Conditions: Hepatitis C
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 106
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine whether 24 weeks of Daclatasvir and Sofosbuvir with Ribavirin is safe and effective in the treatment of genotype 3 hepatitis C infected patients with liver cirrhosis.

Detailed description:

Arms:
arm 1: Oral dosing of DCV 60 mg tablet once daily + SOF 400 mg tablet once daily + RBV 1000-1200 mg tablet per day (weight based) for 24 weeks.

Interventions: intervention 1: DCV intervention 2: SOF intervention 3: RBV
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol document:
Prot_001.pdf: 
Page:
1
Protocol Number:
AI444379
IND Number:
79,599
121,165
EUDRACT Number
2015-004331-12
Date:
14-Dec-2015
Clinical Protocol AI444379
A Phase 3 Evaluation of Daclatasvir and Sofosbuvir with Ribavirin in Cirrhotic Subjects with 
Genotype 3 Chronic Hepatitis C Infection
Medical Monitor
Eugene Scott Swenson, MD, PhD
24-hr Emergency Telephone Number
USA: 1-866-470-2267
International: +1-248-844-7390
Bristol-Myers Squibb Research and Development
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
Route 206 & Province Line Road
Lawrenceville, NJ 08543
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS-sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, 
copying, disclosure or dissemination of this information is strictly prohibited unless 
expressly authorized in writing by BMS. Any supplemental information (eg, amendments) 
that may be added to this document is also confidential and proprietary to BMS and must 
be kept in confidence in the same manner as the contents of this document. Any person 
who receives this document without due authorization from BMS is requested to return it 
to BMS or promptly destroy it. All other rights reserved. References to BMS in this 
protocol may apply to partners to which BMS has transferred obligations, eg, a Contract 
Research Organization (CRO).
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date:  14-Dec-2015
2
DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Original 
Protocol
14-Dec-2015
Not applicable
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
SYNOPSIS
Clinical Protocol AI444379
Protocol Title: A Phase 3 Evaluation of Daclatasvir and Sofosbuvir with Ribavirin in Cirrhotic Subjects with 
Genotype 3 Chronic Hepatitis C Infection
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s):

Daclatasvir (DCV): in tablet form at the dose of 60 mg (unless otherwise dictated by concomitant cART) once 
daily, by mouth for 24 weeks

Sofosbuvir (SOF): in tablet form at the dose of 400 mg once daily, by mouth for 24 weeks

Ribavirin (RBV): in tablet form at the dose of 1000-1200 mg per day, weight based twice daily by mouth for 
24 weeks
o
For subjects weighing < 75 kg at Day1, the total dose is 1000 mg/day. Subjects should take 400 mg 
(2 x 200 mg tablets) in the morning with a meal, and 600 mg (3 x 200 mg tablets) in the evening with a 
meal
o
For subjects weighing 75 kg at Day 1, the total dose is 1200 mg/day. Subjects should take 600 mg 
(3 x 200 mg tablets) in the morning and in the evening with a meal
Study Phase: 3
Research Hypothesis:
Combination therapy with DCV and SOF plus RBV for 24 weeks is safe and demonstrates an SVR12 rate greater 
than the threshold SVR rate in chronically infected subjects with HCV GT-3 and cirrhosis.
Objectives:
Primary Objective

To demonstrate the SVR12 rate, defined as HCV RNA < LLOQ target  detected (TD) or target not detected 
(TND) at follow-up Week 12 in subjects treated with 24 weeks of DCV+SOF+RBV therapy is greater than the 
historical threshold SVR rate 
Key Secondary Objective

To assess the impact of baseline NS5A resistance-associated polymorphisms on the SVR12 rate
Secondary Objectives

To assess safety, as measured by the frequency of deaths, serious adverse events (SAE)s, discontinuation due to 
adverse events (AE)s, Grade 3/4 AEs and Grade 3/4 laboratory abnormalities; 

To assess antiviral activity, as measured by:
o
The proportion of subjects who achieve HCV RNA < LLOQ, TD or TND at each of the following 
Weeks: 1, 2, 4, 8, 12, 16, 20, 24, and EOT; post-treatment Week 4 and 24
o
The proportion of subjects who achieve HCV RNA <LLOQ, TND at each of the following Weeks: 1, 2, 4, 
8, 12, 16, 20, 24, and EOT
Study Design:  
AI444379 is an open-label trial evaluating the combination therapy of DCV+ SOF with RBV for 24 weeks in
subjects infected with HCV GT-3 with compensated cirrhosis. The study will include approximately 75 subjects. 
Date: 14-Dec-2015
3
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Subjects will receive the combination of DCV 60 mg QD (unless concomitant HIV regimen dictates otherwise) + 
SOF 400 mg QD + RBV (weight based 1000 mg-1200 mg daily) for 24 weeks. HCV RNA will be available for 
review by the clinical site personnel. After treatment is completed subjects will be followed for 24 weeks. Subjects 
who discontinue early should be followed for 24 weeks post-treatment.
The primary analysis is SVR12 and the final analysis is SVR24.
Duration of study:
The screening/enrollment period is anticipated to be approximately 8 weeks from FPFV to LPFV. Study duration 
will be 52 weeks (4 week screening period, 24 weeks of therapy, and 24 weeks of follow-up).
Study Population:
The key subject population will be subjects chronically infected with HCV GT-3 with compensated cirrhosis. 
Subjects with cirrhosis who are mono-infected with HCV genotype 3 or coinfected with HCV genotype 3 and HIV-1 
will be permitted to enroll.
Study Drug: includes both Investigational [Medicinal] Products (IP/IMP) and Non-investigational 
[Medicinal] Products (Non-IP/Non-IMP) as listed:
Study Drug for AI444379
Medication 
Potency 
IP/Non-IP 
Daclatasvir, BMS-790052
60 mg
IP
Daclatasvir, BMS-790052
30 mg
IP
Sofosbuvir
400 mg
IP
Ribavirin
200 mg
IP
Study Design
Subjects with GT-3 Infection with Cirrhosis
DCV/S OF/RBV
x24 weeks
Follow-up
N=75
Day 1
Week 24
Week 36
Week 48
Primary 
Analysis 
SVR12
Date: 14-Dec-2015
4
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Study Assessments:
On treatment visits will occur at Weeks, 1, 2, 4, 8, 12, 16, 20, and 24/EOT. Following discontinuation or completion 
of therapy, safety will be assessed through post-treatment Week 4, while efficacy and/or resistance will be assessed 
through post-treatment Week 24.
Statistical Considerations:
Sample Size:
This is an open-label trial evaluating the combination therapy of DCV+ SOF with RBV for 24 weeks in subjects 
infected with HCV GT-3 with compensated cirrhosis. The study will include approximately 75 subjects. 
For the efficacy analysis, the target sample size of 75 can provide with a 95% confidence that the lower bound of the 
observed SVR12 rate will exceed 82% with an observed SVR rate of 91%. The primary objective is to determine 
whether the SVR12 rate, is higher than the historical threshold. The threshold rate is estimated at 79% and is based 
on the upper bound of the SVR rate from GT3 Cirrhotic subjects in the ALLY 3 study, where SVR12 rate is 63% 
with a confidence interval of (43.7%, 78.9%).  
The lower bound of the two-sided 95% confidence interval (CI) of the SVR12 from this study will be used to 
compare to the historical threshold (79%). For the primary objective, with 75 subjects it would take a minimum of 
an observed SVR12 rate of 91% (68/75; 95% CI: 81.7%, 96.2%) for the lower bound of the 95% CI to exceed the 
threshold, and conclude the SVR12 rate of 24-week DCV/SOF/RBV treatment is higher than the historical threshold
Endpoints:
Primary Endpoint

Proportion of subjects with SVR12, defined as HCV RNA < LLOQ, target detected (TD) or target not detected 
(TND) at follow-up Week 12 in all treated subjects.
Key Secondary Endpoint

The proportion of subjects who achieve SVR12 in the presence and absence of NS5A resistance-associated 
polymorphisms.
Secondary Endpoint(s)

On treatment safety, as measured by frequency of deaths, serious adverse events (SAE)s, discontinuation due to 
adverse events (AE)s, Grade 3/4 AEs and Grade 3/4 laboratory abnormalities

The proportion of subjects who achieve HCV RNA < LLOQ, TD or TND at each of the following Weeks: 1, 2, 
4, 8, 12, 16, 20, 24, and EOT; post-treatment Week 4 and 24

The proportion of subjects who achieve HCV RNA <LLOQ, TND at each of the following Weeks: 1, 2, 4, 8, 
12, 16, 20, 24, and EOT
Analyses:
Results will be presented for treated subjects. Demographics, baseline characteristics and safety data will also be 
presented.
Categorical variables will be summarized using counts and percents. Continuous variables will be summarized with 
univariate statistics (eg, mean, median, standard deviation).
Longitudinal summaries of safety and efficacy endpoints will use pre-defined visit week windows. Windows around 
planned measurement times will be constructed based on the midpoint between planned study visits. Laboratory 
measures will be summarized using standard international values and units, and US units will be provided in the 
appendix.
Date: 14-Dec-2015
5
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
On-treatment endpoints will be assessed using measurements from the start of study therapy through the last dose of 
study therapy plus 7 days. Follow-up endpoints will be assessed with measurements after the last dose of study 
therapy plus 7 days.
Schedule of analyses:
The primary analysis will be performed after all subjects have completed post-treatment Week 12 (SVR12). A final 
analysis (SVR24) will be performed at study completion. Additional interim efficacy analyses may be performed 
prior to post-treatment 12 to support external data presentations or correspondences with health authorities.
Date: 14-Dec-2015
6
2.0
Approved
930095055
2.0
v


TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
SYNOPSIS .................................................................................................................... 
TABLE OF CONTENTS .............................................................................................. 
1 INTRODUCTION AND STUDY RATIONALE ..................................................... 
1.1 Study Rationale ................................................................................................. 
1.1.1 Infection with Genotype 3 HCV ............................................................... 
1.1.2 Daclatasvir / Sofosbuvir Combination (DCV+SOF) ............................... 
1.1.3 Rationale for Study Design ...................................................................... 
1.1.3.1 Rationale for use of DCV and SOF with RBV in patients infected 
with GT-3 HCV ..................................................................................... 
1.1.3.2 Rationale for Treatment of Cirrhotic Subjects................................ 
1.1.3.3 Rationale for 24-Week Treatment Duration ................................... 
1.1.3.4 Rationale for use in subjects with HCV/HIV coinfection................ 
1.1.3.5 Rationale for Dose Selection .......................................................... 
1.2 Research Hypothesis ......................................................................................... 
1.3 Objectives(s) ..................................................................................................... 
1.3.1 Primary Objective .................................................................................... 
1.3.2 Key Secondary Objective ......................................................................... 
1.3.3 Secondary Objectives ............................................................................... 
1.3.4 Exploratory Objectives ............................................................................ 
1.4 Product Development Background ................................................................... 
1.4.1 Daclatasvir ............................................................................................... 
1.4.1.1 Study AI444040 ............................................................................... 
1.4.1.2 Study AI444216 (ALLY-2) ............................................................... 
1.4.1.3 Study AI444218 (ALLY-3) ............................................................... 
1.4.1.4 Study AI444326 (ALLY-3+) ............................................................ 
1.4.2 Sofosbuvir ................................................................................................ 
1.4.3 Safety of DCV and SOF ........................................................................... 
1.4.4 No Observed Drug Interaction between DCV and SOF .......................... 
1.5 Overall Risk/Benefit Assessment ..................................................................... 
2 ETHICAL CONSIDERATIONS ............................................................................... 
2.1 Good Clinical Practice ...................................................................................... 
2.2 Institutional Review Board/Independent Ethics Committee ............................. 
2.3 Informed Consent.............................................................................................. 
3 INVESTIGATIONAL PLAN .................................................................................... 
3.1 Study Design and Duration ............................................................................... 
3.2 Post Study Access to Therapy ........................................................................... 
3.3 Study Population ............................................................................................... 
3.3.1 Inclusion Criteria ..................................................................................... 
3.3.2 Exclusion Criteria .................................................................................... 
3.3.3 Women of Childbearing Potential ........................................................... 
3.4 Concomitant Treatments ................................................................................... 
3.4.1 Prohibited and/or Restricted Treatments................................................. 
1
2
3
7
11
11
11
14
16
16
18
20
20
20
25
25
25
25
25
25
26
26
26
27
28
29
29
30
31
32
34
34
34
34
35
35
37
37
37
41
43
44
44
Clinical Protocol
BMS-790052
AI444379
daclatasvir
Date: 14-Dec-2015
7
2.0
Approved
930095055
2.0
v


