A Follow-up Study to Assess Resistance and Durability of Response to AbbVie Direct-Acting Antiviral Agent (DAA) Therapy (ABT-493 and/or ABT-530) in Subjects Who Participated in Phase 2 or 3 Clinical Studies for the Treatment of Chronic Hepatitis C Virus (HCV) Infection
Phase: PHASE2
Conditions: Hepatitis C
Sponsor: AbbVie

NCT02441283

ABT-493, ABT-530
M13-576 Protocol Amendment 3
EudraCT 2015-000452-24
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1.1
Protocol Amendment:  Summary of Changes
Previous Protocol Versions
Protocol
Date 
Original
22 December 2014
Amendment 1
03 April 2015
Amendment 2
19 July 2016
Amendment 2.01 (UK Only)
19 January 2017
The purpose of this amendment is to:
●
Section 1.2, Synopsis, update the phase of the study from Phase 2 to Phase 2/3 
to be consistent with the rest of the document.
Rationale:  To make the update to this page that was not made in previous 
version of the document.
●
Section 1.2, Synopsis – Objectives, Section 4.0 – Study Objectives, 
Section 5.3.1 – Clinical Laboratory Tests, Clinical Laboratory Tests Table 1, 
Section 5.3.3.1 – Clinical Variables:  Remove collection of alpha fetoprotein.
Rationale:  Alpha fetoprotein is an unreliable test for screening for liver 
disease including hepatocellular carcinoma (HCC) and is no longer 
recommended in the AASLD HCV guidelines (2017)29 for this purpose. 
●
Section 1.2, Synopsis, Main Inclusion:  Incorporate language from 
Administrative Change 1 for Inclusion Criterion 3 to clarify the criterion by 
adding a sentence to note that subjects who have been retreated with a 
commercially available anti-HCV treatment are able to enroll in the study 
greater than 2 years after the last dose of the AbbVie DAA therapy from the 
previous AbbVie clinical study.
Rationale:  The 2 year timeframe should not apply to subjects who have been 
retreated, for whom we will not be collecting blood samples to evaluate the 
persistence of resistance substitutions.  The additional text clarifies the intent 
of Protocol Amendment 2, which allowed the enrollment of these retreated 
subjects.  The inclusion criteria should have been amended at that time but 

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was not, therefore this administrative change is necessary.  The change will 
not have impact on the safety or well-being of subjects enrolled in the study.
●
Section 5.2.1, Inclusion Criteria:  Incorporate clarification language from 
Administrative Change 1 for Inclusion Criterion 3 – Clarify the criterion by 
adding a sentence to note that subjects who have been retreated with a 
commercially available anti-HCV treatment are able to enroll in the study 
greater than 2 years after the last dose of the AbbVie DAA therapy from the 
previous AbbVie clinical study.
Rationale:  The 2 year timeframe should not apply to subjects who have been 
retreated, for whom we will not be collecting blood samples to evaluate the 
persistence of resistance substitutions.  The additional text clarifies the intent 
of Protocol Amendment 2, which allowed the enrollment of these retreated 
subjects.  The inclusion criteria should have been amended at that time but 
was not, therefore this administrative change is necessary.  The change will 
not have impact on the safety or well-being of subjects enrolled in the study.
●
Section 5.3.1.1, Collection of Liver Diagnostic Results:   Screening for 
Hepatocellular Carcinoma (HCC) by liver ultrasound has been added to the 
final study visit for cirrhotic subjects, in order to screen them for development 
of HCC as part of long-term follow-up.
Rationale:  Subjects with cirrhosis may be at-risk for developing HCC, and 
therefore will be screened for HCC by liver ultrasound testing at the final visit.
!
Section 5.3.4, Safety Variables, Incorporate language from Amendment 2.01 
(UK only):  Revise wording to clarify that the investigator is responsible for 
collecting Serious Adverse Event data.
Rationale:  To clarify the language to say that the investigator collects Serious 
Adverse Event data.  The previous language was redundant.
!
Section 6.0, Adverse Events, Incorporate language from Amendment 2.01 (UK 
only):  Revise wording to clarify that the investigator is responsible for 
collecting Serious Adverse Event data.
Rationale:  To clarify the language to say that the investigator collects Serious 
Adverse Event data.  The previous language was redundant.

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!
Section 6.5, Adverse Event Reporting, Incorporate language from 
Amendment 2.01 (UK only):  Add language regarding reporting of Suspected 
Unexpected Serious Adverse Reactions (SUSAR).
Rationale:  To clarify that AbbVie is responsible for the reporting of Suspected 
Unexpected Serious Adverse Reactions (SUSAR).
!
Section 7.0, Protocol Deviations, Incorporate language from Amendment 2.01 
(UK only):  Clarify language to state that the investigator is responsible for 
reporting protocol deviations to the Independent Ethics Committee 
(IEC)/Independent Review Board (IRB) and to AbbVie.
Rationale:  To clarify to whom investigators should report protocol 
deviations.
!
Section 9.0, Ethics, Incorporate language from Amendment 2.01 (UK only):  
Clarify that all protocol amendments must be approved by the Independent 
Ethics Committee (IEC)/Independent Review Board (IRB as well as 
Regulatory Authority(ies), if required by local regulations, and to clarify that 
the Sponsor is responsible for reporting Suspected Unexpected Serious 
Adverse Reactions.
Rationale:  To clarify requirements for approval of protocol amendments and 
reporting of Suspected Unexpected Serious Adverse Reactions.
●
Section 13.0, Completion of the Study, Incorporate language from 
Amendment 2.01 (UK only):  Clarify that the Clinical Study report will be 
provided by AbbVie to the Regulatory Authority(ies), if required by local 
regulations.
Rationale:  To clarify the responsibility of providing the Clinical Study Report 
to Regulatory Authority(ies), if required by local regulations.
!
Appendix C, Study Activities A and B, Incorporate language from 
Amendment 2.01 (UK only):  Clarify the need for collection of total bilirubin 
at Month 12 and Month 18 for calculating Child-Pugh in cirrhotic subjects.
Rationale:  To clarify that total bilirubin is required at Month 12 and 
Month 18 for calculation of the Child-Pugh for cirrhotic subjects.
●
Appendix C, Study Activities A and B:  Screening for Hepatocellular 
Carcinoma (HCC) by liver ultrasound has been added to the final study visit 

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for cirrhotic subjects only in order to screen them for development of HCC as 
part of long-term follow-up.
Rationale:  Subjects with cirrhosis may be at-risk for developing HCC, and 
therefore will be screened for HCC by liver ultrasound testing at the final visit.
An itemized list of all changes made to the protocol under this amendment can be found 
in Appendix F.

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1.2
Synopsis
AbbVie Inc.
Protocol Number:  M13-576
Name of Study Drug:  Not applicable.  There is no 
AbbVie Investigational Product administered.
Phase of Development:  2/3
Name of Active Ingredient:  There is no AbbVie 
Investigational Product administered.
Date of Protocol Synopsis:  09 October 2017
Protocol Title:  A Follow-up Study to Assess Resistance and Durability of Response to AbbVie 
Direct-Acting Antiviral Agent (DAA) Therapy (ABT-493 and/or ABT-530) in Subjects Who Participated 
in Phase 2 or 3 Clinical Studies for the Treatment of Chronic Hepatitis C Virus (HCV) Infection
Objectives:  
The primary objectives of this study are as follows:
!
Assess the durability of response for subjects who achieved SVR12 with a regimen including 
ABT-493 and/or ABT-530.
!
Assess the emergence and persistence of specific HCV amino acid variants associated with drug 
resistance in subjects who experience virologic failure.
The secondary objectives of the study are as follows:
!
Summarize medical events related to progression of liver disease including: 
o
Events of hepatic decompensation (per Section 5.3.1.1), 
o
Change in Child-Pugh classification, 
o
Liver transplantation, 
o
Hepatocellular carcinoma,
o
Death.
!
Summarize results of the following laboratory tests and scores:  FibroTest, APRI, IP-10, alpha 
fetoprotein (if collected under a previous protocol version), FibroScan, and liver biopsy.
Investigators:  Multicenter
Study Sites:  Approximately 35 sites
Study Population:
This Phase 2/3, multicenter study will be conducted in subjects who received at least one dose of an 
ABT-493- and/or ABT-530-containing regimen at any dose level in a prior AbbVie Phase 2 or 3 study 
for the treatment of chronic HCV and elect to enroll in this study.
Number of Subjects to be Enrolled:
Approximately 400.
An attempt will be made to enroll all virologic failures who will not receive immediate treatment with a 
regimen containing ABT-493/ABT-530.

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Methodology:  
At the Day 1 Visit, subjects will provide written (signed and dated) informed consent prior to any study 
specific procedures being performed.  The investigator will evaluate whether the subject meets all of the 
eligibility criteria prior to enrollment in this rollover study.
Subjects will have completed the post-treatment period of the prior AbbVie HCV clinical study.  All 
subjects will be followed for approximately 3 years following their last dose of DAA in the previous 
AbbVie HCV clinical study, with the exception of re-treated subjects who will be followed through post-
treatment Week 12.  The 3 years will be inclusive of any post-treatment period in the prior study, as well 
as any gap between the end of the prior study and enrollment into this study.
Subjects who are not re-treated will return to the study site for their scheduled visits on an outpatient 
basis at Month 3, Month 6 and every 6 months thereafter for approximately 3 years after the last dose of 
DAA in the previous clinical study.  Subjects with virologic failure who receive re-treatment will only 
have one additional outpatient visit subsequent to beginning re-treatment, at post-treatment Week 12 to 
assess the SVR12 result, and then they will discontinue from the study.
Diagnosis and Main Criteria for Inclusion/Exclusion:
Main Inclusion:  
1.
The subject has received at least one dose of an ABT-493- and/or ABT-530-containing regimen in a 
prior AbbVie HCV Phase 2 or 3 study which has been conducted under a US IND (see Appendix D 
for list of eligible prior studies).
2.
The interval between the last dose of the AbbVie DAA therapy from the previous clinical study and 
enrollment in Study M13-576 must be no longer than 2 years for subjects who have not been 
retreated.  Subjects who have been treated with a commercially-available anti-HCV treatment may be 
enrolled greater than 2 years after the last dose of the AbbVie DAA therapy from the previous
clinical study.
3.
The subject must voluntarily sign and date the informed consent form approved by an Independent 
Review Board or Ethics Committee prior to the initiation of any study-specific procedures.
4.
Subject completed the post-treatment period of an eligible prior study.
Main Exclusion:  
1.
The investigator considers the subject unsuitable for the study for any reasons (e.g., failure to comply 
with study procedures in the prior AbbVie clinical study).
2.
Receipt of any investigational HCV antiviral treatment after receiving ABT-493 and/or ABT-530 in 
the prior study.
3.
Subjects who experienced non-virologic treatment failures due to premature discontinuation of study 
drug in the prior study of ABT-493/ABT-530.
4.
Participation in AbbVie's Study M15-942 protocol for re-treatment for virologic failures in the prior 
Phase 2 or 3 study.
Investigational Products:
There is no AbbVie Investigational Product administered.
Criteria for Evaluation:
Efficacy:
Virologic response will be assessed by HCV RNA in log10 IU/mL at various time points.

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Criteria for Evaluation (Continued):
Resistance:
The persistence of amino acid variants associated with drug resistance will be assessed by population, 
and/or deep sequencing at the Day 1 Visit, and at various subsequent time points, as appropriate, for a 
period of up to 3 years after the subject's last dose of DAA therapy in the prior AbbVie clinical study.
Liver Disease Progression:
Liver Disease progression will be assessed by laboratory test results (FibroTest and APRI) and the 
recording of medical events related to progression of liver disease including, events of hepatic 
decompensation (per Section 5.3.1.1), change in Child-Pugh classification, liver transplantation, 
hepatocellular carcinoma, death.
Safety:
Only serious adverse events related to study procedures or those considered by the investigator to be 
reasonably related to exposure to ABT-530 and/or ABT-493 in a prior study will be assessed.
Statistical Methods:
Efficacy:
The primary efficacy endpoints are the percentage of subjects who maintain a sustained virologic 
response and the percentage of subjects who relapse or have new HCV infection at any time up to the last 
follow-up in this study out of subjects who achieved SVR12 in the previous study and enroll in this study.  
The summary will be separate for subjects who have probable relapse as distinguished from subjects who 
have probable new HCV infection based on DNA sequence phylogenetic analysis of HCV drug target 
genes.  In addition, the time to relapse or new infection from the end of DAA treatment for subjects who 
achieved HCV RNA < LLOQ at the end of treatment in the previous study and from SVR12 time point for 
the subset of subjects who achieved SVR12 in the previous study will be displayed graphically using 
Kaplan-Meier curves.
Resistance:
The variants at each amino acid position by population and/or deep sequencing at available post-baseline 
time points compared to baseline and prototypic reference standard sequences will be summarized by 
DAA target genes and accompanying listings will be provided.
Safety:
Serious adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
and tabulated by system organ class (SOC) and preferred term (PT).  A summary of medical events 
related to the progression of liver disease and shifts in laboratory measurements will be provided.

