Open-label Rollover Study of Cenicriviroc for the Treatment of Liver Fibrosis in Adult Subjects With Nonalcoholic Steatohepatitis (NASH)
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis, Liver Cirrhosis, Non-alcoholic Fatty Liver Disease
Sponsor: Tobira Therapeutics, Inc.

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Cenicriviroc mesylate
Clinical Study Protocol 3152-201-002
Page 1 of 83
Amendment 1
19-May-21
Title:
Open-label Rollover Study of Cenicriviroc for the 
Treatment of Liver Fibrosis in Adult Subjects with 
Nonalcoholic Steatohepatitis (NASH) 
Protocol Number:
3152-201-002
Product:
Cenicriviroc (CVC)
Phase of Study:
2
Sponsor:
Tobira Therapeutics, Inc., a subsidiary of Allergan plc
701 Gateway Blvd, Suite 300
South San Francisco, CA 94080
United States of America
EudraCT Number:
2016-004754-15
Date of Protocol
01 December 2016
Date of Global
Amendment 1
14 Apr 2018

Tobira Therapeutics, Inc., a subsidiary of Allergan plc
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Clinical Study Protocol 3152-201-002
Page 2 of 83
 Amendment 1
19-May-21
Purpose of Amendment
The purpose of Global Protocol Amendment 1 (dated 14 Apr 2018) for Study 3152-201-002 
is to provide details regarding the rollover of additional subjects from the AURORA Study 
(3152-301-002) into Study 3152-201-002.
A summary of changes is provided in Table 1-1. Additional administrative edits were also 
made, but not specifically noted (eg, corrected spelling, punctuation, grammar, abbreviation, 
and style errors) including global edits required for consistency (eg, “study drug”, “subjects”, 
abbreviation use).
This amendment is considered to be nonsubstantial based on the criteria set forth in 
Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union because it neither significantly impacts the safety or physical/mental 
integrity of subjects nor the scientific value of the study.
Table 1-1
Summary of Changes in Global Protocol Amendment 1
Protocol Sections
Summary of Changes
Rationale for Changes
Section 1 Emergency Contacts
Added “Adverse Events of Special 
Interest”
Administrative addition for 
completeness.
Section 4 Synopsis; Section 5.4 
Study Rationale; Section 7.1 
Overall Study Design and Plan; 
Added text to clarify eligibility 
criteria for subjects from 
AURORA (3152-301-002)
entering this study (3152-201-002).
Subjects from the following studies 
will be eligible to receive 
open-label CVC 150 mg once 
daily:

Subjects who have completed 
both Treatment Period 1 and 
Treatment Period 2 (Year 1 and 
Year 2), of the CENTAUR study 
(652-2-203), regardless of their 
treatment assignment in the 
CENTAUR study (CVC or 
placebo).

Subjects who have completed 
the AURORA study (3152-301-
002) as a result of progression to 
cirrhosis or reaching an 
adjudicated liver-related clinical 
outcome in either Part 1 or Part 2 
of the study, regardless of their 
treatment assignment (CVC or 
placebo). Refer to Section 8.2 for 
additional details. 
Revision needed to enable subjects 
from AURORA to enter the study.

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Amendment 1
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Protocol Sections
Summary of Changes
Rationale for Changes
Section 5.4: The open-label 
rollover protocol will be conducted 
to offer continued access to CVC 
to subjects who completed the 
CENTAUR study, progressed to 
cirrhosis, or reached an adjudicated 
liver related clinical outcome and 
completed the AURORA study.
Section 4 Synopsis; Section 7.1 
Overall Study Design and Plan
Removed the specific regions 
involved from the synopsis; 
updated approximate number of 
study centers.
Administrative revision.
Section 4 Synopsis; Section 8.1 
Number of Subjects
Number of subjects was updated to 
include those from both 
CENTAUR and AURORA.
Subjects from both CENTAUR and 
AURORA sites are included in this 
study.
Section 4 Synopsis;
Updated target population to 
include those from both 
CENTAUR and AURORA.
Subjects from both CENTAUR and 
AURORA sites are included in this 
study.
Section 4 Synopsis; Section 8.2
Inclusion Criteria (#1, 2, )
Revised text to clarify eligibility 
criteria for subjects from 
AURORA (3152-301-002) and 
CENTAUR (652-2-203) to enter 
this study (3152-201-002).
IC 1: Subjects who have either:
Completed both Treatment 
Period 1 and Treatment Period 2 
(Year 1 and Year 2) of the 
CENTAUR study (652-2-203), 
including a Year 2 liver biopsy
Completed the AURORA study
(3152-301-002) as a result of 
reaching an adjudicated 
liver-related clinical outcome in 
Part 1 or Part 2 of the study of:
o Histopathologic progression to 
cirrhosis
o MELD score ≥ 15
o Ascites (requiring intervention, 
ie, large volume paracentesis 
≥1L or initiation of a diuretic)
o Hospitalization (as defined by 
a stay of ≥ 24 hours) for onset of: 
variceal bleed, hepatic 
encephalopathy (defined by a 
West Haven Stage of ≥2), 
spontaneous bacterial peritonitis 
(confirmed by diagnostic 
paracentesis  with positive 
ascitic fluid bacterial culture)
Revision needed to enable subjects 
from AURORA to enter the study
#1: Revised text to clarify eligibility 
criteria for subjects from AURORA 
to enter this study.

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Clinical Study Protocol 3152-201-002
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Amendment 1
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Protocol Sections
Summary of Changes
Rationale for Changes
IC 2: Has been determined to be in 
a stable medical condition 
(minimum of approximately 
3 months from the date of the 
clinical event in AURORA to the 
Baseline Visit of this study) based 
on medical history or physical 
examination, in the opinion of 
investigator. Inclusion criterion 
applies only to subjects coming 
from the AURORA study (3152-
301-002).
#2: To ensure qualified participants 
rollover into this study.

Tobira Therapeutics, Inc., a subsidiary of Allergan plc
Cenicriviroc mesylate
Clinical Study Protocol 3152-201-002
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Amendment 1
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Protocol Sections
Summary of Changes
Rationale for Changes
Section 4 Synopsis; Section 10.1 
Baseline
Added text to clarify eligibility 
criteria for subjects from 
AURORA (3152-301-002)
entering this study (3152-201-002).
Subjects will be required to 
rollover to this continued access 
study within 1 month of 
completing their final visit 
assessments in either the 
CENTAUR study or the AURORA 
study. Eligible subjects who 
completed these studies, prior to 
initiation of this protocol at their 
study center, will be allowed to 
participate in this rollover study.
Text edited to align with revisions 
needed to enable subjects from 
AURORA to enter the study
Section 4 Synopsis; Section 12 
Statistics
Text updated to reflect there would 
be no inferential statistical testing.
Administrative revision for 
accuracy.
Section 4 Synopsis
Sample size was updated to reflect
approximate number of subjects.
Subjects from both CENTAUR and 
AURORA sites are included in this 
study
Section 5.3 Clinical Studies with 
CVC
Updated text to reflect updated 
numbers of patients exposed to 
CVC per January 2018 
Development Safety Update 
Report [DSUR] cutoff
Provides updated exposure numbers
and aligns with AURORA.

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Amendment 1
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Protocol Sections
Summary of Changes
Rationale for Changes
Section 5.3.1 Phase 1 
Pharmacokinetic Studies in 
Healthy Subjects
Section was rewritten to align with 
AURORA.
Section was revised to align with 
AURORA.
Section 5.3.3 Phase 2b Study in 
Subjects with NASH and Liver 
Fibrosis
Section was rewritten to align with 
AURORA.
Revisions required to capture up-to-
date information for this rollover 
study, to distinguish information 
specific to Treatment Period 2 (Year 
2) and Treatment Period 1 (Year 1), 
and to align with AURORA.
Section 7.1; Overall Study Design 
and Plan (Figure 7-1)
Deleted CENTAUR specific text
and updated footnotes.
Revisions to Figure 7-1 Study 
Design Schematic required to
accurately reflect rollover study.
Section 9.1 Treatments 
Administered; Section 9.2.4 Study 
Drug Dispensing and Collection; 
Section 9.4 Study Drug with food 
Administration; Section 11.2 
Assessments of Drug 
Accountability and Medication 
Adherence
Deleted text instructing subjects to 
take the study drug in the morning
and clarified they are to take 1 
table.
Revised for accuracy.
Section 9.2.2 Packaging and 
Labeling; Section 9.8 Treatment 
Adherence; Appendix 20.1 
Schedule of Assessments
Added text specifying visit 
window (± 2 weeks)
Administrative revision.
Section 9.2.5 Investigational 
Product Accountability
Deleted text regarding destruction 
of study drug and referred readers 
to the Pharmacy Manual.
Administrative revision
Section 9.3 Randomization
Clarified subjects will retain their 
subject identification number from 
either the CENTAUR study or 
AURORA study.
Edited to reflect retention of subject 
identification numbers.
Section 9.6 Prior and 
Concomitant Therapy; Appendix 
20.4 Disallowed Medications
Revisions to text were made to 
align with AURORA.
Updated to mirror content and 
revisions in the more recent 
AURORA protocol.
Section 9.7 Additional 
Restrictions and Precautions; 
Section 10.1 Baseline
Deleted text regarding 
photosensitivity.
Text regarding photosensitivity was 
removed for consistency with 
AURORA.
Section 10.3 Discontinuation Visit
Deleted “Early” when referring to 
Discontinuation Visit.
Revisions needed to align with 
changes to the Schedule of 
Assessments
Section 10.3 1-Month Follow-up 
and Section 10.4 Discontinuation 
Visit
Reversed the order of sections so 
Discontinuation Visit precedes 
1-Month Follow-up
Revisions needed to align with 
changes to the Schedule of 
Assessments.

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Protocol Sections
Summary of Changes
Rationale for Changes
Section 10.6 Criteria for 
Discontinuation of Study 
Treatment
Edited text to read as follows:
Study drug must be discontinued in 
the following instances:

Confirmation of ALT or AST 
elevations meeting the following 
criteria for suspected DILI23 (the 
required confirmatory 
measurement should be obtained 
within 48 to 72 hours after the 
laboratory results become 
available):
o When the baseline values are 
< 2 × ULN, discontinue if ALT 
and/or AST increases to 
>3 × ULN and > 5 × baseline 
measure
o When the baseline values are 
≥2 × ULN but < 5 x ULN, 
discontinue if ALT and/or AST 
increases to > 3 × baseline 
measure
o When the baseline values are 
≥5 × ULN, discontinue if ALT 
and/or AST increases to 
> 2 × baseline measure
Section was revised to align with 
AURORA.
Section 11.1.1.1.2 Treatment-
Emergent Adverse Events; 
Section 12.1 Safety
Added definition of TEAE
Clarified data involving TEAEs
Included for completeness and 
clarification.
Section 11.1.1.1.9 Overdose
Edited text to read as follows: 
An overdose is defined as a 
subject’s report of taking more 
than 1 tablet of study drug (ie, 
more than 1 tablet per day of 
CVC). Overdose per se will not be 
reported as an AE or SAE unless it 
is an intentional overdose taken 
with possible suicidal/self-harming 
intent. Such overdoses should be 
reported regardless of sequelae. 
For reporting purposes, overdose 
will be considered an SAE only if 
any of the seriousness criteria are 
met (see definition in 
Section 11.1.1.1.10).
Included for completeness and 
clarification.
Section 11.1.1.1.11 Adverse 
Events of Special Interest
Added text defining AEs of 
Special Interest and reporting 
requirements.
Included to align more closely with 
CPT and other NASH protocols.
Section 11.1.1.5 Reporting of 
Serious Adverse Events
Deleted specific directions where 
to send completed Safety Report 
Forms and referred Section 1 for 
contact information.

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Protocol Sections
Summary of Changes
Rationale for Changes
Section 11.1.1.6 Follow-up of 
AEs and SAEs
Added text expanding the 
definition of which subjects should 
have a PK sample obtained.
Included for completeness and 
clarification.
Section 11.1.2.1 Measurement of 
Laboratory Assessments
Clarified site performing urine 
pregnancy testing.
Administrative revision
Section 11.1.3.2 Grade 3 
Laboratory Abnormality or 
Clinical Event; Excluding ALT 
and AST; Section 11.1.3.3 Grade 
4 Laboratory Abnormality or 
Clinical Event; Excluding ALT 
and AST
ALP and bilirubin were added.
Text was edited to include 
“Confirmatory measurements to be 
obtained within 48 to 72 hours of 
re-occurring Grade 3 laboratory 
abnormalities considered clinically 
nonsignificant, unrelated to study 
drug, and associated with pre-
existing medical history should be 
performed per the discretion of the 
investigator and in consultation 
with the medical monitor.”
Edits made for clarification and 
alignment with AURORA.
Appendix 20.1 Schedule of 
Assessments
Deleted “Period and Open-label 
Treatment” as table headers.
Added Discontinuation Visit and 
corresponding footnote.
Clarified footnote regarding 
rollover requirements. 
Added footnotes clarifying 
continuation of study visits, and 
defining subject visit window.
Included obtaining FSH from 
postmenopausal women only.
Deleted the Note in footnotes; 
deleted “early” when describing 
the Discontinuation Visit.
Renumbered footnotes as needed.
Not applicable
Needed as part of study design.
Needed to align with descriptive 
within the Schedule of Assessment 
table.

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Clinical Study Protocol 3152-201-002
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Protocol Sections
Summary of Changes
Rationale for Changes
Appendix 20.4 Disallowed 
Medications
Revised the list and tables of 
disallowed medications. Added a 
table identifying drugs to be taken
with precaution during intake of 
study drug. Revision now allow for 
coadministration of P-gp inhibitors 
with CVC.
Modifications required for 
consistency with AURORA

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Clinical Study Protocol 3152-201-002
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1. EMERGENCY CONTACTS
In emergency situations, the investigator should contact the clinical research associate or 
medical monitor assigned to the site. Please refer to the site study binder for contact details.
Serious Adverse Event/Pregnancy Reporting/Adverse Events of Special Interest
Email: 
Fax: 
(Back-up Fax: 

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2. TABLE OF CONTENTS
1.
EMERGENCY CONTACTS ............................................................................................... 10
2.
TABLE OF CONTENTS...................................................................................................... 11
2.1.
List of In-Text Tables............................................................................................... 13
2.2.
List of In-Text Figures ............................................................................................. 13
3.
LIST OF ABBREVIATIONS............................................................................................... 14
4.
SYNOPSIS ............................................................................................................................. 16
5.
INTRODUCTION................................................................................................................. 19
5.1.
Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis................... 19
5.2.
CVC Mechanism of Action...................................................................................... 19
5.3.
Clinical Studies with CVC....................................................................................... 20
5.3.1.
Phase 1 Pharmacokinetic Studies in Healthy Subjects ............................ 20
5.3.2.
Phase 1 Pharmacokinetic Study in Subjects with Hepatic 
Impairment .................................................................................................. 21
5.3.3.
Phase 2b Study in Subjects with NASH and Liver Fibrosis.................... 22
5.4.
Study Rationale ........................................................................................................ 29
5.5.
Dose Rationale .......................................................................................................... 30
6.
STUDY OBJECTIVES......................................................................................................... 31
7.
INVESTIGATIONAL PLAN............................................................................................... 32
7.1.
Overall Study Design and Plan ............................................................................... 32
8.
STUDY POPULATION........................................................................................................ 33
8.1.
Number of Subjects.................................................................................................. 33
8.2.
Inclusion Criteria ..................................................................................................... 33
8.3.
Exclusion Criteria .................................................................................................... 34
9.
TREATMENTS..................................................................................................................... 35
9.1.
Treatments Administered........................................................................................ 35
9.2.
Study Drug................................................................................................................ 35
9.2.1.
Investigational Product............................................................................... 35
9.2.2.
Packaging and Labeling.............................................................................. 35
9.2.3.
Storage.......................................................................................................... 35
9.2.4.
Study Drug Dispensing and Collection...................................................... 35
9.2.5.
Investigational Product Accountability..................................................... 36
9.3.
Randomization.......................................................................................................... 36
9.4.
Study Drug Administration..................................................................................... 36
9.5.
Blinding ..................................................................................................................... 37
9.6.
Prior and Concomitant Therapy............................................................................. 37
9.7.
Additional Restrictions and Precautions................................................................ 39
9.8.
Treatment Adherence .............................................................................................. 39
10.
STUDY PROCEDURES....................................................................................................... 40
10.1.
Baseline...................................................................................................................... 40