3.4.1.1 Prohibited and/or Restricted Treatments for Subjects on DCV and 
SOF ....................................................................................................... 
3.4.1.2 Prohibited and/or Restricted Treatments for Subjects on RBV ...... 
3.4.2 Dose selection of DCV for those on ART ................................................. 
3.4.2.1 Prohibited and/or Restricted Treatments for Subjects on cART 
regimens ................................................................................................ 
3.4.3 Change of cART regimens ....................................................................... 
3.4.4 Definitions for HIV management ............................................................. 
3.4.5 Other Restrictions and Precautions ......................................................... 
3.5 Discontinuation of Subjects following any Treatment with Study Drug .......... 
3.6 Post Study Drug Study Follow up .................................................................... 
3.6.1 Withdrawal of Consent ............................................................................ 
3.6.2 Lost to Follow-Up .................................................................................... 
4 STUDY DRUG .......................................................................................................... 
4.1 Investigational Product ..................................................................................... 
4.2 Non-investigational Product ............................................................................. 
4.3 Storage and Dispensing..................................................................................... 
4.4 Method of Assigning Subject Identification ..................................................... 
4.5 Selection and Timing of Dose for Each Subject ............................................... 
4.5.1 Dose Modifications .................................................................................. 
4.5.2 Dose Interruptions ................................................................................... 
4.6 Blinding/Unblinding ......................................................................................... 
4.7 Treatment Compliance ...................................................................................... 
4.8 Destruction of Study Drug ................................................................................ 
4.9 Return of Study Drug ........................................................................................ 
4.10 Retained Samples for Bioavailability / Bioequivalence ................................. 
5 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
5.1 Flow Chart/Time and Events Schedule ............................................................. 
5.1.1 Retesting During Screening or Lead-in Period ....................................... 
5.2 Study Materials ................................................................................................. 
5.3 Safety Assessments ........................................................................................... 
5.3.1 Laboratory Assessments........................................................................... 
5.3.2 Imaging Assessment for the Study............................................................ 
5.3.3 Adverse Events Assessment ...................................................................... 
5.3.4 Vital Signs and Physical Examinations ................................................... 
5.3.5 Electrocardiogram ................................................................................... 
5.4 Efficacy Assessments ........................................................................................ 
5.4.1 Primary Efficacy Assessment ................................................................... 
5.4.2 Secondary Efficacy Assessments .............................................................. 
5.5 Pharmacokinetic Assessments .......................................................................... 
5.6 Biomarker Assessments .................................................................................... 
5.7 Outcomes Research Assessments ..................................................................... 
5.8 Other Assessments ............................................................................................ 
5.8.1 HCV Virologic Resistance Testing ........................................................... 
5.8.2 HIV Resistance Testing ............................................................................ 
5.8.3 Brief Questionnaire/Interim Phone Contacts .......................................... 
44
45
45
47
47
47
48
48
50
50
50
50
52
52
52
53
53
54
55
55
55
56
56
56
57
57
64
64
64
64
67
68
68
68
68
68
68
68
69
69
69
69
70
70
Clinical Protocol
BMS-790052
AI444379
daclatasvir
Date: 14-Dec-2015
8
2.0
Approved
930095055
2.0
v


6 ADVERSE EVENTS ................................................................................................. 
6.1 Serious Adverse Events .................................................................................... 
6.1.1 Serious Adverse Event Collection and Reporting .................................... 
6.2 Nonserious Adverse Events .............................................................................. 
6.2.1 Nonserious Adverse Event Collection and Reporting .............................. 
6.3 Laboratory Test Result Abnormalities .............................................................. 
6.4 Pregnancy .......................................................................................................... 
6.5 Overdose ........................................................................................................... 
6.6 Potential Drug Induced Liver Injury (DILI) ..................................................... 
6.7 Other Safety Considerations ............................................................................. 
7 DATA MONITORING COMMITTEE AND OTHER EXTERNAL COMMITTEES
................................................................................................................................. 
8 STATISTICAL CONSIDERATIONS....................................................................... 
8.1 Sample Size Determination ............................................................................... 
8.2 Populations for Analyses .................................................................................. 
8.3 Endpoints .......................................................................................................... 
8.3.1 Primary Endpoint..................................................................................... 
8.3.2 Key Secondary Endpoint .......................................................................... 
8.3.3 Secondary Endpoints ............................................................................... 
8.3.4 Exploratory Endpoint(s) .......................................................................... 
8.4 Analyses ............................................................................................................ 
8.4.1 Demographics and Baseline Characteristics........................................... 
8.4.2 Efficacy Analyses ..................................................................................... 
8.4.2.1 Primary Efficacy ............................................................................. 
8.4.2.2 Secondary Efficacy.......................................................................... 
8.4.3 Safety Analyses......................................................................................... 
8.4.4 Pharmacokinetic Analyses ....................................................................... 
8.4.5 Biomarker Analyses ................................................................................. 
8.4.6 Outcomes Research Analyses .................................................................. 
8.4.7 Pharmacodynamics .................................................................................. 
8.4.8 Other Analyses ......................................................................................... 
8.5 Interim Analyses ............................................................................................... 
9 STUDY MANAGEMENT ........................................................................................ 
9.1 Compliance ....................................................................................................... 
9.1.1 Compliance with the Protocol and Protocol Revisions ........................... 
9.1.2 Monitoring ............................................................................................... 
9.1.2.1 Source Documentation .................................................................... 
9.1.3 Investigational Site Training.................................................................... 
9.2 Records ............................................................................................................. 
9.2.1 Records Retention .................................................................................... 
9.2.2 Study Drug Records ................................................................................. 
9.2.3 Case Report Forms .................................................................................. 
9.3 Clinical Study Report and Publications ............................................................ 
10 GLOSSARY OF TERMS ........................................................................................ 
11 LIST OF ABBREVIATIONS .................................................................................. 
12 REFERENCES ........................................................................................................ 
70
71
72
73
73
73
74
74
75
75
75
75
75
76
76
76
77
77
77
77
78
78
78
79
79
79
80
80
80
80
80
80
80
80
81
81
82
82
82
82
82
83
84
85
90
Clinical Protocol
BMS-790052
AI444379
daclatasvir
Date: 14-Dec-2015
9
2.0
Approved
930095055
2.0
v


APPENDIX 1 DSM IV: DIAGNOSTIC CRITERIA FOR DRUG AND ALCOHOL 
ABUSE ................................................................................................................... 
APPENDIX 2 DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF 
ADULT AND PEDIATRIC ADVERSE EVENTS PUBLISH DATE: 
DECEMBER, 2004 ................................................................................................. 
95
96
Clinical Protocol
BMS-790052
AI444379
daclatasvir
Date: 14-Dec-2015
10
2.0
Approved
930095055
2.0
v






























Clinical Protocol
AI444379
BMS-790052
daclatasvir
1.2
Research Hypothesis 
Combination therapy with DCV and SOF plus RBV for 24 weeks is safe and demonstrates an 
SVR12 rate greater than the threshold SVR rate in chronically infected subjects with HCV GT-3 
and cirrhosis.
1.3
Objectives(s)
1.3.1
Primary Objective
To demonstrate the SVR12 rate, defined as HCV RNA < LLOQ target detected (TD) or target
not detected (TND) as follow-up Week 12 in subjects treated with 24 weeks of DCV+SOF+RBV 
therapy is greater than the historical threshold SVR rate.
1.3.2
Key Secondary Objective

To assess the relationship between efficacy and NS5A resistance-associated polymorphisms.
1.3.3
Secondary Objectives

To assess safety, as measured by the frequency of deaths, serious adverse events (SAE)s, 
discontinuation due to adverse events (AE)s, Grade 3/4 AEs and Grade 3/4 laboratory 
abnormalities

To assess antiviral activity, as measured by:
o
The proportion of subjects who achieve HCV RNA < LLOQ, TD or TND at each of the 
following Weeks: 1, 2, 4, 8, 12, 16, 20, 24, and EOT; post-treatment Week 4 and 24
o
The proportion of subjects who achieve HCV RNA <LLOQ, TND at each of the 
following Weeks: 1, 2, 4, 8, 12, 16, 20, 24, and EOT
1.3.4
Exploratory Objectives
Date: 14-Dec-2015
25
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
1.4
Product Development Background
Date: 14-Dec-2015
26
2.0
Approved
930095055
2.0
v
















Clinical Protocol
AI444379
BMS-790052
daclatasvir
2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
International Conference on Harmonisation (ICH) and in accordance with the ethical principles 
underlying European Union Directive 2001/20/EC and the United States Code of Federal 
Regulations, Title 21, Part 50 (21CFR50).
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.
All potential serious breaches must be reported to BMS immediately. A serious breach is a 
breach of the conditions and principles of GCP in connection with the study or the protocol, 
which is likely to affect, to a significant degree, the safety or physical or mental integrity of the 
subjects of the study or the scientific value of the study.
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or
where there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
2.2
Institutional Review Board/Independent Ethics Committee 
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from
the IRB/IEC for the protocol, consent form, subject recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects. The 
investigator or BMS should also provide the IRB/IEC with a copy of the Investigator Brochure 
or product labeling information to be provided to subjects and any updates. 
The investigator or BMS should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
2.3
Informed Consent
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given to subjects, their legally acceptable representatives
(as per country guidelines) are clearly and fully informed about the purpose, potential risks, and 
other critical issues regarding clinical studies in which the subject volunteers to participate. 
BMS will provide the investigator with an appropriate (ie, Global or Local) sample informed 
consent form which will include all elements required by ICH, GCP and applicable regulatory 
Date: 14-Dec-2015
34
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
requirements. The sample informed consent form will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:

Provide a copy of the consent form and written information about the study in the language
in which the subject is most proficient prior to clinical study participation. The language 
must be non-technical and easily understood. 

Allow time necessary for subject or subject's legally acceptable representative to inquire 
about the details of the study.

Obtain an informed consent signed and personally dated by the subject or the subject's 
legally acceptable representative and by the person who conducted the informed consent 
discussion. 

Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent 
form and any other information to be provided to the subjects, prior to the beginning of the 
study, and after any revisions are completed for new information.
If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the subject.
Revise the informed consent whenever important new information becomes available that is 
relevant to the subject's consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the subject's 
willingness to continue participation in the study. This communication should be documented. 
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules applicable to regulatory requirements, the subjects' signed ICF 
and, in the US, the subjects’ signed HIPAA Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to subject records. 
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
3
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
The study design schematic is presented in Figure 3.1-1.
Date: 14-Dec-2015
35
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Figure 3.1-1:
Subjects with GT-3 Infection with Cirrhosis
AI444379 is an open-label trial evaluating the combination therapy of DCV + SOF with RBV for 
24 weeks in subjects infected with HCV GT-3 with compensated cirrhosis. Subjects with 
cirrhosis who are mono-infected with HCV genotype 3 or coinfected with HCV genotype 3 and 
HIV-1 infection will be permitted to enroll. The study will include approximately 75 subjects. 
Subjects will receive the combination of DCV 60 mg QD (unless otherwise dictated by 
concomitant combination anti-retroviral therapy [cART] therapy) + SOF 400 mg QD + RBV 
(weight based 1000 mg-1200 mg daily) for 24 weeks. HCV RNA will be available for review by 
the clinical site personnel. After treatment is completed, subjects will be followed for 24 weeks. 
Subjects who discontinue early should be followed for 24 weeks post-treatment.
The primary analysis is SVR12 and the final analysis is SVR24.
Duration of study:  
The screening/enrollment period is anticipated to be approximately 8 weeks from FPFV to 
LPFV. Study duration will be 52 weeks (4 week screening period, 24 weeks of therapy, and
24 weeks of follow-up).
Virologic Failure:
Virologic breakthrough is defined as: 
1. Any confirmed 1 log10 increase in HCV RNA from nadir, OR;
2. Any confirmed HCV RNA LLOQ after HCV RNA <LLOQ, TD or TND while on 
treatment 
Study Design
Subjects with GT-3 Infection with Cirrhosis
DCV/S OF/RBV
x24 weeks
Follow-up
N=75
Day 1
Week 24
Week 36
Week 48
Primary 
Analysis 
SVR12
Date: 14-Dec-2015
36
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Subjects who meet a definition of viral breakthrough will discontinue therapy. If discontinuation 
of therapy is required, this must occur no later than the next study visit following confirmation of 
breakthrough.
Viral relapse is defined as:
Confirmed HCV RNA LLOQ in post-treatment follow-up after HCV RNA < LLOQ, 
TND at EOT
Long-term follow-up study:  Following completion of the follow-up period of the study, select 
subjects at selected sites may be asked to enroll into a separate long term observational 3 year 
follow-up study to evaluate durability of response (if SVR is achieved) or persistence of possible 
drug-resistant virus (if treatment failure occurs). It is not a requirement for all subjects to enroll 
into the long term follow-up, and this option may not be available.
3.2
Post Study Access to Therapy
At the end of the study, BMS will not continue to provide BMS supplied study drug to 
subjects/investigators unless BMS chooses to extend the study. The investigator should ensure 
that the subject receives appropriate standard of care to treat the condition under study.
3.3
Study Population
For entry into the study, the following criteria MUST be met.
3.3.1
Inclusion Criteria
1) Signed Written Informed Consent
a) Freely given informed consent must be obtained from subjects prior to clinical trial 
participation, including informed consent for any screening procedures conducted to 
establish subject eligibility for the study.
2) Target Population
a) Subjects must be able to understand and agree to comply with the prescribed dosing 
regimens and procedures, report for regularly scheduled study visits, and reliably 
communicate with study personnel about adverse events and concomitant medications.
b) Subjects chronically infected with HCV genotype 3, as documented by positive HCV 
RNA at screening and either:
i)
Positive anti-HCV antibody, HCV RNA , or a positive HCV genotype test at least 
6 months prior to screening; OR
ii) Liver biopsy consistent with chronic HCV infection at screening (or a liver biopsy 
performed within 36 months prior to enrollment with evidence of chronic Hepatitis C 
such as the presence of fibrosis).
c) HCV RNA 10,000 IU/mL at Screening 
d) Subjects who are HCV-treatment naive with no previous exposure to any:
Date: 14-Dec-2015
37
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
i.
Interferon formulation (ie IFN, peg-IFN) or RBV
ii.
HCV direct acting antivirals (DAAs)
OR
e) Subjects who are HCV-treatment experienced:
i.
All anti-HCV therapies (for example, IFNα with or without RBV, SOF/RBV, 
cyclophilin inhibitors and inhibitors of microRNA) are permitted with the 
exception of previous exposure to NS5A inhibitors. 
ii.
All permitted prior anti-HCV therapies must be discontinued or completed 
12 weeks prior to screening. 
Documentation of prior virologic response to treatment is desirable but not strictly 
required.  
f)
Subjects with compensated cirrhosis. Determination of cirrhosis status is required prior to 
randomization. A biopsy is not needed for participation. Cirrhosis will be defined as any 
one of the following:
i.
Liver biopsy at any time prior to Screening showing cirrhosis (Metavir > F3, 
Ishak > 4, or equivalent), OR
ii.
Most recent Fibroscan with a result of 14.6 kPa within 1 year of 
Baseline/Day 1, OR
iii.
FibroTest score of AND an APRI of 2 at Screening
In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above 
criteria, a liver biopsy is required. Liver biopsy supersedes Fibroscan which supersedes
FibroTest.
g) Body Mass Index (BMI) of 18 to 40 kg/m2, inclusive at Screening.
h) Subject Re-enrollment: 
This study permits the re-enrollment of a subject that has 
discontinued the study as a pre-treatment failure (ie, subject has not been randomized / has 
not been treated) up to one time. If re-enrolled, the subject must be re-consented.
i)
Subjects with HCV monoinfection or HCV/HIV-1 coinfection.
i.
Subjects with HCV/HIV-1 coinfection must currently be receiving cART (See 
section 3.4.2 for permitted cART), have CD4 cell count >200 cells/µL at 
screening, HIV RNA < 40 copies/mL at screening and must be <200 copies/mL 
within 8 weeks prior to screening. 
3) Age and Reproductive Status
a) Males and Females, 18 years of age
b) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 
24 hours prior to the start of study drug.
Date: 14-Dec-2015
38
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
c) Women must not be breastfeeding
d) WOCBP must agree to follow instructions for method(s) of contraception for the 
following duration:
i.
For the duration of treatment and for a total of 6 months post-treatment 
completion or time specified by country-specific RBV label, whichever is longer.
e) Men who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception for the following duration:
i.
For the duration of treatment with RBV and for 6 months post-treatment 
completion, or per local guidelines, whichever is longer. In addition, male 
subjects must be willing to refrain from sperm donation during this time
f)
Azoospermic males are exempt from contraceptive requirements. WOCBP who are 
continuously not heterosexually active are also exempt from contraceptive requirements, 
and still must undergo pregnancy testing as described in this section.  
Investigators shall counsel WOCBP, and male subjects who are sexually active with WOCBP, 
on the importance of pregnancy prevention and the implications of an unexpected pregnancy. 
Investigators shall advise on the use of highly effective methods of contraception, which have a 
failure rate of < 1% when used consistently and correctly.
At a minimum, subjects must agree to use two methods of contraception. This would include:
1) Any 2 Highly Effective Methods indicated below, or 
2) 1 Highly Effective method and one Less Effective Method.
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
Highly effective methods of contraception have a failure rate of < 1% when used consistently 
and correctly. WOCBP and female partners of male subjects, who are WOCBP, are expected to 
use at least one of the highly effective methods of contraception listed below in addition to 
another highly effective method or less effective method. Male subjects must inform their female 
partners who are WOCBP of the contraceptive requirements of the protocol and are expected to 
adhere to using contraception with their partner. Contraception methods are as follows:
1) Hormonal methods of contraception including oral contraceptive pills containing combined 
estrogen + progesterone, vaginal ring, injectables, implants and intrauterine devices (IUDs) 
such as Mirena.
2) Nonhormonal IUDs, such as ParaGard
3) Bilateral tubal occlusion
4) Vasectomised partner with documented azoospermia 90 days after procedure
Vasectomised partner is a highly effective birth control method provided that partner 
is the sole sexual partner of the WOCBP trial participant and that the vasectomised 
partner has received medical assessment of the surgical success.
Date: 14-Dec-2015
39
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
5) Intrauterine hormone-releasing system (IUS).
6) Complete abstinence
Complete abstinence is defined as the complete avoidance of heterosexual intercourse 
(refer to Glossary of Terms)
Complete abstinence is an acceptable form of contraception for all study drugs and 
must be used throughout the duration of the study treatment plus the following:
o
For both WOCBP and men receiving RBV: 6 months post-treatment completion 
or time specified by country-specific RBV label, whichever is longer.
It is not necessary to use any other method of contraception when complete 
abstinence is elected.
Subjects who choose complete abstinence must continue to have pregnancy tests, as 
specified in Section 6.4.
Acceptable alternate methods of highly effective contraception must be discussed in 
the event that the subject chooses to forego complete abstinence.
The reliability of sexual abstinence needs to be evaluated in relation to the duration of 
the clinical trial and the preferred and usual lifestyle of the subject.
Less Effective Methods of Contraception (Can only be utilized in combination with one highly 
effective method):

Male or female condom with or without spermicide *

Diaphragm with spermicide

Cervical cap with spermicide

Vaginal sponge with spermicide

For female partner, who is a WOCBP, of a male subject participating in the study may use
Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action (Note: Progestogen only hormonal contraception is NOT an 
acceptable method of contraception for WOCBP female subjects).
*A male and a female condom must not be used together
Azoospermic males, women who are not of childbearing potential and WOCBP who abstain 
from heterosexual activity on a continuous basis are exempt from contraceptive requirements. 
However, WOCBP who abstain from heterosexual activity on a continuous basis must still 
undergo pregnancy testing.
UNACCEPTABLE METHODS OF CONTRACEPTION
1) Periodic abstinence (calendar, symptothermal, post-ovulation methods)
2) Withdrawal (coitus interruptus)
3) Spermicide only
4) Lactation amenorrhea method (LAM)
Date: 14-Dec-2015
40
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
3.3.2
Exclusion Criteria
1) Target Disease Exceptions
a) HCV genotypes other than GT-3 infection and mixed genotype infections are not 
permitted. 
b) Absence of cirrhosis (subject must meet inclusion criteria of compensated cirrhosis).
2) Medical History and Concurrent Diseases
a) Liver or any other organ transplant (including hematopoietic stem cell transplants) other 
than cornea and hair;
b) Current or known history of cancer (except in situ carcinoma of the cervix or adequately 
treated basal or squamous cell carcinoma of the skin) within 5 years prior to screening;
c) Documented or suspected HCC, as evidenced by previously obtained imaging studies or 
liver biopsy (or on a screening imaging study/liver biopsy if this was performed);
d) Evidence of decompensated liver disease including, but not limited to, radiologic criteria, 
a history or presence of ascites, bleeding varices, or hepatic encephalopathy;
e) Evidence of an ongoing medical condition contributing to chronic liver disease other than 
HCV (such as, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic 
liver disease, alcoholic liver disease, toxin exposures);
f)
History of chronic hepatitis B virus (HBV) as documented by HBV serologies 
(eg, HBsAg-seropositive). Subjects with resolved HBV infection may participate 
(eg, HBsAb-seropositive with concurrent HBsAg-seronegative);
g) Any gastrointestinal disease or surgical procedure that may impact the absorption of 
study drug. (Subjects who have had cholecystectomy are permitted to enter the study);
h) Known history of genetic coagulopathy including, but not limited to, hemophilia;
i)
Uncontrolled diabetes (any subject with a confirmed screening HbA1c 8.5 must be 
excluded);
j)
Confirmed, uncontrolled hypertension (any screening systolic blood pressure 
160 mmHg or diastolic blood pressure 100 mmHg should be excluded);
k) Active substance abuse as defined by DSM-IV, Diagnostic Criteria for Drug and Alcohol 
Abuse (Appendix 1), which in the opinion of the investigator would make the candidate 
inappropriate for participation in this study
l)
Active severe psychiatric disorders including but not limited to, schizophrenia, psychosis, 
bipolar disorder, post-traumatic stress disorder, mania, etc.;
m) Inability to tolerate oral medication;
n) Poor venous access that would impair the subject's ability to comply with the study 
protocol;
o) Prior NS5A treatment failures;
Date: 14-Dec-2015
41
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
p) Discontinuations of prior SOF/RBV treatment due to intolerance and/or exacerbations of 
anemia;
q) Subjects infected with HIV-2;
r)
Presence of AIDS-defining opportunistic infections or any AIDS diagnosis within 
12 weeks prior to study entry (AIDS-defining opportunistic infections as defined by the 
CDC);
s) The following conditions are exclusion criteria for the use of RBV, based on the label:
i.
History of hemoglobinopathies (eg, thalassemia major or sickle cell anemia), 
diagnoses associated with an increased baseline risk for anemia (eg, spherocytosis), 
hemolytic anemia, or diseases in which anemia would be medically problematic;
ii.
History of cardiomyopathy, active unstable coronary artery disease (including 
angina), ventricular arrhythmia, congestive heart failure (other than fluid overload 
due to hepatic insufficiency), pulmonary hypertension or other clinically significant 
cardiac disease;
iii.
Historical or current electrocardiogram (ECG) finding indicative of cardiovascular 
instability, including but not limited to evidence of myocardial ischemia, unstable 
re-entry phenomena, other significant dysrhythmias, and/or uncontrolled 
hypertension
iv.
History of hypersensitivity to drugs with a similar biochemical structure to RBV;
v.
Any other criteria that would exclude the subject from receiving RBV, per the local 
label
3) Physical and Laboratory Test Findings
a) Alanine aminotransferase (ALT) 10x ULN
b) Total bilirubin 2 mg/dL (34 mol/L), unless due to Atazanavir/Ritonavir treatment or 
subject has a documented history of Gilbert’s disease
c) Albumin < 3.0 g/dL (30 g/L);
d) Platelets < 50 x 103 cells/L;
e) ANC < 0.75 x 103 cells/L;
f)
Hemoglobin < 10 g/dL (100 g/L);
g) Creatinine Clearance (CrCl) 50 mL/min (as estimated by Cockcroft and Gault);
h) Alpha fetoprotein (AFP):
i.
AFP > 100 ng/mL (> 82.6 IU/mL) OR
ii.
AFP 50 and 100 ng/mL (41.3 IU/mL and 82.6 IU/ mL) requires a liver 
ultrasound and subjects with findings suspicious for HCC are excluded.
i)
QTcF or QTcB > 500 mSec
Date: 14-Dec-2015
42
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
4) Allergies and Adverse Drug Reaction
a) History of hypersensitivity to drugs with a similar biochemical structure to DCV, SOF, 
and RBV
b) Any other criteria or known contraindication that would exclude the subject from 
receiving DCV, SOF, and RBV
5) Prohibited Treatments and/or Therapies
a) Exposure to any investigational drug or placebo within 4 weeks of study drug 
administration
b) Use of amiodarone for 60 day time period prior to start of treatment
Refer to Section 3.4.1 for prohibited and/or restricted treatments during treatment, re-treatment 
and post-treatment
6) Sex and Reproductive Status
a) Males and females who do not or cannot meet the requirements outlined in Inclusion 
Criteria 3
b) Male subjects must confirm that their female sexual partners are not pregnant at the time 
of screening
7) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific 
circumstances a person who has been imprisoned may be included or permitted to 
continue as a subject. Strict conditions apply and Bristol-Myers Squibb approval is 
required).
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness
c) Any other medical, psychiatric, and/or social reason which, in the opinion of the 
investigator would make the subject inappropriate for the study
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and that the results of the study can be used. It is imperative that subjects fully meet all 
eligibility criteria.
3.3.3
Women of Childbearing Potential
Women of childbearing potential (WOCBP) is defined as any female who has experienced 
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral 
oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in 
a woman over age 45 years in the absence of other biological or physiological causes. In 
addition, females under the age of 55 years must have a serum follicle stimulating hormone, 
(FSH) level > 40 mIU/mL to confirm menopause.
Date: 14-Dec-2015
43
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
*Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgment in checking serum FSH levels. 

