CTRI

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CTRI Number

CTRI/2017/08/009304 [Registered on: 08/08/2017] Trial Registered Prospectively

Last Modified On:

09/02/2018

Post Graduate Thesis

Type of Trial

Interventional

Type of Study

Drug

Study Design

Randomized, Parallel Group, Placebo Controlled Trial

Public Title of Study

A clinical experimental study to check the effect and benefits of Selonsertib in patients with Non alcoholic hepatitis (NASH) and Bridging (F3) Fibrosis

Scientific Title of Study

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib in Subjects with Nonalcoholic Steatohepatitis (NASH) and Bridging (F3) Fibrosis

Trial Acronym

Secondary IDs if Any

Secondary ID	Identifier
GS-US-384-1943 Original dated 19 Dec 2016	Protocol Number

Details of Principal Investigator or overall Trial Coordinator (multi-center study)

Name
Designation
Affiliation
Address
Phone
Fax
Email

Details of Contact Person
Scientific Query

Name	Dr Rupa Desai
Designation	Global-Clinical Operations Head
Affiliation	Klinera Corporation India
Address	Klinera Corporation India, 401, Hill View Industrial Estate, LBS Marg, Ghatkopar West, Mumbai 400 086. MAHARASHTRA India Mumbai MAHARASHTRA 400086 India
Phone	02225091470
Fax	02225004588
Email	rupa.d@klinera.com

Details of Contact Person
Public Query

Name	Prashant Honrao
Designation	Project Manager-Clinical Operations
Affiliation	Klinera Corporation India
Address	Klinera Corporation India, 401, Hill View Industrial Estate, LBS Marg, Ghatkopar West, Mumbai 400 086. MAHARASHTRA India Mumbai MAHARASHTRA 400086 India
Phone	02225091470
Fax	02225004588
Email	hprashant@klinera.com

Source of Monetary or Material Support

Gilead Sciences Inc 333 Lakeside Drive Foster City, CA 94404, USA

Primary Sponsor

Name	Gilead Sciences Inc
Address	Gilead Sciences Inc 333 Lakeside Drive Foster City, CA 94404, USA
Type of Sponsor	Pharmaceutical industry-Global

Details of Secondary Sponsor

Name	Address
Klinera Corporation India	Klinera Corporation India 401 Industrial Hill View Ghatkopar west, Mumbai-400086

Countries of Recruitment

Australia
Canada
France
Germany
Hong Kong
India
Israel
Italy
Malaysia
Singapore
Spain
Switzerland
Taiwan
United Kingdom
United States of America

Sites of Study

Details of Ethics Committee
Modification(s)

No of Ethics Committees= 18
Name of Committee	Approval Status
Drug Trial Ethics Committee,Dayanand Medical College & Hospital, Dr. Ajid Sood	Submittted/Under Review
Ethics Committee for Research , Fortis Flt. Lt. Rajan Dhall Hospital, Dr. S. K. Acharya	Approved
Ethics Committee Global Hospital, Dr. Samir Shah	Approved
Ethics Committee, Dispur Hospitals Pvt. Ltd, Dr.B D Goswami	Submittted/Under Review
Institute of Post Graduation Medical Education & Research Oversight Committee, Dr Abhijit Chowdhury	Approved
Institutional Ethics Committe Sanjay Gandhi Postgraduate Institute of medical sciences Bioethics cell Dr Vivek Saraswat	Submittted/Under Review
Institutional Ethics Committee, AIIMS, Dr. Shalimar	Approved
Institutional Ethics Committee, Gleneagles Global Hospital, Dr Dharmesh Kapoor	Approved
Institutional Ethics Committee,Institute of Liver & Biliary Sciences, Dr. S. K. Sarin	Approved
Institutional Ethics Committee,Midas Multispeciality Hospital Pvt LTD, Dr. Shrikant Mukewar	Approved
Institutional Ethics Committee,Sparsh Hospitals & Critical Care(P) Ltd. Dr. Sarat Chandra Panigrahi	Approved
Institutional Ethics Committee,Sunshine Hospitals, Dr. Ravi Shankar	Approved
Institutional Ethics Committee,VGM Hospital, Dr. VGM Prasad	Submittted/Under Review
Institutional Ethics Committee- Postgraduate Institute of Medical Education and Research; Dr. Ajay Duseja	Submittted/Under Review
Manipal University Ethics Committee, Dr. V Tantry	Approved
Shree Giriraj Hospital Research Ethics Committee, Dr. Chetan Mehta	Approved
Surat Institute of Digestive Sciences Ethics Committee, Dr. Rajiv Mehta	Approved
The Ethics Committee, SMS Medical College and Attached Hospital, Dr. Sandeep Nijhawan	Approved

