24`' Apr, 2012

TO, Dr. Sapan Paudya, Principal Investigator Rheumatic Disease Clinic Ahmedabad.

1. Protocol: A 3921024: T#w,1duib.(CP-6",5501: "A long term, open4abel Follow-up study of Tasocitinib (CP-69(!,550) for treatment of Rheumatoid Arthritis."

Subject: Ethics Committee approval for the conduct of the referenced -study.

Dear Dr. Pandys,

The Ethics Committee of Care Institute of Medical Sciences reviewed and discussed of the above mentioned study at the meeting held on 10 Apr, 2012 at 4:00 pm. at Cam Institute of Medical Sciences.

The Ethics committee has reviewed and discussed the following study documents for the above referenced study:

1. Protocol Final Amendment 13 version 24 December 2010

2, Informed Consent Document version 20 January 2012 in English and Translations in Hindi and Gujarati.

3. Investigator's Brochure version June 2011 and Summary of Changes version 30 June 2011

A Pnfi-tv T mtpre-

Sr. No. AER NO. Adverse Event Report Type Country SUSAR Date

Other Serious Criteria: Medically Sign ilficantSmall

1 2011107507 cell lung cancer tSmall cell Follow up 3 Japan

07-Jun- lung cancerlMembmnous nephropathy [Membranous n2phrop#ftl Other Serious Criteria:

_ "'1E r 04-Jun-

2. 2008026847 Medically Follow up 3 STATES I I Sipificantpancreatitis Page I of 15

CIMS Hospitals W. Shukan Mail, Off Science City Road, Sofa, Ahmedabad-380 060, Gujarat, INDIA Ph.: +91-79-27712771-75 (5 lines) Fax - +91-79-2771 2770 Mobile: +9198250 66664,98250 66668

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[Pancreatitis]Anema [Anemia Shortness of breath [Shortness of breath]Fevers [Fever]Gallstones Gallstones

Encephalopathy by BK Virus [Encephalopaithyl 1 2010111732

Encephalopathy by BK virus

3. K virus infection] Follow up 5 Brazil 10-Jun- 10-Jun-

Sepals [ ~l 11 Right Knee Arthroplasty infection [BK. virus Infection] Pneumonia Pneumonia

4, 2011107568 Bladder turnour [Bladder Follow up l Slovakia 13-Jun- neoplasm] 11

5. 2011079624 Pertussis [Pertussis] Follow up 1 United States 16-Jun-11

tinier Serious Criteria: Medically Si nificantmetastatic small cell carcinoma of pulmonary

6. 2011047176 primary '(Small`cell lung Initial United States 17-Jun- cancer metastaticlElevated 11 liver function tests [Liver function tests raised]abdominal pain Abdominal painj

Encephalopathy by BK virus [Encephalitis viral] Sepjs [Sepsis]

7. 2010111732 Right Knee Arthropla ty FOLLO UP: Brazil 17-Jun- Infection ['Prosthesis related 9 l l Infection] Pneumonia [Pneumonia] Seizure f Seizure

8. 2011066271 Grypttococcal meningitis Follow up 3 KOREA, 17-Jun- fCryptococcat meningitis] R.EPUBL 11 Tuberculous KOREA, 20-Jun-

2011015999 meningoencephatitis Follow up 5 REPUBL 11 Tuberculosis of central

nervous systemiTuberculous spondylitis [Bone tuberculusis]disseminted tuberculosis [Disseminated tuberrcu osis]hepatotoxidity [Hepatotoxicity]DRESS syndrome ERESS s dmm

9. 2011107507 Membranous nephropathy Follow up 2 Japan 21-Jun- IMembratmous tiro ath 11

10. 2011124786 Probable osteosarcoma Initial Mexico 22-Jun-

Other Serious Criteria: 22-Jun- 11. 20111075£8 Medically SignifmcantBtadder Fallow up 2 SLOVAKIA 11

turnout` Bladder neo lasm Appendicitis (Append itis]Septicernia

12 201 [Septicemia]Cardic and Follow up s Brazil 24-Jun- respiratory arrests [Cardiac it arrestlCadic and respiratory crests [Respiratory arrest

13. 201 1079624 ~"~ssis [Pertussis] Follow up 2 United States 2 1 Jun-It

Encephalitis by BK Virus[Ence0alitis viral]Seps s [Sepsis]Right 29-Jul-

14. 20101 11732 Knee Arthroplasty infection[ Follow Up: 7 Brazil 11 Prosthesis related infection'neumonia Pneumonia Seizure Seizure

