Trial Outcomes & Findings for Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Participants With Liver Fibrosis (NCT NCT02217475)

Last Updated: 2019-05-10

Results Overview

Hepatic histological improvement in Nonalcoholic Fatty Liver Disease Activity Score (NAS) at Year 1 was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. Evaluation of fibrosis stage was based on the nonalcoholic steatohepatitis clinical research network (NASH CRN) fibrosis staging system, which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. Worsening of fibrosis stage was defined as progression of NASH CRN fibrosis stage.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

289 participants

Primary outcome timeframe

Year 1

Results posted on

2019-05-10

Participant Flow

In total, 812 participants were screened, and 289 participants were randomized to treatment period 1. Of the 289 participants randomized, 250 participants completed Treatment Period 1. A total of 242 participants entered Treatment Period 2 and 212 completed.

Participant milestones

Participant milestones
Measure	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo/Cenicriviroc (CVC) 150 mg Placebo-matching CVC tablet, once daily in the morning with food in Year 1 then CVC 150 mg tablet, once daily in the morning with food in Year 2.	CVC 150mg/CVC 150 mg CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2.
Treatment Period 1 (Year 1) STARTED	72	72	145
Treatment Period 1 (Year 1) Safety Analysis Set	72	72	144
Treatment Period 1 (Year 1) COMPLETED	62	64	124
Treatment Period 1 (Year 1) NOT COMPLETED	10	8	21
Discontinued After Period 1 STARTED	62	64	124
Discontinued After Period 1 COMPLETED	60	61	121
Discontinued After Period 1 NOT COMPLETED	2	3	3
Treatment Period 2 (Year 2) STARTED	60	61	121
Treatment Period 2 (Year 2) COMPLETED	58	59	109
Treatment Period 2 (Year 2) NOT COMPLETED	2	2	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo/Cenicriviroc (CVC) 150 mg Placebo-matching CVC tablet, once daily in the morning with food in Year 1 then CVC 150 mg tablet, once daily in the morning with food in Year 2.	CVC 150mg/CVC 150 mg CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2.
Treatment Period 1 (Year 1) Protocol Deviation (with non-compliance)	0	1	0
Treatment Period 1 (Year 1) Adverse Event	4	5	9
Treatment Period 1 (Year 1) Lost to Follow-up	1	0	0
Treatment Period 1 (Year 1) Subject Withdrew Consent	5	2	11
Treatment Period 1 (Year 1) Other Miscellaneous Reasons	0	0	1
Discontinued After Period 1 Adverse Event	1	2	0
Discontinued After Period 1 Participant Withdrew Consent	1	1	2
Discontinued After Period 1 Physician Decision	0	0	1
Treatment Period 2 (Year 2) Adverse Event	0	1	5
Treatment Period 2 (Year 2) Lost to Follow-up	0	1	2
Treatment Period 2 (Year 2) Subject Withdrew Consent	2	0	2
Treatment Period 2 (Year 2) Physician Decision	0	0	2
Treatment Period 2 (Year 2) Other Miscellaneous Reasons	0	0	1

Baseline Characteristics

Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Participants With Liver Fibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CVC 150mg/CVC 150 mg n=145 Participants CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2.	Placebo/Cenicriviroc (CVC) 150 mg n=72 Participants Placebo-matching CVC tablet, once daily in the morning with food in Year 1 then CVC 150 mg tablet, once daily in the morning with food in Year 2.	Placebo/Placebo n=72 Participants Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Total n=289 Participants Total of all reporting groups
Age, Continuous	54.6 years STANDARD_DEVIATION 10.22 • n=5 Participants	55.3 years STANDARD_DEVIATION 10.38 • n=7 Participants	52.1 years STANDARD_DEVIATION 11.37 • n=5 Participants	54.1 years STANDARD_DEVIATION 10.59 • n=4 Participants
Sex: Female, Male Female	73 Participants n=5 Participants	39 Participants n=7 Participants	40 Participants n=5 Participants	152 Participants n=4 Participants
Sex: Female, Male Male	72 Participants n=5 Participants	33 Participants n=7 Participants	32 Participants n=5 Participants	137 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	23 Participants n=5 Participants	18 Participants n=7 Participants	7 Participants n=5 Participants	48 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	122 Participants n=5 Participants	51 Participants n=7 Participants	65 Participants n=5 Participants	238 Participants n=4 Participants
Race/Ethnicity, Customized Not reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian	6 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants	21 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized White	129 Participants n=5 Participants	63 Participants n=7 Participants	58 Participants n=5 Participants	250 Participants n=4 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants

PRIMARY outcome

Timeframe: Year 1

Population: Intent-to-treat (ITT) population included all randomized participants regardless of starting treatment.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=145 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participant With Hepatic Histological Improvement in NAS by ≥ 2 Points With at Least 1-Point Reduction in Either Lobular Inflammation or Hepatocellular Ballooning and no Concurrent Worsening of Fibrosis at Year 1	27 Participants	23 Participants	—	—	—

SECONDARY outcome

Timeframe: Year 1

Population: ITT population included all randomized participants regardless of starting treatment.

Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=145 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage and Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1	4 Participants	7 Participants	—	—	—

SECONDARY outcome

Timeframe: Year 2

Population: ITT population Year 2 included all participants who had an evaluable year 1 biopsy and received at least 1 dose of study drug during Year 2.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=178 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage and Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2	2 Participants	5 Participants	—	—	—

SECONDARY outcome

Timeframe: Year 1

Population: ITT population included all randomized participants regardless of starting treatment.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=145 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 1	8 Participants	11 Participants	—	—	—

SECONDARY outcome

Timeframe: Year 2

Population: ITT population Year 2 included all participants who had an evaluable year 1 biopsy and received at least 1 dose of study drug during Year 2.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=178 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 2	3 Participants	11 Participants	—	—	—

SECONDARY outcome

Timeframe: Year 1

Population: ITT population included all randomized participants regardless of starting treatment.

The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=145 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1	15 Participants	29 Participants	—	—	—

SECONDARY outcome

Timeframe: Year 2

Population: ITT analysis set Year 2 included all participants who have an evaluable year 1 biopsy and who received at least one dose of study drug during Year 2 (after the 1 year biopsy).

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=178 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2	8 Participants	27 Participants	—	—	—

SECONDARY outcome

Timeframe: Years 1 and 2

Population: Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.

A TEAE was defined as any adverse event that started or worsened on or after the start of the study medication and up to 30 days after the discontinuation of the study medication. An SAE was defined as any untoward medical occurrence that, at any dose, results in death, was life threatening, requires hospitalization or results in prolongation of existing hospitalization, results in disability/incapacity, or was a congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=72 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo n=72 Participants Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation TEAEs	137 Participants	68 Participants	70 Participants	—	—
Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation Deaths	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation SAEs	25 Participants	8 Participants	12 Participants	—	—
Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation TEAEs Leading Study Drug to Discontinuation	14 Participants	8 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: Years 1 and 2

Population: Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.

