Safety and Efficacy of Simtuzumab (SIM, GS-6624) in Adults With Advanced Liver Fibrosis But Not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)

Phase 2

Terminated

Brief Summary: The primary objective of this study is to evaluate whether SIM (formerly referred to as GS-6624) is effective at preventing the histologic progression of liver fibrosis and the clinical progression to cirrhosis in participants with NASH.

It will consist of 2 phases:

* Randomized Double-Blind Phase

* Open-Label Phase (optional)

Recruitment & Eligibility

Inclusion Criteria

Adults with chronic liver disease due to NASH defined as macrovesicular steatosis involving > 5% of hepatocytes on a liver biopsy with associated lobular inflammation
Stage 3-4 fibrosis by Ishak score on a liver biopsy
Exclusion of other causes of liver disease including viral hepatitis and alcoholic liver disease
Must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 x Central Laboratory Upper Limit of Normal (clULN)
Must have serum creatinine < 2.0 mg/dL
A negative serum pregnancy test is required for females of childbearing potential
All sexually active females of childbearing potential must agree to use a protocol recommended method of contraception during intercourse throughout the study and for 90 days following the last dose of study medication
Lactating females must agree to discontinue nursing before starting study treatment
Males, if not vasectomized, are required to use barrier contraception (condom plus spermicide) during heterosexual intercourse from the screening through the study completion and for 90 days following the last dose of study drug.

Key

Exclusion Criteria

Pregnant or breast feeding
Cirrhosis of the liver
Any history of hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding
Weight reduction surgery in the past 5 years
Positive for hepatitis C virus (HCV) RNA
Positive for HBsAg
Alcohol consumption greater than 21oz/week for males or 14oz/week for females
Positive urine screen for amphetamines, cocaine or opiates (i.e. heroin, morphine) at screening.
Clinically significant cardiac disease
History of malignancy, other than non-melanomatous skin cancer, within 5 years prior to screening
Major surgical procedure within 30 days prior to screening or the presence of an open wound
Known hypersensitivity to the investigation product or any of its formulation excipients
History of bleeding diathesis within 6 months of screening
Unavailable for follow-up assessment or concern for individual's compliance with the protocol procedures;
Participation in an investigational trial of a drug or device within 30 days prior to screening
BMI < 18 kg/m^2

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary Outcome Measures

Name	Time	Method
Event Free Survival (EFS) Using Kaplan-Meier	Baseline up to the time of progression to cirrhosis or last dose date (maximum: 240 weeks in the Blinded Phase), which ever occurred first	The EFS was the primary clinical efficacy endpoint and was assessed by the time to progression to cirrhosis. Participants were considered to have become cirrhotic if they had a post-baseline biopsy consistent with cirrhosis or developed overt signs and symptoms of cirrhosis. All overt signs and symptoms went through an adjudication process and were confirmed before they were considered for the EFS analysis.
Change From Baseline in MQC on Liver Biopsy	Baseline to Week 96

Secondary Outcome Measures

Name	Time	Method

Locations (68): Mayo Clinic Hospital
🇺🇸
Phoenix, Arizona, United States
Southern California Liver Centers
🇺🇸
Coronado, California, United States
University of California, San Diego (UCSD)
🇺🇸
San Diego, California, United States
University of California San Francisco (UCSF)
🇺🇸
San Francisco, California, United States
University of Colorado
🇺🇸
Aurora, Colorado, United States
Miami Veterans Administration Healthcare System
🇺🇸
Miami, Florida, United States
Tampa General Hospital
🇺🇸
Tampa, Florida, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Indianapolis Gastroenterology Research Foundation
🇺🇸
Indianapolis, Indiana, United States
Iowa Digestive Disease Center
🇺🇸
Clive, Iowa, United States
Scroll for more (58 remaining)
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States