Conditions: Hepatitis C Virus (HCV)
Keywords: Chronic Hepatitis C Virus (HCV) Genotype 1 to 6 Asian non-cirrhotic Human Immunodeficiency Virus co-infection Treatment-naïve Treatment-experienced interferon
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 546
Healthy volunteers: no

Brief summary:
This study will evaluate the efficacy and safety of glecaprevir/pibrentasvir (ABT-493/ABT-530) in non-cirrhotic chronic hepatitis C virus (HCV) genotype (GT)1 to GT6-infected Asian participants with or without human immunodeficiency virus (HIV) co-infection who are HCV treatment-naïve or treatment-experienced with interferon (IFN) with or without ribavirin (RBV), OR sofosbuvir with RBV with or without IFN.

Detailed description:
Randomization was stratified by geographic region (China, South Korea, Singapore), genotype (GT1, GT2, combined GT3 - 6), and HCV/HIV co-infection status (co-infected, not co-infected). In China, eligible participants were randomized to Arm A or Arm B (defined below) in the following ratios: 2:1 for GT1, 2:1 for GT2, and 2:1 for combined GT3-6. In South Korea and Singapore, eligible participants were randomized to Arm A or Arm B in the following ratios: 2:1 for GT1 and 2:1 for GT2.

All Primary and Secondary Outcome Measures were pre-specified to be analyzed only in Arm A.

Arms:
arm 1: Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 or 16 weeks during the double-blind (DB) treatment period.

Participants received treatment for 8 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks. arm 2: Participants received placebo to glecaprevir/pibrentasvir for 8 or 16 weeks during the DB treatment period followed by glecaprevir/pibrentasvir (300 mg/120 mg) once daily for 8 or 16 weeks during the open-label (OL) treatment period.

In each period participants received treatment for 8 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks.

Interventions: intervention 1: Placebo intervention 2: Glecaprevir/Pibrentasvir
Intervention descriptions: intervention 1: Matching placebo tablet for oral administration intervention 2: Coformulated tablet for oral administration

Protocol document:
Prot_001.pdf: 
ABT-493, ABT-530
M15-592 Protocol
1
1.0
Title Page
Clinical Study Protocol M15-592
A Randomized, Double-Blind, Placebo-Controlled, 
Multicenter Study to Evaluate the Efficacy and 
Safety of ABT-493/ABT-530 in Treatment-Naïve and 
Treatment-Experienced, Non-Cirrhotic Asian Adults 
with Chronic Hepatitis C Virus Genotype (GT) 1 to 
GT6 Infection With or Without Human 
Immunodeficiency Virus Co-Infection
AbbVie Investigational
  Product:
ABT-493, ABT-530
Date:
03 April 2017
Development Phase:
3
Study Design:
This is a randomized, double-blind, placebo-controlled study.
Investigators:
Multicenter.  Investigator information is on file at AbbVie.
Sponsor:
AbbVie Inc. (AbbVie)*
Sponsor/Emergency 
  Contact:
* The specific contact details of the AbbVie legal/regulatory entity (person) within the relevant country are 
provided within the clinical trial agreement with the Investigator/Institution and in the Clinical Trial 
Application with the Competent Authority.
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other 
applicable regulatory requirements, including the archiving of essential documents.
Confidential Information
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
NCT03222583


ABT-493, ABT-530
M15-592 Protocol
2
1.1
Synopsis
AbbVie Inc.
Protocol Number:  M15-592
Name of Study Drug:  ABT-493/ABT-530 
Phase of Development:  3
Name of Active Ingredient:  ABT-493/ABT-530
Date of Protocol Synopsis:  03 April 2017
Protocol Title:  A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the 
Efficacy and Safety of ABT-493/ABT-530 in Treatment-Naïve and Treatment-Experienced, 
Non-Cirrhotic Asian Adults with Chronic Hepatitis C Virus Genotype (GT) 1 to GT6 Infection With or 
Without Human Immunodeficiency Virus Co-Infection
Objectives:
The primary objectives of this study are to compare, among the combined group of GT1 to GT6-infected 
subjects, among the GT1-infected subjects, and among the GT2-infected subjects, the percentage of 
subjects achieving SVR12, (HCV RNA < lower limit of quantification [LLOQ] 12 weeks after the last 
actual dose of study drug) to a historical SVR12 rate and to assess the safety following 8 or 16 weeks of 
treatment with the ABT-493/ABT-530 combination regimen in treatment-naïve and treatment-
experienced non-cirrhotic adults with chronic hepatitis C virus (HCV) GT1 to GT6 infection with or 
without human immunodeficiency virus (HIV) co-infection.
The secondary objectives are to assess the percentage of subjects with on-treatment HCV virologic 
failure, the percentage of subjects with post-treatment relapse of HCV infection and the percentage of 
HCV/HIV co-infected subjects achieving SVR12.
An additional objective is to assess the pharmacokinetics of ABT-493 and ABT-530 in Asian HCV-
infected adults.
Investigators:  Multicenter
Study Sites:  Approximately 50 sites
Study Population:
Chronic HCV GT1, 2, 3, 4, 5 or 6-infected Asian male and female adults aged 18 years or older, without 
cirrhosis, with or without HIV co-infection who are HCV treatment-naïve or treatment-experienced to 
interferon (IFN) (alpha, beta or pegylated interferon [pegIFN]) with or without ribavirin (RBV) OR 
sofosbuvir with RBV with or without IFN.
Number of Subjects to be Enrolled:  Approximately 504 subjects
Methodology:
This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the 
efficacy, safety and pharmacokinetics of ABT-493/ABT-530 in non-cirrhotic chronic HCV GT1 to 
GT6-infected Asian adult subjects with or without HIV co-infection who are HCV treatment-naïve or 
HCV treatment-experienced with IFN (alpha, beta or pegIFN) with or without RBV OR sofosbuvir with 
RBV with or without IFN.


ABT-493, ABT-530
M15-592 Protocol
3
Methodology (Continued):
Approximately 504 subjects meeting the eligibility criteria will be enrolled.  A minimum of 
150 GT1-infected subjects, a minimum of 150 GT2-infected subjects and approximately 60 GT3, 4, 5 or 
6-infected subjects from China will be enrolled into this study.  Approximately 105 GT1-infected 
subjects and approximately 39 GT2-infected subjects will also be enrolled into this study from the 
regional Asian countries of South Korea and Singapore.  Of the approximately 504 subjects, a maximum 
of 50 HCV/HIV co-infected subjects will be enrolled. 
In China, subjects will be randomized to receive active treatment (Arm A) or placebo (Arm B) in a 
2:1 ratio for each of the GT1 and GT2-infected groups and the combined GT3 to GT6-infected groups.  
In each regional Asian country, each of the GT1 and GT2-infected groups will be randomized in a 
2:1 ratio to Arm A or Arm B.
Arm A:
ABT-493/ABT-530 300 mg/120 mg for 8 or 16 weeks
Arm B:
Matching Placebo for 8 or 16 weeks followed by open-label ABT-493/ABT-530 
300 mg/120 mg QD for 8 or 16 weeks
This study will consist of three periods:
Double-Blind (DB) Treatment Period:  Eligible subjects will be randomized to receive 
ABT-493/ABT-530 300 mg/120 mg once daily (QD) (Arm A) or placebo QD (Arm B) for 8 or 
16 weeks.
Treatment duration will differ among subjects based on HCV GT and HCV treatment experience 
(8 weeks of treatment for GT1, 2, 3, 4, 5 and 6-infected subjects with the exception of 16 weeks for 
treatment-experienced GT3-infected subjects).
Scheduled visits in the DB Treatment Period for subjects assigned to receive 16 weeks of treatment will 
consist of Day 1 and Weeks 1, 2, 4, 8, 12, and 16; for subjects assigned to receive 8 weeks of treatment, 
scheduled visits will consist of Day 1 and Weeks 1, 2, 4 and 8.
AbbVie, investigators and subjects will be blinded to drug assignment, HCV virologic results and 
specific safety laboratory results for the duration of the DB Treatment Period.  HCV virologic results 
will be reviewed and individual HCV virologic failure criteria will be applied to those subjects 
randomized to active drugs by an un-blinded independent reviewer.  Upon reaching the end of the DB 
period or premature discontinuation of study drugs, subjects, investigators and AbbVie will be un-
blinded to drug assignment for each subject.  Subjects randomized to active drugs will enter the Post-
Treatment (PT) Period; subjects randomized to placebo will enter the Open-label (OL) Treatment Period.
Subjects randomized to placebo who prematurely discontinue placebo during the DB Treatment Period 
will be eligible for open-label treatment at the final scheduled DB visit (Week 8 or Week 16) and not at 
the time of discontinuation of placebo.
Open-Label (OL) Treatment Period:  Subjects who are randomized to the placebo arm during the DB 
Treatment Period (Arm B) will receive open-label ABT-493/ABT-530 300 mg/120 mg QD for either 8 
or 16 weeks in the OL Treatment Period.
Treatment duration will differ among subjects based on HCV GT and HCV treatment experience
(8 weeks of treatment for GT1, 2, 3, 4, 5 and 6-infected subjects with the exception of 16 weeks for 
treatment-experienced GT3-infected subjects).


ABT-493, ABT-530
M15-592 Protocol
4
Methodology (Continued):
In the OL Treatment Period, visits will occur at Weeks 1, 2, 4, 8, 12, and 16 for subjects assigned to 
receive 16 weeks of treatment; for subjects assigned to receive 8 weeks of treatment, scheduled visits 
will occur at Weeks 1, 2, 4 and 8.  OL Day 1 will be the day after the final scheduled DB visit (Week 8 
or Week 16) and subjects will not return for a visit; rather, the subjects will be instructed to take their 
first dose of ABT-493/ABT-530 at home.  Study procedures, including assessment of adverse events, 
vital signs, adherence, concomitant medications, HCV RNA, HCV resistance, HIV-1 RNA and HIV 
resistance (as applicable), pharmacokinetic assays, and clinical laboratory tests will be conducted at each 
visit.
Post-Treatment (PT) Period:  Subjects randomized to active drug (Arm A) who complete or prematurely 
discontinue study drug during the DB Treatment Period and subjects randomized to placebo (Arm B) 
who complete the OL Treatment Period or prematurely discontinue study drug during the OL Treatment 
Period, will be followed for 24 weeks to monitor safety and to evaluate efficacy and the emergence 
and/or persistence of HCV resistance-associated substitutions (RASs).  
Baseline HCV resistance samples will be collected for all subjects, but HCV resistance analysis of 
baseline and post-baseline samples will be performed only for subjects who experience virologic failure.
During the PT Period, all subjects will have visits at Weeks 4, 12, and 24 following completion of either 
the DB Treatment Period (for subjects randomized to ABT-493/ABT-530 in the DB Treatment Period) 
or the OL Treatment Period (for subjects randomized to placebo in the DB Treatment Period).  Study 
procedures to monitor safety, HCV RNA, HIV-1 RNA and HIV resistance (as applicable), and the 
emergence and/or persistence of HCV resistance-associated substitutions will be conducted during these 
visits.
Diagnosis and Main Criteria for Inclusion/Exclusion:
Main Inclusion:
1.
Male or female of Asian descent and at least 18 years of age at time of Screening.
2.
If female, subject must be either (as defined in section 5.2.4 of the protocol) postmenopausal, OR 
permanently surgically sterile OR for Women of Childbearing Potential practicing at least one 
protocol specified method of birth control, starting at Study Day 1 (or earlier) through at least 
30 days after the last dose of study drug.
3.
Females of childbearing potential must have a negative serum pregnancy test result at Screening, 
and a negative urine pregnancy test at Study Day 1.
Females of non-childbearing potential (either postmenopausal or permanently surgically sterile as 
defined in the protocol) at Screening do not require pregnancy testing.
4.
Screening laboratory result indicating HCV GT1, 2, 3, 4, 5 or 6-infection.
5.
Subject has positive HCV antibody (Ab) and plasma HCV RNA viral load ≥ 1000 IU/mL at 
Screening Visit.
6.
Chronic HCV infection defined as one of the following:
!
Positive for HCV Ab or HCV RNA at least 6 months before Screening; 
!
A liver biopsy consistent with chronic HCV infection.
7.
Subject must be HCV treatment-naïve (i.e., subject has not received any approved or investigational 
HCV treatment) or treatment-experienced (i.e., subject has failed prior HCV treatment with IFN 
[alpha, beta or pegIFN] with or without RBV OR sofosbuvir with RBV with or without IFN).  
Previous HCV treatment must have been completed ≥ 8 weeks prior to screening.


