	  
	
Local Coordination/Supervision (June 2012 • September 2013)

	 	
per Month

	 	
PM

	 	
per month

	 	
3296

	 	
16.00

	 	
52,743

	 	  
	
Local Coordination/Supervision (October 2013 - November 2013)

	 	
per Month

	 	
PM

	 	
per month

	 	
3353

	 	
2.00

	 	
6,706

	 	  
	
Project Assistance (March 2012 • November 2013)

	 	
per Month

	 	
PA

	 	
per rronth

	 	
2054

	 	
21.00

	 	
43,144

	 	  
	  	 	  	 	  	 	  	 	  	 	  	 	
Subtotal

	 	
$118,068

	
Safety Monitoring

	 	  	 	  	 	  	 	  	 	  	 	  	 	  
	
Safety Administration

	 	
Includes Set-up, Maintenance and Completion Activities

	 	
Safety Officer

	 	
per study

	 	
4597

	 	
1.00

	 	
4,597

	 	  
	
Handling of SAEs (Notifications)

	 	
All Events - Assume 1 SAE

	 	
Safety Officer

	 	
per SAE

	 	
330

	 	
1.00

	 	
330

	 	  
	
Medical Review of SAEs and Narrative Creation

	 	
All Events - Assume 1 SAE

	 	
Medical Monitor

	 	
per SAE

	 	
851

	 	
1.00

	 	
851

	 	  
	
Reporting to Local Authorities

	 	
Assume 1 Reportable Event

	 	
Safety Officer

	 	
per SAE

	 	
659

	 	
1.00

	 	
659

	 	  
	
Safety Management Plan (review)

	 	 	 	
Safety Officer

	 	
per study

	 	
659

	 	
1.00

	 	
659

	 	  
	
Teleconference

	 	
Assume 1 hour teleconference

	 	
Safety Officer

	 	
per telecon

	 	
165

	 	
1.00

	 	
165

	 	  
	  	 	  	 	  	 	  	 	  	 	  	 	
Subtotal

	 	
$7,261

	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  
	  	 	  	 	  	 	  	 	  	 	  	 	
TOTAL

	 	
$263,821

 

	
INCResearch Australia Pty Limited

	
Prana Work Order 1000504 v4 3rd August 2012

 

  

  

  

 

 

INDIRECT COSTS

 

	
Expense/Item

	 	
Comments

	 	
Unit Cost

	 	
Number

of Units

	 	
Item Cost

AUD$

	 	
AUD$

	  	 	  	 	  	 	  	 	  	 	  
	
Investigator’s/Monitor’s Meeting Attendance

	 	  	 	  	 	  	 	  	 	  
	
Travel/Attendance Costs

	 	
Airfares, accommodation & meals provided by Client, $500 - taxis, currency exchange, meals in transit, phone

	 	
$500/person

	 	
2

	 	
1,000

	 	  
	  	 	  	 	  	 	  	 	
Subtotal

	 	
$1,000

	
Site Visits

	 	  	 	  	 	  	 	  	 	  
	
Other Site visit Costs

	 	
Parking/tolls/meals and incidentals for site visits

	 	
$50/day

	 	
35

	 	
1,750

	 	  
	  	 	  	 	  	 	  	 	
Subtotal

	 	
$1,750

	
General Expenses

	 	  	 	  	 	  	 	  	 	  
	
Couriers, Express Post, Teleconferences

	 	 	 	
$7,000

	 	
1

	 	7,000	 	
 

	
Copying (Excluding ethics submissions), postage, telecommunications (excluding teleconferences), stationery (files)

	 	
$70/site/month, 5 sites for 21 months

	 	
$350/month

	 	
21

	 	
7,350

	 	  
	  	 	  	 	  	 	  	 	
Subtotal

	 	
$14,350

	  	 	  	 	  	 	  	 	  	 	  
	  	 	  	 	  	 	  	 	
TOTAL

	 	
$17,100

 

	
INCResearch Australia Pty Limited

	
Prana Work Order 1000504 v4 3rd August 2012

 

  

  

  

 

 

Change Orders/Changes in Scope

 

INC Research’s participation in this study is based upon the parameters outlined in Attachment A – Services and Attachment B – Project Schedule. Unless otherwise specified in this Work Order, all study Services will be performed under the INC Research Standard Operating Procedures (SOPs). If the scope of the study varies from these study parameters, a Contract Modification (CM) may be necessary. A CM may be due to, but is not limited to, the following project specific situations that change the study parameters (i.e., timeline1, number of subjects or sites) or the scope of work (i.e., additional services; tasks for current services; or costs for current services are modified). These changes in scope may modify the time or costs (direct or indirect) required to complete the study. Requests to engage additional contractors or to incur additional costs with existing contractors engaged by INC Research are considered changes in scope. Accordingly, negotiating efforts to secure confidentiality agreements and service agreements with newly engaged contractors are also considered changes in scope.

 

Once a CM is identified, INC Research will log the out-of-scope activities in a Change Order Log and obtain written acknowledgement from the Sponsor confirming the scope of the possible CM. Once the out-of-scope services reach an estimated 3% of direct project costs (or $10,000, whichever is reached first), a Change Notification Form (CNF) will be submitted to the Sponsor for verification of the project change and to determine if INC Research should wait to begin out-of-scope trial activities or continue while good faith negotiations move towards an executed Change Order (CO).

 

A CO shall be completed once the following threshold amount is reached (which is based on the original contract value of the study).

 

	  	
o

	
$100,000 threshold if contract value is less than $3,000,000; or

	  	
o

	
$300,000 threshold if contract value is over $3,000,000.

 

If out of scope activities do not reach the threshold amount for longer than 180 days since the first CNF or particular CO was initiated, then a CO shall be issued once the time threshold is reached.

 

If out of scope activities do not reach the value or time thresholds prior to end of study, then a CO shall be issued and signed by Sponsor prior to release of the final project deliverable.

 

1 An increase in the study timeline may increase the inflation calculation. Change orders will only address an increase in costs due to inflation for uncompleted activities if the study timeline is pushed into a new calendar year

 

	
INCResearch Australia Pty Limited

	
Prana Work Order 1000504 v4 3rd August 2012 

 

  

  

  

 

 

CHANGE ORDER N°1 to Work Order #1000504

 

This Change Order number 1 to Work Order #1000504 (hereinafter “Change Order”) is made and entered into as of the date of last signature (hereinafter “Effective Date”) by and between Prana Biotechnology Limited (hereinafter “Sponsor”) with an office located at Level 2, 369 Royal Parade, Parkville VIC 3052, Australia and INCResearch Australia Pty Limited, together with its parent company, subsidiaries and legal affiliates (hereinafter “INC Research”) with principal offices located at 124 Lipson Street, Port Adelaide SA 5015, Australia.

