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Clinical Trial Results:
CENTAUR: Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Subjects with Liver Fibrosis

Summary
EudraCT number	2014-003164-21
Trial protocol	BE GB IT DE ES FR
Global end of trial date	22 Jun 2017

Results information
Results version number	v1(current)
This version publication date	31 May 2019
First version publication date	31 May 2019
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

652-2-203

ISRCTN number

US NCT number

NCT02217475

WHO universal trial number (UTN)

Sponsor organisation name

Tobira Therapeutics, Inc., an affiliate of Allergan plc

Sponsor organisation address

Clonshaugh Business and Technology Park, Coolock, Dublin, Ireland, D17 E400

Public contact

Clinical Trials Registry Team, Allergan plc, 001 877‐277‐8566, IR-CTRegistration@allergan.com

Scientific contact

Therapeutic Area, Head, Allergan plc, 001 862-261-7000, IR-CTRegistration@Allergan.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

22 Jun 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

22 Jun 2017

Was the trial ended prematurely?

Main objective of the trial

To evaluate hepatic histological improvement in nonalcoholic fatty liver disease (NAFLD) activity score (NAS) at Year 1, relative to the Screening biopsy, defined by a minimum 2-point improvement in NAS with at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning AND with no concurrent worsening of fibrosis stage (worsening defined as progression of NASH Clinical Research Network [CRN] fibrosis stage) at Year 1.

Protection of trial subjects

All study participants were required to read and sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Sep 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 166

Country: Number of subjects enrolled

Australia: 15

Country: Number of subjects enrolled

China: 14

Country: Number of subjects enrolled

France: 37

Country: Number of subjects enrolled

Belgium: 15

Country: Number of subjects enrolled

Germany: 12

Country: Number of subjects enrolled

Spain: 10

Country: Number of subjects enrolled

Italy: 8

Country: Number of subjects enrolled

United Kingdom: 7

Country: Number of subjects enrolled

Poland: 5

Worldwide total number of subjects

289

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

236

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

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

Period 1 title

Treatment Period 1 (Year 1)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Carer, Assessor, Subject

Are arms mutually exclusive

Yes

Placebo/Placebo

Arm description

Placebo-matching cenicriviroc (CVC) tablet in Years 1 and 2.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Year 1.

Placebo/Cenicriviroc (CVC) 150 mg

Arm description

Placebo-matching CVC tablet in Year 1 then CVC 150 mg tablet in Year 2.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Year 1.

CVC 150mg/CVC 150 mg

Arm description

CVC 150 mg tablet in Years 1 and 2.

Arm type

Experimental

Investigational medicinal product name

Cenicriviroc (CVC)

Investigational medicinal product code

TBR-652

Other name

Cenicriviroc mesylate

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

CVC 150 mg tablet, once daily in the morning with food in Year 1.

Number of subjects in period 1	Placebo/Placebo	Placebo/Cenicriviroc (CVC) 150 mg	CVC 150mg/CVC 150 mg
Started	72	72	145
Safety Analysis Set	72	72	144
Completed	62	64	124
Not completed	10	8	21
Subject Withdrew Consent	5	2	11
Adverse event, non-fatal	4	5	9
Lost to follow-up	1	-	-
Other Miscellaneous Reasons	-	-	1
Protocol Deviation (with non-compliance)	-	1	-

Period 2 title

Discontinued After Period 1

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo/Placebo

Arm description

Placebo-matching cenicriviroc (CVC) tablet in Years 1 and 2.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Placebo/Cenicriviroc (CVC) 150 mg

Arm description

Placebo-matching CVC tablet in Year 1 then CVC 150 mg tablet in Year 2.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

CVC 150mg/CVC 150 mg

Arm description

CVC 150 mg tablet in Years 1 and 2.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	Placebo/Placebo	Placebo/Cenicriviroc (CVC) 150 mg	CVC 150mg/CVC 150 mg
Started	62	64	124
Completed	60	61	121
Not completed	2	3	3
Physician decision	-	-	1
Subject Withdrew Consent	1	1	2
Adverse event	1	2	-

Period 3 title

Treatment Period 2 (Year 2)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo/Placebo

Arm description

Placebo-matching cenicriviroc (CVC) tablet in Years 1 and 2.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Year 2.

Placebo/Cenicriviroc (CVC) 150 mg

Arm description

Placebo-matching CVC tablet in Year 1 then CVC 150 mg tablet in Year 2.

Arm type

Experimental

Investigational medicinal product name

Cenicriviroc (CVC)

Investigational medicinal product code

TBR-652

Other name

Cenicriviroc mesylate

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

CVC 150 mg tablet, once daily in the morning with food in Year 2.

CVC 150mg/CVC 150 mg

Arm description

CVC 150 mg tablet in Years 1 and 2.

Arm type

Experimental

Investigational medicinal product name

Cenicriviroc (CVC)

Investigational medicinal product code

TBR-652

Other name

Cenicriviroc mesylate

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

CVC 150 mg tablet, once daily in the morning with food in Year 2.

Number of subjects in period 3	Placebo/Placebo	Placebo/Cenicriviroc (CVC) 150 mg	CVC 150mg/CVC 150 mg
Started	60	61	121
Completed	58	59	109
Not completed	2	2	12
Physician decision	-	-	2
Subject Withdrew Consent	2	-	2
Adverse event, non-fatal	-	1	5
Lost to follow-up	-	1	2
Other Miscellaneous Reasons	-	-	1

Baseline characteristics

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Reporting group title

Placebo/Placebo

Reporting group description

Placebo-matching cenicriviroc (CVC) tablet in Years 1 and 2.

Reporting group title

Placebo/Cenicriviroc (CVC) 150 mg

Reporting group description

Placebo-matching CVC tablet in Year 1 then CVC 150 mg tablet in Year 2.

Reporting group title

CVC 150mg/CVC 150 mg

Reporting group description

CVC 150 mg tablet in Years 1 and 2.

Reporting group values	Placebo/Placebo	Placebo/Cenicriviroc (CVC) 150 mg	CVC 150mg/CVC 150 mg	Total
Number of subjects	72	72	145	289
Age categorical
Units: Subjects
Adults (18-64 years)	57	60	119	236
From 65-84 years	15	12	26	53
Age Continuous
Units: years
arithmetic mean (standard deviation)	52.1 ( 11.37 )	55.3 ( 10.38 )	54.6 ( 10.22 )	-
Sex: Female, Male
Units: Subjects
Female	40	39	73	152
Male	32	33	72	137
Race/Ethnicity, Customized
Units: Subjects
Hispanic or Latino	7	18	23	48
Not Hispanic or Latino	65	51	122	238
Not reported	0	2	0	2
Unknown	0	1	0	1
Race/Ethnicity, Customized
Units: Subjects
Asian	9	6	6	21
American Indian or Alaska Native	1	0	0	1
Black or African American	2	1	5	8
Native Hawaiian or Other Pacific Islander	0	0	3	3
White	58	63	129	250
Other	2	2	2	6

End points

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Reporting group title

Placebo/Placebo

Reporting group description

Placebo-matching cenicriviroc (CVC) tablet in Years 1 and 2.

Reporting group title

Placebo/Cenicriviroc (CVC) 150 mg

Reporting group description

Placebo-matching CVC tablet in Year 1 then CVC 150 mg tablet in Year 2.

Reporting group title

CVC 150mg/CVC 150 mg

Reporting group description

CVC 150 mg tablet in Years 1 and 2.

Reporting group title

Placebo/Placebo

Reporting group description

Placebo-matching cenicriviroc (CVC) tablet in Years 1 and 2.