Vital signs included blood pressure, temperature, heart rate, and respiration rate. Vital signs were reviewed by the Investigator for clinically significant changes.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=72 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo n=72 Participants Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Clinically Significant Changes in Vital Signs	0 Participants	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Years 1 and 2

Population: Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.

Grade 3-4 abnormal clinical laboratory values that occurred in ≥2% participants were reported. Criteria used for various parameters was:Fasting glucose Grade3:\>250 - 500 mg/dL and Grade4: \>500 mg/dL; Alanine aminotransferase(ALT)Grade3:\>5.0 - 20.0 ×Upper Limit of Normal(ULN)and Grade4:\>20.0 ×ULN; Aspartate aminotransferase(AST)Grade3: \>5.0 - 20.0 ×ULN and Grade4: \>20.0 ×ULN; Activated partial thromboplastin(APT)/Partial thromboplastin time(PTT)Grade3: \>2.5×ULN; Triglycerides Grade3 \>500 - 1000 mg/dL and Grade4: \>1000 mg/dL; Gamma-glutamyl transferase(GGT)Grade3: \>5.0 - 20.0 ×ULN and Grade4: \>20.0 ×ULN; Creatine kinase Grade 3: \>5.0 - 10.0 ×ULN and Grade4: \>10.0 ×ULN; Uric acid Grade3:(ULN - 10 mg/dL; ULN - 0.59 mmol/L) and Grade4: \>10 mg/dL; Amylase Grade3: \>2.0 - 5.0 ×ULN and Grade4: \>5.0 ×ULN; Lipase Grade3: \>2.0 - 5.0 xULN and Grade4: \>5.0 xULN; Phosphorus Grade3: \<2.0 - 1.0 mg/dL and Grade4: \<1.0 mg/dL and Absolute neutrophil Grade3: \<1.0 - 0.5 × 109/L and Grade4: \<0.5 × 109/L.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo n=121 Participants Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg n=61 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo n=60 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Clinical Laboratory Abnormalities Fasting glucose (Grade 3)	17 Participants	13 Participants	10 Participants	6 Participants	5 Participants
Number of Participants With Clinical Laboratory Abnormalities Fasting glucose (Grade 4)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Laboratory Abnormalities ALT (Grade 3)	17 Participants	17 Participants	4 Participants	3 Participants	2 Participants
Number of Participants With Clinical Laboratory Abnormalities ALT (Grade 4)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Laboratory Abnormalities AST (Grade 3)	7 Participants	10 Participants	1 Participants	3 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities AST (Grade 4)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Laboratory Abnormalities APT/PTT (Grade 3)	4 Participants	2 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With Clinical Laboratory Abnormalities Triglycerides (Grade 3)	5 Participants	7 Participants	6 Participants	5 Participants	2 Participants
Number of Participants With Clinical Laboratory Abnormalities Triglycerides (Grade 4)	3 Participants	3 Participants	2 Participants	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities GGT (Grade 3)	8 Participants	7 Participants	8 Participants	2 Participants	2 Participants
Number of Participants With Clinical Laboratory Abnormalities GGT (Grade 4)	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Clinical Laboratory Abnormalities Creatine kinase (Grade 3)	6 Participants	7 Participants	1 Participants	2 Participants	4 Participants
Number of Participants With Clinical Laboratory Abnormalities Creatine kinase (Grade 4)	2 Participants	2 Participants	3 Participants	1 Participants	0 Participants
Number of Participants With Clinical Laboratory Abnormalities Uric acid (Grade 3)	9 Participants	8 Participants	4 Participants	3 Participants	2 Participants
Number of Participants With Clinical Laboratory Abnormalities Uric acid (Grade 4)	11 Participants	6 Participants	5 Participants	1 Participants	6 Participants
Number of Participants With Clinical Laboratory Abnormalities Amylase (Grade 3)	6 Participants	1 Participants	4 Participants	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Amylase (Grade 4)	3 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Clinical Laboratory Abnormalities Lipase (Grade 3)	4 Participants	2 Participants	3 Participants	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Lipase (Grade 4)	5 Participants	0 Participants	3 Participants	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Phosphorus (Grade 3)	5 Participants	2 Participants	2 Participants	1 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Phosphorus (Grade 4)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Laboratory Abnormalities Absolute neutrophil (Grade 3)	2 Participants	3 Participants	3 Participants	0 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities Absolute neutrophil (Grade 4)	2 Participants	1 Participants	1 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Years 1 and 2

Population: Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.

A 12-lead ECG was performed. ECG results were reviewed by the Investigator for clinically notable abnormalities.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=72 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo n=72 Participants Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Clinically Abnormal in Electrocardiogram (ECG) Findings	0 Participants	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Year 2

Population: Full Analysis Set (FAS) in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.

Hepatic histological improvement in NAS at Year 2 was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=215 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Hepatic Histological Improvement in NAS at Year 2	7 Participants	24 Participants	—	—	—

SECONDARY outcome

Timeframe: Year 1

Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.

NAS was calculated using the following 3 categorical features: steatosis which was scaled from 0-3 (steatosis score is defined as 0= \<5%, 1= 5 - 33%, 2= \>33 - 66%, and 3= \>66%), lobular inflammation which was scaled from 0-3 (lobular inflammation score defined as 0= no foci, 1= \< 2 foci/200x, 2= 2-4 foci/200x, and 3= \> 4 foci/200x), and hepatocellular ballooning which was scaled from 0-2 (hepatocellular ballooning score is defined as 0=none, 1=few balloon cells, 2=many cells/prominent ballooning). A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=126 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 Baseline (Steatosis)	1.4 score on a scale Standard Deviation 0.55	1.3 score on a scale Standard Deviation 0.57	—	—	—
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 Change from Baseline (Steatosis)	-0.1 score on a scale Standard Deviation 0.66	-0.2 score on a scale Standard Deviation 0.56	—	—	—
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 Baseline (Lobular Inflammation)	2.5 score on a scale Standard Deviation 0.56	2.4 score on a scale Standard Deviation 0.58	—	—	—
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 Change from Baseline (Lobular Inflammation)	-0.1 score on a scale Standard Deviation 0.79	-0.1 score on a scale Standard Deviation 0.88	—	—	—
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 Baseline (Hepatocellular Ballooning)	1.5 score on a scale Standard Deviation 0.50	1.5 score on a scale Standard Deviation 0.50	—	—	—
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 Change from Baseline (Hepatocellular Ballooning)	-0.2 score on a scale Standard Deviation 0.75	-0.1 score on a scale Standard Deviation 0.75	—	—	—