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10.2.
Open-label Treatment Period (Months 3, 6, 9, 12, 15, 18, 21, 24, etc., until 
CVC becomes commercially available or if development is discontinued, as 
applicable)................................................................................................................. 41
10.3.
Discontinuation Visit................................................................................................ 41
10.4.
1-Month Follow-up................................................................................................... 42
10.5.
Missed Scheduled Visits........................................................................................... 42
10.6.
Criteria for Discontinuation of Study Treatment.................................................. 42
11.
STUDY ASSESSMENTS...................................................................................................... 44
11.1.
Assessments of Safety............................................................................................... 44
11.1.1. Adverse Events and Serious Adverse Events............................................ 44
11.1.2. Laboratory Assessments............................................................................. 51
11.1.3. Toxicity Management ................................................................................. 51
11.2.
Assessments of Drug Accountability and Medication Adherence........................ 59
12.
STATISTICS ......................................................................................................................... 60
12.1 
Safety ......................................................................................................................... 60
13.
QUALITY CONTROL AND QUALITY ASSURANCE................................................... 61
13.1.
Sponsor Audits.......................................................................................................... 61
13.2.
Inspection by Regulatory Authorities..................................................................... 61
14.
ETHICS AND PROTECTION OF HUMAN SUBJECTS ................................................ 62
14.1.
Compliance Statement ............................................................................................. 62
14.2.
Institutional Review Board/Independent Ethics Committee................................ 62
14.3.
Informed Consent..................................................................................................... 63
14.4.
Subject Confidentiality ............................................................................................ 63
14.5.
Study Conduct .......................................................................................................... 64
14.6.
Study Discontinuation.............................................................................................. 64
15.
DATA HANDLING AND RECORD KEEPING ............................................................... 65
15.1.
Data Management Responsibilities......................................................................... 65
15.2.
Data Handling and Record Keeping....................................................................... 65
15.2.1. Data Collection and Retrieval .................................................................... 65
15.2.2. Records Retention ....................................................................................... 65
15.2.3. Study Monitoring and Access to Source Documents................................ 66
16.
PUBLICATION POLICY .................................................................................................... 67
17.
REFERENCES...................................................................................................................... 69
18.
SPONSOR’S SIGNATURE PAGE...................................................................................... 71
19.
INVESTIGATOR’S SIGNATURE PAGE.......................................................................... 72
20.
APPENDICES ....................................................................................................................... 73
20.1.
Schedule of Assessments .......................................................................................... 74
20.2.
National Cancer Institute Common Terminology Criteria for Adverse 
Events (NCI CTCAE) .............................................................................................. 76
20.3.
Information on Contraception Effectiveness......................................................... 78
20.4.
Disallowed Medications ........................................................................................... 79
20.5.
Clinical Laboratory Tests........................................................................................ 82

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2.1.
List of In-Text Tables
Table 1-1
Summary of Changes in Global Protocol Amendment 1..................................2
Table 5-1
CENTAUR Study: Effect of 1 Year of Treatment with CVC Versus Placebo 
on Fibrosis Endpoints (Year 1 Data) ................................................................24
Table 11-1
Management of Subjects with Confirmed ALP, ALT, AST, or Bilirubin 
Elevations With or Without Liver-related Clinical Symptoms......................56
Table 11-2
Reference Ranges for Key Liver Parameters ..................................................58
Table 20-1
Schedule of Assessments ....................................................................................74
2.2.
List of In-Text Figures
Figure 7-1
Study Design Schematic.....................................................................................32

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3. LIST OF ABBREVIATIONS
Abbreviation
Definition 
ADL
activities of daily living
ADR
adverse drug reaction
AE
adverse event
AESI
adverse event(s) of special interest
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANA
antinuclear antibody
AST
aspartate aminotransferase
BCRP
breast cancer resistance protein 
BUN
blood urea nitrogen
CCR
C-C chemokine receptor
CI
confidence interval
Cmax
maximum concentration of drug
Cmin
minimum plasma concentration
CPK
creatine phosphokinase
CRN
Clinical Research Network 
CVC
cenicriviroc
CYP
cytochrome P450
DILI
drug-induced liver injury
ECmin50
half-maximal response 
ECG
electrocardiogram
eCRF
electronic case report form
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
HCC
hepatocellular carcinoma 
HRT
hormonal replacement therapy
ICF
informed consent form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IgG
immunoglobulin G
INR
international normalized ratio
IRB
Institutional Review Board

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Abbreviation
Definition 
ITT
intent-to-treat
LC1
liver cytosol type 1
LDH
lactate dehydrogenase
LKM1
liver/kidney microsome type 1
MedDRA
Medical Dictionary for Regulatory Activities
MELD
model for end-stage liver disease
MIP
macrophage inflammatory protein
mITT
modified intent-to-treat
NAFLD
nonalcoholic fatty liver disease
NAS
a nonalcoholic fatty liver disease activity score 
NASH
nonalcoholic steatohepatitis
NCI CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
PD
pharmacodynamic
P-gp
P-glycoprotein
PK
pharmacokinetic
PPI
proton pump inhibitor
RANTES
regulated on activation normal T-cell expressed and secreted
SAE
serious adverse event
SAR
suspected adverse reaction
SMA
smooth muscle antibodies
SUSAR
suspected unexpected serious adverse reaction
t1/2
half-life
T2DM
type-2 diabetes mellitus
TE
transient elastography
TEAE
treatment-emergent adverse event
tmax
time to maximum plasma concentration
Tobira
Tobira Therapeutics, Inc., a subsidiary of Allergan plc
ULN
upper limit of normal
US
United States 

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4. SYNOPSIS
Title
Open-label Rollover Study of Cenicriviroc for the Treatment of Liver Fibrosis in 
Adult Subjects with Nonalcoholic Steatohepatitis (NASH)
Study Number 
3152-201-002
Clinical Phase
2
Indication
Treatment of liver fibrosis in adult subjects with NASH 
Objectives
Study Objectives:

To provide open-label treatment with cenicriviroc (CVC) to subjects who 
have previously participated in CVC studies

To assess the long-term safety of continued treatment with CVC for 
subjects who have previously participated in CVC studies 
Study Design
Subjects from the following studies will be eligible to receive open-label CVC 
150 mg once daily:

Subjects who have completed both Treatment Period 1 and Treatment 
Period 2 (Year 1 and Year 2) of the CENTAUR study (652-2-203),
regardless of their treatment assignment in the CENTAUR study (CVC 
or placebo).

Subjects who have completed the AURORA study (3152-301-002) as a
result of progression to cirrhosis or reaching an adjudicated liver-related 
clinical outcome in either Part 1 or Part 2 of the study regardless of their 
treatment assignment (CVC or placebo). Refer to Section 8.2 for 
additional details.
Subjects will be required to rollover to this continued access study within 1 month 
of completing their final visit assessments in either the CENTAUR or AURORA 
study. Eligible subjects who completed these studies, prior to initiation of this 
protocol at their study center, will be allowed to participate in this rollover study. 
Subjects will attend regular study visits for continued safety assessment at the start 
of this open-label rollover study (Baseline), then every 3 months thereafter for the 
duration of the study, or at the discretion of the investigator. A central laboratory 
will be used for laboratory assessments. 
Treatment Duration
This is a rollover study in which CVC treatment will continue to be provided until 
it is commercially available or if development is terminated, as applicable. 
Number of Subjects
It is expected that a total of approximately 560 subjects may rollover from both 
the CENTAUR study (652-2-203) and the AURORA study (3152-301-002).
Number of Study Centers
Up to approximately 480 centers 
Target Population
Adult subjects with NASH who have completed both Treatment Period 1 and 
Treatment Period 2 in the CENTAUR study (652-2-203), or who have completed 
the AURORA study (3152-301-002) as a result of progression to cirrhosis or 
reaching an adjudicated liver-related clinical outcome in either Part 1 or Part 2 of 
the study.

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Inclusion Criteria
1.
Subjects who have either:

Completed both Treatment Period 1 and Treatment Period 2 (Year 1 and 
Year 2) of the CENTAUR study (652-2-203), including a Year 2 liver 
biopsy.

Completed the AURORA study (3152-301-002) as a result of reaching an 
adjudicated liver-related clinical outcome in Part 1 or Part 2 of the study 
of:
o  Histopathologic progression to cirrhosis
o  Model for end-stage liver disease (MELD) score ≥15
o  Ascites (requiring intervention, ie, large volume paracentesis ≥1L or 
initiation of a diuretic)
o  Hospitalization (as defined by a stay of ≥24 hours) for onset of: 
variceal bleed, hepatic encephalopathy (defined by a West Haven 
Stage of ≥2), spontaneous bacterial peritonitis (confirmed by 
diagnostic paracentesis with positive ascitic fluid bacterial culture)
2.
Has been determined to be in a stable medical condition (minimum of 
3 months from the date of the clinical event in AURORA to the Baseline Visit 
of this study) based on medical history or physical examination, in the opinion 
of investigator. Inclusion criterion applies only to subjects coming from the 
AURORA study (3152-301-002).
Exclusion Criteria
2.
Prior or planned liver transplantation
3.
Other known causes of chronic liver disease, such as the following:

Alcoholic liver disease

Primary biliary cirrhosis

Primary sclerosing cholangitis

Autoimmune hepatitis

Wilson’s disease, hemochromatosis, or iron overload

Alpha-1-antitrypsin (A1AT) deficiency

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Test Article 
CVC 150-mg tablet
Dosage and
Administration
Open-label CVC 150 mg, administered orally once daily with food.
Reference Therapy
Not applicable
Study Procedures/
Frequency

Scheduled laboratory tests (serum chemistries and hematologic assessments) 
will be performed at Baseline and every 3 months (Months 3, 6, 9, 12, 15, 
18, 21, 24 etc., until CVC becomes commercially available or if 
development is terminated). A central laboratory will be used to process 
blood/serum samples.

Subject safety will be assessed at scheduled study visits. Unscheduled visits 
may also be used, at the discretion of the investigator.
Safety Evaluation
A central laboratory will be used for laboratory assessments which are required 
per protocol. All adverse events (AEs), adverse drug reactions (ADRs) serious 
adverse events (SAEs), suspected unexpected serious adverse reactions 
(SUSARs), and treatment discontinuation due to AEs will be collected.  
Long-term safety with CVC will be assessed.
Statistical Analysis
No inferential statistical testing will be conducted for this continued access study. 
Summaries of demographics, baseline characteristics, treatment exposure and 
safety parameters will be analyzed by descriptive statistics for the continuous 
variables and frequency counts with incidence rates for the dichotomous or 
categorical variables.
Sample Size
Approximately 560 subjects are expected to roll over from both the CENTAUR 
study (652-2-203) and the AURORA study (3152-301-002) to receive open-label 
CVC. 

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5. INTRODUCTION
Cenicriviroc mesylate (CVC) is a novel, once-daily, orally active and potent inhibitor of 
ligand binding to C-C chemokine receptor (CCR) type 2 (CCR2) and type 5 (CCR5), 
currently in clinical development for the treatment of liver fibrosis in adult subjects with 
nonalcoholic steatohepatitis (NASH).
5.1.
Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis
Nonalcoholic fatty liver disease (NAFLD) is a common, often “silent,” liver disease 
associated with obesity-related disorders, such as type-2 diabetes mellitus (T2DM) and the
metabolic syndrome, occurring in people who consume little or no alcohol, and is 
characterized by the accumulation of fat in the liver with no other apparent causes.1-11 At the 
beginning of the NAFLD spectrum is simple or bland steatosis, which is characterized by a 
build-up of fat within the liver. Liver steatosis without inflammation is usually described as 
benign or nonprogressive. NASH is usually described as a severe form of NAFLD where 
steatosis is complicated by liver-cell injury and inflammation, with or without fibrosis. The 
rising prevalence of obesity-related disorders has contributed to a rapid increase in the 
prevalence of NASH. Approximately 10% to 20% of subjects with NAFLD will progress to 
NASH.12 Due to the growing epidemic of obesity and diabetes worldwide, NASH is 
projected to become the most common cause of advanced liver disease and the most common 
indication for liver transplantation.13-16 The burden of NASH, combined with a lack of any 
approved therapeutic interventions, represents an unmet medical need.
5.2.
CVC Mechanism of Action 
In vitro data with CVC has demonstrated that it blocks the binding of C-C motif chemokine 
ligand 2 (CCL2; also known as monocyte chemotactic protein 1 [MCP-1]) to CCR2, and also 
blocks the binding of CCR5 ligands, CCL3 (also known as macrophage inflammatory protein 
[MIP]-1), CCL4 (also known as MIP-1) and CCL5 (also known as regulated on activation 
normal T-cell expressed and secreted [RANTES]), to CCR5. Ex vivo experiments showed 
that nanomolar concentrations of CVC achieved 98% receptor occupancy of CCR2 on human 
monocytes and ~90% receptor occupancy for CCR5 on human CD4+ and CD8+ T-cells. 
Additionally, CVC was an efficient inhibitor of monocyte and human lymphocyte (primarily 
T-cells) migration in vitro. 
The mechanistic rationale for the use of CVC as an anti-inflammatory and anti-fibrotic agent 
in liver disease, such as liver fibrosis associated with NASH, is as follows. First, CVC 
treatment decreases the recruitment and migration of CCR2-expressing monocytes to the site 
of liver injury, mainly via CCR2 antagonism, thereby reducing the infiltration of 
pro-inflammatory, monocyte-derived macrophages into the liver.17,18 Second, CCR5 
antagonism by CVC is expected to impair the migration, activation, and proliferation of 
collagen-producing activated hepatic stellate cells and myofibroblasts, therefore reducing 
fibrogenesis.19,20