 

RECITALS

 

WHEREAS, Sponsor and INC Research have entered into Work Order #1000504 (hereinafter “Agreement”) to perform Services for Protocol # PBT2-203 for study entitled: A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Tolerability, and Efficacy of PBT2 in Patients with Early to Mid-stage Huntington Disease (hereinafter “Study”), which was signed by Sponsor and INC Research on 14th August 2012, and

 

WHEREAS, during the course of the performance of the Study, Sponsor and INC Research have identified changes in assumptions; and

 

WHEREAS, Sponsor desires to retain additional services from INC Research and INC Research desires to supply such services to Sponsor under the terms and conditions set forth herein; and

 

WHEREAS, Sponsor and INC Research agree that all other terms and conditions of the Agreement shall remain in full force and effect, unless specifically agreed otherwise in this Change Order; and

 

WHEREAS, Sponsor and INC Research agree that the services and costs covered by this Change Order are additional to the services and costs covered by the Agreement;

 

NOW THEREFORE, subject to the terms, conditions and covenants hereinafter set forth, INC Research and Sponsor agree as follows:

 

SECTION I: CHANGES IN SCOPE

 

This section contains an overview of the changes in assumptions, timelines, and revision in Scope of services. In summary, this Change Order mainly reflects the following changes:

 

Direct Costs

	
●

	
Addition of seven (7) x One Day Monitoring Visits, to be invoiced only if required.

	
●

	
Addition of eight (8) x Two Day Monitoring Visits, to be invoiced only if required.

	
●

	
Addition of one (1) x Four Day Monitoring Visit.

	
●

	
Addition of nine (9) x Serious Adverse Events (SAE) Notifications, to be invoiced only if required.

	
●

	
Addition of four (4) x Reporting to Local Authorities of SAEs, to be invoiced only if required.

	
●

	
Addition of 6 Monthly Suspected Unexpected Serious Adverse Reaction (SUSAR) Line Listings time for Safety Officer, to be invoiced only if required.

 

INC Research, LLC – CONFIDENTIAL

 

	
INCResearch Australia Pty Limited - 1000504

	
Prana Change Order #1, v2, 10th April 2013

 

  

Page 1 of 8

  

 

 

INC Research, LLC Change Order Form

 

Indirect Costs

	
●

	
Addition of twenty-seven (27) x Other Site Visit Costs.

 

The parties hereby agree the total cost associated with this Change Order is AUD $48,505.00.

 

SECTION II: COSTS OVERVIEW

 

The additional deliverables and tasks performed by INC Research are specified in Attachment A. This Attachment includes an overview of the total prices of deliverables in the original agreement and previous change orders, and an overview of the additional total prices of the new deliverables and services. The total amount of all contracted deliverables (original agreement including all change orders) is shown in Attachment A.

 

A summary of both direct and indirect costs related to the original agreement and all changes in scope as occurred is provided in the table below:

	  	  	  	  	  	  	  	  	  
	  	  	
Effective Date

	  	
Direct Costs

AUD$

	  	
Indirect Costs

AUD$

	  	
Grand Total

AUD$

	
Original Contract

	  	
14th August 2012

	  	
$263,821.00

	  	
$17,100.00

	  	
$280,921.00

	
Change Order # 1

	  	
Upon Execution

	  	
$47,155.00

	  	
$1,350.00

	  	
$48,505.00

	
Total Contract Value

	  	  	  	
$310,976.00

	  	
$18,450.00

	  	
$329,426.00

 

INC Research, LLC – CONFIDENTIAL

	
INCResearch Australia Pty Limited - 1000504

	
Prana Change Order #1, v2, 10th April 2013

 

  

Page 2 of 8

  

 

 

Revised Direct Costs

	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	
Service/Item

	  	
Comments

	  	
Responsibility

	  	
Unit

	  	
Unit

Cost

(AUD)

	  	
Original

Number

of Units

	  	
CO#1

Number

of Units

	  	
Original

Item

Cost

(AUD$)

	  	
CO#1

Item

Cost

(AUD$)

	  	
TOTAL

COST

AUD$

	
Study Start Up Activities

	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	
Study Training/Internal Kick Off Meeting

	  	
Familiarisation, Protocol, IB

	  	
CRA

	  	
per CRA

	  	
1123

	  	
3

	  	
0

	  	
3,370

	  	
0

	  	  
	
Study Training/Internal Kick Off Meeting

	  	
Familiarisation, Protocol, IB

	  	
PM

	  	
per PM

	  	
1290

	  	
1

	  	
0

	  	
1,290

	  	
0

	  	  
	
Essential Document Collection

	  	
Creation, Collection and Tracking

	  	
CRA

	  	
per site

	  	
1123

	  	
5

	  	
0

	  	
5,616

	  	
0

	  	  
	
Study Files

	  	
Set-up of Study Master Files and Investigator Site Files

	  	
PA

	  	
per study

	  	
749

	  	
1

	  	
0

	  	
749

	  	
0

	  	  
	
CRA Administration (March 2012-May 2012)

	  	
Communications - Customer, Site, Project Manager

	  	
CRA

	  	
per month

	  	
3019

	  	
3

	  	
0

	  	
9,056

	  	
0

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	
Subtotal

	  	
20,080

	  	
0

	  	
$20,080

	
Customer Project Team Meetings

	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	
Customer Kick-off Meeting

	  	
Teleconference

	  	
PM

	  	
per PM

	  	
322

	  	
1

	  	
0

	  	
322

	  	
0

	  	  
	
Sponsor Teleconference Participation

	  	
21 x 1 hour Telecon

	  	
PM

	  	
per telecon

	  	
165

	  	
21

	  	
0

	  	
3,456

	  	
0

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	
Subtotal

	  	
3,778

	  	
0

	  	
$3,778

	
Investigator’s/Monitor’s meeting

	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	
Travel Time

	  	
4 hours Return

	  	
PM

	  	
per PM

	  	
645

	  	
1

	  	
0

	  	
645

	  	
0

	  	  
	
Travel Time

	  	
8 hours Return

	  	
CRA

	  	
per CRA

	  	
1123

	  	
1

	  	
0

	  	
1,123

	  	
0

	  	  

