AURORA: A Study for the Efficacy and Safety of Cenicriviroc (CVC) for the Treatment of Liver Fibrosis in Adults With Nonalcoholic Steatohepatitis (NASH) (AURORA)
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ClinicalTrials.gov Identifier: NCT03028740 |
Recruitment Status :
Terminated
(This study was terminated early due to lack of efficacy based on the results of the planned interim analysis of Part 1 data.)
First Posted : January 23, 2017
Results First Posted : March 10, 2022
Last Update Posted : March 10, 2022
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Condition or disease | Intervention/treatment | Phase |
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Nonalcoholic Steatohepatitis | Drug: Placebo Drug: Cenicriviroc | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 1778 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Treatment |
Official Title: | AURORA: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Cenicriviroc for the Treatment of Liver Fibrosis in Adult Subjects With Nonalcoholic Steatohepatitis |
Actual Study Start Date : | April 5, 2017 |
Actual Primary Completion Date : | January 12, 2021 |
Actual Study Completion Date : | March 9, 2021 |

Arm | Intervention/treatment |
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Placebo Comparator: Placebo
Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.
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Drug: Placebo
Cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. |
Experimental: Cenicriviroc 150 mg
Participants received cenicriviroc, 150 milligrams (mg), tablet, orally, once daily for up to approximately 40 months.
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Drug: Cenicriviroc
Cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months.
Other Name: CVC |
- Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage and No Worsening of Steatohepatitis on Liver Histology at Month 12 [ Time Frame: Month 12 ]Fibrosis stage was evaluated using the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant nonalcoholic fatty liver disease activity score (NAS) categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.
- Time to First Occurrence of Adjudicated Events in the Full Study Cohort [ Time Frame: From first dose of study drug to onset of first occurrence of the event (Up to approximately 42 months) ]Time to first occurrence from Baseline was defined as the number of days from the first dose of randomized investigational product to the onset of the first occurrence of any of the following adjudicated events: death (all cause), histopathologic progression to cirrhosis, liver transplant, model for end stage liver disease (MELD) score ≥15, ascites, hospitalization for onset of: variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis. MELD is a scoring system for assessing the severity of chronic liver disease and uses the participant's values for total bilirubin, serum creatinine, and the international normalized ratio for prothrombin time to predict survival. MELD score ranges from 6 (less ill) to 40 (gravely ill) with scores and mortality probability being: Score 40=71.3% mortality; Scores 30-39=52.6% mortality; Scores 20-29=19.6% mortality; Scores10-19=6.0% mortality; Score 9 or less=1.9% mortality.
- Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages and No Worsening of Steatohepatitis on Liver Histology at Month 12 [ Time Frame: Month 12 ]Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.
- Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis at Month 12 [ Time Frame: Month 12 ]Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.
- Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis at Month 12 [ Time Frame: Month 12 ]Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.
- Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage and No Worsening of Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort [ Time Frame: Month 12 ]Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.
- Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort [ Time Frame: Month 12 ]Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.
- Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages and No Worsening of Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort [ Time Frame: Month 12 ]Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.
- Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort [ Time Frame: Month 12 ]Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.
- Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage and No Worsening of Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort [ Time Frame: Month 60 ]Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.
- Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort [ Time Frame: Month 60 ]Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.
- Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages and No Worsening of Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort [ Time Frame: Month 60 ]Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.
- Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort [ Time Frame: Month 60 ]Fibrosis stage was evaluated using NASH CRN Fibrosis Staging System with stages 0=None, 1=Perisinusoidal or periportal, 1A=Mild, zone 3, perisinusoidal, 1B=Moderate, zone 3, perisinusoidal, 1C=Portal/periportal, 2=Perisinusoidal and portal/periportal, 3=Bridging fibrosis, 4=Cirrhosis.

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Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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).

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03028740

Study Director: | Gerardo Rodriguez | Allergan |
Documents provided by Tobira Therapeutics, Inc.:
Responsible Party: | Tobira Therapeutics, Inc. |
ClinicalTrials.gov Identifier: | NCT03028740 |
Other Study ID Numbers: |
3152-301-002 2016-004566-26 ( EudraCT Number ) 1001 ( Registry Identifier: Registro Nacional Estudios Clinicos (RNEC) ) |
First Posted: | January 23, 2017 Key Record Dates |
Results First Posted: | March 10, 2022 |
Last Update Posted: | March 10, 2022 |
Last Verified: | November 2021 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Fatty Liver Non-alcoholic Fatty Liver Disease Liver Cirrhosis Fibrosis Pathologic Processes Liver Diseases Digestive System Diseases |
Cenicriviroc CCR5 Receptor Antagonists Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents |