AURORA: A Study for the Efficacy and Safety of Cenicriviroc (CVC) for the Treatment of Liver Fibrosis in Adults With Nonalcoholic Steatohepatitis (NASH)

Tobira Therapeutics

Status and phase: Terminated; Phase 3

Conditions: Nonalcoholic Steatohepatitis

Treatments: Drug: Cenicriviroc; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03028740

2016-004566-26 (EudraCT Number)

1001

3152-301-002

Details and patient eligibility

About

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.

Full description

The AURORA study will be conducted in 2 parts. Part 1 will examine the surrogate endpoint of improvement in fibrosis of at least 1 stage (nonalcoholic steatohepatitis clinical research network [NASH CRN]) and no worsening of steatohepatitis at Month 12. Participants from Part 1 will continue into Part 2 and additional participants will be newly randomized in Part 2 to determine long-term clinical outcomes composed of histopathologic progression to cirrhosis, liver-related clinical outcomes, and all-cause mortality.

Enrollment: 1,778 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,778 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.

Treatment:

Drug: Placebo

Cenicriviroc 150 mg

Experimental group

Description:

Participants received cenicriviroc, 150 milligrams (mg), tablet, orally, once daily for up to approximately 40 months.

Treatment:

Drug: Cenicriviroc