Document:

exhibit_4-28.htm

Exhibit 4.28

 

		
Prana Biotechnology Limited

 

WORK AUTHORISATION

Reference: WA002 (PBT2-204)

 

This Work Authorisation is between Prana Biotechnology Limited of Level 2, 369 Royal Parade, Parkville, VIC 3052, Australia (hereinafter “Customer”) and INCResearch Australia Pty Limited ACN 080 425 387 & ABN 67 080 425 387, 124 Lipson Street, Port Adelaide 5015 SA (hereinafter “INC”) and relates to the Master Services Agreement dated 28th September 2011, (the “Master Agreement”). Pursuant to the Master Agreement, INC has agreed to provide certain services in accordance with written work authorisations, such as this one, entered into from time-to-time describing such services.

 

	
Study Title:

	
Randomised, Double-blind, Placebo-controlled, Parallel-group, Phase 2 Study to Evaluate the Effect of One Dose of PBT2 (250mg daily) for 52 Weeks on Aβ Deposition in the Brains of Patients with Mild Alzheimer’s Disease Compared to Placebo and to Evaluate the Safety and Tolerability of PBT2 (250mg daily) for 52 Weeks in Patients with Mild Alzheimer’s Disease

 

The parties hereby agree as follows:

 

1. Work Authorisation. This document constitutes a “Work Authorisation” under the Master Agreement and this Work Authorisation and the services contemplated herein are subject to the terms and provisions of the Master Agreement.

 

2. Services and Payment of Fees and Expenses. The specific services contemplated by this Work Authorisation (the “Services”) and the related payment terms and obligations are set forth in the following attachments, which are incorporated herein by reference:

 

	
SCOPE OF WORK

	
ATTACHMENT 1

	
PROJECT BUDGET & SCHEDULE OF PAYMENT

	
ATTACHMENT 2

 

3. Term. The term of this Work Authorisation shall commence on the 28th September 2011 and shall continue until 31st December 2013, unless this Work Authorisation is terminated in accordance with the Master Agreement or extended by written agreement.

 

4. Amendments. No modification, amendment, or waiver of this Work Authorisation shall be effective unless in writing and duly executed and delivered by each party to the other.

 

5. Currency Exchange. All amounts are stated in Australian Dollars (AUD). This will also be the prime currency for invoicing and payment on this project.

 

ACKNOWLEDGED, ACCEPTED AND AGREED TO:

	  	  	  	  	  
	
Prana Biotechnology Limited

	  	
INCResearch Australia Limited

	  	  	  
	
By:

		  	
By:

	
	  	  	  	  	  
	
Name:

	
Dianne Angus

	  	
Name:

	
Garth Tierney

	  	  	  	  	  
	
Title:

	
Chief Operating Officer

	  	
Title:

	
General Manager

	  	  	  	  	  
	
Date:

	
2 April 2012

	  	
Date:

	
18 April 2012

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	
 

 

  

Page 1 of 17

  

 

Prana Biotechnology Limited

 

Attachment 1:

SCOPE OF WORK

 

	
1.

	
ASSUMPTIONS-SERVICES

	  	  
	
1.1

	
General Assumptions

	
GENERAL

	  	  
	
Phase

	  	
II

	
Number of Study Sites + Location

	  	
3 sites in Melbourne

	
Number of Subjects Screened

	  	
Not Specified

	
Number of Subjects Randomised

	  	
40

	
Local Study Sponsor - Australia

	  	
Prana

	
SOPs to be Used

	  	
INC

	
CLINICAL

	  	  
	
Site Identification

	  	
Sites have been identified by Prana

	
Investigator Meeting (length, location)

	  	
1 day meeting in Melbourne

	
Monitoring Frequency or Total No.

	  	
13 one-day visits per site

	
Visits/Site

	  	  
	
Paper or eCRF

	  	
Paper

	
No. CRF pages/Subject

	  	
80 pages

	
% SDV

	  	
100

	
Monitor Location

	  	
Melbourne

	
Project Manager

	  	
Prana

	
SAFETY REPORTING and MEDICAL MONITORING

	
No. (%) of SAEs Expected

	  	
Assume 1

	
SAEs Initially Reported to...

	  	
INC

	
SAE Reporting to Local Regulatory Authority

	  	
INC

	
Medical Monitor

	  	
Prana (INC as back up)

	
BIOMETRICS

	  	  
	
CRF Design

	  	
INC

	
Medical Coding of Adverse Events

	  	
MedDra

	
Medical Coding Medications

	  	
WHO Drug

	
Data Entry

	  	
Double DE

	
Number of Datasets

	  	
25

	
No. of Check Programs per panel

	  	
7

	
Expected Query rate

	  	
7 queries per 100 pages

	
Laboratory data

	  	
Central labs: Safety data (electronic) Local labs: None

	
Exports

	  	
2 (draft and final)

	
Frequency of Reporting

	  	
Monthly Data Management Metrics

	
DSMC requirements

	  	
3 (10%, 40%, 70%)

	
Statistics tasks

	  	
Input to Protocol, Randomisation, Statistical Analysis Plan, Statistical Analyses, DSMB, Statistical Text for CSR

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	
 

 

  

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Prana Biotechnology Limited

 

	
1.2

	
Timelines Assumptions

	
Timelines

	  	
Start

	  	
End

	
Start-up

	  	
1-Oct-11

	  	
10-Oct-11

	
Recruitment

	  	
11-Oct-11

	  	
10-Jun-12

	
Treatment

	  	
11-Jun-12

	  	
10-Jul-13

	
Follow-up

	  	
11-Jul-13

	  	
10-Aug-13

	
Study Conduct

	  	
11-Oct-11

	  	
10-Jul-13

	
Close-out

	  	
10-Aug-13

	  	
10-Oct-13

	
Total Duration

	  	
1-Oct-11

	  	
10-Oct-13

 

In the event that any of these tasks cannot be completed by the End dates above, INC will notify the Customer immediately, providing:

 

reasons for the delay;

revised End dates;

any impact on costs; and

where any delay is caused by INC due to factors within their control, the Customer requires INC to show how any lost time can be made up.

 

The Customer acknowledges that, subject to clause 33, INC and the Customer will meet to agree any additional costs for any delays that INC can establish to, the Customer’s reasonable satisfaction are outside of the control of INC.

	  	  
	
1.3

	
Detailed Transfer of Responsibilities

	
ACTIVITY

	  	
Customer/ Third

Party

	  	
INC

	
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

	  	
NA

	  	
NA

	
Complete Ethics Submissions and Follow-up

	  	
ü

	  	  
	
Respond to Issues Raised by the Ethics Committee

	  	
ü

	  	  
	
Regulatory Submissions (CTN)

	  	

ü

	  	  
	
Import/Export Permit Handling

	  	

ü

	  	  
	
Investigator’s Meeting

	  	  	  	  
	
Attend Investigator’s Meeting

	  	

ü

	  	

ü

	
Present at Investigator’s Meeting

	  	

ü

	  	

ü

	
Organise Investigator’s Meeting

	  	

ü

	  	  

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	
 

 

  

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Prana Biotechnology Limited

 

	
ACTIVITY

	  	
Customer/ Third

Party

	  	
INC

	
Investigational Product (IP)

	  	  	  	  
	
IP Packaging and Labelling

	  	

ü

	  	  
	
IP Storage

	  	

ü

	  	  
	
IP Distribution

	  	

ü

	  	  
	
IP Accountability

	  	  	  	

ü

	
IP Destruction

	  	

ü

	  	  
	
Site Visits

	  	  	  	  
	
Site Initiation Visits

	  	

 

	  	

ü

	
Monitoring Visits

	  	

 

	  	

ü

	
Unblinded Monitoring Visits

	  	
NA

	  	
NA

	
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

	  	  
	
Produce/Distribute Newsletters

	  	

ü

	  	  
	
Archiving of Study Files Post-study

	  	

ü

	  	  
	
Safety Reporting & Medical Monitoring

	  	  	  	  
	
Initial Receipt and Handling of SAEs

	  	  	  	

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

	
Six-monthly SUSAR Line Listings

	  	  	  	

ü

	
Annual Update of IB or Annual Safety Report (EU

	  	

ü

	  	  
	
Medical Monitoring

	  	

ü

	  	

ü (back up)

	
Biometrics

	  	  	  	  
	
Data Mgt – CRF Design and Development

	  	

ü

	  	

ü

	
Data Mgt – CRF Approval

	  	

ü

	  	  
	
Data Mgt – Database Design and Build

	  	  	  	

ü

	
Data Mgt – Database Consistency Check Programming

	  	  	  	

ü

	
Data Mgt – Data Validation Manual/Data Management Plan

	  	  	  	

ü

	
Data Mgt – Data Entry

	  	  	  	

ü

	
Data Mgt – Medical Coding

	  	  	  	

ü

	
Data Mgt – Quality Control

	  	  	  	

ü

	
Data Mgt – Generation of Data Queries

	  	  	  	

ü

	
Data Mgt – Delivery of Clean Verified CRFs to Customer

	  	  	  	

ü

	
Statistics – Sample Size Determination

	  	

ü

	  	  

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	
 

 

  

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Prana Biotechnology Limited

	
ACTIVITY

	  	
Customer/ Third

Party

	  	
INC

	
Statistics – Input to Protocol

	  	
ü

	  	  
	
Statistics – Generation of Randomisation Schedule and Provision of Randomisation Envelopes.

