REF/2014/01/ CTRI Website URL -

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1 Clinical Trial Details (PDF Generation Date :- Sat, 05 May :20:40 GMT) CTRI Number Last Modified On 08/03/2018 Post Graduate Thesis Type of Trial Type of Study Study Design Public Title of Study Scientific Title of Study CTRI/2014/01/ [Registered on: 16/01/2014] - Trial Registered Prospectively No Interventional Drug Randomized, Parallel Group, Active Controlled Trial Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg-Negative, Chronic Hepatitis B A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg-Negative, Chronic Hepatitis B Secondary IDs if Any Secondary ID Identifier Details of Principal Investigator or overall Trial Coordinator (multi-center study) GS-US Amendment 1: 12 Jul 2013 Designation Affiliation Protocol Number Details of Principal Investigator Details Contact Person (Scientific Query) Details Contact Person (Public Query) Phone Fax Designation Affiliation Details Contact Person (Scientific Query) Dr Vaishali Karadkar Medical Monitor Klinera Corporation Phone Fax Designation Affiliation 801, Neelkanth Corporate Park, Near Vidyavihar Station, Vidhyavihar West, vkaradkar@klinera.com Details Contact Person (Public Query) Mr Sunil Verma Clinical Trial Project Manager Klinera Corporation 801, Neelkanth Corporate Park, Near Vidyavihar Station, Vidhyavihar West, page 1 / 7

2 Source of Monetary or Material Support Primary Sponsor Details of Secondary Sponsor Countries of Recruitment Sites of Study Phone Fax > Gilead Sciences, Inc. Source of Monetary or Material Support Primary Sponsor Details Gilead Sciences Inc Gilead Sciences, Inc. 333 Lakeside Drive Foster City, CA USA Type of Sponsor KlinEra Corporation List of Countries Australia Canada China France Germany Hong Kong Italy Japan New Zealand Poland Romania Russian Federation Spain Taiwan Turkey United Kingdom United States of America Viet Nam of Principal Investigator Dr Shalimar Dr Aejaz Habeeb Pharmaceutical industry-global 401, Hill View Industrial Estate, Ghatkopar West, of Site Site Phone/Fax/ All Institute of Medical Sciences Gastroenterology and Human Nutrition, Room number: 3105, 3rd Floor, Teaching Block, All Institute of Medical Sciences, Ansari Nagar, New Delhi, Delhi New Delhi DELHI Centre for Liver Zafar Garh, Research & Diagnostics Kanchanbagh,,Deccan College of Hyderabad Medical Sciences and Andhra Pradesh com page 2 / 7

3 Dr Y K Chawla Allied Hospitals Hepatology, Postgraduate Institute of Medical Education and Research Hyderabad ANDHRA PRADESH Hepatology, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh ,(UT) Chandigarh CHANDIGARH Dr Sachin Palnitkar Global Hospital Lakadi Ka Pul, Hyderabad , Andhra Pradesh, Hyderabad ANDHRA PRADESH Dr Manoj Kumar Sharma Dr Samir Shah Dr Abhijit Chowdhury Dr Rajiv Mehta Dr Ramesh Rooprai Dr Shobna Bhatia Institute of Liver and Biliary Sciences Institute of Liver Diseases, HPB Surgery and Transplant, Global Hospitals Institute of Post Graduate Medical Education And Research Nirmal Hospital Pvt. Ltd. S.R. Kalla Memorial Gastro & General Hospital Seth GS Medical College and KEM Hospital Ground Floor, OPD Block, D-1 Vasant Kunj New Delhi Delhi New Delhi DELHI Hepatology, Institute of Liver Diseases, HPB Surgery and Transplant, Global Hospitals Dr. E. Borges Road, Hospital Avenue, Opp. Shirodkar High School, Parel, , Maharashtra, Ronald ross building, 9 floor, 244 A, J.C. Bose Road, Kolkata , West Bengal Kolkata WEST BENGAL Ring Road, Surat, Gujarat Surat GUJARAT 78, Dhuleshwar Garden, Sardar Patel Marg, C-Scheme, Jaipur , Rajsthan, Jaipur RAJASTHAN 9th floor, Dept. of Gastroenterology, Acharya Donde Marg, Parel, , Maharashtra ykchawla@gmail.com Palnitkarsachin@gmail. com manojkumardm@gmail. com drshahsamir@gmail.co m chaudhuria@gmail.com rmgastro@yahoo.com rameshroop@gmail.co m shobna.bhatia@gmail.c om page 3 / 7