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1.3
List of Abbreviations and Definition of Terms
Abbreviations
AE
Adverse event
DAA
Direct-acting antiviral agent
DNA
Deoxyribonucleic acid
eCRF
Electronic Case Report Form
EDC
Electronic data capture
FDA
US Food and Drug Administration
GCP
Good Clinical Practice
GGT
Gamma-glutamyl transpeptidase
HCV
Hepatitis C virus
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IP-10
Interferon gamma-induced protein 10
IRB
Institutional Review Board
LLOD
Lower limit of detection
LLOQ
Lower limit of quantification
MedDRA
Medical Dictionary for Regulatory Activities
PegIFN
Pegylated-interferon
RBV
Ribavirin
RNA
Ribonucleic acid
SAE
Serious adverse event
SVR
Sustained virologic response

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2.0
Table of Contents
1.0
Title Page ...............................................................................1
1.1
Protocol Amendment:  Summary of Changes ......................................... 2
1.2
Synopsis................................................................................................. 6
1.3
List of Abbreviations and Definition of Terms........................................ 9
2.0
Table of Contents ................................................................10
3.0
Introduction......................................................................... 13
3.1
Differences Statement .......................................................................... 20
3.2
Benefits and Risks................................................................................ 20
4.0
Study Objectives..................................................................20
5.0
Investigational Plan.............................................................21
5.1
Overall Study Design and Plan:  Description ........................................ 21
5.2
Selection of Study Population............................................................... 22
5.2.1
Inclusion Criteria.................................................................................. 22
5.2.2
Exclusion Criteria................................................................................. 23
5.2.3
Prior and Concomitant Therapy............................................................ 23
5.3
Efficacy and Safety Assessments/Variables.......................................... 25
5.3.1
Efficacy and Safety Measurements Assessed and Flow Chart ............... 25
5.3.1.1
Study Procedures.................................................................................. 25
5.3.2
Efficacy Variables................................................................................ 29
5.3.3
Resistance Variables............................................................................. 30
5.3.3.1
Clinical Variables................................................................................. 30
5.3.4
Safety Variables ................................................................................... 30
5.4
Removal of Subjects from Therapy or Assessment ............................... 31
5.4.1
Discontinuation of Individual Subjects ................................................. 31
5.4.2
Discontinuation of Entire Study............................................................ 31
5.5
Treatments ........................................................................................... 32
5.5.1
Method of Assigning Subject ID Numbers............................................ 32
5.6
Discussion and Justification of Study Design........................................ 32
5.6.1
Discussion of Study Design and Choice of Control Groups .................. 32
5.6.2
Appropriateness of Measurements........................................................ 32
5.6.3
Suitability of Subject Population .......................................................... 32

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6.0
Adverse Events .................................................................... 33
6.1
Definitions ........................................................................................... 33
6.1.1
Adverse Event...................................................................................... 33
6.1.2
Serious Adverse Events........................................................................ 34
6.2
Adverse Event Severity ........................................................................ 35
6.3
Relationship to Study Procedures or Study Drug Exposure in the 
Prior Study........................................................................................... 36
6.4
Adverse Event Collection Period.......................................................... 37
6.5
Adverse Event Reporting...................................................................... 37
6.6
Pregnancy............................................................................................. 39
7.0
Protocol Deviations .............................................................39
8.0
Statistical Methods and Determination of Sample 
Size ....................................................................................... 40
8.1
Statistical and Analytical Plans............................................................. 40
8.1.1
Efficacy................................................................................................ 40
8.1.2
Resistance ............................................................................................ 41
8.1.3
Safety................................................................................................... 43
8.2
Determination of Sample Size .............................................................. 43
9.0
Ethics....................................................................................44
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) ......................................................................................... 44
9.2
Ethical Conduct of the Study................................................................ 45
9.3
Subject Information and Consent.......................................................... 45
10.0
Source Documents and Case Report Form 
Completion ..........................................................................45
10.1
Source Documents................................................................................ 45
10.2
Case Report Forms ............................................................................... 46
11.0
Data Quality Assurance ......................................................47
12.0
Use of Information ..............................................................47
13.0
Completion of the Study .....................................................48
14.0
Investigator's Agreement....................................................49
15.0
Reference List...................................................................... 50

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List of Tables
Table 1.
Clinical Laboratory Tests ..................................................................... 28
Table 2.
Child-Pugh Classification of Severity of Cirrhosis................................ 60
List of Figures
Figure 1.
Serious Adverse Event Collection......................................................... 37
List of Appendices
Appendix A.
Responsibilities of the Clinical Investigator.......................................... 53
Appendix B.
List of Protocol Signatories .................................................................. 55
Appendix C.
Study Activities A and B ...................................................................... 56
Appendix D.
List of Prior Eligible Studies................................................................. 59
Appendix E.
Child-Pugh Score and Category............................................................ 60
Appendix F.
Protocol Amendment:  List of Changes ................................................ 61

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3.0
Introduction
Hepatitis C viral (HCV) infection is a global health problem, with over 170 million 
individuals infected worldwide.1  There are 6 major HCV genotypes, with genotype 1 
(GT1) being most prevalent worldwide, including in the United States.  HCV genotypes 2 
(GT2) and 3 (GT3) infections are more common in Latin America (5% to 30%), Europe 
(20% to 40%) and Asia (30% to 45%).2,3  Recent data suggest that HCV GT3 causes 12% 
of HCV infections in the United States.4  HCV GT4 is commonly found in parts of Africa 
and the Middle East, particularly in Egypt, GT5 is primarily found in South Africa, and 
GT6 is primarily found in south-east Asia.5  Depending on various risk factors, between 
10% and 40% of patients with chronic HCV infection will develop cirrhosis.6  Death 
related to the complications of cirrhosis may occur at an incidence of approximately 4% 
per year; hepatocellular carcinoma occurs in this population at an estimated incidence of 
1% to 5% per year.6  Patients diagnosed with hepatocellular carcinoma have a 33% 
probability of death during the first year.6  Successful treatment of HCV has been shown 
to significantly reduce the risk of disease progression and related mortality as well as the 
development of hepatocellular carcinoma.7,8
Since the identification of HCV in the early 1990's, the mainstay of treatment, until the 
recent development of direct acting antivirals (DAAs), had been interferon alpha (IFN).  
Despite multiple advances in treatment with IFN, including co-administration with 
ribavirin (RBV), development of pegylated interferon (pegIFN), suboptimal efficacy in 
many populations and poor safety and tolerability limit widespread use of these therapies 
for HCV-infected patients.
Further advances in treatment for HCV GT1 infection have been the addition of DAAs,
such as an HCV nonstructural (NS) 3/4A protease inhibitor (PI) (telaprevir, boceprevir, or 
simeprevir), the HCV NS5A inhibitor daclatasvir, or the HCV nucleotide NS 5B RNA 
polymerase inhibitor (sofosbuvir) to pegIFN/RBV (PR).  This latter regimen 
demonstrated increased sustained virologic response (SVR) rates in PR treatment-naïve 
(TN) HCV GT1-infected patients from 55% to 90%; however, response rates are lower in 

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a number of subpopulations including blacks, Hispanics, PR-experienced patients, and 
cirrhotics.9-14  Many of the current approved treatments for HCV GT1 include use of PR, 
which is associated with considerable, often treatment limiting toxicities (fever, chills, 
rigor, fatigue, depression, and anemia).  The addition of first generation PIs to a PR 
regimen has resulted in additional toxicities (anorectal discomfort) and augmented others 
(anemia, rash).15,16
As of October 2014, an IFN- and RBV-free combination of SOF plus NS5A inhibitor 
ledipasvir has been approved in the US for the treatment of chronic HCV GT1 infection, 
including an option of 8-week therapy in non-cirrhotic patients with HCV viral load 
< 6 million at baseline.17  As of late December 2014, an IFN-free combination of 
ombitasvir (NS5A inhibitor), paritaprevir (protease inhibitor), dasabuvir (non-nucleoside 
NS5b polymerase inhibitor) and ritonavir, given with or without RBV, has been approved 
for the treatment of chronic HCV GT1 infection.18  These newest pegIFN free treatments 
provide a significant advance over all prior HCV treatment options.
Additionally, subjects that have failed DAAs with or without PR are likely to have mutant 
HCV variants and therefore have limited future treatment options.  Current data on DAA 
resistance are generally limited to clinical trials of telaprevir, boceprevir, simeprevir, and 
the NS5A inhibitor daclatasvir.  In the telaprevir Phase 3 clinical trials, 
treatment-emergent NS3 resistance substitutions emerged in the majority of isolates from 
subjects who did not achieve SVR12.  Further, these resistance-associated substitutions 
persisted following treatment failure.19  HCV replicon variants with patient-derived 
telapravir-associated resistance showed a wide variation of in-vitro resistance to 
telapravir, depending on the amino-acid substitutions involved.  Generally, the in vitro 
replication capacity of telapravir-resistant variants was lower than that of wild-type virus20
suggesting reduced viral fitness.  For subjects treated with daclatasvir-containing 
regimens, daclatasvir resistance-associated NS5A substitutions emerged in almost all 
subjects who failed these treatments while some of these substitutions were detected in a 
small number of baseline samples.21-23  Replicons with these substitutions demonstrated 
various level of resistance to daclatasvir in vitro.  Many of the NS5A resistance-associated 

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substitutions also persisted after treatment.22,23  Emergence of resistance to DAAs may be 
even more common in the clinical setting where adherence may be lower than what has 
been observed in the clinical trials.
The aim of treatment of chronic HCV infection is to achieve a sustained virologic 
response (SVR).  HCV infection is cured in more than 99% of patients who achieve an 
undetectable HCV RNA 24 weeks after treatment completion.6  The validity of using 
undetectable HCV RNA at 12 weeks after completion of therapy (SVR12) has been 
accepted by regulatory authorities in the U.S. and Europe given that the concordance with 
SVR24 approaches 99%.6 The long-term durability of SVR has been demonstrated among 
subjects with HCV infection with multiple different genotypes treated with IFN-based 
regimens (i.e., IFN alone or IFN plus RBV).  For example, among the first 103 patients 
treated at the U.S. National Institutes of Health, 100 patients, or 97%, maintained SVR at 
a median follow-up of 7.5 years.24
Although achievement of an SVR has been associated with laboratory and histological 
improvements in chronic HCV,25 the SVR endpoint is a surrogate for the ultimate aim of 
therapy, which is prevention of progression to cirrhosis, end-stage liver disease, 
hepatocellular carcinoma, and death from liver disease.24  These "hard" clinical endpoints, 
however, generally take years to decades to occur, making them impractical and unethical 
primary endpoints for clinical trials of HCV therapies.  Thus the relationship between 
SVR to clinical outcomes must be evaluated through long-term follow-up studies.
In contrast to what is known from studies from IFN-based regimens, little data is available 
to date for SVR and long-term clinical outcomes for subjects who have been treated with 
DAA plus IFN and RBV, or IFN and RBV-free all DAA regimens.  Such studies are 
needed in order to demonstrate the long-term benefits of DAAs, whether given with IFN 
and/or RBV, or given as all-DAA regimens.
AbbVie is currently developing 2 "next generation" DAA drugs for use together or in 
combination with a third DAA or Ribavirin.  AbbVie's next generation DAAs, including 
ABT-493, an NS3/4A protease inhibitor and ABT-530, an NS5A inhibitor are denoted 

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"next generation" compounds because each demonstrated potent antiviral activity against 
all major HCV GTs in vitro with no or little loss of potency against known common 
single resistance mutants.
ABT-493
ABT-493, (3aR,7S,10S,12R,21E,24aR)-7-tert-butyl-N-[(1R,2R)-2-(difluoromethyl)-1-
{[(1-methylcyclopropyl)sulfonyl] carbamoyl}cyclopropyl]-20,20-difluoro-5,8-dioxo-
2,3,3a,5,6,7,8,11,12,20,23,24a-dodecahydro-1H,10H-9,12-methanocyclopenta[18,19] 
[1,10,17,3,6]trioxadiazacyclononadecino[11,12-b]quinoxaline-10-carboxamide, is an 
NS3/4A PI with potent, pangenotypic activity and a high barrier to resistance with activity 
against common variants that emerge following exposure to first generation PIs.  In the 
HCV subgenomic replicon assay, ABT-493 is active against replicons with NS3 from 
GT1, 2, 3, 4, and 6.  ABT-493 activity against GT5 NS3 is unknown because a replicon 
with GT5 NS3 is not available.  Based on findings that each of 5 well characterized HCV 
PIs, including 2 linear and 3 macrocyclic PIs, demonstrated similar activity against GT2a, 
5a, and 6a NS3 protease,26 it is predicted ABT-493 would inhibit NS3 protease of GT5a 
with activity similar to that of GT2a and 6a.  In resistant colony selection experiments 
with chimeric replicons containing GT1-4 or GT6 NS3, ABT-493 selected fewer resistant 
colonies than ABT-450 in most replicons, indicating overall it has a higher genetic barrier 
to resistance than ABT-450 in vitro.  Furthermore, in GT1-4 replicons, the overall 
resistance profile of ABT-493, which selects mostly A156 variants, is different from that 
of ABT-450, which selects predominantly R155 and D/Q168 variants.  ABT-493 
maintains most of its activity in vitro against common HCV GT1-4 R155 or D/Q168 
variants that are resistant to ABT-450.  AbbVie is developing ABT-493 to be used in 
combination with other AbbVie DAAs for the treatment of chronic HCV infection.
In Phase 2a Study M13-595, preliminary results showed the ABT-493 exposures in 
subjects with HCV-infection were 2-fold of healthy subjects following 100, 200 or 
700 mg QD dosing and 4.9-fold of healthy subjects following 400 mg QD dosing.  
ABT-493 exposures following 200 mg QD dosing in cirrhotic patients were 
approximately 5- to 6-fold of the exposure in non-cirrhotic HCV-infected patients.

