A Single Arm, Open Label, Multicenter Study to Evaluate the Efficacy and Safety of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment Naïve Adults With Chronic Hepatitis C Virus (HCV) Genotypes 1 - 6 Infection and Aspartate Aminotransferase to Platelet Ratio Index (APRI) ≤ 1
Phase: PHASE3
Conditions: Hepatitis C Virus (HCV)
Sponsor: AbbVie

NCT03212521

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TABLE OF CONTENTS
1
SYNOPSIS
5
2
INTRODUCTION
8
2.1
BACKGROUND AND RATIONALE
8
2.2
BENEFITS AND RISKS TO SUBJECTS
10
3
STUDY OBJECTIVES AND ENDPOINTS
11
3.1
OBJECTIVES
11
3.2
PRIMARY ENDPOINT
12
3.3
SECONDARY ENDPOINTS
12
3.4
EXPLORATORY ENDPOINTS
12
3.5
SAFETY ENDPOINTS
12
4
INVESTIGATIONAL PLAN
12
4.1
OVERALL STUDY DESIGN AND PLAN
12
4.2
DISCUSSION OF STUDY DESIGN
13
5
STUDY ACTIVITIES
14
5.1
ELIGIBILITY CRITERIA
14
5.2
CONTRACEPTION RECOMMENDATIONS
17
5.3
PROHIBITED MEDICATIONS AND THERAPY
18
5.4
PRIOR AND CONCOMITANT THERAPY
18
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
19
5.6
FOLLOW-UP FOR SUBJECT WITHDRAWAL FROM STUDY
20
5.7
STUDY DRUG
21
5.8
RANDOMIZATION/DRUG ASSIGNMENT
21
5.9
PROTOCOL DEVIATIONS
22
6
SAFETY CONSIDERATIONS
22
6.1
COMPLAINTS AND ADVERSE EVENTS
22
6.2
TOXICITY MANAGEMENT
25
6.3
PRODUCT COMPLAINT
25

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7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
26
7.1
STATISTICAL AND ANALYTICAL PLANS
26
7.2
DEFINITION FOR ANALYSIS POPULATIONS
26
7.3
STATISTICAL ANALYSES
26
8
ETHICS
28
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD (IEC/IRB)
28
8.2
ETHICAL CONDUCT OF THE STUDY
28
8.3
SUBJECT CONFIDENTIALITY
28
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
29
10 DATA QUALITY ASSURANCE
29
11 COMPLETION OF THE STUDY
29
12 REFERENCES
29
LIST OF TABLES
TABLE 1.
IDENTITY OF STUDY DRUG
21
LIST OF FIGURES
FIGURE 1.
STUDY DESIGN SCHEMATIC
13
LIST OF APPENDICES
APPENDIX A.
STUDY SPECIFIC ABBREVIATIONS AND TERMS
31
APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
34
APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
35
APPENDIX D.
ACTIVITY SCHEDULE
36

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APPENDIX E.
PROTOCOL AMENDMENT SUMMARY OF CHANGES
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2 INTRODUCTION
2.1 Background and Rationale
Why Is This Study Being Conducted
Hepatitis C viral infection is a global health problem, with over 184 million individuals infected 
worldwide.1  Successful treatment of HCV has been shown to significantly reduce the risk of disease 
progression and related mortality.2,3  The advent of DAAs has dramatically changed the HCV treatment 
outcomes, with SVR rates over 90% with shorter treatment durations and improved tolerability 
compared to peginterferon based regimens.  However with the first generation DAAs,4 there is still a 
need for a comprehensive patient assessment, including determination of fibrosis status, genotype and 
subtype, and baseline characteristics (such as quantitative viral load) in order to determine the best 
treatment strategy (regimen, duration, addition of RBV).  The next generation DAAs are typically 
pangenotypic but the optimal treatment duration still depends on fewer key baseline characteristics 
such as cirrhosis status and GT.2  Fibrosis status is usually assessed by liver biopsy (an invasive method) 
or a noninvasive method such as transient elastography which is currently not available worldwide.5  
Due to prior limitations on treatment availability, patients with advanced liver disease were prioritized 
to receive treatment with DAAs.5  As these patient populations have consistently achieved SVR, the 
focus is shifting to patients with milder forms of liver disease (i.e., non-cirrhotic) for whom HCV 
treatment is also cost effective (as these patients have a low risk of developing cirrhosis after achieving 
SVR).3,5-7  In addition, some models have shown that scaling up therapy for the patient population with 
mild liver disease is a key strategy towards HCV eradication by impacting disease prevalence and 
transmission.5
AbbVie's next generation DAAs include GLE, an HCV NS3/4A PI, and PIB, an HCV NS5A inhibitor.  Each 
DAA has potent antiviral activity against the major HCV GTs in vitro with no or little loss of potency 
against common single-position NS3 and NS5A resistance-associated substitutions.  
Glecaprevir/pibrentasvir fixed-dose combination tablets have been developed for the treatment of 
chronic HCV infection.8,9
The GLE/PIB registrational program assessed a broad population including subjects with compensated 
liver disease and subjects with severe renal insufficiency across all GTs using a single GLE/PIB dose of 
300 mg/120 mg QD.  Supportive Phase 2 studies used the Phase 2 formulation of separate GLE and PIB 
tablets, with each tablet containing 100 mg and 40 mg, respectively.  Treatment arms from these 
supportive Phase 2 studies using the regimen selected for registrational studies (GLE 300 mg plus PIB 
120 mg) were pooled with arms from the registrational studies for analyses of efficacy and safety.  
Treatment-naïve and treatment experienced subjects to any combination of pegylated interferon, RBV, 
sofosbuvir, NS5A inhibitors, or PIs were allowed in the program.  In addition, the program included 
subjects with HIV co-infection (Study M13-590), subjects with chronic kidney disease Stages 4 – 5, 
including those on hemodialysis (Study M15-462), subjects with compensated cirrhosis 
(Studies M14-172, M15-462, and M14-868 Part 3), and subjects with or without cirrhosis who failed a 
previous regimen containing an NS5A inhibitor and/or an NS3/4A PI (Study M15-410).