15. 2011136379 Mass at left lower lobe[Lung Initial

Korea, Republ 30-Jun- mass coat 11 Uterine squamous intraepithelial lesion Class 09-Jul-

16. 2011062-158 Hlb[Cervical high grade Fallow Up: 2 Japan 11 squattmous intraepithelial lesion Probable ostevsarcoma

17. 2011124786 [osteosarcoma]hemarthrosis Follow up I Mexico

19-Jul-I 1 of the right arm

Hemarthrosis involving

t` axmi

18. 2011066271 Cryptwcoccal meningitis Follow Up.-4 Korea, Republ 21-Jul- total meni itls coat: 11

Gastric Cancer[Gastric

19. 2010037109 cancerlMetastases to lymph

Fallow tip: 8 Japan 28-Jul-

nodees~[Metastasees to lymph l 1 nodes

20. 2011079624 Pertussis[Pertussis] Follow Up: 3 United Shies 29-Jul-11

Encephalitis by BK Virus[Encephatitis viral]Sepsis [Sepsis]Right 29-Jul-

21. 2010111732 Knee Arthroplasty infection[ Follow Up: 7 Brazil 11 Prosthesis related infectionlPneurnonia [ Pneumonia Seizure f Seizure] Pulmonary 03-Jul-

22. 2010096310 cryptc cosis[Pulmonary Follow UP : 7 Australia 11 psis

Pulmonary 03-Jul- 23. 2010096310 cryptococcosis[Pulmonarry Follow UP:7 Australia 11

tococeosis Pulmonary 03-Jul-

24. 2010096310 cryptococcosis [Pulxnonaty Follow UP : 7 Australia l l ctyptoc,occosisl

25 2011079624 Pertussis [P+ertussis] Follow Up : 4 United States 10- Au -11

26. 2011124786 Pertuss ,is [Pertussis] Follow Up: 2 Mexico 12- Au -11

27 2011079624 Pertussis[Pertussis] Fallow Up: 5 United States 17- Act -11

Uterine squarnous intraepithelial lesion Class 19-

28. 2011062158 lllb[Cervical high grade Follow UP : 3 Japan Aug-11 'intmepithelial squamous

lesion] Uterine squa rnous

29= 2Ul 1062158 intraepithelial lesion Class 111b[ Cervical high grade

allow Up: 3 Japan 19- Aug-11

squarnous intraeithelial

<i

r~

lesion Normal sill ovary

t carcinoma syndrome stage 4 [Ovarian cancer)'etast ases to lymph nodes [Muses to

30. 2010028035 lymph ncides]t;arcinotnatous Fallow tap: 13 Japan 25- pleurisy [Carcinomatous Aug-1 I pleurisy]Caa cinornatous peritonitis [Carcinomatous peritonitislOmenturn tumour t)menturn neo lasrn

Tuberculous meningoencephalitis t Tuberculosis of central nervous system]Tuberculous

20110 , 5999 span ylit s [Bone Follow Up: 7 Korea Repub~l., 01 -Sep- Follow 11

tuberculosis tDisseminated tuberculosis1hepatotoxicity [Hepatotoxicity]DRESS svndrome IDRESS svndromel

Follow Up: 7 Korea Republ.. 41-sep- ll

probable osteosarcorna t0steosarcormajhemarthrosis 01-Sep-

31 2011124785 of the right arm Follow Up: 3 Mexico 1 I [Hemarthrosis involving u r arm. Synovial sarcoma [Synovial sarrarnalhernarthrosisrif the 06-Sep-

34. 2011 I24?85 right ann [Hemarthrosis Fallow Up: 4 Mexico 1 I

35. 1 2011042207

and leptomeningtis [Meningitis]Lumbar 4-5 infectious spondylitis [Infective spondylitisleervical and thoracic epidural abscess [Epidurr d abscets1both psoas, anal abscess Follow Up: 9 [Abseess]Methicillin Resistant Staphylococcus Aurcus bacterernia [Staphylococcus aureus bacteremia]small bowel fistula [Intestinal fistula]parytic ileus

