Study of Safety and Efficacy of Tropifexor (LJN452) in Patients With Non-alcoholic Steatohepatitis (NASH)
Condition: Non-alcoholic Steatohepatitis (NASH)
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: Tropifexor (LJN452); Placebo
Intervention description: Comparison of different doses of drug; Comparator
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This was a randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose finding, 3-part (Parts A, B, and C), adaptive design study to assess the safety, tolerability, and efficacy of six doses of tropifexor as compared to placebo in subjects with NASH. Each study part had a screening period followed by a double-blind, randomized, treatment period, and a post-treatment follow-up period.
This study was extended based on safety and efficacy results in Part A and available long-term toxicology coverage; Part C was added to explore 48 weeks of treatment at higher doses with paired biopsies in F2/3 NASH patients.
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 350.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: LJN452; non-alcoholic steatohepatitis; NASH; phase 2; adaptive design; randomized

Summary:

      The purpose of the study was to assess the effects of different doses of tropifexor (LJN452)
      with respect to safety, tolerability, and on markers of liver inflammation in patients with
      NASH
    

Eligibility criteria:

        Inclusion Criteria:

          -  male/female patients, 18 years or older

          -  written informed consent

          -  Part A and B patients : presence of NASH by histological evidence (liver biopsy
             obtained 2 years or less prior to randomization) with fibrosis level of F1, F2 or F3
             (fibrosis in the absence of cirrhosis) and no diagnosis of chronic liver disease and
             elevated alanine aminotransferase (ALT) OR phenotypic diagnosis based on elevated ALT,
             BMI and diagnosis of Type 2 diabetes mellitus (DM)

          -  Part C patients: presence of NASH by histological evidence (liver biopsy obtained
             during the Screening period or 6 months or less prior to randomization) with fibrosis
             level of F2 or F3 and no diagnosis of chronic liver disease

        And ( All Parts):

          -  ALT ≥ 43 IU/L (males) or ≥ 28 IU/L (females)

          -  Liver fat equal to or higher than 10% by MRI

        Exclusion Criteria:

          -  previous exposure to OCA

          -  patients taking prohibited medications

          -  patients taking the following medicines UNLESS on a stable dose (within 25% of
             baseline dose) for at least 1 month before randomization: (for Part C patients, dose
             must be stable for at least 1 month prior to biopsy through Screening : anti- diabetic
             medications, insulin, beta-blockers, thiazide diuretics, fibrates, statins, niacin,
             ezetimibe, vitamin E (if doses > 200 IU/day; doses > 800 IU/day are prohibited),
             thyroid hormone, psychotropic medications, estrogen or estrogen containing birth
             control

          -  pregnant or nursing (lactating) women

          -  current or history of significant alcohol consumption for a period of more than 3
             consecutive months within 1 year prior to screening

          -  uncontrolled diabetes mellitus

          -  new use of GLP-1 agonists such as liraglutide, exenatide, lixisenatide, albiglutide or
             dulaglutide within 3 months of screening

          -  presence of cirrhosis

          -  hepatic decompensation or severe liver impairment

          -  previous diagnosis of other forms of chronic liver disease

          -  patients with contraindications to MRI imaging