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A total of 2,376 subjects were randomized or enrolled in the registrational studies or supportive Phase 2 
studies to receive GLE 300 mg QD and PIB 120 mg QD.  Of these, 2,369 subjects received at least 1 dose 
of study drug.8-13
In treatment naïve subjects with compensated cirrhosis GLE/PIB achieved SVR12 rates over 98%, 
including in subjects with GT3, with 12 weeks of therapy as in SURVEYOR II Part 3 (Study M14-868 –
GT3).10
Based on the efficacy data presented above, the 8-week treatment duration is anticipated to achieve 
high SVR12 rates in GT1 – 6-infected treatment-naïve subjects without cirrhosis.10,12
In Phase 3 trial, ENDURANCE-1 (M13-590), that has explored chronic HCV GT1 treatment naïve adult 
subjects without cirrhosis, the administration GLE/PIB for 8 weeks has shown SVR12 rates of 99.1% 
(348/351 including 1 subject with missing data).  This was non-inferior to the 12 week arm data.11  In the 
combined analysis from Phase 2, SURVEYOR II-Part 4 study that has explored chronic GT2, 4, 5 and 6 
treatment-naïve adult subjects without cirrhosis, the administration GLE/PIB for 8 weeks has shown 
SVR12 rates of 96.5% (196/203, including 3 subjects with missing data).12  These results were similar to 
12 weeks of GLE/PIB in this population.  For chronic HCV GT3 treatment-naïve adult subjects without-
cirrhosis, the SVR12 rate for 8 weeks of therapy was 94.9% (149/157 including 2 subjects with missing 
data), also non-inferior to 12 weeks of therapy as demonstrated in ENDURANCE-3 (Study M13-594).13
While a pangenotypic regimen that has high efficacy across all treatment-naïve non-cirrhotic patients 
with 8 week treatment duration is very attractive for treatment simplification and scaling up 
therapy6,7,14, the need for a comprehensive patient evaluation with more complex diagnostic tests such 
as liver biopsy and transient elastography to identify cirrhosis can still be a barrier to access to 
treatment.5  Some guidelines recommend that serum biomarkers can be used in the absence of 
transient elastography.4,5,7,14  The World Health Organization (WHO) guidelines state that non-invasive 
monitoring is considered to be preferable to invasive testing.  The WHO considers that APRI, Fibrosis-4 
score (FIB-4) and transient elastography are the most useful tests for assessing the stage of liver 
disease.5  Several serum biomarkers have been evaluated to identify patients with cirrhosis or advanced 
fibrosis.  Among these, the APRI has been extensively studied and a meta-analysis including more than 
16,000 patients has shown mean accuracy of 0.84 to identify non-cirrhotic patients with a cut off ≤ 1.6  
The negative predictive value, i.e., the probability of identifying non-cirrhotic patients when in a 
population with an estimated cirrhosis prevalence of around 18% for APRI ≤ 1 using sensitivity and 
specificity reported in this meta-analysis was calculated to be around 94%.  In addition, APRI is a widely 
available low cost test that is very easy to perform and is validated to diagnose fibrosis and cirrhosis.5,6  
The APRI cut off ≤ 1 is recommended in guidelines to rule out cirrhosis.6,7,14  Being able to easily identify 
patients that are eligible for 8 week treatment could simplify treatment algorithms and reserve liver 
biopsy and transient elastography for those patients who really need a more advanced evaluation. 
This study is being conducted to further assess the safety and efficacy of 8 weeks of GLE/PIB 
combination regimen (300 mg GLE/120 mg PIB, QD) in treatment-naïve adults with chronic HCV GT1 –
GT6 infection and APRI ≤ 1.

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Clinical Hypothesis
The clinical hypothesis of this study is that 8 weeks of therapy with GLE/PIB in treatment-naïve GT1 –
GT6 subjects that have APRI ≤1 will achieve high efficacy rates as observed in treatment-naïve, 
non-cirrhotic subjects evaluated in Phase 2 – 3 clinical trials for 8 weeks.
2.2 Benefits and Risks to Subjects
Chronic HCV infection is a major global health problem impacting quality of life, morbidity, as well as 
mortality.  Evidence suggests that effective treatment of HCV can cure the infection as well as improve 
liver function.1-3
The GLE/PIB regimen is an oral, RBV-free pangenotypic regimen that provides high SVR12 rates ≥ 95% in 
subjects with compensated liver disease infected with HCV GT1 – GT6, with the majority of subjects 
treated for 8 – 12 weeks.  Low relapse rates < 3% were observed in GT1 – GT6 treatment-naïve subjects 
without cirrhosis following 8 weeks of treatment, demonstrating no benefit of an additional 4 weeks of 
treatment.  Among these subjects, an 8-week regimen of GLE/PIB achieved SVR rates similar to 
12 weeks of treatment and to the only currently approved pangenotypic HCV regimen.  However, 
GLE/PIB achieved similar efficacy with a significant reduction of the duration of treatment, which may 
improve subjects' adherence, access to treatment, and convenience, and also reduce the burden 
associated with additional medical visits and procedures.
Based on safety data from the registrational and supportive clinical trials where 2369 HCV-infected 
subjects were treated, the fixed-dose combination of GLE/PIB demonstrated a favorable safety profile.  
The most frequent GLE/PIB related adverse events (AEs) include headache, fatigue and nausea, and 
were mostly Grade 1 (mild) in severity.  Grade 3 or higher AEs and serious adverse events (SAEs) were 
uncommon, occurring in 3.8% and 3.1%, of subjects, respectively.  Similarly, the overall rate of study 
drug discontinuations due to AEs was low (0.5%).8,9  Safety in subjects with cirrhosis was shown to be 
similar to subjects without cirrhosis.8,9
Potential risks that may occur with GLE/PIB therapy include hepatotoxicity, development of viral 
resistance, and the development of toxicities from drug-drug interactions (DDIs).  The potential risks for 
GLE/PIB can be monitored, mitigated and managed in clinical practice.
No trends in liver chemistry abnormalities have been observed in Phase 2 and Phase 3 studies, including 
in subjects with compensated cirrhosis.  ALT elevation from nadir to > 5 × ULN occurred in 3/2367 (0.1%) 
of subjects; none of these subjects prematurely discontinued study drug due to the elevation in ALT.  
Similarly, Grade 3 increases in bilirubin were rare (0.4%), predominantly indirect, and without bilirubin-
related AEs.  There were no cases identified consistent with drug-induced liver injury.
While there is a risk for the development of amino acid substitutions conferring resistance to GLE and/or 
PIB in subjects who fail the therapy, it may be possible to successfully retreat these subjects.
The risk of toxicities from DDIs are addressed and mitigated by the product information, which ensures 
awareness of these risks by both subjects and healthcare providers.  Appropriate recommendations for 
dose adjustments of certain medications or avoidance of coadministration with other specific 
medications are provided in the product information.