	  	  	  	

ü

	
Statistics – Statistical Analysis Plan

	  	  	  	

ü

	
Statistics – Produce Tables, Figures and Listings

	  	  	  	

ü

	
Statistics – Interim Analysis

	  	  	  	

ü

	
Statistics – Analysis and Reporting

	  	  	  	

ü

	
Medical Writing

	  	  	  	  
	
Provision of Top Line Data/results 4 weeks post database lock

	  	  	  	

ü

	
Provision of draft Clinical Study Report 7 weeks post database lock

	  	  	  	

ü

	
Provision of final Clinical Study Report 10 weeks post database lock

	  	  	  	

ü

 

Service & Expense Assumptions are as per agreed Proposal and Cost Estimate, version 5, dated 15th September 2011.

 

Study Start up and Document Management

	  	  	  
	
●

	
Study training/kick-off/familiarisation is included to train the project team on the following:-

	  	
●

	
Protocol

	  	
●

	
Investigators’ Brochure

	  	
●

	
Therapeutic Area Training (by INC’s Chief Medical Officer whose time is a value add service not charged to our Customers)

	  	
●

	
SOPs 

	 	●	CRF
	  	
●

	
Monitoring Guidelines

 

An internal INC kick-off meeting will be held via teleconference at the beginning of the project for all members of the INC study team.

	  	  
	
●

	
Customer kick-off meeting: The Customer will provide training for the CRA(s)/study team on the following;

	
●

	
Study protocol

	
●

	
Investigational product 

	●	CTMS (if applicable)
	
●

	
Relevant client procedures or plans

	  	
(Amount of time to be discussed and agreed between INC and the Customer).

	  	  
	
●

	
A Study Manual/Monitoring Manual will be produced for this study. This may include explanations of the following, but will vary depending on the Customer’s and the study requirements; applicable SOPs, communication procedures, initiation and monitoring visit procedures and reporting, source document verification (SDV) guidelines, protocol violation procedures, AE and SAE recording, concomitant medication recording, screen failures, withdrawals and early termination visits, investigational product (IP) handling, query resolution.

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	
 

 

  

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Prana Biotechnology Limited

	  	  
	
●

	
Clinical Trial Notification (CTN) Handling – Prana will complete all forms and arrange submission of the regulatory applications to the relevant health authorities Therapeutic Goods Administration.

	  	  
	
●

	
Ethics committee submissions includes Pl/consent customisation, completion of application, coordination of copies, coordination of any follow up required. Prana will be responsible for this task.

	  	  
	
●

	
A 1.5 day Investigator’s meeting is scheduled in 2011, which will be organised by Prana. This will include a session for training the INC team.

	  	  
	
●

	
Limited time has been allocated for the preparation of presentations. This will be a shared responsibility between the Customer and INC. Additional time may be required depending on the nature of the presentations that INC is required to develop.

	  	  
	
Study Conduct and Monitoring

	  	  
	
●

	
Study initiation visits include visit preparation, time on site, report completion after visits, follow-up correspondence with sites, post visit document handling and issue resolution.

	  	  
	
●

	
Monitoring Visits

	  	
It has been calculated that 39 monitoring days onsite will be required. This calculation is based on 40 patients, 100% SDV and an 80 page CRF. This assumes that it is possible to monitor an average of 85 CRF pages/day. It has been assumed that monitoring visits includes visit preparation, time on site, report completion after visits, follow-up correspondence with sites, post visit document handling and issue resolution.

	  	  
	
●

	
Due to the varying rates of enrolment across sites, the INC Project Manager will have the discretion to reallocate monitoring visits across and between all sites as required. The number of monitoring visits will be assessed on an ongoing basis to determine if more or less monitoring visits are required. This will be discussed and agreed with the Customer on an ongoing basis.

	  	  
	
●

	
Close-out visits includes visit preparation, time on site, report completion after visits, follow-up correspondence with sites, post visit document handling and issue resolution.

	  	  
	
●

	
CRA site management includes: ongoing communications with study sites, regular contacts with site between visits, communications with the Project Manager and the Customer, issue resolution between visits, management of study files and liaison with data management.

	  	  
	
Project Management

	  	  
	
●

	
Project Management will be handled by Prana.

	  	  
	
●

	
Teleconferences - It has been assumed that there will be monthly teleconferences for the project team for the period (October 2011 – October 2013).

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	
 

 

 

  

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Prana Biotechnology Limited

 

Safety Reporting and Medical Monitoring (Optional Service)

	  	  
	
●

	
SAE reporting process (To be confirmed).

	  	
SAEs will be reported directly to INC. INC will then conduct a medical review of the SAE and provide a final report to Prana. INC will be responsible for reporting the SAE to the local regulatory authorities.

	  	  
	
●

	
For the purposes of this proposal, it has been assumed there will be a total of 1 SAE during the course of the trial which is reportable event. There will be 1 SAE Follow up. This provides a unit cost, in the case that there are more SAEs/reportable events and/or follow-ups these will be billed to Prana.

	  	  
	
●

	
The INC Safety Officer will be responsible for the development of a study specific SAE Flow Chart. This will involve liaison with Prana’s Safety Officer or Department.

	  	  
	
●

	
Safety administration – includes familiarisation, set-up, correspondence, tracking, customer liaison, filing, study completion and archiving and has been estimated from October 2011 – July 2013.

	  	  
	
●

	
Investigator notification letters – Includes preparation and oversight

	  	  
	
●

	
The Medical Monitor will be provided by Prana. If required INC can provide a Medical Monitor on a retainer for an additional monthly fee, this will include professional advice in relation to inclusion/exclusion criteria, therapeutic area and review and narrative creation of SAEs.

 

Data Management

 

CRF Design

INC will design the CRF using the final protocol and its associated schedules and employing INC’s set of standard pages combined with any example CRF pages provided by the client. Modules of the CRF will be drafted and once agreed will be replicated according to the study visit schedule to form the complete book. When the complete book is assembled navigation prompts will be added to form the final CRF.

 

The CRFs will be printed as 3 part NCR to provide for original, data management and site copies.

 

Database Design and Build

A database will be designed employing an annotated CRF which will detail on a blank CRF all database fields, code lists and database structures. This will be presented to the client in PDF format for approval prior to commencement of database build. The design of the database will be to INC internal database standards or CDISC (conversion to be costed).

 

INC will perform all necessary programming tasks, including developing and testing the database modules, data entry screens and code lists. The database will be maintained until conclusion and archive of the study.

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	
 

 

  

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Prana Biotechnology Limited

 

Data Validation Manual (DVM)

INC will prepare a Data Validation Manual. This will include detailed descriptions in the following categories, as applicable for the project:

	  	  
	
●

	
CRF tracking and filing guidelines

	
●

	
Data entry guidelines

	
●

	
Pre-review guidelines

	
●

	
List of electronic edit checks to be performed

	
●

	
List of self-evident corrections and abbreviations

	
●

	
Electronic data integration plan

	
●

	
Local safety laboratory data handling procedures

	
●

	
Medical coding guidelines

	
●

	
Serious adverse event reconciliation guidelines

	
●

	
Quality control plan

	
●

	
Query reconciliation plan

 

The Data Validation Manual will be forwarded to the Customer for authorization prior to the commencement of data processing for the study.