SECONDARY outcome

Timeframe: Year 2

Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=159 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 Baseline (Steatosis)	1.5 score on a scale Standard Deviation 0.54	1.3 score on a scale Standard Deviation 0.52	—	—	—
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 Change from Baseline (Steatosis)	-0.4 score on a scale Standard Deviation 0.56	-0.2 score on a scale Standard Deviation 0.50	—	—	—
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 Baseline (Lobular Inflammation)	2.4 score on a scale Standard Deviation 0.63	2.4 score on a scale Standard Deviation 0.54	—	—	—
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 Change from Baseline (Lobular Inflammation)	0.1 score on a scale Standard Deviation 0.72	0.0 score on a scale Standard Deviation 0.84	—	—	—
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 Baseline (Hepatocellular Ballooning)	1.5 score on a scale Standard Deviation 0.50	1.5 score on a scale Standard Deviation 0.50	—	—	—
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 Change from Baseline (Hepatocellular Ballooning)	-0.1 score on a scale Standard Deviation 0.68	0.0 score on a scale Standard Deviation 0.83	—	—	—

SECONDARY outcome

Timeframe: Year 1

Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.

Hepatic histological improvement in NAS was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in either steatosis, lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. Worsening was defined as progression of NASH CRN fibrosis stage.

Outcome measures

Outcome measures
Measure	Placebo n=143 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Hepatic Histological Improvement With a Minimum 2-Point Improvement in NAS With at Least a 1-Point Improvement in More Than 1 Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 1	24 Participants	22 Participants	—	—	—

SECONDARY outcome

Timeframe: Year 2

Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=215 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Hepatic Histological Improvement With a Minimum 2-Point Improvement in NAS With at Least a 1-point Improvement in More Than 1 Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 2	6 Participants	20 Participants	—	—	—

SECONDARY outcome

Timeframe: Year 1

Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.

Resolution of NASH was defined as having no hepatocellular ballooning (grade 0) and minimal to no lobular inflammation (grade 1 or 0) with no concurrent worsening of fibrosis stage (worsening defined as progression of NASH CRN fibrosis stage).

Outcome measures

Outcome measures
Measure	Placebo n=143 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Resolution of NASH Using a Modified Definition Based on Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 1	7 Participants	6 Participants	—	—	—

SECONDARY outcome

Timeframe: Year 2

Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=215 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Number of Participants With Resolution of NASH Using a Modified Definition Based on Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 2	1 Participants	9 Participants	—	—	—

SECONDARY outcome

Timeframe: Year 1

The morphometric quantitative collagen on liver biopsy was determined as percent collagen area (PCA) using Sirius red stain on liver biopsy at Year 1. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=123 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=121 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1 Baseline	2.49 percent collagen area Standard Deviation 2.004	2.37 percent collagen area Standard Deviation 1.827	—	—	—
Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1 Change from Baseline to Year 1	-0.14 percent collagen area Standard Deviation 2.389	0.02 percent collagen area Standard Deviation 2.357	—	—	—

SECONDARY outcome

Timeframe: Year 2

The morphometric quantitative collagen on liver biopsy was determined as percent collagen area (PCA) using Sirius red stain on liver biopsy at Year 2. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=51 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=150 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2 Baseline	2.57 percent collagen area Standard Deviation 2.156	2.48 percent collagen area Standard Deviation 1.892	—	—	—
Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2 Change from Baseline to Year 2	-0.17 percent collagen area Standard Deviation 2.576	-0.09 percent collagen area Standard Deviation 2.160	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Year 1

The hepatic tissue fibrogenic protein α-SMA level was determined as percent α-SMA + area using α-SMA stain on liver biopsy at Year 1. A positive change from Baseline indicates worsening.

Outcome measures

Outcome measures
Measure	Placebo n=122 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=122 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1 Baseline	2.41 percentage of α-SMA positive cells/area Standard Deviation 2.264	2.49 percentage of α-SMA positive cells/area Standard Deviation 2.885	—	—	—
Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1 Change from Baseline to Year 1	0.77 percentage of α-SMA positive cells/area Standard Deviation 3.529	0.79 percentage of α-SMA positive cells/area Standard Deviation 3.861	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Year 2

The hepatic tissue fibrogenic protein α-SMA level was determined as percent α-SMA + area using α-SMA stain on liver biopsy at Year 2. A positive change from Baseline indicates worsening.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=152 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2 Change from Baseline to Year 2	2.10 percentage of α-SMA positive cells/area Standard Deviation 4.533	1.38 percentage of α-SMA positive cells/area Standard Deviation 3.793	—	—	—
Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2 Baseline	2.47 percentage of α-SMA positive cells/area Standard Deviation 2.679	2.44 percentage of α-SMA positive cells/area Standard Deviation 2.505	—	—	—

SECONDARY outcome

Timeframe: Year 1

The morphometric quantitative fat content was done to find out the amount of fat accumulated in the liver. A liver biopsy was performed to determine percent fat area, at Year 1. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=123 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=121 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1 Baseline	22.42 percent fat area Standard Deviation 10.016	21.58 percent fat area Standard Deviation 8.740	—	—	—
Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1 Change from Baseline to Year 1	-3.39 percent fat area Standard Deviation 9.120	-2.79 percent fat area Standard Deviation 8.127	—	—	—

SECONDARY outcome

Timeframe: Year 2

The morphometric quantitative fat content was done to find out the amount of fat accumulated in the liver. A liver biopsy was performed to determine percent fat area, at Year 2. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=150 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2 Change from Baseline to Year 2	-5.06 percent fat area Standard Deviation 9.739	-2.96 percent fat area Standard Deviation 9.230	—	—	—
Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2 Baseline	23.30 percent fat area Standard Deviation 10.300	21.62 percent fat area Standard Deviation 9.575	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Year 1

The participant's histologic fibrosis stage was determined using the NASH CRN system and Ishak scale score assessment at Year 1. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 where, 0=None to 4=Cirrhosis. The histologic fibrosis stage based on the Ishak assessment was divided into 1 to 6 stages. Fibrosis was staged with the Ishak scale (ranging from 0=No fibrosis to 6=Cirrhosis). A positive change from Baseline indicates worsening.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=126 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 Baseline (NASH CRN Fibrosis Stage)	2.1 score on a scale Standard Deviation 0.86	2.0 score on a scale Standard Deviation 0.85	—	—	—
Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 Baseline (Ishak Fibrosis Stage)	2.2 score on a scale Standard Deviation 1.00	2.2 score on a scale Standard Deviation 1.05	—	—	—
Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 Change from Baseline (Ishak Fibrosis Stage)	0.2 score on a scale Standard Deviation 1.10	0.0 score on a scale Standard Deviation 1.20	—	—	—
Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 Change from Baseline (NASH CRN Fibrosis Stage)	0.2 score on a scale Standard Deviation 0.92	0.0 score on a scale Standard Deviation 1.00	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Year 2