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Pharmacological class risks include Hepatitis B Virus (HBV) reactivation with DAA treatment.  As the risk 
of HBV reactivation in subjects treated with GLE/PIB has not been studied, HBV co-infected subjects will 
be excluded from the study.
Aminotransferase/platelet ratio index score ≤ 1 has a high negative predictive value in the general 
chronic hepatitis C population.  Additional eligibility criteria of normal platelets and normal albumin as 
well as the absence of previous diagnosis of cirrhosis have been added to mitigate the risk of including 
cirrhotic subjects.  Also according to WHO analysis, the potential increase in treatment availability 
resulting from increased access to low-cost, non-invasive monitoring and reduced risk of adverse events 
from liver biopsy was felt to outweigh the potential harms of false-negative case identification by APRI.5
Given the potential for achieving high rates of SVR in naïve non-cirrhotic subjects with HCV GT1 – GT6 
infection and the favorable safety profile of GLE/PIB, the overall benefit-risk balance of the GLE/PIB 
regimen is, therefore, positive and supports the use in subjects with chronic HCV with compensated liver 
disease, including subjects with renal impairment and HIV-1 co-infection. 
For further details, please see findings from completed studies, including safety data in the GLE/PIB 
Investigator Brochure and addendum.8,9
3 STUDY OBJECTIVES AND ENDPOINTS
3.1 Objectives
The primary objective of this study is: 
•
To demonstrate the efficacy (by achieving high SVR12 rate) and safety of 8 weeks of treatment 
with the GLE/PIB combination regimen in treatment-naïve adults with HCV GT1 – GT6 infection 
with APRI ≤ 1.  The primary efficacy objective will be assessed based on mITT population across 
GTs HCV GT1 – GT6.
The secondary objectives of this study are:
•
To demonstrate the efficacy (by achieving high SVR12 rate) of 8 weeks of treatment with the 
GLE/PIB combination regimen in treatment naïve adults with HCV GT1 – GT6 infection with APRI 
≤ 1 based on ITT population.  
•
Assess the percentage of subjects with HCV on-treatment virologic failures across GTs in adults 
with HCV GT1 – GT6 infection with APRI ≤ 1 based on ITT population.
•
Assess the percentage of subjects with HCV virologic relapse across GTs in adults with HCV GT1 –
GT6 infection with APRI ≤ 1 based on ITT population.

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3.2 Primary Endpoint
The primary efficacy endpoint is the percentage of subjects who achieve SVR12 (HCV RNA < LLOQ 
12 weeks after the last actual dose of study drug) across genotypes in adults with HCV GT1 – GT6 based 
on mITT population. 
3.3 Secondary Endpoints
Secondary endpoints are:
•
Percentage of subjects who achieve SVR12 (HCV RNA < LLOQ 12 weeks after the last actual dose 
of study drug) across GTs in adults with HCV GT1 – GT6 based on ITT population
•
Percentage of subjects with on-treatment virologic failure based on ITT population
•
Percentage of subjects with post-treatment relapse based on ITT population
3.4 Exploratory Endpoints
•
SVR12 in subjects with APRI ≤ 0.7 and APRI ≤ 0.5 based on ITT population
•
Percentage of subjects with virologic failure with Fibrotest > 0.75 based on ITT population
•
Percentage of subjects with SVR12 by key groups (HCV genotype and subtype; age) based on ITT 
population
•
Adherence to treatment based on ITT population
3.5 Safety Endpoints
Safety evaluations include AE monitoring, physical examinations, vital sign measurements, 
electrocardiogram (ECG), and clinical laboratory testing (hematology, chemistry including hepatic 
function parameters) as a measure of safety and tolerability for the entire study duration.
4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
The schematic of the study is shown in Figure 1.  Further details regarding study procedures are located 
in the Operations Manual.
This is a Phase 3b, multicenter, non-randomized, open label study to evaluate the efficacy and safety of 
GLE/PIB in HCV treatment-naïve adult subjects with chronic HCV GT1 – 6 and APRI ≤ 1 for 8 weeks.
The study is designed to enroll approximately 230 subjects (maximum of 20% [46] enrollment of 
GT3-infected subject) at approximately 43 sites worldwide. 

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This study will consist of a Screening Period, a Treatment Period, and a Post-Treatment Period.
Screening Period:  Subjects have up to 35 days following the Screening Visit to confirm eligibility and 
enroll into the study.
Treatment Period:  Eligible subjects will be enrolled to receive GLE/PIB 300 mg/120 mg QD for 8 weeks.
Post-Treatment (PT) Period:  Subjects who complete or prematurely discontinue the Treatment Period 
will be followed for 12 weeks (Wks) after their last dose of study drug to evaluate efficacy and to 
monitor HCV RNA, and the emergence and persistence of viral substitutions.
Figure 1.
Study Design Schematic
4.2
Discussion of Study Design
Appropriateness of Measurements
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All efficacy 
measurements in this study are standard parameters used for assessing disease activity in subjects with 
HCV.  All clinical and laboratory procedures in this study are standard and generally accepted.
Suitability of Subject Population
This subject population will include treatment-naïve subjects only.  While data from registrational and 
Phase 2 supportive trials shows that high SVR12 rates can be achieved with 8 weeks of GLE/PIB, slightly 
lower rates were achieved in treatment-experienced subjects across all GTs.  To reduce the risk of Post-
Treatment relapse, treatment-experienced subjects will be excluded from this study.
Aminotransferase/platelet ratio index ≤ 1 has been shown to have high sensibility and therefore high 
predictive negative value in ruling out cirrhosis.  It is very likely that the population that will be included 
in this study using this biomarker will be non-cirrhotic.  However, in order to decrease the risk of 

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enrolling truly cirrhotic subjects, subjects with clinical signs of cirrhosis, history of decompensation, or 
with lab abnormalities compatible with cirrhosis (low platelets and/or low albumin) will be excluded 
from this study.
Hepatitis C virus-infected subjects with chronic HCV infection have moderate stable elevations of AST 
and ALT levels and are considered representative of the population who will receive anti-HCV therapy.  
This study will include stable subjects with HIV/HCV co-infection, as this sub-population is shown to have 
similar results as mono-infected treatment-naïve non cirrhotic subjects with 8 weeks treatment duration 
in Study M14-730.  As HBV co-infected subjects may have some alteration in APRI scores (due to 
inflammation) and it is difficult to interpret the APRI score in HBV/HCV co-infected population, subjects 
co-infected with HBV will be excluded from the population.  
The age range selected for this study, 18 years of age or older, is also intended to be representative of 
the target population.  Similarly, a substantial portion of the HCV-infected population have a relatively 
high body mass index, and given the acceptable safety and pharmacokinetic profiles of GLE/PIB in 
previous studies, this protocol will enroll subjects without a body mass index restriction.
Glecaprevir/pibrentasvir has shown similar efficacy and safety in subjects at all stages of renal 
impairment, including subjects with chronic kidney disease Stage 4 or 5 and in dialysis.  However, as 
subjects with creatinine clearance < 30 mL/minute can show falsely low APRI levels which may increase 
the risk of enrolling a truly cirrhotic subject.  Therefore, subjects with creatinine clearance 
< 30 mL/minute will be excluded from this study.
Selection of Dose in the Study
The dose of GLE/PIB (300 mg/120 mg by mouth QD) to be used in this study is the proposed label-
recommended dose.  These doses have been administered to over 2,300 subjects in the registrational 
program, and have shown high SVR12 rates with a favorable safety profile.  The maximum dose of 
GLE/PIB will not exceed 300 mg/120 mg per day for up to 8 weeks.
Selection of Treatment Duration
Treatment duration was selected based on available data (SVR12 rates) from 12-week and 8-week 
treatment groups receiving GLE/PIB combinations (Studies M13-590, M15-464, M13-594, M13-583, and 
M14-868) in HCV GT1 – GT6-infected non-cirrhotic subjects as well as exposure-response modeling and 
simulations.  With robust antiviral activity demonstrated in in vitro and in vivo studies, the 8-week 
GLE/PIB 300 mg/120 mg combination is predicted to be optimal across HCV non-cirrhotic, treatment-
naïve GT1 – GT6-infected subjects.  
5 STUDY ACTIVITIES
5.1 Eligibility Criteria
Subjects must meet all of the following criteria in order to be included in the study.  Anything other than 
a positive response to the statements below will result in exclusion from study participation.