 

INC Research, LLC – CONFIDENTIAL

 

	
INCResearch Australia Pty Limited - 1000504

	
Prana Change Order #1, v2, 10th April 2013

 

  

Page 3 of 8

  

 

 

INC Research, LLC Change Order Form

 

	
Service/Item

	  	
Comments

	  	
Responsibility

	  	
Unit

	  	
Unit

Cost

(AUD)

	  	
Original

Number

of Units

	  	
CO#1

Number

of Units

	  	
Original

Item

Cost

(AUD$)

	  	
CO#1

Item

Cost

(AUD$)

	  	
TOTAL

COST

AUD$

	
Attendance

	  	
Assume 1.5 day Meeting, 1 PM

	  	
PM

	  	
per PM

	  	
1934

	  	
1

	  	
0

	  	
1,934

	  	
0

	  	  
	
Attendance

	  	
Assume 1.5 day Meeting, 2 CRAs

	  	
CRA

	  	
per CRA

	  	
1685

	  	
2

	  	
0

	  	
3,370

	  	
0

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	
Subtotal

	  	
7,072

	  	
0

	  	
$7,072

	
Site Visits

	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	
Study Initiation

	  	
Includes Preparation, Travel, Time On-site, Reporting and Follow-up

	  	
CRA

	  	
per visit

	  	
1404

	  	
5

	  	
0

	  	
7,020

	  	
0

	  	  
	
Monitoring Visits (1 Day Visits)

	  	
Including Preparation, Travel, 1 day On-site, Reporting and Follow-up - only if required

	  	
CRA

	  	
per visit

	  	
1579

	  	
25

	  	
7

	  	
39,478

	  	
11,054

	  	  
	
Monitoring Visits (2 Day Visits)

	  	
Including Preparation, Travel, 2 days On-site, Reporting and Follow-up - only if required

	  	
CRA

	  	
per visit

	  	
3015

	  	
0

	  	
8

	  	
0

	  	
24,117

	  	  
	
Monitoring Visits (4 Day Visits)

	  	
Including Preparation, Travel, 4 days On-site, Reporting and Follow-up

	  	
CRA

	  	
per visit

	  	
5886

	  	
0

	  	
1

	  	
0

	  	
5,886

	  	  
	
Closeout Visits

	  	
Includes Preparation, Travel, Time On-site, Reporting and Follow-up

	  	
CRA

	  	
per visit

	  	
1752

	  	
5

	  	
0

	  	
8,761

	  	
0

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	
Subtotal

	  	
55,258

	  	
41,057

	  	
$96,315

	
Site Management

	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	
Site Management (June 2012 - September 2013)

	  	
per Month

	  	
CRA

	  	
per month

	  	
3086

	  	
16

	  	
0

	  	
49,383

	  	
0

	  	  
	
Site Management (October 2013 - November 2013)

	  	
per Month

	  	
CRA

	  	
per month

	  	
1460

	  	
2

	  	
0

	  	
2,920

	  	
0

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	
Subtotal

	  	
52,303

	  	
0

	  	
$52,303

 

INC Research, LLC – CONFIDENTIAL

 

	
INCResearch Australia Pty Limited - 1000504

	
Prana Change Order #1, v2, 10th April 2013

 

  

Page 4 of 8

  

 

 

INC Research, LLC Change Order Form

	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	
Service/Item

	  	
Comments

	  	
Responsibility

	  	
Unit

	  	
Unit

Cost

(AUD)

	  	
Original

Number

of Units

	  	
CO#1

Number

of Units

	  	
Original

Item

Cost

(AUD$)

	  	
CO#1

Item

Cost

(AUD$)

	  	
TOTAL

COST

AUD$

	
Project Management

	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	
Local Coordination/Supervision (March 2012 - May 2012)

	  	
per Month

	  	
PM

	  	
per month

	  	
5158

	  	
3

	  	
0

	  	
15,475

	  	
0

	  	  
	
Local Coordination/Supervision (June 2012 - September 2013)

	  	
per Month

	  	
PM

	  	
per month

	  	
3296

	  	
16

	  	
0

	  	
52,743

	  	
0

	  	  
	
Local Coordination/Supervision (October 2013 - November 2013)

	  	
per Month

	  	
PM

	  	
per month

	  	
3353

	  	
2

	  	
0

	  	
6,706

	  	
0

	  	  
	
Project Assistance (March 2012-November 2013)

	  	
per Month

	  	
PA

	  	
per month

	  	
2054

	  	
21

	  	
0

	  	
43,144

	  	
0

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	
Subtotal

	  	
118,068

	  	
0

	  	
$118,068

	
Safety Monitoring

	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	
Safety Administration

	  	
Includes Set-up, Maintenance and Completion Activities

	  	
Safety Officer

	  	
per study

	  	
4597

	  	
1

	  	
0

	  	
4,597

	  	
0

	  	  
	
Handling of SAEs (Notifications)

	  	
All Events - Assume 10

	  	
Safety Officer

	  	
per SAE

	  	
330

	  	
1

	  	
9

	  	
330

	  	
2,967

	  	  
	
Medical Review of SAEs and Narrative Creation

	  	
All Events - Assume 1 SAE

	  	
Medical Monitor

	  	
per SAE

	  	
851

	  	
1

	  	
0

	  	
851

	  	
0

	  	  
	
Reporting to Local Authorities

	  	
All Events - Assume 5

	  	
Safety Officer

	  	
per SAE

	  	
659

	  	
1

	  	
4

	  	
659

	  	
2,637

	  	  
	
6-Monthly SUSAR Line Listing

	  	
Preparation, distribute and tracking

	  	
Safety Officer

	  	
per study

	  	
494

	  	
0

	  	
1

	  	
0

	  	
494

	  	  
	
Safety Management Plan (review)

	  	  	  	
Safety Officer

	  	
per study

	  	
659

	  	
1

	  	
0

	  	
659

	  	
0

	  	 

 

INC Research, LLC – CONFIDENTIAL

 

	
INCResearch Australia Pty Limited - 1000504

	
Prana Change Order #1, v2, 10th April 2013

 

  

Page 5 of 8

  

 

 

INC Research, LLC Change Order Form

 

	
Service/Item

	  	
Comments

	  	
Responsibility

	  	
Unit

	  	
Unit

Cost

(AUD)

	  	
Original

Number

of Units

	  	
CO#1

Number

of Units

	  	
Original

Item

Cost

(AUD$)

