A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients
Condition: Primary Biliary Cholangitis
MeSH terms: Cholangitis; Liver Cirrhosis, Biliary
Intervention: Part 1: LJN452; Part 1: Placebo; Part 2: LJN452 Dose level 1; Part 2: Placebo; Part 2: LJN452 Dose level 2
Intervention description: LJN452 capsules administered once daily for 28 days; Matching placebo capsules administered once daily for 28 days; LJN452 capsules administered once a day for 12 weeks; Matching placebo to LJN452 administered once a day for 12 weeks; LJN452
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Primary Biliary Cirrhosis, PBC; Primary Biliary Cholangitis

Summary:

      A multi-part study to assess safety, tolerability and efficacy of tropifexor (LJN452) in
      patients with primary biliary cholangitis
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years

          -  Diagnosis of PBC as demonstrated by the presence of at least 2 of the following 3
             diagnostic criteria:

               -  History of alkaline phosphatase (ALP) elevated above upper limit of normal (ULN)
                  for at least 6 months

               -  Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low
                  titer (<1:80) PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or
                  antibodies against the major M2 components (PDC-E2, 2-oxo-glutaric acid
                  dehydrogenase complex))

               -  Previous liver biopsy findings consistent with PBC

          -  At least 1 of the following markers of disease severity:

               -  ALP ≥ 1.67 × ULN

               -  Total bilirubin > ULN but < 1.5 × ULN

          -  In addition, patients must meet the following biochemical criteria at enrollment:

               -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 × ULN

               -  Total bilirubin ≤ 1.5 × ULN

               -  INR ≤ ULN

          -  Taking UDCA for at least 12 months, or for at least 6 months and has reached maximal
             response to UDCA with a plateau in alkaline phosphatase, with no changes in dose for ≥
             3 months prior to Day 1.

          -  Patients must weigh at least 40 kg to participate in the study, and must have a body
             mass index (BMI) within the range of 18 - 40 kg/m2. BMI = Body weight (kg) / [Height
             (m)]2

        Exclusion Criteria:

          -  Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they are using highly effective methods of contraception for
             30 days before randomization, during dosing and for 30 days following the end of
             treatment.

          -  Presence of other concomitant liver diseases.

               -  Cirrhosis with complications, including history or presence of:

               -  Variceal bleed

               -  Uncontrolled ascites

               -  Encephalopathy

               -  Spontaneous bacterial peritonitis

          -  Significant hepatic impairment as defined by Child-Pugh classification of B or C,
             history of liver transplantation, current placement on a liver transplant list or
             current Model for End Stage Liver Disease (MELD) score ≥15.

          -  History of conditions that may cause increases in ALP (e.g., Paget's disease).

          -  Use of investigational drugs, or immunosuppressive drugs at the time of enrollment, or
             within 5 half-lives, or 30 days of randomization, whichever is longer; or longer if
             required by local regulations. Use of high dose oral steroids to treat co-morbid
             conditions (e.g., airways disease) will be allowed but must be properly documented as
             such in concomitant medications.

          -  Currently taking obeticholic acid or have taken obeticholic acid within 30 days of
             randomization

          -  Previous participation in CLJN452X2201 and received study medication within three
             months of randomization (or longer if required by local regulations).