Reporting group title

Placebo/Cenicriviroc (CVC) 150 mg

Reporting group description

Placebo-matching CVC tablet in Year 1 then CVC 150 mg tablet in Year 2.

Reporting group title

CVC 150mg/CVC 150 mg

Reporting group description

CVC 150 mg tablet in Years 1 and 2.

Reporting group title

Placebo/Placebo

Reporting group description

Placebo-matching cenicriviroc (CVC) tablet in Years 1 and 2.

Reporting group title

Placebo/Cenicriviroc (CVC) 150 mg

Reporting group description

Placebo-matching CVC tablet in Year 1 then CVC 150 mg tablet in Year 2.

Reporting group title

CVC 150mg/CVC 150 mg

Reporting group description

CVC 150 mg tablet in Years 1 and 2.

Subject analysis set title

CVC 150 mg/CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2.‌

Subject analysis set title

Placebo/CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

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.‌

Subject analysis set title

Placebo/Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.‌

Subject analysis set title

Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.

Subject analysis set title

Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet or 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.

Subject analysis set title

CVC 150 mg (Year 1)

Subject analysis set type

Sub-group analysis

Subject analysis set description

CVC 150 mg tablet, once daily in the morning with food in Year 1.

Subject analysis set title

Placebo (Year 1)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet once daily in the morning with food in Year 1.

Subject analysis set title

CVC 150 mg/CVC 150 mg (Year 2)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet, once daily in the morning with food in Years 1 and 2. Included AEs that occurred in Year 2.

Subject analysis set title

Placebo/CVC 150 mg (Year 2)

Subject analysis set type

Sub-group analysis

Subject analysis set description

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. Included AEs that occurred in Year 2.

Subject analysis set title

Placebo/Placebo (Year 2)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2.Observed Clinically significant vital signs in Year 2.

Subject analysis set title

CVC 150 mg/CVC 150 mg (Year 2)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet, once daily in the morning with food in Years 1 and 2. Observed clinically abnormal ECG findings in Year 2.

Subject analysis set title

Placebo/CVC 150 mg (Year 2)

Subject analysis set type

Sub-group analysis

Subject analysis set description

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. Observed clinically abnormal ECG findings in Year 2.

Subject analysis set title

Placebo/Placebo (Year 2)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Observed clinically abnormal ECG findings in Year 2.

Subject analysis set title

Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet or 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.

Subject analysis set title

Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.

Subject analysis set title

Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet or 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.

Subject analysis set title

Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.

Subject analysis set title

Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.

Subject analysis set title

Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet or 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.

Subject analysis set title

Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.

Subject analysis set title

Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet or 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.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.

Subject analysis set title

Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet or 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.

Subject analysis set title

CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cenicriviroc 150 mg tablet or 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.

Subject analysis set title

Placebo then CVC 150 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

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.

Subject analysis set title

Placebo then Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.

Primary: Number of Participants 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

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End point title

Number of Participants 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

End point description

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

End point type

Primary

End point timeframe

Year 1

End point values	Placebo	CVC 150 mg
Number of subjects analysed	144	145
Units: participants	27	23

Statistical Analysis 1

Comparison groups

Placebo v CVC 150 mg

Number of subjects included in analysis

289

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5194

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.816

Confidence interval

level

95%

sides

2-sided

lower limit

0.439

upper limit

1.516

Secondary: 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

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End point title

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

End point description

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. ITT population included all randomised participants regardless of starting treatment.

End point type

Secondary

End point timeframe

Year 1

End point values	Placebo	CVC 150 mg
Number of subjects analysed	144	145
Units: participants	4	7

Statistical Analysis 1

Comparison groups

Placebo v CVC 150 mg

Number of subjects included in analysis

289

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0388

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.934

Confidence interval

level

95%

sides

2-sided

lower limit

1.035

upper limit

3.614

Secondary: 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

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End point title

End point description

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. 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.

End point type

Secondary

End point timeframe

Year 2

End point values	Placebo	CVC 150 mg
Number of subjects analysed	57	178
Units: participants	2	5

Statistical Analysis 1

Comparison groups

Placebo v CVC 150 mg

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.592

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.249

Confidence interval

level

95%

sides

2-sided

lower limit

0.553

upper limit

2.821

Secondary: Number of Participants with Complete Resolution of Steatohepatitis with no Concurrent Worsening of Fibrosis Stage at Year 1

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End point title

Number of Participants with Complete Resolution of Steatohepatitis with no Concurrent Worsening of Fibrosis Stage at Year 1

End point description

End point type

Secondary

End point timeframe

Year 1

End point values	Placebo	CVC 150 mg
Number of subjects analysed	144	145
Units: participants	8	11

Statistical Analysis 1

Comparison groups

Placebo v CVC 150 mg

Number of subjects included in analysis

289

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4941

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.396

Confidence interval

level

95%

sides

2-sided

lower limit

0.537

upper limit

3.628

Secondary: Number of Participants with Complete Resolution of Steatohepatitis with no Concurrent Worsening of Fibrosis Stage at Year 2

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End point title

Number of Participants with Complete Resolution of Steatohepatitis with no Concurrent Worsening of Fibrosis Stage at Year 2

End point description

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. 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.

End point type

Secondary

End point timeframe

Year 2

End point values	Placebo	CVC 150 mg
Number of subjects analysed	57	178
Units: participants	3	11

Statistical Analysis 1

Comparison groups

Placebo v CVC 150 mg

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8434

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.142

Confidence interval

level

95%

sides

2-sided

lower limit

0.305

upper limit

4.277

Secondary: Number of Participants with Improvement in Fibrosis by at Least 1 Stage (NASH CRN system) and no Worsening of Steatohepatitis at Year 1

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End point title

Number of Participants with Improvement in Fibrosis by at Least 1 Stage (NASH CRN system) and no Worsening of Steatohepatitis at Year 1

End point description

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. ITT population included all randomised participants regardless of starting treatment.

End point type

Secondary

End point timeframe

Year 1

End point values	Placebo	CVC 150 mg
Number of subjects analysed	144	145
Units: participants	15	29

Statistical Analysis 1

Comparison groups

Placebo v CVC 150 mg

Number of subjects included in analysis

289

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0234

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.201

Confidence interval

level

95%

sides

2-sided

lower limit

1.113

upper limit

4.352

Secondary: Number of Participants with Improvement in Fibrosis by at Least 1 Stage (NASH CRN system) and no Worsening of Steatohepatitis at Year 2

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End point title

Number of Participants with Improvement in Fibrosis by at Least 1 Stage (NASH CRN system) and no Worsening of Steatohepatitis at Year 2

End point description

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. 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).

End point type

Secondary

End point timeframe

Year 2

End point values	Placebo	CVC 150 mg
Number of subjects analysed	57	178
Units: participants	8	27

Statistical Analysis 1

Comparison groups

Placebo v CVC 150 mg

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7474

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.154

Confidence interval

level

95%

sides

2-sided

lower limit

0.484

upper limit

2.752

Secondary: Number of Participants with Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation

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End point title

Number of Participants with Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation

End point description

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 hospitalisation or results in prolongation of existing hospitalisation, results in disability/incapacity, or was a congenital anomaly/birth defect. Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.

End point type

Secondary

End point timeframe

Years 1 and 2

End point values	CVC 150 mg/CVC 150 mg	Placebo/CVC 150 mg	Placebo/Placebo
Number of subjects analysed	144	72	72
Units: participants
Deaths	0	0	0
TEAEs	137	68	70
SAEs	25	8	12
TEAEs Leading Study Drug to Discontinuation	14	8	5

No statistical analyses for this end point

Secondary: Number of Participants with Clinically Significant Changes in Vital Signs

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End point title

Number of Participants with Clinically Significant Changes in Vital Signs

End point description

Vital signs included blood pressure, temperature, heart rate, and respiration rate. Vital signs were reviewed by the Investigator for clinically significant changes. Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.