	  	
CO#1

Item

Cost

(AUD$)

	  	
TOTAL

COST

AUD$

	
Teleconference

	  	
Assume 1 hour teleconference

	  	
Safety Officer

	  	
per telecon

	  	
165

	  	
1

	  	
0

	  	
165

	  	
0

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	
Subtotal

	  	
7,261

	  	
6,098

	  	
$13,360

	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	
TOTAL

	  	
263,821

	  	
47,155

	  	
$310,976

 

Revised Indirect Costs

 

	
Expense/Item

	  	
Comments

	  	
Unit Cost

	  	
Original

Number

of Units

	  	
CO#1

Number

of Units

	  	
Original

Item

Cost

AUD$

	  	
CO#1

Item

Cost

AUD$

	  	
TOTAL

COST

AUD$

	
Investigator’s/Monitor’s Meeting Attendance

	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	
Travel/Attendance Costs

	  	
Airfares, accommodation & meals provided by Client, $500 - taxis, currency exchange, meals in transit, phone

	  	
$500/person

	  	
2

	  	
0

	  	
1,000

	  	
0

	  	  
	  	  	  	  	  	  	  	  	
Subtotal

	  	
1,000

	  	
0

	  	
$1,000

	
Site Visits

	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	
Other Site visit Costs

	  	
Parking/tolls/meals and incidentals for site visits

	  	
$50/day

	  	
35

	  	
27

	  	
1,750

	  	
1,350

	  	  
	  	  	  	  	  	  	  	  	
Subtotal

	  	
1,750

	  	
1,350

	  	
$3,100

	
General Expenses

	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	
Couriers, Express Post, Teleconferences

	  	  	  	
$7,000

	  	
1

	  	
0

	  	
7,000

	  	
0

	  	  

 

INC Research, LLC – CONFIDENTIAL

 

	
INCResearch Australia Pty Limited - 1000504

	
Prana Change Order #1, v2, 10th April 2013

 

  

Page 6 of 8

  

 

 

INC Research, LLC Change Order Form

 

	
Copying (Excluding ethics submissions), postage, telecommunications (excluding teleconferences), stationery (files)

	  	
$70/site/month, 5 sites for 21 months

	  	
$350/month

	  	
21

	  	
0

	  	
7,350

	  	
0

	  	  
	  	  	  	  	  	  	  	  	
Subtotal

	  	
14,350

	  	
0

	  	
$14,350

	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	
TOTAL

	  	
17,100

	  	
1,350

	  	
$18,450

 

INC Research, LLC – CONFIDENTIAL

 

	
INCResearch Australia Pty Limited - 1000504

	
Prana Change Order #1, v2, 10th April 2013

 

  

Page 7 of 8

  

 

 

SIGNATURE

 

COUNTERPARTS. This Change Order may be signed in counterparts and said counterparts shall be treated as though signed as one document. The parties acknowledge legal validity of facsimile, portable document format or other commercially acceptable electronic exchange of copies of the documents, which are essential for Change Order execution. A party which uses a facsimile, portable document format or other commercially acceptable electronic exchange copy of an authorized person’s signature in the documents guaranties its authenticity.

 

IN WITNESS WHEREOF, the undersigned have caused this Change Order to be executed by a duly authorized individual on behalf of each requisite party effective as of the day and year last written below.

	  	  	  
	
Prana Biotechnology Limited

	  	
INCResearch Australia Pty Limited

	                          	  	                          
	
Signature By:

	  	
Signature By:

	
DIANNE ANGUS

	  	
Garth Tierney

	
Name (print)

	  	
Name (print)

	
C.O.O

	  	
Executive Vice President, Asia/Pacific

	
Title

	  	
Title

	
16 / April / 2013

	  	
24/04/2013

	
Date

	  	
Date

 

INC Research, LLC – CONFIDENTIAL

 

	
INCResearch Australia Pty Limited - 1000504

	
Prana Change Order #1, v2, 10th April 2013

 

Page 8 of 8exhibit_4-27.htm

Exhibit 4.27

 

 

WORK ORDER

INC Research Project # 1002213

Protocol # PBT2-203

 

This Work Order (hereinafter “Work Order”) is between Prana Biotechnology Limited (hereinafter “Sponsor”) with principal offices located at Level 2, 369 Royal Parade, Parkville VIC 3052 Australia and INCResearch Australia Pty Limited, together with its parent company, subsidiaries and legal affiliates (hereinafter “INC Research”) with offices located at 124 Lipson Street, Port Adelaide SA 5015 Australia and relates to the Master Services Agreement effectively dated 22nd September 2011 which expressly incorporates this Work Order hereto by reference into the Master Services Agreement. Pursuant to the Master Services Agreement, INC Research has agreed to perform certain services in accordance with written work orders, such as this one, entered into from time to time describing such services.

 

This document constitutes a Work Order under the Master Services Agreement and this Work Order and the Services contemplated herein are subject to the terms and provisions of the Master Services Agreement.

	  	  
	
1.

	
SERVICES: INC Research will render such services (hereinafter “Services”) as may be necessary to complete in a professional manner the project described below:

	  	  
	  	
Protocol # PBT2-203: A randomized, double-blind, placebo controlled study to assess the safety and tolerability and efficacy of PBT2 in patients with early to mid-stage Huntington disease.

	  	  
	  	
INC Research will perform the Services as specified in Attachment A to this Work Order.

	  	  
	
2.

	
PROJECT SCHEDULE: The major project milestones and target dates are described in Attachment B to this Work Order. Both parties agree that the Project Schedule is a reasonable schedule for the Services to be performed and will put forth all reasonable efforts to comply with these dates.

	  	  
	
3.

	
COMPENSATION AND EXPENSES: Sponsor shall pay the fees for INC Research’s Services in accordance with the Project Budget and Payment Schedule provided in Attachment C of this Work Order. INC Research shall invoice Sponsor for taxes or duties actually incurred by INC Research which are imposed upon INC Research by any governmental agency, including, but not limited to Value Added Tax, Stamp Tax, and/or General Sales Tax, as a result of this Agreement with the exception of taxes based on INC Research’s income.

 

	
INCResearch Australia Pty Limited - 1002213

	  
	
Prana Biotechnology Limited Work Order, Version 3, 30th January 2013

	
 

 

  

1

  

 

 

	
4.

	
NOTICES AND PAYMENTS: All communications, notices and payments required under this Work Order shall be mailed by first class mail, postage prepaid, or by overnight carriers, to the respective parties at the addresses set forth below, or to such other addresses as the parties may from time to time specify in writing.

