Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Biliary Cholangitis Without Cirrhosis
Condition: Primary Biliary Cholangitis
MeSH terms: Cholangitis; Liver Cirrhosis, Biliary
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: 71.0
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 biliary cholangitis (PBC).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Meets all of the following conditions

               -  Definite or probable PBC as defined by at least 2 of the 3 following criteria:

                    -  Serum alkaline phosphatase (ALP) > the upper limit of normal (ULN)

                    -  Presence of anti-mitochondrial antibodies (AMA) in serum (≥ 1:40 on
                       immunofluorescence)

                    -  Liver histological findings consistent with PBC including nonsuppurative,
                       destructive cholangitis affecting mainly the interlobular bile and septal
                       bile ducts

               -  Serum ALP > 1.67 x ULN and/or total bilirubin >ULN but ≤ 2 x ULN

               -  Ursodeoxycholic acid (UDCA) use at a stable dose for at least 12 months or
                  intolerant of UDCA with no UDCA use for at least 12 months before screening

          -  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) > 5 x ULN

          -  Total bilirubin > 2 x ULN

          -  International normalized ratio (INR) > 1.2 unless on anticoagulant therapy

          -  Other causes of liver disease including viral, metabolic, alcoholic, and other
             autoimmune conditions. Participants 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.

          -  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)

               -  History of decompensated liver disease, including ascites, hepatic encephalopathy
                  or variceal bleeding

               -  Liver stiffness > 16.9 kPa by FibroScan®

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.