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is > 40 mIU/ml at any time during the washout period, the woman can be considered 
postmenopausal.
3.4
Concomitant Treatments
3.4.1
Prohibited and/or Restricted Treatments
3.4.1.1
Prohibited and/or Restricted Treatments for Subjects on DCV and SOF
The use of amiodarone is prohibited and must be discontinued 60 days prior to the start of 
treatment.
The following treatments are prohibited during dosing with DCV and SOF and should be
discontinued at least one week prior to Day 1 of study drug.

Strong inhibitors of CYP3A4 are prohibited, including, but not limited to: ketoconazole, 
troleandomycin, itraconazole, voriconazole, mibefradil, clarithromycin, telithromycin, 
grapefruit juice and grapefruit-containing products, Seville oranges, juices and products that 
contain Seville oranges, conivaptan, nefazodone, etc

Strong CYP3A4 inducers are prohibited, including but not limited to: rifampin, rifabutin, 
rifapentin, dexamethasone, phenytoin, carbamazepine, phenobarbital, St John's wort, etc

Strong P-gp inhibitors are prohibited (eg, ketoconazole, indinavir, lapatinib, quinidine, 
ranolazine, erythromycin, clarithromycin, and azithromycin (azithromycin will be allowed 
for a duration of 7 days or less or once weekly)

CYP3A substrates with narrow therapeutic index are prohibited, including but not limited to 
alfentanil, cisapride, dihydroergotamine, ergotamine, fentanyl, pimozide, and quinidine

P-gp inducers are prohibited, including but not limited to, avasimibe, carbamazepine, 
oxcarbazepine, phenytoin, rifampin, rifabutin, rifapentine, St John’s wort, and boosted 
tipranavir
The following treatments should be used with caution during dosing with DCV and SOF.

Substrates of OATP1B1 and OTAP1B3 should be used with caution (eg, glyburide, 
bosentan, rosuvastatin, pravastatin, and pitavastatin)

Substrates of BCRP should be used with caution (eg, rosuvastatin)
Date: 14-Dec-2015
44
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir

P-gp substrates with a narrow therapeutic index (eg, digoxin) should be used with caution 
and at the lowest efficacious dose with appropriate monitoring (eg, therapeutic drug 
monitoring)
3.4.1.2
Prohibited and/or Restricted Treatments for Subjects on RBV
The use of erythropoiesis-stimulating agents (ESAs) is discouraged. The risks and benefits of the 
use of ESAs for the management of HCV treatment-related anemia has not been standardized nor 
established in well controlled clinical trials. Although the use of ESA for the treatment of HCV 
treatment-related anemia is at the investigator’s discretion, the following guidelines are 
recommended (please refer to the ESAs product information for additional information): 

ESAs should not be initiated until the hemoglobin (Hb) falls below 10g/dL

Iron assessments should be obtained prior to and during treatment with ESA

Iron supplementation should be initiated for deficient subjects and to maintain transferrin 
saturation at a level that will support erythropoiesis

Once an ESA is initiated, Hb levels and blood pressure must be monitored weekly until Hb 
level stabilizes

Treatment should target a Hb level sufficient to avoid transfusion

ESA dose should be titrated to treatment response

ESA dose should be reduced if the Hb increases by more than 1 g/dL in a 2-week period

ESA dose should not exceed those recommended for currently approved indications

ESAs should not be used in subjects at increased risk for thromboembolic events, 
cardiovascular events, including those with inadequately controlled hypertension, and in 
subjects diagnosed with malignancies
The cost of ESAs or granulocyte colony-stimulating factors will not be reimbursed by the 
Sponsor because of the rationale above.
Date: 14-Dec-2015
45
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
46
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
3.4.2.1
Prohibited and/or Restricted Treatments for Subjects on cART 
regimens
Most of the commonly used ART will be allowed as outlined in Table 3.4.2-1. Alternative cART 
medications not listed may be considered only after review with the BMS medical monitor.
Use of any other cART therapy within one month prior to Day 1 of study drug dosing and 
throughout the treatment period of the trial is prohibited.
Co-administration 
of 
a 
non-nucleoside 
reverse 
transcriptase 
inhibitor 
(NNRTI) 
(excluding rilpivirine) with a boosted protease inhibitor (PI) is prohibited.
3.4.3
Change of cART regimens
For subjects receiving cART and requiring a change in therapy, the choice of antiretrovirals will 
be determined by the investigator on the basis of the HIV viral resistance profile and the 
subject’s HIV treatment history. Refer to Table 3.4.2-1 and local country label for guidance.
cART should remain unchanged throughout the duration of the study unless changes are required 
in the opinion of the investigator (ie, confirmed on-treatment HIV RNA 400 copies/mL, 
treatment-limiting antiretroviral toxicity, etc) in consultation with the BMS medical monitor. 
The choice of permitted antiretroviral regimen will be determined by the investigator on the basis 
of prior treatment history (including HIV viral resistance profile for the subject), local HIV 
treatment guidelines, and expert opinion.
3.4.4
Definitions for HIV management
This section provides definitions for the clinical management of subjects with regard to HIV 
viral rebound and virologic failure during the study.
HIV Virologic Failure is defined as:
Confirmed HIV RNA value 400 copies/mL. Measurements are confirmed by a second plasma 
HIV RNA level 400 copies/mL redrawn within 2 to 4 weeks from original sample.
HIV Viral rebound is defined as:
A confirmed plasma HIV RNA level 200 copies/mL. Confirmation should be within 2-4 weeks 
after the original rebound sample.
HIV Viral blip is defined as: 

An isolated detectable HIV RNA (40 copies/mL) level that is followed by a return to 
virologic suppression.
Date: 14-Dec-2015
47
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Subjects meeting the criteria for viral rebound or virologic failure at any time during the study 
will be managed as follows:

Those with a confirmatory HIV RNA of < 200 copies/mL may continue on their assigned 
HIV treatment

Those subjects with a confirmed HIV RNA of 200 copies/mL may remain on assigned 
HCV and HIV treatment at the discretion of the investigator, in consultation with the BMS 
Medical Monitor

An HIV viral resistance test will be conducted automatically in subjects with confirmed HIV 
RNA 400 copies/mL and the result forwarded to the study site 

Subjects with Genotypic and/or Phenotypic resistance to one or more assigned antiretroviral 
treatment may be allowed to switch to a different antiretroviral therapy. The choice of the 
new antiretroviral therapy will be those permitted by the protocol and determined by the 
investigator on the basis of the HIV viral resistance profile for the subject and local 
guidelines for treatment of HIV infected subjects

Further management will be at the discretion of the investigator in consultation with the BMS 
Medical Monitor
Subjects who require discontinuation due to HIV virologic failure should comply with protocol 
specified follow-up procedures
3.4.5
Other Restrictions and Precautions

Medications with known or potential anti-HCV activity other than the assigned study 
treatment are prohibited during the on treatment period

Any prescription or herbal product which is not prescribed by the investigator or licensed 
physician for treatment of a specific clinical condition is prohibited

Methadone and buprenorphine should be used with caution. These drug levels may change 
with concomitant use of DCV and SOF

Long-term treatment (2 weeks) with agents that are immunosuppressive, or have a high 
risk for nephrotoxicity or hepatotoxicity, should be discussed with the central medical 
monitor
3.5
Discontinuation of Subjects following any Treatment with Study Drug 
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:

Subject’s request to stop study treatment

Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the 
opinion of the investigator, indicates that continued participation in the study is not in the 
best interest of the subject

Termination of the study by Bristol-Myers Squibb (BMS)
Date: 14-Dec-2015
48
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness

Pregnancy

Laboratory or Clinical Criteria: If any of the following laboratory or clinical criteria is 
obtained for any patient, the result must be repeated /confirmed within 72 hours and the BMS 
central medical monitor should be informed. If the results are confirmed, the patient must 
discontinue treatment. Clinical criteria must have Principal Investigator or Sub-Investigator 
assessment prior to proceeding to permanent discontinuation

Evidence of confirmed hepatic decompensation (Child-Pugh Class B or C, Score > 6)

ALT > 2 baseline and 5 ULN, and either total bilirubin > 2 ULN or INR > 2

Any Grade 4 AE or clinically significant laboratory abnormality considered study 
drug-related (see Section 6.3 for laboratory abnormality AE reporting requirements).

Virologic Breakthrough (confirmatory results must be obtained 2 weeks from the original 
result) defined as:

Confirmed 1 log10 IU/mL HCV RNA on-treatment increase from nadir, or

Confirmed increase in HCV RNA LLOQ if HCV RNA previously declined to < LLOQ 
TD/TND.
If discontinuation of therapy is required, this must occur no later than the next study visit.
Any subject who receives anti-HCV therapy in the post-treatment period prior to Post-Treatment 
Week 4 (ie, a subject who discontinued therapy due to an AE or virologic failure), who then 
chooses to receive an alternative therapy (outside of the study), should discontinue from the 
study after completing the Post-Treatment Week 4 safety visit (see Table 5.1-3). If the subject 
receives HCV therapy after Post-Treatment Week 4, the subject should be discontinued from the 
study as soon as possible, following completion of the procedures outlined in the Post-Treatment 
Week 24 visit.
The investigator must notify the BMS Medical Monitor/designee in the event that a female 
subject becomes pregnant within 24 hours and submit information to WWS on the pregnancy 
form within 24 hours. The study drug should be discontinued after pregnancy has been 
confirmed.
All subjects who discontinue study drug should comply with protocol specified follow-up 
procedures as outlined in Section 5. The only exception to this requirement is when a subject 
withdraws consent for all study procedures including post-treatment study follow-up or loses the 
ability to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either 
a psychiatric or physical illness).
The end of the study is defined as the date of the last visit for the last subject to complete the 
study. The last visit is defined as the last post-treatment follow up subject visit.
Date: 14-Dec-2015
49
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
If study treatment is discontinued prior to the subject’s completion of the study, the reason for 
the discontinuation must be documented in the subject’s medical records and entered on the 
appropriate case report form (CRF) page.
3.6
Post Study Drug Study Follow up
In this study, Post-Treatment Follow up Week 12 is a key endpoint of the study. Post study 
follow-up is of critical importance and is essential to preserving subject safety and the integrity 
of the study. Subjects who discontinue study drug must continue to be followed for collection of 
outcome and/or survival follow-up data as required and in line with Section 5 until death or the 
conclusion of the study (Post-Treatment Week 24).
3.6.1
Withdrawal of Consent
Subjects who request to discontinue study drug will remain in the study and must continue to be 
followed for protocol specified follow-up procedures. The only exception to this is when a 
subject specifically withdraws consent for any further contact with him/her or persons previously 
authorized by subject to provide this information. Subjects should notify the investigator of the 
decision to withdraw consent from future follow-up in writing, whenever possible. The 
withdrawal of consent should be explained in detail in the medical records by the investigator, as 
to whether the withdrawal is from further treatment with study drug only or also from study 
procedures and/or post treatment study follow-up, and entered on the appropriate CRF page. In 
the event that vital status (whether the subject is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed in 
accordance with local law.
3.6.2
Lost to Follow-Up
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. Lost to 
follow-up is defined by the inability to reach the subject after a minimum of three documented 
phone calls, faxes, or emails as well as lack of response by subject to one registered mail letter. 
All attempts should be documented in the subject’s medical records. If it is determined that the 
subject has died, the site will use permissible local methods to obtain the date and cause of death.
If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the subject’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining subject’s contact 
information or other public vital status data necessary to complete the follow-up portion of the 
study. The site staff and representative will consult publicly available sources, such as public 
health registries and databases, in order to obtain updated contact information. If after all 
attempts, the subject remains lost to follow-up, then the last known alive date as determined by 
the investigator should be reported and documented in the subject’s medical records.
4
STUDY DRUG
Study drug includes both Investigational [Medicinal] Product (IP/IMP) and Non-investigational 
[Medicinal] Product (Non-IP/Non-IMP) and can consist of the following:
Date: 14-Dec-2015
50
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Table 4-1:
Study Drugs for AI444379
Product Description / 
Class and Dosage Form
Potency
IP/
Non-IMP
Blinded or 
Open Label
Packaging/ Appearance
Storage Conditions
(per label)
Daclatasvira
(BMS-790052-05),
HCV NS5A inhibitor,
Film Coated Tablet
60 mg 
(as the free base)
IP
Open Label
33 tablets per bottle. Each tablet is 
plain, green, biconvex, pentagonal 
and film-coated.
Store at 15°C-25°C (59°F-77°F). 
Store in a tightly closed container.
Daclatasvira
(BMS-790052-05),
HCV NS5A inhibitor,
Film Coated Tablet
30 mg 
(as the free base)
IP
Open Label
33 tablets per bottle. Each tablet is 
plain, green, biconvex, pentagonal 
and film-coated.
Store at 15°C-25°C (59°F-77°F). 
Store in a tightly closed container.
Sofosbuvir (SOF)b
nucleotide NS5B 
polymerase inhibitor,
Film Coated Tablet
400 mg
IP 
Open Label
28 tablets per bottle. Yellow, 
capsule-shaped, film-coated tablet 
debossed with “GSI” on one side 
and “7977” on the other side.
Store at 15°C-25°C (59°F-77°F). 
Store in original container.
Ribavirin (RBV)b, 
nucleoside analogue,
Film Coated Tablet
200 mg
IP 
Open Label
168 tablets per bottle. Capsule-
shaped, light blue color, film-
coated tablet debossed with 
“200”on one side and logo “3RP” 
on the other side. 
Store at 25 °C (77 °F). Excursions 
permitted between 15 °C and 30 °C 
(59 °F to 86 °F). Keep bottle tightly 
closed.
a Daclatasvir will be provided as the Phase 3 clinical presentation for 30 mg and 60 mg film-coated tablets.
b Commercially available Sofosbuvir (Sovaldi®) and Ribavirin (Ribasphere®) will be procured and distributed by BMS. Storage for SOF should be in 
accordance with the SmPC. Storage for RBV should be in accordance with the package insert. SOF and RBV will be supplied by BMS, but may be sourced 
locally if necessary.
Date: 14-Dec-2015
51
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
4.1
Investigational Product
4.2
Non-investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or 
therapeutic reasons, as components of the standard of care for a given diagnosis, may be
considered as non-investigational products. 
Additionally, in this protocol, cART medications are considered non-investigational study drug 
and will not be provided by the sponsor. HIV medications will be obtained by the investigating 
sites standard prescribing procedures. Marketed product will be utilized for this study and should 
be stored in accordance with the package insert or summary of product characteristics (SmPC). 
4.3
Storage and Dispensing
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
regarding the quality or appearance of the study drug arise, the study drug should not be 
dispensed and contact BMS immediately.
Study drug not supplied by BMS will be stored in accordance with the package insert.
Investigational product documentation (whether supplied by BMS or not) must be maintained 
that includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
Date: 14-Dec-2015
52
2.0
Approved
930095055
2.0
v






