Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults With Primary Sclerosing Cholangitis (PSC)
Condition: Primary Sclerosing Cholangitis (PSC)
MeSH terms: Cholangitis; Cholangitis, Sclerosing
Intervention: Simtuzumab; Placebo
Intervention description: Subcutaneous injections weekly for a total of 96 injections; Subcutaneous injections weekly for a total of 96 injections
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 235.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: PSC; Sclerosis; Monoclonal antibody; LOXL2; Simtuzumab; Primary sclerosing cholangitis; Liver fibrosis; Liver disease; MRCP; MRE; Liver biopsy

Summary:

      The purpose of this study is to evaluate whether simtuzumab (GS-6624) is effective at
      preventing the progression of liver fibrosis in adults with primary sclerosing cholangitis
      (PSC).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Adult Individuals (aged 18-70) with chronic cholestatic liver disease of at least 6
             months.

          -  Liver biopsy consistent with PSC: If a liver biopsy has been performed within 3 months
             of the screening visit, tissue from that biopsy may be used as the screening biopsy.
             Slides would be re-cut from the existing tissue block and submitted for central reader
             assessment. Some individuals with PSC may have a normal liver biopsy, in the event of
             a normal liver biopsy, the individual must have an abnormal magnetic resonance
             cholangiopancreatography (MRCP).

          -  MRCP consistent with PSC: Some individuals with PSC may have a normal MRCP; in the
             event of a normal MRCP, the individual must have an abnormal liver biopsy.

          -  Exclusion of other causes of liver disease including viral hepatitis ,alcoholic liver
             disease,primary biliary cirrhosis and secondary sclerosing cholangitis

          -  Must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 x
             the Central Laboratory Upper Limit of Normal (clULN)

          -  Must have serum creatinine < 2.0 mg/dL

          -  A negative serum pregnancy test is required for female individuals of childbearing
             potential

          -  All sexually active female individuals 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

          -  Males if not vasectomized, are required to use barrier contraception (condom plus
             spermicide) during 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

          -  Evidence of hepatic decompensation present, including ascites, episodes of hepatic
             encephalopathy, variceal bleeding or a prolonged prothrombin time/international
             normalized ratio (PT/INR)

          -  Positive for hepatitis C virus (HCV) RNA

          -  Positive for HBsAg

          -  Positive for anti-mitochondrial antibody

          -  Alcohol consumption greater than 21oz/week for males or 14oz/week for females

          -  Moderately active ulcerative colitis (UC) defined as either a partial Mayo score of >
             4, bleeding score of >1, or current use of oral corticosteroid therapy and/or any
             inhibitor of Tumor necrosis factor-α (TNF-α) or α4β7 integrin antagonist

          -  Positive urine screen for amphetamines, cocaine or opiates (i.e. heroin, morphine) at
             screening. Individuals on stable methadone or buprenorphine maintenance treatment for
             at least 6 months prior to screening may be included in the study. Individuals 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 cholangiocarcinoma

          -  History of other cancers,other than non-melanomatous skin cancer, within 5 years prior
             to screening

          -  Ascending cholangitis within 60 days of screening

          -  Presence of a percutaneous drain or bile duct stent

          -  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

          -  Major surgical procedure within 30 days prior to screening or the presence of an open
             wound

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.