End point type

Secondary

End point timeframe

Years 1 and 2

End point values	CVC 150 mg/CVC 150 mg	Placebo/CVC 150 mg	Placebo/Placebo
Number of subjects analysed	144	72	72
Units: participants	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Clinical Laboratory Abnormalities

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End point title

Number of Participants with Clinical Laboratory Abnormalities

End point description

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:>5.0xULN; 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. Safety Analysis Set Year 1 and Year 2.

End point type

Secondary

End point timeframe

Years 1 and 2

End point values	CVC 150 mg (Year 1)	Placebo (Year 1)	CVC 150 mg	Placebo then CVC 150 mg	Placebo then Placebo
Number of subjects analysed	144	144	121	61	60
Units: participants
Fasting glucose (Grade 3)	17	13	10	6	5
Fasting glucose (Grade 4)	0	0	0	0	0
ALT (Grade 3)	17	17	4	3	2
ALT (Grade 4)	0	0	0	0	0
AST (Grade 3)	7	10	1	3	1
AST (Grade 4)	0	0	0	0	0
APT/PTT (Grade 3)	4	2	1	1	2
Triglycerides (Grade 3)	5	7	6	5	2
Triglycerides (Grade 4)	3	3	2	0	1
GGT (Grade 3)	8	7	8	2	2
GGT (Grade 4)	1	1	1	0	0
Creatine kinase (Grade 3)	6	7	1	2	4
Creatine kinase (Grade 4)	2	2	3	1	0
Uric acid (Grade 3)	9	8	4	3	2
Uric acid (Grade 4)	11	6	5	1	6
Amylase (Grade 3)	6	1	4	0	1
Amylase (Grade 4)	3	0	2	0	0
Lipase (Grade 3)	4	2	3	0	1
Lipase (Grade 4)	5	0	3	0	1
Phosphorus (Grade 3)	5	2	2	1	1
Phosphorus (Grade 4)	0	0	0	0	0
Absolute neutrophil (Grade 3)	2	3	3	0	1
Absolute neutrophil (Grade 4)	2	1	1	1	1

No statistical analyses for this end point

Secondary: Number of Participants with Clinically Abnormal Electrocardiogram (ECG) Findings

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End point title

Number of Participants with Clinically Abnormal Electrocardiogram (ECG) Findings

End point description

A 12-lead ECG was performed. ECG results were reviewed by the Investigator for clinically notable abnormalities. Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.

End point type

Secondary

End point timeframe

Years 1 and 2

End point values	CVC 150 mg/CVC 150 mg	Placebo/CVC 150 mg	Placebo/Placebo
Number of subjects analysed	144	72	72
Units: participants	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Hepatic Histological Improvement in NAS at Year 2

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End point title

Number of Participants with Hepatic Histological Improvement in NAS at Year 2

End point description

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

End point type

Secondary

End point timeframe

Year 2

End point values	Placebo	CVC 150 mg
Number of subjects analysed	72	215
Units: participants	7	24

No statistical analyses for this end point

Secondary: Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1

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End point title

Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1

End point description

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

End point type

Secondary

End point timeframe

Year 1

End point values	Placebo	CVC 150 mg
Number of subjects analysed	126	126
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (Steatosis)	1.4 ( 0.55 )	1.3 ( 0.57 )
Change from Baseline (Steatosis)	-0.1 ( 0.66 )	-0.2 ( 0.56 )
Baseline (Lobular Inflammation)	2.5 ( 0.56 )	2.4 ( 0.58 )
Change from Baseline (Lobular Inflammation)	-0.1 ( 0.79 )	-0.1 ( 0.88 )
Baseline (Hepatocellular Ballooning)	1.5 ( 0.50 )	1.5 ( 0.50 )
Change from Baseline (Hepatocellular Ballooning)	-0.2 ( 0.75 )	-0.1 ( 0.75 )

No statistical analyses for this end point

Secondary: Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2

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End point title

Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2

End point description

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. 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 analysed is the number of participants with data available for analysis at the given time-point.

End point type

Secondary

End point timeframe

Year 2

End point values	Placebo	CVC 150 mg
Number of subjects analysed	54	159
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (Steatosis)	1.5 ( 0.54 )	1.3 ( 0.52 )
Change from Baseline (Steatosis)	-0.4 ( 0.56 )	-0.2 ( 0.50 )
Baseline (Lobular Inflammation)	2.4 ( 0.63 )	2.4 ( 0.54 )
Change from Baseline (Lobular Inflammation)	0.1 ( 0.72 )	0.0 ( 0.84 )
Baseline (Hepatocellular Ballooning)	1.5 ( 0.50 )	1.5 ( 0.50 )
Change from Baseline (Hepatocellular Ballooning)	-0.1 ( 0.68 )	0.0 ( 0.83 )

No statistical analyses for this end point

Secondary: 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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Year 1

End point values	Placebo	CVC 150 mg
Number of subjects analysed	143	144
Units: participants	24	22

No statistical analyses for this end point

Secondary: 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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Year 2

End point values	Placebo	CVC 150 mg
Number of subjects analysed	72	215
Units: participants	6	20

No statistical analyses for this end point

Secondary: 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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Year 1

End point values	Placebo	CVC 150 mg
Number of subjects analysed	143	144
Units: participants	7	6

No statistical analyses for this end point

Secondary: 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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Year 2

End point values	Placebo	CVC 150 mg
Number of subjects analysed	72	215
Units: participants	1	9

No statistical analyses for this end point

Secondary: Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1

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End point title

Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1

End point description

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

End point type

Secondary

End point timeframe

Year 1

End point values	Placebo	CVC 150 mg
Number of subjects analysed	123	121
Units: percent collagen area
arithmetic mean (standard deviation)
Baseline	2.49 ( 2.004 )	2.37 ( 1.827 )
Change from Baseline to Year 1	-0.14 ( 2.389 )	0.02 ( 2.357 )

No statistical analyses for this end point

Secondary: Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2

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End point title

Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2

End point description

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

End point type

Secondary

End point timeframe

Year 2

End point values	Placebo	CVC 150 mg
Number of subjects analysed	51	150
Units: percent collagen area
arithmetic mean (standard deviation)
Baseline	2.57 ( 2.156 )	2.48 ( 1.892 )
Change from Baseline to Year 2	-0.17 ( 2.576 )	-0.09 ( 2.160 )

No statistical analyses for this end point

Secondary: Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1

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End point title

Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1

End point description

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

End point type

Secondary

End point timeframe

Baseline (Day 1) to Year 1

End point values	Placebo	CVC 150 mg
Number of subjects analysed	122	122
Units: percentage of α-SMA positive cells/area
arithmetic mean (standard deviation)
Baseline	2.41 ( 2.264 )	2.49 ( 2.885 )
Change from Baseline to Year 1	0.77 ( 3.529 )	0.79 ( 3.861 )

No statistical analyses for this end point

Secondary: Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2

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End point title

Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2

End point description

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

End point type

Secondary

End point timeframe

Baseline (Day 1) to Year 2

End point values	Placebo	CVC 150 mg
Number of subjects analysed	52	152
Units: percentage of α-SMA positive cells/area
arithmetic mean (standard deviation)
Baseline	2.47 ( 2.679 )	2.44 ( 2.505 )
Change from Baseline to Year 2	2.10 ( 4.533 )	1.38 ( 3.793 )

No statistical analyses for this end point

Secondary: Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1

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End point title

Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1

End point description

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

End point type

Secondary

End point timeframe

Year 1

End point values	Placebo	CVC 150 mg
Number of subjects analysed	123	121
Units: percent fat area
arithmetic mean (standard deviation)
Baseline	22.42 ( 10.016 )	21.58 ( 8.740 )
Change from Baseline to Year 1	-3.39 ( 9.120 )	-2.79 ( 8.127 )