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=159 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 Baseline (NASH CRN Fibrosis Stage)	2.0 score on a scale Standard Deviation 0.88	2.1 score on a scale Standard Deviation 0.85	—	—	—
Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 Change from Baseline (NASH CRN Fibrosis Stage)	0.0 score on a scale Standard Deviation 0.89	0.0 score on a scale Standard Deviation 1.08	—	—	—
Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 Baseline (Ishak Fibrosis Stage)	2.1 score on a scale Standard Deviation 1.00	2.2 score on a scale Standard Deviation 1.04	—	—	—
Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 Change from Baseline (Ishak Fibrosis Stage)	0.1 score on a scale Standard Deviation 1.21	0.0 score on a scale Standard Deviation 1.26	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Year 1

Portal inflammation on liver biopsy was graded from 0 to 4 where 0= None, 1= Mild, 2= Moderate, and 3= Marked. A positive change from Baseline indicates worsening.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=124 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1 Baseline	1.6 score on a scale Standard Deviation 0.63	1.5 score on a scale Standard Deviation 0.64	—	—	—
Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1 Change from Baseline to Year 1	0.0 score on a scale Standard Deviation 0.76	0.2 score on a scale Standard Deviation 0.74	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Year 2

Portal inflammation on liver biopsy was graded from 0 to 4 where 0= None, 1= Mild, 2= Moderate, and 3= Marked. A positive change from Baseline indicates worsening.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=159 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2 Baseline	1.5 score on a scale Standard Deviation 0.64	1.6 score on a scale Standard Deviation 0.67	—	—	—
Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2 Change from Baseline to Year 1	0.1 score on a scale Standard Deviation 0.75	0.2 score on a scale Standard Deviation 0.72	—	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0) to Months 3, 6 and 12

APRI is the ratio of aspartate aminotransferase (AST) to platelet count. It is calculated using formula, APRI = (AST level \[/ULN\] / platelet counts \[10\^9/L\]) \* 100. An APRI index of \<=0.50 indicated the absence of significant fibrosis and an index of \> 1.50 indicated the presence of significant fibrosis. A negative change from Baseline indicates decreased fibrosis.

Outcome measures

Outcome measures
Measure	Placebo n=143 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 Baseline (Month 3)	0.649 ratio Standard Deviation 0.3661	0.596 ratio Standard Deviation 0.4089	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 Change from Baseline to Month 3	-0.005 ratio Standard Deviation 0.3012	0.065 ratio Standard Deviation 0.3152	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 Baseline (Month 6)	0.663 ratio Standard Deviation 0.3811	0.578 ratio Standard Deviation 0.3794	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 Change from Baseline to Month 6	0.009 ratio Standard Deviation 0.3968	0.102 ratio Standard Deviation 0.4536	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 Baseline (Month 12)	0.662 ratio Standard Deviation 0.3915	0.580 ratio Standard Deviation 0.3939	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 Change from Baseline to Month 12	0.066 ratio Standard Deviation 0.5572	0.093 ratio Standard Deviation 0.3852	—	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0) to Months 15, 18 and 24

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=215 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 Baseline (Month 15)	0.619 ratio Standard Deviation 0.3157	0.584 ratio Standard Deviation 0.3572	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 Change from Baseline to Month 15	0.002 ratio Standard Deviation 0.3422	0.118 ratio Standard Deviation 0.4095	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 Baseline (Month 18)	0.620 ratio Standard Deviation 0.3305	0.586 ratio Standard Deviation 0.3612	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 Change from Baseline to Month 18	0.038 ratio Standard Deviation 0.4033	0.133 ratio Standard Deviation 0.4269	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 Baseline (Month 24)	0.633 ratio Standard Deviation 0.3156	0.584 ratio Standard Deviation 0.3617	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 Change from Baseline to Month 24	-0.020 ratio Standard Deviation 0.4721	0.086 ratio Standard Deviation 0.4153	—	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0) to Months 3, 6 and 12

Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, alanine aminotransferase (ALT), AST and age that is calculated using formula: FIB-4 = (Age \[years\] x AST \[U/L\]) / (platelets \[10\^9/L\] x (square root of ALT \[U/L\])). A FIB-4 index of \< 1.45 indicated no or moderate fibrosis and an index of \> 3.25 indicated extensive fibrosis/cirrhosis. A positive change from Baseline indicates increased fibrosis.

Outcome measures

Outcome measures
Measure	Placebo n=143 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 Baseline (Month 3)	1.444 ratio Standard Deviation 0.6753	1.417 ratio Standard Deviation 0.6893	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 Change from Baseline to Month 3	0.021 ratio Standard Deviation 0.4236	0.071 ratio Standard Deviation 0.4209	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 Change from Baseline to Month 6	0.015 ratio Standard Deviation 0.4591	0.099 ratio Standard Deviation 0.5246	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 Baseline (Month 6)	1.500 ratio Standard Deviation 0.7268	1.388 ratio Standard Deviation 0.6771	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 Baseline (Month 12)	1.503 ratio Standard Deviation 0.7442	1.398 ratio Standard Deviation 0.6834	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 Change from Baseline to Month 12	0.106 ratio Standard Deviation 0.6876	0.117 ratio Standard Deviation 0.5069	—	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0) to Months 15, 18 and 24

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=215 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 Baseline (Month 15)	1.409 ratio Standard Deviation 0.6706	1.440 ratio Standard Deviation 0.6714	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 Change from Baseline to Month 15	0.075 ratio Standard Deviation 0.5982	0.213 ratio Standard Deviation 0.6462	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 Baseline (Month 18)	1.389 ratio Standard Deviation 0.6699	1.440 ratio Standard Deviation 0.6895	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 Change from Baseline to Month 18	0.094 ratio Standard Deviation 0.5891	0.219 ratio Standard Deviation 0.5559	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 Baseline (Month 24)	1.426 ratio Standard Deviation 0.6841	1.444 ratio Standard Deviation 0.6838	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 Change from Baseline to Month 24	0.064 ratio Standard Deviation 0.8103	0.166 ratio Standard Deviation 0.6086	—	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0) to Months 6 and 12

Hyaluronic acid is a non-invasive hepatic fibrosis marker. A negative change from Baseline indicates decreased fibrosis.

