AURORA: Phase 3 Study for the Efficacy and Safety of CVC for the Treatment of Liver Fibrosis in Adults With NASH

• ClinicalTrials.gov Identifier: NCT03028740
• Recruitment Status: Recruiting
• First Posted: January 23, 2017
• Last Update Posted: October 8, 2019
• Sponsor: Tobira Therapeutics, Inc.
• Information provided by (Responsible Party): Tobira Therapeutics, Inc.

Tracking Information

• First Submitted Date: January 13, 2017
• First Posted Date: January 23, 2017
• Last Update Posted Date: October 8, 2019
• Actual Study Start Date: April 20, 2017
• Estimated Primary Completion Date: October 14, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2017)

• Superiority of CVC compared to placebo on liver histology at Month 12 relative to the Screening biopsy [ Time Frame: Measurements at Baseline and 12 months ]
  Proportion of subjects with improvement in fibrosis by at least 1 stage (NASH CRN system) AND no worsening of steatohepatitis
• Superiority of CVC compared to placebo on the composite endpoint of histopathologic progression to cirrhosis, liver-related clinical outcomes, and all-cause mortality [ Time Frame: Time to accrue a pre-specified number of adjudicated events, End of Study, estimated to be 5 years ]

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03028740 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures (submitted: January 18, 2017): Effect of CVC compared to placebo on liver histology at Month 60 relative to the Screening biopsy for the proportion of subjects with improvement in fibrosis by at least 1 stage AND no worsening of steatohepatitis [ Time Frame: Time to accrue a pre-specified number of adjudicated events, End of Study, estimated to be 5 years ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: AURORA: Phase 3 Study for the Efficacy and Safety of CVC for the Treatment of Liver Fibrosis in Adults With NASH
• Official Title: AURORA: A Phase 3 Study to Evaluate the Efficacy and Safety of Cenicriviroc for the Treatment of Liver Fibrosis in Adult Subjects With Nonalcoholic Steatohepatitis
• Brief Summary: The AURORA study will be conducted to confirm the efficacy and safety of cenicriviroc (CVC) for the treatment of liver fibrosis in adult subjects with NASH.
• Detailed 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. Subjects from Part 1 will continue into Part 2 and additional subjects 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Nonalcoholic Steatohepatitis

Intervention

• Drug: Cenicriviroc
  1 tablet QD
  Other Name: CVC
• Drug: Placebo
  1 tablet QD

Study Arms

• Experimental: Drug: Cenicriviroc
  150 mg cenicriviroc
  Intervention: Drug: Cenicriviroc
• Placebo Comparator: Drug: Placebo
  Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 18, 2017): 2000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 28, 2028
• Estimated Primary Completion Date: October 14, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male and female subjects 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
• Subjects included in Part1 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. Subjects 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 mU/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
• AST > 200 IU/L in males and females at Screening
• ALT > 250 IU/L in males and > 200 IU/L in females at Screening
• HbA1c > 10% at Screening
• Serum albumin < 3.5 g/dL at Screening
• Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) equation
• Platelet count < 100,000/mm3
• Total bilirubin > 1.5 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 SGLT1 inhibitor, or a thiazolidinedione (TZD) for less than 6 months prior to the Screening period liver biopsy. Subjects 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, subjects need to be on stable therapy for at least 6 months prior to the day historical liver biopsy was performed).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials Registry Team; 1-877-277-8566; IR-CTRegistration@allergan.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Mexico, New Zealand, Norway, Peru, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Singapore, Slovenia, Spain, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT03028740
• Other Study ID Numbers: 3152-301-002; 2016-004566-26 ( EudraCT Number ); 1001 ( Registry Identifier: Registro Nacional Estudios Clinicos (RNEC) )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Tobira Therapeutics, Inc.
• Study Sponsor: Tobira Therapeutics, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Eduardo B Martins; Allergan

• PRS Account: Tobira Therapeutics, Inc.
• Verification Date: October 2019