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If female, subject must be either post-menopausal, permanently surgically sterile (bilateral 
oophorectomy, bilateral salpingectomy or hysterectomy) or a woman of childbearing potential (WOCBP) 
and must practice at least one of the following methods of birth control, throughout the study including 
30 days after the last study drug dose is given.
!
Contraceptives and/or hormonal replacement therapies containing only progestins (such as 
those containing norethindrone, desogestrel, or levonorgestrel) or those containing progestins 
with non-ethinyl estradiol estrogens (e.g., esterified or conjugated) associated with inhibition of 
ovulation initiated at least 1 month prior to study Baseline Day 1.
!
Bilateral tubal occlusion/ligation.
!
Intrauterine device (IUD).
!
Intrauterine hormone-releasing system (IUS).
!
Vasectomized sexual partner(s) (the vasectomized partner(s) provided the vasectomized partner 
has received medical assessment of the surgical success and is the sole sexual partner of the 
trial participant).
•
Male or female condom with or without spermicide.
•
Cap, diaphragm or sponge with spermicide.
•
A combination of male condom with either cap, diaphragm or sponge with spermicide (double 
barrier method).
!
True abstinence:  Refraining from heterosexual intercourse when this is in line with the 
preferred and usual lifestyle of the subject (periodic abstinence [e.g., calendar, ovulation, 
symptothermal, post-ovulation methods] and withdrawal are not acceptable).
For male study subjects no contraception is required.
5.3 Prohibited Medications and Therapy
Subjects must be able to safely discontinue any prohibited medications or supplements listed in 
Section 5 at least 14 days or 10 half-lives (whichever is longer) prior to the first dose of any study drug 
and not use these during the entire Treatment Period and for 14 days following discontinuation of study 
drug.  Subjects must be consented for the study prior to discontinuing any prohibited medications for 
the purpose of meeting study eligibility.
Contraceptives and/or hormonal replacement therapies containing only progestins (such as those 
containing norethindrone, desogestrel, or levonorgestrel) or those containing progestins with non-
ethinyl estradiol estrogens (e.g., esterified or conjugated) may be used with GLE/PIB at the discretion of 
the Investigator.
5.4 Prior and Concomitant Therapy
The investigator should confirm that a concomitant medication/supplement can be safely administered 
with study drug.  Some medications may require dose adjustments due to the potential for DDIs.

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Any medication/supplement or vaccine (including over-the-counter or prescription medicines, vitamins 
and/or supplements) that the subject is receiving from the time of signing the consent through the 
Treatment Period and 30 days after study drug is stopped, must be recorded in the electronic case 
report form (eCRF) along with the reason for use, date(s) of administration including start and end 
dates, and dosage information including dose, route and frequency.  The investigator should review all 
concomitant medications for any potential drug-drug interactions.
During the Post-Treatment Period, all medications taken will be recorded until 30 days following the last 
dose of study drug.  After 30 days post-treatment, during the Post-Treatment Period, only antiviral 
therapies related to the treatment of HCV and medications prescribed in association with a SAE will be 
recorded in eCRF.  The AbbVie Primary Therapeutic Area Medical Director should be contacted if there 
are any questions regarding concomitant or prior therapies.
During the Post-Treatment Period, investigators should reassess concomitant medications/supplements 
and subjects may resume previously prohibited medications/supplements or revert to pre-study doses, 
14 days following discontinuation of study drug, if applicable.
Any questions regarding concomitant or prior therapy should be raised to the AbbVie Emergency 
Medical Contact.
Prior and Concomitant HIV-1 Therapy
If a subject is on an HIV-1 ART regimen, it must include at least 1 of the ARV agents defined in eligibility 
criterion 10.
Subjects will maintain the same dose and dosing interval of their HIV-1 ART regimen upon initiating the 
study drug regimen.
Subjects must remain on the same HIV-1 ART regimen for the entire Treatment Period.  Any change to 
an allowed HIV-1 ART regimen during the Treatment Period must be discussed with the AbbVie 
Therapeutic Area MD prior to the change, unless the change is being made to address an immediate 
safety concern.
Subjects receiving any other HIV-1 ART in addition to those listed in eligibility Criterion 10 would not be 
eligible for enrollment in the study.
5.5 Withdrawal of Subjects and Discontinuation of Study
A subject may voluntarily withdraw or be withdrawn from the study at any time for reasons including, 
but not limited to, the following: 
•
Clinically significant abnormal laboratory results or AEs, which rule out continuation of the study 
drug, as determined by the Investigator or the AbbVie Therapeutic Area Medical Director.
•
The Investigator believes it is in the best interest of the subject.
•
The subject requests withdrawal from the study.
•
Eligibility criteria violation was noted after the subject started study drug, when continuation of 
the study drug would place the subject at risk.

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•
Introduction of prohibited medications or dosages when continuation of the study drug would 
place the subject at risk.
•
The subject becomes pregnant while on study drug and the investigator, after discussion with 
the subject, concludes that the benefit of continuing therapy does NOT outweigh the risk.
•
Subject is significantly non-compliant with study procedures which would put the subject at risk 
for continued participation in the trial.
The following criteria will be considered evidence of HCV virologic failure for the purposes of subject 
management:
•
Confirmed increase from nadir in HCV RNA (defined as 2 consecutive HCV RNA measurement of 
> 1 log10 IU/mL above nadir) at any time point during study drug treatment.
or
•
Confirmed HCV RNA ≥ 100 IU/mL (defined as 2 consecutive HCV RNA measurements 
≥100 IU/mL) after HCV RNA < LLOQ during study drug treatment.
When confirmatory testing is required, it should be completed as soon as possible and the subject 
should remain on study drug treatment until the virologic failure criteria has been confirmed.  Subjects 
meeting the virologic failure criteria will be discontinued from study drug and will continue to be 
followed in the Post-Treatment Period for the emergence and persistence of resistant viral variants until 
12 weeks post-treatment.
For subjects to be considered lost to follow-up, reasonable attempts must be made to obtain 
information on the final status of the subject.  At a minimum (unless otherwise required by local 
regulations), 2 phone calls must be made and 1 certified letter must be sent and documented in the 
subject's source documentation. 
AbbVie may terminate this study prematurely, either in its entirety or at any site.  The Investigator may 
also stop the study at his/her site if he/she has safety concerns.  If AbbVie terminates the study for 
safety reasons, AbbVie will promptly notify the Investigator.
Refer to Section 6.2 for additional discontinuation criteria relating to Toxicity Management.
5.6 Follow-Up for Subject Withdrawal from Study
In order to minimize missing data for efficacy and safety assessments, subjects who prematurely 
discontinue study drug treatment should continue to be followed for all regularly scheduled visits, 
unless they have decided to discontinue the study participation entirely (withdrawal of informed 
consent).  Subjects should be advised on the continued scientific importance of their data even if they 
discontinue treatment with study drug early.
If, during the course of study drug administration, the subject prematurely discontinues (D/C), the 
procedures outlined for the applicable Premature D/C Visit should be completed.  Ideally this should 
occur on the day of study drug discontinuation, but no later than 2 days after their final dose of study 
drug and prior to the initiation of any other anti-HCV therapy.  However, these procedures should not 

