Overview

This trial is active, not recruiting.

Condition non-alcoholic steatohepatitis (nash)
Treatments simtuzumab, placebo
Phase phase 2
Sponsor Gilead Sciences
Start date December 2012
End date July 2016
Trial size 222 participants
Trial identifier NCT01672866, 2012-002488-88, GS-US-321-0105

Summary

This study will evaluate whether simtuzumab (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 non-alcoholic steatohepatitis (NASH).

It will consist of 2 phases:

- Randomized Double-Blind Phase

- Open Label Phase (optional)

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
During the Randomized Double-Blind Phase, participants will receive simtuzumab 75 mg once weekly for up to 240 weeks. During the optional Open Label Phase, participants will receive simtuzumab 125 mg for up to an additional 240 weeks.
simtuzumab GS-6624
Simtuzumab administered by subcutaneous injection weekly
(Experimental)
During the Randomized Double-Blind Phase, participants will receive simtuzumab 125 mg once weekly for up to 240 weeks. During the optional Open Label Phase, participants will receive simtuzumab 125 mg for up to an additional 240 weeks.
simtuzumab GS-6624
Simtuzumab administered by subcutaneous injection weekly
(Placebo Comparator)
During the Randomized Double-Blind Phase, participants will receive placebo to match simtuzumab once weekly for up to 240 weeks. During the optional Open Label Phase, participants will receive simtuzumab 125 mg for up to an additional 240 weeks.
simtuzumab GS-6624
Simtuzumab administered by subcutaneous injection weekly
placebo
Placebo to match simtuzumab administered by subcutaneous injection weekly

Primary Outcomes

Measure
Change from baseline in morphometric quantitative collagen on liver biopsy
time frame: Baseline; Week 96
Event free survival (EFS)
time frame: Up to 240 weeks

Secondary Outcomes

Measure
Safety data including adverse events, extent of exposure, laboratory evaluations, and immunogenicity
time frame: Up to 480 weeks plus 30 days

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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 must refrain from sperm donation from Day 0 throughout the study period and for a period of 90 days following the last dose of study drug 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

Additional Information

Official title A Phase 2b, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and Efficacy of GS-6624, a Monoclonal Antibody Against Lysyl Oxidase-Like Molecule 2 (LOXL2), in Subjects With Advanced Liver Fibrosis But Not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Gilead Sciences.