Clinical Protocol
AI444379
BMS-790052
daclatasvir
4.6
Blinding/Unblinding
Not applicable.
4.7
Treatment Compliance
Assessment of study medication will be performed at each study visit. The subject should be 
instructed to bring all unused study medication containers to each visit as well as any empty 
bottles. The dates and number of tablets dispensed and returned must be recorded on the drug 
accountability form maintained on-site. Opened containers of daclatasvir (BMS-790052-05), as 
appropriate, are collected every 4 weeks and new bottles are dispensed. Opened containers of 
sofosbuvir (SOF) and RBV should be returned to the subject and dosing should continue from 
the in-use container. However, if site SOPs do not allow return of open containers of study drug, 
local SOPs may be followed. All study drug, including in-use containers, should be collected at 
end of treatment visit.
Subjects will be instructed to record dosing in a dosing diary which will be reviewed at each 
visit, in combination with drug accountability to confirm treatment compliance. Sites should 
discuss with the subject if there are discrepancies between the diary and the drug log to reconcile 
actual dosing at each visit
Date: 14-Dec-2015
55
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
4.8
Destruction of Study Drug
For this study, study drugs (those supplied by BMS or sourced by the investigator) such as 
partially used study drug containers, vials and syringes may be destroyed on site. 
Any unused study drugs can only be destroyed after being inspected and reconciled by the 
responsible Study Monitor unless study drug containers must be immediately destroyed as 
required for safety, or to meet local regulations (eg, cytotoxics or biologics). 
On-site destruction is allowed provided the following minimal standards are met:

On-site disposal practices must not expose humans to risks from the drug.

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.

Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request.

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal 
vendor must be documented.

Accountability and disposal records are complete, up-to-date, and available for the Monitor 
to review throughout the clinical trial period.
If conditions for destruction cannot be met the responsible Study Monitor will make 
arrangements for return of study drug.
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
4.9
Return of Study Drug
If study drug will not be destroyed upon completion or termination of the study, all unused 
and/or partially used study drug that was supplied by BMS must be returned to BMS. The return 
of study drug will be arranged by the responsible Study Monitor. 
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept. 
4.10
Retained Samples for Bioavailability / Bioequivalence
Not Applicable. 
Date: 14-Dec-2015
56
2.0
Approved
930095055
2.0
v
















Clinical Protocol
AI444379
BMS-790052
daclatasvir
5.1.1
Retesting During Screening or Lead-in Period
Retesting of laboratory parameters and/or other assessments within any single Screening or 
Lead-in period will be permitted (in addition to any parameters that require a confirmatory 
value).
Any new result will override the previous result (ie, the most current result prior to 
Randomization) and is the value by which study inclusion will be assessed, as it represents the 
subject’s most current, clinical state.
Laboratory parameters and/or assessments that are included in Table 5.1-1, Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified subjects. Consultation 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant.
5.2
Study Materials
The site will provide all required materials for the tests performed locally (ie, relevant clinical 
laboratory tests). The site will have available a well-calibrated scale for recording body weight, a 
12-lead ECG machine, and a calibrated sphygmomanometer and thermometer for vital sign 
assessments. The site will have a monitored refrigerator, and freezer (-20°C or below), as well as 
containers and dry ice for shipment and storage of blood samples. A refrigerated centrifuge is 
also recommended. The site will provide all materials required for accurate source 
documentation of study activities and for housing patients during the study.
BMS will provide a BMS-approved protocol and any amendments or administrative letters 
(if required). Case report forms (electronic or hard copy) will be provided by BMS. Central 
Laboratory will provide labels and tubes for the collection of all required materials for the 
clinical laboratory tests performed by the Central Laboratory. Investigational products will be 
supplied by BMS. BMS will also provide the Investigator Brochure, and the IRT manual. Dosing 
diaries may be provided by BMS.
5.3
Safety Assessments
Only data for the procedures and assessments specified in this protocol should be submitted to 
BMS on a case report form. Additional procedures and assessments may be performed as part of 
the subject’s standard medical care; however, data for these assessments should remain in the 
subject’s medical record and should not be provided to BMS, unless specifically requested from 
the sponsor.
5.3.1
Laboratory Assessments
The following assessment listed in Table 5.3.1-1 will be analyzed by a central laboratory or other 
BMS specified laboratory. Subjects are not required to be fasting prior to any laboratory 
assessments.
Date: 14-Dec-2015
64
2.0
Approved
930095055
2.0
v






Clinical Protocol
AI444379
BMS-790052
daclatasvir
All protocol-specified laboratory tests specified in Table 5.3.1-1 must be analyzed and reported 
by the central lab. In exceptional cases when local laboratory tests are performed, central lab 
samples should be submitted at the same time, if possible (in addition to the time points specified 
in Section 5.1). In an effort to limit laboratory data collection, only relevant local lab results 
should be reported on the appropriate Supplementary Lab CRF pages. Refer to Section 6.3 for 
guidance on the reporting of lab abnormalities. 
Pregnancy testing must be completed for WOCBP monthly during post-treatment (Weeks 4, 8, 
12, 16, 20, and 24) for WOCBP receiving RBV (see Table 5.1-3). Pregnancy testing may be 
performed at home if an in-office visit is otherwise not required. Telephone contacts are required 
to obtain results for all subjects who perform post-treatment at-home pregnancy testing. 
Although testing may be performed with home pregnancy testing kits, any positive result must 
be confirmed by serum pregnancy testing at study site.
The Roche COBASAmpliPrep/COBASTaqManHCV Test (LLOQ = 15 IU/mL) will be 
used to measure HCV RNA levels. The Versant HCV genotype 2.0 assay (LIPA) will be used for 
all genotype/subtype assessments. For samples where HCV genotype or subtype results are 
unavailable or inconclusive, the Abbott RealTime HCV Genotype II assay or viral sequence 
analysis may be used for genotype/subtype assessments. HCV RNA and HCV genotype will be 
analyzed by the central laboratory. 
5.3.2
Imaging Assessment for the Study
Not Applicable.
Date: 14-Dec-2015
67
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
5.3.3
Adverse Events Assessment
Subjects will be closely monitored throughout the study for AEs. Adverse events should be 
reported at study visits outlined in Table 5.1-2 and Table 5.1-3. Subjects who discontinue 
assigned therapy early should proceed to all post-treatment follow-up visits as indicated in Table 
5.1-3. All study drug-related AEs must be followed until resolution or stabilization.
5.3.4
Vital Signs and Physical Examinations
Vital signs (seated blood pressure and heart rate), weight, and physical measurements and 
examinations must be performed at study visits outlined in Table 5.1-1, Table 5.1-2 and Table 
5.1-3. Physical measurements including height and weight for calculation of BMI will be 
performed at screening. 
All subjects should be evaluated by qualified study site personnel at every visit, capable of 
making proper safety assessments based on the clinical history obtained from the subject.
A full physical examination will be performed at the Screening visit. A targeted physical exam 
should be performed during on treatment visits, when deemed necessary by the investigator 
when safety or other assessments warrant additional physical examination. A targeted physical 
examination may be performed by a qualified professional guided by the examiner’s 
observations and/or subject complaints on new or changed conditions, symptoms or concerns. 
Targeted physical exam includes assessment of heart, lung and abdomen.
5.3.5
Electrocardiogram
A 12-lead ECG performed while the subject is resting in a supine position will be recorded at 
study visits outlined in Table 5.1-1 and Table 5.1-2. The ECG should be recorded after the 
subject has been supine for at least 5 minutes.
5.4
Efficacy Assessments
Only data for the procedures and assessments specified in this protocol should be submitted to 
BMS on a CRF. Additional procedures and assessments may be performed as part of the 
subject’s standard medical care; however data for these assessments should remain in the 
subject’s medical record and should not be provided to BMS, unless specifically requested by the 
sponsor.
5.4.1
Primary Efficacy Assessment
The HCV RNA collected at post-treatment follow-up Week 12, for subjects treated with DCV + 
SOF + RBV for 24 weeks will be used for the primary antiviral assessment in this study.
5.4.2
Secondary Efficacy Assessments
HCV RNA collected at each of the following Weeks: 1, 2, 4, 8, 12, 16, 20 and 24 (EOT); post-
treatment Weeks 4 and 24 will be used for the secondary antiviral assessment in this study.
5.5
Pharmacokinetic Assessments
Date: 14-Dec-2015
68
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
5.7
Outcomes Research Assessments
Not Applicable
5.8
Other Assessments 
5.8.1
HCV Virologic Resistance Testing
Date: 14-Dec-2015
69
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
5.8.2
HIV Resistance Testing
Plasma samples for HIV resistance testing will be collected at Baseline and all on-treatment, 
post-treatment, visits and are tested upon rebound or virologic failure. An HIV viral resistance 
test will be automatically conducted following confirmation of HIV RNA levels of 
400 copies/mL and the result will be forwarded to the study site. Results should be confirmed 
within 2-4 weeks after the visit where HIV RNA was 400 copies/mL. The investigators may 
request a resistance test if HIV RNA levels are lower (between 200 – 400 copies/mL) based upon 
clinical experience.
5.8.3
Brief Questionnaire/Interim Phone Contacts
A brief questionnaire will be completed by the subject on Day 1 to include the subject’s e-mail 
address, name of the subject’s primary care physician and 2 non-residing contacts in case the 
subject cannot be reached for their study assessments. This questionnaire will be reviewed for 
the confirmation or modification (as applicable) by the subject at the end of treatment visit and 
all post-treatment follow-up visits.
During the post-treatment follow-up phase, sites will be required to perform an interim telephone 
contact with the subject on a monthly basis when the subject is not required to come for an 
in-office visit (ie, Weeks 8, 16, and 20). The purpose of phone contacts is to verify the subjects 
continuation in the study, verify the results of home pregnancy testing if applicable, and to 
confirm with the subject the date of his/her next study visit.
6
ADVERSE EVENTS
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation subject administered study drug and that 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease 
Date: 14-Dec-2015
70
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
temporally associated with the use of study drug, whether or not considered related to the study 
drug.
The causal relationship to study drug is determined by a physician and should be used to assess 
all adverse events (AE). The causal relationship can be one of the following:
Related: There is a reasonable causal relationship between study drug administration and 
the AE.
Not related: There is not a reasonable causal relationship between study drug 
administration and the AE.
The term "reasonable causal relationship" means there is evidence to suggest a causal 
relationship. 
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a subject. (In order to prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs.)
BMS will be reporting adverse events to regulatory authorities and ethics committees according 
to local applicable laws including European Directive 2001/20/EC and FDA Code of Federal 
Regulations 21 CFR Parts 312 and 320.
6.1
Serious Adverse Events
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: 

results in death

is life-threatening (defined as an event in which the subject was at risk of death at the time of 
the event; it does not refer to an event which hypothetically might have caused death if it
were more severe)

requires inpatient hospitalization or causes prolongation of existing hospitalization 
(see NOTE below)

results in persistent or significant disability/incapacity

is a congenital anomaly/birth defect 

is an important medical event (defined as a medical event(s) that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [eg, medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above.) 
Examples of such events include, but are not limited to, intensive treatment in an emergency 
room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not 
result in hospitalization.) Potential drug induced liver injury (DILI) is also considered an 
important medical event. (See Section 6.6 for the definition of potential DILI.)
Suspected transmission of an infectious agent (eg, pathogenic or nonpathogenic) via the study 
drug is an SAE.
Date: 14-Dec-2015
71
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Although pregnancy, overdose, cancer, and potential drug induced liver injury (DILI) are not 
always serious by regulatory definition, these events must be handled as SAEs. (See 
Section 6.1.1 for reporting pregnancies).
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 

a visit to the emergency room or other hospital department < 24 hours, that does not 
result in admission (unless considered an important medical or life-threatening event)

elective surgery, planned prior to signing consent

admissions as per protocol for a planned medical/surgical procedure

routine health assessment requiring admission for baseline/trending of health status 
(eg, routine colonoscopy)

medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases

admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (eg, lack of housing, economic 
inadequacy, caregiver respite, family circumstances, administrative reason).

