Safety and Efficacy of Simtuzumab (SIM, GS-6624) in Adults With Advanced Liver Fibrosis But Not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)
Condition: Liver Fibrosis Due to NASH
MeSH terms: Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Fibrosis
Intervention: Placebo; SIM
Intervention description: Placebo to match SIM via subcutaneous injection every week; Subcutaneous injection every week
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 222.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: NASH; noncirrhotic; Monoclonal antibody; LOXL2; Simtuzumab; Nonalcoholic Steatohepatitis; NAFLD; Liver biopsy; MRE; Liver fibrosis; Ishak

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)
    

Eligibility criteria:

        Key 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.