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5.3.
Clinical Studies with CVC
Overall, as of January 2018, approximately 1154 subjects have been exposed to CVC in 
completed and ongoing clinical studies (January 2018 Development Safety Update Report 
[DSUR] cutoff). 
5.3.1.
Phase 1 Pharmacokinetic Studies in Healthy Subjects
Initial human pharmacokinetic (PK) data for CVC was obtained in 2003 when the molecule 
was being developed by Takeda Pharmaceutical. The first 2 Phase 1 studies of CVC 
(Study 2080/16 [RCP-001] and Study 001 [01-03-TL-652-001]) established CVC’s 
bioavailability in humans and demonstrated that CVC was not excreted in urine, that plasma 
drug exposure was nearly dose proportional up to single doses of 400 mg, and that M-II and 
M-I were the major and minor metabolites, respectively, in humans. More importantly, the 
studies established rapid attainment of clinically significant drug levels, with a time to 
maximum plasma concentration (tmax) of 3 to 6 hours, and the possibility of once-daily 
dosing with a half-life (t1/2) of 34 to 42 hours.
Tobira conducted its first clinical study with CVC tablet formulation at doses up to 800 mg in 
2008 (Study 652-1-101) and confirmed that CVC was readily absorbed with median tmax 
occurring about 3 to 6 hours postdose across the dose levels. CVC was eliminated from 
plasma with a mean t1/2 of approximately 30 to 40 hours across the wide dose range studied, 
suggesting linear elimination kinetics. Evaluation of single oral dose administration of the 
Phase 3 formulation of CVC 150 mg in Study 3152-101-002 suggested that food increases 
exposure of CVC by 5.2-fold with a mean t1/2 of approximately 40 hours.
CVC was well tolerated in all of the single-dose studies, with no clinically important findings 
with respect to vital signs, electrocardiogram (ECG) findings, physical examinations, or 
laboratory tests for any subject. A few subjects had mild, usually isolated elevations in 
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) while on CVC.
Study 102 (652-1-102) was the first multiple-dose study in humans. This randomized, 
double-blind, placebo-controlled, multiple-dose study was conducted in cohorts of 12 healthy 
adult male and female subjects. In Part 2 of Study 102, CVC at doses of 25 to 200 mg once 
daily was readily and well absorbed following single (Day 1) or repeated (Day 10) doses 
with a high-fat meal, achieving peak plasma concentrations about 3 to 6 hours postdose. The 
mean t1/2 of CVC following repeated doses was similar to that after a single dose, averaging 
approximately 35 to 40 hours across dose regimens, indicating that the elimination kinetics of 
CVC were unchanged following repeated doses.
In Study 102, 2 subjects experienced adverse events (AEs) that resulted in discontinuation of 
study drug: Grade 4 AST/ALT in 1 subject, and a Grade 2 AST elevation and an elevated 
lactate dehydrogenase (LDH) in the other subject.
The safety, tolerability, and PK of the Phase 3 formulation following once daily escalating 
doses of CVC (450 and 900 mg) and combination with a single dose of 100 mg ritonavir 
were evaluated in Study 3152-107-002. Steady state levels of CVC, M-1, and M-II 
metabolites were achieved with once daily dosing of 450 or 900 mg CVC with a high-fat

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meal for 7 days. Comparison of PK parameters suggested dose-proportional increase in
maximum concentration of drug (Cmax) and AUC0-of CVC and M-1 metabolite, while M-II 
exposure increased less than proportionally. Coadministration of CVC with a single dose of 
100 mg ritonavir resulted in increased CVC Cmax and AUC0-by 33.5% and 20.4%, 
respectively. Overall, multiple-dose administration of 450 and 900 mg CVC with a high-fat 
meal and coadministration with single dose of ritonavir 100 mg was safe and well tolerated.
The PK, safety, and tolerability of CVC were assessed in several drug-drug interaction 
studies. In clinical studies, potent cytochrome P450 (CYP)3A4 inhibitors such as ritonavir, 
darunavir/ritonavir combination, and atazanavir/ritonavir combination increased the exposure 
of CVC by 3.55-fold, 3.13-fold, and 3.89-fold, respectively. The exposure of midazolam, a 
substrate of CYP3A4, is increased by 1.84-fold when coadministered with 150 mg CVC. 
CVC increased the exposure of rosuvastatin (breast cancer resistance protein [BCRP] 
substrate) by 3.52-fold, atorvastatin and simvastatin (CYP3A4 substrates) by 1.37-fold and 
2.48-fold, respectively. However, no significant increase in the exposure of digoxin 
(P-glycoprotein [P-gp] substrate) and caffeine (CYP1A2 substrate) was observed 
(Study 652-124). 
Based on clinical data as well as in vitro drug interaction studies, potent CYP3A4 inhibitors 
could significantly increase CVC exposure. Since CYP2C8 is identified to contribute to 
metabolism of CVC, potent CYP2C8 inhibitors may increase exposure of CVC. CVC was 
identified as a P-gp substrate in vitro; however, based on currently available exposure-safety 
CVC data (Study 3152-107-002), coadministration of CVC with P-gp inhibitors is not 
expected to result in any clinically meaningful increase in CVC exposure. CVC can be 
coadministered with P-gp substrates such as digoxin. Caution is recommended while 
coadministering substrates of CYP3A4 with narrow therapeutic index (eg, midazolam). It is 
also recommended not to exceed the suggested maximum daily dose of rosuvastatin (BCRP 
substrate) and other statins (atorvastatin, lovastatin, pravastatin and simvastatin). The 
detailed list of disallowed medications and the list of medications that are allowed but with 
specific restrictions are provided in Appendix 20.4.
5.3.2.
Phase 1 Pharmacokinetic Study in Subjects with Hepatic Impairment
A Phase 1 open-label study (Study 121 [652-1-121]) in subjects with hepatic impairment was 
conducted. This study was designed to evaluate the PK, safety, and tolerability of CVC in 
subjects with mild and moderate hepatic impairment (Child Pugh A and B) compared with
matched subjects with normal hepatic function. CVC exposures were not increased in 
subjects with mild hepatic impairment relative to matched healthy control subjects. 
Cenicriviroc exposures were increased in subjects with moderate hepatic impairment relative 
to matched healthy control subjects. On Day 14, subjects with moderate hepatic impairment 
had CVC exposures approximately 29% (maximum plasma concentration [Cmax]) to 55% 
(area under the concentration time curve to the last measurable concentration [AUC0-tau]) 
higher compared with healthy matched controls. In subjects with hepatic impairment, a 
longer half-life was observed compared with healthy control subjects with normal hepatic 
function (Day 14, t1/2 geometric mean: 37.6 hours [moderate] and 29.7 hours [mild] vs
22.4 hours [matched healthy controls, moderate] and 22.0 hours [matched healthy controls, 
mild]). Based on the magnitude of these observed differences in exposure in subjects with 

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mild or moderate hepatic impairment, it is unlikely that a CVC dose adjustment will be
required.
In Study 121, CVC showed a favorable safety profile with few treatment-related AEs and 
with only 1 AE (mild vomiting; mild hepatic impairment subject) leading to treatment 
discontinuation. Two subjects (both with long-standing history of hepatitis C and liver 
cirrhosis) experienced Grade 3 (5.1 to 10.0 × upper limit of normal [ULN]) or Grade 4 
(> 10.0 × ULN) elevations in liver transaminases during the study; however, these returned 
to their prior grade of severity, and both subjects completed the 14-day dosing period and all 
study visits with no further sequelae. Both of these subjects had bilirubin levels within 
normal limits.
5.3.3.
Phase 2b Study in Subjects with NASH and Liver Fibrosis 
The Phase 2b study (CENTAUR; Study 652-2-203) was a randomized, double-blind, 
placebo-controlled, multinational 2-year study. The study was designed to determine the 
efficacy and safety of CVC for the treatment of NASH in adult subjects with liver fibrosis.
The study population included subjects with a nonalcoholic fatty liver disease activity score 
(NAS) ≥ 4 and liver fibrosis Stage 1 to 3 based on the NASH Clinical Research Network 
(CRN) criteria who were at increased risk of disease progression due to the presence of 
T2DM, body mass index (BMI) > 25 kg/m2, and meeting at least 1 of the criteria for 
metabolic syndrome, or bridging fibrosis (NASH CRN Stage 3) and/or definite NASH 
(NAS ≥5). Subjects were randomized in a 2:1:1 ratio to receive 1 of 3 treatments as follows:

CVC 150 mg once daily for 2 years (Arm A; CVC/CVC group)

Placebo once daily for 1 year followed by CVC 150 mg once daily for an additional 
1 year (Arm B; placebo/CVC group)

Placebo once daily for 2 years (Arm C; placebo/placebo group)
Fibrosis stage, NASH status, and NAS were assessed in serial liver biopsies read by a central 
pathologist at baseline, Year 1, and Year 2. The central pathologist remained blinded to 
individual subject treatment assignment throughout the conduct of the study.
A total of 289 subjects (intent-to-treat [ITT] population) were randomized into the 
CENTAUR study.21 Overall, 39 of 289 subjects (13.5%) withdrew early during Year 1 
(Treatment Period 1), with the most commonly reported reasons for early discontinuation 
during Year 1 being due to AEs and withdrawal of consent. A total of 250 subjects (86.5%) 
completed Year 1 and 242 subjects (83.7%) entered Year 2 (Treatment Period 2). During 
Year 2, 16 subjects (5.5%) withdrew early, with the most commonly reported reason for 
early discontinuation during Year 2 being due to AEs, which were more commonly reported 
in the CVC/CVC group (3.4%, 5 subjects) compared with the placebo/CVC group (1.4%, 
1 subject) and the placebo/placebo group (0 subjects).
Overall, 47.4% (137/289) of subjects were male and 52.6% (152/289) were female. Most 
subjects were white (86.5% [250/289]) and not Hispanic or Latino (82.4% [238/289]). The 
mean age at screening was 54.1 years. Except for documented evidence of T2DM, the 

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treatment groups were well balanced with respect to demographics and baseline 
characteristics. A higher percentage of subjects in the CVC/CVC group (58.6%) and 
placebo/CVC group (52.8%) than in the placebo/placebo group (40.3%) had documented 
evidence of T2DM.
Efficacy Results at Year 1
In the ITT population, 23 (15.9%) subjects in the CVC group achieved the primary efficacy 
endpoint (defined as a decrease in NAS by ≥2 points with at least a 1-point reduction in 
either lobular inflammation or hepatocellular ballooning AND no worsening of fibrosis stage 
at Year 1 relative to the Screening biopsy), compared with 27 (18.8%) subjects in the placebo 
group (p=0.5194, odds ratio [OR]: 0.8, 95% confidence interval [CI]: 0.44 - 1.52). 
Although a statistically significant difference between the CVC and combined placebo 
groups was not achieved for the primary endpoint at Year 1, analyses of the key secondary 
endpoints (the composite summation [S1] of the 2 key secondary endpoints, “complete 
resolution of steatohepatitis and no concurrent worsening of fibrosis stage [S2]” and 
“improvement in fibrosis and no worsening of steatohepatitis [S3]”) were conducted as 
prespecified and presented for full disclosure of data. Results for the key secondary efficacy 
endpoints using the ITT population are summarized in Table 2, and briefly were as follows:

A higher proportion of subjects in the CVC group (Arm A) (7 subjects, 4.8%) than in
the placebo group (Arms B+C) (4 subjects, 2.8%) achieved the composite summation
(S1) of the 2 key secondary endpoints (S2+S3) at Year 1.

A similar proportion of subjects receiving CVC or placebo achieved S2 at Year 1.

Twice as many subjects in CVC group (Arm A) than in the placebo group 
(Arms B+C) achieved S3 at Year 1.

In the subgroup of subjects with higher fibrosis stage and disease activity (ie, ITT 
population Year 1 excluding subjects with baseline NASH CRN Stage 1 fibrosis) at 
baseline, a higher proportion of subjects in CVC group (Arm A) compared with the 
placebo group (Arms B+C) showed improvement in fibrosis by ≥ 1 stage (NASH 
CRN) and no worsening of steatohepatitis (S3) at Year 1. Also, a higher proportion of 
subjects in CVC group (Arm A) (8 subjects, 8.2%) compared with the placebo group 
(Arms B+C) (3 subjects, 3.1%) had a ≥ 2 stage improvement in fibrosis AND no 
worsening of steatohepatitis at Year 1.

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Table 5-1
CENTAUR Study: Effect of 1 Year of Treatment with CVC Versus Placebo on 
Fibrosis Endpoints (Year 1 Data)
Number of Subjects (%)
Analysis Population
Endpoint/Statistic
CVC/CVC
(Arm A)
(n = 145)
Placebo/CVC (Arm 
B) + 
Placebo/Placebo 
(Arm C)
(n = 144)
Odds Ratio 
(95% CI)
p-value
ITT Population Year 1
Primary endpoint: 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
23 (15.9)
27 (18.8)
0.816
(0.439, 1.516)
p = 0.5194a
S1: summation of key secondary endpoints S2 
and S3
7 (4.8)
4 (2.8)
1.934 
(1.035, 3.614)
p = 0.0388b
S2: complete resolution of steatohepatitis and 
no concurrent worsening of fibrosis stage
11 (7.6) 
8 (5.6)
1.396 
(0.537, 3.628)
p = 0.4941b
S3: improvement in fibrosis by ≥1 stage 
(NASH CRN) AND no worsening of 
steatohepatitis
29 (20.0)
15 (10.4)
2.201 
(1.113, 4.352)
p = 0.0234b
ITT Population Excluding Subjects with 
Baseline NASH CRN Fibrosis Stage 1
(n = 98)
(n = 96)
S3: improvement in fibrosis by ≥1 stage 
(NASH CRN) AND no worsening of 
steatohepatitis
23 (23.5)
13 (13.5)
p = 0.0708d
Improvement in fibrosis stage by ≥2 stages 
AND no worsening of steatohepatitis
8 (8.2)
3 (3.1)
p = 0.1237e
CRN = Clinical Research Network; CVC = cenicriviroc
a
Two-sided p-value < 0.05 indicates statistical significance of the study primary endpoint.
b
The odds ratio, 95% CI, and p-value was from ordinal logistic regression models with factors for 
randomized treatment group, NAS at screening (4 or 5), and fibrosis stage (2 or > 2). Two-sided p-value 
< 0.05 indicated statistical significance of the secondary endpoint. S1 was tested first and if significant, 
testing for S2 and S3 were also to be performed at a 0.05 level of significance.
c
The p-values for S2 and S3 were from the logistic regression analysis with adjustment for the randomization 
strata
d
P-values are from a CMH test with adjustment for NAS at baseline (4 or ≥ 5) and fibrosis stage at baseline 
(2 or > 2). Two-sided p-value < 0.05 indicated statistical significance of the secondary endpoint. S1 was 
tested first and if significant, testing for S2 and S3 were also to be performed at a 0.05 level of significance.
e
P-values are from a CMH test with adjustment for NAS at baseline (4 or ≥ 5) and fibrosis stage at baseline 
(2 or > 2).

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Efficacy Results at Year 2
Overall, the results from the final Year 2 analysis supported the clinically meaningful 
antifibrotic effect of CVC treatment observed in the Year 1 primary analysis. Improvement in 
fibrosis AND no worsening of steatohepatitis were re-assessed in a prespecified analysis 
among Year 1 placebo nonresponder subjects who received CVC (Arm B; placebo/CVC 
group) as compared with those who continued to receive placebo in Arm C from Year 1 to 
Year 2, which was therefore independent of the Year 1 primary analysis. Year 1 placebo 
nonresponders were defined as ITT subjects who were randomized to receive placebo during 
Year 1, did not achieve a ≥ 1-stage improvement in fibrosis AND no worsening of 
steatohepatitis) at Year 1, and were in the Phase 3 Eligible subgroup (ie, subjects with a 
diagnosis of NASH and NASH CRN fibrosis Stage of 2 or 3 assessed on the Year 1 biopsy). 
Results of the analysis showed that a higher proportion of Year 1 placebo nonresponder 
subjects who received CVC (Arm B, placebo/CVC group) (24.4%, 10/41 subjects) 
experienced an improvement in fibrosis by ≥ 1 stage AND no worsening of steatohepatitis 
compared with subjects who remained on placebo (Arm C, placebo/placebo group) (17.1%, 
6/35 subjects) from Year 1 to Year 2. Similarly, improvement in fibrosis by ≥ 1 stage 
regardless of effect on steatohepatitis was reported in 39.0% of placebo/CVC subjects 
(Arm B) versus 28.6% of placebo/placebo subjects (Arm C).
A similar and consistent antifibrotic response was observed in the pooled analysis of subjects 
treated with CVC for 1 year (subjects in Arm A who received CVC during Year 1 and Arm B 
group who received CVC during Year 2) (19.9%, 41/206 subjects) compared with subjects 
treated with placebo for 1 year (Arm C; data from Year 1) (11.1%, 8/72 subjects).
At Year 2, a similar proportion of subjects in the CVC/CVC (Arm A) and placebo/placebo 
(Arm C) groups achieved improvement in fibrosis stage by ≥1 stage AND no worsening of 
steatohepatitis (12.8% [15/117] versus 14.0% [8/57], respectively). Results were similar 
using the modified intent-to-treat (mITT) population. Similar to the overall ITT population, 
in the subgroup of subjects with Stage 2 or 3 fibrosis at baseline, a similar proportion of 
subjects in Arm A and Arm C achieved improvement in fibrosis stage by ≥1 stage AND no 
worsening of steatohepatitis (18.7% and 18.9%, respectively).
However, in the subgroup of subjects with fibrosis Stage 2 or 3 at baseline (ie, including only 
subjects who could improve by 2 or more stages), a greater proportion of subjects receiving 
CVC achieved a ≥ 2-stage improvement in fibrosis AND no worsening of steatohepatitis at
Year 2 relative to subjects receiving placebo (9.3% [7/75] in the CVC/CVC group [Arm A] 
versus 2.7% [1/37] in the placebo/placebo group [Arm C], from baseline to Year 2). When 
only subjects with Stage 3 fibrosis were included in the analysis, 14.0% (6/43) of subjects 
receiving CVC versus 4.2% (1/24) of subjects receiving placebo achieved a ≥ 2-stage 
improvement in fibrosis AND no worsening of steatohepatitis at Year 2.
To determine the durability of histological improvement over 2 years, improvement in 
fibrosis by ≥ 1 stage (regardless of steatohepatitis status) was assessed in subjects with 
available biopsy results at all 3 timepoints (baseline, Year 1, and Year 2 [mITT Population, 
Year 2]). Results from this analysis showed that the proportion of CVC/CVC-treated subjects

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in Arm A who achieved improvement in fibrosis by ≥ 1 stage at the end of Year 1 and 
maintained this antifibrotic effect at Year 2 was twice the number of placebo/placebo-treated 
subjects in Arm C (60% [18/30] vs 30% [3/10], respectively). Notably, 86% (12/14) of 
subjects in the CVC/CVC group (Arm A) with Stage 3 fibrosis at baseline that improved by 
at least 1 stage at Year 1 maintained the improvement in fibrosis stage (antifibrotic benefit) at 
Year 2 compared with 60% (3/5) subjects in the placebo/placebo group (Arm C). It is worth 
noting that, of 36 responders in the CVC/CVC group (Arm A) at Year 1, 6 had missing 
Year 2 biopsy data including 4 subjects who were CRN Stage 3 at baseline.
The placebo/placebo group showed substantial variability in the change in fibrosis from 
baseline to Year 1 and to Year 2, which was not readily apparent when simply measuring the 
proportion of placebo responders at each time point. In fact, most placebo-treated subjects 
who improved by ≥ 1 stage at Year 1 relative to baseline subsequently worsened from Year 1 
to Year 2. Similarly, the majority of placebo-treated subjects who worsened by ≥ 1 stage at 
Year 1 relative to baseline subsequently improved from Year 1 to Year 2. These findings 
potentially reflect the fluctuations in histological features of steatohepatitis and liver fibrosis 
over the course of the disease and likely represent the natural history of NASH.
Collectively, the results from the Year 1 primary analysis and Year 2 final analysis 
demonstrate the antifibrotic effects associated with CVC treatment in adults with NASH and 
liver fibrosis. Although there was no apparent effect of CVC on steatohepatitis, CVC-treated 
subjects were more likely to achieve fibrosis improvement by at least 1 stage (following 
1 year of treatment) or 2 stages (observed following 1 and 2 years of treatment) and 
experience a sustained antifibrotic response as assessed by 3 serial biopsies conducted at 
yearly intervals over a 2-year period.
Safety
The safety profile over 1 year of treatment (Treatment Period 1) was analyzed at Year 1 for 
subjects receiving CVC (CVC Arm A) compared with subjects receiving placebo (placebo 
Arms B+C). The safety profile over 2 years of treatment (Treatment Periods 1 and 2) was 
analyzed at Year 2 for subjects who received at least 1 dose of study drug during Year 2 
(Safety Analysis Set Year 2). Results from both analyses are presented herein.
Safety Results at Year 1
The overall incidence of treatment-emergent adverse events (TEAEs) during Treatment 
Period 1 was similar between subjects in the CVC Arm A and placebo Arms B+C (93.1% vs
92.4%, respectively). The incidence of study drug-related AEs was 41.7% in the CVC Arm A 
and 37.5% in placebo Arms B+C. No subjects died during Treatment Period 1. Seventeen 
subjects (11.8%) in the CVC Arm A and 11 subjects (7.6%) in placebo Arms B+C
experienced a serious adverse event (SAE); only 1 SAE of Grade 2 arrhythmia was deemed 
related to study drug, which resolved while the subject remained on blinded study drug. 
Overall, 7.6% of subjects discontinued study drug due to an AE (CVC, 6.3% of subjects; 
placebo, 9.0% of subjects).

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Overall, the most commonly reported TEAEs regardless of causality were diarrhea 
(51 subjects, 17.7%), headache (43 subjects, 14.9%), nausea (33 subjects, 11.5%), fatigue 
(38 subjects, 13.2%), and abdominal pain upper (33 subjects, 11.5%). The most notable 
differences for AEs reported in ≥10% of subjects in any group were: diarrhea, nausea, and 
arthralgia, reported more commonly in CVC Arm A compared with placebo Arms B+C 
(20.8% vs 14.6%; 17.4% vs 9.0%; and 12.5% vs 4.2% of subjects, respectively); abdominal 
pain upper and back pain, reported less commonly in CVC Arm A than in placebo 
Arms B+C (9.7% vs 13.2%; 7.6% vs11.8% of subjects, respectively).
The most commonly reported study drug-related AEs in CVC Arm A were diarrhea (9.0% of 
subjects), nausea (8.3% of subjects), and flatulence (4.9% of subjects). The most commonly 
reported study drug-related AEs in placebo Arms B+C were headache (7.6% of subjects), 
fatigue (4.2% of subjects), and ALT increased (3.5% of subjects). The most frequently 
reported study drug-related clinical TEAEs of at least moderate (Grade 2) severity occurring 
in ≥2% of subjects in any treatment group were fatigue (2.8%) and diarrhea (2.1%) in CVC
Arm A and headache (3.5%) in placebo Arms B+C.
The incidence of Grade 3 or 4 AEs was similar between CVC Arm A and placebo Arms B+C 
(26.4% vs 25.7% of subjects). The most commonly reported Grade 3 or 4 AEs in CVC 
Arm A were ALT increased (6.3% of subjects), AST increased (2.8% of subjects), gamma-
glutamyl transferase (GGT) increased (2.8% of subjects), arthralgia (2.8% of subjects), and 
back pain (2.1% of subjects). The most commonly reported Grade 3 or 4 AEs in placebo 
Arms B+C were ALT increased (6.3% of subjects), arthralgia (2.1% of subjects), and back 
pain (2.1% of subjects). A total of 3 Grade 3- 4 TEAEs of hepatobiliary disorders were 
reported during Year 1: 1 AE of autoimmune hepatitis and 1 AE of cholelithiasis in CVC 
Arm A and 1 AE of autoimmune hepatitis in placebo Arms B+C. A greater number of 
participants in CVC Arm A (22.2%) experienced treatment-related TEAEs of at least Grade 2 
severity than in the placebo Arms B+C (13.9%). The most frequently reported study drug-
related clinical TEAEs in any treatment group were fatigue (2.8%) and diarrhea (2.1%) in the 
CVC Arm A and headache (3.5%) in the placebo Arms B+C.
The incidence of treatment-emergent Grade 3 or 4 laboratory abnormalities was generally 
similar between groups. Grade 4 uric acid elevations, which occurred in subjects with 
increased baseline values, and asymptomatic Grade 3 amylase elevations were observed 
more frequently in the CVC Arm A than the placebo Arms B+C (7.6% vs 4.2% and 4.2% vs 
0.7%, respectively). During Year 1, 9.7% of subjects (14/144) in CVC Arm A and 7.6% of 
subjects (11/144) in placebo Arms B+C met protocol-defined biochemical criteria for 
suspected drug-induced liver injury (DILI).
Safety Results at Year 2
The mean duration of exposure was comparable across all treatment groups in the safety 
analysis set for Year 2 (694.0, 713.3, and 708.7 days for the CVC/CVC [Arm A], 
placebo/CVC [Arm B], and placebo/placebo [Arm C] groups, respectively).
For subjects who received at least 1 dose of study drug in Year 2 (N = 242), the safety profile 
of CVC 150 mg in subjects treated daily with CVC for 1 (placebo/CVC group) or 2 years

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(CVC/CVC group) was comparable to that observed in subjects treated with placebo 
(placebo/placebo) and consistent with that reported after 1 year of CVC treatment.21 The 
overall incidence of TEAEs during the study was similar across the treatment groups 
(≥75.0% of subjects in each group). Overall (N = 242), the 3 most frequently reported AEs 
regardless of causality were nasopharyngitis (7.4%, 18 subjects), upper respiratory tract 
infection (6.6%, 16 subjects), fatigue (6.6%, 16 subjects). The following TEAEs were 
experienced more frequently in CVC Arm A than placebo Arm C: nasopharyngitis (9.1% 
versus 3.3%), upper respiratory tract infection (6.6% versus 5.0%), urinary tract infection 
(7.4% versus 0), nausea (5.8% versus 3.3%), arthralgia (5.0% versus 3.3%), fatigue (9.1% 
versus 5.0%), ALT increased (5.0% versus 3.3%), cough (5.0% versus 0).
Fewer treatment-related TEAEs were reported overall in Treatment Period 2 than in 
Treatment Period 1; 34/242 (14.0%) subjects versus 114/288 (39.6%), respectively. The 
number of subjects in the CVC/CVC group (Arm A) (15.7%) who experienced treatment-
related TEAEs was comparable to that reported in placebo/placebo group (Arm C) (15.0%) 
and lower in placebo/CVC group (Arm B) (9.8%). A greater number of subjects in 
CVC/CVC group (Arm A) (8.3%) experienced treatment-related TEAEs of at least Grade 2 
severity than in the placebo/placebo group (Arm C) (5.0%). The most frequently reported 
study treatment-related TEAE in any treatment group was fatigue (3.3%) in the CVC/CVC 
group (Arm A) and ALT increased (3.3%) in the placebo/placebo group (Arm C). This was 
consistent with that reported after 1 year of treatment. 21
Overall, the number of participants in the CVC/CVC group (Arm A) (14.9%) who 
experienced Grade 3-4 TEAEs, regardless of causality, was comparable to that reported in 
the placebo/placebo group (Arm C) (15.0%) during Treatment Period 2. The most frequently 
reported Grade 3-4 TEAE for both the CVC/CVC and placebo/placebo groups was ALT 
increased (2.5% in CVC/CVC [Arm A] and 3.3% in placebo/placebo [Arm C]).
No deaths occurred during the study. Through 2 years of the study, 10.3% (25/242) of 
subjects had at least 1 SAE (Safety Analysis Set for Year 2). No other SAE occurred in 
> 1 subject except osteoarthritis (2 subjects in CVC/CVC [Arm A]). Overall, 6 of 242 (2.5%) 
subjects withdrew study drug due to a TEAE, including 3 subjects due to increased ALT, 
1 subject due to nausea, and 1 subject due to diverticulitis in the CVC/CVC group (Arm A), 
and 1 subject with abdominal discomfort in the placebo/CVC group (Arm B).
Of the subjects who received at least 1 dose of study drug during Year 2, 4.1% of subjects in 
CVC/CVC group (Arm A) experienced an AE leading to discontinuation, while no subjects 
in the placebo/placebo group (Arm C) discontinued due to an AE. The only AE leading to 
discontinuation, regardless of causality, reported in at least 2 subjects in CVC/CVC group 
(Arm A) was ALT increased (3 subjects, 2.5%); all were Grade 3 severity. For subjects who 
crossed over after 1 year of placebo treatment to CVC treatment, only 1 subject experienced 
an AE leading to discontinuation (abdominal discomfort) after crossing over.
The incidence of treatment-emergent Grade 3 or 4 laboratory abnormalities during Year 2 
was generally similar across the treatment groups. In total, 3.3% (4/121) subjects in 
CVC/CVC group (Arm A), 3.3% (2/61) subjects in the placebo/CVC group (Arm B), and 
1.7% (1/60) subjects in the placebo/placebo group (Arm C) met any protocol-defined 

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biochemical criterion for suspected DILI. Hepatobiliary disorders during Treatment Period 2 
were reported in 5/242 (2.1%) subjects overall. Of note, among the subjects who met the 
criterion for suspected DILI during Year 1, 2 hepatobiliary AEs of “autoimmune hepatitis” 
were reported during Year 1 (1 subject in CVC Arm A group [Grade 3] and 1 subject in the 
placebo Arms B+C [Grade 3]), and these subjects did not continue treatment during Year 2. 
One additional subject in the CVC group (Arm A) had a postbaseline liver biopsy 
“suggestive of autoimmune hepatitis or a drug hepatoxicity mimicking autoimmune 
hepatitis,” which was performed in the context of treatment-emergent Grade 3 elevations in 
liver transaminases.
No meaningful changes in vital signs, ECGs, or anthropometric parameters were observed.
Pharmacokinetics/Pharmacodynamics
Findings from the pharmacokinetic/pharmacodynamic (PK/PD) Year 1 efficacy analyses of 
CENTAUR were consistent with those of previous studies, which served as the basis for 
selection of the CVC dose of 150 mg evaluated in this study. In CENTAUR, the CVC dose 
of 150 mg daily provided > 77% of subjects being exposed to minimum plasma 
concentration (Cmin) values that exceed the Cmin associated with half-maximal response 
(ECmin50; most conservative ECmin50 of 50 ng/mL, based on data from the HIV Phase 2 
program), providing an expectation of substantial and near maximal antagonism of 
CCR2/CCR5 in most subjects at this dose. When using the ECmin50 of 40 ng/mL, which was 
based on changes in CCL2 and CCL4 levels (ie, reciprocal increases in CCL2 and CCL4 
levels observed due to effective CCR2 and CCR5 blockade by CVC) observed in the 
CENTAUR study, > 84% of CVC-treated subjects achieved this target concentration.
Results from a drug interaction study (Study 652-123) have shown that administration of a 
proton pump inhibitor (PPI) 90 minutes prior to CVC, dosed at 150 mg, resulted in 
significantly decreased CVC concentrations. In the CENTAUR study, PPIs were allowed 
with specific dosing instructions (ie, dosing of PPIs at least 2 hours after CVC 150 mg daily 
dose) and were used in 44% of all subjects. Although fewer subjects achieved an ECmin50 of 
40 ng/mL when using PPIs (84.5%) compared with those who did not (94.3%), a similar 
proportion of subjects in both groups achieved the key efficacy endpoint of improvement in 
fibrosis by at least 1 stage AND no worsening of steatohepatitis: 21.0% for PPI users versus 
25.0% for nonusers, respectively (mITT). Therefore, the dose of 150 mg appears sufficient 
when managing coadministration of CVC with commonly used concomitant medications, 
such as PPIs.
Taken together, along with the lack of apparent exposure-response for efficacy in this study, 
the main findings from the PK/PD analyses further support that the CVC 150 mg dose was 
able to maximize CCR2/CCR5 blockade in most subjects and support its evaluation in the 
Phase 3 program. 
5.4.
Study Rationale
The clinically important results from the Phase 2b CENTAUR study are robust and suggest 
that CVC treatment may be disease modifying in adult patients with liver fibrosis as a result 

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of NASH, particularly when considering the comprehensive and clinically relevant evidence 
which demonstrates that liver fibrosis, regardless of other histological components of 
steatohepatitis, is the only histologic feature independently associated with all-cause 
mortality and liver-related outcomes in patients with NAFLD.22 Cenicriviroc appears to be 
safe with no notable differences observed in previous clinical studies in the incidence of 
TEAEs and laboratory abnormalities, including liver transaminase elevations, which were 
generally similar between treatment groups. Safety findings in CENTAUR were consistent 
with that of the extensive clinical experience with CVC.
The open-label rollover protocol will be conducted to offer continued access to CVC to 
subjects who completed the CENTAUR study, progressed to cirrhosis, or reached an 
adjudicated liver-related clinical outcome and completed the AURORA study. In addition, 
this study will evaluate the safety and tolerability of CVC with long-term treatment.
5.5.
Dose Rationale
A dose of CVC 150 mg will be evaluated for the treatment of liver fibrosis in adult subjects 
with NASH in the open label rollover study.
This dose was evaluated in the CENTAUR study (652-2-203) and selected based on the 
clinical activity, PK, PD, and safety data from prior studies (652-1-110, 652-1-111, 652-120, 
652-1-121, 652-1-122, 652-123, 652-124, 652-2-202, and 652-2-201), which together 
support:

Evidence of meaningful clinical efficacy of CVC 150 mg in subjects with NASH and 
liver fibrosis in the CENTAUR study (Study 652-2-203)

Evidence that CVC 150 mg is safe and well tolerated subjects with NASH and liver 
fibrosis in the CENTAUR study (Study 652-2-203)

CVC dose of 150 mg provides an expectation of effective primary pharmacology
(ie, CCR2 and CCR5 antagonism)

Evidence of improvement in systemic inflammation biomarkers support underlying 
CVC pharmacology, and

The dose of 150 mg appears sufficient when managing coadministration of CVC with 
commonly used concomitant medications, such as PPIs.