Admission for administration of anticancer therapy in the absence of any other SAEs 
(applies to oncology protocols)
6.1.1
Serious Adverse Event Collection and Reporting
Sections 5.6.1 and 5.6.2 in the Investigator Brochure (IB) represent the Reference Safety 
Information to determine expectedness of serious adverse events for expedited reporting. 
Following the subject’s written consent to participate in the study, all SAEs, whether related or 
not related to study drug, must be collected, including those thought to be associated with 
protocol-specified procedures. All SAEs must be collected that occur during the screening period 
and within 30 days of discontinuation of dosing.
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure. 
An SAE report must be completed for any event where doubt exists regarding its seriousness. 
If the investigator believes that an SAE is not related to study drug, but is potentially related to 
the conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship must be specified in the narrative section of the SAE Report Form.
SAEs, whether related or not related to study drug, and pregnancies must be reported to BMS 
(or designee) within 24 hours of awareness of the event. SAEs must be recorded on the SAE 
Report Form; pregnancies on a Pregnancy Surveillance Form (electronic or paper forms). The 
preferred method for SAE data reporting collection is through the eCRF. The paper 
SAE/pregnancy surveillance forms are only intended as a back-up option when the eCRF system 
Date: 14-Dec-2015
72
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
is not functioning. In this case, the paper forms are to be transmitted via email or confirmed 
facsimile (fax) transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
For studies capturing SAEs through electronic data capture (EDC), electronic submission is the 
required method for reporting. In the event the electronic system is unavailable for transmission, 
paper forms must be used and submitted immediately. When paper forms are used, the original 
paper forms are to remain on site.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact
Information list.
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports must include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, the SAE report must be updated and submitted within 24 hours to BMS 
(or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs must be followed to resolution or stabilization.
6.2
Nonserious Adverse Events
A nonserious adverse event is an AE not classified as serious.
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug. Nonserious 
AE information should also be collected from the start of a placebo lead-in period or other 
observational period intended to establish a baseline status for the subjects.
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Section 6.1.1). Follow-up is also required for nonserious AEs that cause 
interruption or discontinuation of study drug and for those present at the end of study treatment 
as appropriate. All identified nonserious AEs must be recorded and described on the nonserious 
AE page of the CRF (paper or electronic). 
Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form electronic) as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning.

Any laboratory test result that is clinically significant or meets the definition of an SAE 

Any laboratory test result abnormality that required the subject to have study drug 
discontinued or interrupted
Date: 14-Dec-2015
73
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir

Any laboratory test result abnormality that required the subject to receive specific corrective 
therapy.
It is expected that wherever possible, the clinical rather than laboratory term would be used by 
the reporting investigator (eg, anemia versus low hemoglobin value).
If grading of laboratory abnormalities is reported as AE or SAE, the Division of AIDS table for 
Grading the Severity of Adult and Pediatric Adverse Events should be used (Appendix 2).
6.4
Pregnancy
If, following initiation of the study drug, it is subsequently discovered that a study subject is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 half-lives after product administration, the investigator must immediately notify the BMS 
Medical Monitor/designee of this event and complete and forward a Pregnancy Surveillance 
Form to BMS Designee within 24 hours of awareness of the event and in accordance with SAE 
reporting procedures described in Section 6.1.1.
The study drug should be permanently discontinued after pregnancy has been confirmed. 
The investigator must immediately notify the BMS (or designee) Medical Monitor of this event 
and complete and forward a Pregnancy Surveillance Form to BMS (or designee) within 24 hours 
of awareness of the event and in accordance with SAE reporting procedures described in 
Section 6.1.1. 
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
6.5
Overdose
All occurrences of overdose must be reported as SAEs (see Section 6.1.1 for reporting details).

DCV: total daily dose > 200 mg 

SOF: total daily dose > 800 mg

RBV: total daily dose > 20 mg/kg/day
Alternatively, an overdose is defined as the accidental or intentional administration of any dose 
of a product that is considered both excessive and medically important. All occurrences of 
overdose must be reported as an SAE (see Section 6.1.1 for reporting details).
Date: 14-Dec-2015
74
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
6.6
Potential Drug Induced Liver Injury (DILI)
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, 
meeting the defined criteria, must be reported as SAEs (see Section 6.1.1 for reporting details).
Potential drug induced liver injury is defined as: 

ALT 5 times baseline or nadir value, whichever is lower, AND 10 x ULN (upper limit of 
normal 
AND

Total bilirubin 2 x ULN
AND

No other immediately apparent possible causes of ALT elevation and hyperbilirubinemia, 
including, but not limited to, acute viral hepatitis, cholestasis, pre-existing hepatic disease 
excluding HCV or the administration of other drug(s), herbal medications or substances 
known to be hepatotoxic
After the initial event, subsequent monitoring should be discussed with the BMS Medical 
Monitor.
6.7
Other Safety Considerations
Any 
significant 
worsening 
noted 
during 
interim 
or 
final 
physical 
examinations, 
electrocardiogram, x-ray filming, any other potential safety assessment required or not required 
by protocol should also be recorded as a nonserious or serious AE, as appropriate, and reported 
accordingly. 
7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
Not applicable
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
Date: 14-Dec-2015
75
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
8.2
Populations for Analyses

Enrolled subjects are those who signed an informed consent form and are assigned a Subject 
Identification number (PID)

Randomized subjects are enrolled subjects who received a treatment assignment from the 
central randomization center

Treated subjects are randomized subjects who received at least 1 dose of study therapy

Follow-up subjects are treated subjects who continue into the follow-up period, as indicated 
on the end of treatment subject status Case Report Form (CRF).
8.3
Endpoints
Efficacy analyses will evaluate HCV RNA as measured by the Roche COBAS
AmpliPrep/COBASTaqManHCV Test (LLOQ = 15 IU/mL) 
8.3.1
Primary Endpoint
Proportion of subjects with SVR12, defined as HCV RNA < LLOQ, target detected (TD) or 
target not detected (TND) at follow-up Week 12 in all treated subjects. Missing HCV RNA data 
at follow-up Week 12 will be imputed using the Next Value Carried Backwards 
(NVCB) approach, i.e., missing HCV RNA data in the follow-up Week 12 window 
Date: 14-Dec-2015
76
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
will be imputed using the next and closest available HCV RNA measurement after
the follow-up Week 12 HCV RNA window.
8.3.2
Key Secondary Endpoint

The proportion of subjects who achieve SVR12 in the presence and absence of baseline 
NS5A resistance-associated polymorphisms.
8.3.3
Secondary Endpoints

On treatment safety, as measured by frequency of deaths, serious adverse events (SAE)s, 
discontinuation due to adverse events (AE)s, Grade 3/4 AEs and Grade 3/4 laboratory 
abnormalities;

The proportion of subjects who achieve HCV RNA < LLOQ, TD or TND at each of the 
following Weeks: 1, 2, 4, 8, 12, 16, 20, 24, and EOT; post-treatment Week 4 and 24;

The proportion of subjects who achieve HCV RNA <LLOQ, TND at each of the following 
Weeks: 1, 2, 4, 8, 12, 16, 20, 24, and EOT
8.3.4
Exploratory Endpoint(s) 
8.4
Analyses
Results will be presented for treated subjects. Demographics, baseline characteristics and safety 
data will also be presented.
Categorical variables will be summarized using counts and percents. Continuous variables will 
be summarized with univariate statistics (eg, mean, median, standard deviation).
Longitudinal summaries of safety and efficacy endpoints will use pre-defined visit week 
windows. Windows around planned measurement times will be constructed based on the 
midpoint between planned study visits. Laboratory measures will be summarized using standard 
international values and units, and US units will be provided in the appendix.
On-treatment endpoints will be assessed using measurements from the start of study therapy 
through the last dose of study therapy plus 7 days. Follow-up endpoints will be assessed with 
measurements after the last dose of study therapy plus 7 days.
Date: 14-Dec-2015
77
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
8.4.1
Demographics and Baseline Characteristics
The following will be summarized by treatment for treated subjects:

Demographics including: gender, age, race and ethnicity

Physical measurements at baseline: height, weight, body mass index (BMI)

Disease characteristics at baseline: HCV RNA level, IL28B SNP genotype, HIV positive, 
and fibrosis stage

Laboratory tests at baseline

Prior medications. Prior medications are those taken before the first dose of study therapy
8.4.2
Efficacy Analyses
Efficacy endpoints during the on-treatment period will be based on HCV RNA measurements 
closest to the planned visits within pre-defined visit windows. Efficacy endpoints during the 
follow-up period will be based on the last HCV RNA measurements in pre-defined visit 
windows.
The primary analysis for the proportions of patients meeting the efficacy endpoints will be for all 
treated subjects.
For binary efficacy endpoints including secondary efficacy endpoints, response rates and 2-sided 
95% exact Binomial confidence intervals (CIs) will be estimated for each treatment arm.
8.4.2.1
Primary Efficacy 
The primary analysis will be performed after all subjects have completed post-treatment 
Week 12 (SVR12). A final analysis (SVR24) will be performed at study completion.
The primary analysis for the primary endpoint SVR12 will use all treated subjects, and missing 
HCV RNA data at follow-up Week 12 will be imputed using the Next Value Carried Backwards 
(NVCB) approach, ie, missing HCV RNA data in the follow-up Week 12 window will be 
imputed using the next and closest available HCV RNA measurement after the follow-up 
Week 12 HCV RNA visit window.
The lower bound of the SVR12 95% confidence interval (CI) will be used to compare to the 
historical threshold of 79%. If it exceeds 79%, it can be concluded that the primary objective is 
achieved.
The following sensitivity analyses on the primary endpoint will also be conducted:

Sensitivity analysis using mITT: SVR12 rates and two-sided 95% CIs will use all treated 
subjects. The SVR12 status for subjects with missing follow-up Week 12 HCV RNA will be 
counted as non-responders

Sensitivity analysis using observed values: SVR12 rates and two-sided 95% CIs will use 
observed values. The numerator is based on subject meeting the response criteria. However, 
the denominator is based on treated subjects with HCV RNA at post-treatment Week 12
Date: 14-Dec-2015
78
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
8.4.2.2
Secondary Efficacy
The following efficacy endpoints will be summarized for treated subjects:

The proportion of subjects who achieve HCV RNA < LLOQ, TD/TND at each of the 
following Weeks: 1, 2, 4, 8, 12,16, 20, 24 and EOT; post-treatment Week 4 and 24 

The proportion of subjects who achieve HCV RNA < LLOQ, TND at each of the following 
Weeks: 1, 2, 4, 8,12, 16, 20, 24 and EOT 
8.4.3
Safety Analyses
Safety data will be summarized for treated subjects.
Deaths will be listed for enrolled subjects regardless of onset.
The frequencies of the following safety events will be summarized by study period (on treatment 
and follow-up) for treated subjects:

SAEs

AEs leading to discontinuation of study therapy (regardless of onset)