 

	  	  	  
	  	
If to Sponsor:

	  
	  	  	
Carolyn Stone

	  	  	
Clinical Program Manager

	  	  	
Prana Biotechnology Limited

	  	  	
Level 2

	  	  	
369 Royal Parade

	  	  	
Parkville VIC 3052 Australia

	  	  	
cstone@pranabio.com

	  	  	  
	  	  	
Cc: Caroline Herd

	  	  	
cherd@pranabio.com

	  	  	  
	  	
If to INC Research:

	  

 

	  	
For Communications:

	
Contracts Management

	  	  	
INCResearch Australia Pty Limited

	  	  	
124 Lipson Street

	  	  	
Port Adelaide SA 5015 Australia

	  	  	
Phone: +61 (0) 8 7202 1500

	  	  	
Facsimile: +61 (0) 8 7202 1599

	  	  	  
	  	
For Payments (Via Wire):

	  
	  	  	  
	  	
Beneficiary Bank:

	
HSBC Bank Australia Ltd

	  	
Beneficiary Bank Address:

	
Ground Floor, 55 Grenfell Street

	  	  	
Adelaide SA 5000, Australia

	  	
Account Name:

	
INCResearch Australia Pty Limited

	  	
BSB (Routing Number):

	 
	  	
Account Number:

	 
	  	
Swift:

	 

 

	
5.

	
TRANSFER OF OBLIGATIONS: Sponsor assigns the responsibilities pertaining to the Study to INC Research as indicated in Attachment A, Services,

 

	
INCResearch Australia Pty Limited - 1002213

	  
	
Prana Biotechnology Limited Work Order, Version 3, 30th January 2013

	
 

  

2

  

 

 

IN WITNESS WHEREOF, the undersigned have caused this Work Order to be executed by a duly authorized individual on behalf of each requisite party effective as of the day and year last written below. In the event that the parties execute this Work Order by exchange of electronically signed copies or facsimile signed copies, the parties agree that, upon being signed by both parties, this Work Order shall become effective and binding and that facsimile copies and/or electronic signatures will constitute evidence of the existence of this Work Order with the expectation that original documents may later be exchanged in good faith. Thereafter, the parties agree that in connection with request for information that either party may need from the other related to the Services provided hereunder, both parties expressly permit communication via facsimile to the extent allowed by applicable laws and regulations to be disseminated in that manner.

 

Prana Biotechnology Limited

	  	  	 
	
By:

		 
	
Name:  

	
Dianne Angus

	 
	
Title:

	
C.O.O.

	 
	
Date:

	
27-3-2013

	 

 

INCResearch Australia Pty Limited

 

	
By:

		 
	
Name:  

	
Garth Tierney

	 
	
Title:

	
Regional General Manager, Australia and South East Asia

	 
	
Date

	
28/3/2013

	 

 

	
INCResearch Australia Pty Limited - 1002213

	  
	
Prana Biotechnology Limited Work Order, Version 3, 30th January 2013

	
 

 

  

3

  

 

IN WITNESS WHEREOF, the undersigned have caused this Work Order to be executed by a duly authorized individual on behalf of each requisite party effective as of the day and year last written below. In the event that the parties execute this Work Order by exchange of electronically signed copies or facsimile signed copies, the parties agree that, upon being signed by both parties, this Work Order shall become effective and binding and that facsimile copies and/or electronic signatures will constitute evidence of the existence of this Work Order with the expectation that original documents may later be exchanged in good faith. Thereafter, the parties agree that in connection with request for information that either party may need from the other related to the Services provided hereunder, both parties expressly permit communication via facsimile to the extent allowed by applicable laws and regulations to be disseminated in that manner.

 

Prana Biotechnology Limited

	  	  	 
	
By:

		 
	
Name:  

	
Dianne Angus

	 
	
Title:

	
C.O.O.

	 
	
Date:

	
27-3-2013

	 

 

INCResearch Australia Pty Limited

 

	
By:

	  	 
	
Name:  

	
Garth Tierney

	 
	
Title:

	
Regional General Manager, Australia and South East Asia

	 
	
Date:

	  	 

 

	
INCResearch Australia Pty Limited - 1002213

	  
	
Prana Biotechnology Limited Work Order, Version 3, 30th January 2013

	
 

  

3

  

 

 

ATTACHMENT A

Services

	  	  
	
Project Specifications

	
GENERAL

	  
	
Drug Name

	
PBT2

	
Indication

	
Huntington Disease

	
Phase

	
II

	
PROJECT MANAGEMENT

	
Number of Sponsor

Teleconferences

	
12 x 1 hour Teleconference monthly

Up to 4 Face to Face meetings if needed

	
STATISTICAL ANALYSIS/MEDICAL WRITING

	
Number of Statistical Analyses

	
19

	
Number of Unique

Tables/Listings/Figures for Final

Analysis

	
14 Unique Tables / 38 Listings / 36 Figures

	
Number Replicate Tables for

Final Analysis

	
20 Replicate Tables

	
Import of Biomarker, PK, ECG

and Imaging data

	
2 transfers for each data type

	
Final Deliverable

	
Final Analysis Sets and Clinical Study Report

	  	  
	
AUDIT SERVICES

	
Number of Countries

	
2 (USA & Australia)

	
Number of Audits

	
2 X GCP Audit & 1 X Vendor Audit

	
Travel Expense

	
The travel cost and travel time will depend upon the

location of sites and external service provider selected.

 

	
INCResearch Australia Pty Limited - 1002213

	  
	
Prana Biotechnology Limited Work Order, Version 3, 30th January 2013

	
 

 

  

4

  

 

	
ACTIVITY

	
Prana

	
INC

Research

	
1.

	
Pre-Trial Regulatory Filing/Country Level

	  	  
	
1.1

	
Compile relevant regulatory documents

	
X

	  
	
1.2

	
Obtain regulatory approval

	
X

	  
	
1.3

	
Answer regulatory queries

	
X

	  
	
1.4

	
Manage interactions with regulatory authorities

	
X

	  
	
2.

	
Study Documents Preparation/Study Docs

	  	  
	
2.1

	
Design Study

	
X

	  
	
3.

	
Protocol Versions

	  	  
	
3.1

	
Write protocol

	
X

	  
	
3.2

	
QC approved protocol

	
X

	  
	
3.3

	
Print final protocol copies in English

	
X

	  
	
3.4

	
Final protocol translations and certification

	
X

	  
	
3.5

	
Printing of translation of protocol

	
X

	  
	
4.