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6. STUDY OBJECTIVES
Primary Objective:
The primary objective of this study is to provide open-label treatment with CVC to subjects 
who have previously participated in CVC studies.
Secondary Objective:
The secondary objective of this study is to assess the long-term safety of continued treatment 
with CVC for subjects who have previously participated in CVC studies. 

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7. INVESTIGATIONAL PLAN
7.1.
Overall Study Design and Plan
This is a Phase 2, open-label, multi-center, study (up to approximately 480 centers) to 
provide open-label CVC to subjects with liver fibrosis in the treatment of nonalcoholic 
steatohepatitis.
Subjects from the following studies will be eligible to receive open-label CVC 150 mg once 
daily:

Subjects who have completed both Treatment Period 1 and Treatment Period 2 
(Year 1 and Year 2) of the CENTAUR study (652-2-203), regardless of their 
treatment assignment in the CENTAUR study (CVC or placebo).

Subjects who have completed the AURORA study (3152-301-002) as a result of 
progression to cirrhosis or reaching an adjudicated liver-related clinical outcome in 
either Part 1 or Part 2 of the study, regardless of their treatment assignment (CVC or 
placebo). Refer to Section 8.2 for additional details. 
Subjects will be required to rollover to this continued access study within 1 month of
completing their final visit assessments in either the CENTAUR or AURORA study. Eligible 
subjects who completed these studies, prior to initiation of this protocol at their study center, 
will be allowed to participate in this rollover study. 
Subjects will undergo study visits for safety assessments at the start of this continued access 
study (Baseline), then every 3 months for the duration of the study, or at the discretion of the 
investigator. A central laboratory will be used for laboratory assessments, including any 
deemed necessary by the investigator; all other study assessments will be conducted locally.
This is a rollover study in which CVC treatment will continue to be provided until it is 
commercially available or if development is terminated, as applicable.
The study design is illustrated in Figure 7-1.
Figure 7-1
Study Design Schematic
Open-Label Period
CVC 150 mg once daily
Safety 
Follow-up
Year 1
Year 2; and ongoing
1-month 
Follow-up
Baseline 
Day 1a
Months 3, 6, 9, 12, 15, 18, 21, 24b
a
Subjects completing Treatment Periods 1 and 2 of the CENTAUR study or completing the AURORA study as 
a result of progression to cirrhosis or reaching an adjudicated liver-related clinical outcome in either Part 1 or Part 2 of 
the study, regardless of their treatment assignment (CVC or placebo), must provide informed consent to 
Study 3152-201-002 before receiving open label CVC. Subjects are required to rollover to 
Study 3152-201-002 within 1 month of completing their final visit assessments in either the CENTAUR or 
AURORA study. Subjects who completed the CENTAUR or the AURORA study, prior to initiation of this 
protocol at their study center, will be allowed to participate in this rollover study.
b
Subjects will continue to be seen every 3 months until CVC becomes commercially available or if 
development is terminated, as applicable. 

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8. STUDY POPULATION
8.1.
Number of Subjects 
It is expected that a total of approximately 560 subjects may rollover from both the 
CENTAUR study (652-2-203) and AURORA study (3152-301-002) (refer to Section 7.1).
8.2.
Inclusion Criteria
For a subject to be eligible for participation in this study, all of the following criteria must 
apply.
1. Subjects who have either:

Completed both Treatment Period 1 and Treatment Period 2 (Year 1 and Year 2) of 
the CENTAUR study (652-2-203), including a Year 2 liver biopsy

Completed the AURORA study and who reached an adjudicated liver-related clinical 
outcome in Part 1 or Part 2 of the study of:
o
Histopathologic progression to cirrhosis
o
MELD score ≥15
o
Ascites (requiring intervention, ie, large volume paracentesis ≥ 1L or initiation of 
a diuretic)
o
Hospitalization (as defined by a stay of ≥24 hours) for onset of: variceal bleed, 
hepatic encephalopathy (defined by a West Haven Stage of ≥2), spontaneous 
bacterial peritonitis (confirmed by diagnostic paracentesis with positive ascitic 
fluid bacterial culture)
2. Has been determined to be in a stable medical condition (minimum of approximately 
3 months from the date of the clinical event in AURORA to the Baseline Visit of this 
study) based on medical history or physical examination, in the opinion of investigator.
Inclusion criterion applies only to subjects coming from the AURORA study 
(3152-301-002).

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8.3.
Exclusion Criteria
A subject will not be eligible for participation in this study if any of the following criteria 
apply.
1.
2. Prior or planned liver transplantation
3. Other known causes of chronic liver disease, such as the following:

Alcoholic liver disease

Primary biliary cirrhosis

Primary sclerosing cholangitis

Autoimmune hepatitis

Wilson’s disease, hemochromatosis, or iron overload

Alpha-1 antitrypsin (A1AT) deficiency

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9. TREATMENTS
9.1.
Treatments Administered
Eligible subjects will receive open-label CVC 150 mg, 1 tablet administered orally once daily 
with food.
9.2.
Study Drug
9.2.1.
Investigational Product
Chemical Name:
(S)-8-[4-(2-Butoxyethoxy)phenyl]-1-isobutyl-N-(4-{[(1-propyl-
1H-imidazol-5-yl)methyl]sulfinyl}phenyl)-1,2,3,4-tetrahydro-1-
benzazocine-5-carboxamide monomethane sulfonate 
Generic Name:
Cenicriviroc mesylate
Abbreviated Name:
CVC
Laboratory Designation:
TBR-652
Trade Name:
Not applicable
The CVC drug product is formulated with fumaric acid (160 mg) and other excipients, 
including microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, 
magnesium stearate, and Opadry® II yellow (film coating).
The CVC drug product is provided as 150-mg yellow-coated, immediate release tablets for 
oral administration. 
9.2.2.
Packaging and Labeling
The study drug will be supplied, as described above, by Sponsor and will be packaged in 
high-density polyethylene (HDPE) bottles containing desiccant, and induction sealed. The 
site pharmacist, investigator, or designee will dispense study drugs. Dispensed supplies will 
contain sufficient drug to cover the visit window period (± 2 weeks).
All labels for CVC will meet all applicable requirements of the United States (US) Food and 
Drug Administration (FDA) and Annex 13 of Good Manufacturing Practices and/or all local 
regulations, as applicable.
9.2.3.
Storage
All study drug should be stored at controlled room temperature (refer to the packaging or 
study/pharmacy manual). CVC tablets will continue to be monitored for stability at ICH
recommended storage conditions. 
9.2.4.
Study Drug Dispensing and Collection
Study drug will be supplied in a bottle containing medication for each subject, which is 
sufficient for a monthly dosing supply. 
 
 

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Subjects will be instructed that 1 tablet of study drug must be taken once daily with food.
9.2.5.
Investigational Product Accountability
Responsibility for drug accountability at the study site rests with the investigator; however, 
the investigator may assign some of the drug accountability duties to an appropriate 
pharmacist or designee. Inventory and accountability records must be maintained and must 
be readily available for inspection by the study monitor and are open to inspection at any 
time by any applicable regulatory authorities.
The investigator or designee will be expected to collect and retain all used, unused, and 
partially used containers of study drug. The investigator or designee must maintain records 
that document the following:

Study drug delivery to the study site

Inventory at the site

Storage conditions

Use by each subject, including tablet counts from each supply dispensed

Return of study drug to the investigator or designee.
These records should include dates, quantities, batch/serial numbers (if available), and the 
unique code numbers (if available) assigned to the study drug and study subjects.
The study drug must be used only in accordance with the protocol. The investigator will also 
maintain records adequately documenting that the subjects were provided the study drug
specified.
Completed accountability records will be archived by the site. Guidance and information 
regarding the final disposition of all study drug are provided in the Pharmacy Manual.
9.3.
Randomization
This is an open-label study; no randomization procedures will be performed. Subjects will 
retain their subject identification number from either the CENTAUR study or AURORA 
study.
9.4.
Study Drug Administration
Subjects will take 1 tablet of open-label CVC daily for the duration of the study or upon 
study discontinuation. 
Subjects will be instructed that 1 tablet of study drug must be taken once daily with food.
Subjects will bring their study drug bottle to the clinic for drug accountability.  
If a subject has missed a dose of study drug and is still within 12 hours of the time it is 
usually taken, the subject should take a dose of the missed drug as soon as possible, with 
food. The subject may then continue the usual dosing schedule. If the subject has missed a 

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dose of a study drug more than 12 hours after the time it is usually taken, subject should not 
take the missed dose and simply resume the usual dosing schedule. The subject should not 
take a double dose to make up for a missed dose or take more than 1 tablet within 12 hours.
9.5.
Blinding
No blinding is planned for this open-label study.
9.6.
Prior and Concomitant Therapy
A prior medication is defined as a (nonstudy) medication taken at any time during 30 days 
before first study drug intake and stopped before the date of first dose of study drug. Any 
prior medication received within 30 days before the first dose of study drug will be recorded 
in the electronic case report form (eCRF).
All medications (or treatments) other than study drug taken or received by the subject at any 
time during the study from first intake of study drug through the 1-Month Follow-up Visit 
after last study drug intake (or final visit, for subjects who do not complete a Follow-up 
Visit) will be considered concomitant medications (or treatments). This includes medications 
ongoing at the time of first study drug intake and medications started after first study drug 
intake. A new concomitant medication will be a (nonstudy) medication started or for which 
the dose increased between first study drug intake through the 1-Month Follow-up Visit after 
last study drug intake (or final visit, for subjects who do not complete a Follow-up Visit). All 
concomitant medications and treatments other than study drug, taken or received at any time 
during the study from first intake of study drug through to the 1-Month Follow-up Visit, will
be recorded in the eCRF. 
A subsequent medication is defined as a (nonstudy) medication taken after the date of the 
1-Month Follow-up Visit (or 30 days after last intake of study drug, if no 1-Month Follow-up 
Visit occurs). Any subsequent medication taken after the 1-Month Follow-up Visit (or 
30 days after last intake of study drug, if no 1-Month Follow-up Visit occurs) will be 
recorded in the eCRF.
Subjects will be allowed to continue their usual standard-of-care medications that are not 
specifically excluded by the protocol. The detailed list of disallowed medications and the list 
of medications that are allowed but with specific restrictions are provided in Appendix 20.4. 
The following classes of medications are disallowed at any time during the open-label 
treatment period, from Baseline through the 1-Month Follow-up Visit, if applicable:

Potent CYP3A4 inhibitors and CYP3A4 inducers will be excluded

Potent CYP2C8 inhibitors will be excluded

Drugs with narrow therapeutic windows that are sensitive CYP3A4 substrates will be
excluded (ie, drugs that should not be coadministered with weak CYP3A4 inhibitors 
such as CVC)
The disallowed concomitant medications commonly administered to patients with NASH are 
provided in Appendix 20.4. 

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Should subjects have a need to initiate treatment with any disallowed concomitant 
medication, the medical monitor must be consulted prior to initiation of the new medication. 
In instances where a disallowed medication is initiated prior to discussion with the medical 
monitor, the investigator must notify the Sponsor or designee as soon as he/she is aware of 
the use of the excluded medication to discuss the subject's continued participation in the 
study.
The following medications are allowed, but should be used with caution as CVC (a weak
CYP3A4 inhibitor and BCRP inhibitor) may increase exposure of these CYP3A4 and BCRP 
substrates or these medications may affect the absorption of CVC. If used, these medications 
should be used at the doses recommended in Appendix 20.4. Clinical monitoring and dose 
titration are recommended to achieve the desired clinical response. 
Lipid Lowering Agents: 
Atorvastatin, simvastatin, pravastatin, and lovastatin (CYP3A4 substrates), and rosuvastatin 
(BCRP substrate)
Pitavastatin use is allowed without dose restriction.
Other Medications to be Used with Caution
Intravenous midazolam use is allowed at the discretion of the investigator for surgical 
outpatient procedures; however, if given for biopsies performed during this study, or for any 
procedure requiring this medication after intake of study drug, the first dose should be 
reduced by 50% of the recommended dose and titrated according to the desired clinical 
response. 
Intravenous alfentanil or fentanyl are not allowed for biopsies performed during the 
open-label study or for any procedures requiring these medications after intake of study drug. 
When required, acid-reducing agents should be administered at least 2 hours after the CVC 
dose to ensure that adequate CVC concentrations are maintained. When possible, use of an 
H2 receptor antagonist (except cimetidine) or antacids is preferred over a PPI. It is 
recommended to start with the lowest dose of these agents and titrate according to clinical 
response. 

If H2 receptor antagonists (eg, famotidine or ranitidine) are used, these should 
preferably be given from 2 to 12 hours after administration of study drug at a dose 
that does not exceed doses comparable to famotidine 40 mg daily.  

If antacids (eg, aluminum hydroxide, calcium carbonate, magnesium carbonate, 
magnesium hydroxide, or bismuth subsalicylate) are used, these should preferably be 
given at least 4 hours after administration of study drug due to their immediate effect 
in increasing gastric pH. 

If PPIs (eg, omeprazole, lansoprazole, esomeprazole, pantoprazole, rabeprazole, or 
dexlansoprazole) must be utilized, these should preferably be given approximately 
3 hours after administration of study drug at a dose that does not exceed doses 
comparable to omeprazole 20 mg daily. Due to the prolonged acid-reducing effect of 

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PPIs (~16 – 24 hours), it is advised to follow these dosing recommendations to reduce 
their potential impact on CVC absorption at subsequent dosing. 
9.7.
Additional Restrictions and Precautions
Subjects should refrain from strenuous physical activity (eg, weight lifting, strenuous yard
work, intensive exercise workouts) for 48 hours prior to study visits and laboratory 
evaluations.
If a liver biopsy is required, it is allowed. However, the medical monitor must be notified of 
the scheduled biopsy. Data from the pathology reading of liver biopsies will be collected on 
the eCRF. 
9.8.
Treatment Adherence
Subjects will bring all of their study-supplied pill bottles to every clinic visit, and clinic staff 
will assess adherence based on the number of remaining pills less any overage provided to 
cover the visit window (± 2 weeks). Subjects who miss doses must be counseled on the 
importance of adhering to their daily dosing schedule. 