No statistical analyses for this end point

Secondary: Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2

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End point title

Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2

End point description

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

End point type

Secondary

End point timeframe

Year 2

End point values	Placebo	CVC 150 mg
Number of subjects analysed	50	150
Units: percent fat area
arithmetic mean (standard deviation)
Baseline	23.30 ( 10.300 )	21.62 ( 9.575 )
Change from Baseline to Year 2	-5.06 ( 9.739 )	-2.96 ( 9.230 )

No statistical analyses for this end point

Secondary: Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1

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End point title

Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1

End point description

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

End point type

Secondary

End point timeframe

Baseline (Day 1) to Year 1

End point values	Placebo	CVC 150 mg
Number of subjects analysed	126	126
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (NASH CRN Fibrosis Stage)	2.1 ( 0.86 )	2.0 ( 0.85 )
Change from Baseline (NASH CRN Fibrosis Stage)	0.2 ( 0.92 )	0.0 ( 1.00 )
Baseline (Ishak Fibrosis Stage)	2.2 ( 1.00 )	2.2 ( 1.05 )
Change from Baseline (Ishak Fibrosis Stage)	0.2 ( 1.10 )	0.0 ( 1.20 )

No statistical analyses for this end point

Secondary: Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2

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End point title

Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2

End point description

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 negative change from Baseline indicates improvement. FAS in Year 2 included all participants who were randomised and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analysed is the number of participants with data available for analysis at the given time-point.

End point type

Secondary

End point timeframe

Baseline (Day 1) to Year 2

End point values	Placebo	CVC 150 mg
Number of subjects analysed	54	159
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (NASH CRN Fibrosis Stage)	2.0 ( 0.88 )	2.1 ( 0.85 )
Change from Baseline (NASH CRN Fibrosis Stage)	0.0 ( 0.89 )	0.0 ( 1.08 )
Baseline (Ishak Fibrosis Stage)	2.1 ( 1.00 )	2.2 ( 1.04 )
Change from Baseline (Ishak Fibrosis Stage)	0.1 ( 1.21 )	0.0 ( 1.26 )

No statistical analyses for this end point

Secondary: Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1

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End point title

Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1

End point description

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

End point type

Secondary

End point timeframe

Baseline (Day 1) to Year 1

End point values	Placebo	CVC 150 mg
Number of subjects analysed	126	124
Units: score on a scale
arithmetic mean (standard deviation)
Baseline	1.6 ( 0.63 )	1.5 ( 0.64 )
Change from Baseline to Year 1	0.0 ( 0.76 )	0.2 ( 0.74 )

No statistical analyses for this end point

Secondary: Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2

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End point title

Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2

End point description

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

End point type

Secondary

End point timeframe

Baseline (Day 1) to Year 2

End point values	Placebo	CVC 150 mg
Number of subjects analysed	54	159
Units: score on a scale
arithmetic mean (standard deviation)
Baseline	1.5 ( 0.64 )	1.6 ( 0.67 )
Change from Baseline to Year 1	0.1 ( 0.75 )	0.2 ( 0.72 )

No statistical analyses for this end point

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12

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End point title

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	143	144
Units: ratio
arithmetic mean (standard deviation)
Baseline (Month 3) (n=127,133)	0.649 ( 0.3661 )	0.596 ( 0.4089 )
Change from Baseline to Month 3 (n=127,133)	-0.005 ( 0.3012 )	0.065 ( 0.3152 )
Baseline (Month 6) (n=128,127)	0.663 ( 0.3811 )	0.578 ( 0.3794 )
Change from Baseline to Month 6 (n=128,127)	0.009 ( 0.3968 )	0.102 ( 0.4536 )
Baseline (Month 12) (n=117,117)	0.662 ( 0.3915 )	0.580 ( 0.3939 )
Change from Baseline to Month 12 (n=117,117)	0.066 ( 0.5572 )	0.093 ( 0.3852 )

No statistical analyses for this end point

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24

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End point title

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	72	215
Units: ratio
arithmetic mean (standard deviation)
Baseline (Month 15) (n=59, 167)	0.619 ( 0.3157 )	0.584 ( 0.3572 )
Change from Baseline to Month 15 (n=59, 167)	0.002 ( 0.3422 )	0.118 ( 0.4095 )
Baseline (Month 18) (n=53, 167)	0.620 ( 0.3305 )	0.586 ( 0.3612 )
Change from Baseline to Month 18 (n=53, 167)	0.038 ( 0.4033 )	0.133 ( 0.4269 )
Baseline (Month 24) (n=56, 158)	0.633 ( 0.3156 )	0.584 ( 0.3617 )
Change from Baseline to Month 24 (n=56, 158)	-0.020 ( 0.4721 )	0.086 ( 0.4153 )

No statistical analyses for this end point

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12

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End point title

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	143	144
Units: ratio
arithmetic mean (standard deviation)
Baseline (Month 3) (n=127, 133)	1.444 ( 0.6753 )	1.417 ( 0.6893 )
Change from Baseline to Month 3 (n=127, 133)	0.021 ( 0.4236 )	0.071 ( 0.4209 )
Baseline (Month 6) (n=128, 127)	1.500 ( 0.7268 )	1.388 ( 0.6771 )
Change from Baseline to Month 6 (n=128, 127)	0.015 ( 0.4591 )	0.099 ( 0.5246 )
Baseline (Month 12) (n=117, 117)	1.503 ( 0.7442 )	1.398 ( 0.6834 )
Change from Baseline to Month 12 (n=117, 117)	0.106 ( 0.6876 )	0.117 ( 0.5069 )

No statistical analyses for this end point

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24

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End point title

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	72	215
Units: ratio
arithmetic mean (standard deviation)
Baseline (Month 15) (n=59, 167)	1.409 ( 0.6706 )	1.440 ( 0.6714 )
Change from Baseline to Month 15 (n=59, 167)	0.075 ( 0.5982 )	0.213 ( 0.6462 )
Baseline (Month 18) (n=53, 167)	1.389 ( 0.6699 )	1.440 ( 0.6895 )
Change from Baseline to Month 18 (n=53, 167)	0.094 ( 0.5891 )	0.219 ( 0.5559 )
Baseline (Month 24) (n=56, 158)	1.426 ( 0.6841 )	1.444 ( 0.6838 )
Change from Baseline to Month 24 (n=56, 158)	0.064 ( 0.8103 )	0.166 ( 0.6086 )

No statistical analyses for this end point

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12

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End point title

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12

End point description

Hyaluronic acid is a non-invasive hepatic fibrosis marker. A negative change from Baseline indicates decreased fibrosis. FAS in Year 1 included all participants who were randomised and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

Baseline (Month 0) to Months 6 and 12

End point values	Placebo	CVC 150 mg
Number of subjects analysed	143	144
Units: ng/mL
arithmetic mean (standard deviation)
Baseline (Month 6) (n=128, 128)	68.7 ( 107.63 )	68.2 ( 78.88 )
Change from Baseline to Month 6 (n=128, 128)	-2.4 ( 75.03 )	10.7 ( 79.58 )
Baseline (Month 12) (n=122, 121)	70.7 ( 110.49 )	69.5 ( 80.56 )
Change from Baseline to Month 12 (n=122, 121)	-0.2 ( 81.30 )	10.9 ( 58.46 )

No statistical analyses for this end point

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24

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End point title

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24

End point description

Hyaluronic acid is a non-invasive hepatic fibrosis marker. A positive change from Baseline indicates increased fibrosis. FAS in Year 2 included all participants who were randomised and received at least 1 dose of study drug, had a measurable Screening biopsy and had no major eligibility violations. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

