Simtuzumab (SIM, GS-6624) in the Treatment of Cirrhosis Due to NASH
Condition: Liver Fibrosis Due to NASH
MeSH terms: Liver Cirrhosis; Fibrosis
Intervention: Placebo; SIM
Intervention description: Placebo to match SIM intravenous infusion over 30 minutes every 2 weeks; Intravenous infusion over 30 minutes every 2 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 259.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: NASH; cirrhosis; Compensated Liver disease; Monoclonal antibody; LOXL2; Simtuzumab; Nonalcoholic Steatohepatitis; Hepatic venous pressure gradient; HVPG; NAFLD; MRE; Liver biopsy; Liver fibrosis; Ishak

Summary:

      The primary objective of this study is to evaluate the safety and efficacy of SIM (formerly
      referred to as GS-6624) in adults with compensated cirrhosis due to Non-Alcoholic
      Steatohepatitis (NASH). It will consist of 2 phases:

        -  Randomized Double-Blind Phase

        -  Open-Label Phase (optional)
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Adults with cirrhosis of the liver defined as an Ishak fibrosis stage ≥ 5

          -  Liver biopsy consistent with NASH or cryptogenic cirrhosis

          -  Exclusion of other causes of liver disease including viral hepatitis and alcoholic
             liver disease

          -  The liver biopsy sample must be determined to be adequate for evaluation by the
             Central pathologist

          -  Must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 x
             the upper limit of the normal range (ULN)

          -  Must have serum creatinine < 2.0 mg/dL

          -  A negative serum pregnancy test is required for female subjects of childbearing
             potential

          -  All sexually active female subjects of childbearing potential must agree to use a
             protocol recommended method of contraception during heterosexual 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

          -  Male subjects, 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

          -  Any history of hepatic decompensation including ascites, hepatic encephalopathy or
             variceal bleeding

          -  Weight reduction surgery in the past 5 year

          -  Child-Pugh-Turcotte (CPT) score >7; Model for End-Stage Liver Disease (MELD) score >
             12 and Body Mass Index (BMI) <18kg/m2

          -  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. 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

          -  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 subject's compliance with the
             protocol procedures;

          -  Participation in an investigational trial of a drug or device within 30 days prior to
             screening

          -  History of solid-organ transplant; poor venous access or requirement for permanent or
             semi-permanent central vein catheter such as portacath

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.