Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Participants With Liver Fibrosis
Condition: Nonalcoholic Steatohepatitis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis
Intervention: Cenicriviroc; Placebo
Intervention description: CVC 150 mg, administered orally once daily and taken every morning with food.; Placebo administered orally once daily and taken every morning with food.
Intervention MeSH terms: Cenicriviroc
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 289.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether cenicriviroc is effective and safe in the
      treatment of nonalcoholic steatohepatitis (NASH) in adult participants with liver fibrosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult participants aged between 18-75

          -  Histological evidence of NASH, based on biopsy, with a Nonalcoholic fatty liver
             disease Activity Score (NAS) of >= 4 with at least 1 in each component of NAS

          -  Histological evidence of liver fibrosis defined as NASH Clinical Research Network
             (CRN) System Stage 1 to 3

          -  Meeting any of the 3 major criteria (a, b, c):

               1. Documented evidence of type 2 diabetes mellitus

               2. High body mass index (> 25 kg/m^2) with at least one of the following criteria of
                  metabolic syndrome, as defined by the National Cholesterol Education Program:

                    -  Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm
                       or 35 inches (female)

                    -  Dyslipidemia: Triglycerides ≥ 1.7 mmol/L (150 mg/dL)

                    -  Dyslipidemia: High-density lipoprotein (HDL)-cholesterol < 40 mg/dL (male),
                       < 50 mg/dL (female)

                    -  Blood pressure ≥ 130/85 mmHg (or currently being treated for hypertension)

                    -  Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dL)

               3. Bridging fibrosis (NASH CRN Stage 3) and/or definite NASH (NAS ≥ 5)

          -  Agree to have one liver biopsy at Screening, one at Year 1, and one at the end of
             study treatment (Year 2)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × upper limit
             of normal (ULN)

        Exclusion Criteria:

          -  Hepatitis B surface Antigen (HBsAg) positive

          -  Hepatitis C antibody (HCVAb) positive with the following 2 exceptions:

               1. Participants previously treated for viral hepatitis C with at least a 1-year
                  period since documented sustained virologic response at Week 12 (post-treatment)
                  may be eligible if all other eligibility criteria are met

               2. Participants with presence of hepatitis C antibody but negative hepatitis C virus
                  ribonucleic acid RNA without treatment (i.e., spontaneous clearance) may be
                  eligible if all other eligibility criteria are met

          -  Prior or planned liver transplantation

          -  Other known causes of chronic liver disease, including alcoholic liver disease

          -  History of cirrhosis and/or hepatic decompensation including ascites, hepatic
             encephalopathy or variceal bleeding

          -  Alcohol consumption greater than 21 units/week for males or 14 units/week for females
             (one unit of alcohol is ½ pint of beer [285 mL], 1 glass of spirits [25 mL] or 1 glass
             of wine [125 mL])

          -  Human immunodeficiency virus (HIV)-1 or HIV-2 infection

          -  Weight reduction through bariatric surgery in the past 5 years or planned during the
             conduct of the study (including gastric banding)

          -  Females who are pregnant or breastfeeding

          -  Any other clinically significant disorders or prior therapy that, in the opinion of
             the investigator, would make the participant unsuitable for the study or unable to
             comply with the dosing and protocol requirements.