Korea, R.epubl 08-Sep-(cont.) 1 11

carcinoma syndrome stage 4 [Ovarian cancer]Metastases to lymph nodes [Metastases to lymph nodes]Carcinomatous pleurisy [Carcinomatous pleurisy]Carcinomatous peritonitis [Carcinomatous peritonitis]Omentum tumour [CJrnemum neoplasm] ntracranial pachymeningitis

and leptomeningitis [Meningitis]Lumbar 4-5 infectious spondylitis [Infective spondylitisicervical and thoracic epidural abscess [Epidural abscesslboth psoas, renal abscess [.Abscess]Methicillin Resistant Staphylococcus Aureus bacteremia [Staphylococcus aureus bacteremia]small bowel fistula [Intestinal

6 of 15

Follow Up: 14 1 Japan 08-Sep- 1 11

2011042207 Fallow Up: 9 Korea Republ.- 08-Sep- 11

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CIMS Hospitals: Nr. Sfuakan lk aN, Off Science Oty Road, Sofa, Akt ►13odabad-M 060r Guiwat INDIA Ph.: +91-79-27712771-75 (5 firm) Fax +91-79-27712770 Mole: +9198250 66664, 98250 66668

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Par9 ` is ileus Tuberculous Perirardi is [Pericarditis tuberculous]Tuberculous

38. 2010167550 lymphaderioPathy [lymph Fallow Up: 4 Korea Republ.. 09-Sep- node 11. tuberculosis]Tuberculous Pleural effusion [Tuberculous

leuris Gastric cancer [Gastric

39, 2010037109 c,cer]Metasta,e, to lymph Follow UP; 9 Japan 14-S:ep-

nodes [Metastases to lymph l t nodes lrttracranial pachymeningitis and ieptomeningitis Menin,8iti jf,unnbar. 4-5

infectious spondylitis va*ctive spo dylitis]cervical and thoracic epidural abscess [Epidural abscess]both psoas,

40. 2010028035 rental abscess Follow Up: 15

Japan 16-Sep-11 [Absss]Methicillin

Resistant Staphylococcus Aureus bacteremia [Staphylococcus aureus actere is}small bowel

fistula [intestinal fistulajpalytic ileus

anal ic.ileus (drug-induced) autoimmune 20-Sep-

41 2011193470 hepatitis [Autoirmnune Initial Poland 11 hepatitis]

Ventricular fibrillation [Ventricular fibrillation]

42. 2010144260 Variant angina [Variant Follow Up: 7 Japan 19-Sep- angina] 11 Hypokalaemia LHypqka1aemai]

43. 2010097119 Mycobacterium avium Follow UP: 10 Japan

Page 7 of 15

CWS Hospitals : Nr. Shukan Mall, Off Science City Road, Sola, Ahmed-380 060, Guj at, INDIA Ph.: +91-79-27712771-75 (5 lines) Fax: +91-19-27712770 Mo lle : +9198260 66664, 98250 66668

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complex infection i 1 [Mycobacterium avium complex infection]

Gastro esophageal ulcer 44. 2011025597 ["'Phageal ulcer]Castre

eso*gml ulcer [Gastric Fallow Up: 4 Philippines 22-Sep- 1 t

ulcer Mycobacterium avium

45. 2010097119 complex infection [Mycobacterium aviurn

Follow UP: 10 Japan 22_cep-11

cqMplex infection Ventricular fibrillation [Ventricular

46: 201,0144260 brillationl Variant angina Follow UP: 8 Japan 2il-Sep-

[Variant l l anginalHypokalaetnia H ` kalaemia

Small cell lung cancer [small

47: 201 l l4?7507 cell lung cancer] Follow UP: 6 Japan 29-Sep- Membranous nephropathy l l

ennbranous ne thyj Gastro esophageal ulcer

48. 2011025597 ul e , [t stric

Follow Up 5 Philipinnes I9~'-

ulcer Pneurno ystis pneumonia

49 2009232180 [ intaniataemia Follow Up: 1 Japan 2 9- ep-

Arsemia'

50. 2+009314810 Pager's disease ofthe breast Waget's disease of t1 breast Follow Up: I Japan 11 Intracranial pachymeningitis and leptomeningitis [MeningitislLumbar 4-5

51. 24 i 1042247 infectious spondylitis [Infective spondylitisjcervicai Follow Up: 10 Korea Republ.. 30-Sep-

11 and thoracic epidural abscess [Epidural abscess)both psoas, I renal abscess

Rage 8 of 15

CIMS Ha a ; Nr. Shin Mali, Off Science City Road, Sola, Ahmedabad-380 060, Guiatat, INCA Ph.: +91-79-2771 2771-75 (5 tines) Fax: +91 -79-27712770 MdWle .* +91198250 66664, 98250 66668

w+nrWAMS.Me

Ctlll<S; Hospftai Pvt_ Ltd.

