Study of Safety, Tolerability, and Efficacy of a Combination Treatment of LJN452 and CVC in Adult Patients With NASH and Liver Fibrosis
Condition: Non-alcoholic Steatohepatitis (NASH)
MeSH terms: Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Fibrosis
Intervention: Tropifexor (LJN452); Cenicriviroc (CVC)
Intervention description: Comparison with monotherapy and different combination doses; Comparison with monotherapy and different combination doses
Intervention MeSH terms: Cenicriviroc
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 193.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Steatohepatitis; NASH; NAFLD; Fatty Liver Disease; Liver; Liver fibrosis

Summary:

      The purpose of this study was to assess the safety, tolerability, and efficacy of a
      combination treatment of tropifexor (LJN452) and cenicriviroc (CVC) in adult patients with
      nonalcoholic steatohepatitis (NASH) and liver fibrosis.
    

Eligibility criteria:

        Inclusion Criteria:

        Written informed consent Male and female patients 18 years or older (at the time of the
        screening visit). Patients must weigh at least 50 kg (110 lb) and no more than 200 kg (440
        lb) to participate in the study.

        Able to communicate well with the investigator, to understand and comply with the
        requirements of the study.

        Adequate liver biopsy sample for evaluation by Central Reader. Presence of NASH as
        demonstrated by histologic evidence based on liver biopsy - NASH with fibrosis stage F2/F3,
        demonstrated on liver biopsy during the screening period. Alternatively, a historical
        biopsy can be used if performed within 6 months prior to screening.

        Exclusion Criteria:

        Use of other investigational drugs within 5 half-lives of enrollment or within 30 days
        whichever is longer.

        History of hypersensitivity to any of the study drugs or its excipients or to drugs of
        similar chemical classes.

        Previous exposure to elafibranor, CVC, tropifexor, obeticholic acid (OCA), LMB763 or other
        FXR agonist.

        Participated in a clinical trial and treated with any investigational product being
        evaluated for the treatment of liver fibrosis or NASH in the 6 months before screening.

        Patients taking medications prohibited by the protocol. History of treated or untreated
        malignancy of any organ system, other than localized basal cell carcinoma of the skin or
        treated cervical intraepithelial neoplasia, within the past 5 years, regardless of whether
        there is evidence of local recurrence or metastases .

        Pregnant or nursing (lactating) women. Women of child-bearing potential. Current or history
        of significant alcohol consumption for a period of more than 3 consecutive months within 1
        year prior to screening (significant alcohol consumption is defined as more than 20 g/day
        in females and more than 30 g/day in males, on average) and/or a score on the modified
        AUDIT questionnaire ≥ 8.

        Inability to reliably quantify alcohol consumption. History or evidence of ongoing drug
        abuse, within the last 6 months prior to randomization.

        Prior or planned (during the study) bariatric surgery. Uncontrolled diabetes defined as
        HbA1c ≥ 9% at screening Clinical evidence of hepatic decompensation or severe liver
        impairment. Previous diagnosis of other forms of chronic liver disease. Calculated eGFR
        less than 60 mL/min (using the MDRD formula). History of biliary diversion History of liver
        transplantation or planned liver transplant. Known positivity for HIV. History or current
        diagnosis of ECG abnormalities indicating significant risk of safety for the patient to
        participate.

        History of inflammatory bowel disease. Patients who are not candidates for liver biopsy.
        Presence of cirrhosis on liver biopsy (F4 by NASH CRN System) or medical history Patients
        with an abnormal platelet count (referring to reference ranges from the central lab).