 

Consistency Check Programming

After the Data Validation Manual has been authorized INC will develop the consistency check programs. Programs will check for problems with structural integrity, missing data, the logical consistency of data and the reasonability of data against set upper and lower ranges. In addition, listings will arrange data in convenient order so that cross checks of adverse events and other study data can be conducted as a back up to the CRA’s manual review.

 

Approximately 140 electronic CRF consistency checks as agreed with the Customer will be programmed. In addition 35 structural checks and manual listings will be programmed as required.

 

For appropriate checks (specified in the Data Validation Manual), output will be produced in the form of data query forms ready for review by the Clinical Data Associate. For others the output will be in the form of discrepancy listings which will be reviewed in full by the Clinical Data Associate.

 

All programming will be fully QC’d and validated using data entered into a test database prior to the programs being applied to the production databases.

 

Data Entry

Prior to data entry the completed CRF pages will be pre-coded (as defined in the data validation guidelines) by INC to allow efficient and timely entry of the data. The data will then be entered into the project database using validated data entry guidelines. The data entry will be via the entry and verification technique. This will involve entry by two independent data entry clerks.

 

Electronic Data

Electronic data for the study will be identified. For this project safety data is expected.

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	 

 

  

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Prana Biotechnology Limited

 

During the database setup process a data transfer specification will be prepared for each electronic source of data. This will describe the agreed format of the data to be transferred, the frequency, the data structure and whether partial or cumulative transfers are expected. The transfer plan will be signed off by INC and the third party supplier. INC will seek one test transfer of data from the supplier and confirm that the data is being transferred in the agreed format prior to production transfers being received.

 

Upon receipt of electronic data INC will check the file for structural integrity and cross check it with relevant CRF data. Any discrepancies found will be queried for resolution with the supplier and/or the investigator.

 

Query Management

Upon successful entry of the data consistency checks will be run regularly across the database. We will review the data for completeness, logical consistency and reasonability of numeric values. We will also perform a manual review of key safety data – particularly adverse events and medications. Any discrepancies found will assessed and where necessary data queries issued. All queries will be provided to clinical operations for resolution with the study site.

 

All queries will be uniquely numbered and tracked electronically. On receipt of resolved queries, the Clinical Data Associate will update the query log, then, edit the database and CRF as appropriate.

 

Computer generated query resolution is an ongoing process that begins when the first CRF is received and processed, and continues through to study completion.

 

Medical Coding

Medical coding of adverse events will be conducted employing the MedDRA 14.0 coding dictionary. Coding of medications will be conducted using the WHO drug dictionary Q2, 2010.

 

Auto-encoders will be created for the study to code all unique adverse event terms and medications. This means that common terms are coded directly from the dictionary and repetitive terms only need to be coded once. Coding commences with the clarification of any unclear adverse event or medication terms. This may involve the use of data queries. When all terms are clear the medical coder will undertake the medical coding utilizing the auto-encoder. After events and medications are coded listings of coded items are submitted for medical review and any miscoding updated. Clients may also be involved in this review process according to their preference.

 

Quality Control

Patient’s data will be checked according to the QC plan which will be fully detailed in the Data Validation Manual. For this study it is proposed that 100% of CRF pages be compared to the database for 10% of the patients. In addition a 100% QC of all critically defined data will be conducted as patients become frozen awaiting lock.

 

Database Lock

At the end of data processing, when all queries have been resolved and SAE reconciliation completed the database will be frozen. Before the database lock a final error rate will be calculated. If above 0.1% then an additional 10% of data will be QC’d and the error rate recalculated. If the error rate is still above 0.1 then 100% of the data is QC’d. When the QC has been satisfactorily completed and authorization has been received from the Customer, the database will be locked.

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	
 

 

  

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Prana Biotechnology Limited

 

Statistics

 

A randomization schedule will be generated programmatically and provided as a master list to authorized personnel. Individual subjects’ blind break envelopes will be provided to the PI.

 

A draft Statistical Analysis Plan (SAP) will be prepared in accordance with SOPs and will include specifications for all tables, listings and figures to be produced. This will also detail how the study population will be defined for the study and how key efficacy and safety data will be analysed.

 

The Customer will review the draft SAP and any feedback/review will be incorporated into the final analysis plan, which will be approved by the Customer prior to the statistical analysis.

 

After the SAP is finalized the analysis datasets will be defined and programmed.

 

After database lock a review of the data and protocol violations will be conducted and patients allocated to the study populations applicable for the study.

 

The study blind will be broken and we will perform the SAS programming and QC processes and produce the agreed tables, listings and figures.

 

The statistician will analyse the data using the methods agreed in the SAP; determine the statistical results for the study, and provide text for inclusion in the study report.

 

A maximum of 35 tables (15 unique and 20 repeat formatted tables), 35 associated listings, 0 figures and 10 analysis endpoints are budgeted using SAS V9.2.

 

A Data Safety Monitoring Committee will meet after approximately 10%, 40% and 70% of total study treatment has occurred. It is anticipated that listings as described in the SAP for the final analysis will be able to be produced for these meetings. However extra programmed listings can be provided (as required) according to the unit cost of listings in the study budget.

 

At the end of the study INC will prepare a final statistical package including:

	  	  
	
●

	
Final Statistical Analysis Plan

	
●

	
Tables, figure, and listings, in an industry-common electronic format, such as SAS, Adobe PDF or Microsoft Word, that will be mutually agreed upon prior to the transfer.

	
●

	
A summary and list of protocol deviations and other anomalies known to INC staff.

 

INC will provide the transfer on CD-R media

 

Medical Writing (Optional Service)

	  	  
	
●

	
The final Clinical Study Report (CSR) for this study will be to International Conference on Harmonisation (ICH) format taking into account any relevant guidelines. The expected length of the report is 30-40 pages of prepared text plus tables and listings as appendices.

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	
 

 

  

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Prana Biotechnology Limited

 

	
●

	
We assume one review cycle (i.e., an initial draft report is prepared for client review and following receipt of Customer comments a final report can be issued).

	 	 
	
●

	
We assume that the final report is delivered to the customer in an electronic format.

	 	 
	
●

	
Prana may wish to include an optional of 8 hours QA review. A quality control check is automatically incorporated.

	 	 
	
●

	
Additional services (e.g., full electronic compilation) can be provided at additional cost

 

It is only possible to provide estimates for Medical Writing services at this stage. We will discuss specific requirements with Prana so that we can that we can tailor our services to meet the Prana’s needs. Due to the nature of Medical Writing the time required to complete a project depends on a number of factors including the CSR template to be used, the length of a document, the complexity of the study, the nature of the study results and the amount of supporting literature provided by the Customer.

 

The CSR can be developed using a client-provided CSR template if requested by the client but the use of INC’s CSR template has been costed in this proposal.

 

Expense Assumptions

 

INC will always obtain the best possible prices to minimise expenditure. Expenses are invoiced separately on a pass through basis and relevant receipt copies are always included, except for general expenses, as outlined below. All amounts specified are in Australian dollars.

 

Customer Project Team Meeting

	  	  
	
●

	
INC assumes that the Customer Project Kick-off meeting will be held in Melbourne, and therefore, there will be no travel expenses.

	  	  
	
Investigator’s Meeting Expenses

	  	  
	
●

	
An Australian investigator meeting will be held in Melbourne.

	  	  
	
Travel Related Expenses (Airfares/Accommodation/Taxis)

	  	  
	
●

	
As all monitoring will be regionalised there are no travel related expenses for site visits.

	  	  
	
Site Visit Expenses (Parking/Meals/Tolls/Incidentals)

	  	  
	
●

	
An allowance of $50 per day has been estimated for site visits.

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	
 

 

  

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Prana Biotechnology Limited

 

General Expenses/Other

	  	  
	
●

	
Costs related to couriers, and teleconference call will be passed though at cost.

	  	  
	
●

	
A general expense has been calculated to include photocopying (excluding ethics submission copying), stationery (files), express post costs, standard postage and communications (excluding teleconferences). This will be billed at a set rate for the duration of the study.

	  	  
	
●

	
CRF printing – this has been estimated at $2,500, assuming this will be on 3 part no-carbon required (NCR) paper.

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	
 

 

  

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Prana Biotechnology Limited

 

Attachment 2:

 

	
PROJECT BUDGET & PAYMENT SCHEDULE

 

	
1. 