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Antiviral activity of ABT-493 monotherapy for 3 days was evaluated in treatment-naïve 
HCV genotype 1-infected patients over a range of doses up to 700 mg QD of ABT-493.  
Preliminary data show that the 200 mg dose of ABT-493 provides strong anti-viral 
activity (e.g., greater than 3 log10 decline of HCV plasma RNA in all available patients) 
and was selected as ABT-493 dose to be further evaluated in this study.
In general ABT-493 has been well-tolerated when administered to over 320 healthy 
volunteers and 49 HCV GT1-infected subjects.
Preliminary data are suggestive of possible dose/responsive transaminase and bilirubin 
elevations.  ABT-493 doses of 700 mg and 1200 mg have been associated with few 
incidences of asymptomatic Grade 2 (n = 1) and Grade 3 (n = 2) ALT elevations in 
healthy volunteers.  One subject experienced a Grade 3 ALT elevation at the 1200 mg 
dose level (Study M13-586) which resulted in treatment discontinuation, and another 
subject experienced a Grade 3 ALT elevation at the 700 mg dose level in Study M14-066 
which resolved after dosing was concluded without intervention.  Based on the integrated 
pharmacokinetic exposures of ABT-493 and safety data in Phase 1 studies, a shallow 
trend was observed for ALT elevation when ABT-493 AUC was higher than 
60000 ng•h/mL, which is approximately 64× higher than projected mean AUC exposures 
at ABT-493 200 mg in non-cirrhotics and 12× higher – for cirrhotics.
Bilirubin elevations (primarily indirect hyperbilirubinemia) initiated independently and 
did not mirror the course of ALT elevations.  Observed few total bilirubin elevations were 
asymptomatic and likely contributed by the known ABT-493 inhibition of organic anion 
transporter polypeptides, including OATP1B1, which is the transporter responsible for 
clearing indirect bilirubin from blood.  Based on integrated pharmacokinetic exposures of 
ABT-493 and safety data in Phase 1 studies, a shallow trend was observed for bilirubin 
elevations when ABT-493 AUC was higher than 25,000 ng•h/mL, which is approximately 
27× higher than projected mean AUC exposures at ABT-493 200 mg for non-cirrhotics 
and 5× higher – for cirrhotics.  All ALT, AST and bilirubin elevations 
improved/normalized following completion or discontinuation (n = 1) of ABT-493 
dosing.

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In summary, ABT-493 is a potent, pangenotypic NS3/4A PI with potential for treatment 
of chronic HCV infection.  A detailed discussion of the preclinical toxicology, 
metabolism, and pharmacology can be found in the Investigator's Brochure.27
ABT-530
ABT-530, Methyl {(2S,3R)-1-[(2S)-2-{6-[(2R,5R)-1-{3,5-difluoro-4-[4-(4-
fluorophenyl)piperidin-1-yl]phenyl}-5-(5-fluoro-2-{(2S)-1-[N-(methoxycarbonyl)-O-
methyl-L-threonyl] pyrrolidin-2-yl}-1H-benzimidazol-6-yl) pyrrolidin-2-yl]-5-fluoro-1H-
benzimidazol-2-yl}pyrrolidin-1-yl]-3-methoxy-1-oxobutan-2-yl}carbamate, is an NS5A 
inhibitor with pangenotypic activity and a high barrier to resistance.  ABT-530 is highly 
active against HCV replicons containing wild-type HCV NS5A from GT1, 2, 3, 4, 5, and 
6.  ABT-530 retains activity against all common single nucleotide change resistance 
associated variants in NS5A in all GTs.  ABT-530 is > 100-fold more active than the 
first generation NS5A inhibitors (ombitasvir, daclatasvir, and ledipasvir) against key 
resistance-associated variants selected by these inhibitors in the clinic at NS5A amino 
acid positions 28, 30, 31, and 93.  ABT-530 selected very few or no resistant colonies in 
HCV replicons with NS5A from GTs 1 – 6 at 10-fold or 100-fold over its EC50 value 
indicating it has a high genetic barrier to resistance in vitro.  Measured in this way, the 
genetic barrier to resistance for ABT-530 is higher than ombitasvir across all GTs.  
AbbVie is developing ABT-530 to be used in combination with other AbbVie DAAs for 
the treatment of chronic HCV infection.
Pharmacokinetics of ABT-530 has been evaluated up to 600 mg QD.  ABT-530 reached a 
Tmax around 3 to 5 hours, with an elimination half-life of 12 to 17 hours.  ABT-530 
exposures increased in a greater than dose-proportional manner across the 1.5 mg to 
120 mg dose range and approximately dose proportionally from the 120 mg to 600 mg 
single doses.  The mean percentages of the ABT-530 dose excreted as unchanged drug in 
urine were less than 0.004%, indicating minimum renal elimination for ABT-530.
In Phase 2a Study M13-595, preliminary results showed same dose ABT-530 exposures 
in subjects with HCV infection were similar to those observed in healthy subjects.

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Antiviral potency of ABT-530 monotherapy for 3 days in HCV GT1-infected patients was 
evaluated over a range of doses up to 400 mg QD of ABT-530.  Preliminary data show 
that the 40 mg and 120 mg doses of ABT-530 provide similar strong anti-viral potency 
(e.g., greater than 3 log10 decline of HCV plasma RNA in all available patients) and were 
selected as ABT-530 doses to be further evaluated in Phase 2 studies.
In general ABT-530 has been well tolerated when administered to over 320 healthy 
volunteers and 40 HCV GT1-infected subjects.  To date, most AEs reported were Grade 1 
in severity, demonstrated no pattern or resulted in study drug discontinuation.  
Additionally, no pattern of laboratory abnormalities has been observed.
In summary, ABT-530 has the potential to address an unmet need in the treatment of 
chronic HCV infection.  A detailed discussion of the preclinical toxicology, metabolism, 
and pharmacology can be found in the Investigator's Brochure.28
ABT-493 and ABT-530
Additive or synergistic in vitro anti-HCV activity has been demonstrated with the 
combination of ABT-493 and ABT-530.
When ABT-493 was given in combination with ABT-530 in healthy volunteers, 
preliminary results showed ABT-493 exposures were not significantly changed when 
co-administered with ABT-530 (≤ 31% difference); however, the exposure of ABT-530 
increased in an ABT-493-dose-dependent manner (from 1.5-fold at 100 mg ABT-493 up 
to 3- to 4-fold at 400 mg ABT-493).
Drug-drug interaction (DDI) studies have also been conducted to evaluate the 
co-administration effects of ABT-493 and ABT-530 on substrates of P-gp, BCRP, 
OATP1B1/1B3, OAT3 and CYP3A4.  Studies are summarized in the investigator 
brochures.27,28

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The safety profile of co-administered ABT-493 and ABT-530 in healthy volunteers is 
consistent with that of the individual compounds, also as described in the investigator 
brochures.27,28
3.1
Differences Statement
This is the first study evaluating the long-term durability of SVR, persistence of DAA 
resistance, and clinical outcomes for subjects who received AbbVie Next Generation 
DAA regimen compounds (ABT-493 and/or ABT-530) in efficacy trials.  In addition, the 
duration of follow-up in this study is significantly longer than the follow-up duration for 
current and planned phase 2 and 3 studies for ABT-493 and ABT-530.
3.2
Benefits and Risks
There are no expected direct benefits for subjects who enroll in this study, except that 
early identification of relapse may allow initiation of other treatment.  Subjects may 
experience discomfort or inconvenience related to study procedures.
4.0
Study Objectives
The primary objectives of this study are as follows:
●
Assess the durability of response for subjects who achieved SVR12 with a 
regimen including ABT-493 and/or ABT-530.
●
Assess the persistence of specific HCV amino acid variants associated with 
drug resistance in subjects who experienced virologic failure.
The secondary objectives of the study are as follows:
●
Summarize medical events related to progression of liver disease including but 
not limited to:  events of hepatic decompensation, change in Child-Pugh 
classification, liver transplantation, hepatocellular carcinoma and/or, death.
●
Summarize results of the following laboratory tests and scores:  FibroTest, 
APRI, IP-10, alpha fetoprotein (if collected under a previous protocol version), 
FibroScan, and liver biopsy.

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5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
This Phase 2/3, multicenter study will be offered to subjects who received at least one 
dose of an ABT-493- and/or ABT-530-containing regimen at any dose level in an eligible 
prior AbbVie Phase 2 or 3 study for the treatment of chronic HCV and elect to enroll in 
this study.  The subject must have completed the follow-up period of the prior eligible 
AbbVie study.
It is anticipated that approximately 400 subjects will participate in this study.  An attempt 
will be made to enroll all virologic failures who will not receive immediate re-treatment 
with a regimen containing ABT-493/ABT-530.
At the Day 1 Visit, subjects will provide written (signed and dated) informed consent 
prior to any study specific procedures being performed.  The investigator will evaluate 
whether the subject meets all of the eligibility criteria specified in Section 5.2.1 and 
Section 5.2.2 prior to enrollment in this rollover study.
Subjects will be followed for a total of approximately 3 years after their last dose of DAA 
in the previous HCV clinical study.  The 3 years will be inclusive of any post-treatment 
period in the prior study, as well as any gaps between the end of the prior study and 
enrollment in this study.  Subjects must complete the full post-treatment period of the 
prior study before enrolling into Study M13-576.  Once a subject has reached 3 years 
post-DAA therapy, participation in this study will be completed, except for subjects 
enrolled with virologic failure who receive re-treatment with a HCV antiviral regimen 
other than investigational ABT-493/ABT-530.  Subjects who are retreated with 
investigational ABT-493/ABT-530 are not allowed in this study.  Subjects who are re-
treated with HCV regimens other than investigational ABT-493/ABT-530 will have only 
one further assessment for treatment outcome 12 weeks after stopping that therapy or 
earlier if already known (in cases of treatment failure).  (See Appendix C, Table B, Study 
Activities for Virologic Failures Receiving Re-Treatment).

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Subjects who have not been re-treated will return to the study site for their scheduled 
visits on an outpatient basis as described in Section 5.3.1 until approximately 3 years after 
their last dose of DAA in the previous clinical study (See Appendix C, Table A, Study 
Activities for SVR and Non-SVR Subjects Not Receiving Re-Treatment).
Some of the study visits and visit activities (including but not limited to clinical laboratory 
tests and concomitant medication assessment) may be optionally conducted in the home 
or non-hospital/clinic environment as arranged by the Investigator with the agreement of 
the subject, and with the prior approval of the sponsor. 
5.2
Selection of Study Population
Subjects who meet the inclusion criteria and who do not meet any of the exclusion criteria 
will be eligible for enrollment in the study.
5.2.1
Inclusion Criteria
A subject will be eligible for study participation if he or she meets the following criteria:
1.
The subject is male or female 18 years of age or older.
2.
The subject has received at least one dose of an ABT-493- and/or ABT-530 
containing regimen in a prior AbbVie HCV Phase 2 or 3 study (see Appendix D for 
list of eligible prior studies).
3.
The interval between the last dose of the AbbVie DAA therapy from the previous 
clinical study and enrollment in Study M13-576 must be no longer than 2 years for 
subjects who have not been retreated.  Subjects who have been treated with a 
commercially-available anti-HCV treatment may be enrolled greater than 2 years 
after the last dose of the AbbVie DAA therapy from the previous clinical study.
4.
The subject must voluntarily sign and date the informed consent form approved by 
an Independent Review Board or Ethics Committee prior to the initiation of any 
study-specific procedures.
5.
Subject completed the post-treatment period of an eligible prior study.