IRB Reg Nei: lRt7Cs 0006900 (Rdcow4w M cis Dopmumt of H"M Wo KXrA n Sortie")

[Abscess]Methici l lin Resistant Staphylococcus Aureus bactenemia [Staphylococcus aureus bacteremia]small bowel fistula [Intestinal fistdla]paralytic ileus

oral is ileus elevated traasaminases due to 5-Oct-

52. 2011193470 autoimmune hepatitis Followup: I Poland I I Autointmune he atit s

Synovial sarcoma [Syn.ovial

53. 2011124786 sar na]hemarthrosis of the right arm [Hemarthrosis Followup: 6 Mexico

7-Oct- 11

involving upper arm Acute cytaegalovrus hepatitis [ ytamegalovirus hepatiti ]+Cytomegalovirus

54. 2010136883 infection [C;ytumegalovirus Fallow Up: 8 Chile

10-Oct-1 I infection]Acute myopathy

[Acute myopathy]Dee+p vein thrombosis right leg [Deep vein thrombosis le Normal sized ovary carcinoma syndrome stage 4 [Ovarian concer]Metastases to lymph nodes [Metastases to lymph nodes]Carcinomatous 11-Oct-

55. 2010028035 pleurisy Warcinomatous Followup: 16 Japan 11 pleurisy]Carcino matous peritonitis [Carcinomatous peritanitis]Carcin€ matous peritonitis [Omentum neoplasm)

56. 2010159734 Right cubital tunnel syndrome Followup: 4 Japan

12-Oct- Cubital tunnels Brame 11.

TTP (Ibrombotic

57. 2010113840 thrum vcytopenic purpura) Fallow Up: I Japan

12-Oct- [Thrombotic 11 thromboc o epic

Page 9 of 15

CMAS Hospitals : Nr. Shuk Mail,O f Science City Road, Sofa, Ahmedabad-380 060, Gujarat, INDIA Ph.: +91-79-277127'71-78 ( Knes) Fax: +91-79,-27712770 Mobile: +0198260 68864, 98250 66668

.dmS.m0

arthritis Reactive arthritis Pustulosis psoriasis [Psoriasis

78. 2011306216 pustular] Follow up: I Brazil 13 Jan Erythrodermic psoriasis 2012

hrodemie oflasis

79. 2011222880 Erythfoderm'c psoriasis initial Brazil 13 :flan Nythrodermit Moria is 2012 Thrombocytopenia [Thrombocytopenia] Leukocytosis (Leukocytosis]

80. 201001522? Sepsis [SePsiis] FQLLOWUP: BULGARIA LGAR lA 19 Jan 2012 Hepatesplenomegaly 4 [Hepatosplenomegaly] Vertebral fracture [Vertebral fracture suspected chronic obstructive

81. 2012007821 pulmonary disease [Chronic INITIAL GERMANY 20 Jan obstructive pulmonary 2012 dise~se

2011066271 Cryptococcai meningitis FOLLOW-UP: KOREA, REPUDL

20 Jan [Cryptococcal meningitis] 5 2012 continue..

83. 20112881,22 Myocarditis [Myocarditis] 1~+CaLt,O'VVL1P; Germany 20 San 2012

non-sustained ventricular 23 Jan 84. 2012007603 tachycardia [Non-sustained Initial AUSTRALIA 2012

ventricular tachycardia j

85. 2011.222880 Erythrodermic psoriasis Fallow Up: I Brazil 24 Jan hrodermic soriasis~ 2012

CTT.gAR T: rtA f ct ng-

Clinical Trial Safety Update Report dated 14 Reporting period ( 17 May 2011 through 16 Nov Jan 2004 2011 Clinical Trial Safety Update Report; dated I8 Reporting period (+Ill May 2011 through 31 Oct Dec 2002 201 1 )