	
PAYMENT SCHEDULE AND INVOICING

 

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 is liable to pay GST in respect of any Services provided pursuant to this Agreement, INC may add the GST amount to invoices provided to Customer for the Services. Provided that the relevant invoice complies with the requirements of a tax invoice to enable Customer to claim a credit or refund of GST, Customer 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 Customer GST will not be applicable.

 

All Clinical Services will be on a unit basis comprising of fixed units (e.g. File Management, Site Management and Management/Supervision) which will be invoiced monthly at the fixed cost as per the Cost Sheet and variable units (e.g. Site Visits), which will be invoiced according to actual number of units incurred each month.

 

Data Management/Statistics and Medical Writing will be invoiced on a milestone basis.

 

A percentage of the contract value will be payable upfront upon execution of the Work Authorisation.

 

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

 

INC will invoice the Customer for Data Management/Statistics/Medical Writing according to the following schedule:

 

	 	

●

	

Execution of agreement

	

20%

	 	

●

	

Database Complete

	

20%

	 	

●

	

100% data entered

	

20%

	 	

●

	

Data base Lock

	

20%

	 	

●

	

1st Draft Study Report

	

10%

	 	

●

	

Final Study Report

	

10%

 

INC will invoice the Customer for provision of services on a monthly basis. This will include any service units incurred during the previous month.

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	

 

 

  

Page 13 of 17

  

 

Prana Biotechnology Limited

 

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 may increase fees beyond the period stated and any additional costs will be prior approved in writing by the Customer.

 

Disbursements will be invoiced separately on a monthly basis and will include copies of receipts where relevant.

 

Payment will be due within 30 days of date of invoices. 

Invoices will be submitted to the following E mail address:

 

	

Email:

	

krowe@pranabio.com

	

Cc:

	

Peneamor@bigpond.net.au and dangus@pranabio.com

 

Attention:    Kerry Rowe

 

Payment will be made by electronic transfer as follows:

 

Bank Name: Bank of South Australia (A Division of St George Bank Limited)

 

Swift Code: 

 

BSB (Routing Number): 

 

Account Number: 

 

Account Name: INCResearch Australia Pty Limited

 

	
2. 

	
CONTACTS & COMMUNICATION

 

The key Customer contact person for project related issues, contract and financial issues is Pene Amor. The key contact for INC for project related matters is Belinda Fricke. The key contact for contract related matters is Garth Tierney.

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	
 

 

  

Page 14 of 17

  

 

Prana Biotechnology Limited

 

4.1    Budget- Services

	

Service/Item

	  	

Comments

	  	

Responsibility

	  	

Unit

	  	

Unit Cost

	  	

Number 

of Units

	  	

Item Cost

	  	

AUD$

	

Study Start Up Activities

	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	

Study Training/ Internal Kick Off Meeting

	  	

Familiarisation, Protocol. IB, CRF, procedures etc.

	  	

CRA

	  	

per CRA

	  	

1080

	  	

1.00

	  	

1,080

	  	

‘

	

Essential document collection

	  	

Creation, Collection and tracking

	  	

CRA

	  	

per site

	  	

1350

	  	

3.00

	  	

4,050

	  	  
	

Study Manual/Monitoring Manual Development

	  	  	  	

Med Writer / PM

	  	

per manual

	  	

3100

	  	

1

	  	

3,100

	  	  
	

Study Files

	  	

Set up of study master files and Investigator site files

	  	

PA

	  	

per study

	  	

720

	  	

1.00

	  	

720

	  	  
	

File Management

	  	

per month

	  	

PA

	  	

per month

	  	

283

	  	

24.00

	  	

6,787

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	

Subtotal

	  	

$15,737

	

Customer Project Team Meetings

	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	

Teleconference participation

	  	

25 x 1 hour Telecon, 1 CRAs

	  	

CRA

	  	

per telecon

	  	

138

	  	

25.00

	  	

3.450

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	

Subtotal

	  	

$3,450

	

Investigator’s/Monitor’s Meeting

	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	

Preparation of Presentations

	  	

Trident & Customer shared responsibility

	  	

CRA

	  	

per meeting

	  	

1620

	  	

1.00

	  	

1.620

	  	  
	

Attendance

	  	

assume 1 day meeting, 1 CRA

	  	

CRA

	  	

per CRA

	  	

1080

	  	

1.00

	  	

1,080

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	

Subtotal

	  	

$2,700

	

Site Visits

	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	

Study Initiation

	  	

Incl. prep, travel, on-site, reporting & follow-up

	  	

CRA

	  	

per visit

	  	

1620

	  	

3.00

	  	

4,860

	  	  
	

Monitoring Visits (1 Day visits)

	  	

Incl. prep, travel, 1 day on-site, reporting & follow-up 13 visits/site

	  	

CRA

	  	

per visit

	  	

1932

	  	

39.00

	  	

75,348

	  	  
	

Closeout visits

	  	

Incl. prep, travel, on-site, reporting & follow-up

	  	

CRA

	  	

per visit

	  	

2070

	  	

3.00

	  	

6,210

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	

Subtotal

	  	

$86,418

	

Site Management

	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	

Site Management (October 2011 - July 2013)

	  	

per month

	  	

CRA

	  	

per month

	  	

1780

	  	

22.00

	  	

39,164

	  	  
	

Site Management (August 2013 - September 2013)

	  	

per month

	  	

CRA

	  	

per month

	  	

828

	  	

2.00

	  	

1,656

	  	  
	

Management/Supervision

	  	

per month

	  	

Management

	  	

per month

	  	

340

	  	

24.00

	  	

8,160

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	

Subtotal

	  	

$48,980

	

Safety Monitoring

	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	

Safety Administration

	  	

Incl. set up, maintenance and completion activities

	  	

Safety Officer

	  	  	  	

3979

	  	

1.00

	  	

3,979

	  	  
	

Initial Receipt and handling SAEs

	  	

All events - assume 1 SAE

	  	

Safety Officer

	  	

per SAE

	  	

330

	  	

1.00

	  	

330

	  	  
	

Medical Review of SAEs and Narrative creation

	  	

Optional - as required

	  	

Medical Monitor

	  	

per SAE

	  	

838

	  	

0,00

	  	

0

	  	  
	

Reporting to local Authorities

	  	

Assume 1 Reportable events

	  	

Safety Officer

	  	

per SAE

	  	

660

	  	

1.00

	  	

660

	  	  
	

Follow up of SAEs

	  	

Assume 2 hours/Follow-up/SAE, 1 Follow-ups

	  	

Safety Officer

	  	

per follow-up

	  	

330

	  	

1.00

	  	

330

	  	  
	

Investigator Notification Letters

	  	

preparation and oversight

	  	

Safety Officer

	  	

per letter

	  	

165

	  	

1.00

	  	

165

	  	  
	

Med Monitor Retainer (June 12 - Oct 13)

	  	  	  	

Medical Monitor

	  	

per month

	  	

419

	  	

16.00

	  	

6,704

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	

Subtotal

	  	

$12,167

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	

 

 

  

Page 15 of 17

  

 

Prana Biotechnology Limited

 

	 Service/Item	 	
Comments

	 	
Responsibility

	 	
Unit

	 	
Unit Cost

	 	

Number 

of Units

	 	
Item Cost

	 	
AUD$

	

Data Management & Statistics

	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	

CRF Design

	  	

25 unique pages. 80 pages of CRF and 11 pages of questionnaire. 91 Total pages.   One print run.