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interfere with the initiation of any new treatments or therapeutic modalities that the investigator feels 
are necessary to treat the subject's condition.  Following discontinuation of study drug, the subject will 
be treated in accordance with the investigator's best clinical judgment.  All attempts must be made to 
determine the date of the last study drug dose and the primary reason for discontinuation of study drug 
or study participation.  The last dose of any study drug and reason for discontinuation will be recorded 
in the eCRF.  The subject should then begin the Post Treatment Period where the subject will be 
monitored for 12 weeks for HCV RNA, and the emergence and persistence of resistant viral variants.
If a subject is discontinued from study drug or the Post-Treatment Period with an ongoing adverse event 
or an unresolved laboratory result that is significantly outside of the reference range, the investigator 
will attempt to provide follow-up until a satisfactory clinical resolution of the laboratory result or 
adverse event is achieved.
5.7 Study Drug
Identity of Study Drug
Information about the study drug to be used in this study is presented in Table 1.
Table 1.
Identity of Study Drug
Study Drug 
Manufacturer
Mode of 
Administration
Dosage Form
Strength
Glecaprevir/pibrentasvir 
AbbVie
Oral
Film-coated tablet
100 mg/40 mg
Three tablets of GLE/PIB combination will be taken QD, beginning on Day 1 (baseline), and should be 
taken at approximately the same time each day.  The study drug must be taken with food. 
Glecaprevir/pibrentasvir combination tablets will be packaged in bottles with quantities sufficient to 
accommodate the study design.  Each kit label will contain a unique kit number.  This kit number which 
is assigned to a subject identifies the appropriate study drug to be dispensed at the subject's 
corresponding study visit.  Each kit will be labelled as required per country requirements.  Labels must 
remain affixed to the kits.  All blank spaces on the label will be completed by the site staff prior to 
dispensing to the subjects.
Subject will be instructed to return all drug containers (even if empty) to the study site personnel at 
each study visit.  The study site personnel will document compliance.
AbbVie will not supply drug other than GLE/PIB combination. 
5.8 Randomization/Drug Assignment
This is not applicable as this study is non-randomized/open label.

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5.9 Protocol Deviations
The Investigator is responsible for complying with all protocol requirements, written instructions and 
applicable laws regarding protocol deviations.  Protocol deviations are prohibited except when 
necessary to eliminate an immediate hazard to study subjects.  If a protocol deviation occurs (or is 
identified), the Investigator is responsible for notifying IEC/IRB, regulatory authorities (as applicable) and 
AbbVie.
6 SAFETY CONSIDERATIONS 
6.1 Complaints and Adverse Events
Complaints
A complaint is any written, electronic, or oral communication that alleges deficiencies related to the 
physical characteristics, identity, quality, purity, potency, durability, reliability, safety, effectiveness, or 
performance of a product.  Complaints associated with any component of this investigational product 
must be reported to the AbbVie.
Medical Complaints/Adverse Events and Serious Adverse Events
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with 
this treatment.  An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not the event is considered causally related to the use of the 
product.
An AE can result from use of the drug as stipulated in the protocol or labeling, as well as from accidental 
or intentional overdose, drug abuse, or drug withdrawal.  Any worsening of a pre-existing condition or 
illness is considered an AE.  Worsening in severity of a reported AE should be reported as a new AE.  
Laboratory abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, meets protocol specific 
criteria (see Section 6.2 regarding toxicity management) and/or if the investigator considers them to be 
AEs.
An elective surgery/procedure scheduled to occur during a study will not be considered an AE if the 
surgery/procedure is being performed for a pre-existing condition and the surgery/procedure has been 
pre-planned prior to study entry.  However, if the pre-existing condition deteriorates unexpectedly 
during the study (e.g., surgery performed earlier than planned), then the deterioration of the condition 
for which the elective surgery/procedure is being done will be considered an AE.
The investigators will monitor each subject for clinical and laboratory evidence of AEs on a routine basis 
throughout the study.  All AEs will be followed to a satisfactory conclusion.  
If an adverse event meets any of the following criteria, it is to be reported to AbbVie as a serious 
adverse event within 24 hours of the site being made aware of the serious adverse event:

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Grading System for Adverse Events (a semi-colon indicates 'or' within the description of the grade).
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.
Adverse Event Relationship to Study Drug
For the purpose of medical management, all AEs and laboratory abnormalities that occur during the 
study must be evaluated by the Investigator.  All AEs and laboratory abnormalities deemed "clinically 
significant" based on the medical judgment of the Investigator will be managed and followed to a 
satisfactory clinical resolution.  
The investigator will use the following definitions to assess the relationship of the adverse event to the 
use of study drug:
Reasonable Possibility – After consideration of factors including timing of the event, biologic plausibility, 
clinical judgment, and potential alternative causes, there is sufficient evidence (information) to suggest 
a causal relationship.
No Reasonable Possibility – After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is insufficient evidence 
(information) to suggest a causal relationship.
Pregnancy
While not an AE, pregnancy in a study subject must be reported to AbbVie within 1 working day of the 
site becoming aware of the pregnancy.  Information regarding a pregnancy occurring up to 30 days after 
end of treatment in a study subject and the outcome of the pregnancy will be collected.
The medical outcome for either mother or infant, meeting any serious criteria including an elective or 
spontaneous abortion, stillbirth, or congenital anomaly is considered an SAE and must be reported to 
AbbVie within 24 hours of the site becoming aware of the event.
In the event that a positive result is obtained on a pregnancy test for a subject or a subject reports 
becoming pregnant during the Treatment Period, the administration of study drug may be continued at 
the Principal Investigator's discretion after discussion with the subject, if the benefit of continuing study 

