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

	
 







 




  





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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.







 



	
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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).







 



	
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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.


 



	
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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.


 



	
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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.


 



	
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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.







 



	
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●

	
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.







 



	
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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.













	
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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 8