	  	

Data Operations Assoc Manager

	  	

1 study

	  	

14520

	  	

1.00

	  	

14,520

	  	  
	

Database design and build

	  	  	  	

DBA/CDA

	  	

1 Data set

	  	

463

	  	

25.00

	  	

11,563

	  	  
	

Database / Consistency Check programming

	  	  	  	

DBA/CDA

	  	

1 Check

	  	

53

	  	

208.25

	  	

11,114

	  	  
	

Data Validation Manual / Data Management Plan

	  	  	  	

CDA

	  	

1 DVM/DMP

	  	

3400

	  	

1.00

	  	

3.400

	  	  
	

Data entry

	  	

Double Data Entry 40 patients × 80 CRF pages plus 40 × 11 questionaires=3640 total pages. Cost per extra page=5.87

	  	

DE

	  	

1 page

	  	

6

	  	

3640.00

	  	

21,385

	  	  
	

Medical Coding

	  	

MedDRA - AE, WHO - Drug

	  	

DBA/CDA

	  	

1 Coded term

	  	

6

	  	

800.00

	  	

5,036

	  	  
	

Data Cleaning / Monitoring

	  	

3200 CRF pages. Cost per extra page=$5.10                  224 Queries. 

Cost per extra query=$42.50

	  	

CDA

	  	

1 study

	  	

29617

	  	

1.00

	  	

29,617

	  	  
	

Quality Control

	  	

10% of all patients, 100% of all critical data   (15% critical / 85% non critical)

	  	

CDA

	  	

1 page

	  	

3

	  	

811.40

	  	

2,391

	  	  
	

Import laboratory data

	  	

1 central lab

	  	

DBA/CDA

	  	

1  study

	  	

3680

	  	

1.00

	  	

3,680

	  	  
	

Data exports

	  	

Assume 2 exports

	  	

DBA

	  	

1  export

	  	

360

	  	

2.00

	  	

720

	  	  
	

Database maintenance

	  	

Study Duration = 18 months

	  	

DBA

	  	

1  month

	  	

0

	  	

18.00

	  	

4,320

	  	  
	

DM & Statistics - Project Management

	  	

Client meetings & corresp, DM metrics. 1hrs/month x 18 months

	  	

DM

	  	

1 month

	  	

120

	  	

18.00

	  	

1,530

	  	  
	

Input to protocol

	  	

Text and sample size calcualtion / power

	  	

Statistician

	  	

1 hour

	  	

200

	  	

4,00

	  	

800

	  	  
	

Generation of Randomisation schedule

	  	

1 Schedule.     40 Envelopes. Cost per

	  	

Statistician

	  	

1

	  	

1175

	  	

1.00

	  	

1,175

	  	  
	

Statistical Analysis Plan

	  	

Includes text and table and Isting shells

	  	

Statistician

	  	

1 Statistical

	  	

5840

	  	

1.00

	  	

5,840

	  	  
	

Identify Protocol Deviations and define Analysis

	  	

Unblinding, Protocol deviations and

	  	

Statistician

	  	

1 study

	  	

1600

	  	

1.00

	  	

1,600

	  	  
	

Analysis Datasets

	  	

Specification, Programming   & QC

	  	

SAS Programmer

	  	

1 study

	  	

4800

	  	

1.00

	  	

4,800

	  	  
	

Production of Tables & Listings

	  	

15 Unique tables.   Cost per extra $720 20 Repeat tables. Cost per extra $240 0 Figures. Cost per extra S420 35 Listings. Cost per extra S300

	  	

SAS Programmer

	  	

1 study

	  	

26100

	  	

1.00

	  	

26,100

	  	  
	

Statistical Analysis

	  	

10 analysis endpoints. Cost per extra $400

	  	

Statistician

	  	

1 analysis endpoint

	  	

400

	  	

10.00

	  	

4,000

	  	  
	

Provision of data to DSMB

	  	

Assumes interim running and QC of  6 TFLs in row ‘Programming Tables and listings.

	  	

Statistician

	  	

1  meeting

	  	

960

	  	

3.00

	  	

2,880

	  	  
	

Input to Final report

	  	

Text for inclusion in study report.

	  	

Statistician

	  	

1  hour

	  	

2400

	  	

1.00

	  	

2,400

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	

Subtotal

	  	

$158,869

	

Medical Writing (Optional)

	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	

Clinical study report (CSR)

	  	  	  	

Medical Writer

	  	

per CSR

	  	

22497

	  	

1.00

	  	

22,497

	  	  
	

QA review of CSR

	  	

Optional for Client

	  	

Medical Writer

	  	

per CSR

	  	

2769

	  	

1.00

	  	

2,769

	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	

Subtotal

	  	

$25,266

	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	

TOTAL

	  	

$353,588

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	

 

 

  

Page 16 of 17

  

 

Prana Biotechnology Limited

 

4.2    Budget- Expenses

	

Expense/Item

	  	

Comments

	  	

Unit Cost

	  	

Number 

of Units

	  	

Item Cost 

AUD$

	  	

AUD$

	

Site Visits

	  	  	  	  	  	  	  	  	  	  
	

Other Site visit Costs

	  	

Parking/tolls/meals and incidentals for site visits

	  	

$50/day

	  	

45.00

	  	

2,250

	  	  
	  	  	  	  	  	  	  	  	

Subtotal

	  	

$2,250

	

General Expenses

	  	  	  	  	  	  	  	  	  	  
	

General Expenses - Couriers, Postage, Telecommunications, Copying, stationery (files)

	  	

$70/site/month, 3 sites for 25 months

	  	

$210/month

	  	

25

	  	

5,250

	  	  
	

CRF Printing

	  	  	  	

$2,500

	  	

1

	  	

2,500

	  	  
	  	  	  	  	  	  	  	  	

Subtotal

	  	

$7,750

	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	

TOTAL

	  	

$10,000

 

	
WA002 PBT2-204 (800089) V4, 2nd April 2012

	

 

 

  

Page 17 of 17

  

 

27 June 2012

 

		
 

  

1st Amendment to Work Order # 800089 (PBT2-204)

 

This 1st Amendment to 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 28th 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.

 

	
Study Title:

	
Randomised, Double-blind, Placebo-controlled, Parallel-group, Phase 2 Study to Evaluate the Effect of One Dose of PBT2 (250mg daily) for 52 weeks on Ab Deposition in the Brains of Patients with Mild Alzheimer’s Disease Compared to Placebo and to Evaluate the Safety and Tolerability of PBT2 (250mg daily) for 52 weeks in Patients with Mild Alzheimer’s Disease

 

The parties hereby agree as follows: 

 

Amendment Summary:

 

	
Agreement

	 	
Details

	
Original Agreement

	 	
WA002

	
Date of Original Agreement

	 	
Version 4, doted 2nd April 2012

	
Amendment number

	 	
Amendment #1

	
Version & Date of Amendment

	 	
Version 2, doted 27th June 2012

	
Project ID (INC internal code)

	 	
800089

	
Client

	 	
Prono Biotechnology Limited

	
Client Project Code

	 	
PBT2-204

	
Description of Amendment

	 	  	
●

	
Additional 2 sites – RMH and Geelong Private

	  	 	  	
●

	
1 additional CRA

	  	 	  	
●

	
Reduction in 1 day Monitoring visits

	  	 	  	
●

	
Addition of 2 day Monitoring visits

	  	 	  	
●

	
Deletion of Medical Monitor retainer

	  	 	  	
●

	
Site Management adjustment

 

	
Prana 800089 (PBT2-204) version 2, 27th June 2012 

	
 

 

  

Page 1 of 6

  

 

	
Costs Implication for Amendment

	 	
Direct Costs (Services)

	  	 	  	
●

	
Study Training for additional 1 CRA @  $540/CRA = $540.00

	  	 	  	
●

	
Additional 2 Sites Essential Document Collection @ $1350/site = $2,700.00

	  	 	  	
●

	
Additional 14 months File Management  for 2 new sites @ $283/month = $3,959.00

	  	 	  	
●

	
16 x 1 hour Teleconference participation  for additional 1 CRA @ $138/telecom = $2,208.00

	  	 	  	
●

	
2 additional Study Initiation Visits @ $1620/visit = $3,240.00

	  	 	  	
●

	
Reduction of 19 x 1 day monitoring visits @ $1932/visit = -$36,708.00

	  	 	  	
●

	
15 x 2 day monitoring visits @ $3174/visit = $47,610.00

	  	 	  	
●

	
2 additional Close out Visits @ $2070/visit = $4,140.00

	  	 	  	
●

	
Addition of 2 months of Site Management for 1 site @ $593.50/month = $1,187.00

	  	 	  	
●

	
Addition of 6 months of Site Management for 2 sites @ $1187/month = $7,121.00

	  	 	  	
●

	
Reduction in 8 months of Site Management of 3 sites @ $1780/month = -$14,240.00

	  	 	  	
●

	
12 months Site Management for 2 new sites @ $1187/month = $14,242.00

	  	 	  	
●

	
2 months Site Management for 2 new sites @ $552/month = $1,104.00

	  	 	  	
●

	
Deletion of Medical Monitor retainer =  -$6,704.00 

	 	 	 	 	-    Total Cost $30,398.00
	  	 	
Indirect Costs (Expenses)

	  	 	  	
●

	
15 days of additional Other Site Visit costs @ $50/day = $750.00

	  	 	  	
●

	
Additional General Expenses for 2 new sites for 16 months @ $140/month = $2,240.00 

	 	 	 	 	-    Total Cost = $2,990.00
	
Total Cost Implication for Amendment

	 	
$33,388.00

 

	
Prana 800089 (PBT2-204) version 2, 27th June 2012 

	
 

 

  

Page 2 of 6

  

 

Budget Summary:

 

	
Work Order

	 	
Services

	 	
Expenses

	 	
Total 

Contract

	
Original Work Order

	 	
$353,588.00

	 	
$10,000.00

	 	
$363,588.00

	
Amendment #1

	 	
$30,398.00

	 	
$2,990.00

	 	
$33,388.00

	
Revised Contract Value

	 	
$383,986.00

	 	
$12,990.00

	 	
$396,976.00

 

Details of Amendment 1

 

Assumption - General Services

 

	
GENERAL

	
Phase

	
II

	
Number of Study Sites + Location

	
5 sites in Melbourne

	
Number of Subjects Screened

	
Not Specified

	
Number of Subjects Randomised

	
40

	
Local Study Sponsor – Australia

	
Prana

	
SOPs to be Used

	
INC

	
CLINICAL

	
Site Identification

	
Sites have been identified by Prana

	
Investigator Meeting (length, location)

	
1 day meeting in Melbourne

	
Monitoring Frequency or Total No. Visits/Site

	
4 x 1 day visits and 3 x 2 day visit per site

	
Paper or eCRF

	
Paper

	
No. CRF pages/Subject

	
80 pages

	
% SDV

	
100

	
Monitor Location

	
Melbourne x 2

	
Project Manager

	
Prana

	
SAFETY REPORTING and MEDICAL MONITORING

	
No. (%) of SAEs Expected

	
Assume 1

	
SAEs Initially Reported to...

	
INC

	
SAE Reporting to Local Regulatory Authority

	
INC

	
Medical Monitor

	
Prana (INC as back up)

	
BIOMETRICS

	
CRF Design

	
INC

	
Medical Coding of Adverse Events

	
MedDra

	
Medical Coding Medications

	
WHO Drug

	
Data Entry

	
Double DE

	
Number of Datasets

	
25

	
No. of Check Programs per panel

	
7

 

	
Prana 800089 (PBT2-204) version 2, 27th June 2012 

	
 

 

  

Page 3 of 6

  

	

Expected Query rate

	

7 queries per 100 pages

	

Laboratory data

	

Central labs: Safety data (electronic) 

Local labs: None

	

Exports

	

2 (draft and final)

	

Frequency of Reporting

	

Monthly Data Management Metrics

	

DSMC requirements

	

3 (10%, 40%, 70%)

	

Statistics tasks

	

Input to Protocol, Randomisation, Statistical Analysis Plan, Statistical Analyses, DSMB, Statistical Text for CSR

 

Amendment 1 to Budget Services

 

	

Service/Item

	 	

Comments

	 	

Responsibility

	 	

Unit

	 	

Unit Cost

	 	

Number of Units

	 	

Item Cost

	 	

AUD$

	

Study Start Up Activities

	 	

 

	 	  	 	  	 	  	 	  	 	  	 	  
	

Study Training/ Internal Kick Off Meeting

	 	

Familiarisation, Protocol, IB, CRF, procedures etc.

	 	

CRA

	 	

per CRA

	 	

1080

	 	

1.00

	 	

1,080

	 	  
	

Study Training

	 	

Familiarisation etc.

	 	

CRA

	 	

per CRA

	 	

540

	 	

1.00

	 	

540

	 	  
	

Essential document collection

	 	

Creation, Collection and tracking

	 	

CRA

	 	

per site

	 	

1350

	 	

5.00

	 	

6,750

	 	  
	

Study Manual/Monitoring Manual Development

	 	

 

	 	

Med Writer / PM

	 	

per manual

	 	

3100

	 	

1

	 	

3,100

	 	  
	

Study Files

	 	

Set up of study master files and Investigator site files

	 	

PA

	 	

per study

	 	

720

	 	

1.00

	 	

720

	 	  
	

File Management

	 	

per month

	 	

PA

	 	

per month

	 	

283

	 	

24.00

	 	

6,787

	 	  
	

File Management - 2 new sites

	 	

per month from August 2012

	 	

PA

	 	

per month

	 	

283

	 	

14.00

	 	

3,959

	 	  
	

 

	 	

 

	 	  	 	  	 	  	 	  	 	

Subtotal

	 	

$22.937

	

Customer Project Team Meetings

	 	

 

	 	  	 	  	 	  	 	  	 	  	 	  
	

Teleconference participation

	 	

25 x 1 hour Telecon, 1 CRAs

	 	

CRA

	 	

per telecon

	 	

138

	 	

25.00

	 	

3,450

	 	  
	

Teleconference participation

	 	

16 x monthly hour Telecon, 1 CRA

	 	

CRA

	 	

per telecon

	 	

138

	 	

16.00

	 	

2,208

	 	  
	

 

	 	

 

	 	  	 	  	 	  	 	  	 	

Subtotal

	 	

$5,658

	

Investigator’s Monitor’s Meeting

	 	

 

	 	  	 	  	 	  	 	  	 	  	 	  
	

Preparation of Presentations

	 	

Trident & Customer shared responsibility

	 	

CRA

	 	

per meeting

	 	

1620

	 	

1.00

	 	

1,620

	 	  
	

Attendance

	 	

assume 1 day meeting, 1 CRA

	 	

CRA

	 	

per CRA

	 	

1080

	 	

1.00

	 	

1,080

	 	  
	

 

	 	

 

	 	  	 	  	 	  	 	  	 	

Subtotal

	 	

$2,700

	

Site Visits

	 	

 

	 	  	 	  	 	  	 	  	 	  	 	  
	

Study Initiation

	 	

Incl. prep, travel, on-site, reporting & follow-up

	 	

CRA

	 	

per visit

	 	

1620

	 	

5.00

	 	

8,100

	 	  
	

Monitoring Visits (1 Day visits)

	 	

Incl. prep, travel, 1 day on-site, reporting & follow-up 4 visits/site

	 	

CRA

	 	

per visit

	 	

1932

	 	

20.00

	 	

38,640

	 	  
	

Monitoring Visits (2 Day visits)

	 	

Incl. prep, travel, 2 day’s on-site, reporting & follow-up 3 visits/site

	 	

CRA

	 	

per visit

	 	

3174

	 	

15.00

	 	

47,610

	 	  
	

Closeout visits

	 	

Incl. prep, travel, on-site, reporting & follow-up

	 	

CRA

	 	

Per visit

	 	

2070

	 	

5.00

	 	

10,350

	 	  
	

 

	 	

 

	 	  	 	  	 	  	 	  	 	

Subtotal

	 	

$104,700

	

Site Management

	 	

 

	 	  	 	  	 	  	 	  	 	  	 	  
	

Site Management (October 2011 - Nov 2011)

	 	

1 site

	 	

CRA

	 	

per month

	 	

593

	 	

2.00

	 	

1,187

	 	  
	

Site Management (Dec 2011 - May 2012)

	 	

2 sites

	 	

CRA

	 	

per month

	 	

1187

	 	

6.00

	 	

7,121

	 	  
	

Site Management (June 2012 - July 2013)

	 	

3 sites

	 	

CRA

	 	

per month

	 	

1780

	 	

14.00

	 	

24,923

	 	  
	

Site Management (August 2012 - July 2013)

	 	

per month - 2 new sites

	 	

CRA

	 	

per month

	 	

1187

	 	

12.00

	 	

14,242

	 	  
	

Site Management (August 2013 - September 2013)

	 	

3 sites

	 	

CRA

	 	

per month

	 	

828

	 	

2.00

	 	

1,656

	 	  
	

Site Management (August 2013 - September 2013)

	 	

per month - 2 new sites

	 	

CRA

	 	

per month

	 	

552

	 	

2.00

	 	

1,104

	 	  
	

Management/Supervision

	 	

per month

	 	

Management

	 	

per month

	 	

340

	 	

24.00

	 	

8,160

	 	  
	

 

	 	

 

	 	  	 	  	 	  	 	  	 	

Subtotal

	 	

$58,392

	

Safety Monitoring

	 	

 

	 	  	 	  	 	  	 	  	 	  	 	  
	

Safety Administration

	 	

Incl. set up, maintenance and completion activities

	 	

Safety Officer

	 	  	 	

3979

	 	

1.00

	 	