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drug is felt to outweigh the potential risk.  If a subject is discontinued, the subject will be monitored for 
SVR in the Post-Treatment Period.
6.2 Toxicity Management
The management of specific AEs and laboratory parameters is described below and in the Operations 
Manual.  This includes the following laboratory abnormalities: 
If a subject experiences a post-baseline increase in ALT to > 5 × ULN which is also > 2 × baseline 
value, the subject should have a confirmatory ALT measurement performed.
If, the ALT increase is confirmed to be > 5 × ULN which is also > 2 × baseline value, the 
recommendations below should be followed:
!
Complete hepatic questionnaire.
!
Evaluate for alternate etiology of ALT elevation; document in the source, update the 
medical history and concomitant medications eCRF (if applicable), and obtain Anti-hepatitis 
A virus immunoglobulin M (HAV IgM), Anti-hepatitis A virus total (HAV Total), Anti-HBc IgM, 
Anti-HBc Total, Anti-HBs, HBV DNA, HBsAg, Anti-hepatitis E virus immunoglobulin M (HEV 
IgM), Anti-hepatitis E virus immunoglobulin G (HEV IgG) and HEV RNA, and other additional 
tests, as appropriate. 
!
Manage the subject as medically appropriate.
!
Repeat ALT, AST, total and fractionated bilirubin, alkaline phosphatase and international 
normalized ratio (INR) within 1 week.  Repeat liver chemistries as indicated until resolution.
Discontinue study drug if any of the following is observed at any time:
•
ALT level is ≥ 20 × ULN in the absence of an alternate etiology.
•
Increasing direct bilirubin or INR or onset of symptoms/signs of hepatitis.
•
At the discretion of the investigator.
Alternate management of ALT increases is permitted with approval of the AbbVie Therapeutic Area 
Medical Director.
6.3 Product Complaint
A Product Complaint is any complaint related to the biologic or drug component of the product. 
For a product this may include, but is not limited to, damaged/broken product or packaging, product 
appearance whose color/markings do not match the labeling, labeling discrepancies/inadequacies in the 
labeling/instructions (example: printing illegible), missing components/product, or packaging issues.
Product Complaints concerning the investigational product must be reported to AbbVie within 24 hours 
of the study site's knowledge of the event.  Product Complaints occurring during the study will be 
followed up to a satisfactory conclusion.

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7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
Complete and specific details of the statistical analysis will be described and fully documented in the 
Statistical Analysis Plan (SAP).  The SAP will be finalized prior to the database lock.  The statistical 
analyses will be performed using a statistical analysis system (SAS) (SAS Institute Inc., Cary, NC, USA).
7.2 Definition for Analysis Populations
The Intention-to-Treat (ITT) population includes all enrolled subjects who received at least 1 dose of 
study drug.  The ITT population will be used for all secondary and exploratory efficacy analyses as well as 
for baseline analyses.
The mITT population includes all enrolled subjects who received at least 1 dose of study drug, excluding 
subjects who did not achieve SVR12 for reasons other than virologic failure.  The mITT population will be 
used for the primary efficacy analysis. 
The Safety Analysis Set consists of all subjects who received at least 1 dose of study drug. 
7.3 Statistical Analyses
Primary Analysis
The primary efficacy endpoint is the percentage of subjects who achieve SVR12 (HCV RNA < LLOQ 
12 weeks after the last actual dose of study drug) across genotypes in adults with HCV GT1 – GT6.  The 
primary endpoint will be analyzed based on mITT population. 
The secondary efficacy endpoints of SVR12, on-treatment virologic failure, and post-treatment relapse 
will be analyzed across genotypes in adults with HCV GT1 – GT6 based on ITT population.
For the analysis of post-treatment HCV virologic relapse, completion of treatment is defined as any 
subject with study drug duration of 52 days or greater. 
The number and percentage of subjects achieving SVR12 will be summarized along with a two-sided 95% 
confidence interval using the normal approximation to the binomial distribution, unless the number of 
subjects who fail to achieve SVR12 is less than 5, where the Wilson's score method will be used for the 
confidence interval instead.  A summary of reason for SVR12 non-response (e.g., on-treatment virologic 
failure, relapse, other) will be provided.
The efficacy of 8-week treatment duration for subjects with APRI ≤ 1 based on mITT population will be 
established if the lower boundary of two-sided 95% confidence interval for the percentage of subjects 
achieving SVR12 is greater than 92.4% among HCV GT1 – GT6 subjects. 

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The efficacy of 8-week treatment duration for subjects with APRI ≤ 1 based on ITT population will be 
established if the lower boundary of two-sided 95% confidence interval for the percentage of subjects 
achieving SVR12 is greater than 91.4% among HCV GT1- GT6 subjects.
In order to control the Type I error rate, a fixed sequence testing procedure will be used for the SVR12
endpoints.  Only if success has been demonstrated for the primary endpoint of SVR12 based on mITT 
population, will the testing proceed to the first secondary endpoint of SVR12 based on ITT population. 
The multiplicity controlled efficacy endpoints will be tested sequentially in the following order:
1.
Efficacy of the 8-week treatment duration based on mITT population:  If this endpoint is 
statistically significant, then proceed to the following efficacy endpoint.  If this endpoint is 
not statistically significant then stop the testing procedure and declare that no endpoints in 
the study met statistical significance.  
2.
Efficacy of the 8-week treatment duration based on ITT population:  If this endpoint is 
statistically significant, then declare the SVR12 endpoint is statistically significant for both 
mITT and ITT populations.  If not, then announce that SVR12 endpoint is statistically 
significant only for mITT population.
For on-treatment virologic failure and post-treatment relapse, the number and percentage of subjects 
will be summarized along with a two-sided 95% confidence interval using Wilson's score method.
Further details on the primary and other efficacy analyses are provided in the SAP.
Sample Size Estimation
It is planned to enroll approximately 230 adult subjects with chronic HCV GT1 – GT6 infection with APRI 
≤ 1 who are HCV treatment-naïve in the study.  The enrollment will be monitored to have approximately 
maximum 46 GT3-infected subjects (20% of total subjects).
With approximately 230 GT1 – GT6 infected subjects (with 46 GT3 subjects) in mITT analysis, this study 
has approximately 90% power to demonstrate efficacy of the 8-week treatment in terms of SVR12 rate 
(i.e., a two-sided 95% lower confidence bound above 92.4%), assuming that 98% of the GT1, GT2, GT4, 
GT5, and GT6-infected subjects with APRI ≤ 1 and 94% of the GT3-infected subjects with APRI ≤ 1 
achieve SVR12.
With 230 GT1 – GT6 infected subjects (with 46 GT3 subjects) in ITT analysis, this study has approximately 
83% power to demonstrate efficacy of the 8-week treatment in terms of SVR12 rate (i.e., a two-sided 
95% lower confidence bound above 91.4%), assuming that 97% of the GT1, GT2, GT4, GT5, and 
GT6-infected subjects with APRI ≤ 1 and 93% of the GT3-infected subjects with APRI ≤ 1 achieve SVR12.
Efficacy for the 8-week regimen in this study is established by demonstrating similarity to the historical 
control regimen of GLE/PIB administered for 8 weeks in treatment-naïve subjects without cirrhosis.  The 
SVR12 rate of the historical control regimen is calculated, and a threshold is determined by subtracting a 
non-inferiority margin of 6% from the historical SVR12 rate.  Efficacy is established if the lower 95% 
confidence boundary of the SVR12 rate in the 8-week regimen is greater than the threshold.  Efficacy for 
the 8-week regimen in this study is established by demonstrating the lower boundary of 95% CI for 
SVR12 rate is higher than a cut off value (92.4% and 91.4% for mITT and ITT population, respectively).

