Trial Outcomes & Findings for AURORA: A Study for the Efficacy and Safety of Cenicriviroc (CVC) for the Treatment of Liver Fibrosis in Adults With Nonalcoholic Steatohepatitis (NASH) (NCT NCT03028740)

Last Updated: 2022-03-10

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

1778 participants

Primary outcome timeframe

Month 12

Results posted on

2022-03-10

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg Participants received cenicriviroc, 150 milligrams (mg), tablet, orally, once daily for up to approximately 40 months.
Overall Study STARTED	593	1185
Overall Study Full Study Cohort: Received Study Drug	589	1180
Overall Study Participated in Part 1	432	861
Overall Study Part 1: Received Study Drug	429	859
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	593	1185

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg Participants received cenicriviroc, 150 milligrams (mg), tablet, orally, once daily for up to approximately 40 months.
Overall Study Did not Receive Study Drug	4	5
Overall Study Adverse Event	8	26
Overall Study Lack of Efficacy	0	1
Overall Study Withdrawal by Subject	48	101
Overall Study Lost to Follow-up	30	54
Overall Study Physician Decision	4	11
Overall Study Protocol Violation	4	8
Overall Study Non-compliance with Study Drug	0	2
Overall Study Study Terminated by Sponsor	467	917
Overall Study Protocol-specified Withdrawal Criteria Met	27	55
Overall Study Reason not Specified	1	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=589 Participants Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg n=1180 Participants Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months.	Total n=1769 Participants Total of all reporting groups
Age, Continuous	55.8 years STANDARD_DEVIATION 11.04 • n=5 Participants	55.2 years STANDARD_DEVIATION 10.76 • n=7 Participants	55.4 years STANDARD_DEVIATION 10.86 • n=5 Participants
Sex: Female, Male Female	354 Participants n=5 Participants	749 Participants n=7 Participants	1103 Participants n=5 Participants
Sex: Female, Male Male	235 Participants n=5 Participants	431 Participants n=7 Participants	666 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	172 Participants n=5 Participants	315 Participants n=7 Participants	487 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	417 Participants n=5 Participants	865 Participants n=7 Participants	1282 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) Asian	22 Participants n=5 Participants	45 Participants n=7 Participants	67 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants	38 Participants n=7 Participants	52 Participants n=5 Participants
Race (NIH/OMB) White	539 Participants n=5 Participants	1075 Participants n=7 Participants	1614 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=429 Participants Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg n=859 Participants Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months.
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 Interval 21.5 to 29.9	22.3 percentage of participants Interval 19.6 to 25.2

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=589 Participants Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg n=1180 Participants Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months.
Time to First Occurrence of Adjudicated Events in the Full Study Cohort	NA days Median, lower and upper limit of 95% confidence interval (C.I.) were not estimable due to low number of participants with events.	NA days Median, lower and upper limit of 95% C.I. were not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=429 Participants Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg n=859 Participants Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months.
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 Interval 6.0 to 11.3	6.6 percentage of participants Interval 5.1 to 8.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=348 Participants Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg n=692 Participants Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months.
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 Interval 28.6 to 38.4	30.6 percentage of participants Interval 27.3 to 34.2

SECONDARY outcome

Timeframe: Month 12

Outcome measures

Outcome measures
Measure	Placebo n=348 Participants Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg n=692 Participants Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months.
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	8.8 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=589 Participants Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg n=1180 Participants Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months.
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 Interval 21.2 to 29.2	22.0 percentage of participants Interval 19.4 to 24.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=373 Participants Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg n=741 Participants Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months.
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 Interval 28.7 to 38.2	30.5 percentage of participants Interval 27.3 to 33.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=589 Participants Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg n=1180 Participants Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months.
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 Interval 5.9 to 11.1	6.8 percentage of participants Interval 5.2 to 8.6

SECONDARY outcome

Timeframe: Month 12

Outcome measures

Outcome measures
Measure	Placebo n=373 Participants Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg n=741 Participants Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months.
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	8.9 percentage of participants

SECONDARY outcome

Timeframe: Month 60

Population: No data was collected as the study was terminated and no participants reached the Month 60 timepoint.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 60

Population: No data was collected as the study was terminated and no participants reached the Month 60 timepoint.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 60

Population: No data was collected as the study was terminated and no participants reached the Month 60 timepoint.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 60

Population: No data was collected as the study was terminated and no participants reached the Month 60 timepoint.

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.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 70 serious events

Other events: 218 other events

Deaths: 2 deaths

Cenicriviroc 150 mg

Serious events: 159 serious events

Other events: 425 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=589 participants at risk Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.	Cenicriviroc 150 mg n=1180 participants at risk Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months.
Gastrointestinal disorders Nausea	6.6% 39/589 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.	8.8% 104/1180 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.
Gastrointestinal disorders Diarrhoea	9.5% 56/589 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.	7.8% 92/1180 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.
Gastrointestinal disorders Abdominal pain upper	4.4% 26/589 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.	5.4% 64/1180 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.
Gastrointestinal disorders Abdominal pain	5.1% 30/589 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.	4.7% 56/1180 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.
General disorders Fatigue	5.6% 33/589 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.	6.3% 74/1180 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.
Infections and infestations Urinary tract infection	5.6% 33/589 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.	4.8% 57/1180 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.
Infections and infestations Upper respiratory tract infection	6.6% 39/589 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.	3.5% 41/1180 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 35/589 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.	5.8% 68/1180 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.
Musculoskeletal and connective tissue disorders Back pain	6.1% 36/589 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.	4.6% 54/1180 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.
Nervous system disorders Headache	5.1% 30/589 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.	5.4% 64/1180 • From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined.

Additional Information

Therapeutic Area, Head

Allergan

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER