Safety and Tolerability of Cilofexor in Participants With Primary Sclerosing Cholangitis (PSC) and Compensated Cirrhosis
Condition: Primary Sclerosing Cholangitis; Compensated Cirrhosis
MeSH terms: Liver Cirrhosis; Cholangitis; Cholangitis, Sclerosing; Fibrosis
Intervention: Cilofexor
Intervention description: Tablets administered orally once daily
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to assess the safety and tolerability of escalating
      doses of cilofexor (CILO) in participants with primary sclerosing cholangitis (PSC) and
      compensated cirrhosis.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Diagnosis PSC based on cholangiogram (magnetic resonance cholangiopancreatography
             [MRCP], endoscopic retrograde cholangiopancreatography [ERCP], or percutaneous
             transhepatic cholangiogram [PTC]) or liver biopsy

          -  Individuals have evidence of cirrhosis based on historical liver biopsy, abdominal
             imaging [magnetic resonance imaging (MRI), computed tomography (CT), or Ultrasound],
             or a screening FibroScan®, enhanced liver fibrosis (ELF)™, or FibroTest®.

          -  Individual has the following laboratory parameters at the Screening visit, as
             determined by the central laboratory:

               -  Estimated glomerular filtration rate (eGFR) > 60 milliliter/minute (mL/min), as
                  calculated by the Cockcroft-Gault equation

               -  Alanine aminotransferase (ALT) ≤ 5 x upper limit of the normal (ULN)

               -  Total 2 milligram/deciliter (mg/dL), unless the individual is known to have
                  Gilbert's syndrome or hemolytic anemia

               -  International normalized ratio (INR) ≤ 1.4, unless due to therapeutic
                  anticoagulation

               -  Platelet count ≥ 75,000/microliter (μL). Individuals with evidence of high-risk
                  esophageal or gastric varices in the opinion of the investigator are excluded

               -  Negative anti-mitochondrial antibody

        Key Exclusion Criteria:

          -  Current or prior history of any of the following

               -  Decompensated liver disease, including ascites, hepatic encephalopathy (HE), or
                  variceal hemorrhage

               -  Liver transplantation

               -  Cholangiocarcinoma or hepatocellular carcinoma (HCC).

          -  Model for End-stage Liver Disease (MELD) score > 12 at Screening, unless due to an
             alternate etiology such as therapeutic anticoagulation

          -  Child-Pugh (CP) score > 6 at Screening, unless due to an alternative etiology such as
             Gilbert's syndrome or therapeutic anticoagulation

          -  Current moderate to severely active inflammatory bowel disease (IBD) (including
             ulcerative colitis, Crohn's disease, and indeterminate colitis).

               -  Note: Individuals with IBD who currently have an external ostomy bag and/or
                  proctocolectomy are not subject to this exclusion criterion and need not undergo
                  IBD Symptom Severity Assessment.

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.