Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis
Condition: Primary Sclerosing Cholangitis
MeSH terms: Cholangitis; Cholangitis, Sclerosing
Intervention: Cilofexor; Placebo to match cilofexor
Intervention description: Tablet(s) administered orally once daily with food; Tablet(s) administered orally once daily with food
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 52.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to evaluate the safety and tolerability of cilofexor
      in adults with primary sclerosing cholangitis (PSC).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Diagnosis of PSC based on cholangiogram (magnetic resonance cholangiopancreatography
             (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or percutaneous
             transhepatic cholangiogram (PTC)) within the previous 12 months

          -  Serum alkaline phosphatase (ALP) > 1.67 x upper limit of the normal range (ULN)

          -  For individuals on ursodeoxycholic acid (UDCA), the dose of UDCA must have been stable
             for at least 12 months prior to screening through the end of treatment. For
             individuals not on UDCA, no UDCA use for at least 12 months before screening through
             the end of treatment

          -  For individuals being administered biologic treatments (eg, antitumor necrosis factor
             (TNF) or anti-integrin monoclonal antibodies), immunosuppressants or systemic
             corticosteroids, the dose must have been stable at least 3 months prior to screening
             and anticipated to remain stable throughout the trial

          -  Screening FibroSURE/FibroTest® <0.75 unless a historical liver biopsy within 12 months
             of screening does not reveal cirrhosis. In adults with Gilbert's syndrome or
             hemolysis, FibroSURE/FibroTest® will be calculated using direct bilirubin instead of
             total bilirubin.

        Key Exclusion Criteria:

          -  Alanine aminotransferase (ALT) > 10 x ULN

          -  Total bilirubin > 2 x ULN

          -  International normalized ratio (INR) > 1.2 unless on anticoagulant therapy

          -  Small-duct PSC (histologic evidence of PSC with normal bile ducts on cholangiography)

          -  Other causes of liver disease including secondary sclerosing cholangitis and viral,
             metabolic, alcoholic, and other autoimmune conditions. Individuals with hepatic
             steatosis may be included if there is no evidence of nonalcoholic steatohepatitis
             (NASH) in the opinion of the investigator or on liver biopsy;

          -  Ascending cholangitis within 60 days of screening

          -  Presence of a percutaneous drain or bile duct stent

          -  Use of fibrates or obeticholic acid within 3 months prior to screening through the end
             of treatment

          -  Cirrhosis of the liver as defined by any of the following:

               -  Historical liver biopsy demonstrating cirrhosis (eg, Ludwig stage 4 or Ishak
                  stage ≥ 5)

               -  Prior history of decompensated liver disease, including ascites, hepatic
                  encephalopathy or variceal bleeding

               -  Liver stiffness > 14.4 kilopascal (kPa) by FibroScan

          -  Current, active inflammatory bowel disease (IBD) defined as a partial Mayo score of >
             1 and/or a score on the Rectal Bleeding domain > 0.

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.