Baseline (Month 0) to Months 18 and 24

End point values	Placebo	CVC 150 mg
Number of subjects analysed	72	215
Units: ng/mL
arithmetic mean (standard deviation)
Baseline (Month 18) (n=58, 170)	46.4 ( 32.67 )	79.6 ( 111.36 )
Change from Baseline to Month 18 (n=58, 170)	5.7 ( 34.66 )	1.4 ( 81.20 )
Baseline (Month 24) (n=57, 164)	46.6 ( 32.91 )	79.7 ( 112.46 )
Change from Baseline to Month 24 (n=57, 164)	19.3 ( 70.64 )	13.0 ( 95.00 )

No statistical analyses for this end point

Secondary: Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12

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End point title

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	143	144
Units: ng/mL
arithmetic mean (standard deviation)
Baseline (Month 3) (n=125, 125)	-1.227 ( 1.5255 )	-1.012 ( 1.2558 )
Change from Baseline to Month 3 (n=125, 125)	0.029 ( 0.5150 )	0.087 ( 0.4608 )
Baseline (Month 6) (n=125, 119)	-1.119 ( 1.4935 )	-1.064 ( 1.2403 )
Change from Baseline to Month 6 (n=125, 119)	0.051 ( 0.4747 )	0.094 ( 0.5460 )
Baseline (Month 12) (n=115, 108)	-1.132 ( 1.4609 )	-1.040 ( 1.1393 )
Change from Baseline to Month 12 (n=115, 108)	0.121 ( 0.5117 )	0.139 ( 0.5016 )

No statistical analyses for this end point

Secondary: Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24

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End point title

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	72	215
Units: ng/mL
arithmetic mean (standard deviation)
Baseline (Month 15) (n=59, 158)	-1.252 ( 1.4602 )	-1.051 ( 1.3410 )
Change from Baseline to Month 15 (n=59, 158)	0.057 ( 0.5981 )	0.225 ( 0.5654 )
Baseline (Month 18) (n=53, 158)	-1.284 ( 1.4910 )	-1.057 ( 1.3309 )
Change from Baseline to Month 18 (n=53, 158)	0.046 ( 0.5809 )	0.196 ( 0.5583 )
Baseline (Month 24) (n=54, 147)	-1.245 ( 1.4778 )	-1.100 ( 1.3228 )
Change from Baseline to Month 24 (n=54, 147)	0.046 ( 0.6188 )	0.185 ( 0.6184 )

No statistical analyses for this end point

Secondary: Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12

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End point title

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12

End point description

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

End point type

Secondary

End point timeframe

Baseline (Month 0) to Months 6 and 12

End point values	Placebo	CVC 150 mg
Number of subjects analysed	143	144
Units: ng/mL
arithmetic mean (standard deviation)
Baseline (Month 6) (n=125, 125)	-0.786 ( 0.7179 )	-0.837 ( 0.7238 )
Change from Baseline to Month 6 (n=125, 125)	-0.022 ( 0.4901 )	0.060 ( 0.5228 )
Baseline (Month 12) (n=116, 118)	-0.795 ( 0.7435 )	-0.801 ( 0.7162 )
Change from Baseline to Month 12 (n=116, 118)	-0.064 ( 0.5602 )	0.041 ( 0.5727 )

No statistical analyses for this end point

Secondary: Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24

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End point title

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24

End point description

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

End point type

Secondary

End point timeframe

Baseline (Month 0) to Months 18 and 24

End point values	Placebo	CVC 150 mg
Number of subjects analysed	72	215
Units: ng/mL
arithmetic mean (standard deviation)
Baseline (Month 18) (n=57,164)	-0.931 ( 0.6387 )	-0.758 ( 0.7307 )
Change from Baseline to Month 18 (n=57,164)	-0.129 ( 0.6606 )	-0.087 ( 0.6113 )
Baseline (Month 24) (n=56,157)	-0.940 ( 0.6587 )	-0.765 ( 0.7127 )
Change from Baseline to Month 24 (n=56,157)	-0.024 ( 0.7375 )	0.096 ( 0.6437 )

No statistical analyses for this end point

Secondary: 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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	143	144
Units: U/L
arithmetic mean (standard deviation)
Baseline (Month 3) (n=115, 119)	601.6 ( 431.77 )	594.2 ( 554.20 )
Change from Baseline to Month 3 (n=115, 119)	-56.4 ( 451.14 )	-59.0 ( 485.76 )
Baseline (Month 6) (n=105, 107)	550.3 ( 360.64 )	552.9 ( 393.92 )
Change from Baseline to Month 6 (n=105, 107)	10.6 ( 461.98 )	-26.1 ( 512.88 )
Baseline (Month 12) (n=107, 101)	555.3 ( 356.28 )	567.9 ( 500.53 )
Change from Baseline to Month 12 (n=107, 101)	99.7 ( 824.50 )	107.8 ( 830.28 )

No statistical analyses for this end point

Secondary: 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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	72	215
Units: U/L
arithmetic mean (standard deviation)
CK18M30, Baseline (Month 15(n=51,145)	570.8 ( 297.42 )	536.4 ( 459.06 )
CK18M30,Change from Baseline to Month 15(n=51,145)	-39.6 ( 287.44 )	-13.3 ( 450.16 )
CK18M30, Baseline (Month 18)(n=51,149)	578.8 ( 293.93 )	540.9 ( 453.90 )
CK18M30,Change from Baseline to Month 18(n=51,149)	23.8 ( 402.98 )	57.3 ( 476.92 )
CK18M30, Baseline (Month 24)(n=50,143)	575.4 ( 293.64 )	541.8 ( 462.29 )
CK18M30,Change from Baseline to Month 24(n=50,143)	-30.0 ( 369.60 )	39.7 ( 437.60 )
CK18M65, Baseline (Month 15)(n=51,145)	772.7 ( 337.24 )	687.4 ( 404.83 )
CK18M65,Change from Baseline to Month 15(n=51,145)	134.7 ( 534.46 )	88.6 ( 559.11 )
CK18M65, Baseline (Month 18)(n=51, 149)	777.8 ( 344.07 )	694.8 ( 401.88 )
CK18M65,Change from Baseline to Month 18(n=51,149)	158.0 ( 732.63 )	181.5 ( 620.57 )
CK18M65, Baseline (Month 24)(n=50, 143)	770.2 ( 335.05 )	693.9 ( 409.88 )
CK18M65,Change from Baseline to Month 24(n=50,143)	7.4 ( 570.92 )	124.9 ( 522.08 )

No statistical analyses for this end point

Secondary: Change From Baseline in Weight at Months 3, 6 and 12

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End point title

Change From Baseline in Weight at Months 3, 6 and 12

End point description

A negative change from Baseline represents decreased weight. Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	144	144
Units: kg
arithmetic mean (standard deviation)
Baseline (Month 3) (n=133,138)	97.21 ( 22.368 )	95.59 ( 20.590 )
Change from Baseline to Month 3 (n=133,138)	-0.50 ( 2.652 )	-0.63 ( 2.632 )
Baseline (Month 6) (n=130,132)	97.18 ( 22.224 )	95.18 ( 20.386 )
Change from Baseline to Month 6 (n=130,132)	-0.55 ( 3.319 )	-0.47 ( 3.466 )
Baseline (Month 12) (n=126,122)	96.63 ( 22.139 )	95.06 ( 20.651 )
Change from Baseline to Month 12 (n=126,122)	-0.08 ( 4.301 )	-0.28 ( 4.166 )

