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\.~~DflFc.STERLING HOSPITAL ETHICS COMMITTEEDate: 23 A'iig~20ffl--, .Ref.: SH/SSl.&~gtr65018-2004-1681-201 0

To,Dr. Shrenik Shah,(PI- T05018-2004)R s D DepartmentSterling Hospital,Sterling Hospital Road,Memnagar,Ahmedabad-380052Gujarat, India.

Reference Protocol Title: T05018-2004: A Phase 2, Randomized, Open-label (with Blinded Plasminogen Activator and Placebo ControlGroups) Study to Evaluate the Effects of Different Intra-thrombusInfusion Regimens of Plasmin (Human) Compared toPlasminogen Activator and Placebo In Patients With Acute LowerExtremity Native Artery or Bypass Graft Occlusion

Subject Ethics Committee approval of the study documents for conduct ofreferenced study at Sterling Hospital.

Dear Dr. Shah,

This is with reference to your earlier letter Ref.: SH/EC/RNDIT05018-2004-1615-2010and study documents sent on 24 July 2010 for submission and review.

Sterling Hospital Ethics Committee at Sterling Hospital, Ahmedabad has reviewed anddiscussed your application to conduct the clinical trial entitled clinical study protocolT05018-2004 "A Phase 2, Randomized, Open-label (with Blinded PlasminogenActivator and Placebo Control Groups) Study to Evaluate the Effects of Different Intra-thrombus Infusion Regimens of Plasmin (Human) Compared to Plasminogen Activatorand Placebo In Patients With Acute Lower Extremity Native Artery or Bypass GraftOcclusion" on 21 Aug 2010.

Following documents were reviewed and approved by Ethics Committee.

1. Clinical Study Protocol T05018-2004, version 1.0 dated 30-Mar-10 (control copynumber: 80-92)

2. Investigator's Brochure for TAL-05-00018/Plasmin (Human), version 8, dated 14-Apr-2010 (control copy number: 80-92)

3. PIS/ICF in English, Gujarati and Hindi

• T05018-2004_SampleMasterV1.0-14May1 0_lndiaMasterV1.0-25May1 O_ShahV1.0-18Jun10

• T05018-2004 _SampleMasterV1. 0-14May1 0-,ndiaMasterV1. 0-2SMay1 0_Shah

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Sterling Hospitals, Sterling Hospital Road, Ahmedabad 380 052. Phone & Fax: +91·79·40011622.

V1.0-18Jun10_Gujarati translation 19Jun1 0• T05018-2004_SampleMasterV1.0-14May1 0_lndiaMasterV1.0-25May1 O_Shah

V1.0-18Jun1 O_Hindi translation 19Jun1 0

It was observed that Back translation of the PISIICF from Hindi to English and fromGujarati to English and the translation/ back translation certificates was not provided.Kindly provide it to us for our review once they are available with you, for EC notification.

4. Patient reference material: Emergency Card in English, Gujarati and Hindi

• 24May1 0_V1_ T05018-2004_Emergency Card_English• 24May10_ V1_ T05018-2004_Emergency Card_Hindi• 24May1 0_V1_ T05018-2004_Emergency Card_Gujarati

It was observed that back translation of the Emergency card from Hindi to English andfrom Gujarati to English and its relevant certificates was not provided. Kindly provide it tous for our review once they are available with you, for EC notification.

5. Draft CRF: Mock ups eCRFs, 25-May-10 (Draft) Version 1.

6. Copy of Investigator's undertaking to Kendle as per Schedule Y Appendix VII.

7. Draft Clinical Trial Agreement (Version 03Feb2009)

8. Copy of Insurance Certificate/Policy dated 19-May-2010.

9. Copy CV of the Principal Investigator.

10. Copy Regulatory Authority (DCGI) application submission letter acknowledgedby DCGI.

Following members of Ethics Committee were present during the Ethics Committeemeeting held at 9:00 a.m on 21 Aug 2010 at 8th floor, R & 0 Department, SterlingHospital, Sterling Hospital Road, Memnagar, Ahmedabad- 380052

No. Members Name designation Gender

1 Dr. Gaurang Shah Chairman M

2 Dr. Lubna Mansuri Member secretary F

3 Dr. M.D. Shukla Non Medical Scientist M

4 Mr. Pranav Bhatt Legal Expert M

5 Mr. Vijay Patel Legal Expert M

6 Ms. Bhoomee Thakrar social worker F7 Mr. Shardul Radadiya lay person M

8 Dr. Somesh Chandra Clinician M

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At the Ethics Committee meeting the above-mentioned documents were examined anddiscussed. After due consideration, the committee has decided to approve the conduct of thestudy and the study related documents subject to some suggestion. The suggestion are givenbelow:

1) On page 84/ 104 of Protocol - Ref: 8 mentioned in references be provided for furtherinformation to SHEC members.

This committee approval is granted to you subject to permission from the Drug ControllerGeneral of India, New Delhi for conduct of this study and has advised to take steps toregister this study in Clinical Trial Registry at earliest.

We have noted that biological samples from the study patients participating in this studywill be sent to the central laboratory for analysis as required by the protocol and theEthics Committee does not have any objection to the same. Please refer below detailsof the central laboratory.

• Quest Diagnostics Clinical TrialsUnit B1, Parkway West Industrial Estate,Cranford Lane, Heston,Middlesex, TW5 9QA, UK

• Quest Diagnostics Nichols Institute33608 Ortega Highway,San Juan Capistrano,CA 92675-2042, USA

• Focus Diagnostics, Inc.5785 Corporate Avenue,Cypress, CA 90630, USA

• Speciality Laboratories27027 Tourney Road,Valencia, CA 91355, USA

• Quest Diagnostics Clinical Trials - Biomarker27027 Tourney Road,Valencia, CA 91355, USA

It was observed that Institutional/Local laboratories i.e. Sterling Hospital PathologyDepartment, Sterling Hospital, Sterling Hospital Road, Ahmedabad-380052 will also beused to perform protocol specified clinical investigations.

We have also noted that the Sponsor has agreed for reasonable reimbursement ofconveyance cost to patient, on actuals per visit (a reasonable amount agreeable to bothsponsor and PI) and the Ethics Committee does not have any objection to it

The Institutional Ethics Committee expects to be informed about the progress of thestudy, any SAE occurring in the course of the study, any changes in the protocol andpatient information/informed consent and study related documents and asks to be

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informed of study completion and/or discontinuation with reasons. The committee alsoasks to be provided a copy of the final report.

We have noted that neither you nor any of your proposed study team members waspresent during the decision-making procedures of the Ethics Committee.

It is confirmed that our Ethics committee is constituted and functions as per ICIH GCPguidelines and Good clinical practice guidelines issued by the Central Drug StandardsControl Organization and Ethical guidelines for Biomedical Research on Humansubjects, issued by the Indian council of Medical Research

Yours sincerely,

Q~*~~~1lc)Dr. ~urang ShahChairperson of the Sterling Hospital Ehtics Committee.

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