Page 12 of 15

CIMS H"p► iss : Nr. Snukan Mail, Off Science a City Road, Sda, Attmadab€td-380 060, Gujarat, INMA PK : +91-79-27712771-75 (5 1in") Fax: +94-M27712770 Motsile . +9198260 ,66664,98250 66668

www rims r

5. BlankCase R4)6rt Forns version 47 February 2011

6. Following Questi+ maires in English and the translations in Hindi and Gujarati

a EQ-51) HEALTH QUESTIONNAIRE

b. IrtAE T-FATIGUE SCALE (Version 4)

11. Patient ID card for use to be given to the patients In this study, patients will be given ID cards at the time of baseline visit aft randomization (enclosed for your reference). This III card has inflomation such as patient's'narmeleontad details, identification as a study participant and serv=es as a referees to any other physicieWconsultant for their to know and contact the site and principal investigator Besides this, there is no othor steady reed information on this ID card. As per ICH-GCP guideline 8.2.7 any document givers to the patient may require ESC approval.

In view of this, please find enclosed the }dent ID card for your review & please grant the approval for the use of the san=e.

12. In the study we wilt be using the followirsg proposed method of patient accrual:

• Subjects who have participated in the A3921€I69 study and who fit the eligibility criteria would be enrolled in this study,

Page 13 of 15

61MS Hospitals : Nr. Shukan Mail, Off Science City Road, Seta, Ahwaiabad-389 WO, Gujarat, 1001A W: +91-79-27712771-75 (S sines) Fax. +91-79-27712770 Mobile: +9198250 66664,98250 W668

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'av,._ .1 E d

3 Ethic's Committee , e of

W Cims Came Institute of Medical Sciences

DIMS Hospital Pvt. Ltd.

IRS Re9d. No: IROG 0006900 (RO

13. Principal Investigator's current C'V'

14. Insurance policy for period Ist January 201.2 to 31st December 2012 (i copy).

15. Investigator's undertaking

16. Investigator's agreement with the sponsor (draft template) version November 2011.

17. We will be using the below mentioned lab as the central lab for all protocol specified investigations in the stuffy and local labs at our institute will be used in emergency.

The fallowing members of the Mics Committee were present at the meeting.

Name Qualification Designation/ Role in EC Affiliations as Abstained from to the voting Institution Yes/No

Dr. Pad22p Bhatt Ph.D., D.I.M. Pharmr Olo 'st / Chairman No No Dr. Chirag Desai MD DM Clinician / Member No Yes Dr. Paris Doshi MD Clinician / Member No No Dr. AdarshJit MD DM, Pharmacologist I Member No Into Singh. Dipioinate NB,

D.P`hann Mrs. Rash mi Shah. M.A. Social Worker/Member No No W' Ushakant B.Com, MICA Social Worker/Member No No Shah Mrs. Komal Shah MSE(Masters in Member Associate Yes Yes

Software Secretary I Member Engineerm&2

Mr. Hemant Shah B.Com, LL.B Advocate / Member No No Mr. Bhagirath B.Com, LL.B Advocate/Member NO No Oza Mr. Ramesh BA Member/ Lay Person No No Kohl! Ms, Zuber Arab M.Pltaa~m Member Secret Yes Yes

Page 14 of IS

CWS Hka outs : Nr. Shukan Mail, tat# Science City Road , Sole , Ahmedabad-380 060, Gujarat , lND A Ph.: +91 -79-2771 2771 -75 (5 lines) Fax , +91 -79-2771 2770 Mob4o : +919825066664,98250 66668

w ww ciins.me

tal Pvt. Ltd.

IROG 0006900 of HOSM Ow HWW &KWON)

The committee approves the documents submitted for the review in its presented form subject to DCGI notification & approval.

We confirm that none of your study staff member was present during the decision-making / voting procedures of this meeting. Also the EC member secretary Mr. Zuber Arab abstained from voting during this meetin&

Kindly note that the Ethics Committee of Care Institute of Medical Sciences works in accordance with the Indian GCP, ICH GCP guidelines and Schedule-Y.

Yours truly,

~14 ~4 )2-

Dr. Parloop Bhatt Chairperson Ethics Committee of Care Institute of Medical Sciences

Page 15 of 15

CIMS Hospitals: Nr. Shukan Mail, Of ScWnt* City Road, Sofa, Ahmedabad-380 060, Gujarat, INDIA Ph.: +91-79-27712771-76 (6 lines) Fax: +91-79-27712770 Mobile: +9198250 66664,98260 66668

www.cims.me