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Rationale for Inclusion Criteria
1, 2, 3 and 5 
To select the appropriate subject population for evaluation
4
In accordance with harmonized Good Clinical Practice (GCP)
5.2.2
Exclusion Criteria
A subject will not be eligible for study participation if he/she meets any of the following 
criteria:
1.
The investigator considers the subject unsuitable for the study for any reasons 
(e.g., failure to comply with study procedures in the prior AbbVie clinical study).
2.
Receipt of any investigational HCV antiviral treatment after receiving ABT-493 
and/or ABT-530 in the prior study.
3.
Subjects who experienced non-virologic treatment failures due to premature 
discontinuation of study drug in the prior study of ABT-493/ABT-530.
4.
Participation in AbbVie's Study M15-942 for re-treatment for virologic failures 
following the prior Phase 2 or 3 study.
Rationale for Exclusion Criteria
1 and 2 
To ensure safety of the subjects throughout the study
3 and 4
To select the appropriate subject population for evaluation
5.2.3
Prior and Concomitant Therapy
The HCV drug treatment regimen and its duration given as a part of the subject's 
participation in the prior AbbVie HCV study, as well as all other past HCV treatment 
regimens and their durations received by the subject, will be recorded in the eCRF.  
Commercially available prescription medications for the treatment of HCV therapy, 
including regimens containing commercially available glecaprevir/pibrentasvir (GLE/PIB, 

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investigationally known as ABT-493/ABT-530), initiated after the completion of a 
subject's participation in the previous clinical study (either prior to or during participation 
in this study) are permitted, and the regimen received and duration will be recorded in the 
eCRF.  Subjects enrolled with virologic failure who undergo re-treatment with a HCV 
antiviral regimen not containing investigational ABT-493/ABT-530 will be followed until 
completing the post-treatment Week 12 visit after receiving their re-treatment regimen, 
after which they will discontinue from the study.  If a subject with virologic failure is 
enrolled into this study and later enrolls in the AbbVie Study M15-942, such subjects will 
discontinue from Study M13-576.
The use of investigational medications is not allowed during participation in this study.  
Subjects who are enrolled in the Study M13-576 and who take an investigational 
medicine as a participant in a separate trial will be required to discontinue participation in 
the Study M13-576.
Information regarding medication or vaccine use (including over-the-counter medications, 
vitamins, and/or herbal supplements) will not be collected in this study with the exception 
of: 
●
Prescription medications taken for the treatment of HCV since the completion 
or discontinuation of the previous clinical study (either prior to or during this 
study).
●
Any medications taken for treatment of an SAE as defined in Section 6.0.
This information will be collected at each study visit and will be recorded in the electronic 
case report form (eCRF).  The medication name along with the reason for use, date(s) of 
administration including start and end dates, and dosage information including dose, route 
and frequency will be recorded.
The AbbVie Therapeutic Area Medical Director should be contacted if there are any 
questions regarding concomitant or prior therapy(ies).

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5.3
Efficacy and Safety Assessments/Variables
5.3.1
Efficacy and Safety Measurements Assessed and Flow 
Chart
Study procedures described in this protocol are summarized in Appendix C.
5.3.1.1
Study Procedures
Informed Consent
Signed informed consent will be obtained from the subject before any study procedures 
are performed.  Details about how informed consent will be obtained and documented are 
provided in Section 9.3.
Medical History Relating to Liver Disease or HCV Infection
Documentation of any significant changes in the medical history related to liver disease 
and/or HCV infection that are considered to be clinically significant by the investigator 
and occur since the completion of the prior AbbVie clinical study will be collected at the 
Day 1 Visit and recorded on the appropriate Medical Events eCRF for all subjects, except 
for those subjects entering the study on a re-treatment regimen.  For subjects entering the 
study on a re-treatment regimen, this information will be collected for changes that 
occurred since the prior AbbVie clinical study but before the start of the re-treatment 
regimen only.  Significant events related to liver disease progression include the 
development of cirrhosis, events indicative of hepatic decompensation, (including:  
variceal bleeding, new ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, 
hepato-renal syndrome, hepatic hydrothorax or other evidence of  hepatic decompensation 
considered to be significant by the investigator), change in the Child-Pugh category 
(e.g., change from Child-Pugh Class A to Child-Pugh Class B), the occurrence of 
hepatocellular carcinoma and/or liver transplantation.  See Appendix E for details of 
Child-Pugh score and classification.  In addition, history of past HCV drug treatment 
during the prior study and before the prior study will be collected at the Day 1 Visit.

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Recording Medical Events Related to Liver Disease, HCV Infection or the Event of 
Death
Any events (i.e., diagnoses) related to liver disease progression and/or HCV infection that 
are considered to be clinically significant by the investigator and begin or worsen after 
Day 1 will be captured on the appropriate Medical Events eCRF until the end of the study 
or initiation of re-treatment for HCV (if applicable).  Significant events related to liver 
disease progression include the development of cirrhosis, events indicative of hepatic 
decompensation, (including:  variceal bleeding, new ascites, spontaneous bacterial 
peritonitis, hepatic encephalopathy, hepato-renal syndrome, hepatic hydrothorax or other 
evidence of hepatic decompensation considered to be significant by the investigator), 
change in the Child-Pugh category (e.g., change from Child-Pugh Class A to Child-Pugh 
Class B), the occurrence of hepatocellular carcinoma, liver transplantation and/or death.
Collection of Liver Diagnostic Results
Any results from liver diagnostic testing performed outside of the study (i.e., FibroScan, 
Liver U/S, and/or Liver Biopsy) will be collected at the study visits indicated in 
Appendix C for all subjects, until the end of the study or initiation of re-treatment for 
HCV (if applicable).
Hepatocellular Carcinoma Screening:  Liver Ultrasound
HCC screening will be required as a protocol-specified study procedure only at the Final 
visit, as indicated in Appendix C, for subjects with cirrhosis only.  At any other time 
during the study, HCC screening should be performed according to standard of care.
At the Final visit, subjects with cirrhosis will be required to perform a liver ultrasound to 
screen for HCC, unless the subject has a liver ultrasound, CT or MRI performed for HCC 
screening within 3 months prior to that visit, in which case the result of that US, CT or
MRI will be used as the result for the Study Visit assessment.  A positive ultrasound result 
suspicious of HCC will be confirmed with CT scan or MRI.  Alternate methods of 
screening for HCC (i.e., MRI or CT) at a study visit should be discussed with the TA MD.

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Clinical Laboratory Tests
Samples will be obtained for the clinical laboratory tests, including FibroTest and APRI, 
IP-10, and quantitative HCV RNA PCR, INR and serum Albumin at the visits specified in 
Appendix C for all subjects, until the end of the study or initiation of re-treatment for 
HCV (if applicable).
A certified central laboratory will be utilized to process and provide results for the clinical 
laboratory tests.
Sites should refer to the laboratory manual provided by the central laboratory, AbbVie, or 
its designee for instructions regarding the collection, processing, and shipping of all 
laboratory samples.  The certified laboratory chosen for this study is Covance.  Depending 
on the location of the study site, samples will be sent initially to one of the following 
addresses, where the specimen will be analyzed or sent to a different location for analysis 
or storage:
Covance
8211 SciCor Drive
Indianapolis, IN  46214 USA
Covance 
7 rue Marcinhes
1217 Geneva
Meyrin Switzerland
Covance
1 International Business Park
#05-12A/B The Synergy
Singapore 609917

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Table 1.
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Additional Tests
Platelet counta,c
Total bilirubinb
GGTb
Alpha2-macroglobulinb
Aspartate aminotransferase 
(AST)a
Alanine aminotransferase (ALT)
Haptoglobinb
Apolipoprotein A1b
IP-10
HCV-RNA
INR
Serum Albumin
a.
Performed for APRI.
b.
Performed for FibroTest and Child-Pugh assessment.
c.
Platelet count may be done as part of complete blood count (cbc).
Interferon Gamma-Induced Protein 10 (IP-10) Levels
A plasma sample for IP-10 testing will be collected at the study visits indicated in 
Appendix C for all subjects, until the end of the study or initiation of re-treatment for 
HCV (if applicable).
HCV RNA Levels
A plasma sample for HCV RNA levels will be collected as indicated in Appendix C until 
the end of the study or initiation of re-treatment for HCV (if applicable).  Plasma HCV 
RNA levels will be determined for each sample collected by the central laboratory using 
the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Quantitative Test, v2.0.  For 
this assay, the lower limit of quantification (LLOQ) is 15 IU/mL for all HCV genotypes.
If a subject's HCV RNA level changes from < LLOQ to ≥ LLOQ during the study, 
confirmatory testing should be completed as soon as possible but no later than 2 weeks 
after the study visit corresponding with the possible HCV RNA relapse.

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HCV Resistance Testing Sample
A plasma sample for HCV resistance testing will be collected at the study visits, indicated 
in Appendix C for all subjects, until the end of the study or initiation of re-treatment for 
HCV (if applicable).
Archive Plasma Sample
An archive plasma sample should be collected at the study visits, indicated in Appendix C
for all subjects, until the end of the study or initiation of re-treatment for HCV (if 
applicable).  Archive plasma samples are being collected for possible additional analyses, 
including but not limited to, viral load, HCV gene sequencing, HCV resistance testing, 
and other possible predictors of response, as determined by AbbVie.
Documentation of Medications for the Treatment of HCV or Treatment of an SAE
All prescription medications taken for the treatment of HCV since the completion of the 
previous study (either prior to or during this study) or any medications taken for the 
treatment of an SAE related to study procedures in this study or reasonably related to 
exposure to ABT-493 and/or ABT-530 in the prior study will be recorded in the subject's 
source documentation at each visit beginning with the Day 1 Visit and captured on the 
appropriate eCRF.
5.3.2
Efficacy Variables
The primary efficacy outcome variables are:
1.
The percentage of subjects who maintain SVR out of those who achieved SVR12 in 
the prior study with an ABT-493- and/or ABT-530-containing regimen.
2.
The percentage of subjects who relapse or have new HCV infection at any time up 
to the last follow-up in this study out of subjects who achieved SVR12 in the 
previous study and enroll in this study.

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5.3.3
Resistance Variables
The primary resistance outcome variables are:  The persistence of resistance-associated 
amino acid variants will be assessed by population and/or deep sequencing for a period up 
to 3 years after the subject's last dose of DAA therapy in the prior AbbVie clinical study.
5.3.3.1
Clinical Variables
Clinical Variables
The Clinical variables (secondary outcomes) are:
●
Variables related to liver disease progression will be monitored and 
summarized as described in the study procedures (Section 5.3.1.1), including 
but not limited to:
○
Events of hepatic decompensation (as described in Section 5.3.1.1),
○
Change in Child-Pugh classification,
○
Liver transplantation,
○
Hepatocellular carcinoma,
○
Death.
Results of the following laboratory tests and studies will be summarized:  IP-10, 
FibroTest, APRI, alpha fetoprotein, (if collected under a previous protocol version) 
FibroScan, liver biopsy.  FibroScan and liver biopsy will not be performed as study 
procedures, but any available results from source documents will be summarized.
5.3.4
Safety Variables
Only serious adverse events related to study procedures or those that meet seriousness 
criteria outlined in Section 6.0 and are considered reasonably related to ABT-530 and/or 
ABT-493 drug exposure in a prior study (Appendix D) by the investigator will be 
collected.  Events that are considered related to underlying disease, events that are 
accidental (i.e., road traffic accidents), and elective procedures (i.e., hip replacement) 

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would not be routinely considered related to ABT-530 and/or ABT-493 exposure in the 
previous study.
5.4
Removal of Subjects from Therapy or Assessment
5.4.1
Discontinuation of Individual Subjects
Each subject has the right to withdraw from the study at any time.  In addition, the 
investigator may discontinue a subject from the study at any time if the investigator 
considers it necessary for any reason, including the occurrence of a serious adverse event 
or noncompliance with the protocol.  In the event that a subject withdraws or is 
discontinued from the study, the reasons for the discontinuation from the study will be 
recorded in the eCRF and an assessment of serious adverse events as described in 
Section 6.0 will be performed as soon as possible after discontinuation from the study.
Subjects who experienced virology failure in the prior study and have received HCV re-
treatment will be followed until the Post-Treatment Week 12 visit for assessment of 
SVR12, and then discontinued from the study.
If a subject is discontinued from the study with an ongoing serious adverse event as 
described in Section 6.0, the investigator will attempt to provide follow-up until a 
satisfactory clinical resolution of the serious adverse event is achieved.
5.4.2
Discontinuation of Entire Study
AbbVie may terminate this study prematurely, either in its entirety or at any study site, for 
reasonable cause provided that written notice is submitted in advance of the intended 
termination.  The investigator may also terminate the study at his/her site for reasonable 
cause, after providing written notice to AbbVie in advance of the intended termination.  
Advance notice is not required by either party if the study is stopped due to safety 
concerns.