Outcome measures

Outcome measures
Measure	Placebo n=143 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 Baseline (Month 12)	70.7 ng/mL Standard Deviation 110.49	69.5 ng/mL Standard Deviation 80.56	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 Change from Baseline to Month 12	-0.2 ng/mL Standard Deviation 81.30	10.9 ng/mL Standard Deviation 58.46	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 Baseline (Month 6)	68.7 ng/mL Standard Deviation 107.63	68.2 ng/mL Standard Deviation 78.88	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 Change from Baseline to Month 6	-2.4 ng/mL Standard Deviation 75.03	10.7 ng/mL Standard Deviation 79.58	—	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0) to Months 18 and 24

Hyaluronic acid is a non-invasive hepatic fibrosis marker. A positive change from Baseline indicates increased fibrosis.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=215 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 Change from Baseline to Month 24	19.3 ng/mL Standard Deviation 70.64	13.0 ng/mL Standard Deviation 95.00	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 Baseline (Month 18)	46.4 ng/mL Standard Deviation 32.67	79.6 ng/mL Standard Deviation 111.36	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 Change from Baseline to Month 18	5.7 ng/mL Standard Deviation 34.66	1.4 ng/mL Standard Deviation 81.20	—	—	—
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 Baseline (Month 24)	46.6 ng/mL Standard Deviation 32.91	79.7 ng/mL Standard Deviation 112.46	—	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0) to Months 3, 6 and 12

NFS is calculated using formula: NFS = -1.675 + 0.037 \* age (years) + 0.094 \* Body mass index (BMI) (kg/m\^2) + 1.13 \* Impaired fasting glucose (IFG)/diabetes (yes = 1, no = 0) + 0.99 \* Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ratio - 0.013 × platelet (\*10\^9/L) - 0.66 \* albumin (g/dL). A negative change from Baseline indicates decreased fibrosis.

Outcome measures

Outcome measures
Measure	Placebo n=143 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 Baseline (Month 3)	-1.227 ng/mL Standard Deviation 1.5255	-1.012 ng/mL Standard Deviation 1.2558	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 Change from Baseline to Month 3	0.029 ng/mL Standard Deviation 0.5150	0.087 ng/mL Standard Deviation 0.4608	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 Baseline (Month 6)	-1.119 ng/mL Standard Deviation 1.4935	-1.064 ng/mL Standard Deviation 1.2403	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 Change from Baseline to Month 6	0.051 ng/mL Standard Deviation 0.4747	0.094 ng/mL Standard Deviation 0.5460	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 Baseline (Month 12)	-1.132 ng/mL Standard Deviation 1.4609	-1.040 ng/mL Standard Deviation 1.1393	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 Change from Baseline to Month 12	0.121 ng/mL Standard Deviation 0.5117	0.139 ng/mL Standard Deviation 0.5016	—	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0) to Months 15, 18 and 24

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=215 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 Change from Baseline to Month 18	0.046 ng/mL Standard Deviation 0.5809	0.196 ng/mL Standard Deviation 0.5583	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 Change from Baseline to Month 24	0.046 ng/mL Standard Deviation 0.6188	0.185 ng/mL Standard Deviation 0.6184	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 Baseline (Month 15)	-1.252 ng/mL Standard Deviation 1.4602	-1.051 ng/mL Standard Deviation 1.3410	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 Change from Baseline to Month 15	0.057 ng/mL Standard Deviation 0.5981	0.225 ng/mL Standard Deviation 0.5654	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 Baseline (Month 18)	-1.284 ng/mL Standard Deviation 1.4910	-1.057 ng/mL Standard Deviation 1.3309	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 Baseline (Month 24)	-1.245 ng/mL Standard Deviation 1.4778	-1.100 ng/mL Standard Deviation 1.3228	—	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0) to Months 6 and 12

The markers of fibrosis assessed in this test comprised hyaluronic acid (CHA), tissue inhibitor of metalloproteinase (CTIMP1) and procollagen III N-terminal peptide (CP3NP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during activation of the stellate cell. The ELF tests were performed on Centaur device and the composite score was calculated as follows: ELF score = 2.278 + 0.851 ln(CHA) + 0.751 ln (CP3NP) + 0.394 ln(CTIMP1). ELF score \< 7.7: no to mild fibrosis; ≥ 7.7 - \< 9.8: Moderate fibrosis; ≥ 9.8 - \< 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis. A negative change from Baseline indicates decreased fibrosis.

Outcome measures

Outcome measures
Measure	Placebo n=143 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 Baseline (Month 6)	-0.786 ng/mL Standard Deviation 0.7179	-0.837 ng/mL Standard Deviation 0.7238	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 Change from Baseline to Month 6	-0.022 ng/mL Standard Deviation 0.4901	0.060 ng/mL Standard Deviation 0.5228	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 Baseline (Month 12)	-0.795 ng/mL Standard Deviation 0.7435	-0.801 ng/mL Standard Deviation 0.7162	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 Change from Baseline to Month 12	-0.064 ng/mL Standard Deviation 0.5602	0.041 ng/mL Standard Deviation 0.5727	—	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0) to Months 18 and 24

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=215 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 Change from Baseline to Month 18	-0.129 ng/mL Standard Deviation 0.6606	-0.087 ng/mL Standard Deviation 0.6113	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 Baseline (Month 24)	-0.940 ng/mL Standard Deviation 0.6587	-0.765 ng/mL Standard Deviation 0.7127	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 Baseline (Month 18)	-0.931 ng/mL Standard Deviation 0.6387	-0.758 ng/mL Standard Deviation 0.7307	—	—	—
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 Change from Baseline to Month 24	-0.024 ng/mL Standard Deviation 0.7375	0.096 ng/mL Standard Deviation 0.6437	—	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0) to Months 3, 6 and 12

Caspase-cleaved cytokeratin levels (CK18M30) and total M-65 (CK-18 \[M-65\]) were measured as biomarkers of hepatocyte apoptosis. A negative change from Baseline indicates decreased hepatocyte apoptosis.