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In the registrational studies, different SVR12 rates based on mITT population have been observed among 
GT3- and non-GT3-infected treatment-naïve subjects without cirrhosis assigned to 8 weeks of GLE/PIB 
treatment.  In these studies, approximately 98.9% and 96.2% SVR12 has been observed among non-
cirrhotic, treatment naïve chronic HCV GT1, GT2, GT4, GT5, and GT6-infected subjects and GT3 subjects, 
respectively.11-13  Hence, for the non-cirrhotic GT1 – GT6-infected subjects, based on mITT population, 
the historical SVR12 rate of 98.4% is estimated based on a weighted average of 80% GT1, GT2, GT4, GT5, 
and GT6 historical rate and 20% GT3 historical rate.  To establish cut off for efficacy based on mITT 
population, a margin of 6% is applied to the historical control rate of 98.4%, resulting in a threshold of 
92.4%.
Historical SVR12 rate based on ITT population depends on the non-virologic failure in a study.  Study-to-
study variability has been observed in non-virologic failure rates, and is typically around 1%.  The 
observed rate of non-virologic failure in the registrational program is 1.2% (29/2369).11-13  For this 
reason, this study assumes that the historical SVR12 rate based on ITT population for treatment naïve 
non-cirrhotic subjects is 97.4% (with 1% non virologic failure).  To establish cut off for efficacy based on 
ITT population, a margin of 6% is applied to the historical control rate of 97.4%, resulting in a threshold 
of 91.4%.
8 ETHICS
8.1 Independent Ethics Committee/Institutional Review Board 
(IEC/IRB)
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IEC/IRB for review and approval.  Approval of both the protocol and the consent form 
must be obtained before any participant is enrolled.  Any amendment to the protocol will require review 
and approval by the IEC/IRB before the changes are implemented to the study.  In addition, all changes 
to the consent form will be IEC/IRB approved. 
8.2 Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, Operations Manual, International 
Conference for 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 Investigator are specified in Appendix B. 
8.3 Subject Confidentiality
To protect subjects' confidentiality, all subjects and their associated samples will be assigned numerical 
study identifiers or "codes."  No identifiable information will be provided to AbbVie. 

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9 SOURCE DOCUMENTS AND CASE REPORT FORM 
COMPLETION
The Investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported.  All source documents should be attributable, legible, contemporaneous, original, 
accurate, and complete to ensure accurate interpretation of data.  Clinical site monitoring is conducted 
to ensure that the rights and well-being of human subjects are protected, that the reported trial data 
are accurate, complete, and verifiable, and that the conduct of the trial is in compliance with the 
currently approved protocol, ICH Good Clinical Practice (GCP), and applicable local regulatory 
requirement(s).
10 DATA QUALITY ASSURANCE
AbbVie will ensure that the clinical trial is conducted with a quality management system that will define 
quality tolerance limits in order to ensure human subject protection and reliability of study results.  Data 
will be generated, documented and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements. 
11 COMPLETION OF THE STUDY
The end-of-study is defined as the date of the last subject's last visit.
12 REFERENCES
1.
Mohd Hanafiah K, Groeger J, Flaxman AD, et al.  Global epidemiology of hepatitis C virus 
infection:  new estimates of age-specific antibody to HCV seroprevalence.  Hepatology.  
2013;57(4):1333-42.
2.
Zhang J, Nguyen D, Hu KQ.  Chronic hepatitis c virus infection:  a review of current direct-
acting antiviral treatment strategies.  N Am J Med Sci (Boston).  2016;9(2):47-54.
3.
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):509-516.
4.
American Association for the Study of Liver Diseases.  Hepatitis C guidance:  AASLD-IDSA 
recommendations for testing, managing, and treating hepatitis C.  Available at:  
http://www.hcvguidelines.org.  Updated:  24 February 2016.  Changes made:  
10 March 2016.
5.
World Health Organization.  Guidelines for the screening care and treatment of persons with 
chronic hepatitis C infection.  Updated version, April 2016.  Available at:  www.who.int.  
Accessed on:  01 December 2016.
6.
Chou R, Wasson N.  Blood tests to diagnose fibrosis or cirrhosis in patients with chronic 
hepatitis C virus infection:  a systematic review.  Ann Intern Med.  2013;158(11):807-20.

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7.
Hepatitis C Virus Infection Consensus Statement Working Group.  Australian 
recommendations for the management of hepatitis C virus infection:  a consensus 
statement 2016.  Melbourne:  Gastroenterological Society of Australia, 2016.
8.
AbbVie.  Glecaprevir/pibrentasvir Investigator's Brochure Edition 2.  06 September 2016.
9.
AbbVie.  Glecaprevir/pibrentasvir Investigator's Brochure Edition 2 Addendum 1.  
November 2016.
10.
Wyles D, Poordad F, Wang S, et al.  SURVEYOR-II, part 3:  efficacy and safety of 
glecaprevir/pibrentasvir (ABT-493/ABT-530) in patients with hepatitis C virus genotype 3 
infection with prior treatment experience and/or cirrhosis.  Hepatology.  
2016;64 (Suppl 1):62A.
11.
Zeuzem S, Feld J, Wang S, et al.  ENDURANCE-1:  a phase 3 evaluation of the efficacy and 
safety of 8- versus 12-week treatment with glecaprevir/pibrentasvir (formerly 
ABT-493/ABT-530) in HCV genotype 1 infected patients with or without HIV-1 co-infection 
and without cirrhosis.  Hepatology.  2016;64 (Suppl 1):132A.
12.
Hassanein T, Wyles D, Wang S, et al.  Glecaprevir/Pibrentasvir demonstrates high SVR rates 
in patients with HCV genotype 2, 4, 5, or 6 infection without cirrhosis following an 8-week 
treatment duration (SURVEYOR-II, Part 4).  Hepatology.  2016;64 (Suppl 6):1128A.
13.
Foster G, Gane E, Asatryan A, et al.  ENDURANCE-3:  safety and efficacy of 
glecaprevir/pibrentasvir compared to sofosbuvir plus daclatasvir in treatment-naïve HCV 
genotype 3-infected patients without cirrhosis.  J Hepatol.  2017;66 (Suppl 1):S33.
14.
European Association of the liver, Asociacion Latinoamericana para el Estudio del Higado.  
EASL-ALEH Clinical Practice Guidelines:  Non-invasive tests for evaluation of liver disease 
severity and prognosis.  J Hepatol.  2015;63:237-64.
15.
US Dept. of Health and Human Services.  Common Terminology Criteria for Adverse Events 
(CTCAE) Version 4.0.  28 May 2009.  Available from:  
https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf.