ABT-493, ABT-530
M15-592 Protocol
5
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Inclusion (Continued):
8.
Body Mass Index (BMI) is ≥ 18.0 kg/m2 at the time of Screening.  BMI is calculated as weight 
measured in kilograms (kg) divided by the square of height measured in meters (m).
9.
Subject must be documented as non-cirrhotic, defined as meeting one of the following criteria:
!
A liver biopsy within 24 months prior to or during screening demonstrating the absence of 
cirrhosis, e.g., a METAVIR, Batts-Ludwig, Knodell, IASL, Scheuer, or Laennec fibrosis score 
of ≤ 3, Ishak fibrosis score of ≤ 4; or
!
A FibroScan® score of < 12.5 kPa within 6 months of Screening or during the Screening Period; 
or
o
Subjects with indeterminate FibroScan® score (12.5 ≤ score < 14.6), must have a 
qualifying liver biopsy.
!
A screening FibroTest score of ≤ 0.48 and Aspartate Aminotransferase to Platelet Ratio Index 
(APRI) < 1.
o
Subjects with indeterminate FibroTest (0.48 < result < 0.75), or conflicting FibroTest 
and APRI results (e.g., FibroTest ≤ 0.48, but APRI ≥ 1) must have a qualifying liver 
FibroScan® or biopsy.
10. Must voluntarily sign and date an informed consent form, approved by an Institutional Review 
Board (IRB)/Independent Ethics Committee (IEC) prior to the initiation of any screening or study 
specific procedures.
11. Subjects must be able to understand and adhere to the study visit schedule and all other protocol 
requirements.
In addition to Inclusion Criteria 1 through 11, subjects enrolled with HCV GT1 to 6 and HIV-1 co-
infection, must also meet the following criteria per local standard practice:
12. Positive test result for Human Immunodeficiency Virus antibody (HIV Ab) at Screening.
13. Naïve to treatment with any antiretroviral therapy (ART) (and have no plans to initiate ART 
treatment while participating in this study) 
or
On a stable, qualifying HIV-1 ART regimen (allowed regimens will be based on AbbVie approval) 
for at least 8 weeks prior to screening.
14. Subjects naïve to ART must have CD4+ count ≥ 500 cells/mm3 (or CD4+ % ≥ 29%) at Screening.
15. Subjects on stable ART must have the following:
!
CD4+ count ≥ 200 cells/mm3 (or CD4+ % ≥ 14%) at Screening; and
!
Plasma HIV-1 RNA below LLOQ by an approved plasma HIV-1 RNA quantitative assay 
(including but not limited to Roche COBAS® Ampliprep/COBAS® Taqman HIV-1 Test, v 2.0) 
at Screening and at least once during the 12 months prior to Screening.
Main Exclusion:
1.
Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the 
study or for approximately 30 days after the last dose of study drug.
2.
Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that 
could preclude adherence to the protocol in the opinion of the investigator.


ABT-493, ABT-530
M15-592 Protocol
6
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion (Continued):
3.
Positive test result at Screening for hepatitis B surface antigen (HBsAg) or hepatitis B virus (HBV) 
DNA > LLOQ if HBsAg is negative.
4.
HCV genotype performed during screening indicating co-infection with more than one HCV 
genotype.
5.
Requirement for and inability to safely discontinue contraindicated medications or supplements at 
least 2 weeks or 10 half-lives (whichever is longer) prior to the first dose of any study drug.
6.
Clinically significant abnormalities, other than HCV infection or HCV/HIV co-infection, based 
upon the results of a medical history, physical examination, vital signs, laboratory profile, and a 
12-lead electrocardiogram (ECG) that make the subject an unsuitable candidate for this study in the 
opinion of the investigator, including, but not limited to:
!
Uncontrolled diabetes as defined by a glycated hemoglobin (hemoglobin A1C) level > 8.5% at 
the Screening Visit.
!
Active or suspected malignancy or history of malignancy (other than basal cell skin cancer or 
cervical carcinoma in situ) in the past 5 years.
!
Uncontrolled cardiac, respiratory, gastrointestinal, hematologic, neurologic, psychiatric, or 
other medical disease or disorder, which is unrelated to the existing HCV infection.
7.
Any cause of liver disease other than chronic HCV-infection, including but not limited to the 
following:
!
Hemochromatosis
!
Alpha-1 antitrypsin deficiency
!
Wilson's disease
!
Autoimmune hepatitis
!
Alcoholic liver disease
!
Steatohepatitis on liver biopsy considered to be the primary cause of the liver disease rather 
than concomitant/incidental with HCV infection
8.
Screening laboratory analyses showing any of the following abnormal laboratory results:
!
ALT > 10 × upper limit of normal (ULN)
!
AST > 10 × ULN
!
Estimated Glomerular filtration rate adjusted for the Chinese population (eGFR) 
< 50 mL/min/1.73 m2 as estimated by the MDRD method, modified for the Chinese population 
(C-MDRD), according to the following formula:
eGFR = 175 × (Serum Creatinine)–1 234 × (Age)–0 179 × (0.79 if Female)
!
Direct bilirubin > ULN
!
Albumin < lower limit of normal (LLN)
!
International normalized ratio (INR) > 1.5 × ULN, unless subject has known hemophilia or is 
on a stable anticoagulant regimen affecting INR
!
Hemoglobin < 11 g/dL for women; < 12 g/dL for men
!
Platelets < 90,000 cells per mm3
!
Absolute neutrophil count (ANC) < 1000 cells/μL


ABT-493, ABT-530
M15-592 Protocol
7
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion (Continued):
9.
History of solid organ transplantation.
10. Receipt of any investigational product within a time period equal to 10 half-lives of the product, if 
known, or a minimum of 6 weeks (whichever is longer) prior to study drug administration.
11. Any current or past clinical evidence of decompensated liver disease such as ascites noted on 
physical exam, use of diuretics for ascites, hepatic encephalopathy or esophageal variceal bleeding.
12. Requirement for chronic use of systemic immunosuppressants including, but not limited to, 
corticosteroids (prednisone equivalent of > 10 mg/day for > 2 weeks), azathioprine, or monoclonal 
antibodies (e.g., infliximab).
13. Chronic human immunodeficiency virus, type 2 (HIV-2) infection.
14. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to 
receive ABT-493/ABT-530.
15. History of severe, life-threatening or other significant sensitivity to any excipients of the study 
drugs.
16. Patients who can't participate in study per local law.
Additional Exclusion Criteria for Subjects with HCV/HIV Co-Infection:
17. For subjects on stable ART, taking anti-retroviral agent(s) other than those permitted based on 
AbbVie approval.
18. Treatment for an AIDS-associated opportunistic infection (OI) within 12 months of Screening or 
prophylaxis for an AIDS-associated opportunistic infection within 6 months of Screening.
19. Diagnosis of any clinical AIDS-defining event within 12 months prior to Screening.  A list of these 
events may be found in Appendix D of the protocol.
Investigational Products:
ABT-493/ABT-530 100 mg/40 mg Film-coated tablet or matching 
placebo
Doses
ABT-493/ABT-530 300 mg/120 mg QD (3 tablets)
Mode of Administration:
Oral
Duration of Treatment:
Subjects will receive ABT-493/ABT-530 or matching placebo for 8 or 16 weeks.  Subjects assigned to 
receive placebo will be treated for 8 or 16 weeks with ABT-493/ABT-530 after being administered 
matching placebo for 8 or 16 weeks.  Treatment duration will differ among subjects based on HCV GT 
and treatment experience (8 weeks of treatment for treatment-naïve and treatment-experienced GT1, 2, 
3, 4, 5 and 6-infected subjects with the exception of 16 weeks for treatment-experienced 
GT3-infected subjects).
Criteria for Evaluation:
Efficacy:
Plasma HCV RNA (IU/mL) will be assessed at each DB, OL and Post-Treatment Visit.
Safety:
Safety and tolerability will be assessed by monitoring adverse events, physical examinations, clinical 
laboratory tests, 12-Lead ECGs, and vital signs.