	
Study Guide Versions

	  	  
	
4.1

	
Prepare study procedures manual

	
X

	  
	
4.2

	
Print study procedures manual

	
X

	  
	
5.

	
Investigator Brochure & Study Aids

	  	  
	
5.1

	
Prepare Clinical Investigator Brochure

	
X

	  
	
5.2

	
Print Clinical Investigator Brochure

	
X

	  
	
5.3

	
Prepare study aids

	
X

	  
	
5.4

	
Print study aids

	
X

	  
	
6.

	
Informed Consent Form

	  	  
	
6.1

	
Write template Participant Information Sheet (PIS) and Informed Consent Form (CF)

	
X

	  
	
6.2

	
Review site specific PIS and ICF

	
X

	  
	
6.3

	
Translations of PIS and ICF

	
X

	  
	
7.

	
Participant Diaries

Pre-Study Preparation and Recruitment/Study

	  	  
	
7.1

	
Design and finalise diary cards or equivalent

	
X

	  

 

	
INCReseareh Australia Pty Limited - 1002213

	  
	
Prana Biotechnology Limited Work Order, Version 3, 30th January 2013

	
 

 

  

5

  

 

 

	
7.2

	
Translate diary cards

	
X

	  
	
7.3

	
Print diary cards

	
X

	  
	
7.4

	
Site/Sponsor Trial Master File organisation

	
X

	  
	
7.5

	
Prepare study site files

	
X

	  
	
7.6

	
Print study site files

	
X

	  
	
8.

	
Evaluation Visits

	  	  
	
8.1

	
Identify trial sites

	
X

	  
	
8.2

	
Select Site investigators

	
X

	  
	
8.3

	
Evaluate trial site

	
X

	  
	
8.4

	
Prepare and finalise confidentiality agreement for investigators

	
X

	  
	
8.5

	
Pre-study visits

	
X

	  
	
9.

	
Negotiation Visits

	  	  
	
9.1

	
Prepare, negotiate and execute site contractual agreement and budget.

	
X

	  
	
10.

	
Ethics

	  	  
	
10.1

	
Preparation/Co-ordination of IEC/IRB submission

	
X

	  
	
10.2

	
Investigator/Patient indemnity agreement

	
X

	  
	
10.3

	
Obtain Local IEC/IRB approval

	
X

	  
	
10.4

	
Pay Ethics Committee

	
X

	  
	
11.

	
Investigator Meetings

	  	  
	
11.1

	
Planning/ Administration of Investigator Meetings

	
X

	  
	
11.2

	
Prepare Investigator Meetings Binders/ materials

	
X

	  
	
11.3

	
Attendance/Input at Investigator Meetings

	
X

	  
	
11.4

	
Train Investigator and Site Personnel

	
X

	  
	
12.

	
CRO Training/Trainings

	  	  
	
12.1

	
Administration and responsibility for monitor training (SOP, protocol, IMP)

	
X

	  
	
12.2

	
Attendance/input for monitor training

	
X

	  
	
13.

	
Project Management

	  	  
	
13.1

	
Administer and track site payments

	
X

	  
	
13.2

	
Collect pre-study documents e.g. 1572s, CVs, IEC/IRB approvals

	
X

	  
	
13.3

	
Development & maintenance of project databases

	
X

	  

 

	
INCResearch Australia Pty Limited - 1002213

	  
	
Prana Biotechnology Limited Work Order, Version 3, 30th January 2013

	
 

 

  

6

  

 

	
13.4

	
Preparation of status reports

	
X

	  
	
13.5

	
PM Meetings & telephone contacts with Prana

	  	
X

	
13.6

	
Establishment & maintenance of project files -statistical & CSR only

	  	
X

	
13.7

	
Periodic budget & contract review

	
X

	
X

	
14.

	
Safety/ Pharmacovigilance

	  	  
	
14.1

	
24/7 Medical Monitor Hotline

	
X

	  
	
14.2

	
Generate data for Annual Safety Report (if applicable)

	
X

	  
	
15.

	
Central Laboratory

	  	  
	
15.1

	
Identification of Central Laboratories

	
X

	  
	
15.2

	
Pre-Qualification Audit of Central Laboratories

	
X

	  
	
15.3

	
Selection of Central Laboratories

	
X

	  
	
15.4

	
Payment of Central Laboratories

	
X

	  
	
15.5

	
Management of Central Laboratories

	
X

	  
	
15.6

	
Organise Project Teleconferences

	
X

	  
	
15.7

	
Provide status reports

	
X

	  
	
15.8

	
Review of clinical laboratory data

	
X

	  
	
15.9

	
Lab Data transfer to study database

	
X

	  
	
16.

	
Audits

	  	  
	
16.1

	
Conduct of GCP audit

	  	
X

	
16.2

	
QA site audits (as per audit plan)

	  	
X

	
16.3

	
Final QA audit of report, database, sites (if required) and systems

	  	
X

	
17.

	
Site Initiation Visits/Initiation Days

	  	  
	
17.1

	
Conduct site initiation visits & provide written reports

	
X

	  
	
18.

	
Site Monitoring/Monitor Days

	  	  
	
18.1

	
Monitor sites regularly (per GCP)

	
X

	  
	
18.2

	
Source data verification (SDV) of CRFs

	
X

	  
	
18.3

	
Provide written monitoring reports

	
X

	  
	
18.4

	
Review Monitoring Visit Reports

	
X

	  
	
18.5

	
Perform Drug/Accountability at Site

	
X

	  
	
19.

	
Site Close-Out

	  	  
	
19.1

	
Perform final drug accountability

	
X

	  
	
19.2

	
Disposal of unused supplies

	
X

	  

 

	
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19.3

	
Conduct site close-out visit & provide written reports

	
X

	  
	
20.

	
Site management/Site Months

	  	  
	
20.1

	
Telephone sites as required

	
X

	  
	
20.2

	
Shipment and tracking of completed CRFs to Data Management (if applicable)

	
X

	  
	
20.3

	
Provide status reports

	
X

	  
	
21.

	
IMP Packaging and Distribution/Completed Pts

	  	  
	
21.1

	
Supply IMP to Clinical Trial Supply ESP

	
X

	  
	
21.2

	
Source and supply of ancillary clinical trial supplies

	
X

	  
	
21.3

	
Shipment and co-ordination of IMP to sites

	
X

	  
	
21.4

	
Drug tracking: Sponsor → Sites → Destruction

	
X

	  
	
22.