No statistical analyses for this end point

Secondary: Change From Baseline in Weight at Months 15, 18 and 24

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End point title

Change From Baseline in Weight at Months 15, 18 and 24

End point description

A negative change from Baseline represents decreased weight. Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	60	182
Units: kg
arithmetic mean (standard deviation)
Baseline (Month 15) (n=59,174)	98.25 ( 24.087 )	95.32 ( 20.749 )
Change from Baseline to Month 15 (n=59,174)	0.15 ( 3.448 )	-0.44 ( 4.257 )
Baseline (Month 18) (n=58,173)	96.98 ( 22.210 )	95.23 ( 20.823 )
Change from Baseline to Month 18 (n=58,173)	0.05 ( 4.194 )	-0.16 ( 4.458 )
Baseline (Month 24) (n=58,166)	96.98 ( 22.210 )	95.19 ( 20.972 )
Change from Baseline to Month 24 (n=58,166)	-0.91 ( 5.649 )	-0.56 ( 5.081 )

No statistical analyses for this end point

Secondary: Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12

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End point title

Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12

End point description

The body mass index is a value derived from the mass (weight in kgs) and height (in centimetres) 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. Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	144	144
Units: kg/m^2
arithmetic mean (standard deviation)
Baseline (Month 3) (n=133,135)	34.129 ( 7.2492 )	33.706 ( 5.7812 )
Change from Baseline to Month 3 (n=133,135)	-0.172 ( 0.9200 )	-0.232 ( 0.9500 )
Baseline (Month 6) (n=130,129)	34.196 ( 7.3086 )	33.547 ( 5.6037 )
Change from Baseline to Month 6 (n=130,129)	-0.182 ( 1.1558 )	-0.196 ( 1.2500 )
Baseline (Month 12) (n=126,119)	34.029 ( 7.1358 )	33.374 ( 5.6631 )
Change from Baseline to Month 12 (n=126,119)	-0.013 ( 1.7507 )	-0.145 ( 1.4891 )

No statistical analyses for this end point

Secondary: Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24

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End point title

Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24

End point description

The body mass index is a value derived from the mass (weight in kgs) and height (in centimetres) 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. Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	60	182
Units: kg/m^2
arithmetic mean (standard deviation)
Baseline (Month 15) (n=59,171)	34.713 ( 8.0431 )	33.392 ( 5.9669 )
Change from Baseline to Month 15 (n=59,171)	-0.006 ( 1.2799 )	-0.113 ( 1.6311 )
Baseline (Month 18) (n=58,170)	34.473 ( 7.8964 )	33.345 ( 5.9443 )
Change from Baseline to Month 18 (n=58,170)	-0.039 ( 1.5931 )	-0.040 ( 1.7153 )
Baseline (Month 24) (n=58,163)	34.473 ( 7.8964 )	33.278 ( 6.0012 )
Change from Baseline to Month 24 (n=58,163)	-0.393 ( 2.0613 )	-0.178 ( 1.8515 )

No statistical analyses for this end point

Secondary: Change From Baseline in Waist Circumference at Months 3, 6 and 12

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End point title

Change From Baseline in Waist Circumference at Months 3, 6 and 12

End point description

A negative change from Baseline represents decreased in waist circumference. Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	144	144
Units: cm
arithmetic mean (standard deviation)
Baseline (Month 3) (n=131,135)	110.35 ( 14.866 )	110.25 ( 13.406 )
Change from Baseline to Month 3 (n=131,135)	0.07 ( 5.147 )	0.05 ( 5.396 )
Baseline (Month 6) (n=129,129)	110.42 ( 14.986 )	110.12 ( 13.561 )
Change from Baseline to Month 6 (n=129,129)	0.42 ( 8.827 )	-0.54 ( 5.876 )
Baseline (Month 12) (n=123,118)	109.77 ( 14.617 )	110.02 ( 13.711 )
Change from Baseline to Month 12 (n=123,118)	0.44 ( 6.584 )	-1.10 ( 6.255 )

No statistical analyses for this end point

Secondary: Change From Baseline in Waist Circumference at Months 15, 18 and 24

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End point title

Change From Baseline in Waist Circumference at Months 15, 18 and 24

End point description

A negative change from Baseline represents decreased in waist circumference. Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	60	182
Units: cm
arithmetic mean (standard deviation)
Baseline (Month 15) (n=57,172)	110.19 ( 14.360 )	110.26 ( 14.486 )
Change from Baseline to Month 15 (n=57,172)	0.52 ( 5.520 )	-0.18 ( 6.280 )
Baseline (Month 18) (n=56,170)	109.48 ( 12.703 )	110.25 ( 14.517 )
Change from Baseline to Month 18 (n=56,170)	1.36 ( 7.966 )	-0.21 ( 6.578 )
Baseline (Month 24) (n=58,163)	109.36 ( 12.608 )	110.08 ( 14.606 )
Change from Baseline to Month 24 (n=58,163)	0.11 ( 7.907 )	-1.00 ( 6.503 )

No statistical analyses for this end point

Secondary: Change From Baseline in Hip Circumference at Months 3, 6 and 12

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End point title

Change From Baseline in Hip Circumference at Months 3, 6 and 12

End point description

A negative change from Baseline represents decreased hip circumference. Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	144	144
Units: cm
arithmetic mean (standard deviation)
Baseline (Month 3) (n=129,130)	114.92 ( 16.150 )	112.35 ( 13.802 )
Change from Baseline to Month 3 (n=129,130)	-0.30 ( 4.921 )	-0.11 ( 6.475 )
Baseline (Month 6) (n=127,124)	115.09 ( 16.270 )	112.16 ( 13.320 )
Change from Baseline to Month 6 (n=127,124)	-0.84 ( 4.396 )	-0.18 ( 5.715 )
Baseline (Month 12) (n=121,113)	114.46 ( 15.970 )	111.66 ( 13.376 )
Change from Baseline to Month 12 (n=121,113)	-0.25 ( 5.876 )	-0.08 ( 7.474 )

No statistical analyses for this end point

Secondary: Change From Baseline in Hip Circumference at Months 15, 18 and 24

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End point title

Change From Baseline in Hip Circumference at Months 15, 18 and 24

End point description

A negative change from Baseline represents decreased hip circumference. Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	60	182
Units: cm
arithmetic mean (standard deviation)
Baseline (Month 15) (n=58,165)	114.56 ( 17.500 )	113.00 ( 14.183 )
Change from Baseline to Month 15 (n=58,165)	-0.06 ( 5.361 )	-0.83 ( 7.050 )
Baseline (Month 18) (n=55,162)	114.28 ( 17.871 )	112.70 ( 14.168 )
Change from Baseline to Month 18 (n=55,162)	0.55 ( 7.791 )	-0.90 ( 6.066 )
Baseline (Month 24) (n=58,157)	114.34 ( 17.408 )	112.88 ( 14.225 )
Change from Baseline to Month 24 (n=58,157)	-0.95 ( 7.700 )	-1.21 ( 6.677 )

No statistical analyses for this end point

Secondary: Change From Baseline in Forearm Circumference at Months 3, 6 and 12

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End point title

Change From Baseline in Forearm Circumference at Months 3, 6 and 12

End point description

A negative change from Baseline represents decreased forearm circumference. Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	144	144
Units: cm
arithmetic mean (standard deviation)
Baseline (Month 3) (n=127,132)	32.95 ( 7.346 )	33.38 ( 4.835 )
Change from Baseline to Month 3 (n=127,132)	0.97 ( 6.023 )	0.10 ( 6.486 )
Baseline (Month 6) (n=126,126)	32.70 ( 7.290 )	33.25 ( 4.734 )
Change from Baseline to Month 6 (n=126,126)	0.82 ( 6.748 )	-0.01 ( 3.447 )
Baseline (Month 12) (n=120,115)	32.51 ( 7.277 )	33.09 ( 4.771 )
Change from Baseline to Month 12 (n=120,115)	0.83 ( 6.656 )	-0.43 ( 3.516 )