Outcome measures

Outcome measures
Measure	Placebo n=143 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 Baseline (Month 3)	601.6 U/L Standard Deviation 431.77	594.2 U/L Standard Deviation 554.20	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 Change from Baseline to Month 3	-56.4 U/L Standard Deviation 451.14	-59.0 U/L Standard Deviation 485.76	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 Baseline (Month 6)	550.3 U/L Standard Deviation 360.64	552.9 U/L Standard Deviation 393.92	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 Change from Baseline to Month 6	10.6 U/L Standard Deviation 461.98	-26.1 U/L Standard Deviation 512.88	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 Baseline (Month 12)	555.3 U/L Standard Deviation 356.28	567.9 U/L Standard Deviation 500.53	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 Change from Baseline to Month 12	99.7 U/L Standard Deviation 824.50	107.8 U/L Standard Deviation 830.28	—	—	—

SECONDARY outcome

Timeframe: Baseline (Month 0) to Months 15, 18 and 24

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=215 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 CK-18(M30), Baseline (Month 18)	578.8 U/L Standard Deviation 293.93	540.9 U/L Standard Deviation 453.90	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 CK-18(M30), Change from Baseline to Month 18	23.8 U/L Standard Deviation 402.98	57.3 U/L Standard Deviation 476.92	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 CK-18(M30), Baseline (Month 24)	575.4 U/L Standard Deviation 293.64	541.8 U/L Standard Deviation 462.29	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 CK-18(M30), Change from Baseline to Month 24	-30.0 U/L Standard Deviation 369.60	39.7 U/L Standard Deviation 437.60	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 CK-18(M65), Change from Baseline to Month 24	7.4 U/L Standard Deviation 570.92	124.9 U/L Standard Deviation 522.08	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 CK-18(M30), Baseline (Month 15)	570.8 U/L Standard Deviation 297.42	536.4 U/L Standard Deviation 459.06	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 CK-18(M30), Change from Baseline to Month 15	-39.6 U/L Standard Deviation 287.44	-13.3 U/L Standard Deviation 450.16	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 CK-18(M65), Baseline (Month 15)	772.7 U/L Standard Deviation 337.24	687.4 U/L Standard Deviation 404.83	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 CK-18(M65), Change from Baseline to Month 15	134.7 U/L Standard Deviation 534.46	88.6 U/L Standard Deviation 559.11	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 CK-18(M65), Baseline (Month 18)	777.8 U/L Standard Deviation 344.07	694.8 U/L Standard Deviation 401.88	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 CK-18(M65), Change from Baseline to Month 18	158.0 U/L Standard Deviation 732.63	181.5 U/L Standard Deviation 620.57	—	—	—
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 CK-18(M65), Baseline (Month 24)	770.2 U/L Standard Deviation 335.05	693.9 U/L Standard Deviation 409.88	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Months 3, 6 and 12

Population: Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.

A negative change from Baseline represents decreased weight.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Weight at Months 3, 6 and 12 Baseline (Month 3)	97.21 kg Standard Deviation 22.368	95.59 kg Standard Deviation 20.590	—	—	—
Change From Baseline in Weight at Months 3, 6 and 12 Change from Baseline to Month 3	-0.50 kg Standard Deviation 2.652	-0.63 kg Standard Deviation 2.632	—	—	—
Change From Baseline in Weight at Months 3, 6 and 12 Baseline (Month 12)	96.63 kg Standard Deviation 22.139	95.06 kg Standard Deviation 20.651	—	—	—
Change From Baseline in Weight at Months 3, 6 and 12 Change from Baseline to Month 12	-0.08 kg Standard Deviation 4.301	-0.28 kg Standard Deviation 4.166	—	—	—
Change From Baseline in Weight at Months 3, 6 and 12 Baseline (Month 6)	97.18 kg Standard Deviation 22.224	95.18 kg Standard Deviation 20.386	—	—	—
Change From Baseline in Weight at Months 3, 6 and 12 Change from Baseline to Month 6	-0.55 kg Standard Deviation 3.319	-0.47 kg Standard Deviation 3.466	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Months 15, 18 and 24

Population: Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.

A negative change from Baseline represents decreased weight.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=182 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Weight at Months 15, 18 and 24 Baseline (Month 15)	98.25 kg Standard Deviation 24.087	95.32 kg Standard Deviation 20.749	—	—	—
Change From Baseline in Weight at Months 15, 18 and 24 Change from Baseline to Month 15	0.15 kg Standard Deviation 3.448	-0.44 kg Standard Deviation 4.257	—	—	—
Change From Baseline in Weight at Months 15, 18 and 24 Baseline (Month 18)	96.98 kg Standard Deviation 22.210	95.23 kg Standard Deviation 20.823	—	—	—
Change From Baseline in Weight at Months 15, 18 and 24 Change from Baseline to Month 18	0.05 kg Standard Deviation 4.194	-0.16 kg Standard Deviation 4.458	—	—	—
Change From Baseline in Weight at Months 15, 18 and 24 Baseline (Month 24)	96.98 kg Standard Deviation 22.210	95.19 kg Standard Deviation 20.972	—	—	—
Change From Baseline in Weight at Months 15, 18 and 24 Change from Baseline to Month 24	-0.91 kg Standard Deviation 5.649	-0.56 kg Standard Deviation 5.081	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Months 3, 6 and 12

The body mass index is a value derived from the mass (weight in kgs) and height (in centimeters) of an individual and is calculated as the body mass divided by the square of the body height. A negative change from Baseline represents decreased BMI.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 Baseline (Month 3)	34.129 kg/m^2 Standard Deviation 7.2492	33.706 kg/m^2 Standard Deviation 5.7812	—	—	—
Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 Change from Baseline to Month 3	-0.172 kg/m^2 Standard Deviation 0.9200	-0.232 kg/m^2 Standard Deviation 0.9500	—	—	—
Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 Baseline (Month 6)	34.196 kg/m^2 Standard Deviation 7.3086	33.547 kg/m^2 Standard Deviation 5.6037	—	—	—
Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 Change from Baseline to Month 6	-0.182 kg/m^2 Standard Deviation 1.1558	-0.196 kg/m^2 Standard Deviation 1.2500	—	—	—
Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 Baseline (Month 12)	34.029 kg/m^2 Standard Deviation 7.1358	33.374 kg/m^2 Standard Deviation 5.6631	—	—	—
Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 Change from Baseline to Month 12	-0.013 kg/m^2 Standard Deviation 1.7507	-0.145 kg/m^2 Standard Deviation 1.4891	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Months 15, 18 and 24

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=182 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 Change from Baseline to Month 15	-0.006 kg/m^2 Standard Deviation 1.2799	-0.113 kg/m^2 Standard Deviation 1.6311	—	—	—
Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 Baseline (Month 18)	34.473 kg/m^2 Standard Deviation 7.8964	33.345 kg/m^2 Standard Deviation 5.9443	—	—	—
Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 Baseline (Month 15)	34.713 kg/m^2 Standard Deviation 8.0431	33.392 kg/m^2 Standard Deviation 5.9669	—	—	—
Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 Change from Baseline to Month 18	-0.039 kg/m^2 Standard Deviation 1.5931	-0.040 kg/m^2 Standard Deviation 1.7153	—	—	—
Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 Baseline (Month 24)	34.473 kg/m^2 Standard Deviation 7.8964	33.278 kg/m^2 Standard Deviation 6.0012	—	—	—
Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 Change from Baseline to Month 24	-0.393 kg/m^2 Standard Deviation 2.0613	-0.178 kg/m^2 Standard Deviation 1.8515	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Months 3, 6 and 12