ABT-493, ABT-530
M15-592 Protocol
8
Criteria for Evaluation (Continued):
Patient Reported Outcomes (PROs):
Health state utility will be measured using the EuroQol-5-Dimensions-3 Level (EQ-5D-3L) instrument.  
The Fatigue Severity Scale (FSS) will be used to measure the severity of fatigue and its effect on 
lifestyle and activities.
Resistance:
For subjects receiving active study drugs who experience virologic failure, the following HCV resistance 
information will be tabulated and summarized:  1) HCV amino acid variants at baseline at signature 
resistance-associated positions relative to the appropriate prototypic reference sequence; 2)  HCV amino 
variants at signature resistance-associated positions relative to the appropriate prototypic reference 
sequence in available post-baseline samples; and 3) HCV amino acid variants relative to the baseline 
sequence in available post-baseline samples.
HIV-1 drug resistance genotyping for protease, reverse transcriptase and integrase sequences may be 
performed for protocol-defined eligible specimens.
Pharmacokinetic:
Individual plasma concentrations of ABT-493 and ABT-530, and possible metabolites of ABT-493 and 
ABT-530 will be tabulated and summarized.  Values for pharmacokinetic parameters of ABT-493, 
ABT-530 and possible metabolites of ABT-493 and ABT-530 including apparent clearance (CL/F) and 
apparent volume of distribution (V/F) will be estimated using population pharmacokinetic modeling 
procedures. 
Plasma concentrations of HIV-1 ARTs for individual subjects, or a group of subjects or for the entire 
study may be analyzed based on safety, HCV RNA and/or plasma HIV-1 RNA results.
Statistical Methods:
The primary analysis will occur after all Arm A subjects have completed the Post-Treatment (PT) 
Week 12 Visit or prematurely discontinued the study.  The primary analysis will summarize data through 
PT Week 12 for Arm A subjects and data through the DB Treatment Period for Arm B subjects.  The 
data for the primary analysis will be locked after data cleaning, and data collected after this lock will be 
added to a new version of the database.  An interim analysis will occur after all Arm A subjects have 
completed the PT Week 24 Visit or prematurely discontinued the study and all Arm B subjects have 
completed the PT Week 12 Visit or prematurely discontinued the study.  The data for the interim 
analysis will be locked after data cleaning.  Data collected after this lock will be added to a new version 
of the database which will be cleaned and locked at the end of the study.
Efficacy:
The primary efficacy endpoint variable is SVR12 (HCV RNA < LLOQ 12 weeks after the last actual 
dose of study drug) for the subjects treated with ABT-493/ABT-530 in the DB Treatment Period 
(Arm A).  In order to control the Type I error rate, a fixed sequence testing procedure will be used for 
the ranked primary efficacy endpoints.  Only if success has been demonstrated for the first primary 
endpoint will the testing proceed to the second primary endpoint.  Similarly, only if success has been 
demonstrated for the second primary endpoint will the testing proceed to the third primary endpoint.


ABT-493, ABT-530
M15-592 Protocol
9
Statistical Methods (Continued):
Efficacy (Continued):
The three ranked primary efficacy endpoints are:
1.
The percentage of Arm A subjects from the combined group of GT1 to 6-infected subjects 
achieving SVR12.  The percentage of these subjects with SVR12 will be non-inferior to the historical 
SVR12 rate of 96% if the lower confidence bound (LCB) of the 2-sided 95% confidence interval 
(CI) for the percentage is > 90%.
2.
The percentage of Arm A subjects from the group of GT1-infected subjects achieving SVR12.  The 
percentage of these subjects with SVR12 will be non-inferior to the historical SVR12 rate of 97% if 
the LCB of the 2-sided 95% CI for the percentage is > 91%.
3.
The percentage of Arm A subjects from the group of GT2-infected subjects achieving SVR12.  The 
percentage of these subjects with SVR12 will be non-inferior to the historical SVR12 rate of 95% if 
the LCB of the 2-sided 95% CI for the percentage is > 89%. 
The normal approximation to the binomial distribution will be used to calculate each CI unless the rate 
for the primary endpoint is 100%, in which case the Wilson's score method will be used for the 
calculation of the CI.
The secondary efficacy endpoints are:
!
The percentage of Arm A subjects with on-treatment HCV virologic failure (defined as 
confirmed increase of > 1 log10 IU/mL above nadir during treatment, confirmed HCV RNA 
≥100 IU/mL after HCV RNA < LLOQ during treatment, or HCV RNA ≥ LLOQ at the end of 
treatment with at least 6 weeks of treatment), and 
!
The percentage of Arm A subjects with post-treatment relapse of HCV infection (defined as 
confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after the last dose of 
study drug among subjects who completed treatment as planned with HCV RNA < LLOQ at 
the end of treatment, excluding re-infection), and
!
The percentages of Arm A HCV/HIV co-infected subjects achieving SVR12.
For the secondary endpoints, the number and percentage of Arm A subjects will be presented along with
95% Wilson score CIs.  These endpoints will be summarized for the combined group of GT1 to 
6-infected Arm A subjects, the group of GT1-infected Arm A subjects, and the group of GT2-infected 
Arm A subjects.
Additional efficacy endpoints include:  SVR4, SVR24, and the percentage of subjects who relapsed after 
achieving SVR12.


ABT-493, ABT-530
M15-592 Protocol
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Statistical Methods (Continued):
Safety:
All subjects who receive at least one dose of study drug will be included in the safety analyses.  Safety 
summaries will be provided for each treatment arm during the DB Treatment Period and for Arm B 
during the OL Treatment Period; comparisons will be made between treatment arms in the DB 
Treatment Period.  Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA).  The number and percentage of subjects with treatment-emergent adverse events (i.e., any 
event that begins or worsens in severity after initiation of study drug) will be tabulated by primary 
System Organ Class (SOC) and MedDRA preferred term.  The tabulation of the number of subjects with 
treatment-emergent adverse events also will be provided by grade and relationship to study drug.  
Change from baseline in laboratory tests and vital signs measurements to each time point of collection 
will be summarized, and values that meet toxicity grades (laboratory tests only) or are potentially 
clinically significant, according to predefined criteria, will be summarized.
PROs:
Changes from baseline in the patient reported outcome (PRO) measures at each visit will be summarized 
for each treatment arm; changes from baseline during the DB Treatment Period will be compared 
between treatment arms using ANCOVA models with a treatment group factor and the baseline score as 
a covariate.
Resistance:
For all subjects receiving active study drugs who experience HCV virologic failure, the HCV amino acid 
variants at signature resistance-associated positions in NS3 and NS5A at baseline identified by 
population or deep sequencing and comparison to the appropriate prototypic reference sequence will be 
analyzed.
The following resistance information will be analyzed for subjects receiving active study drugs who 
experience HCV virologic failure and who have an available post-baseline sample with HCV RNA 
≥1000 IU/mL:  1) the HCV amino acid variants in NS3 and NS5A identified by population or deep 
sequencing and comparison to the baseline sequence, 2) the HCV amino acid variants at signature 
resistance-associated positions in NS3 and NS5A identified by population or deep sequencing and
comparison to the appropriate prototypic reference sequence, and 3) the persistence of HCV viral amino 
acid variants in NS3 and NS5A by population or deep sequencing.
If any subject on stable HIV-1 ART develops a confirmed, quantifiable plasma HIV-1 RNA level 
(HIV-1 RNA ≥ 200 at one assessment and ≥ 500 copies/mL on repeat testing) after starting the study, the 
HIV-1 protease, reverse transcriptase, and integrase sequences may be analyzed.
Pharmacokinetic:
For all subjects who receive active study drug, individual plasma concentration of ABT-493, ABT-530, 
and possible metabolites of ABT-493 and ABT-530 will be tabulated and summarized for each visit.  
Additional summaries and analyses of concentration data may be performed if appropriate and useful in 
the interpretation of the data.  Population pharmacokinetic analyses will be performed using the actual 
sampling time relative to dosing.  Pharmacokinetic models will be built using a non-linear mixed-effects 
modeling approach.


ABT-493, ABT-530
M15-592 Protocol
11
1.2
List of Abbreviations and Definition of Terms
Abbreviations
Ab
Antibody
AE
Adverse event
ALT
Alanine aminotransferase
ANC
Absolute neutrophil count
ANCOVA
Analysis of covariance
ANOVA
Analysis of variance
APRI
Aminotransferase to platelet ratio index
aPTT
Activated partial thromboplastin time 
AST
Aspartate aminotransferase
ART
Antiretroviral therapy
AUC
Area Under the Concentration Curve
BMI
Body mass index
BUN
Blood urea nitrogen
CI
Confidence interval 
CL/F
Apparent Oral Clearance
CPK
Creatine phosphokinase
CR/CL
Creatinine clearance
CRF
Case report form
DAA
Direct-acting antiviral agent
DB
Double-blind
DDI
Drug-drug interaction
DNA 
Deoxyribonucleic acid
D/C
Discontinuation
EC
Ethics Committee
ECG
Electrocardiogram
eCRF
Electronic case report form
EDC
Electronic data capture
EOT
End of treatment
EQ-5D-3L
EuroQol 5 Dimensions 3 Levels Health State Instrument
EU
European Union
FSS
Fatigue Severity Scale


ABT-493, ABT-530
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GCP
Good Clinical Practice
GGT
Gamma-glutamyl transferase
GT
Genotype
HBsAg
Hepatitis B surface antigen
HBV
Hepatitis B Virus
hCG
Human Chorionic Gonadotropin
HCV
Hepatitis C virus
HCV Ab
Hepatitis C virus antibody
Hemoglobin A1c
Glycated hemoglobin
HIV
Human immunodeficiency virus
HIV Ab
Human immunodeficiency virus antibody
ICH
International Conference on Harmonization
IEC
Independent ethics committee
IFN
Interferon
IL28B
Interleukin 28B
INR
International normalized ratio
IRB
Institutional Review Board
IRT
Interactive Response Technology
IU
International units
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
LCB
Lower confidence bound
LLN
Lower limit of normal
LLOQ
Lower limit of quantification
MedDRA
Medical Dictionary for Regulatory Activities
NONMEM
Non-linear mixed-effect modeling
NS3A
Nonstructural viral protein 3A
NS4A
Nonstructural viral protein 4A
NS5A
Nonstructural viral protein 5A
NS5B
Nonstructural viral protein 5B
OATP
Organic anion transporting polypeptide
OL
Open-label
PegIFN
Pegylated-interferon alfa-2a or alfa-2b
PegIFN/RBV
Combination of pegylated-interferon alfa-2a or alfa-2b and ribavirin


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PI
Protease Inhibitor
PK
Pharmacokinetic
PR
pegIFN/RBV
PRO
Patient Reported Outcome
PT
Post-Treatment
QD
Once daily
RBC
Red blood cells
RBV
Ribavirin
RNA
Ribonucleic acid
SAE
Serious adverse event
SAS
Statistical Analysis System
SD
Standard Deviation
SF-36v2
Short Form 36-Version 2 Health Status Survey
SGOT
Serum glutamic oxaloacetic transaminase
SGPT
Serum glutamic pyruvic transaminase
SOC
System Organ Class/Standard of Care
SUSAR
Suspected Unexpected Serious Adverse Reaction 
SVR
Sustained virologic response
SVR4
Sustained virologic response 4 weeks post dosing
SVR12
Sustained virologic response 12 weeks post dosing
SVR24
Sustained virologic response 24 weeks post dosing
TDF
Tenofovir disoproxil fumarate
TE-PRS
Treatment-experienced with regimens containing interferon, pegylated interferon, 
ribavirin, and/or sofosbuvir
ULN
Upper limit of normal
US
United States
VAS
Visual Analog Scale
V/F
Apparent Volume of distribution
WBC
White blood cells
WOCBP
Women of child-bearing potential


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Pharmacokinetic and Statistical Abbreviations
AUC
Area under the plasma concentration-time curve
AUC24
AUC for the 24-hour dosing interval
β
Apparent terminal phase elimination rate constant
CL/F
Apparent oral plasma clearance
Cmax
Maximum observed plasma concentration
Ctrough
Pre-dose trough plasma concentration
t1/2
Terminal phase elimination half-life
Tmax
Time to maximum observed plasma concentration (Cmax)
Definition of Terms
Study Drug
ABT-493 and ABT-530
Study Day 1
First day of study drug (active or placebo) dosing 
Treatment Period
Day 1 through last dose of study drug
DB Treatment Period
Double-Blind Treatment Period
OL Treatment Period
Open-Label Treatment Period
Post-Treatment Period
Day after the last dose of study drug through Post-Treatment Week 24 or 
Post-Treatment Discontinuation


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2.0
Table of Contents
1.0
Title Page ...............................................................................1
1.1
Synopsis................................................................................................. 2
1.2
List of Abbreviations and Definition of Terms...................................... 11
2.0
Table of Contents ................................................................ 15
3.0
Introduction......................................................................... 20
3.1
Differences Statement .......................................................................... 33
3.2
Benefits and Risks................................................................................ 33
4.0
Study Objective ................................................................... 34
4.1
Primary Objective ................................................................................ 34
4.2
Secondary Objective............................................................................. 34
5.0
Investigational Plan.............................................................35
5.1
Overall Study Design and Plan:  Description ........................................ 35
5.1.1
Screening ............................................................................................. 37
5.1.1.1
Rescreening.......................................................................................... 37
5.1.2
Double-Blind Treatment Period............................................................ 38
5.1.3
Open-Label Treatment Period............................................................... 40
5.1.4
Post-Treatment Period.......................................................................... 41
5.2
Selection of Study Population............................................................... 41
5.2.1
Inclusion Criteria.................................................................................. 41
5.2.2
Exclusion Criteria................................................................................. 44
5.2.3
Prior and Concomitant Therapy............................................................ 47
5.2.3.1
Prior HCV Therapy .............................................................................. 48
5.2.3.2
Prior and Concomitant HIV-1 Therapy................................................. 49
5.2.3.3
Concomitant Therapy........................................................................... 50
5.2.3.4
Prohibited Therapy............................................................................... 50
5.2.4
Contraception Recommendations ......................................................... 52
5.3
Efficacy, Pharmacokinetic, Pharmacogenetic and Safety 
Assessments/Variables ......................................................................... 54
5.3.1
Efficacy and Safety Measurements Assessed and Flow Chart ............... 54
5.3.1.1
Study Procedures.................................................................................. 54
5.3.1.2
Meals and Dietary Requirements.......................................................... 63


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5.3.1.3
Blood Samples for Pharmacogenetic Analysis ...................................... 63
5.3.2
Drug Concentration Measurements....................................................... 64
5.3.2.1
Collection of Samples for Analysis....................................................... 64
5.3.2.2
Handling/Processing of Samples........................................................... 65
5.3.2.3
Disposition of Samples......................................................................... 65
5.3.2.4
Measurement Methods ......................................................................... 66
5.3.3
Efficacy Variables................................................................................ 66
5.3.3.1
Primary Variable .................................................................................. 66
5.3.3.2
Secondary Variables............................................................................. 67
5.3.4
HCV Resistance Variables.................................................................... 67
5.3.5
HIV Resistance Variables..................................................................... 67
5.3.6
Safety Variables ................................................................................... 67
5.3.7
Pharmacokinetic Variables ................................................................... 68
5.3.8
Pharmacogenetic Variables................................................................... 68
5.4
Removal of Subjects from Therapy or Assessment ............................... 69
5.4.1
Discontinuation of Individual Subjects ................................................. 69
5.4.1.1
HCV Virologic Stopping Criteria ......................................................... 70
5.4.1.2
Failure to Maintain HIV Virologic Suppression.................................... 71
5.4.2
Discontinuation of Entire Study............................................................ 72
5.5
Treatments ........................................................................................... 73
5.5.1
Treatments Administered...................................................................... 73
5.5.2
Identity of Investigational Product........................................................ 74
5.5.2.1
Packaging and Labeling........................................................................ 74
5.5.2.2
Storage and Disposition of Study Drug................................................. 75
5.5.3
Method of Assigning Subjects to Treatment Groups ............................. 75
5.5.4
Selection and Timing of Dose for Each Subject.................................... 75
5.5.5
Blinding ............................................................................................... 76
5.5.5.1
Blinding of Investigational Product ...................................................... 77
5.5.6
Treatment Compliance ......................................................................... 77
5.5.7
Drug Accountability ............................................................................. 78
5.6
Discussion and Justification of Study Design........................................ 79
5.6.1
Discussion of Study Design and Choice of Control Groups .................. 79
5.6.2
Appropriateness of Measurements........................................................ 85


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5.6.3
Suitability of Subject Population .......................................................... 86
5.6.4
Selection of Doses in the Study ............................................................ 86
5.6.4.1
Rationale for Dose Selections............................................................... 86
5.6.4.1.1
ABT-493 and ABT-530 Doses ............................................................. 86
5.6.4.2
Rationale for Duration Selections ......................................................... 89
5.6.4.3
Risk of Development of Resistance Mutations During 
Combination DAA Trials ..................................................................... 90
6.0
Complaints........................................................................... 91
6.1
Medical Complaints ............................................................................. 91
6.1.1
Definitions ........................................................................................... 92
6.1.1.1
Adverse Event...................................................................................... 92
6.1.1.2
Serious Adverse Events........................................................................ 92
6.1.2
Adverse Event Severity ........................................................................ 94
6.1.3
Relationship to Study Drug................................................................... 94
6.1.4
Adverse Event Collection Period.......................................................... 95
6.1.5
Adverse Event Reporting...................................................................... 96
6.1.6
Pregnancy............................................................................................. 97
6.1.7
Toxicity Management........................................................................... 98
6.1.7.1
Management of Increases in ALT......................................................... 98
6.1.8
Collection of Data Regarding Known AIDS-Associated 
Opportunistic Infections ....................................................................... 99
6.2
Product Complaint................................................................................ 99
6.2.1
Definition............................................................................................. 99
6.2.2
Reporting ............................................................................................100
7.0
Protocol Deviations ........................................................... 100
8.0
Statistical Methods and Determination of Sample 
Size ..................................................................................... 101
8.1
Statistical and Analytical Plans............................................................101
8.1.1
Demographics .....................................................................................103
8.1.2
Efficacy...............................................................................................104
8.1.2.1
Primary Efficacy Endpoint ..................................................................104
8.1.2.2
Secondary Efficacy Endpoints.............................................................105
8.1.2.3
Sensitivity Analysis.............................................................................106