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5.5
Treatments
Treatment will not be provided to subjects as part of this study.
5.5.1
Method of Assigning Subject ID Numbers
For subjects enrolling from a Phase 2 study, subjects will receive a new subject number 
for this study which will be composed of a single digit (1, 2, 3, …) used to identify the 
prior AbbVie study and the subject number assigned to them from the prior AbbVie 
clinical study.  For subjects enrolling from the Phase 3 studies, subjects will retain their 
subject number as assigned to them from the prior AbbVie clinical study.
5.6
Discussion and Justification of Study Design
5.6.1
Discussion of Study Design and Choice of Control Groups
This is a rollover study to assess resistance and durability of response to ABT-493 and/or 
ABT-530 in subjects who have participated in Phase 2 or 3 clinical studies with these 
agents for the treatment of chronic HCV.  No AbbVie study drug will be administered in 
this study.  As such, the absence of randomization, blinding or control groups is 
appropriate.  No quantitative analyses or tests of statistical significance are planned; 
statistical analyses will be purely descriptive.
5.6.2
Appropriateness of Measurements
Standard laboratory procedures will be utilized in this study.
5.6.3
Suitability of Subject Population
The intention of this study is to assess the durability of response in subjects who had 
previously achieved SVR and the emergence and persistence of resistance-associated 
amino acid variants selected by exposure to AbbVie DAA treatment in subjects who fail 
previous treatment.  Therefore, subjects who received at least one dose an ABT-493-
and/or ABT-530-containing regimen in a prior eligible AbbVie Phase 2 or 3 trial 
(Appendix D), for the treatment of HCV are eligible to participate.  This population is 

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appropriate because all such subjects will have been well described clinically and 
virologically prior to starting AbbVie DAA treatment and the duration and magnitude of 
their exposure to AbbVie DAA treatment will be well documented.
6.0
Adverse Events
As this is a non-drug interventional study, only serious adverse events that the investigator 
considers reasonably related to interventional study procedures (i.e., venipunctures) or 
those considered reasonably related to ABT-530 and/or ABT-493 exposure in the prior 
study (Appendix D) by the investigator will be collected.  Events that are considered 
related to underlying disease, events that are accidental (i.e., road traffic accidents), and 
elective procedures (i.e., hip replacement) would not be routinely considered related to 
ABT-530 and/or ABT-493 drug exposure.
The investigator will assess and record any such serious adverse event in detail including 
the date of onset, event diagnosis (if known) or sign/symptom, severity, time course (end 
date, ongoing, intermittent), and any action(s) taken.  For adverse events to be considered 
intermittent, the events must be of similar nature and severity.  Serious adverse events 
related to study procedures or reasonably related to exposure to ABT-493 and/or 
ABT-530 in the prior study, whether in response to a query, observed by site personnel, or 
reported spontaneously by the subject will be collected.
These serious adverse events will be followed to a satisfactory conclusion.
6.1
Definitions
6.1.1
Adverse Event
An adverse event (AE) in this study is defined as any untoward medical occurrence in a 
patient or clinical investigation subject that occurs as a result of a study procedure, or is 
considered by the investigator to be reasonably related to exposure to ABT-493 and/or 
ABT-530 in the previous study.  Worsening in severity of a reported adverse event should 
be reported as a new adverse event.

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6.1.2
Serious Adverse Events
If an adverse event meets any of the following criteria and is causally related to study 
procedures (i.e., venipunctures) or those considered by the investigator to be reasonably 
related to exposure to ABT-493 and/or ABT-530 in the previous study, it is to be reported 
to AbbVie as a serious adverse event (SAE) within 24 hours of the site being made aware 
of the serious adverse event.
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would have 
resulted in immediate fatality if medical intervention had not 
been taken.  This does not include an event that would have 
been fatal if it had occurred in a more severe form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any 
length of time or prolongs the subject's hospital stay.  This 
does not include an emergency room visit or admission to an 
outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that 
results in fetal loss.
Persistent or 
Significant 
Disability/Incapacity
An event that results in a condition that substantially 
interferes with the activities of daily living of a study subject.  
Disability is not intended to include experiences of relatively 
minor medical significance such as headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle).

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Important Medical 
Event Requiring 
Medical or Surgical 
Intervention to 
Prevent Serious 
Outcome
An important medical event that may not be immediately 
life-threatening or result in death or hospitalization, but based 
on medical judgment may jeopardize the subject and may 
require medical or surgical intervention to prevent any of the 
outcomes listed above (i.e., death of subject, life-threatening, 
hospitalization, prolongation of hospitalization, congenital 
anomaly, or persistent or significant disability/incapacity).  
Additionally, any elective or spontaneous abortion or 
stillbirth is considered an important medical event.  Examples 
of such events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or 
drug abuse.
For serious adverse events with the outcome of death, the date and cause of death will be 
recorded on the appropriate case report form.
6.2
Adverse Event Severity
The investigator will rate the severity of each adverse event according to the National 
Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 
Version 4).
The table of clinical toxicity grades "National Cancer Institute Common Terminology 
Criteria for Adverse Events, Version 4" is available from the Cancer Therapy Evaluation 
Program (CTEP) website at:  http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf and is to be used in the grading of adverse events.  Below 
are the general grading categories.  However, the investigator should always search NCI 
CTC AE for a given diagnostic/symptomatic AE term to identify and apply specific 
grading details for that AE entity.
Grading system for Adverse Events (a semi-colon indicates 'or' within the description of 
the grade.

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Grade 1
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated
Grade 2
Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental ADL*
Grade 3
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL**
Grade 4
Life-threatening consequences; urgent intervention indicated
Grade 5
Death related to AE
ADL = Activities of Daily Living
*
Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc.
**
Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden.
6.3
Relationship to Study Procedures or Study Drug Exposure 
in the Prior Study
The investigator will use the following definitions to assess the relationship of the adverse 
event to a study procedure or to exposure to ABT-530 and/or ABT-493 in the previous 
study:
Reasonable 
Possibility
An adverse event where there is evidence to suggest a causal 
relationship between the study procedure or ABT-530 and/or 
ABT-493 exposure in the previous study and the adverse event.
No Reasonable 
Possibility
An adverse event where there is no evidence to suggest a causal 
relationship between the study procedure or ABT-530 and/or 
ABT-493 exposure in the previous study and the adverse event.
For causality assessments, events assessed as having a reasonable possibility of being 
related to a study procedure, or to ABT-530 and/or ABT-493 exposure in the previous 
study will be considered "associated."  Events assessed as having no reasonable 
possibility of being related to a study procedure or ABT-530 and/or ABT-493 exposure in 
the previous study will be considered "not associated."

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6.4
Adverse Event Collection Period
All serious adverse events that occur during the current study period, and are considered 
related to a study procedure (like an SAE related to venipuncture), or reasonably related to 
exposure to ABT-530 and/or ABT-493 that was administered during the previous study 
period (note:  no study drugs are administered during the current study period) will be 
collected from the time of the Day 1 Visit of the current study period through the last 
study procedure or discontinuation from study, whichever is later.
Serious adverse event information will be collected as shown in Figure 1.
Figure 1.
Serious Adverse Event Collection
*
Serious adverse events considered related to study procedures (like an SAE due to venipuncture), or considered 
related to drugs that were administered during the prior study period (no study drugs administered during the 
current study period).
6.5
Adverse Event Reporting
In the event of a serious adverse event (as described in Section 6.4), the Investigator will 
notify Clinical Pharmacovigilance within 24 hours of the site being made aware of the 
serious adverse event by entering the serious adverse event data into the electronic data 
capture (EDC) system.  Serious adverse events that occur prior to the site having access to 
the RAVE® system or if RAVE is not operable should be faxed to AbbVie Clinical 
Pharmacovigilance within 24 hours of being made aware of the serious adverse event.
FAX to:
Email:  

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For safety concerns, contact the Antiviral Safety Team at:
Antiviral Safety Team
1 North Waukegan Road
North Chicago, IL  60064
USA
Office:
eFax:
Email:
For any subject safety concerns, please contact the physician listed below:
Therapeutic Area Medical Director:
Antiviral Clinical Project Team
1500 Seaport Boulevard
Redwood City, CA  94063
USA
Telephone Contact Information:
Office:
eFax:
Fax:
Mobile:
Email:
Should, in case of subject safety concerns or medical emergencies, the Therapeutic Area 
Medical Director be unavailable, please call the following central back-up number:
Phone:  
The sponsor will be responsible for Suspected Unexpected Serious Adverse Reactions 
(SUSAR) reporting for the Investigational Medicinal Product (IMP) in accordance with 

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Directive 2001/20/EC.  The reference document used for SUSAR reporting in the EU 
countries will be the most current version of the Investigator's Brochure.
6.6
Pregnancy
In the event of a subject entering Study M13-576, within 7 months of the last dose of 
study medication in the prior study, who is pregnant, the pregnancy must be reported to 
AbbVie as an occurrence relating to the prior study, and according to the requirements of 
that study.  The pregnancy will not be reported in Study M13-576.
7.0
Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol unless when 
necessary to eliminate an immediate hazard to study subjects.  The principal investigator 
is responsible for complying with all protocol requirements, and applicable global and 
local laws regarding protocol deviations.  If a protocol deviation occurs (or is identified) 
after a subject has been enrolled, the principal investigator is responsible for notifying 
Independent Ethics Committee (IEC)/Independent Review Board (IRB) and the following 
AbbVie representatives:
Primary Contact:
1 North Waukegan Road
North Chicago, IL  60064
USA
Office:
Fax:
Email:
Such contact must be made as soon as possible to permit a review by AbbVie to 
determine the impact of the deviation on the subject and/or the study.  AbbVie will assess 
all protocol deviations and determine if the deviation requires reporting to the Regulatory 

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Authority(ies), if required by local regulations, as a serious breach of GCP and the 
protocol.  Protocol waivers are not permitted.
8.0
Statistical Methods and Determination of Sample 
Size
8.1
Statistical and Analytical Plans
Analyses will be conducted on all subjects who enroll in this study without receiving re-
treatment prior to enrolling in this study, denoted as the full analysis set.  Subjects who 
are virologic failures who receive re-treatment prior to enrollment in this study will be 
summarized separately and are excluded from the full analysis set.
Descriptive statistics will be provided for demographic variables for all subjects in the full 
analysis set.
8.1.1
Efficacy
Efficacy analyses will be conducted in all enrolled subjects as specified above including 
data up to the last follow-up in this study prior to any HCV re-treatment.  The number and 
percentage of subjects in the full analysis set who maintain SVR in this study will be 
summarized out of subjects in the full analysis set who achieved SVR12 in the previous 
study.  The number and percentage of subjects who relapse or have new HCV infection 
will be summarized out of subjects in the full analysis set who achieved SVR12 in the 
previous study.  The time to relapse or new infection from the end of DAA treatment for 
subjects who achieved HCV RNA < LLOQ at the end of treatment in the previous study 
will be displayed graphically using Kaplan-Meier curves.  Similarly, the time to relapse or 
new infection from SVR12 time point for the subset of subjects who achieved SVR12 in the 
previous study will also be displayed graphically using Kaplan-Meier curves.  These 
summaries will be separate for subjects who have probable relapse as distinguished from 
subjects who have probable new HCV infection based on AbbVie's evaluation of DNA 
sequence of HCV drug target genes.

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For subjects in the full analysis set, HCV RNA measurements taken after the start of 
another anti-viral HCV treatment (after completion of AbbVie DAA treatments in 
previous study) will be excluded from the analyses.
A listing of subjects who are re-treated will be provided summarizing HCV treatment 
regimen and SVR outcome.
8.1.2
Resistance
The following subjects in the full analysis set will have resistance testing conducted:  
(1) those with on-treatment virologic failure (VF) in the previous study; (2) those with 
post-treatment relapse prior to enrollment in Study M13-576; and (3) those who become 
viremic (with HCV) during Study M13-576.
A listing by subject will be produced for all subjects entering Study M13-576 who 
experienced VF (as defined above) that includes HCV subtype, IL28B genotype, time 
point of VF, HCV RNA level at each evaluated time point, time point(s) sequenced, and 
assessment of possibility of new infection.  The study report will include a description of 
the methods and results used to distinguish between virologic relapse and new infection in 
subjects suspected to have a new infection.
Only samples with an HCV RNA level of ≥ 1000 IU/mL will undergo sequence analysis 
in order to allow accurate assessment of the products of amplification.  For subjects who 
experience VF before or during Study M13-576, the sample closest in time after the 
failure with an HCV RNA level ≥ 1000 IU/mL will be used if the HCV RNA level at the 
time of VF is < 1000 IU/mL.
The regions of interest for population and/or deep sequencing from all evaluated time 
points in this study are those encoding complete NS3/4A, and/or NS5A (based on regimen 
received in the earlier study).  Subtype-specific prototypic reference strains for sequence 
analyses will be utilized.

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For each DAA target, signature resistance-associated amino acid positions will be 
identified by AbbVie Clinical Virology.
The following definitions will be used in the resistance analyses:
●
Baseline sample:  sample collected before the first dose of DAA study drug in 
the previous study.
●
Baseline variant:  a variant (by population or deep sequencing) in the baseline 
sample determined by comparison of the amino acid sequence of the baseline 
sample to the appropriate prototypic reference amino acid sequence for a given 
DAA target (NS3/4A or NS5A).
●
Post-baseline variant by population or deep sequencing:  an amino acid variant 
in a post-baseline time point sample that was not detected at baseline and is 
detectable by population or deep sequencing in a given DAA target (NS3/4A 
or NS5A).
For all subjects who experience VF (whether before or during enrollment in 
Study M13-576), a listing by subject of all baseline variants relative to prototypic 
reference sequence at signature resistance-associated amino acid positions will be 
provided for each DAA target (NS3 and/or NS5A as appropriate).
For all subjects who experience VF (whether before or during enrollment in 
Study M13-576), the HCV amino acid sequence as determined by population or deep 
sequencing at available post-baseline time points (including previous study and 
Study M13-576) with an HCV RNA level of ≥ 1000 IU/mL will be compared to the 
baseline and appropriate prototypic reference amino acid sequences.  A listing by subject 
and time point of all post-baseline variants detected by population or deep sequencing 
relative to the baseline amino acid sequences will be provided for each DAA target 
(NS3/4A and/or NS5A as appropriate).  A listing by subject and time point of all 
post-baseline variants (by population or deep sequencing) at signature 
resistance-associated amino acid positions relative to the appropriate prototypic reference 
amino acid sequences will be provided.