4 Details of Ethics Committee Regulatory Clearance Status from DCGI Health Condition / Problems Studied of Committee Approval Status Date of Approval Is Independent Ethics Committee? All Institute of Medical Sciences Ethics Committee; New Delhi; Dr. Shalimar Institute of Liver and Biliary Sciences Ethics Committee, New Delhi- Dr. Manoj Kumar Sharma Committee (IEC) II. Seth G SMedical College and KEM hospital,, ; Dr.Shobna Bhatia Committee, Deccan College of Medical Sciences and Allied Hospitals, Hyderabad, Dr. Aejaz Habeeb Committee, Global Hospital- Dr. Sachin Palnitkar Committee, Institute of Liver Diseases, HPB Surgery and Transplant, Global Hospitals, Dr Samir Shah Committee- Postgraduate Institute of Medical Education and Research; Chandigarh, Dr. Ajay Duseja IPGME&R Research Oversight Committee, Kolkata, Dr. Abhijit Chowdhury Nirmal Hospital Private Limited Ethics Committee, Surat; Dr. Rajiv Mehta S. R. Kalla Memorial Ethical committee for Human research- Dr. Ramesh Roop Rai Status Approved 10/02/2017 No Approved 10/03/2014 No Approved 14/10/2017 No Approved 16/11/2013 No Approved 07/06/2014 No Approved 07/03/2014 No Approved 09/06/2014 No Approved 24/03/2014 No Approved 07/01/2014 No Approved 12/03/2014 No Date Approved/Obtained 13/05/2014 Health Type Condition page 4 / 7

5 Intervention / Comparator Agent Inclusion Criteria Patients Type Details Intervention Drug: Tenofovir alafenamide Tenofovir alafenamide 25 mg tablet administered orally once daily Drug: Tenofovir DF 300 mg tablet administered orally once daily Other : Viread Comparator Agent Age From Age To Gender Details Drug: Placebo to match tenofovir alafenamide Placebo to match tenofovir alafenamide administered as a tablet orally once daily Drug: Placebo to match tenofovir DF Placebo to match tenofovir DF administered as a tablet orally once daily Year(s) Year(s) Both Inclusion Criteria Chronic hepatitis B virus (HBV) HBeAg negative infection Approximately 390 participants will be randomized in a 2:1 ratio (A:B) to the treatment arms and will be stratified by plasma HBV DNA level ( 7 log10 IU/mL, 7 log10 IU/mL - 8 log10 IU/mL, 8 log10 IU/mL) and oral antiviral treatment status (treatment-naïve vs. treatment-experienced). Treatment Arm A: 260 participants TAF 25 mg QD and matched placebo of TDF 300 mg QD total duration of therapy is 144 weeks. Treatment Arm B: 130 participants TDF 300 mg QD and matched placebo of TAF 25 mg QD total duration of therapy is 144 weeks 1 Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures 2 Adult males and non-pregnant, non-lactating females, 18 years of age and older 3 Documented evidence of chronic HBV CHB infection 4 Hepatitis e antigen HBeAg negative, chronic hepatitis B with all of the following HBeAg-negative and hepatitis B e antibody HBeAb positive at screening Screening HBV DNA greater than or equal to 2 x 10 upon 4 IU per ml Screening serum alanine aminotransferase ALT level greater than 60 U/L males or greater than 38 U per L females and greater than 10 x the upper limit of the normal range ULN 5 Treatment-naive participants (defined as lower than 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue, OR treatment-experienced participants defined as participants meeting all entry criteria including HBV DNA and serum ALT criteria and with greater than or equal 12 weeks of previous treatment with any nucleoside or nucleotide analogue 6 Previous treatment with interferon pegylated or non pegylated must have ended at least 6 months prior to the baseline visit. 7 Adequate renal function 8 Normal ECG Exclusion Criteria Exclusion Criteria page 5 / 7

6 Details 1 Females who are breastfeeding 2 Males and females of reproductive potential who are unwilling to use an effective, protocol specified methods of contraception during the study 3 Co-infection with hepatitis C, HIV, or hepatitis D 4 Evidence of hepatocellular carcinoma 5 Any clinical and/or laboratory evidence of hepatic decompensation 6 Abnormal hematological and biochemical parameters, including aspartate aminotransferase AST greater than 10 x ULN 7 Received solid organ or bone marrow transplant 8 History of malignancy within the past 5 years, with the exception of specific cancers that are cured by surgical resection participants under evaluation for possible malignancy are not eligible 9 Currently receiving therapy with immunomodulators eg corticosteroids investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion 10 Subjects receiving ongoing therapy with drugs not to be used with tenofovir alafenamide or tenofovir disoproxil fumarate or subjects with a known hypersensitivity to study drugs, metabolites, or formulation excipients 11 Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance 12 Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements Method of Generating Random Sequence Method of Concealment Blinding/Masking Computer generated randomization Case Record Numbers Participant and Investigator Blinded Primary Outcome Outcome Timepoints The proportion of participants with hepatitis B virus (HBV) DNA less than 29 IU per ml The primary efficacy endpoint is determined by the achievement of HBV DNA less than 29 IU per ml at Week 48. The proportion of subjects with plasma HBV DNA 29 IU/mL at Weeks 96, 144, 240, and 384 The proportion of subjects with plasma HBV DNA 29 IU/mL(target not detected) at Weeks 48, 96, 144, 240, and 384 Week 48 Week 96 Week 144 Week 240 Week 384 Secondary Outcome Outcome Timepoints Percent change from baseline in hip and spine bone mineral density (BMD) at Week 48 Change from baseline in serum creatinine at Week 48..The proportion of subjects in each treatment arm with tolerability failure (defined as an adverse event [AE] leading to permanent discontinuation of study drug) at Weeks 48, and 96, 144, 240, and 384 will be summarized. Change from baseline in serum creatinine will be Week 24, 48, 72, 96, 120, and 144, and every 48 weeks until Week 384/ED. page 6 / 7

7 Powered by TCPDF ( REF/2014/01/ Target Sample Size Phase of Trial Phase 3 Date of First Enrollment () Date of First Enrollment (Global) Estimated Duration of Trial Recruitment Status of Trial (Global) Recruitment Status of Trial () Publication Details Brief Summary assessed at every visit and summarized through Week 384/ED. Total Sample Size=390 Sample Size from =240 24/01/ /09/2013 Years=4 Months=7 Days=0 Completed Completed Not applicable The purpose of this study is to evaluate the safety and efficacy of tenofovir alafenamide (TAF) compared to that of tenofovir disoproxil fumarate (TDF) in treatment naive and experienced adult subjects with chronic hepatitis B virus (HBV) infection, as determined by the achievement of HBV DNA less than 29 IU/mL at Week 48 infection,.to compare the efficacy of TAF 25 mg QD versus TDF 300 mg QD for the treatment of HBeAg-negative, chronic hepatitis B in regard to the proportion of subjects with plasma HBV DNA levels below 29 IU/mL at Weeks 96 and 144. To compare the biochemical (ALT normalization) response of TAF 25 mg QD versus TDF 300 mg QD for the treatment of HBeAg-negative, chronic hepatitis B at Weeks 48, 96, and 144.To compare the serological response (loss of HBsAg with seroconversion to anti-hbs) of TAF 25 mg QD versus TDF 300 mg QD for the treatment of HBeAg-negative, chronic hepatitis B at Weeks 48, 96, and 144.The duration of double-blind treatment is 144 weeks (96 weeks under Amendments 1 and 2). At Week 144, all subjects remaining on blinded treatment will be switched to the open-label TAF 25 mg QD extension period for up to an additional 240 weeks (Week 144 throughweek 384/ED). Subjects already assigned to open-label TAF 25 mg QD at Week 96 per Amendment 1 or 2 will continue on open-label TAF 25 mg QD through Week 384/ED. All subjects who complete the double-blind period of treatment are eligible for participation in the open-label TAF 25 mg QD extension period. Subjects who permanently discontinue study drug(either prematurely [ED] or at the end of study [Week 384]) for reasons other than HBsAg loss with confirmed seroconversion to anti-hbs, will be followed every 4 weeks for 24 weeks off treatment or until initiation of alternative, commercially available HBV therapy, whichever occurs first. page 7 / 7