No statistical analyses for this end point

Secondary: Change From Baseline in Forearm Circumference at Months 15, 18 and 24

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End point title

Change From Baseline in Forearm Circumference at Months 15, 18 and 24

End point description

A negative change from Baseline represents decreased forearm circumference. Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	60	182
Units: cm
arithmetic mean (standard deviation)
Baseline (Month 15) (n=57,168)	32.88 ( 7.783 )	32.91 ( 5.662 )
Change from Baseline to Month 15 (n=57,168)	1.61 ( 6.534 )	0.01 ( 5.052 )
Baseline (Month 18) (n=55,166)	32.63 ( 7.718 )	32.87 ( 5.696 )
Change from Baseline to Month 18 (n=55,166)	1.79 ( 6.715 )	0.02 ( 4.709 )
Baseline (Month 24) (n=57,159)	32.79 ( 7.660 )	33.02 ( 5.561 )
Change from Baseline to Month 24 (n=57,159)	0.78 ( 6.124 )	-0.64 ( 4.408 )

No statistical analyses for this end point

Secondary: Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12

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End point title

Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12

End point description

A negative change from Baseline represents decreased tricep skinfold thickness. Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	144	144
Units: mm
arithmetic mean (standard deviation)
Baseline (Month 3) (n=127,131)	28.32 ( 13.677 )	25.41 ( 12.593 )
Change from Baseline to Month 3 (n=127,131)	-1.21 ( 6.548 )	-0.62 ( 8.704 )
Baseline (Month 6) (n=128,125)	28.53 ( 13.763 )	25.38 ( 12.769 )
Change from Baseline to Month 6 (n=128,125)	-2.72 ( 8.091 )	-1.52 ( 9.287 )
Baseline (Month 12) (n=122,115)	28.54 ( 13.981 )	25.14 ( 12.969 )
Change from Baseline to Month 12 (n=122,115)	-1.34 ( 9.389 )	-0.26 ( 10.653 )

No statistical analyses for this end point

Secondary: Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24

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End point title

Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24

End point description

A negative change from Baseline represents decreased tricep skinfold thickness. Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. 'n' is the number of participants with data available for analysis at both Baseline and the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Placebo	CVC 150 mg
Number of subjects analysed	60	182
Units: mm
arithmetic mean (standard deviation)
Baseline (Month 15) (n=57,170)	29.84 ( 14.422 )	25.41 ( 13.212 )
Change from Baseline to Month 15 (n=57,170)	-1.45 ( 9.364 )	-1.59 ( 8.918 )
Baseline (Month 18) (n=55,168)	29.84 ( 14.655 )	25.07 ( 12.856 )
Change from Baseline to Month 18 (n=55,168)	-2.27 ( 8.854 )	-2.64 ( 8.864 )
Baseline (Month 24) (n=56,160)	29.91 ( 14.532 )	24.82 ( 13.025 )
Change from Baseline to Month 24 (n=56,160)	-3.11 ( 8.553 )	-1.33 ( 10.521 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline to Year 2

Adverse event reporting additional description

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

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

CVC 150mg/CVC 150 mg

Reporting group description

CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2.

Reporting group title

Placebo/Cenicriviroc (CVC) 150 mg

Reporting group description

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.

Reporting group title

Placebo/Placebo

Reporting group description

Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.