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The number and percentage of subjects with post-baseline variants at signature amino acid 
positions by population or deep sequencing, listed by amino acid position and variant 
within a DAA target at Post-Treatment Week 24, 48 or time points up to Post-Treatment 
Week 144 (3 years) compared to baseline will be summarized, along with the number of 
subjects for whom sequence information was obtained for each DAA target and overall.  
Additionally, the number and percentage of subjects in whom a signature variant persisted 
at Post-Treatment Week 24, 48 or time points up to Post-Treatment Week 144 (3 years), 
out of the total number of subjects with that variant at the VF time point and at 
Post-Treatment Week 24, 48 or time points up to post-treatment Week 144 (3 years) will 
be summarized by DAA target (NS3 and/or NS5A, as appropriate), and variant.  If a 
signature variant is detectable in a sample by population or deep sequencing at a later time 
point, then the variant is imputed as being detectable at earlier time windows even if the 
sample from the earlier time window from that subject is not sequenced.
If no resistance-associated variants are detected by population or deep sequencing in a 
given target for a subject either at the time of failure or in a post-treatment sample, then 
that target may not be sequenced in subsequent samples from that subject.
Time to loss of key resistance-associated variants will be summarized.
8.1.3
Safety
Serious adverse events will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) and tabulated by system organ class (SOC) and preferred term 
(PT).1  A summary of medical events related to the progression of liver disease and shifts 
in laboratory measurements will be provided.
8.2
Determination of Sample Size
No sample size determination was conducted for this study.  The objective of the study is 
to characterize the persistence of amino acid variants in subjects enrolled in AbbVie DAA 
studies who experienced virologic failure, and the durability of response in subjects who 
achieved SVR.  Thus, the number of subjects enrolled in the current trial will be partially 

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based on the number of subjects who experienced virologic failure in prior studies with 
AbbVie DAA therapies and subsequently agree to participate in the current trial.
The sample size is being increased under protocol Amendment 2 to allow for inclusion of 
a representative sample of subjects from additional studies as listed in Appendix D.
9.0
Ethics
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB)
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigator's Brochure, the informed consent and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and 
any other necessary documents be reviewed by an IEC/IRB.  The IEC/IRB will review the 
ethical, scientific and medical appropriateness of the study before it is conducted.  
IEC/IRB approval of the protocol, informed consent and subject information and/or 
advertising, as relevant, will be obtained prior to the authorization of drug shipment to a 
study site.
Any amendments to the protocol will require IEC/IRB approval and approval by 
Regulatory Authority(ies), if required by local regulations, prior to implementation of any 
changes made to the study design.  The investigator will be required to submit, maintain 
and archive study essential documents according to ICH GCP.
Any serious adverse events that meet the reporting criteria, as dictated by local 
regulations, will be reported to both responsible Ethics Committees and Regulatory 
Agencies, as required by local regulations.  During the conduct of the study, the 
investigator should promptly provide written reports (e.g., ICH Expedited Reports, and 
any additional reports required by local regulations) to the IEC/IRB of any changes that 
affect the conduct of the study and/or increase the risk to subjects.  Written documentation 
of the submission to the IEC/IRB should also be provided to AbbVie.

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9.2
Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) guidelines, applicable regulations and guidelines governing clinical 
study conduct and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical investigator are specified in Appendix A.
9.3
Subject Information and Consent
The investigator or his/her representative will explain the nature of the study to the 
subject, and answer all questions regarding this study.  Prior to any study-related 
screening procedures being performed on the subject, the informed consent statement will 
be reviewed and signed and dated by the subject, the person who administered the 
informed consent, and any other signatories according to local requirements.  A copy of 
the informed consent form will be given to the subject and the original will be placed in 
the subject's medical record.  An entry must also be made in the subject's dated source 
documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy.
Information regarding incentives for subjects and information regarding provisions for 
treating and/or compensating subjects who are harmed as a consequence of participation 
in the study can be found in the informed consent form.
10.0
Source Documents and Case Report Form 
Completion
10.1
Source Documents
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects' diaries or 
evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents.

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The investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents.
10.2
Case Report Forms
Case report forms (CRF) must be completed for each subject screened/enrolled in this 
study.  These forms will be used to transmit information collected during the study to 
AbbVie and regulatory authorities, as applicable.  The CRF data for this study are being 
collected with an electronic data capture (EDC) system called Rave® provided by the 
technology vendor Medidata Solutions Incorporated, NY, USA.  The EDC system and the 
study-specific electronic case report forms (eCRFs) will comply with Title 21 CFR 
Part 11.  The documentation related to the validation of the EDC system is available 
through the vendor, Medidata, while the validation of the study-specific eCRFs will be 
conducted by AbbVie and will be maintained in the Trial Master File at AbbVie.
The investigator will document subject data in his/her own subject files.  These subject 
files will serve as source data for the study.  All eCRF data required by this protocol will 
be recorded by investigative site personnel in the EDC system.  All data entered into the 
eCRF will be supported by source documentation.
The investigator or an authorized member of the investigator's staff will make any 
necessary corrections to the eCRF.  All change information, including the date and person 
performing the corrections, will be available via the audit trail, which is part of the EDC 
system.  For any correction, a reason for the alteration will be provided.  The eCRFs will 
be reviewed periodically for completeness, legibility, and acceptability by AbbVie 
personnel (or their representatives).  AbbVie (or their representatives) will also be allowed 
access to all source documents pertinent to the study in order to verify eCRF entries.  The 
principal investigator will review the eCRFs for completeness and accuracy and provide 
his or her electronic signature and date to eCRFs as evidence thereof.
Medidata will provide access to the EDC system for the duration of the trial through a 
password-protected method of internet access.  Such access will be removed from 

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investigator sites at the end of the site's participation in the study.  Data from the EDC 
system will be archived on appropriate data media (CD-ROM, etc.) and provided to the 
investigator at that time as a durable record of the site's eCRF data.  It will be possible for 
the investigator to make paper printouts from that media.
11.0
Data Quality Assurance
Computer logic and manual checks will be created to identify items such as inconsistent 
study dates.  Any necessary corrections will be made to the eCRF.
12.0
Use of Information
All information concerning AbbVie DAA therapies and AbbVie operations, such as 
AbbVie patent applications, formulas, manufacturing processes, basic scientific data, or 
formulation information, supplied by AbbVie and not previously published, is considered 
confidential.
The information developed during the conduct of this clinical study is also considered 
confidential and will be used by AbbVie in connection with the development of AbbVie 
DAA therapy.  This information may be disclosed as deemed necessary by AbbVie to 
other clinical investigators, other pharmaceutical companies, and governmental agencies.  
To allow for the use of the information derived from this clinical study and to ensure 
complete and thorough analysis, the investigator is obligated to provide AbbVie with 
complete test results and all data developed in this study and to provide direct access to 
source data and documents for study-related monitoring, audits, IRB review, and 
regulatory inspection.
This confidential information shall remain the sole property of AbbVie, shall not be 
disclosed to others without the written consent of AbbVie, and shall not be used except in 
the performance of this study.
The investigator will maintain a confidential subject identification code list of all subjects 
enrolled in the study, including each subject's name, subject number, address, phone 

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number, and emergency contact information.  This list will be maintained at the study site 
with other study records under adequate security and restricted access, and will not be 
retrieved by AbbVie.
13.0
Completion of the Study
The investigator will conduct the study in compliance with the protocol and complete the 
study within the timeframe specified in the contract between the investigator and AbbVie.  
Continuation of this study beyond this date must be mutually agreed upon in writing by 
both the investigator and AbbVie.  The investigator will provide a final report to the 
IEC/IRB following conclusion of the study, and will forward a copy of this report to 
AbbVie or their representative.  AbbVie will provide the Clinical Study Report to 
Regulatory Authority(ies), if required by local regulations.
The investigator must retain any records related to the study according to local 
requirements.  If the investigator is not able to retain the records, he/she must notify 
AbbVie to arrange alternative archiving options.
AbbVie will select the signatory investigator from the investigators who participate in the 
study.  Selection criteria for this investigator will include level of participation as well as 
significant knowledge of the clinical research, investigational drug and study protocol.  
The signatory investigator for the study will review and sign the final study report in 
accordance with regulatory authority guidance.
The end-of-study is defined as the date of the last subject's last visit.

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14.0
Investigator's Agreement
1.
I have received and reviewed the Investigator's Brochure for ABT-493 and 
ABT-530.
2.
I have read this protocol and agree that the study is ethical.
3.
I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines.
4.
I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.
5.
I agree that all electronic signatures will be considered the equivalent of a 
handwritten signature and will be legally binding.
Protocol Title: 
A Follow-up Study to Assess Resistance and Durability of Response 
to AbbVie Direct-Acting Antiviral Agent (DAA) Therapy (ABT-493 
and/or ABT-530) in Subjects Who Participated in Phase 2 or 3 
Clinical Studies for the Treatment of Chronic Hepatitis C Virus 
(HCV) Infection
Protocol Date:
09 October 2017
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)

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15.0
Reference List
1.
World Health Organization.  Worldwide Statistics for HCV.  Weekly 
Epidemiological Record No. 49.  10 December 1999.
2.
Kershenobich D, Razavi HA, Sánchez-Avila JF, et al.  Trends and projections of 
hepatitis C virus epidemiology in Latin America.  Liver Int.  
2011;31 (Suppl 2):18-29.
3.
Sievert W, Altraif I, Razavi HA, et al.  A systematic review of hepatitis C virus 
epidemiology in Asia, Australia and Egypt.  Liver Int.  2011;31 (Suppl 2):61-80.
4.
Manos MM, Shvachko VA, Murphy RC, et al.  Distribution of hepatitis C virus 
genotypes in a diverse US integrated health care population.  J Med Virol.  
2012;84(11):1744-50.
5.
Sy T, Jamal MM.  Epidemiology of hepatitis C virus (HCV) infection.  Int J Med 
Sci.  2006;3(2):41-6.
6.
European Association for Study of Liver.  EASL Clinical Practice Guidelines:  
management of hepatitis C virus infection.  J Hepatol.  2014;60(2):392-420.
7.
Cardoso AC, Moucari R, Figueiredo-Mendes C, et al.  Impact of peginterferon and 
ribavirin therapy on hepatocellular carcinoma:  incidence and survival in 
hepatitis C patients with advanced fibrosis.  J Hepatol.  2010;52(5):652-7.
8.
Backus LI, Boothroyd DB, Phillips BR, et al.  A sustained virologic response 
reduces risk of all-cause mortality in patients with hepatitis C.  Clin Gastroenterol 
Hepatol.  2011;9(6):509-16.
9.
Jacobson IM, McHutchison JG, Dusheiko G, et al.  Telaprevir for previously 
untreated chronic hepatitis C virus infection.  N Engl J Med.  
2011;364(25):2405-16.
10.
McHutchison JG, Manns MP, Muir AJ, et al.  Telaprevir for previously treated 
chronic HCV infection.  N Engl J Med.  2010;362(14):1292-303.

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11.
Poordad F, Bronowicki JP, Gordon SC, et al.  Factors that predict response of 
patients with hepatitis C virus infection to boceprevir.  Gastroenterology.  
2012;143(3):608-18.
12.
Poordad F, McCone J Jr, Bacon BR, et al.  Boceprevir for untreated chronic HCV 
genotype 1 infection.  N Engl J Med.  2011;364(13):1195-206.
13.
Bacon BR, Gordon SC, Lawitz E, et al.  Boceprevir for previously treated chronic 
HCV genotype 1 infection.  N Engl J Med.  2011;364(13):1207-17.
14.
Zeuzem S, Andreone P, Pol S, et al.  Telaprevir for retreatment of HCV infection.  
N Engl J Med.  2011;364(25):2417-28.
15.
INCIVEK® (telaprevir) [package insert].  Cambridge, MA; Vertex Pharmaceuticals 
Incorporated, 2013.
16.
VICTRELIS™ (boceprevir) capsules [package insert].  Whitehouse Station, NJ; 
Merck & Co., Inc., 2013.
17.
HARVONI® [package insert] Foster City, CA; Gilead Sciences, Inc., 2014.
18.
Viekira Pak® [package insert] North Chicago, IL; AbbVie Inc., 2014.
19.
De Meyer S, Dierynck I, Ghys A, et al.  Characterization of telaprevir treatment 
outcomes and resistance in patients with prior treatment failure:  results from the 
REALIZE trial.  Hepatology.  2012;56(6):2106-15.
20.
Wu S, Kanda T, Nakamoto S, et al.  Hepatitis C virus protease inhibitor-resistance 
mutations: our experience and review.  World J Gastroenterol.  
2013;19(47):8940-8.
21.
Fridell RA, Wang C, Sun JH, et al.  Genotypic and phenotypic analysis of variants 
resistant to hepatitis C virus nonstructural protein 5A replication complex inhibitor 
BMS-790052 in humans:  in vitro and in vivo correlations.  Hepatology.  
2011;54(6):1924-35.
22.
McPhee F, Hernandez D, Yu F, et al.  Resistance analysis of hepatitis C virus 
genotype 1 prior treatment null responders receiving daclatasvir and asunaprevir.  
Hepatology.  2013;58(3):902-11.