A negative change from Baseline represents decreased in waist circumference.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Waist Circumference at Months 3, 6 and 12 Baseline (Month 3)	110.35 cm Standard Deviation 14.866	110.25 cm Standard Deviation 13.406	—	—	—
Change From Baseline in Waist Circumference at Months 3, 6 and 12 Change from Baseline to Month 3	0.07 cm Standard Deviation 5.147	0.05 cm Standard Deviation 5.396	—	—	—
Change From Baseline in Waist Circumference at Months 3, 6 and 12 Baseline (Month 6)	110.42 cm Standard Deviation 14.986	110.12 cm Standard Deviation 13.561	—	—	—
Change From Baseline in Waist Circumference at Months 3, 6 and 12 Change from Baseline to Month 6	0.42 cm Standard Deviation 8.827	-0.54 cm Standard Deviation 5.876	—	—	—
Change From Baseline in Waist Circumference at Months 3, 6 and 12 Baseline (Month 12)	109.77 cm Standard Deviation 14.617	110.02 cm Standard Deviation 13.711	—	—	—
Change From Baseline in Waist Circumference at Months 3, 6 and 12 Change from Baseline to Month 12	0.44 cm Standard Deviation 6.584	-1.10 cm Standard Deviation 6.255	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Months 15, 18 and 24

A negative change from Baseline represents decreased in waist circumference.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=182 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Waist Circumference at Months 15, 18 and 24 Change from Baseline to Month 24	0.11 cm Standard Deviation 7.907	-1.00 cm Standard Deviation 6.503	—	—	—
Change From Baseline in Waist Circumference at Months 15, 18 and 24 Baseline (Month 15)	110.19 cm Standard Deviation 14.360	110.26 cm Standard Deviation 14.486	—	—	—
Change From Baseline in Waist Circumference at Months 15, 18 and 24 Change from Baseline to Month 15	0.52 cm Standard Deviation 5.520	-0.18 cm Standard Deviation 6.280	—	—	—
Change From Baseline in Waist Circumference at Months 15, 18 and 24 Baseline (Month 18)	109.48 cm Standard Deviation 12.703	110.25 cm Standard Deviation 14.517	—	—	—
Change From Baseline in Waist Circumference at Months 15, 18 and 24 Change from Baseline to Month 18	1.36 cm Standard Deviation 7.966	-0.21 cm Standard Deviation 6.578	—	—	—
Change From Baseline in Waist Circumference at Months 15, 18 and 24 Baseline (Month 24)	109.36 cm Standard Deviation 12.608	110.08 cm Standard Deviation 14.606	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Months 3, 6 and 12

A negative change from Baseline represents decreased hip circumference.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Hip Circumference at Months 3, 6 and 12 Baseline (Month 3)	114.92 cm Standard Deviation 16.150	112.35 cm Standard Deviation 13.802	—	—	—
Change From Baseline in Hip Circumference at Months 3, 6 and 12 Change from Baseline to Month 3	-0.30 cm Standard Deviation 4.921	-0.11 cm Standard Deviation 6.475	—	—	—
Change From Baseline in Hip Circumference at Months 3, 6 and 12 Change from Baseline to Month 12	-0.25 cm Standard Deviation 5.876	-0.08 cm Standard Deviation 7.474	—	—	—
Change From Baseline in Hip Circumference at Months 3, 6 and 12 Baseline (Month 6)	115.09 cm Standard Deviation 16.270	112.16 cm Standard Deviation 13.320	—	—	—
Change From Baseline in Hip Circumference at Months 3, 6 and 12 Change from Baseline to Month 6	-0.84 cm Standard Deviation 4.396	-0.18 cm Standard Deviation 5.715	—	—	—
Change From Baseline in Hip Circumference at Months 3, 6 and 12 Baseline (Month 12)	114.46 cm Standard Deviation 15.970	111.66 cm Standard Deviation 13.376	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Months 15, 18 and 24

A negative change from Baseline represents decreased hip circumference.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=182 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Hip Circumference at Months 15, 18 and 24 Baseline (Month 15)	114.56 cm Standard Deviation 17.500	113.00 cm Standard Deviation 14.183	—	—	—
Change From Baseline in Hip Circumference at Months 15, 18 and 24 Change from Baseline to Month 15	-0.06 cm Standard Deviation 5.361	-0.83 cm Standard Deviation 7.050	—	—	—
Change From Baseline in Hip Circumference at Months 15, 18 and 24 Change from Baseline to Month 18	0.55 cm Standard Deviation 7.791	-0.90 cm Standard Deviation 6.066	—	—	—
Change From Baseline in Hip Circumference at Months 15, 18 and 24 Baseline (Month 24)	114.34 cm Standard Deviation 17.408	112.88 cm Standard Deviation 14.225	—	—	—
Change From Baseline in Hip Circumference at Months 15, 18 and 24 Change from Baseline to Month 24	-0.95 cm Standard Deviation 7.700	-1.21 cm Standard Deviation 6.677	—	—	—
Change From Baseline in Hip Circumference at Months 15, 18 and 24 Baseline (Month 18)	114.28 cm Standard Deviation 17.871	112.70 cm Standard Deviation 14.168	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Months 3, 6 and 12

A negative change from Baseline represents decreased forearm circumference.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Forearm Circumference at Months 3, 6 and 12 Baseline (Month 3)	32.95 cm Standard Deviation 7.346	33.38 cm Standard Deviation 4.835	—	—	—
Change From Baseline in Forearm Circumference at Months 3, 6 and 12 Change from Baseline to Month 3	0.97 cm Standard Deviation 6.023	0.10 cm Standard Deviation 6.486	—	—	—
Change From Baseline in Forearm Circumference at Months 3, 6 and 12 Baseline (Month 6)	32.70 cm Standard Deviation 7.290	33.25 cm Standard Deviation 4.734	—	—	—
Change From Baseline in Forearm Circumference at Months 3, 6 and 12 Change from Baseline to Month 6	0.82 cm Standard Deviation 6.748	-0.01 cm Standard Deviation 3.447	—	—	—
Change From Baseline in Forearm Circumference at Months 3, 6 and 12 Baseline (Month 12)	32.51 cm Standard Deviation 7.277	33.09 cm Standard Deviation 4.771	—	—	—
Change From Baseline in Forearm Circumference at Months 3, 6 and 12 Change from Baseline to Month 12	0.83 cm Standard Deviation 6.656	-0.43 cm Standard Deviation 3.516	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Months 15, 18 and 24