3,979

	 	  
	

Initial Receipt and handling SAEs

	 	

All events - assume 1 SAE

	 	

Safety Officer

	 	

per SAE

	 	

330

	 	

1.00

	 	

330

	 	  
	

Medical Review of SAEs and Narrative creation

	 	

Optional - as required

	 	

Medical Monitor

	 	

per SAE

	 	

838

	 	

0.00

	 	

0

	 	  
	

Reporting to local Authorities

	 	

Assume 1 Reportable events

	 	

Safety Officer

	 	

per SAE

	 	

660

	 	

1.00

	 	

660

	 	  
	

Follow up of SAEs

	 	

Assume 2 hours/Follow-up/SAE, 1 Follow ups

	 	

Safety Officer

	 	

per follow-up

	 	

330

	 	

1.00

	 	

330

	 	  
	

Investigator Notification Letters

	 	

preparation and oversight

	 	

Safety Officer

	 	

per letter

	 	

165

	 	

1.00

	 	

165

	 	  
	

 

	 	

 

	 	  	 	  	 	  	 	  	 	

Subtotal

	 	

$5,464

 

	Prana 800089 (PBT2-204) version 2, 27th June 2012	 

 

 

Page 4 of 6

 

 

	  Service/Item	 	
Comments

	 	
Responsibility

	 	
Unit

	 	
Unit Cost

	 	
Number of Units

	 	
Item Cost

	 	
AUD$

	

Data Management & Statistics

	 	

 

	 	  	 	  	 	  	 	  	 	  	 	  
	

CRF Design

	 	

25 unique pages. 80 pages of CRF and 11 pages of questionnaire. 91 Total pages.   One print run.

	 	

Data Operations Assoc Manager

	 	

1 study

	 	

14520

	 	

1.00

	 	

14,520

	 	  
	

Database design and build

	 	

 

	 	

DBA/CDA

	 	

1 Data set

	 	

463

	 	

25.00

	 	

11,563

	 	  
	

Database / Consistency Check programming

	 	

 

	 	

OBA/CDA

	 	

1 Check

	 	

53

	 	

208.25

	 	

11,114

	 	  
	

Data Validation Manual / Data Management Plan

	 	

 

	 	

CDA

	 	

1 DVM/DMP

	 	

3400

	 	

1.00

	 	

3,400

	 	  
	

Data entry

	 	

Double Data Entry 40 patients x 80 CRF pages plus 40 x 11 questionaires=3640 total pages. Cost per extra page=5.87

	 	

DE

	 	

1 page

	 	

6

	 	

3640.00

	 	

21,385

	 	  
	

Medical Coding

	 	

MedDRA - AE, WHO - Drug

	 	

DBA/CDA

	 	

1 Coded term

	 	

6

	 	

800.00

	 	

5,036

	 	  
	

Data Cleaning / Monitoring

	 	

3200 CRF pages. Cost per extra page=$5.10         224 Queries.

Cost per extra query=$42.50

	 	

CDA

	 	

1 study

	 	

29617

	 	

1.00

	 	

29,617

	 	  
	

Quality Control

	 	

10% of all patients, 100% of all critical data (15% critical / 85% non critical)

	 	

CDA

	 	

1 page

	 	

3

	 	

811.40

	 	

2,391

	 	  
	

Impart laboratory data

	 	

1 central lab.

	 	

DBA/CDA

	 	

1 study

	 	

3680

	 	

1.00

	 	

3,680

	 	  
	

Data exports

	 	

Assume 2 exports

	 	

DBA

	 	

1 export

	 	

360

	 	

2.00

	 	

720

	 	  
	

Database maintenance

	 	

Study Duration = 18 months

	 	

DBA

	 	

1 month

	 	

0

	 	

18.00

	 	

4,320

	 	  
	

DM & Statistics - Project Management

	 	

Client meetings & corresp, DM metrics. 1hrs/month x 18 months

	 	

DM

	 	

1 month

	 	

120

	 	

18.00

	 	

1,530

	 	  
	

Input to protocol

	 	

Text and sample size calcualtion / power

	 	

Statistician

	 	

1 hour

	 	

200

	 	

4.00

	 	

800

	 	  
	

Generation of Randomisation schedule

	 	

1 Schedule.   40 Envelopes. Cost per

	 	

Statistician

	 	

1

	 	

1175

	 	

1.00

	 	

1,175

	 	  
	

Statistical Analysis Plan

	 	

Includes text and table and Isting shells

	 	

Statistician

	 	

1 Statistical

	 	

5840

	 	

1.00

	 	

5,840

	 	  
	

Identify Protocol Deviations and define Analysis

	 	

Unblinding. Protocol deviations and

	 	

Statistician

	 	

1 study

	 	

1600

	 	

1.00

	 	

1,600

	 	  
	

Analysis Datasets

	 	

Specification, Programming  & QC

	 	

SAS Programmer

	 	

1 study

	 	

4800

	 	

1.00

	 	

4,800

	 	  
	

Production of Tables 4 Listings

	 	

15 Unique tables. Cost per extra $720 

20 Repeat tables. Cost per extra $240 0 Figures. Cost per extra $420

35 Listings, Cost per extra $300

	 	

SAS Programmer

	 	

1 study

	 	

26100

	 	

1.00

	 	

26,100

	 	  
	

Statistical Analysis

	 	

10 analysis endpoints. Cost per extra $400

	 	

Statistician

	 	

1 analysis endpoint

	 	

400

	 	

10.00

	 	

4,000

	 	  
	

Provision of data to DSMB

	 	

Assumes interim running and QC of 6 TFLs in row Programming Tables and listings.

	 	

Statistician

	 	

1 meeting

	 	

960

	 	

3.00

	 	

2,880

	 	  
	

Input to Final report

	 	

Text for inclusion in study report.

	 	

Statistician

	 	

1 hour

	 	

2400

	 	

1.00

	 	

2,400

	 	  
	

 

	 	

 

	 	  	 	  	 	  	 	  	 	

Subtotal

	 	

$158,869

	

Medical Writing (Optional)

	 	

 

	 	  	 	  	 	  	 	  	 	  	 	  
	

Clinical study report (CSR)

	 	

 

	 	

Medical Writer

	 	

per CSR

	 	

22497

	 	

1.00

	 	

22,497

	 	  
	

QA review of CSR

	 	

Optional for Client

	 	

Medical Writer

	 	

per CSR

	 	

2769

	 	

1.00

	 	

2,769

	 	  
	

 

	 	

 

	 	  	 	  	 	  	 	  	 	

Subtotal

	 	

$25,266

	

 

	 	

 

	 	  	 	  	 	  	 	  	 	  	 	  
	

 

	 	

 

	 	  	 	  	 	  	 	  	 	

TOTAL

	 	

$383,986

 

Amendment 1 to Budget Expenses

 

	

Expense/Item

	 	

Comments

	 	

Unit Cost

	 	

Number

of Units

	 	

Item Cost

AUD$

	 	

AUD$

	

Site Visits

	 	

 

	 	  	 	  	 	  	 	  
	

Other Site visit Costs

	 	

Parking/tolls/meals and incidentals for site visits

	 	

$50/day

	 	

60.00

	 	

3,000

	 	  
	

 

	 	

 

	 	  	 	  	 	

Subtotal

	 	

$3,000

	

General Expenses

	 	

 

	 	  	 	  	 	  	 	  
	

General Expenses - Couriers, Postage, Telecommunications, Copying, stationery (files)

	 	

$70/site/month, 3 sites for 25 months

	 	

$210/month

	 	

25

	 	

5,250

	 	  
	

General Expenses - Couriers. Postage, Telecommunications, Copying, stationery (files)

	 	

$70/site/month, 2 new sites for 16 months

	 	

$140/month

	 	

16

	 	

2,240

	 	  
	 	 	 	 	 	 	 	 	 	 	 
	

CRF Printing

	 	

 

	 	

$2,500

	 	

1

	 	

2,500

	 	  
	

 

	 	

 

	 	  	 	  	 	

Subtotal

	 	

$9,990

	

 

	 	

 

	 	  	 	  	 	  	 	  
	

 

	 	

 

	 	  	 	  	 	

TOTAL

	 	

$12,990

 

	Prana 800089 (PBT2-204) version 2, 27th June 2012	 

 

 

Page 5 of 6

 

 

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:

	

13 July 2012

	 

 