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23.
Wang C, Sun JH, O'Boyle DR, et al.  Persistence of resistant variants in hepatitis C 
virus-infected patients treated with the NS5A replication complex inhibitor 
daclatasvir.  Antimicrob Agents Chemother.  2013;57(5):2054-65.
24.
Koh C, Heller T, Haynes-Williams V, et al.  Long-Term Outcome of Chronic 
Hepatitis C after Sustained Virological Response to Interferon-based Therapy.  
Aliment Pharmacol Ther 2013;37(9):887-94.
25.
Marcellin P, Boyer N, Gervais A, et al., Long-term histologic improvement and 
loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and 
sustained response to interferon-alpha therapy.  Ann Intern Med.  
1997;127(10):875-81.
26.
Gottwein JM, Scheel TK, Jensen TB, et al.  Differential efficacy of protease 
inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant 
viruses.  Gastroenterology.  2011;141(3):1067-79.
27.
AbbVie.  ABT-493 Investigator's Brochure Edition 3.  12 September 2014.
28.
AbbVie.  ABT-530 Investigator's Brochure Edition 3.  12 September 2014.
29.
The American Association for the Study of Liver Diseases and the Infectious 
Diseases Society of America.  HCV guidance:  recommendations for testing, 
managing, and treating hepatitis C.  Last updated:  12 April 2017.  Available from:  
http://www.hcvguidelines.org/sites/default/files/full-guidance-
pdf/HCVGuidance_April_12_2017_b.pdf.

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Appendix A.
Responsibilities of the Clinical Investigator
Clinical research studies sponsored by AbbVie are subject to the Good Clinical Practices 
(GCP) and local regulations and guidelines governing the study at the site location.  In 
signing the Investigator Agreement in Section 14.0 of this protocol, the investigator is 
agreeing to the following:
1.
Conducting the study in accordance with the relevant, current protocol, making 
changes in a protocol only after notifying AbbVie, except when necessary to 
protect the safety, rights or welfare of subjects.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for 
investigational purposes and complying with the requirements relating to informed 
consent and ethics committees (e.g., independent ethics committee [IEC] or 
institutional review board [IRB]) review and approval of the protocol and 
amendments.
4.
Reporting adverse experiences that occur in the course of the investigation(s) to 
AbbVie and the site director.
5.
Reading the information in the Investigator's Brochure/safety material provided, 
including the instructions for use and the potential risks and side effects of the 
investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the 
study about their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making 
those records available for inspection by representatives of AbbVie and/or the 
appropriate regulatory agency, and retaining all study-related documents until 
notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and 
approved the initial clinical investigation and all amendments.

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9.
Reporting promptly, all changes in the research activity and all unanticipated 
problems involving risks to human subjects or others, to the appropriate individuals 
(e.g., coordinating investigator, institution director) and/or directly to the ethics 
committees and AbbVie.
10.
Following the protocol and not make any changes in the research without ethics 
committee approval, except where necessary to eliminate apparent immediate 
hazards to human subjects.

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Appendix B.
List of Protocol Signatories
Name
Title
Functional Area
Clinical
Clinical
Clinical
Statistics

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Appendix C.
Study Activities A and B
Table A.
SVR and Non-SVR Subjects Not Receiving Re-Treatment
Activity
Day 1a
Month 3b,c
Month 6b,c
Month 12b,c
Month 18b,c
Month 24b,c
Month 30b,c
Month 36b,c
Informed Consent
X
Medical History (related to liver disease/HCV 
infection) including past HCV drug treatments 
(during the prior study and before prior study)
X
Assessment of Medical Events Related to Liver 
Disease/HCV Infection
X
X
X
X
X
X
X
Child-Pugh Score and Classification (cirrhotic 
subjects only)d
X
X
X
X
X
X
X
INR
X
X
X
X
X
X
X
Serum Albumin
X
X
X
X
X
X
X
IP-10 Sample
X
X
X
X
X
(if final visit)
X
Clinical Chemistry Tests including FibroTest and 
APRI (see Table 1 for details)
X
X
X
Xf
Xf
X
X
(if final visit)
X
Platelets (for APRI)
X
X
X
X
X
(if final visit)
X
HCV RNA Sample
X
X
X
X
X
X
X
X
HCV Resistance Sample
X
X
X
X
X
X
X
X
Archive Plasma Sample
X
X
X
X
X
X
X
X
Collection of Liver Diagnostic Results
X
X
X
X
X
X
X
X
HCC Screening Liver ultrasound for subjects with 
cirrhosis only (at Final visit only)
Xg
Xg
Xg
Xg
Xg
Xg
Xg
Xg

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Activity
Day 1a
Month 3b,c
Month 6b,c
Month 12b,c
Month 18b,c
Month 24b,c
Month 30b,c
Month 36b,c
Assess for SAE related to Study Procedures or to 
Exposure to ABT-493 and/or ABT-530 in the prior 
study
X
X
X
X
X
X
X
X
Documentation of Medications for the Treatment of 
HCV or Treatment of an SAE Related to Study 
Procedures or to Exposure to ABT-493 and/or 
ABT-530 in the Prior Study
X
X
X
X
X
X
X
X
Collection of re-treatment regimen information and 
dosing dates (if applicable)e
Xe
Xe
Xe
Xe
Xe
Xe
Xe
a.
The interval between the last dose of DAA therapy in the prior AbbVie clinical study and the Day 1 Visit of Study M13-576 must be no longer than 2 years. 
b.
Once a subject has reached approximately 3 years post-DAA therapy, participation in Study M13-576 will be completed.  The study visit which falls closest to 3 years since 
the subject's last dose of AbbVie DAA will be registered as their final visit.
c.
Visit window interval.  Study visits should ideally take place within 3 weeks of the planned visit date.  If the Month 3 visit is more than 6 weeks later than planned it should 
be registered instead as the Month 6 visit.  If a Month 6, 12, 18, 24, 30 or 36 visit is more than 12 weeks later than planned it should be registered as the next visit in the 
schedule.
d.
Child-Pugh Score and Category should be assessed on all cirrhotic subjects (those cirrhotic upon enrollment and those who become cirrhotic during the study) after approval 
of Amendment 2 at the site.
e.
Subjects who are virologic failures and begin a re-treatment regimen during participation in the Study M13-576 will begin following the Study Activities Table B for re-
treated subjects at the time re-treatment begins.
f.
Total bilirubin only will be collected at Month 12 and Month 18 for the Child-Pugh Score for cirrhotic subjects only.
g.
HCC Screening Liver ultrasound will be performed on subjects with cirrhosis at the visit considered the Final visit for the subject, unless the subject has a liver ultrasound, CT 
or MRI performed for HCC screening within 3 months prior to that visit, in which case the result of that US, CT or MRI will be used as the result for Final Study Visit 
assessment.

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Table B.
Virologic Failures Receiving Re-Treatment (Prior to or During Enrollment in Study M13-576)
Activity
Day 1a
SVR12 for Virologic Failures Re-Treated During Study M13-576b,c
Informed Consent
X
Medical History (related to liver disease/HCV infection) occurring since 
the end of the prior AbbVie HCV clinical study but before starting a re-
treatment regimen
Xd
Assessment of Medical Events Related to Liver Disease/HCV Infection 
that occurred after the prior AbbVie HCV clinical study but before 
starting a re-treatment regimen
Xd
Collection of re-treatment regimen information and dosing dates for HCV
X
X
Collection of re-treatment outcome
X
HCC Screening Liver ultrasound for subjects with cirrhosis
Xe
a.
The interval between the last dose of DAA therapy in the prior AbbVie clinical study and the Day 1 Visit of Study M13-576 must be no longer than 2 years.
b.
Subjects who are virologic failures in the prior Phase 2 or 3 study may participate in Study M13-576 and be re-treated at any time after their last dose of study drug in the 
prior study.  They will be followed in Study M13-576 until 12 weeks after the last dose (SVR12) of the re-treatment regimen.
c.
SVR12 assessment may be done by clinic visit or by telephone.  Documentation of the re-treatment outcome will be recorded in the eCRF and supported by an appropriate 
entry in the subject's source document.  Cirrhotic subjects should have a liver ultrasound done at the final visit, therefore conducting the SVR12 assessment should be done by 
clinic visit not by telephone.
d.
Subjects who begin a re-treatment regimen during participation in Study M13-576 will have already had these activities done at Day 1 upon enrollment into the study.  They 
do not need to be repeated when they begin their re-treatment regimen.
e.
HCC Screening Liver ultrasound will be performed on subjects with cirrhosis at the visit considered the Final visit for the subject, unless the subject has a liver ultrasound, CT 
or MRI performed for HCC screening within 3 months prior to that visit, in which case the result of that US, CT or MRI will be used as the result for Final Study Visit 
assessment.  

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Appendix D.
List of Prior Eligible Studies
Subjects who have received at least one dose of an ABT-493 and/or ABT-530-containing 
regimen in any of the following eligible AbbVie HCV Phase 2 or 3 studies meet inclusion 
criteria number 1:
●
M14-213
●
M14-867
●
M14-868
●
M15-410
●
M13-590
●
M15-464
●
M13-594
●
M13-583
●
M14-172
●
M15-462

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Appendix E.
Child-Pugh Score and Category
The Child-Pugh score uses five clinical measures of liver disease (3 laboratory parameters 
and 2 clinical assessments).  Child-Pugh score will be determined only for subjects with 
cirrhosis at the visits indicated in Appendix C.
Table 2.
Child-Pugh Classification of Severity of Cirrhosis
Points Assigned for Observed Findings
Parameter
1
2
3
Total bilirubin, μmol/L (mg/dL)
< 34.2
(< 2)
34.2 – 51.3
(2 – 3)
> 51.3
(> 3)
Serum albumin, g/L (g/dL)
> 35
(> 3.5)
28 – 35
(2.8 – 3.5)
< 28
(< 2.8)
INR
< 1.7
1.7 – 2.3
> 2.3
Ascites*
None
Slight
Moderate to severe
Hepatic encephalopathy**
None
Grade 1 or 2
(or suppressed with 
medication)
Grade 3 or 4
(or refractory)
*
None; Slight ascites = Ascites detectable only by ultrasound examination; Moderate ascites = Ascites manifested 
by moderate symmetrical distension of the abdomen; Severe ascites = Large or gross ascites with marked 
abdominal distension.
**
Grade 0:  normal consciousness, personality, neurological examination, electroencephalogram; Grade 1:  restless, 
sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cps waves; Grade 2:  lethargic, time-disoriented, 
inappropriate behavior, asterixis, ataxia, slow triphasic waves; Grade 3:  somnolent, stuporous, place-disoriented, 
hyperactive reflexes, rigidity, slower waves; Grade 4:  unarousable coma, no personality/behavior, decerebrate, 
slow 2 to 3 cps delta activity.
The Child-Pugh Classification is defined in terms of the sum of the scores for the 
five parameters:
●
A score of 5 or 6 indicates Child-Pugh Category A (mild hepatic impairment).
●
A score of 7, 8, or 9 indicates Child-Pugh Category B (moderate hepatic 
impairment).
●
A score of 10 through 15 indicates Child-Pugh Category C (severe hepatic 
impairment).

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Appendix F.
Protocol Amendment:  List of Changes
The summary of changes is listed in Section 1.1.
Specific Protocol Changes:
Section 1.2  Synopsis
Subsection Phase of Development:
Previously read:
2
Has been changed to read:
2/3
Section 1.2  Synopsis
Subsection Objectives:
Second paragraph, last bullet previously read:
Summarize results of the following laboratory tests and scores:  FibroTest, APRI, IP-10, 
alpha fetoprotein, FibroScan, and liver biopsy.
Has been changed to read:
Summarize results of the following laboratory tests and scores:  FibroTest, APRI, IP-10, 
alpha fetoprotein (if collected under a previous protocol version), FibroScan, and liver 
biopsy.
Section 1.2  Synopsis
Subsection Diagnosis and Main Criteria for Inclusion/Exclusion:
Heading "Main Inclusion:"
Criterion 2 previously read:
The interval between the last dose of the AbbVie DAA therapy from the previous clinical 
study and enrollment in Study M13-576 must be no longer than 2 years.

