AURORA: A Study for the Efficacy and Safety of Cenicriviroc (CVC) for the Treatment of Liver Fibrosis in Adults With Nonalcoholic Steatohepatitis (NASH)
Condition: Nonalcoholic Steatohepatitis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis
Intervention: Placebo; Cenicriviroc
Intervention description: Cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.; Cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months.
Intervention MeSH terms: Cenicriviroc
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1778.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The AURORA study will be conducted to confirm the efficacy and safety of cenicriviroc (CVC)
      for the treatment of liver fibrosis in adult participants with NASH.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female participants aged between 18-75 years

          -  Ability to understand and sign a written informed consent form (ICF)

          -  Histological evidence of NASH based on central reading of the Screening biopsy

          -  Participants included in Part 1 must have histopathological evidence of Stage 2 or 3
             liver fibrosis per the NASH CRN System based on central reading of the Screening
             biopsy slides. Participants newly randomized in Part 2 must have histological evidence
             of Stage 3 liver fibrosis per the NASH CRN System, based on central reading of the
             Screening period biopsy slides. Historical biopsy can be used, provided the criteria
             listed on Item 3a above are fulfilled.

          -  Females of childbearing potential and males participating in the study must agree to
             use at least 2 approved methods of contraception throughout the duration of the study
             and for 30 days after stopping study drug. Females who are postmenopausal must have
             documentation of cessation of menses for ≥12 months and serum follicle-stimulating
             hormone (FSH) ≥30 milliunits (mU)/milliliter (mL) at Screening.

        Exclusion Criteria:

          -  Inability to undergo a liver biopsy

          -  Hepatitis B surface antigen (HBsAg) positive

          -  Hepatitis C antibody (HCVAb) positive

          -  Human immunodeficiency virus (HIV)-1 or HIV-2 infection

          -  Prior or planned liver transplantation

          -  Other known causes of chronic liver disease

          -  History or presence 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

          -  Aspartate transaminase (AST) >200 International units (IU)/liter (L) in males and
             females at Screening

          -  Alanine transaminase (ALT) >250 IU/L in males and >200 IU/L in females at Screening

          -  Hemoglobin A1c (HbA1c) >10% at Screening

          -  Serum albumin <3.5 gram (g)/deciliter (dL) at Screening

          -  Estimated glomerular filtration rate (eGFR) < 50 mL/minute (min)/1.73 meter (m)^2
             according to the Modification of Diet in Renal Disease (MDRD) equation

          -  Platelet count <100,000/millimeter (mm)^3

          -  Total bilirubin >1.5 milligram (mg)/dL

          -  International normalized ratio (INR) >1.3

          -  Model of end stage liver disease (MELD) score >12

          -  Weight reduction, defined as ≥7% of body weight, through bariatric surgery in the past
             5 years or bariatric surgery planned during the conduct of the study (including
             gastric banding and sleeve surgery)

          -  History of malignancy within the past 5 years or ongoing malignancy other than basal
             cell carcinoma, or resected noninvasive cutaneous squamous cell carcinoma

          -  Active, serious infections that require parenteral antibiotic or antifungal therapy
             within 30 days prior to Screening Visit

          -  Clinically significant cardiovascular or cerebrovascular disease within the past 3
             months

          -  Females who are pregnant or breastfeeding

          -  Current or anticipated treatment with radiation therapy, cytotoxic chemotherapeutic
             agents and immunomodulating agents (eg, interleukins, interferons, cyclosporine,
             tacrolimus) except for vaccines or short-term corticosteroids

          -  Receiving a glucagon-like peptide 1 (GLP-1) receptor agonist, a dipeptidyl peptidase 4
             (DPP-4) inhibitor, a sodium-glucose cotransporter 2 (SGLT2) and/or sodium-glucose
             cotransporter (SGLT1) inhibitor, or a thiazolidinedione (TZD) for less than 6 months
             prior to the Screening period liver biopsy. Participants on a stable therapy with a
             GLP-1 receptor agonist, DPP-4 inhibitor, SGLT1 and/or SGLT2 inhibitor, or a TZD for at
             least 6 months prior to the Screening liver biopsy may be considered eligible.
             (Important Note: if a historical biopsy is to be used, participants need to be on
             stable therapy for at least 6 months prior to the day historical liver biopsy was
             performed).