Regulatory Clearance Status from DCGI

Status

Approved/Obtained

Health Condition / Problems Studied

Health Type	Condition
Patients	Nonalcoholic Steatohepatitis (NASH) and Bridging (F3) Fibrosis,

Intervention / Comparator Agent

Type	Name	Details
Comparator Agent	Placebo to match Selonsertib 18 mg Placebo to match Selonsertib 06 mg	Placebo to match Selonsertib 18 mg OD 240 Weeks Placebo to match Selonsertib 06 mg OD 240 Weeks
Intervention	Selonsertib 18 mg Selonsertib 06 mg	Selonsertib 18 mg OD 240 Weeks Selonsertib 06 mg OD 240 Weeks

Inclusion Criteria

Age From	18.00 Year(s)
Age To	70.00 Year(s)
Gender	Both
Details	Subjects must meet all of the following inclusion criteria to be eligible for participation in this study. 1) Willing and able to give informed consent prior to any study specific procedures being performed 2) Liver biopsy consistent with NASH (defined as the presence of at least grade 1 steatosis, hepatocellular ballooning, and lobular inflammation according to the NAFLD Activity Score [NAS]) and bridging (F3 fibrosis) according to the NASH CRN classification, in the opinion of the central reader. a) historical liver biopsy within 6 months of the Screening visit may be accepted as the Screening biopsy if the sample is deemed acceptable for interpretation by the central reader. b) If the subject is deemed ineligible for this study, the liver biopsy, if performed according to protocol specifications and is within 12 months of the Screening visit, may be used to determine eligibility for study GS-US-384-1944. 3) Subject has the following laboratory parameters at the Screening visit, as determined by the central laboratory: I) ALT â‰¤ 8 x ULN II) CLcr â‰¥ 30 mL/min, as calculated by the Cockcroft-Gault equation III) HbA1c â‰¤ 9.5% IV) Total bilirubin â‰¤ 1.5 x ULN 4) Body Mass Index (BMI) â‰¥ 18 kg/m2 at Screening 5) Males and non-pregnant, non-lactating females between 18-70 years of age; inclusive based on the date of the Screening visit 6) Females of childbearing potential (as defined in Appendix 3) must have a negative pregnancy test at Screening and Day 1 7) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in