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Has been changed to read:
The interval between the last dose of the AbbVie DAA therapy from the previous clinical
study and enrollment in Study M13-576 must be no longer than 2 years for subjects who 
have not been retreated.  Subjects who have been treated with a commercially-available 
anti-HCV treatment may be enrolled greater than 2 years after the last dose of the AbbVie 
DAA therapy from the previous clinical study.
Section 4.0  Study Objectives
Second paragraph, last bullet previously read:
Summarize results of the following laboratory tests and scores:  FibroTest, APRI, IP-10, 
alpha fetoprotein, FibroScan, and liver biopsy.
Has been changed to read:
Summarize results of the following laboratory tests and scores:  FibroTest, APRI, IP-10, 
alpha fetoprotein (if collected under a previous protocol version), FibroScan, and liver 
biopsy.
Section 5.1  Overall Study Design and Plan:  Description
Fourth paragraph, fourth and fifth sentence previously read:
Once a subject has reached 3 years post-DAA therapy, participation in this study will be 
completed, except for subjects enrolled with virologic failure who receive re-treatment 
with a new HCV antiviral regimen that does not contain ABT-493/ABT-530.  Subjects 
who are re-treated with HCV regimens other than ABT-493/ABT-530 will have only 
one further assessment for treatment outcome 12 weeks after stopping that therapy or 
earlier if already known (in cases of treatment failure).
Has been changed to read:
Once a subject has reached 3 years post-DAA therapy, participation in this study will be 
completed, except for subjects enrolled with virologic failure who receive re-treatment 
with a HCV antiviral regimen other than investigational ABT-493/ABT-530.  Subjects 

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who are retreated with investigational ABT-493/ABT-530 are not allowed in this study.  
Subjects who are re-treated with HCV regimens other than investigational 
ABT-493/ABT-530 will have only one further assessment for treatment outcome 
12 weeks after stopping that therapy or earlier if already known (in cases of treatment 
failure).
Section 5.2.1  Inclusion Criteria
Criterion 3 previously read:
The interval between the last dose of the AbbVie DAA therapy from the previous clinical 
study and enrollment in Study M13-576 must be no longer than 2 years.
Has been changed to read:
The interval between the last dose of the AbbVie DAA therapy from the previous clinical 
study and enrollment in Study M13-576 must be no longer than 2 years for subjects who 
have not been retreated.  Subjects who have been treated with a commercially-available 
anti-HCV treatment may be enrolled greater than 2 years after the last dose of the AbbVie 
DAA therapy from the previous clinical study.
Section 5.2.3  Prior and Concomitant Therapy
First paragraph, second and third sentence previously read:
Commercially available prescription medications for the treatment of HCV therapy 
initiated after the completion of a subject's participation in the previous clinical study 
(either prior to or during participation in this study) are permitted, and the regimen 
received and duration will be recorded in the eCRF.  Subjects enrolled with virologic 
failure who undergo re-treatment with a new HCV antiviral regimen not containing 
ABT-493/ABT-530 will be followed until completing the post-treatment Week 12 visit 
after receiving their re-treatment regimen, after which they will discontinue from the 
study.  

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Has been changed to read:
Commercially available prescription medications for the treatment of HCV therapy, 
including regimens containing commercially available glecaprevir/pibrentasvir (GLE/PIB, 
investigationally known as ABT-493/ABT-530), initiated after the completion of a 
subject's participation in the previous clinical study (either prior to or during participation 
in this study) are permitted, and the regimen received and duration will be recorded in the 
eCRF.  Subjects enrolled with virologic failure who undergo re-treatment with a HCV 
antiviral regimen not containing investigational ABT-493/ABT-530 will be followed until 
completing the post-treatment Week 12 visit after receiving their re-treatment regimen, 
after which they will discontinue from the study.  
Section 5.3.1.1  Study Procedures
Section Hepatocellular Carcinoma Screening:  Liver Ultrasound
Add:  new section title and text
Hepatocellular Carcinoma Screening:  Liver Ultrasound
HCC screening will be required as a protocol-specified study procedure only at the Final 
visit, as indicated in Appendix C, for subjects with cirrhosis only.  At any other time 
during the study, HCC screening should be performed according to standard of care.
At the Final visit, subjects with cirrhosis will be required to perform a liver ultrasound to 
screen for HCC, unless the subject has a liver ultrasound, CT or MRI performed for HCC 
screening within 3 months prior to that visit, in which case the result of that US, CT or 
MRI will be used as the result for the Study Visit assessment.  A positive ultrasound result 
suspicious of HCC will be confirmed with CT scan or MRI.  Alternate methods of 
screening for HCC (i.e., MRI or CT) at a study visit should be discussed with the TA MD.
Section 5.3.1.1  Study Procedures
Subsection Clinical Laboratory Tests
First paragraph previously read:
Samples will be obtained for the clinical laboratory tests, including FibroTest and APRI, 
IP-10, AFP and quantitative HCV RNA PCR, INR and serum Albumin at the visits 

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specified in Appendix C for all subjects, until the end of the study or initiation of re-
treatment for HCV (if applicable).
Has been changed to read:
Samples will be obtained for the clinical laboratory tests, including FibroTest and APRI, 
IP-10, and quantitative HCV RNA PCR, INR and serum Albumin at the visits specified in 
Appendix C for all subjects, until the end of the study or initiation of re-treatment for 
HCV (if applicable).
Table 1.  Clinical Laboratory Tests
Column "Clinical Chemistry"
Delete:
Alpha Fetoprotein
Section 5.3.3.1  Clinical Variables
Subsection Clinical Variables
Last paragraph, first sentence previously read:
Results of the following laboratory tests and studies will be summarized:  IP-10, 
FibroTest, APRI, alpha fetoprotein, FibroScan, liver biopsy.  
Has been changed to read:
Results of the following laboratory tests and studies will be summarized:  IP-10, 
FibroTest, APRI, alpha fetoprotein, (if collected under a previous protocol version) 
FibroScan, liver biopsy.  
Section 5.3.4  Safety Variables
First sentence previously read:
Only serious adverse events related to study procedures or those that meet seriousness 
criteria outlined in Section 6.0 and are considered reasonably related to ABT-530 and/or 
ABT-493 drug exposure in a prior study (Appendix D) by the investigator will be reported 
as serious adverse events.  

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Has been changed to read:
Only serious adverse events related to study procedures or those that meet seriousness 
criteria outlined in Section 6.0 and are considered reasonably related to ABT-530 and/or 
ABT-493 drug exposure in a prior study (Appendix D) by the investigator will be 
collected.  
Section 6.0  Adverse Events
First paragraph, first sentence previously read:
As this is a non-drug interventional study, only serious adverse events that the investigator 
considers reasonably related to interventional study procedures (i.e., venipunctures) or 
those considered reasonably related to ABT-530 and/or ABT-493 exposure in the prior 
study (Appendix D) by the investigator will be reported as serious adverse events.  
Has been changed to read:
As this is a non-drug interventional study, only serious adverse events that the investigator 
considers reasonably related to interventional study procedures (i.e., venipunctures) or 
those considered reasonably related to ABT-530 and/or ABT-493 exposure in the prior 
study (Appendix D) by the investigator will be collected.  
Section 6.0  Adverse Events
Second paragraph, last sentence previously read:
Serious adverse events related to study procedures or reasonably related to exposure to 
ABT-493 and/or ABT-530 in the prior study, whether in response to a query, observed by 
site personnel, or reported spontaneously by the subject will be recorded.
Has been changed to read:
Serious adverse events related to study procedures or reasonably related to exposure to 
ABT-493 and/or ABT-530 in the prior study, whether in response to a query, observed by 
site personnel, or reported spontaneously by the subject will be collected.

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Section 6.5  Adverse Event Reporting
Add:  new last paragraph
The sponsor will be responsible for Suspected Unexpected Serious Adverse Reactions 
(SUSAR) reporting for the Investigational Medicinal Product (IMP) in accordance with 
Directive 2001/20/EC.  The reference document used for SUSAR reporting in the EU 
countries will be the most current version of the Investigator's Brochure.
Section 7.0  Protocol Deviations
First paragraph, last sentence previously read:
If a protocol deviation occurs (or is identified) after a subject has been enrolled, the 
principal investigator is responsible for notifying Independent Ethics Committee 
(IEC)/Independent Review Board (IRB) regulatory authorities (as applicable), and the 
following AbbVie representatives:
Has been changed to read:
If a protocol deviation occurs (or is identified) after a subject has been enrolled, the 
principal investigator is responsible for notifying Independent Ethics Committee 
(IEC)/Independent Review Board (IRB) and the following AbbVie representatives:
Section 7.0  Protocol Deviations
Last paragraph
Add:  new second and third sentence
AbbVie will assess all protocol deviations and determine if the deviation requires 
reporting to the Regulatory Authority(ies), if required by local regulations, as a serious 
breach of GCP and the protocol.  Protocol waivers are not permitted.
Section 9.1  Independent Ethics Committee (IEC) or Institutional Review Board 
(IRB)
Second paragraph, first sentence previously read:
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  

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Has been changed to read:
Any amendments to the protocol will require IEC/IRB approval and approval by 
Regulatory Authority(ies), if required by local regulations, prior to implementation of any 
changes made to the study design.  
Section 13.0  Completion of the Study
First paragraph
Add:  new last sentence
AbbVie will provide the Clinical Study Report to Regulatory Authority(ies), if required 
by local regulations.
Section 15.0  Reference List
Add:  new Reference 29
The American Association for the Study of Liver Diseases and the Infectious Diseases 
Society of America.  HCV guidance:  recommendations for testing, managing, and 
treating hepatitis C.  Last updated:  12 April 2017.  Available from:  
http://www.hcvguidelines.org/sites/default/files/full-guidance-
pdf/HCVGuidance_April_12_2017_b.pdf.
Appendix B.  List of Protocol Signatories
Previously read:
Name
Title
Functional Area
Clinical
Clinical
Clinical
Statistics

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Has been changed to read:
Name
Title
Functional Area
Clinical
Clinical
Clinical
Statistics

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Appendix C.  Study Activities A and B
Table A.  SVR and Non-SVR Subjects Not Receiving Re-Treatment
Activity "Clinical Chemistry Tests including FibroTest and APRI (see Table 1 for details)" previously read:
Activity
Day 1a
Month 3b,c
Month 6b,c
Month 12b,c
Month 18b,c
Month 24b,c
Month 30b,c
Month 36b,c
Clinical Chemistry Tests including FibroTest and 
APRI (see Table 1 for details)
X
X
X
X
X
(if final visit)
X
Has been changed to read:
Activity
Day 1a
Month 3b,c
Month 6b,c
Month 12b,c
Month 18b,c
Month 24b,c
Month 30b,c
Month 36b,c
Clinical Chemistry Tests including FibroTest and 
APRI (see Table 1 for details)
X
X
X
Xf
Xf
X
X
(if final visit)
X
Appendix C.  Study Activities A and B
Table A.  SVR and Non-SVR Subjects Not Receiving Re-Treatment
Add:  Activity "HCC Screening Liver ultrasound for subjects with cirrhosis only (at Final visit only)"
Activity
Day 1a
Month 3b,c
Month 6b,c
Month 12b,c
Month 18b,c
Month 24b,c
Month 30b,c
Month 36b,c
HCC Screening Liver ultrasound for subjects with 
cirrhosis only (at Final visit only)
Xg
Xg
Xg
Xg
Xg
Xg
Xg
Xg

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Appendix C.  Study Activities A and B
Table A.  SVR and Non-SVR Subjects Not Receiving Re-Treatment
Add:  new table note "f." and "g."
f.
Total bilirubin only will be collected at Month 12 and Month 18 for the Child-Pugh Score for cirrhotic subjects 
only.
g.
HCC Screening Liver ultrasound will be performed on subjects with cirrhosis at the visit considered the Final visit 
for the subject, unless the subject has a liver ultrasound, CT or MRI performed for HCC screening within 3 months 
prior to that visit, in which case the result of that US, CT or MRI will be used as the result for Final Study Visit 
assessment.  
Appendix C.  Study Activities A and B
Table B.  Virologic Failures Receiving Re-Treatment (Prior to or During Enrollment 
in Study M13-576)
Add:  Activity "HCC Screening Liver ultrasound for subjects with cirrhosis"
Activity
Day 1a
SVR12 for Virologic Failures Re-Treated 
During Study M13-576b,c
HCC Screening Liver ultrasound for subjects 
with cirrhosis 
Xe
Appendix C.  Study Activities A and B
Table B.  Virologic Failures Receiving Re-Treatment (Prior to or During Enrollment 
in Study M13-576)
Table note "c."
Add:  new last sentence
Cirrhotic subjects should have a liver ultrasound done at the final visit, therefore 
conducting the SVR12 assessment should be done by clinic visit not by telephone.
Appendix C.  Study Activities A and B
Table B.  Virologic Failures Receiving Re-Treatment (Prior to or During Enrollment 
in Study M13-576)
Add:  new table note "e."
HCC Screening Liver ultrasound will be performed on subjects with cirrhosis at the visit 
considered the Final visit for the subject, unless the subject has a liver ultrasound, CT or 
MRI performed for HCC screening within 3 months prior to that visit, in which case the 
result of that US, CT or MRI will be used as the result for Final Study Visit assessment.