	
Case Report Form

	  	  
	
22.1

	
Select EDC Vendor

	
X

	  
	
22.2

	
Design of eCRF

	
X

	  
	
22.3

	
QC approval of eCRF

	
X

	  
	
22.4

	
QA approved eCRF

	
X

	  
	
22.5

	
Print eCRFs in English (If applicable)

	
X

	  
	
22.6

	
Translation of eCRFs

	
X

	  
	
22.7

	
Prepare eCRF Instruction Manual

	
X

	  
	
23.

	
Date Clean-Up/eCRF Pages

	  	  
	
23.1

	
Issue CRF Queries

	
X

	  
	
25.

	
Data Management

	  	  
	
25.1

	
Data entry

	
X

	  
	
25.2

	
Medical coding (MedDRA & WHO)

	
X

	  
	
25.3

	
Data Validation: CRF pre-entry review

	
X

	  
	
25.4

	
Data Validation: Running validation programs

	
X

	  
	
25.5

	
Data Validation: Query resolution, handling, editing

	
X

	  
	
25.6

	
Data QC/Report

	
X

	  
	
25.7

	
Reconciliation of SAEs

	
X

	  
	
25.8

	
Transfer Laboratory Data

	
X

	
X

	
25.9

	
Database lock

	
X

	  
	
26.

	
Statistics

	  	  

 

	
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26.1

	
Statistical input into study design

	
X

	  
	
26.2

	
Prepare and finalise Statistical Analysis Plan

	  	
X

	
26.3

	
Perform statistical analysis

	  	
X

	
26.4

	
Prepare statistical text for inclusion in the Clinical study report

	  	
X

	
26.5

	
QA checks of statistical text

	  	
X

	
27.

	
Clinical Study Report

	  	  
	
27.1

	
Approval of Style Manual for Clinical Study Report

	
X

	  
	
27.2

	
Prepare ICH format Clinical Study Report

	  	
X

	
27.4

	
Validation of any data conversion

	  	
X

	
27.5

	
Validation of data transfer

	  	
X

	
27.6

	
Review of CSR drafts (x2)

	
X

	
X

	
27.7

	
Provide final copy of ICH format Clinical Study Report (Word & PDF), including all appendices

	  	
X

	
27.8

	
QC of Clinical Study report

	  	
X

	
28.

	
Archiving

	  	  
	
28.1

	
Assistance with archiving of Investigator Study file if required.

	  	
X

	
28.2

	
Database – final archiving

	
X

	  

 

	
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ATTACHMENT B

Project Schedule

 

	
Timelines

	
Start Date

	
End Date

	
1st January 2013

	
1st January 2014

	
Total - 12 Months

 

	
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ATTACHMENT C

Project Budget and Payment Schedule

 

	
Total Cost Summary (AUD)

	
Direct Costs

	
$ 173,754.00

	
Pass-Through Costs

	
$ 2,310.00

	
TOTAL PROJECT COST

	
$ 176,064.00

 

Goods and Services Tax (GST)

 

In Australia all goods and services are subject to GST of 10%. Unless otherwise specified, fees are expressed as exclusive of Goods and Services Tax (GST). Where fees are GST exclusive and INC Research is liable to pay GST in respect of any Services provided pursuant to this Agreement, INC Research may add the GST amount to invoices provide to Sponsor for the Services. Provided that the relevant invoice complies with the requirements of a tax invoice to enable Sponsor to claim a credit or refund of GST, Sponsor shall pay the GST amount at the same time and in the same manner as other amounts invoiced under this Agreement.

 

Where the services are directly contracted by an overseas Sponsor GST will not be applicable.

 

Project Costs and Payment Schedule

 

INC Research’s study budget includes inflation for annual wage/earnings increases at a rate of three percent (3%). If a subsequent change in scope necessitates a revision to the study timeline, any inflationary adjustment will be delineated in applicable invoices as a separate line item rather than embedded in the affected unit price.

 

All services will be invoiced on a unit basis as per the proposed direct cost estimate budget.

 

Upon execution of this Work Order, Sponsor shall make a payment of AUD $34,302.00 (20% of the total direct costs). Thereafter, INC Research will invoice Sponsor on a monthly basis for actual units completed and reconciled at the end of the study.

 

If services requirement exceeding those specified in the cost estimate are required then written approval will be obtained from the Sponsor before conducting the additional services.

	  	  	  
	
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Indirect costs will be invoiced separately on a monthly basis.

 

As some of the study pass-through expenses may be incurred in a currency other than AUD, pass-through expenses will be invoiced to Sponsor in AUD based upon actual invoices, and subject to the exchange rate published in oanda.com at the spot rate on the day the expense is invoiced by INC Research.

 

INC Research shall provide Sponsor with itemized invoicing of all expenses and fees. Undisputed invoices are payable within 30 days of date of Sponsor’s receipt of invoice as per MSA clause 12.

	  	  	  
	
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Direct Costs

 

	
Service/Item

	 	
Comments

	 	
Responsibility

	 	
Unit

	 	
Unit 

Cost 

(AUD)

	 	
Number 

of Units

	 	
Item

Cost

	 	
ALD$

	
Data Management & Statistics

	 	  	 	  	 	  	 	  	 	  	 	  	 	  
	
Project familiarization

	 	
Arrange test data extract from database, assess data structure and data quality. Receive final transfer from HSG

	 	
Clinical Programmer

	 	
1hr

	 	
108

	 	
16.00

	 	
1,728

	 	  
	
HSG Meeting (USA)

	 	
Three days of meetings plus travel time. (Jan Steyn or Melanie Bailey Tippetts and Peter Fursdon). Travel & accommodation arranged by Prana

	 	  	 	
40hrs per person

	 	
8000

	 	
2.00

	 	
16,000

	 	  
	
Database design

	 	
Review annotated CRF and database specification documentations

	 	
Clinical Programmer

	 	
0.5hr/dataset

	 	
30

	 	
25.00

	 	
750

	 	  
	
Data Validation Manual

	 	
Review DVM text/data management plan specifying edit checks

	 	
CDA

	 	
40hrs

	 	
104

	 	
16.00

	 	
1,664

	 	  
	
Import BM, PK, ECG and immunology data

	 	
Electronic transfers of Biomarker, PK, ECG and MRI data (Data transfer plans, test transfers & final transfers)