Serious adverse events	CVC 150mg/CVC 150 mg	Placebo/Cenicriviroc (CVC) 150 mg	Placebo/Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	25 / 144 (17.36%)	8 / 72 (11.11%)	12 / 72 (16.67%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic neoplasm
subjects affected / exposed	0 / 144 (0.00%)	1 / 72 (1.39%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral nerve sheath tumour malignant
subjects affected / exposed	0 / 144 (0.00%)	1 / 72 (1.39%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemangioma of skin
subjects affected / exposed	0 / 144 (0.00%)	1 / 72 (1.39%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	2 / 144 (1.39%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lung disorder
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Bipolar disorder
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Blood triglycerides increased
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Accidental overdose
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ankle fracture
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Joint injury
subjects affected / exposed	0 / 144 (0.00%)	1 / 72 (1.39%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Laceration
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lumbar vertebral fracture
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 144 (0.00%)	1 / 72 (1.39%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Traumatic haemothorax
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Procedural pain
subjects affected / exposed	0 / 144 (0.00%)	1 / 72 (1.39%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coronary artery occlusion
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocardial ischaemia
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Convulsion
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Loss of consciousness
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Paraesthesia
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VIIth nerve paralysis
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Inguinal hernia
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 144 (0.00%)	1 / 72 (1.39%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colitis ischaemic
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Large intestine polyp
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peritoneal haemorrhage
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vasculitis gastrointestinal
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 144 (0.00%)	1 / 72 (1.39%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal failure acute
subjects affected / exposed	0 / 144 (0.00%)	1 / 72 (1.39%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bladder dysplasia
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	2 / 144 (1.39%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psoriatic arthropathy
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 144 (0.00%)	1 / 72 (1.39%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Type 2 diabetes mellitus
subjects affected / exposed	1 / 144 (0.69%)	0 / 72 (0.00%)	0 / 72 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypovolaemia
subjects affected / exposed	0 / 144 (0.00%)	0 / 72 (0.00%)	1 / 72 (1.39%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	CVC 150mg/CVC 150 mg	Placebo/Cenicriviroc (CVC) 150 mg	Placebo/Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	127 / 144 (88.19%)	59 / 72 (81.94%)	60 / 72 (83.33%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	15 / 144 (10.42%)	9 / 72 (12.50%)	5 / 72 (6.94%)
occurrences all number	24	11	7
Blood creatine phosphokinase increased
subjects affected / exposed	3 / 144 (2.08%)	5 / 72 (6.94%)	0 / 72 (0.00%)
occurrences all number	3	5	0
Injury, poisoning and procedural complications
Procedural pain
subjects affected / exposed	5 / 144 (3.47%)	2 / 72 (2.78%)	9 / 72 (12.50%)
occurrences all number	7	2	11
Vascular disorders
Hypertension
subjects affected / exposed	10 / 144 (6.94%)	4 / 72 (5.56%)	3 / 72 (4.17%)
occurrences all number	10	4	3
Nervous system disorders
Headache
subjects affected / exposed	24 / 144 (16.67%)	15 / 72 (20.83%)	9 / 72 (12.50%)
occurrences all number	28	18	9
Dizziness
subjects affected / exposed	13 / 144 (9.03%)	0 / 72 (0.00%)	5 / 72 (6.94%)
occurrences all number	16	0	6
General disorders and administration site conditions
Fatigue
subjects affected / exposed	24 / 144 (16.67%)	10 / 72 (13.89%)	13 / 72 (18.06%)
occurrences all number	35	12	16
Oedema peripheral
subjects affected / exposed	5 / 144 (3.47%)	5 / 72 (6.94%)	3 / 72 (4.17%)
occurrences all number	6	5	3
Pyrexia
subjects affected / exposed	8 / 144 (5.56%)	4 / 72 (5.56%)	1 / 72 (1.39%)
occurrences all number	8	4	1
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	16 / 144 (11.11%)	12 / 72 (16.67%)	10 / 72 (13.89%)
occurrences all number	22	17	11
Diarrhoea
subjects affected / exposed	32 / 144 (22.22%)	14 / 72 (19.44%)	15 / 72 (20.83%)
occurrences all number	38	19	17
Abdominal pain
subjects affected / exposed	18 / 144 (12.50%)	6 / 72 (8.33%)	11 / 72 (15.28%)
occurrences all number	20	9	11
Nausea
subjects affected / exposed	28 / 144 (19.44%)	6 / 72 (8.33%)	8 / 72 (11.11%)
occurrences all number	41	7	11
Abdominal distension
subjects affected / exposed	13 / 144 (9.03%)	4 / 72 (5.56%)	0 / 72 (0.00%)
occurrences all number	15	4	0
Constipation
subjects affected / exposed	13 / 144 (9.03%)	4 / 72 (5.56%)	6 / 72 (8.33%)
occurrences all number	16	4	6
Flatulence
subjects affected / exposed	9 / 144 (6.25%)	3 / 72 (4.17%)	2 / 72 (2.78%)
occurrences all number	10	3	2
Gastrooesophageal reflux disease
subjects affected / exposed	6 / 144 (4.17%)	3 / 72 (4.17%)	4 / 72 (5.56%)
occurrences all number	6	3	4
Vomiting
subjects affected / exposed	18 / 144 (12.50%)	3 / 72 (4.17%)	5 / 72 (6.94%)
occurrences all number	20	3	5
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	16 / 144 (11.11%)	5 / 72 (6.94%)	6 / 72 (8.33%)
occurrences all number	21	7	6
Oropharyngeal pain
subjects affected / exposed	13 / 144 (9.03%)	3 / 72 (4.17%)	4 / 72 (5.56%)
occurrences all number	14	3	5
Nasal congestion
subjects affected / exposed	8 / 144 (5.56%)	0 / 72 (0.00%)	2 / 72 (2.78%)
occurrences all number	8	0	2
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	10 / 144 (6.94%)	3 / 72 (4.17%)	5 / 72 (6.94%)
occurrences all number	14	3	7
Rash
subjects affected / exposed	12 / 144 (8.33%)	3 / 72 (4.17%)	8 / 72 (11.11%)
occurrences all number	14	5	8
Psychiatric disorders
Insomnia
subjects affected / exposed	10 / 144 (6.94%)	2 / 72 (2.78%)	2 / 72 (2.78%)
occurrences all number	10	2	2
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	11 / 144 (7.64%)	11 / 72 (15.28%)	12 / 72 (16.67%)
occurrences all number	13	12	13
Myalgia
subjects affected / exposed	11 / 144 (7.64%)	5 / 72 (6.94%)	3 / 72 (4.17%)
occurrences all number	13	5	4
Muscle spasms
subjects affected / exposed	15 / 144 (10.42%)	4 / 72 (5.56%)	2 / 72 (2.78%)
occurrences all number	16	4	2
Arthralgia
subjects affected / exposed	23 / 144 (15.97%)	4 / 72 (5.56%)	4 / 72 (5.56%)
occurrences all number	30	4	4
Pain in extremity
subjects affected / exposed	14 / 144 (9.72%)	1 / 72 (1.39%)	6 / 72 (8.33%)
occurrences all number	17	1	6
Infections and infestations
Urinary tract infection
subjects affected / exposed	17 / 144 (11.81%)	10 / 72 (13.89%)	4 / 72 (5.56%)
occurrences all number	24	12	4
Nasopharyngitis
subjects affected / exposed	21 / 144 (14.58%)	9 / 72 (12.50%)	7 / 72 (9.72%)
occurrences all number	25	11	9
Upper respiratory tract infection
subjects affected / exposed	18 / 144 (12.50%)	9 / 72 (12.50%)	8 / 72 (11.11%)
occurrences all number	24	10	8
Influenza
subjects affected / exposed	11 / 144 (7.64%)	3 / 72 (4.17%)	3 / 72 (4.17%)
occurrences all number	12	3	4
Sinusitis
subjects affected / exposed	18 / 144 (12.50%)	3 / 72 (4.17%)	9 / 72 (12.50%)
occurrences all number	22	5	12
Bronchitis
subjects affected / exposed	10 / 144 (6.94%)	1 / 72 (1.39%)	7 / 72 (9.72%)
occurrences all number	12	1	10
Ear infection
subjects affected / exposed	5 / 144 (3.47%)	2 / 72 (2.78%)	4 / 72 (5.56%)
occurrences all number	5	2	4
Gastroenteritis
subjects affected / exposed	3 / 144 (2.08%)	1 / 72 (1.39%)	4 / 72 (5.56%)
occurrences all number	3	1	5
Metabolism and nutrition disorders
Type 2 diabetes mellitus
subjects affected / exposed	6 / 144 (4.17%)	5 / 72 (6.94%)	4 / 72 (5.56%)
occurrences all number	7	6	4
Hyperglycaemia
subjects affected / exposed	0 / 144 (0.00%)	4 / 72 (5.56%)	2 / 72 (2.78%)
occurrences all number	0	4	2

More information

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Were there any global substantial amendments to the protocol? Yes

12 Dec 2014

Increase in no. of study centres, inclusion criteria changes to increase age range, clarify, or correct typographical errors.

15 Jun 2016

Updated the study objectives and endpoints.

06 Jun 2017

Added additional secondary and tertiary objectives and efficacy endpoints. Added summary of additional efficacy analyses to be performed at Year 2.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: CENTAUR: Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Subjects with Liver Fibrosis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants 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

Primary: Number of Participants 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

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: Number of Participants with Complete Resolution of Steatohepatitis with no Concurrent Worsening of Fibrosis Stage at Year 1

Secondary: Number of Participants with Complete Resolution of Steatohepatitis with no Concurrent Worsening of Fibrosis Stage at Year 1

Secondary: Number of Participants with Complete Resolution of Steatohepatitis with no Concurrent Worsening of Fibrosis Stage at Year 2

Secondary: Number of Participants with Complete Resolution of Steatohepatitis with no Concurrent Worsening of Fibrosis Stage at Year 2

Secondary: Number of Participants with Improvement in Fibrosis by at Least 1 Stage (NASH CRN system) and no Worsening of Steatohepatitis at Year 1

Secondary: Number of Participants with Improvement in Fibrosis by at Least 1 Stage (NASH CRN system) and no Worsening of Steatohepatitis at Year 1

Secondary: Number of Participants with Improvement in Fibrosis by at Least 1 Stage (NASH CRN system) and no Worsening of Steatohepatitis at Year 2

Secondary: Number of Participants with Improvement in Fibrosis by at Least 1 Stage (NASH CRN system) and no Worsening of Steatohepatitis at Year 2

Secondary: Number of Participants with Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation

Secondary: Number of Participants with Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation

Secondary: Number of Participants with Clinically Significant Changes in Vital Signs

Secondary: Number of Participants with Clinically Significant Changes in Vital Signs

Secondary: Number of Participants with Clinical Laboratory Abnormalities

Secondary: Number of Participants with Clinical Laboratory Abnormalities

Secondary: Number of Participants with Clinically Abnormal Electrocardiogram (ECG) Findings

Secondary: Number of Participants with Clinically Abnormal Electrocardiogram (ECG) Findings

Secondary: Number of Participants with Hepatic Histological Improvement in NAS at Year 2

Secondary: Number of Participants with Hepatic Histological Improvement in NAS at Year 2

Secondary: Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1

Secondary: Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1

Secondary: Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2

Secondary: Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1

Secondary: Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1

Secondary: Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2

Secondary: Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2

Secondary: Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1

Secondary: Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1

Secondary: Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2

Secondary: Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2

Secondary: Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1

Secondary: Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1

Secondary: Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2

Secondary: Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2

Secondary: Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1

Secondary: Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1

Secondary: Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2

Secondary: Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2

Secondary: Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1

Secondary: Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1

Secondary: Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2

Secondary: Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24

Secondary: Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24

Secondary: Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12

Secondary: Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12

Clinical Trial Results:
CENTAUR: Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Subjects with Liver Fibrosis