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10. STUDY PROCEDURES
Study procedures are summarized across all study visits within the Schedule of Assessments
(Table 20-1).
Subjects should refrain from strenuous physical activity (eg, weight lifting, strenuous yard 
work, intensive exercise workouts) for 48 hours prior to study visits and laboratory 
evaluations.
Of note, liver biopsies are not mandated on this study. However, should a liver biopsy be 
conducted at the discretion of the investigator, the site must notify the medical monitor of the 
scheduled biopsy. Data on the liver biopsy will be collected in the eCRF. Additionally, 
transient elastography (TE) is not required in this study, however if assessment of liver 
stiffness is made via TE or liver imaging, these data will be collected in the eCRF.
10.1.
Baseline
Prior to any clinical procedures and evaluations, written signed informed consent must be 
obtained. Subjects will be required to rollover to this continued access study and undergo 
Baseline Visit assessments within 1 month of completing their final visit assessments in 
either the CENTAUR study or AURORA study (except in the case of eligible subjects who
completed these studies prior to initiation of this protocol at their study center, who will be 
allowed to participate in this rollover study). 
At the Baseline Visit, the following procedures and assessments should be conducted:

Informed consent

Confirm inclusion/exclusion criteria

Adverse events and concomitant medications

Symptom-directed physical examination

Medical history

Vital signs (systolic and diastolic blood pressure, temperature, pulse rate, and 
respiration rate)

Height and weight, for determination of body mass index (BMI), waist circumference 
and hip circumference

Urine pregnancy test for females of childbearing potential only. Positive urine 
pregnancy tests will be confirmed with a serum test

Blood draw for determining/obtaining the following:
o
Hematology and serum chemistry laboratory tests (see Section 11.1.2)
o
Coagulation profile, including INR (see Section 11.1.2)
o
FSH from postmenopausal women only (not required if taking hormone 
replacement therapy or surgically sterile)

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o
Blood collection for IgG, anti-SMA (smooth muscle antibodies), anti-LKM1
(liver/kidney microsome type 1), antinuclear antibody (ANA), and anti-LC1 (liver 
cytosol type 1)
o
Plasma and serum samples for storage 

Study drug dispensation (see Section 9.2.4)
10.2.
Open-label Treatment Period (Months 3, 6, 9, 12, 15, 18, 21, 24, etc., until CVC 
becomes commercially available or if development is discontinued, as 
applicable) 
Subjects should return to the clinic every 3 months for general safety assessments. The 
following procedures and assessments are to be conducted at each of the clinic visits:

Adverse events and concomitant medications

Symptom-directed physical examination

Urine pregnancy test for females of childbearing potential only. Positive urine 
pregnancy tests will be confirmed with a serum test.

Blood draw for determining/obtaining the following:
o
Hematology and serum chemistry laboratory tests (see Section 11.1.2)
o
Coagulation profile, including INR (see Section 11.1.2)
o
Plasma and serum samples for storage

Study drug accountability (see Section 9.2.5)
10.3.
Discontinuation Visit 
Subjects may discontinue study treatment at any time for any reason (see Section 10.6)
without bias or penalty to medical care. 
For subjects who discontinue study drug for any reason while the study is ongoing, every 
effort should be made to ensure that they return for discontinuation procedures within 
48 hours after discontinuing study drug. These subjects will be required to return to the clinic 
1 month after the last dose of study drug for a Follow-up Visit (see Section 10.4).
The following procedures and assessments for Discontinuation will be conducted:

Adverse events and concomitant medications

Symptom-directed physical examination

Weight

Urine pregnancy test for females of childbearing potential only (positive urine 
pregnancy tests will be confirmed with a serum test)

Blood draw for determining/obtaining the following:
o
Hematology and serum chemistry laboratory tests (see Section 11.1.2)

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o
Coagulation profile, including INR (see Section 11.1.2)
o
Plasma and serum samples for storage 

Study drug accountability (see Section 9.2.5)
10.4.
1-Month Follow-up
Subjects should undergo follow-up evaluations approximately 1 month after the last dose of 
study drug. Subjects who discontinue study drug will be required to return to the clinic 
1 month after the last dose of study drug for a Follow-up Visit, at which time the following 
procedures and assessments are to be performed:

Adverse events and concomitant medications

Symptom-directed physical examination

Urine pregnancy test for females of childbearing potential only. Positive urine 
pregnancy tests will be confirmed with a serum test

Blood draw for determining/obtaining the following:
o
Hematology and serum chemistry laboratory tests (see Section 11.1.2)
o
Coagulation profile, including INR (see Section 11.1.2)
o
Plasma and serum samples sample for storage

Study drug accountability (see Section 9.2.5)
10.5.
Missed Scheduled Visits
Every attempt should be made to have subjects stay on schedule for study visits (Table 20-1). 
10.6.
Criteria for Discontinuation of Study Treatment

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11. STUDY ASSESSMENTS
No efficacy or PK assessments are planned for this continued access study. 
11.1.
Assessments of Safety
Adverse events will be assessed at each study visit, in addition to safety laboratory 
parameters. 
11.1.1.
Adverse Events and Serious Adverse Events
11.1.1.1.
Definitions
11.1.1.1.1.
Adverse Event
An AE is any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with 
the use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product.
11.1.1.1.2.
Treatment-Emergent Adverse Events
An event will be considered a treatment-emergent adverse event (TEAE) if:

The event began on or after the date of the first dose of study drug; or 

An exacerbation of a chronic or intermittent pre-existing condition, including either 
an increase in frequency and/or intensity of the condition on or after the date of the 
first dose of study drug. 
An AE that occurs more than 30 days after the last dose of study drug will not be counted as 
a TEAE.
11.1.1.1.3.
Adverse Drug Reaction
An adverse drug reaction (ADR) is defined as any adverse event caused by the use of a 
pharmaceutical product. Adverse reactions are a subset of all suspected adverse reactions for 
which there is reason to conclude that the pharmaceutical product caused the event.
11.1.1.1.4.
Suspected Adverse Reaction 
Suspected adverse reaction (SAR) means any adverse event for which there is a reasonable 
possibility that the study treatment caused the adverse event. “Reasonable possibility” means 
there is evidence to suggest a causal relationship between the study treatment and adverse 
event. A suspected adverse reaction implies a lesser degree of certainty about causality than 
adverse reaction, which means an adverse event caused by a study treatment.

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11.1.1.1.5.
Unexpected Adverse Event or Reaction
An adverse event or suspected adverse drug reaction is considered “unexpected” if it is not 
listed in the investigator brochure or is not listed at the specificity or severity that has been 
observed; or, if an investigator brochure is not required or available, is not consistent with the 
risk information described in the general investigational plan. 
11.1.1.1.6.
Events Related to Disease Under Study
Worsening of a pre-existing illness other than the disease under study will be assessed as an 
AE. If such an AE meets the definition of an SAE (see Section 11.1.1.1.10), it must be 
reported as such (see Section 11.1.1.2).
11.1.1.1.7.
Clinically Significant Laboratory Abnormalities
Any laboratory abnormalities deemed clinically significant by the investigator must be 
reported as an AE. A clinically significant abnormality is a confirmed abnormality (by repeat 
testing) that is changed sufficiently from baseline so that in the judgment of the investigator a 
change in management is warranted. This alteration may include: monitoring the laboratory 
test further, initiating other diagnostic tests or procedures, changing ongoing treatment, or 
administering new treatment. 
See Section 11.1.1.2 for details regarding the management and monitoring of laboratory 
abnormalities of interest. 
11.1.1.1.8.
Surgical Procedures
Surgical procedures themselves are not AEs; they are therapeutic measures for conditions 
that require surgery. The condition for which the surgery is required may be an AE, if it 
occurs or is detected during the study period. Planned surgical measures permitted by the 
clinical study protocol and the condition(s) leading to these measures are not AEs, if the 
condition(s) was (were) known before the start of the study treatment. In the latter case, the 
condition should be reported as medical history.
11.1.1.1.9.
Overdose
An overdose is defined as a subject’s report of taking more than 1 tablet of study drug (ie,
more than 1 tablet per day of CVC). Overdose per se will not be reported as an AE or SAE 
unless it is an intentional overdose taken with possible suicidal/self-harming intent. Such 
overdoses should be reported regardless of sequelae. For reporting purposes, overdose will be 
considered an SAE only if any of the seriousness criteria are met (see definition in 
Section 11.1.1.1.10).
11.1.1.1.10.
Serious Adverse Event or Serious Adverse Reaction
An AE or suspected adverse reaction is considered serious if, in the view of either the 
investigator or Sponsor, it results in any of the following outcomes:

Death

Life-threatening AE

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o
An AE or suspected AE is considered life-threatening if, in the view of either the 
investigator or Sponsor, its occurrence places the patient or subject at immediate 
risk of death. It does not include an AE or suspected adverse reaction that, had it 
occurred in a more severe form, might have caused death.

Inpatient hospitalization (ie, admission, overnight stay) or prolongation of existing 
hospitalization

Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions

Congenital anomaly/birth defect

Important medical events
o
An important medical event is one that, when based upon appropriate medical 
judgment, may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed above in the definition of an 
SAE. (Examples of such events include allergic bronchospasm requiring intensive 
treatment at an emergency room or at home, blood dyscrasias, convulsions that do 
not result in inpatient hospitalization, or the development of drug dependency or 
drug abuse.)
11.1.1.1.11.
Adverse Events of Special Interest
An adverse event of special interest (AESI) (serious or nonserious) is one of scientific and 
medical concern specific to the Sponsor’s study drug/device or program, which warrants 
ongoing monitoring and rapid communication by the investigator to the Sponsor. Such an 
event might warrant further investigation in order to characterize and understand it.
Elevations in biochemistry that are associated with liver injury have been identified as a 
potentially important risk and are considered AESI for the study treatment in this protocol. 
Biochemical criteria for suspected DILI cases are defined in Section 11.1.3.4. Cases of 
suspected DILI as defined by the prespecified criteria in Section 11.1.3.4 should be reported 
to the Sponsor within 24 hours on the AESI form (see Section 1) and will be adjudicated by a 
hepatologist with expertise in DILI.
11.1.1.2.
Adverse Event and Clinically Significant Laboratory Abnormality Recording
Treatment-emergent adverse events and laboratory test abnormalities considered to be 
clinically significant should be recorded as adverse events in the CRF. 
The AE or clinically significant laboratory abnormality should be reported in standard 
medical terminology. If known, the diagnosis of the underlying illness or disorder should be 
recorded, rather than its individual symptoms. If a definitive diagnosis is not possible, the 
individual symptoms and signs should be recorded.
If the laboratory abnormalities are part of a clinical constellation of signs and/or symptoms 
that comprise a medical diagnosis, then the terminology for that medical diagnosis should be 
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Adverse events and clinically significant laboratory abnormalities fall into the categories of 
“nonserious” and “serious.” From the time of informed consent and throughout the study, all 
AEs and clinically significant laboratory abnormalities must be recorded in the eCRF, 
regardless of apparent causality from use of the study treatment.
The following information should be captured for all AEs and clinically significant 
laboratory abnormalities: date of onset and end date or outcome (eg, ongoing), severity of the 
event, seriousness of the event, investigator’s opinion of the relationship to investigational 
product (CVC), action taken with regard to any of the study drug and treatment required for 
the AE, cause of the event (if known), and information regarding the resolution/outcome.
Adverse events classified as serious must be recorded on the appropriate SAE reporting tool 
and reported to Sponsor using expeditious handling to comply with regulatory requirements 
(see Section 11.1.1.5).
11.1.1.3.
Adverse Event Classification
The intensity of an AE or clinically significant laboratory abnormality will be graded 
according to the scale below in addition to the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 Table for Grading the 
Severity of Adult Adverse Events (see Appendix 20.2). The clinical significance of the AE is 
determined by the investigator. The investigator is encouraged to consult with the medical 
monitor.

Grade 1 (Mild): Asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated

Grade 2 (Moderate): Minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADL)

Grade 3 (Severe): Medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-
care ADL

Grade 4 (Life-Threatening): Life-threatening consequences; urgent intervention 
indicated

Grade 5 (Death): Death related to AE
When the intensity of an AE changes over time for a reporting period (eg, between visits), 
each change in intensity will be reported as an AE until the event resolves. For example, 
2 separate AEs will be reported if a subject experiences Grade 1 diarrhea for 3 days, meeting 
the definition of an AE, and then after 3 days the event increases to a Grade 3 intensity that 
lasts for 2 days and then resolves. The Grade 1 event will be reported as an AE with a start 
date equal to the day the event met the AE definition and a stop date equal to the day that the 
event increased in intensity from Grade 1 to Grade 3. The Grade 3 event will also be reported 
as an AE with the start date equal to the day the event changed in intensity from Grade 1 to 
Grade 3 and a stop date on the day that the event changed intensity again or resolved. For 
analysis purposes, this will be considered 1 AE for this subject and the maximum intensity 
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The relationship or association of the AE to a study drug should be assessed using clinical 
judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the 
investigational medicinal product. For SAEs, an alternative causality must be 
provided (eg, pre-existing condition, underlying disease, intercurrent illness, or 
concomitant medication)

Yes: A temporal relationship exists between the AE onset and administration of the 
investigational medicinal product that cannot be readily explained by the subject’s 
clinical state or concomitant therapies. Furthermore, the AE appears with some 
degree of certainty to be related, based on the known therapeutic and pharmacologic 
actions or AE profile of the study drug. In case of cessation or reduction of the dose, 
the AE abates or resolves and reappears upon rechallenge. 
It should be emphasized that ineffective treatment should not be considered as causally 
related in the context of adverse event reporting.
The relationship to study procedures (eg, invasive procedures such as venipuncture or liver 
biopsy) should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study 
procedure

Yes: The adverse event occurred as a result of protocol-mandated procedures such as 
venipuncture.
11.1.1.4.
Adverse Event Coding
AE verbatim terms provided by the investigator will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA), Version 16.0 or later.
11.1.1.5.
Reporting of Serious Adverse Events
The Sponsor is required to expedite to regulatory authorities reports of SAEs, serious ADRs, 
or suspected unexpected serious adverse reactions (SUSARs) in line with relevant legislation 
or regulations, including the applicable US FDA Code of Federal Regulations, the European 
Commission Clinical Trials Directive (2001/20/EC), and other country specific legislation or 
regulations. Expectedness of SAEs will be determined by Sponsor using reference safety 
information specified in the Investigator Brochure. 
Any SAE, serious ADR, or SUSAR that occurs during the study from the time of signing the 
informed consent form (ICF) to within 1 month following discontinuation of study treatment, 
regardless of relationship to the study treatment, must be reported within 24 hours to the 
contact below: 
Send completed Safety Report Forms to Global Drug Safety and Epidemiology,
Allergan plc (see Section 1)
The required SAE information must be completed on the SAE Form. The Sponsor may 
request additional information from the investigator to ensure the timely completion of 