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8.1.2.4
Subgroup Analysis ..............................................................................107
8.1.2.5
Additional Efficacy Endpoints.............................................................109
8.1.3
Patient Reported Outcomes .................................................................110
8.1.4
HCV and HIV Resistance Analyses.....................................................111
8.1.5
Safety..................................................................................................113
8.1.5.1
Adverse Events....................................................................................114
8.1.5.2
Clinical Laboratory Data .....................................................................115
8.1.5.3
HIV-1 RNA Data ................................................................................116
8.1.5.4
Vital Signs Data ..................................................................................116
8.1.6
Pharmacokinetic and Exposure-Response Analyses.............................116
8.2
Determination of Sample Size .............................................................119
8.2.1
Justification of Success Criteria for Primary Endpoints........................122
8.3
Randomization Methods......................................................................124
9.0
Ethics.................................................................................. 124
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) ........................................................................................124
9.2
Ethical Conduct of the Study...............................................................125
9.3
Subject Information and Consent.........................................................125
10.0
Source Documents and Case Report Form 
Completion ........................................................................ 126
10.1
Source Documents...............................................................................126
10.2
Case Report Forms..............................................................................126
11.0
Data Quality Assurance .................................................... 127
12.0
Use of Information ............................................................ 128
13.0
Completion of the Study ................................................... 128
14.0
Investigator's Agreement.................................................. 130
15.0
Reference List.................................................................... 131
List of Tables
Table 1.
Prohibited Medications and Supplements ............................................. 51
Table 2.
Clinical Laboratory Tests ..................................................................... 57
Table 3.
Identity of Investigational Products ...................................................... 74


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Table 4.
Overview of Clinical Studies by Subject Population (Phase 2 and 
3 Analysis Set) ..................................................................................... 81
Table 5.
Summary of SVR12, On-Treatment Virologic Failure, and Post-
Treatment Relapse in TN and TE Non-GT3-Infected Subjects by 
Cirrhosis Status (TN + TE-PRS Subjects, Phase 2 and 3 Analysis 
Set)....................................................................................................... 82
Table 6.
SVR12 Rates by Prior Treatment Experience, HCV Genotype, and 
Duration for Non-GT3 Infected Subjects (ITT Population, Phase 2 
and 3 Analysis Set)............................................................................... 83
Table 7.
Summary of SVR12, On-Treatment Virologic Failure, and Post-
Treatment Relapse in TN and TE GT3-Infected Subjects by 
Cirrhosis Status and Treatment Duration (ITT Population, Phase 2 
and 3 Analysis Set)............................................................................... 84
Table 8.
Recommended Treatment Duration for Subjects Without 
Cirrhosis............................................................................................... 85
Table 9.
Summary of Approximate Subject Numbers Expected by 
Subpopulation .....................................................................................121
Table 10.
Historical Data for SOF + RBV for 12 Weeks, GT2-Infected 
Non-Cirrhotic Patients.........................................................................122
Table 11.
SVR12 Rates for Calculation of Historical and Expected SVR12
Rates ...................................................................................................124
List of Figures
Figure 1.
HCV Genotypes Distributions in China ................................................ 22
Figure 2.
Study Schematic................................................................................... 36
Figure 3.
Adverse Event Collection..................................................................... 96
List of Appendices
Appendix A.
Responsibilities of the Clinical Investigator.........................................134
Appendix B.
List of Protocol Signatories .................................................................136
Appendix C.
Study Activities...................................................................................137
Appendix D.
List of AIDS-Associated Opportunistic Infections ...............................144


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3.0
Introduction
Hepatitis C viral (HCV) infection is a global health problem, with over 
184 million individuals infected worldwide.1  There are 7 identified HCV genotypes, with 
genotype (GT) 1 being the most prevalent worldwide.  HCV GTs 2 and 3 infections are 
more common in Latin America (5% to 30%), Europe (20% to 40%) and Asia (30% to 
45%).2-4  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  GT7 has recently been described in 
Central Africa.7
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
In Asia, sub-genotypes 1b, 2a, 2b, 3a, and GT6 are the most common causes of HCV 
infections.3  The frequency of HCV infection in China varies by geographical region 
within the country, age, and population groups.  In a report in 2007, the national 
prevalence in adults was estimated to be 1% to 1.9% (ranging from 0.29% to 9.6% in 
various geographic areas).3  The most common HCV GTs in China are GT1 (67%) and 
GT2 (14%).3
Epidemiology of HCV in China
Chronic HCV infection is recognized as an important cause of chronic hepatitis, cirrhosis, 
and hepatocellular carcinoma in China.9  Epidemiological studies in the mid-1990s 
reported a national prevalence of 3.2%,10 but other reports suggested a prevalence ranging 
from 0.29% to 9.6%.11


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These studies showed that the frequency of HCV infection in China varied by 
geographical region within the country, age, and population groups and also between rural 
and metropolitan areas.  With the Yangtze River as the boundary, the prevalence rate in 
northern China (3.6%) was higher than southern China (2.9%).10  Anti-HCV positive rates 
were reported to increase gradually with age, from 2% in 1 year old to 3.9% in 50 to 
59 year old groups, respectively.10  A study of individuals > 55 years old in the rural 
Henan province found a prevalence of 9.6%,12 while Liu et al, documented a prevalence 
of 0.9% in persons 25 to 65 years old in Anyang.13
In 2006, the National Nutritional Survey estimated that the overall national prevalence is 
approximately 0.43%, which represents approximately 5.1 million Chinese infected with 
HCV.14  A recent study reported that 25 million Chinese were infected with HCV 
chronically and advanced liver diseases were frequently detected.15  Among human 
immunodeficiency virus (HIV)-positive Chinese patients, it is estimated that 60% to 90% 
are co-infected with HCV.14  Among patients with chronic hepatitis B, it is estimated that 
11% to 15% are co-infected with HCV.16,17  In addition, 50% of the patients receiving 
dialysis in China are reported to be infected with HCV.14  Together, these data suggest 
that a significant number of Chinese patients are at risk for the morbidity and mortality 
associated with HCV infection.
An important epidemiologic feature of HCV infections in China is the distribution of GTs 
(Figure 1).  HCV sub-genotype 1b is the most common GT in China with a prevalence of 
66%,18 but it has been reported to be as high as 90% in some areas of southern China.14  
HCV GT2 is the second most common GT, with a prevalence of 14%,18 increasing 
gradually from southern to northern China (Figure 1).14
Other HCV GTs include GT6, which is detected in approximately 10% of cases, 
especially in the south region of China; and GT3 which is reported in approximately 4.3% 
of the cases in China.18  Majority of these chronic HCV-infected patients in China have 
IL28B CC genotype.15