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APPENDIX A. STUDY SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
Ab
Antibody
ADL
Activities of daily living
AE
Adverse event
ALT
Alanine aminotransferase
APRI
Aminotransferase/platelet ratio index
ART
Anti-retroviral treatment
ARV
Anti-retroviral
AST
Aspartate aminotransferase
BID
Twice daily
CRF
Case report form
CTCAE
Common Terminology Criteria For Adverse Events
DAA
Direct-acting antiviral agent
D/C
Discontinuation
DDI
Drug-drug interaction
DNA
Deoxyribonucleic acid
ECG
Electrocardiogram
eCRF
Electronic case report form
FIB-4
Fibrosis-4
FSH
Follicle stimulating hormone
GCP
Good Clinical Practice
GLE
Glecaprevir
GT
Genotype
HAV
Hepatitis A virus
HAV IgM
Hepatitis A virus immunoglobulin M
HBc
Hepatitis B core
HBs
Hepatitis B surface
HBsAg
Hepatitis B surface antigen
HBV
Hepatitis B virus
HCC
Hepatocellular carcinoma
HCV
Hepatitis C virus

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HEV
Hepatitis E virus
HEV IgG
Hepatitis E virus immunoglobulin G
HEV IgM
Hepatitis E virus immunoglobulin M
HIV
Human immunodeficiency virus
HIV-1
Human immunodeficiency virus type 1
ICH
International Conference for Harmonization
IEC
Independent ethics committee
IgG
Immunoglobulin G
IgM
Immunoglobulin M
IMP
Investigational Medical Product
INR
International normalized ratio
IRB
Institutional Review Board
ITT
Intention-to-Treat
IU
International units
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
kPa
kilopascal
L
Liter
LLN
Lower limit of normal
LLOQ
Lower limit of quantification
mITT
Modified Intention-to-Treat
mL
Milliliter
mm
Millimeter
N(t)RTI
Nucleoside/nucleotide reverse transcriptase inhibitor
NS
Nonstructural
NS3
Nonstructural viral protein 3
NS4A
Nonstructural viral protein 4A
NS5A
Nonstructural viral protein 5A
PI
Protease inhibitor
PIB
Pibrentasvir
PO
By mouth
PRO
Patient Reported Outcomes
PT
Post-Treatment
QD
Once daily

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RBV
Ribavirin
RNA
Ribonucleic acid
SAE
Serious adverse event
SAP
Statistical analysis plan
SAS
Statistical Analysis System
SUSAR
Suspected Unexpected Serious Adverse Reaction
SVR12
Sustained virologic response 12 weeks post dosing
TAF
Tenofovir alafenamide
TDF
Tenofovir disoproxil fumarate
ULN
Upper limit of normal
WHO
World Health Organization
Wk
Week
WOCBP
Woman of childbearing potential

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APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol M16-133:  Chronic HCV Genotype 1 – 6:  Glecaprevir/Pibrentasvir Once Daily Therapy in 
Subjects with APRI ≤ 1
Protocol Date:  31 July 2017
Clinical research studies sponsored by AbbVie are subject to the International Conference for
Harmonisation (ICH) Good Clinical Practices (GCP) and local regulations and guidelines governing the 
study at the site location.  In signing the Investigator Agreement, the investigator is agreeing to the 
following:
1.
Conducting the study in accordance with ICH GCP, the applicable regulatory requirements, current 
protocol and Operations Manual, and making changes to a protocol only after notifying AbbVie 
and the appropriate Institutional Review Board (IRB)/Independent Ethics Committee (IEC), except 
when necessary to protect the subject from immediate harm.
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., IEC or IRB) review and approval of the protocol and its amendments.
4.
Reporting complaints that occur in the course of the investigation(s) to AbbVie.
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 protocol and all of its amendments.
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. Providing direct access to source data documents for study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s).
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)

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APPENDIX C. LIST OF PROTOCOL SIGNATORIES
Name
Title
Functional Area
Protocol Author, Medical 
Writing
TA MD
Medical Affairs
Statistics
Clinical Pharmacology
Bioanalysis
CPD

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APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF 
CHANGES
Previous Protocol Versions
Protocol
Date
Version 1.0
25 May 2017
The purpose of this Amendment is to correct minor clerical errors for consistency throughout the 
protocol in addition to the following:
1.
Provide clarification as to what dose of rosuvastatin can be taken with GLE/PIB.
!
Updated Section 5, Study Activities to change the allowed concomitant rosuvastatin
dose from 10 mg to 5 mg based upon the anticipated European Union Summary of 
Product Characteristics label recommendation under Subsection 5.1, Eligibility Criteria, 
Concomitant Medications.
2.
Provide clarification and additional information regarding contraception use during the study.
!
Updated Section 5, Study Activities to add Subsection 5.2, Contraception Recommendations.
3.
Provide definition of serious adverse event, adverse event severity grade, and assessments for 
relationship of adverse event to study drug.
!
Updated Section 6, Safety Considerations to add regulatory definition of serious adverse 
events under subsection Medical Complaints/Adverse Events and Serious Adverse Events.
!
Updated Section 6, Safety Considerations to add definition of adverse event severity grade 
under subsection Adverse Event Definition of Severity Grade.
!
Updated Section 6, Safety Considerations to add the definition of reasonable possibility and 
no reasonable possibility under the subsection Adverse Event Severity and Relationship to 
Study Drug.
4.
Provided clarification on the timing to report a serious adverse event
!
Updated Section 6, Safety Considerations, under subsection Medical Complaints/Adverse
Events and Serious Adverse Events, to add the requirement by the Investigator to report a 
serious adverse event to the Sponsor within 24 hours of becoming aware of a serious 
adverse event.
5.
Provide clarification around the risk-based monitoring approach
!
Updated Section 6, Safety Considerations, under subsection Medical Complaints/Adverse 
Events and Serious Adverse Events, to add the statement that adverse events will be 
monitored throughout the study to identify any which may indicate a risk to subjects.

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!
Updated Section 10, Data Quality Assurance, to add statement regarding the use of a quality 
management system to define quality tolerance limits.
6.
Provide clarification on what vital sign measurements will be measured during each Treatment 
and Post-Treatment Follow-up Visit.
!
Updated Appendix D, Activity Schedule to include a list of what vital signs will be measured:  
systolic and diastolic blood pressure, pulse, and body temperature.
7.
Provide clarification that HIV-1 RNA and flow cytometry will be performed at Post-treatment 
Week 4 Visit as well as the Screening Visit.
!
Updated Appendix D, Activity Schedule to add HIV-1 RNA and flow cytometry to the Post-
Treatment Week 4 Visit study activities.