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accurate safety reports. For questions on SAE reporting, please contact the medical monitor 
(see Section 1 for contact information).
A copy of the submitted SAE form must be retained on file by the investigator. The 
investigator must submit the SAE to the IRB/IEC according to local requirements and retain 
documentation of these submissions in the site study file.
The investigator must take all therapeutic measures necessary for resolution of the SAE. Any 
medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the event description section of the SAE Form.
If the investigator detects an SAE in a study subject after the end of the period of 
observation, and considers the event possibly related to prior study treatment, he/she should 
contact the medical monitor to determine how the event should be documented and reported.
In case of emergency, contact the medical monitor (see Section 1 for contact information).
All investigators will receive a safety letter notifying them of relevant SUSAR reports. The 
investigator should notify the IRB/IEC as soon as is practical, of serious events in writing 
where this is required by local regulatory authorities, and in accordance with the local 
institutional policy.
In accordance with the EU Clinical Trials Directive (2001/20/EC), the Sponsor or specified 
designee will notify worldwide regulatory authorities and the relevant Ethics Committees in 
concerned Member States of applicable SUSARs as individual notifications or through a 
periodic line listing.
11.1.1.6.
Follow-up of AEs and SAEs
Adverse events (including SAEs) will be collected from the time of informed consent, 
throughout the treatment period, until 1 month after the last dose of study drug is 
administered.
All subjects who have AEs, whether considered associated with the use of the investigational 
product or not, must be monitored to determine the outcome. The clinical course of the AE 
will be followed up according to accepted standards of medical practice, even after the end of 
the period of observation, until a satisfactory explanation is found or the investigator 
considers it medically justifiable to terminate follow-up. Should the AE result in death, a full 
pathologist’s report should be supplied if and when available. A plasma sample for PK 
should be collected, preferably within 24 to 48 hours of last intake of study drug, in any 
subject who develops an AE of hepatic injury or decompensation, or if early treatment 
discontinuation was due to an AE. The date and time of the PK draw and the last dose 
of study drug must be recorded in the eCRF.
11.1.1.7.
Pregnancy
If a female subject becomes pregnant during the study, the subject must be instructed to 
discontinue study drug and inform the investigator immediately. The investigator should 
report all pregnancies occurring in a subject or partner of a subject participating in the study
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within 24 hours of becoming aware of the pregnancy. The investigator should counsel the 
subject regarding the possible effects of prior study drug exposure on the fetus and the need 
to inform the study site of the outcome of the pregnancy.
Any pregnancy complication or elective termination of a pregnancy for medical reasons will 
be recorded as an AE or a SAE. Elective abortion procedures, without complications, should 
not be considered as AEs.
All reports of congenital abnormalities/birth defects and spontaneous abortions/miscarriages 
should be reported as an SAE for this study. Furthermore, any SAE occurring as an adverse 
pregnancy outcome post-study must be reported to the CRO Drug Safety.
Pregnancies that occur more than 1 month after the subject has discontinued study drug do 
not require monitoring. 

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11.1.2.
Laboratory Assessments
11.1.2.1.
Measurement of Laboratory Assessments
A central laboratory will perform clinical safety laboratory tests. Urine pregnancy tests will 
be performed at the site using a dipstick method. 
A complete list of all laboratory tests is provided in Appendix 20.5.
Refer to the Manual provided by Sponsor for details on the laboratories for this study. 
Samples for hematology and serum chemistry will be prepared using standard procedures. 
Refer to the laboratory manual provided by Sponsor for further details and specifications for 
sample handling, processing, and shipment.
11.1.2.2.
Clinically Significant Laboratory Abnormalities
Any laboratory test showing abnormal results (including those recorded as AEs) that are 
believed to be possibly/probably related to study drug treatment will be repeated weekly (or 
as often as deemed prudent by the investigator) until the abnormality is resolved, returns to 
baseline, or is otherwise explained. Whenever possible, the etiology of the abnormal findings 
will be documented on the eCRF. See Section 11.1.1.1.7 for a definition of clinically 
significant laboratory abnormalities. 
11.1.3.
Toxicity Management
Clinical events and clinically significant laboratory abnormalities will be graded according 
NCI CTCAE version 4.03 (Appendix 20.2).
11.1.3.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug at the discretion of the investigator.
11.1.3.2.
Grade 3 Laboratory Abnormality or Clinical Event
For detailed management of subjects with ALT, AST, alkaline phosphatase (ALP), or 
bilirubin elevations, see Section 11.1.3.4.
For Grade 3 laboratory abnormalities, a confirmatory measurement should be obtained within 
48 to 72 hours after the laboratory results become available. 

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11.1.3.3.
Grade 4 Laboratory Abnormality or Clinical Event
For detailed management of subjects with ALT, AST, ALP, or bilirubin elevations, see 
Section 11.1.3.4.
For Grade 4 laboratory abnormalities, a confirmatory measurement should be obtained within 
48 to 72 hours after the laboratory results become available. 

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Table 11-1
Management of Subjects with Confirmed ALP, ALT, AST, or Bilirubin Elevations With or Without Liver-related Clinical 
Symptoms

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11.2.
Assessments of Drug Accountability and Medication Adherence
Drug accountability through the assessment of tablet counts will be performed by clinic staff 
at each clinic visit. 
Subjects will be instructed to bring their bottles of study drug (used and unused) with them to 
every visit. The investigator, or designee, will count all returned study drug to determine 
compliance. Subjects will receive sufficient number of study drug bottles and be reminded 
that 1 tablet of study drug must be taken once daily with food.
If the study drug compliance drops below 80% at any given time during the Treatment 
Period, the investigator, or designee, should discuss compliance with subject and counsel the 
subject appropriately. Nonadherence includes missed doses in addition to taking the wrong 
dose. The investigator must encourage compliance with the study drug and with the study 
procedures at all times. 

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12. STATISTICS
No inferential statistical testing will be conducted for this continued access study. Summaries 
of demographics, baseline characteristics, treatment exposure, and safety parameters will be 
analyzed by descriptive statistics for the continuous variables and frequency counts with 
incidence rates for the dichotomous or categorical variables.
12.1 
Safety
Duration of exposure (last day minus first day, plus 1) will be summarized. All AEs will be 
listed for individual subjects showing both verbatim and MedDRA preferred terms. AEs will 
be tabulated by the preferred term and system-organ classification. The occurrence of TEAEs 
will be summarized using MedDRA preferred terms and system organ classifications. 
Summaries will also be provided by severity, seriousness and relationship to study drug.
Descriptive summaries of clinical laboratory results will be presented. Laboratory 
abnormalities will be graded according to NCI CTCAE version 4.03 if recorded as an AE and 
categorized as a TEAE. The number and percentage of subjects experiencing 
treatment-emergent graded toxicities will be summarized by severity grade. Laboratory 
toxicity shifts from baseline to post-baseline assessments will be summarized. Changes from 
baseline in laboratory tests will be summarized.
Prior and concomitant medications will be coded based on a World Health Organization 
preferred term and drug classification. The number and percent of subjects taking 
concomitant medications will be summarized using preferred terms and drug classifications.

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13. QUALITY CONTROL AND QUALITY ASSURANCE
13.1.
Sponsor Audits
During the study, individuals from the Sponsor Quality Assurance department and/or their 
authorized representative may visit the investigator’s site to conduct an audit of the study. 
The purpose of this visit will be to determine the investigator’s adherence to the protocol, 
applicable regulations, and Sponsor’s procedures, in addition to assessing the accuracy of the 
study data. Prior to initiating this audit, the investigator will be contacted by Sponsor to 
arrange a convenient time for this visit. The investigator and staff are expected to cooperate 
with the auditors and allow access to all subject records supporting the eCRFs and other 
study-related documents.
13.2.
Inspection by Regulatory Authorities
At some point during the investigational product’s development program, a regulatory 
authority may visit the investigator to conduct an inspection of the study and the site. The 
investigator and staff are expected to cooperate with the inspectors and allow access to all 
source documents supporting the eCRFs and other study-related documents. The investigator 
must immediately notify Sponsor when contacted by any regulatory authority for purposes of 
conducting an inspection.

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14. ETHICS AND PROTECTION OF HUMAN SUBJECTS
14.1.
Compliance Statement
The investigator agrees to conduct the study in compliance with the protocol, ICH GCP 
guidelines, and all local and national regulations.
The investigator must adhere to the protocol as described in this document and agree that 
deviations to the protocol, with the exception of medical emergencies, must be discussed and 
approved by Sponsor prior to seeking approval from the IRB/IEC. The investigator is 
responsible for enrolling subjects who have met the protocol inclusion and exclusion criteria 
or must have obtained prior documented approval from Sponsor prior to enrollment in the 
study. The IRB/IEC that granted original approval, or the IRB/IEC currently responsible for 
overseeing the conduct of the study, must be notified of all changes in and deviations from 
the protocol that may increase risk to the subject, and/or that may adversely affect the rights 
of the subject or validity of the investigation. The investigator must send a copy of the 
approval letter from the IRB/IEC to Sponsor or CRO and retain the original in the site study 
regulatory file.
14.2.
Institutional Review Board/Independent Ethics Committee
It is the responsibility of the investigator to assure that all aspects of the ethics review are 
conducted in accordance with the Declaration of Helsinki (October 2008) as described in the 
ICH E6: GCP, and/or local laws, whichever provides the greatest level of protection for the 
study participants. The protocol and any information supplied to the subject to obtain 
informed consent, including written ICF(s), subject recruitment procedures 
(eg, advertisements), and written information to be provided to subjects (information 
leaflets), must be reviewed and approved by a qualified IRB/IEC prior to enrollment of 
participants in the study. Prior to initiation of the study, Sponsor must receive documentation 
of the IRB/IEC approval, which specifically identifies the study/protocol, and a list of the 
committee members.
Amendments to the protocol and revisions to the informed consent must also be submitted to 
and, if required, approved by the IRB/IEC.
Investigators must submit progress reports to the IRB/IEC in accordance with the IRB/IEC 
requirements. Annual re-approval of the study must be obtained. Copies of progress reports 
and annual re-approvals must be sent to Sponsor.
When Sponsor provides the investigator with a safety report, the investigator must promptly 
forward a copy to the IRB/IEC.
After completion or termination of the study, the investigator must submit a final report to 
the IRB/IEC and to Sponsor.
The investigator, as part of the records retention requirements for the study, must maintain 
documentation of all submissions, correspondence, and approvals to and from the IRB/IEC.
The investigator is responsible for conducting the study in accordance with the protocol, all 
applicable laws, regulations, and GCP according to ICH guidelines.

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14.3.
Informed Consent
Preparation of the consent form is the responsibility of the investigator and Sponsor or 
designee and must include all elements required by the ICH, GCP, and applicable regulatory 
requirements, and must adhere to GCP and to the ethical principles that have their origin in 
the Declaration of Helsinki.
A template will be provided by Sponsor or designee. Sponsor or designee must review and 
approve all changes to site-specific ICFs.
The consent form must include a statement that Sponsor or designee and regulatory 
authorities have direct access to subject records. Prior to the beginning of the study, the 
investigator must have the IRB/IEC’s written approval/favorable opinion of the written ICF 
and any other information to be provided to the subjects.
Before being enrolled in the clinical study, subjects must consent to participate after the 
nature, scope, and possible consequences of the study have been explained in a form 
understandable to them.
An informed consent document that includes both information about the study and the 
consent form will be prepared and given to the subject. This document will contain all the 
elements required by the ICH E6 Guideline for Good Clinical Practice and any additional 
elements required by local regulations. The document must be in a language understandable 
to the subject and must specify who informed the subject. Where required by local law, the 
person who informs the subject must be a physician.
A copy of the signed consent document must be given to the subject. The original signed 
consent document will be retained by the investigator.
The investigator will not undertake any measures specifically required only for the clinical 
study until valid consent has been obtained.
The investigator must inform the subject’s primary physician about the subject’s 
participation in the trial if the subject has a primary physician and if the subject agrees to the 
primary physician being informed.
14.4.
Subject Confidentiality
Applicable data privacy laws and regulations must be adhered to. The investigator and 
Sponsor are responsible for ensuring that sensitive information is handled in accordance with 
local requirements (eg, Health Insurance Portability and Accountability Act [HIPAA]). 
Appropriate consent and authorizations for use and disclosure and/or transfer (if applicable) 
of protected information must be obtained.
Subject names will not be supplied to Sponsor. Only the subject number and subject initials 
will be recorded in the eCRF, and if the subject name appears on any other document (eg,
laboratory report), it must be obliterated on the copy of the document to be supplied to 
Sponsor. Study findings stored on a computer will be stored in accordance with local data 
protection laws. The subjects will be informed that representatives of Sponsor, IRB/IEC, or 
regulatory authorities may inspect their medical records to verify the information collected, 
and that all personal information made available for inspection will be handled in strictest 
confidence and in accordance with local data protection laws.

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14.5.
Study Conduct
The study will be conducted in compliance with the Declaration of Helsinki (October 2008) 
and the ICH E6 Guideline for GCP. All national, state, and local laws of the pertinent 
regulatory authorities will be followed.
If it is necessary to amend either the protocol or the ICF, the investigator will be responsible 
for ensuring that the IRB/IEC reviews and approves the amended documents. Amended ICFs 
must be obtained and used for obtaining consent from new subjects.
14.6.
Study Discontinuation
Both the Sponsor and the investigator reserve the right to terminate the study, according to 
the terms specified in the study contract. The investigator is to notify the IRB/IEC in writing 
of the study’s completion or early termination, and send a copy of the notification to Sponsor 
or CRO and retain one copy for the site study regulatory file.

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15. DATA HANDLING AND RECORD KEEPING
15.1.
Data Management Responsibilities
Laboratory data will be imported to the database electronically.
All data entry, verification, and validation will be performed in accordance with the current 
standard operating procedures of Sponsor or its designee. The database will be authorized for 
lock once no data queries are outstanding, all study data are considered clean, and all defined 
procedures completed.
15.2.
Data Handling and Record Keeping
15.2.1.
Data Collection and Retrieval
The investigative site will be provided with eCRFs in which to record all the protocol-
specified data for each subject in this study. Entries made in the eCRF must be verifiable 
against source documents, or in certain circumstances as directed by Sponsor, entries will 
have been directly entered into the eCRF; in such cases, the entry in the eCRF will be 
considered as the source data. Data reported in the eCRF that are derived from source 
documents should be consistent with the source documents or the discrepancies should be 
explained.
The investigator will be responsible for reviewing all data and eCRF entries and will sign and 
date the designated pages in each subject’s eCRF, verifying that the information is true and 
correct.
Queries generated by Data Management at Sponsor will be sent to the study site for 
resolution. The investigator is responsible for the review and approval of all responses to 
eCRF queries.
15.2.2.
Records Retention
The investigator must ensure that all records pertaining to the conduct of the clinical study, 
ICFs, drug accountability records, source documents, and other study documentation are 
adequately maintained for a period of 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product.
The investigator must not destroy any records associated with the study without receiving 
approval from Sponsor. The investigator must notify Sponsor in the event of accidental loss 
or destruction of any study records. If the investigator leaves the institution where the study 
was conducted, Sponsor must be contacted to arrange alternative record storage options.
Whenever possible, an original recording of an observation must be retained as the source 
document. However, a photocopy of a record is acceptable provided it is legible and is a 
verified copy of the original document.
All eCRF data entered by the site (including audit trail), as well as computer hardware and 
software (for accessing the data), will be maintained or made available at the site in 

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compliance with applicable record retention regulations. Sponsor will retain the original 
eCRF data and audit trail.
15.2.3.
Study Monitoring and Access to Source Documents
Qualified representatives of Sponsor or its designees (“study monitors”) may monitor the 
study according to a predetermined monitoring plan. Monitoring visits provide Sponsor with 
the opportunities to do the following:

Evaluate the progress of the study

Verify the accuracy and completeness of eCRFs

Assure that all protocol requirements, applicable laws and/or regulations, and 
investigator’s obligations are being fulfilled

Resolve any inconsistencies in the study records
If a monitoring visit is scheduled, the investigator must allow the study monitors to review, at 
mutually convenient times during the study and after the study has been completed, all 
eCRFs and office, hospital, and laboratory records supporting the participation of each 
subject in the study. The eCRFs and other documentation supporting the study must be kept 
up-to-date by the investigator and the research staff at the investigative site. These study 
materials must be available for review by the study monitor, and/or other qualified 
representatives of Sponsor, at each monitoring visit.
The study monitor will review the various records of the study (eCRFs, subject medical and 
laboratory records, and other pertinent data). The study monitor will verify the eCRF data 
against original source documentation for accuracy and completeness. The study monitor will 
identify data discrepancies and collaborate with the investigator and research staff to resolve 
the discrepancies in a timely manner. Protocol deviations will also be identified and recorded 
on a “Protocol Deviation Log.” The study monitor will follow an “Issue Escalation” plan in 
order to ensure that each issue identified during a monitoring visit is appropriately 
documented, reported, and resolved in a timely manner in accordance with the plan’s 
requirements.