A negative change from Baseline represents decreased forearm circumference.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=182 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Forearm Circumference at Months 15, 18 and 24 Baseline (Month 15)	32.88 cm Standard Deviation 7.783	32.91 cm Standard Deviation 5.662	—	—	—
Change From Baseline in Forearm Circumference at Months 15, 18 and 24 Change from Baseline to Month 15	1.61 cm Standard Deviation 6.534	0.01 cm Standard Deviation 5.052	—	—	—
Change From Baseline in Forearm Circumference at Months 15, 18 and 24 Baseline (Month 18)	32.63 cm Standard Deviation 7.718	32.87 cm Standard Deviation 5.696	—	—	—
Change From Baseline in Forearm Circumference at Months 15, 18 and 24 Change from Baseline to Month 18	1.79 cm Standard Deviation 6.715	0.02 cm Standard Deviation 4.709	—	—	—
Change From Baseline in Forearm Circumference at Months 15, 18 and 24 Baseline (Month 24)	32.79 cm Standard Deviation 7.660	33.02 cm Standard Deviation 5.561	—	—	—
Change From Baseline in Forearm Circumference at Months 15, 18 and 24 Change from Baseline to Month 24	0.78 cm Standard Deviation 6.124	-0.64 cm Standard Deviation 4.408	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Months 3, 6 and 12

A negative change from Baseline represents decreased Tricep Skinfold Thickness.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=144 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 Baseline (Month 6)	28.53 mm Standard Deviation 13.763	25.38 mm Standard Deviation 12.769	—	—	—
Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 Change from Baseline to Month 6	-2.72 mm Standard Deviation 8.091	-1.52 mm Standard Deviation 9.287	—	—	—
Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 Baseline (Month 3)	28.32 mm Standard Deviation 13.677	25.41 mm Standard Deviation 12.593	—	—	—
Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 Change from Baseline to Month 3	-1.21 mm Standard Deviation 6.548	-0.62 mm Standard Deviation 8.704	—	—	—
Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 Baseline (Month 12)	28.54 mm Standard Deviation 13.981	25.14 mm Standard Deviation 12.969	—	—	—
Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 Change from Baseline to Month 12	-1.34 mm Standard Deviation 9.389	-0.26 mm Standard Deviation 10.653	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Months 15, 18 and 24

A negative change from Baseline represents decreased Tricep Skinfold Thickness.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.	CVC 150 mg n=182 Participants Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.	Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.	Placebo Then CVC 150 mg Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2.	Placebo Then Placebo Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 Baseline (Month 24)	29.91 mm Standard Deviation 14.532	24.82 mm Standard Deviation 13.025	—	—	—
Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 Change from Baseline to Month 24	-3.11 mm Standard Deviation 8.553	-1.33 mm Standard Deviation 10.521	—	—	—
Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 Baseline (Month 15)	29.84 mm Standard Deviation 14.422	25.41 mm Standard Deviation 13.212	—	—	—
Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 Change from Baseline to Month 15	-1.45 mm Standard Deviation 9.364	-1.59 mm Standard Deviation 8.918	—	—	—
Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 Baseline (Month 18)	29.84 mm Standard Deviation 14.655	25.07 mm Standard Deviation 12.856	—	—	—
Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 Change from Baseline to Month 18	-2.27 mm Standard Deviation 8.854	-2.64 mm Standard Deviation 8.864	—	—	—

Adverse Events

CVC 150mg/CVC 150 mg

Serious events: 25 serious events

Other events: 127 other events

Deaths: 0 deaths

Placebo/Cenicriviroc (CVC) 150 mg

Serious events: 8 serious events

Other events: 59 other events

Deaths: 0 deaths

Placebo/Placebo

Serious events: 12 serious events

Other events: 60 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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

Measure	CVC 150mg/CVC 150 mg n=144 participants at risk CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2.	Placebo/Cenicriviroc (CVC) 150 mg n=72 participants at risk Placebo-matching CVC tablet, once daily in the morning with food in Year 1 then CVC 150 mg tablet, once daily in the morning with food in Year 2.	Placebo/Placebo n=72 participants at risk Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.
Infections and infestations Ear infection	3.5% 5/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	2.8% 2/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Infections and infestations Bronchitis	6.9% 10/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	1.4% 1/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	9.7% 7/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Investigations Blood creatine phosphokinase increased	2.1% 3/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	6.9% 5/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	0.00% 0/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Type 2 diabetes mellitus	4.2% 6/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	6.9% 5/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	2.1% 3/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	1.4% 1/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Procedural pain	3.5% 5/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	2.8% 2/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	12.5% 9/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Investigations Alanine aminotransferase increased	10.4% 15/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	12.5% 9/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	6.9% 5/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	22.2% 32/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	19.4% 14/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	20.8% 15/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain upper	11.1% 16/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	16.7% 12/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	13.9% 10/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	12.5% 18/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	8.3% 6/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	15.3% 11/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	19.4% 28/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	8.3% 6/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	11.1% 8/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal distension	9.0% 13/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	0.00% 0/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	9.0% 13/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	8.3% 6/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Flatulence	6.2% 9/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	4.2% 3/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	2.8% 2/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	4.2% 6/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	4.2% 3/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	12.5% 18/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	4.2% 3/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	6.9% 5/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
General disorders Fatigue	16.7% 24/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	13.9% 10/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	18.1% 13/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
General disorders Oedema peripheral	3.5% 5/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	6.9% 5/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	4.2% 3/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
General disorders Pyrexia	5.6% 8/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	1.4% 1/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	11.8% 17/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	13.9% 10/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	14.6% 21/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	12.5% 9/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	9.7% 7/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	12.5% 18/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	12.5% 9/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	11.1% 8/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Infections and infestations Influenza	7.6% 11/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	4.2% 3/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	4.2% 3/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Infections and infestations Sinusitis	12.5% 18/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	4.2% 3/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	12.5% 9/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	2.8% 2/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	7.6% 11/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	15.3% 11/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	16.7% 12/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	7.6% 11/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	6.9% 5/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	4.2% 3/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	16.0% 23/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	10.4% 15/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	2.8% 2/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	9.7% 14/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	1.4% 1/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	8.3% 6/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Nervous system disorders Headache	16.7% 24/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	20.8% 15/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	12.5% 9/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	9.0% 13/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	0.00% 0/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	6.9% 5/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Psychiatric disorders Insomnia	6.9% 10/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	2.8% 2/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	2.8% 2/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	11.1% 16/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	6.9% 5/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	8.3% 6/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.0% 13/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	4.2% 3/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.6% 8/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	0.00% 0/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	2.8% 2/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	6.9% 10/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	4.2% 3/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	6.9% 5/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash	8.3% 12/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	4.2% 3/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	11.1% 8/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	6.9% 10/144 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	5.6% 4/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.	4.2% 3/72 • Baseline to Year 2 Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.