Nonalcoholic Steatohepatitis
Conditions
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 participants 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. 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.
Interventions
DRUGPlacebo
Cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.
DRUGCenicriviroc
Cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months.
Sponsors
Tobira Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis at Month 12 | 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 | 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 | 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 | 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 2 Stages and No Worsening of Steatohepatitis on Liver Histology at Month 12 | 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 and No Worsening of Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort | 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 | 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 | 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 | 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. |
| 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 | 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 1 Stage Regardless of Effect on Steatohepatitis at Month 12 | 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. |
Countries
Australia, Austria, Belgium, Brazil, Canada, Chile, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Latvia, Mexico, New Zealand, Norway, Poland, Portugal, Puerto Rico, Romania, Russia, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
1778 participants were randomized into the study, of which 1293 participated in Part 1 of the study. The study was terminated early, and Part 2 did not enroll the planned number of participants. Therefore, the Part 1 and Part 2 data were combined and reported as the Full Study Cohort for reporting of the Part 2 efficacy endpoints and the safety endpoints.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | 589 |
| Cenicriviroc 150 mg Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months. | 1,180 |
| Total | 1,769 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 26 |
| Overall Study | Did not Receive Study Drug | 4 | 5 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 30 | 54 |
| Overall Study | Non-compliance with Study Drug | 0 | 2 |
| Overall Study | Physician Decision | 4 | 11 |
| Overall Study | Protocol-specified Withdrawal Criteria Met | 27 | 55 |
| Overall Study | Protocol Violation | 4 | 8 |
| Overall Study | Reason not Specified | 1 | 5 |
| Overall Study | Study Terminated by Sponsor | 467 | 917 |
| Overall Study | Withdrawal by Subject | 48 | 101 |
Baseline characteristics
| Characteristic | Cenicriviroc 150 mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 55.2 years STANDARD_DEVIATION 10.76 | 55.4 years STANDARD_DEVIATION 10.86 | 55.8 years STANDARD_DEVIATION 11.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 315 Participants | 487 Participants | 172 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 865 Participants | 1282 Participants | 417 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 8 Participants | 15 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 45 Participants | 67 Participants | 22 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 52 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 9 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 7 Participants | 9 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 1075 Participants | 1614 Participants | 539 Participants |
| Sex: Female, Male Female | 749 Participants | 1103 Participants | 354 Participants |
| Sex: Female, Male Male | 431 Participants | 666 Participants | 235 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 593 | 6 / 1,185 |
| other Total, other adverse events | 218 / 589 | 425 / 1,180 |
| serious Total, serious adverse events | 70 / 589 | 159 / 1,180 |
Outcome results
Primary
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
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 frame: Month 12
Population: mITT Population for Part 1 included participants randomly assigned to a treatment group who received at least one dose of study drug in Part 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 | 25.5 percentage of participants |
| Cenicriviroc 150 mg | 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 | 22.3 percentage of participants |
p-value: 0.206795% CI: [-8.2, 1.9]Cochran-Mantel-Haenszel
95% CI: [0.6341, 1.1044]
Primary
Time to First Occurrence of Adjudicated Events in the Full Study Cohort
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.
Time frame: From first dose of study drug to onset of first occurrence of the event (Up to approximately 42 months)
Population: mITT Population for the full study cohort included participants randomly assigned to a treatment group who received at least one dose of study drug in Parts 1 and 2 of the study combined.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Occurrence of Adjudicated Events in the Full Study Cohort | NA days |
| Cenicriviroc 150 mg | Time to First Occurrence of Adjudicated Events in the Full Study Cohort | NA days |
Secondary
Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis at 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.
Time frame: Month 12
Population: mITT Population for Part 1 included participants randomly assigned to a treatment group who received at least one dose of study drug in Part 1. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis at Month 12 | 33.3 percentage of participants |
| Cenicriviroc 150 mg | Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis at Month 12 | 30.6 percentage of participants |
p-value: 0.405495% CI: [-8.7, 3.3]Cochran-Mantel-Haenszel
95% CI: [0.6709, 1.1744]
Secondary
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
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.
Time frame: Month 12
Population: mITT Population for Part 1 included participants randomly assigned to a treatment group who received at least one dose of study drug in Part 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 | 8.3 percentage of participants |
| Cenicriviroc 150 mg | 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 | 6.6 percentage of participants |
p-value: 0.282795% CI: [-4.8, 1.5]Cochran-Mantel-Haenszel
95% CI: [0.5032, 1.2229]
Secondary
Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis at 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.
Time frame: Month 12
Population: mITT Population for Part 1 included participants randomly assigned to a treatment group who received at least one dose of study drug in Part 1. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis at Month 12 | 10.3 percentage of participants |
| Cenicriviroc 150 mg | Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis at Month 12 | 8.8 percentage of participants |
Secondary
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
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.
Time frame: Month 12
Population: mITT Population for the full study cohort included participants randomly assigned to a treatment group who received at least one dose of study drug in Parts 1 and 2 of the study combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 | 25.0 percentage of participants |
| Cenicriviroc 150 mg | 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 | 22.0 percentage of participants |
Secondary
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
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.
Time frame: Month 60
Population: No data was collected as the study was terminated and no participants reached the Month 60 timepoint.
Secondary
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
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.
Time frame: Month 12
Population: mITT Population for the full study cohort included participants randomly assigned to a treatment group who received at least one dose of study drug in Parts 1 and 2 of the study combined. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 | 33.2 percentage of participants |
| Cenicriviroc 150 mg | 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 | 30.5 percentage of participants |
Secondary
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
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.
Time frame: Month 60
Population: No data was collected as the study was terminated and no participants reached the Month 60 timepoint.
Secondary
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
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.
Time frame: Month 12
Population: mITT Population for the full study cohort included participants randomly assigned to a treatment group who received at least one dose of study drug for Parts 1 and 2 of the study combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 | 8.3 percentage of participants |
| Cenicriviroc 150 mg | 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 | 6.8 percentage of participants |
Secondary
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
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.
Time frame: Month 60
Population: No data was collected as the study was terminated and no participants reached the Month 60 timepoint.
Secondary
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
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.
Time frame: Month 12
Population: mITT Population for the full study cohort included participants randomly assigned to a treatment group who received at least one dose of study drug in Parts 1 and 2 of the study combined. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 | 9.9 percentage of participants |
| Cenicriviroc 150 mg | 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 | 8.9 percentage of participants |
Secondary
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
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.
Time frame: Month 60
Population: No data was collected as the study was terminated and no participants reached the Month 60 timepoint.