ExclusionCriteria

Details

Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Prior history of decompensated liver disease, including ascites, HE, or variceal bleeding
2) CP score > 6, as determined at Screening
3) MELD score > 12, as determined at Screening
4) Chronic HBV infection (HBsAg positive)
5) Chronic HCV infection (HCV Ab and HCV RNA positive). Subjects cured of HCV infection less than 5 years prior to the Screening visit are not eligible.
6) Other causes of liver disease including, but not limited to, alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (e.g., primary biliary cholangitis, primary sclerosing
cholangitis, and autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, iron
overload, and alpha-1-antitryspin deficiency, based on medical history and centralized review
of liver histology.
7) History of liver transplantation
8) Current or history of HCC
9) Any weight reduction surgery in the 2 years prior to Screening or planned during the study
(weight reduction surgery is disallowed during the study), and malabsorptive weight loss
surgery (e.g., Roux-en-Y or distal gastric bypass) at any time prior to Screening
10) Weight loss > 10% within 6 months of Screening
11) HIV infection (HIV Ab and HIV ribonucleic acid [HIV RNA] positive)
12) Current alcohol consumption greater than 21 oz/week for males or 14 oz/week for females
(1oz/30mL of alcohol is present in 1 12oz/360mL beer, 1 4oz/120mL glass of wine, and a
1 oz/30 mL measure of 40 proof alcohol)
13) Positive urine drug screen for amphetamines, cocaine or opiates (i.e. heroin, morphine) at
Screening. Subjects on stable methadone or buprenorphine maintenance treatment for at least
6 months prior to Screening may be included in the study. Subjects with a positive urine drug
screen due to prescription opioid-based medication are eligible if the prescription and
diagnosis are reviewed and approved by the investigator
14) Unstable cardiovascular disease as defined by any of the following:
a) Unstable angina, myocardial infarction, coronary artery bypass graft surgery or coronary
angioplasty within 6 months prior to Screening
b) Transient ischemic attack or cerebrovascular accident within 6 months prior to Screening
c) Symptomatic obstructive valvular heart disease or hypertrophic cardiomyopathy
d) Congestive heart failure
15) Use of any prohibited concomitant medication as described in Section 5.4. Subjects on
Vitamin E must be on a stable dose for at least 6 months prior to Day 1 and subjects on
thiazolidinediones (TZDs) must be on a stable dose for at least 3 months prior to Day 1
16) History of a malignancy within 5 years of Screening with the following exceptions:
a) Adequately treated carcinoma in situ of the cervix
b) Adequately treated basal or squamous cell cancer or other localized non-melanoma skin
cancer
17) Unable to safely undergo a liver biopsy
18) Participation in another investigational study of a drug or device within 30 days or within 5 half-lives of the prior investigational agent (whichever is longer) prior to Screening
19) Concurrent participation in another therapeutic clinical study
20) Known hypersensitivity to SEL, the metabolites, or formulation excipient
21) Any laboratory abnormality or condition that, in the investigatorâ€™s opinion, could adversely affect the safety of the subject or impair the assessment of study results
22) Presence of any condition that could, in the opinion of the investigator, compromise the
subjectâ€™s ability to participate in the study, including a history of substance abuse or a
psychiatric condition requiring hospitalization or emergency room visit within 2 years of
Screening
23) Unavailable for follow-up assessment or concern for subjectâ€™s compliance with the protocol procedures

Method of Generating Random Sequence

Computer generated randomization

Method of Concealment

Case Record Numbers

Blinding/Masking

Participant and Investigator Blinded

Primary Outcome

Outcome	TimePoints
A stratified Mantel-Haenszel (MH) test will be used to compare the differences in proportion of subjects who achieve a â‰¥ 1-stage improvement in fibrosis without worsening of NASH at Week 48 between each of the SEL arms and the placebo arm, adjusting for stratification factors	Week 48

Secondary Outcome

Outcome	TimePoints
Proportion of subjects who have a â‰¥ 1-stage improvement in fibrosis without worsening of NASH	Week 240

Target Sample Size

Total Sample Size="800"
Sample Size from India="60"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"

Phase of Trial

Phase 3

Date of First Enrollment (India)

30/08/2017

Date of Study Completion (India)

Applicable only for Completed/Terminated trials

Date of First Enrollment (Global)

05/06/2017

Date of Study Completion (Global)

Applicable only for Completed/Terminated trials

Estimated Duration of Trial

Years="4"
Months="8"
Days="0"

Recruitment Status of Trial (Global)
Modification(s)

Open to Recruitment

Recruitment Status of Trial (India)

Open to Recruitment

Publication Details

Not Applicable

Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?

Brief Summary

This is a Phase 3, randomized, double-blind, placebo-controlled study
evaluating the safety and efficacy of SEL in subjects with NASH and
bridging (F3) fibrosis.