	INCResearch Australia Pty Limited	 
	 	 	 
	

By:

	

	 
	 	 	 
	

Name:

	

Garth Tierney

	 
	 	 	 
	

Title:

	

Regional General Manager, Australia and South East Asia

	 
	 	 	 
	

Date:

	

19 July 2012

	 

 

	Prana 800089 (PBT2-204) version 2, 27th June 2012	 

 

 

Page 6 of 6

 

 

 

 

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 l: 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, l0th 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, l0th 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, l0th 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

AUDS

	

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, l0th 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

	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	

Airfares, accommodation &

	  	  	  	  	  	  	  	  	  	  	  	  
	

Travel/Attendance Costs

	  	

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, l0th 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, l0th 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, l0th April 2013

 

Page 8 of 8exhibit_4-29.htm

Exhibit 4.29

 

 

02 October 2013

 

Prana Biotechnology Limited

Level 2, 369 Royal Parade, Parkville 

VIC 3052 Australia

 

	
RE:

	
Letter Agreement for Clinical Trial Services for the 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”. Protocol # PBT2-203

 

Dear Carolyn and Caroline:

 

The purpose of this letter is to set forth an agreement (hereinafter “Letter Agreement”) between Prana Biotechnology Limited (hereinafter “Sponsor”) and INCResearch Australia Pty Limited, together with its parent company, INC Research, LLC, subsidiaries and legal affiliates (hereinafter “INC Research”) to undertake activities (the “Services”) relating to the Study. INC Research shall perform more comprehensive services pending the negotiation and execution of a mutually acceptable work order. The parties agree that this Letter Agreement governs matters of immediate agreement as specified in Attachment A and is a binding contract. The parties agree as follows:

 

	
1.  

	
INC Research shall undertake certain preliminary, preparatory activities prior to the completion of contract negotiations. These activities are listed in Attachment A (“Services”). Until such time as a work order is executed and unless otherwise expressly set forth in this Letter Agreement, INC Research agrees to perform the Services, and so too will Sponsor perform its obligations, in accordance with the terms and conditions set forth in the Master Services Agreement effectively dated 22nd September 2011 (“Master Agreement”).

 

If INC Research is required to engage third parties prior to execution of a work order, then such engagement will be limited only to the third party contractor(s) listed in Attachment B hereto; provided, however that INC Research will be under no obligation to execute any contracts on behalf of Sponsor in connection to the Protocol until adequate funding has been paid in advance to INC Research to cover all associated costs, and Sponsor agrees to pay any cancellation fees incurred beyond INC Research’s control.

 

	
2.  

	
Upon execution of this Letter Agreement, Sponsor will pay to INC Research start-up fees in the amount of AUD $200,000 and pass through costs in the amount of AUD $10,000 to undertake the Services associated with matters of immediate agreement. Payment is to be made to INC Research within three (3) business days following Sponsor’s execution of this Letter Agreement and may become the first milestone payment under the work order. Such payment may be applied toward the final reconciliation of the study budget upon study termination or cancellation in connection with this Letter Agreement or the executed work order, as applicable.

 

	
INCResearch Australia Ply Limited

	  
	
1003687 Prana Biotechnology Limited Letter Agreement with MSA Template v2.0 2nd Oct 13

	
 

 

  

Page 1 of 6

  

 

 

All communications, notices and payments required under this Letter Agreement 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:	 	 
	 	 	 	 
	 	For Communications & Accounts Payable:
	 	 	 	 
	 	 	 	
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

	 	 	 	 
	 	 	 Cc: Sponsor Contracts Management
	 	 	 	
INC Research, LLC

	 	 	 	
3201 Beechleaf Court

	 	 	 	
Suite 600

	 	 	 	
Raleigh, NC 27604-1547

	 	 	 	
Phone: 919-876-9300

	 	 	 	Facsimile: 919-882-0425

 

	
INCResearch Australia Pty Limited

	  
	
1003687 Prana Biotechnology Limited Letter Agreement with MSA Template v2.0 2nd Oct13

	
 

 

  

Page 2 of 6

  

 

 

	 	
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:

	 	
 

 

	
3.  

	
It is understood by the parties that until the time that this Letter Agreement is duly executed by each party, no obligations of performance whatsoever are incumbent on any party. Accordingly, INC Research shall be under no obligation to perform and shall not perform any services or incur any costs until the initial payment is made as described above.

 

	
4.  

	
The parties acknowledge and agree that it is their mutual intent to swiftly negotiate the work order that more completely sets forth their respective rights and obligations in connection with the Services. Accordingly, promptly upon execution of this Letter Agreement if not sooner, the parties shall commence good faith negotiations in an effort to reach agreement on the terms and conditions of such a work order. Should a work order not be executed, Sponsor agrees to pay all costs incurred by INC Research in performing the Services up to the date of termination of negotiations or the end of any necessary winding down period, whichever occurs last (consistent with paragraph 2 above).

 

	
5.  

	
The term of this Letter Agreement shall commence as of the date hereof and end upon the effective date of the work order or 18th October 2013 whichever is earlier. The term of this Letter Agreement may only be extended beyond 18th October 2013 upon written agreement of both parties. Sponsor party may terminate this Letter Agreement for any reason upon fourteen (14) days notice to the other party. The parties agree that upon any cancellation, default, or termination of this Letter Agreement, Sponsor shall have the right to a remittance of any advanced payments to INC Research, less any fees and expenses accrued and incurred.

 

If Sponsor agrees to the foregoing, please execute both counterparts of this letter and return one fully executed counterpart to the undersigned. The remaining counterpart is for Sponsor’s records.

 

Sincerely yours,

 

Andrew Shaw, Esq.

Senior Corporate Counsel

 

	
INCResearch Australia Pty Limited

	  
	
1003687 Prana Biotechnology Limited Letter Agreement with MSA Template v2.0 2nd Oct 13

	
 

 

  

Page 3 of 6

  

 

 

AGREED AND ACCEPTED:

The parties agree that this Letter Agreement is effective and binding and that facsimile copies and/or electronic signatures will constitute evidence of the existence of this Letter Agreement with the expectation that original documents may later be exchanged in good faith.

 

	INCResearch Australia Pty Limited 	 	 	
Prana Biotechnology Limited

	 	 	 	 	 	 	 	 	 	 
	
By:  

		 	 	By:  	 
	 	 	 	 	 	 	 	 
	
Name:

	
Andrew l. Shaw, Esq

	 	 	
Name: 

	Dianne Angus 
	 	 	 	 	 	 	 	 	 
	
Title: 

	Senior Corporate Counsel	           LEGAL	 	
Title: 

	Chief Operating Officer
	 	 	 	 	 	 	 	 	 
	
Date: 

	03 Oct 2013	 	 	
Date: 

	2nd October 2013

 

	
INCResearch Australia Pty Limited

	  
	
1003687 Prana Biotechnology Limited Letter Agreement with MSA Template v2.0 2nd Oct 13

	
 

 

  

Page 4 of 6

  

 

ATTACHMENT A 

 

List of Services

 

During the term of this Letter Agreement, INC Research will perform the following Services1:

 

	
●

	
 Complete CRF design

	

●

	
 Initiate Database Build

	

●

	
 Study Staff Familiarization on Study requirements-completed.

	

●

	
 Sponsor Teleconference Participation, a minimum of one per week.

	

●

	
 Internal Teleconference Participation

	

●

	
 CRA Training Days – 30 Sep 13, Melbourne, Australia and 2 Oct 13, Chicago, USA CRAs and LCRAs to attend (exact numbers to be confirmed)

	

●

	
10 Monitoring Visits – Australia and USA of which at least ten to be completed within the term, subject to sites availability

	

●

	
 Monitoring Visit Report Template Generation- completed

	

●

	
 Initiate LCRA Project Management Activities (Australia and US)

	 	 

1 INC Research may engage in additional activities as requested by the Sponsor, or as necessary to progress the Study toward targeted timelines.

 

	
INCResearch Australia Pty Limited

	  
	
1003687 Prana Biotechnology Limited Letter Agreement with MSA Template v2.0 2nd Oct 13

	
 

 

  

Page 5 of 6

  

 

 

ATTACHMENT B 

 

Permitted Contractors

 

-N.A

 

	
INCResearch Australia Pty Limited

	  
	
1003687 Prana Biotechnology Limited Letter Agreement with MSA Template v2.0 2nd Oct 13

	
 

 

Page 6 of 6

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