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16. PUBLICATION POLICY
Neither the Institute nor the Principal Investigator shall have the right to publish or present 
any materials made available or generated through the Study except as specified herein. 
The Institute and the Principal Investigator shall be free to publish or present site-specific 
results of the Project subject to the following conditions:
a. In the case of a Study conducted at multiple institutions or study sites, Institute and 
Principal Investigator agree that they will not submit a publication or make any presentation 
prior to the initial publication of the joint, multi-center results of the Study, which shall be 
coordinated by Sponsor;
b. Institute and Principal Investigator agree that any authorized publication or presentation 
shall not reveal any of the Sponsor’s Information without the expressed written consent of 
the Sponsor;
c. Institute and Principal Investigator shall send Sponsor a copy of any such proposed 
publication for Sponsor’s review and comment ninety (90) days prior to submission for 
publication and shall not disclose to any third party prior to such submission any data, 
results, discoveries, or inventions arising from the clinical research study regardless of a 
determination of the ownership of rights to such material;
d. Institute and Principal Investigator, upon Sponsor’s request, shall delete any of Sponsor’s 
Information in the proposed publications; and shall not include raw data in such publications, 
except in the case of any information or data to the extent necessary to present the analysis in 
a manner consistent with generally accepted scientific and academic standards; and 
e. Institute and Principal Investigator, upon Sponsor’s request, shall delay submission for any 
publication or presentation while the Sponsor files applications for patents or other 
registrations of intellectual property rights.
Any publication or presentation, including summaries or abstracts will appropriately 
reference the support received from the Sponsor for the conduct of the Project The parties 
agree that any authorized publication or presentation shall comply with applicable guidelines 
set forth by International Committee of Medical Journal Editors (ICMJE) and Good 
Publications Practice for Communicating Company Sponsored Medical Research (GPP2).
Institute agrees that pursuant to any authorized publication or presentation, authors must 
disclose in their manuscripts, journal submissions, and elsewhere as appropriate or required, 
any potential conflicts of interest, including their financial or personal relationship with 
Sponsor, and the names of any individuals who have provided editorial support for any 
manuscript or other publication.
Sponsor shall have the right to identify Institute as the site at which the Study was conducted 
and to identify those individuals responsible for conducting the Study, including Principal 
Investigator, and to provide any other information as necessary to post the Study on 

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www.clinicaltrials.gov or any other applicable public registries as required by applicable 
laws and regulations.

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17. REFERENCES
1.
Sheth SG, Chopra S. Natural history and management of nonalcoholic fatty liver 
disease in adults, UpToDate; 2014; http://www.uptodate.com/contents/natural-history-
and-management-of-nonalcoholic-fatty-liver-disease-in-adults.
2.
Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The 
diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by 
the American Association for the Study of Liver Diseases, American College of 
Gastroenterology, and the American Gastroenterological Association. Hepatology 
2012;55:2005-2023.
3.
McCullough AJ. The clinical features, diagnosis and natural history of nonalcoholic 
fatty liver disease. Clin Liver Dis 2004;8(3):521–533.
4.
Loomba R, Sirlin CB, Schwimmer JB, Lavine JE. Advances in pediatric nonalcoholic 
fatty liver disease. Hepatology 2009;50(4):1282–93.
5.
Torres DM, Williams CD, Harrison SA. Features, diagnosis, and treatment of 
nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2012;10(8):837–858.
6.
Schwenger KJ, Allard JP. Clinical approaches to non-alcoholic fatty liver disease. 
World J Gastroenterol 2014;20(7):1712–23.
7.
Koo SH. Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic 
steatosis. Clin Mol Hepatol 2013;19(3):210–215.
8.
Attar BM, Van Thiel DH. Current concepts and management approaches in 
nonalcoholic fatty liver disease. ScientificWorld Journal 2013;2013:481893
9.
Basaranoglu M, Basaranoglu G, Sentürk H. From fatty liver to fibrosis: a tale of 
"second hit". World J Gastroenterol 2013;19(8):1158–1165.
10.
Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new 
insights. Science 2011;332(6037):1519–1523.
11.
Matteoni CA, Younossi ZA, Gramlich T, et al. Nonalcoholic fatty liver disease: A 
spectrum of clinical and pathological severity. Gastroenterology 
1999;116(6):1413-1419.
12.
World Gastroenterology Organisation Global Guidelines. Nonalcoholic Fatty liver 
Disease and Nonalcoholic Steatohepatitis. June 2012. 
http://www.worldgastroenterology.org/assets/export/userfiles/2012_NASH%20and%20
NAFLD_Final_long.pdf.
13.
Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and 
natural history of non-alcoholic fatty liver disease and nonalcoholic steatohepatitis in 
adults. Aliment Pharmacol Ther 2011;34:274-285.
14.
Charlton MR, Burns JM, Pederson RA, Watt KD, Heimbach JK, Dierkhising RA. 
Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the 
United States. Gastroenterol. 2011;141:1249-1253.

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15.
Vatche G. Agopian et al. Liver Transplantation for Nonalcoholic Steatohepatitis. 
Annals of Surgery 2012;256(4):624-633.
16.
McCullough AJ. Epidemiology of the metabolic syndrome in the USA. J Dig Dis. 
2011;12:333-340.
17.
Mossanen JC, Krenkel O, Ergen C, et al. Chemokine (C-C motif) receptor 2-positive 
monocytes aggravate the early phase of acetaminophen-induced acute liver injury. 
Hepatology 2016 Nov;64(5):1667-1682.
18.
Puengel T, Krenkel O, Mossanen J, et al. The dual CCR2/CCR5 antagonist cenicriviroc 
ameliorates steatohepatitis and fibrosis in vivo by inhibiting the infiltration of 
inflammatory monocytes into injured liver. J Hepatol 2016;64:s159-s182.
19.
Marra F, Tacke F. Roles for chemokines in liver disease. Gastroenterology 
2014;147(3):577-594.
20.
Schwabe RF, Bataller R, Brenner D. Human hepatic stellate cells express CCR5 and 
RANTES to induce proliferation and migration. Am J Physiol Gastrointest Liver 
Physiol 2003;285(5):949-958.
21.
Friedman SL, Ratziu V, Harrison SA, et al. A randomized, placebo-controlled trial of 
cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis. Hepatology. 
2017;Aug 17. doi: 10.1002/hep.29477. [Epub ahead of print].
22.
Angulo P, Kleiner DE, Dam-Larsen S, Adam LA, Bjornsson ES, 
Charatcharoenwitthaya P, et al. Liver fibrosis, but no other histologic features, is 
associated with long-term outcomes of patients with nonalcoholic fatty liver disease. 
Gastroenterology 2015;149:389-397.
23.
FDA Guidance for Industry. Drug-Induced Liver Injury: Premarketing Clinical 
Evaluation. July 2009. Available at 
http://www.fda.gov/downloads/Drugs/.../Guidances/UCM174090.pdf

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18. SPONSOR’S SIGNATURE PAGE
Open-label Rollover Study of Cenicriviroc for the Treatment of Liver Fibrosis in Adult 
Subjects with Nonalcoholic Steatohepatitis (NASH) 
Protocol Issue Date: 01 December 2016
Global Amendment 1 Issue Date 14 Apr 2018
I have reviewed and approved the attached version, cited above, of Protocol 3152-201-002. 
Senior Vice President, Liver Therapeutic Area Head, Allergan plc
Date

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19. INVESTIGATOR’S SIGNATURE PAGE
Open-label Rollover Study of Cenicriviroc for the Treatment of Liver Fibrosis in Adult 
Subjects with Nonalcoholic Steatohepatitis (NASH) 
Protocol Issue Date: 01 December 2016
Global Amendment 1 Issue Date 14 Apr 2018
I have read, understand, and agree to follow the attached version, cited above, of 
Protocol 3152-201-002.
Principal Investigator Name (Print)
                            Signature
Date                                                                              Site Number

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20. APPENDICES

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20.1.
Schedule of Assessments
Table 20-1
Schedule of Assessments

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20.2.
National Cancer Institute Common Terminology Criteria for Adverse Events 
(NCI CTCAE) 
Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010)
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf
Quick Reference
The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI 
CTCAE) is a descriptive terminology which can be utilized for adverse event (AE) reporting. 
A grading (severity) scale is provided for each AE term.
Components and Organization
System Organ Class
System Organ Class (SOC), the highest level of the MedDRA hierarchy, is identified by 
anatomical or physiological system, etiology, or purpose (eg, SOC investigations for 
laboratory test results). CTCAE terms are grouped by MedDRA Primary SOCs. Within each 
SOC, AEs are listed and accompanied by descriptions of severity (grade). 
CTCAE Terms
An adverse event is any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medical treatment or 
procedure that may or may not be considered related to the medical treatment or procedure. 
An AE is a term that is a unique representation of a specific event used for medical 
documentation and scientific analyses. Each CTCAE v4.0 term is a MedDRA lowest level 
term (LLT).
Definitions
A brief definition is provided to clarify the meaning of each AE term.

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Grades
Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique 
clinical descriptions of severity for each AE based on this general guideline:
Grade 1
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated.
Grade 2
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL*.
Grade 3
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self care ADL**.
Grade 4
Life-threatening consequences; urgent intervention indicated.
Grade 5
Death related to AE.
A semi-colon indicates ‘or’ within the description of the grade.
A single dash (-) indicates a grade is not available.
Not all grades are appropriate for all AEs. Therefore, some AEs are listed with fewer than 
5 options for grade selection.
Grade 5 (Death) is not appropriate for some AEs and therefore is not an option.
Activities of Daily Living (ADL)
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc.
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, 
taking medications, and not bedridden.

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20.3.
Information on Contraception Effectiveness
Trussell J. Contraceptive failure in the United States. Contraception 2004;70:89-96.

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20.4.
Disallowed Medications
Caution should always be exercised when administering concomitant medications based on 
the individual medication profile and clinical risk-benefit assessment. 
The subject must not take the following disallowed medications at any time during the study, 
from Screening through the 1-Month Follow-up Visit. 
Disallowed Medications
Medicinal Product 
Class
CYP3A4 Substrates 
with Narrow 
Therapeutic Index
Strong/moderate 
CYP 3A4 
Inducers
Strong 
CYP3A4 
Inhibitors
Strong 
CYP2C8 
Inhibitors
Antibacterials
rifampin, nafcillin 
clarithromycin, 
erythromycin, 
telithromycin 
Anticonvulsants
carbamazepine, 
phenytoin 
Antidepressants
nefazodone 
Antifungals
voriconazole, 
itraconazole, 
ketoconazole, 
posaconazole
Antihistamines
astemizole 
Antipsychotics
pimozide
Ergot Alkaloids
dihydroergotamine, 
ergonovine, ergotamine, 
methylergonovine 
Immunosuppressants
cyclosporine, 
tacrolimus
Lipid-lowering 
Agents
gemfibrozil
Opioids
fentanyl, alfentanil 
IV alfentanil or fentanyl 
are not allowed for 
biopsies performed 
during the open label 
study or for any 
procedures requiring 
these medications after 
intake of study drug.
Sedative/hypnotics
midazolam, triazolam 
Exception: Midazolam 
use is allowed for 
sedation for surgical 
procedures; however, for 
any procedures after 
intake of study drug, the 
first dose should be 

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decreased by 50% of the 
recommended dose and 
titrated according to the 
desired clinical response.
Other
cisapride
Disallowed Medications— BCRP Substrates
Medicinal Product Class
BCRP substrates
Anti-inflammatory drugs
sulfasalazine 
Antimetabolite drugs
methotrexate 
Disallowed Investigational NASH Products
Other
Eg, obeticholic acid, elafibranor, 
selonsertib
Disallowed Medications - Antivirals
Medicinal Product Class
Antivirals
All antivirals for the treatment of HIV, 
HBV, and HCV

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The following medications, if used, should be used with caution as CVC (mild CYP3A4 
inhibitor and BCRP inhibitor) may increase exposure of these CYP3A4 and BCRP substrates 
or these medications may affect the absorption of CVC. If used, these medications should be 
used at the lowest possible dose and for the shortest duration possible considering individual 
subject risk-benefit considerations. Clinical monitoring and dose titration are recommended 
to achieve the desired clinical response. Other medications of a similar class should be 
considered if possible. Consult the individual medication prescribing information for 
additional guidance.
Medicinal Product Class
Drugs that are Allowed but Must be Taken with Precaution During 
Intake of Study Drug (Mechanism)
Acid-reducing agents
(H2 receptor antagonists, antacids, 
proton-pump inhibitors [PPIs])
Acid-reducing agents should be administered at least 2 hours after the 
CVC dose to ensure that adequate CVC concentrations are maintained. 
When possible, use of an H2 receptor antagonist (except cimetidine) or 
antacids is preferred over a proton pump inhibitor (PPI). It is 
recommended to start with the lowest dose of these agents and titrate 
according to clinical response.
H2 receptor antagonists (eg, famotidine or ranitidine) should preferably 
be given from 2 to 12 hours after administration of study drug at a dose 
that does not exceed doses comparable to famotidine 40 mg daily.
Antacids (eg, aluminum hydroxide, calcium carbonate, magnesium 
carbonate, magnesium hydroxide, or bismuth subsalicylate) should 
preferably be given at least 4 hours after administration of study drug 
due to their immediate effect in increasing gastric pH.
PPIs (eg, omeprazole, lansoprazole, esomeprazole, pantoprazole, 
rabeprazole, or dexlansoprazole) should preferably be given 
approximately 3 hours after administration of study drug at a dose that 
does not exceed doses comparable to omeprazole 20 mg daily. Due to 
the prolonged acid-reducing effect of PPIs (~16 – 24 hours), it is 
advised to follow these dosing recommendations to reduce their 
potential impact on CVC absorption at subsequent dosing.
Lipid-lowering agents
atorvastatin, simvastatin, lovastatin, (CYP3A4 substrates); pravastatin 
(CYP3A4 substrate, weak CYP2C8 inhibitor); rosuvastatin (BCRP 
substrate)
The maximum recommended daily doses are as follows: atorvastatin 
40 mg, simvastatin 20 mg, lovastatin 40 mg, pravastatin 40 mg, and 
rosuvastatin 20 mg; pitavastatin use is allowed without dose restriction.
The medical monitor must be consulted prior to use of higher doses of 
statins than those recommended above.
PDE5 enzyme inhibitors
sildenafil, tadalafil, vardenafil (CYP3A4 substrates)
The recommended starting doses for these medications are as follows: 
sildenafil 25 mg, tadalafil 2.5 mg, vardenafil 2.5 mg.
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/uc m093664.htm

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20.5.
Clinical Laboratory Tests 

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