AEs by intensity

Laboratory abnormalities by toxicity grade
The investigators should determine the grade of AEs according to the Division of AIDS 
(DAIDS) of the US National Institutes of Health Table for Grading the Severity of Adult and 
Pediatric Adverse Events (2004) (Appendix 2). The investigators’ terms will be coded and 
grouped by system organ class using the latest version of the Medical Dictionary for Regulatory 
Activities (MedDRA) in production at BMS. AEs will be presented by system organ class and 
preferred term. Presentations will include both non-serious and SAEs, unless otherwise specified. 
If a subject had an AE with different intensities over time, only the worst grade will be reported 
for a study period.
Laboratory toxicities will be graded according to the Division of AIDS (DAIDS) of the US 
National Institutes of Health Table for Grading the Severity of Adult and Pediatric Adverse 
Events (2004) (Appendix 2). The laboratory value during the study period with the worst grade 
will be reported for each test.
8.4.4
Pharmacokinetic Analyses
Date: 14-Dec-2015
79
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
8.4.6
Outcomes Research Analyses
Not Applicable
8.4.7
Pharmacodynamics
8.4.8
Other Analyses 
Analyses for the frequency of genotypic substitutions at baseline, and post-baseline associated 
with virologic failure for each treatment will be conducted.
8.5
Interim Analyses
The primary analysis will be performed after all subjects have completed post-treatment 
Week 12 (SVR12). A final analysis (SVR24) will be performed at study completion. Additional 
interim efficacy analyses may be performed prior to post-treatment Week 12 to support external 
data presentations or for correspondences with health authorities.
9
STUDY MANAGEMENT
9.1
Compliance
9.1.1
Compliance with the Protocol and Protocol Revisions
The study shall be conducted as described in this approved protocol. All revisions to the protocol 
must be discussed with, and be prepared by, BMS. The investigator should not implement any 
deviation or change to the protocol without prior review and documented approval/favorable 
opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate 
hazard(s) to study subjects. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior 
to obtaining IRB/IEC approval/favorable opinion, as soon as possible the deviation or change 
will be submitted to:

IRB/IEC for review and approval/favorable opinion

BMS
Date: 14-Dec-2015
80
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir

Regulatory Authority(ies), if required by local regulations
Documentation of approval signed by the chairperson or designee of the IRB(s)/IEC(s) must be 
sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the 
subject: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS representatives will review data centrally to identify potential issues to determine a 
schedule of on-site visits for targeted review of study records. 
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare 
them with source documents, discuss the conduct of the study with the investigator, and verify 
that the facilities remain acceptable. 
In addition, the study may be evaluated by BMS internal auditors and government inspectors 
who must be allowed access to CRFs, source documents, other study files, and study facilities. 
BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory 
authorities, and promptly forward copies of inspection reports to BMS. 
9.1.2.1
Source Documentation
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or 
entered electronically. If source data are created (first entered), modified, maintained, archived, 
retrieved, or transmitted electronically via computerized systems (and/or any other kind of 
electronic devices) as part of regulated clinical trial activities, such systems must be compliant 
with all applicable laws and regulations governing use of electronic records and/or electronic 
signatures. Such systems may include, but are not limited to, electronic medical/health records 
(EMRs/EHRs), adverse event tracking/reporting, protocol required assessments, and/or drug 
accountability records).
When paper records from such systems are used in place of electronic format to perform 
regulated activities, such paper records should be certified copies. A certified copy consists of a 
copy of original information that has been verified, as indicated by a dated signature, as an exact 
copy having all of the same attributes and information as the original. 
Date: 14-Dec-2015
81
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
9.1.3
Investigational Site Training
Bristol-Myers Squibb will provide quality investigational staff training prior to study initiation. 
Training topics will include but are not limited to: GCP, AE reporting, study details and 
procedure, electronic CRFs, study documentation, informed consent, and enrollment of WOCBP.
9.2
Records
9.2.1
Records Retention
The investigator must retain all study records and source documents for the maximum period 
required by applicable regulations and guidelines, or institution procedures, or for the period 
specified by BMS, whichever is longer. The investigator must contact BMS prior to destroying 
any records associated with the study.
BMS will notify the investigator when the study records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, IRB). Notice of such 
transfer will be given in writing to BMS.
9.2.2
Study Drug Records 
It is the responsibility of the investigator to ensure that a current disposition record of study drug 
(inventoried and dispensed) is maintained at the study site to include investigational products. 
Records or logs must comply with applicable regulations and guidelines and should include:

amount received and placed in storage area

amount currently in storage area

label identification number or batch number 

amount dispensed to and returned by each subject, including unique subject identifiers

amount transferred to another area/site for dispensing or storage

nonstudy disposition (eg, lost, wasted) 

amount destroyed at study site, if applicable

amount returned to BMS

retain samples for bioavailability/bioequivalence, if applicable 

dates and initials of person responsible for Investigational Product dispensing/accountability, 
as per the Delegation of Authority Form.
BMS will provide forms to facilitate inventory control if the investigational site does not have an 
established system that meets these requirements.
9.2.3
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
Date: 14-Dec-2015
82
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the BMS electronic data capture tool, electronic CRFs will be prepared for all 
data collection fields except for fields specific to SAEs and pregnancy, which will be reported on 
the electronic SAE form and Pregnancy Surveillance form, respectively. If electronic SAE form 
is not available, a paper SAE form can be used. Spaces may be left blank only in those 
circumstances permitted by study-specific CRF completion guidelines provided by BMS. 
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by 
the investigator or qualified physician who is a subinvestigator and who is delegated this task on 
the Delegation of Authority Form. For electronic CRFs, review and approval/signature is 
completed electronically through the BMS electronic data capture tool. The investigator must 
retain a copy of the CRFs including records of the changes and corrections.
Each individual electronically signing electronic CRFs must meet BMS training requirements 
and must only access the BMS electronic data capture tool using the unique user account 
provided by BMS. User accounts are not to be shared or reassigned to other individuals.
9.3
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report. 
For this protocol, the Signatory Investigator will be selected as appropriate based on the 
following criteria:

External Principal Investigator designated at protocol development

Involvement in trial design

Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to BMS. Any publications 
or abstracts arising from this study must adhere to the publication requirements set forth in the 
clinical trial agreement (CTA) governing [Study site or Investigator] participation in the study. 
These requirements include, but are not limited to, submitting proposed publications to BMS at 
the earliest practicable time prior to submission or presentation and otherwise within the time 
period set forth in the CTA.
Date: 14-Dec-2015
83
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
10
GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
Complete Abstinence is defined as complete avoidance of 
heterosexual intercourse and is an acceptable form of 
contraception for all study drugs. This also means that 
abstinence is the preferred and usual lifestyle of the patient. 
This does not mean periodic abstinence (eg, calendar, 
ovulation, symptothermal, profession of abstinence for entry 
into a clinical trial, post-ovulation methods) and withdrawal, 
which are not acceptable methods of contraception. Women
must continue to have pregnancy tests. Acceptable alternate 
methods of highly or less effective contraception’s must be 
discussed in the event that the subject chooses to forego 
complete abstinence.
Date: 14-Dec-2015
84
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
11
LIST OF ABBREVIATIONS
Term
Definition
AE
adverse event
AFP
Alpha fetoprotein
ALT
alanine aminotransferase
ANC
absolute neutrophil count
APRI
aspartate aminotransferase platelet ratio index
ART
Anti-retroviral therapy
AST
aspartate aminotransferase
ASV
asunaprevir
AUC
area under the concentration-time curve
AUCTAU
area under the concentration-time curve in one dosing interval
HCG
human chorionic gonadotrophin
BID
bis in die, twice daily
BMI
body mass index
BMS
Bristol-Myers Squibb
BOC
boceprevir 
BUN
blood urea nitrogen
C
Celsius
cART
Combination anti-retroviral therapy
CFR
Code of Federal Regulations 
CHC
chronic hepatitis C
CI
confidence interval
Cm
centimeter
Cmax, CMAX
maximum observed concentration
Cmin, CMIN
trough observed concentration
CrCl
creatinine clearance
CRF
Case Report Form, paper or electronic
CTA
Clinical Trial Agreement
CVR
combined virologic response
CYP
cytochrome p-450
Date: 14-Dec-2015
85
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Term
Definition
D/C
discontinue
DAA
direct acting antiviral
DAIDS
Division of AIDS
DCV
daclatasvir
DCV/ASV
daclatasvir and asunaprevir combination therapy
DCV+SOF
daclatasvir and sofosbuvir combination therapy
DILI
drug-induced liver injury
dL
Deciliter
DMC
Data Monitoring Committee
DSM IV
Diagnostic and Statistical Manual of Mental Disorders (4th Edition)
DUAL
daclatasvir/asunaprevir therapy
EAP
Expanded Access Program
ED50
50% effective concentration
ECG
electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
Eg
exempli gratia (for example)
EOT
End of Treatment
E-R
Exposure-response
ERCP
endoscopic retrograde cholangiopancreatography
ESAs
erythropoiesis-stimulating agents
ESRD
end-stage renal disease
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
G
gram
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GT
genotype
H
hour
Hb
hemoglobin
HBsAg
hepatitis B surface antigen
Date: 14-Dec-2015
86
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Term
Definition
HBV
hepatitis B virus
HCC
heptaocellular carcinoma
HCG
human chorionic gonadotrophin
HCV
hepatitis C virus
HE
hepatic encephalopathy
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
HRT
Hormone Replacement Therapy
IB
Investigator Brochure
ICH
International Conference on Harmonisation 
Ie
id est (that is)
IEC
Independent Ethics Committee
IMP
investigational medicinal products
IND
Investigational New Drug Exemption
INR
international normalized ratio
IRB
Institutional Review Board
IRT
Interactive Response Technology 
IU
International Unit
IUD
intrauterine device
Kg
kilogram
L
liter
LADR
low acceleration dose regimen
LDV
ledipasvir
LLOQ
lower limit of quantification
LT
liver transplant
Mg
milligram
Min
minute
mITT
modified intent-to-treat
mL
milliliter
g
microgram
Date: 14-Dec-2015
87
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Term
Definition
N
number of subjects or observations
N/A
not applicable
NIMP
non-investigational medicinal products 
NVCB
Next Value Carried Backwards
OLT
orthotopic liver transplant
pegIFN
pegylated interferon
PI
protease-inhibitor
PID
Patient Identification Number
PK
pharmacokinetics
PPK
Population pharmacokinetics
QD, qd
quaque die, once daily
QUAD
daclatasvir/asunaprevir/pegylated interferon/ribavirin therapy
RBV
ribavirin
RCI
replication complex inhibitor
SAE
serious adverse event
SAR
serious adverse reaction
SmPC
Summary of Product Characteristics
SNP
single nucleotide polymorphism
SOC
standard of care
SOF
sofosbuvir
SOP
Standard Operating Procedures
SSC
Special Search Categories
SVR
sustained virologic response
TD
target detected
TND
target not detected
TN
Treatment-Naïve
TVR
telaprevir 
ULN
Upper limit of normal
USPI
United States Package Insert
VBT
virologic breakthrough
Date: 14-Dec-2015
88
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Term
Definition
VK
viral kinetics
WBC
white blood cell
WOCBP
women of childbearing potential
Date: 14-Dec-2015
89
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
12
REFERENCES
REFERENCES FOR THE USE OF CONDOMS WITH SPERMICIDE.
Kestelman P. et. al., Efficacy of the Simultaneous Use of Condoms and Spermicides Family 
Planning Perspectives.Vol 23 (5); October 1991.
Gabbay MB, Thomas J, Gibbs A, Hold P. A Randomized Crossover Trial of The Impact of 
Additional Spermicide on Condom Failure Rates. Sex Transm Dis 2008; 35: 862-8.
1
Simmonds P. Viral heterogeneity of the hepatitis C virus. J Hepatol 1999; 31 (Suppl 1): 54 
60. 
2
Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin 
compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a 
randomized trial. Lancet 2001; 358(9286): 958-965. 
3
Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic 
hepatitis C virus infection. N Engl J Med 2002; 347(13): 975-982. 
4
Hadziyannis SJ, Sette H, Jr, Morgan TR, et al. Peginterferon alpha-2a and ribavirin 
combination therapy in chronic hepatitis C: a randomized study of treatment duration and 
ribavirin dose. Ann Intern Med 2004; 140(5):346-355.
5
Jacobson IM, McHutchison JG, Dusheiko G et al. Telaprevir for previously untreated chronic 
hepatitis C virus infection. N Engl J Med 2011;364:2405-2416.
6
Poordad F, McCone J Jr, Bacon BR et al. Boceprevir for untreated HCV genotype 1 
infection. N Engl J Med 2011;364:1195-1206.
7
Lawitz E, Sulkowski MS, Ghalib R et al. Simeprevir plus sofosbuvir, with or without 
ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to 
pegylated interferon and ribavirin and treatment-naïve patients: the COSMOS randomised 
study. Lancet 2014;384:1756-1765.
8
Afdhal N, Zeuzem S, Kwo P et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 
infection. N Engl J Med 2014;370:1889-1898.
9
Ferenci P, Bernstein D, Lalezari J et al. ABT-450/r-ombitasvir and dasabuvir with or without 
ribavirin for HCV. N Engl J Med 2014;370:1983-1992.
10 Nelson DR, Cooper JN, Lalezari JP et al. All-oral 12-week treatment with daclatasvir plus 
sofosbuvir in patients with hepatitis c virus genotype 3 infection: ALLY-3 phase III study. 
Hepatology 2015;61:1127-1135.
11 Messina JP et al. Hepatology. 2015;61:77-87.
12 Manos MM, et al. J Med Virol. 2012;84:1744-1750
Date: 14-Dec-2015
90
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
13 Zarife MA, Silva LK, Silva MB, Lopes GB, Barreto ML, Teixeira Mda G, et al. Prevalence 
of hepatitis C virus infection in north-eastern Brazil: a population-based study. Trans R Soc 
Trop Med Hyg 2006;100(7):663–8.
14 Das BR, Kundu B, Khandapkar R, Sahni S. Geographical distribution of hepatitis C virus 
genotypes in India. Indian J Pathol Microbiol 2002;45(3):323–8.
15 Idrees M, Riazuddin S. Frequency distribution of hepatitis C virus genotypes in different 
geographical regions of Pakistan and their possible routes of transmission. BMC Infect Dis 
2008;8:69.
16 Stamouli M, Panagiotou I, Kairis D, Michopoulou A, Skliris A, Totos G. Genotype 
distribution in chronic hepatitis C patients in Greece. Clin Lab 2012;58(1–2):173–6.
17 Chlabicz S, Flisiak R, Kowalczuk O, Grzeszczuk A, Pytel-Krolczuk B, Prokopowicz, et al. 
Changing HCV genotypes distribution in Poland—relation to source and time of infection. J 
Clin Virol 2008;42(2):156–9.
18 de Vries MJ, te Rijdt B, van Nieuwkerk CM. Genotype distribution amongst hepatitis C 
patients in The Netherlands. Neth J Med 2006;64(4):109–13.
19 Wang Y, Tao QM, Zhao HY, Tsuda F, Nagayama R, Yamamoto K, et al. Hepatitis C virus 
RNA and antibodies among blood donors in Beijing. J Hepatol 1994;21(4):634–40.
20 Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet 
Infect Dis 2005;5:558–567.
21 Bochud PY, Cai T, Overbeck K, et al. Genotype 3 is associated with accelerated fibrosis 
progression in chronic hepatitis C. J Hepatol 2009; 51: 655–66.
22 Probst A, Dang T, Bochud M, et al. Role of Hepatitis C virus genotype 3 in liver fibrosis 
progression – a systematic review and meta-analysis. J Viral Hepat 2011; 18: 745–59.
23 Nkontchou G, Ziol M, Aout M, et al. HCV genotype 3 is associated with a higher 
hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis. J Viral Hepat 
2011; 18: e516–22.
24 Mirandola S, Realdon S, Iqbal J, et al. Liver microsomal triglyceride transfer protein is 
involved in hepatitis C liver steatosis. Gastroenterology 2006; 130: 1661–9.
25 Jackel-Cram C, Babiuk LA, Liu Q. Up-regulation of fatty acid synthase promoter by hepatitis 
C virus core protein: genotype-3a core has a stronger effect than genotype-1b core. J Hepatol 
2007; 46: 999–1008.
26 Jackel-Cram C, Qiao L, Xiang Z, et al. Hepatitis C virus genotype-3a core protein enhances 
sterol regulatory element binding protein-1 activity through the phosphoinositide 3- kinase-
Akt-2 pathway. J Gen Virol 2010; 91:1388–95.
Date: 14-Dec-2015
91
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
27 Aghemo A, et al. The pattern of pegylated interferon-alpha2b and ribavirin treatment failure 
in cirrhotic patients depends on hepatitis C virus genotype. Antivir Ther. 2009;14(4):577-84.
28 Zeuzem S, Hultcrantz R, Bourliere M, et al. Peginterferon alfa-2b plus ribavirin for treatment 
of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J 
Hepatol 2004; 40: 993–9.
29 Shah SR, Patel K, Marcellin P, et al. Steatosis is an independent predictor of relapse 
following rapid virologic response in patients with HCV genotype 3. Clin Gastroenterol 
Hepatol 2011; 9: 688–93.
30 Lawitz E, Mangia A, Wyles D et al., Sofosbuvir for Previously Untreated Chronic Hepatitis 
C Infection, N Engl J Med 2013;368:1878-1887.
31 Jacobson I, Gordon SC, Kowdley KV et al., Sofosbuvir for Hepatitis C Genotype 2 or 3 in 
Patients without Treatment Options, N Engl J Med 2013;368:1867-1877.
32 Zeuzem S, Dusheiko GM, Salupere R et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 
3. N Engl J Med 2014;370:1993-2000.
33 Gane E et al. Sofosbuvir/ledipasvir fixed dose combination is safe and effective in difficult-
to-treat populations including genotype-3 patients, decompensated genotype-1 patients, and 
genotype-1 patients with prior sofosbuvir treatment experience. EASL 2014 (O6).
34 Gane E et al. High efficacy of LDV/SOF regimens for 12 weeks for patients with HCV 
genotype 3 or 6 infection. AASLD 2014 (LB-11).
35 Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management, and treatment of 
hepatitis C: an update. Hepatology2009;49:1335-1374.
36 Shiffman ML, Suter F, Bacon BR, et al. Peginterferon alfa-2a and ribavirin for 16 or 24 
weeks in HCV genotype 2 or 3. N Engl J Med 2007;357:124-134.
37 EASL Clinical Practice Guidelines. EASL recommendations on treatment of hepatitis c 
2015. J Hepatol 2015;63:199-236.
38 AASLD/IDSA/IAS. Recommendations for testing, managing, and treating hepatitis C, 
http://www.hcvguidelines.org. August 2015.
39 Sovaldi product information. Gilead Sciences USA, 2015.
40 Lawitz E, Lalezari JP, Hassanein T et al. Sofosbuvir in combination with peginterferon alfa 
2a and ribavirin for non-cirrhotic, treatment-naïve patients with genotypes 1, 2, and 3 
hepatitis c infection: a randomised, double-blind, phase 2 trial. Lancet Infect Dis 
2013;13:401-408.
41 www.clinicaltrials.gov, Safety and efficacy study of daclatasvir 60mg, sofosbuvir 400mg, 
and ribavirin (dosed based upon weight) in subjects with chronic genotype 3 hepatitis c 
Date: 14-Dec-2015
92
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
infection with or without prior treatment experience and compensated advanced cirrhosis for 
12 or 16 weeks, NCT02319031
42 GT Everson, TT Tran, WJ Towner, et al. Safety and efficacy of treatment with the interferon-
free, ribavirin-free combination of sofosbuvir + GS-5816 for 12 weeks in treatment naive 
patients with genotype 1-6 HCV infection. 49th European Association for the Study of the 
Liver International Liver Congress (EASL 2014). London, April 9-13, 2014. Abstract O111.
43 Foster GR., Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 
3 Infection. N Engl J Med DOI: 10.1056/NEJMoa1512612
44 Poordad F, Lawitz E, Gutierrez JA et al. C-SWIFT: Grazoprevir/Elbasvir plus sofosbuvir in 
cirrhotic and noncirrhotic, treatment naïve patients with hepatitis c virus genotype 1 infection 
for durations of 4, 6 or 8 weeks and genotype 3 infection for durations of 8 or 12 weeks. 
EASL 2015 (abstract).
45 Gao M, Meanwell NA et al., Nature 2010;465:96-100.
46 Sulkowski MS, Gardiner DF, Rodriguez-Torres M et al. Daclatasvir plus sofosbuvir for 
previously treated or untreated chronic HCV infection. N Engl J Med 2014;370:211-221.
47 AI447028 Clinical Study Report: A Phase 3 Study with Asunaprevir and Daclatasvir 
(DUAL) for Null or Partial Responders to Peginterferon Alfa and Ribavirin (P/R), Intolerant 
or Ineligible to P/R Subjects and Treatment-Naive Subjects with Chronic Hepatitis C 
Genotype 1b Infection. Bristol-Myers Squibb Company; 2014. Document Control No. 
930076616.
48 Wyles et al. N Engl J Med. 2015 Aug 20;373(8):714-25
49 Population Pharmacokinetics, Exposure-response, and Viral Kinetic Analyses of HCV NS5A 
inhibitor (BMS-790052) in Disease Patients. Bristol-Myers Squibb Company; 2012. 
Document Control No. 930065448.
50 AI444273 Final Clinical Study Report: A phase 1, open-label, crossover study to evaluate the 
drug interaction between dolutegravir and daclatasvir in healthy adult subjects. Bristol-Myers 
Squibb Company; 2014. Document Control No. 930086397
51 AI444040 Clinical Study Report: Parallel, open-label, randomized study to evaluate the 
safety, pharmocokinetics, and pharmacodynamics of sofosbuvir (PSI-7977) in combination 
with daclatasvir (BMS-790052) with or without ribavirin in treatment-naïve subjects 
chronically infected with hepatitis-C virus genotypes 1,2 or 3. Bristol-Myers Squibb 
Company, 2013. Document Control No. 930072658.
52 Daclatasvir (BMS-790052) Summary of Clinical Efficacy. Bristol-Myers Squibb Company; 
2013. Document Control No. 930074369.
53 Daclatasvir (BMS-790052) Investigator Brochure. Bristol-Myers Squibb Pharmaceutical 
Research Institute.
Date: 14-Dec-2015
93
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
54 Sustained Virologic Response With Daclatasvir Plus Sofosbuvir +/- Ribavirin (RBV) in 
Chronic HCV Genotype (GT) 1-Infected Patients Who Previously Failed Telaprevir (TVR) 
or Boceprevir (BOC). ISDA 2013 Abstract
55 AI444216 Final Clinical Study Report: A phase 3 evaluation of daclatasvir, sofosbuvir, in 
treatment-experienced chronic hepatitis c (genotype 1, 2, 3, 4, 5, or 6) subjects co-infected 
with human immunodeficiency virus (HIV). Bristol-Myers Squibb Company; 2015. 
Document Control No. 90086242.
Date: 14-Dec-2015
94
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
APPENDIX 1
DSM IV: DIAGNOSTIC CRITERIA FOR DRUG AND ALCOHOL 
ABUSE
Criteria for Alcohol & Substance Abuse
1) A maladaptive pattern of substance use leading to clinically significant impairment or 
distress, as manifested by one (or more) of the following, occurring within a 12-month 
period:
a) recurrent substance use resulting in a failure to fulfill major role obligations at work, 
school, or home (eg, repeated absences or poor work performance related to substance 
use; substance-related absences, suspensions, or expulsions from school; neglect of 
children or household)
b) recurrent substance use in situations in which it is physically hazardous (eg, driving an 
automobile or operating a machine when impaired by substance use)
c) recurrent substance-related legal problems (eg, arrests for substance-related disorderly 
conduct)
d) continued substance use despite having persistent or recurrent social or interpersonal 
problems caused or exacerbated by the effects of the substance (eg, arguments with 
spouse about consequences of intoxication, physical fights)
2) The symptoms have never met the criteria for Substance Dependence for this class of 
substance.
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, 
Fourth Edition, Text Revision (Copyright 2000). American Psychiatric Association.
Date: 14-Dec-2015
95
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
APPENDIX 2
DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF 
ADULT AND PEDIATRIC ADVERSE EVENTS PUBLISH DATE: 
DECEMBER, 2004
Date: 14-Dec-2015
96
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
97
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
98
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
99
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
100
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
101
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
102
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
103
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
104
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
105
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
106
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
107
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
108
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
109
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
110
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
111
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
112
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
113
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
114
2.0
Approved
930095055
2.0
v


Clinical Protocol
AI444379
BMS-790052
daclatasvir
Date: 14-Dec-2015
115
2.0
Approved
930095055
2.0
v

SAP_000.pdf: 
990
1.0
Approved 
930118421
1.0
v


991
1.0
Approved 
930118421
1.0
v


992
1.0
Approved 
930118421
1.0
v


993
1.0
Approved 
930118421
1.0
v


994
1.0
Approved 
930118421
1.0
v


995
1.0
Approved 
930118421
1.0
v


996
1.0
Approved 
930118421
1.0
v


997
1.0
Approved 
930118421
1.0
v


998
1.0
Approved 
930118421
1.0
v


999
1.0
Approved 
930118421
1.0
v


1000
1.0
Approved 
930118421
1.0
v


1001
1.0
Approved 
930118421
1.0
v


1002
1.0
Approved 
930118421
1.0
v


1003
1.0
Approved 
930118421
1.0
v


1004
1.0
Approved 
930118421
1.0
v


1005
1.0
Approved 
930118421
1.0
v


1006
1.0
Approved 
930118421
1.0
v