	 	
DBA

	 	
1 lab source

	 	
1122

	 	
4.00

	 	
4,488

	 	  
	
Statistical Analysis Plan (SAP)

	 	
Includes text and table and listing shells

	 	
Statistician

	 	
1 SAP

	 	
9426

	 	
1.00

	 	
9,426

	 	  
	
Identify Protocol Deviations and define Analysis populations

	 	
Unblinding, Protocol deviations and Definition of populations

	 	
Statistician

	 	
I study

	 	
1600

	 	
1.00

	 	
1,600

	 	  
	
Analysis Datasets

	 	
Specification, Programming & QC

	 	
SAS Programmer

	 	
1 study

	 	
21294

	 	
1.00

	 	
21,294

	 	  

 

	
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Service/Item

	 	
Comments

	 	
Responsibility

	 	
Unit

	 	
Unit 

Cost 

(AUD)

	 	
Number 

of Units

	 	
Item

Cost

	 	
AUD$

	
Production of Tables & Listings

	 	
14 Unique tables. Cost per extra $1014 20 Repeat tables. Cost per extra $338 36 Figures, Cost per extra $592 38 Listings. Cost per extra $422

	 	
SAS Programmer

	 	
1 study

	 	
52221

	 	
1.00

	 	
52,221

	 	  
	
Statistical Analysis

	 	
19 analysis endpoints. Cost per extra $424

	 	
Statistician

	 	
1 analysis endpoint

	 	
424

	 	
19.00

	 	
8,056

	 	  
	
Input to Final report

	 	
Text for inclusion in study report

	 	
Statistician

	 	
1 Study

	 	
5088

	 	
1.00

	 	
5,088

	 	  
	
Unit based Data Management Costs

	 	
Program consistency check

	 	
Clinical Programmer

	 	
1 check

	 	
60

	 	
1.00

	 	
60

	 	  
	
Unit based Data Management Costs

	 	
Raise manual data query

	 	
CDA

	 	
1 query

	 	
52

	 	
1.00

	 	
52

	 	  
	  	 	  	 	  	 	  	 	  	 	  	 	
Subtotal

	 	
$122,427

	
Medical Writing

	 	  	 	  	 	  	 	  	 	  	 	  	 	  
	
Clinical Study Report (CSR)

	 	  	 	
Medical Writer

	 	
per CSR

	 	
25418

	 	
1.00

	 	
25,418

	 	  
	  	 	  	 	  	 	  	 	  	 	  	 	
Subtotal

	 	
$25,418

	
Quality Assurance -Site Audits

	 	  	 	  	 	  	 	  	 	  	 	  	 	  
	
Quality Assurance Site Audits

	 	
GCP Audits preparation time

	 	
QAA

	 	
Site Audit

	 	
1314

	 	
2.00

	 	
2,628

	 	  
	  	 	
GCP Audits on-site

	 	
QAA

	 	
Site Audit

	 	
2628

	 	
2.00

	 	
5,255

	 	  
	  	 	
GCP Audits report preparation

	 	
QAA

	 	
Site Audit

	 	
1971

	 	
2.00

	 	
3,941

	 	  
	  	 	
GCP Audits travel time

	 	
QAA

	 	
Site Audit

	 	
1570

	 	
2.00

	 	
3,140

	 	  
	  	 	
Review of Audit reports

	 	
QAA

	 	
Site Audit

	 	
443

	 	
2.00

	 	
886

	 	  
	
QA Audit of Vendor(s)

	 	  	 	
QAA

	 	
Audit

	 	
10059

	 	
1.00

	 	
10,059

	 	  
	  	 	  	 	  	 	  	 	  	 	  	 	
Subtotal

	 	
$25,909

	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  
	  	 	  	 	  	 	  	 	  	 	  	 	
TOTAL

	 	
$173,754

 

	
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Pass-Through Costs

 

	
Expense/Item

	 	
Comments

	 	
Unit Cost 

(AUD)

	 	
Number 

of Units

	 	
Item 

Cost 

AUD$

	 	
AUD$

	
Site Visits

	 	  	 	  	 	  	 	  	 	  
	
Travel Costs (flights/accommodation/taxis)

	 	  	 	
$l,155/visit

	 	
2

	 	
2,310

	 	  
	  	 	  	 	  	 	  	 	
Subtotal

	 	
$2,310

	  	 	  	 	  	 	  	 	  	 	  
	  	 	  	 	  	 	  	 	
TOTAL

	 	
$2,310

 

	
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Change Orders/Changes in Scope

 

INC Research's participation in this study is based upon the parameters outlined in Attachment A - Services and Attachment B - Project Schedule. Unless otherwise specified in this Work Order, all study Services will be performed under the INC Research Standard Operating Procedures (SOPs). If the scope of the study varies from these study parameters, a Contract Modification (CM) may be necessary. A CM may be due to, but is not limited to, the following project specific situations that change the study parameters (i.e., timeline , number of subjects or sites) or the scope of work (i.e., additional services; tasks for current services; or costs for current services are modified). These changes in scope may modify the time or costs (direct or indirect) required to complete the study. Requests to engage additional contractors or to incur additional costs with existing contractors engaged by INC Research are considered changes in scope. Accordingly, negotiating efforts to secure confidentiality agreements and service agreements with newly engaged contractors are also considered changes in scope.

 

Once a CM is identified, INC Research will log the out-of-scope activities in a Change Order Log and obtain written acknowledgement from the Sponsor confirming the scope of the possible CM. Once the out-of-scope services reach an estimated 3% of direct project costs (or $10,000, whichever is reached first), a Change Notification Form (CNF) will be submitted to the Sponsor for verification of the project change and to determine if INC Research should wait to begin out-of-scope trial activities or continue while good faith negotiations move towards an executed Change Order (CO).

 

A CO shall be completed once the following threshold amount is reached (which is based on the original contract value of the study).

 

o    $100,000 threshold if contract value is less than $3,000,000; or

o    $300,000 threshold if contract value is over $3,000,000.

 

If out of scope activities do not reach the threshold amount for longer than 180 days since the first CNF or particular CO was initiated, then a CO shall be issued once the time threshold is reached.

 

If out of scope activities do not reach the value or time thresholds prior to end of study, then a CO shall be issued and signed by Sponsor prior to release of the final project deliverable.

 

1 An increase in the study timeline may increase the inflation calculation. Change orders will only address an increase in costs due to inflation for uncompleted activities if the study timeline is pushed into a new calendar year

 

	
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