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Figure 1.
HCV Genotypes Distributions in China
In summary, the current epidemiology data indicate that HCV infections are an important 
public health problem in China and that the most prevalent GTs in the general population 
countrywide are HCV sub-genotype 1b and GT2.  HCV GT3 and 6 are detected in the 
southern region of China, but their frequency is reported to be increasing in recent years.
HCV-Infection Treatment Options
Until recently, in most countries, treatment of HCV GT1 infection employed a single 
direct-acting antiviral agent (DAA) plus pegylated interferon and ribavirin (PR).  
However, interferon (IFN)-based treatment regimens are associated with considerable, 
often treatment limiting toxicities (fever, chills, rigor, fatigue, depression, and anemia).19
An oral fixed-dose combination of sofosbuvir and ledipasvir (NS5A inhibitor) was 
approved in the United States (US) and Europe for the treatment of GT1 and GT4 HCV 


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infection for non-cirrhotic and cirrhotic patients.20  The combination achieves SVR12 of 
94% – 96% in treatment-naïve GT1 patients with and without cirrhosis and rates of 93% 
in HCV GT4 infected patients with or without cirrhosis.  In addition, an IFN-free 
combination of ombitasvir (NS5A inhibitor), paritaprevir (protease inhibitor), dasabuvir 
(non-nucleoside NS5b polymerase inhibitor) and ritonavir, given with or without ribavirin 
(RBV), was also approved in the US and Europe for the treatment of chronic HCV GT121
and the dual combination of ombitasvir and paritaprevir/ritonavir with RBV is approved 
for treatment of non-cirrhotic GT4 infection in the US21 and for both cirrhotic and non-
cirrhotic GT4 infected patients in the EU.22  When given for 12 weeks, the dual regimen 
with RBV achieves 100% SVR12 (sustained virologic response 12 weeks post dosing) 
rates in the HCV GT4 infected patients without cirrhosis23 and 96% to 100% SVR 
(sustained virologic response) rates in those with cirrhosis when given for 12 or 16 weeks 
respectively.24
Although IFN-free therapies are available for the treatment of GT2 and GT3 infection 
using sofosbuvir plus RBV,25 SVR rates were lower for PR-treatment experienced with or 
without cirrhosis.25
Daclatasvir, an NS5A inhibitor, to be used in combination with sofosbuvir, has been 
approved in the US for treatment of GT3 HCV infection.  However, SVR was found to be 
substantially reduced in patients with compensated cirrhosis.26
The current standard of care for the treatment of chronic HCV infection in China is 
pegylated interferon (pegIFN) combined with RBV for 24 weeks to 72 weeks, depending 
upon the patient's HCV GT, disease status, and response to past treatment(s).  SVR rates 
range from 60% to 75% among GT1b-infected patients and 75% to 85% among primarily 
GT2-, GT3-, and GT6-infected patients;27,28 however, the pegIFN/RBV regimen has a 
well-described burden of toxicity (e.g., severe cytopenia and depression) and cumbersome 
weekly injections, in addition to a long duration of treatment.  Many patients requiring 
treatment are ineligible, and frequently toxicity is treatment limiting.  Treatment of 
chronic HCV in China could be significantly improved with the availability of a 
pangenotypic, all-oral, pegIFN-free regimen that has a higher SVR rate, a better safety 


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profile, and shorter treatment durations.  To this end, AbbVie is developing ABT-530, a 
next generation NS5A inhibitor, and ABT-493, a next generation protease inhibitor (PI),
to be used in combination with each other for the treatment of chronic HCV.
ABT-493
ABT-493 is an NS3/4A PI with potent, and pangenotypic activity.  It demonstrates a high 
genetic barrier to resistance and maintains activity against common variants that emerge 
following exposure to first generation PIs.
A detailed discussion of the preclinical pharmacology and toxicology, in vitro virology 
and metabolism, and clinical data can be found in the Investigator's Brochure.29
ABT-530
ABT-530 is an NS5A inhibitor with potent, and pangenotypic activity.  It demonstrates a 
high genetic barrier to resistance and maintains activity against all common single 
nucleotide change resistance-associated substitutions 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 substitutions.  A detailed discussion of 
the preclinical pharmacology and toxicology, in vitro virology and metabolism, and 
clinical data can be found in the current Investigator's Brochure.30
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, depending on the concentrations tested.31
ABT-493 and ABT-530 combination has been well tolerated when administered to over 
590 healthy volunteers in Phase 1 studies (including Japanese and Han Chinese subjects 
living in the United States).  In addition, 166 subjects were exposed to ABT-493 
monotherapy and 198 subjects were exposed to ABT-530 monotherapy in Phase 2 studies.  
When ABT-493 was given in combination with ABT-530 in healthy volunteers, ABT-493 
exposures were not significantly changed by ABT-530 (≤ 31% difference); however, the 


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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).
The combination of ABT-493 and ABT-530 has also been evaluated in overseas Han 
Chinese subjects at various dose combination levels (ABT-493 + ABT-530:  100 mg + 
120 mg, 200 mg + 120 mg, 300 mg + 120 mg, 200 mg + 80 mg, and 700 mg + 160 mg) in 
Studies M14-066 and M15-432.  Results from these 2 studies showed no observed ethnic 
differences for ABT-493 and ABT-530 at doses evaluated.
The safety profile of coadministered ABT-493 and ABT-530 in healthy volunteers in 
these studies is consistent with that of the individual compounds.
For a more detailed discussion of drug-drug interaction studies please refer to the 
Investigator's Brochures for respective compounds.29,30
ABT-493 + ABT-530 Combination in HCV-Infected Subjects
Data from Global Phase 2b studies demonstrated robust efficacy results for 300 mg 
ABT-493 in combination with 120 mg ABT-530 across HCV GTs with favorable safety 
profiles in HCV-infected subjects.  Thus, this dose combination was proposed for the 
Phase 3 clinical program studies. 
Phase 3 dose and treatment durations for the planned Phase 3 studies were based on 
available SVR4 and SVR12 data from ABT-493 and ABT-530 combination Phase 2b 
studies (Studies M14-867 and M14-868 (Parts 1 and 2)) and exposure-response modeling 
and simulations of antiviral activity.  Based on the results from the Phase 2b studies, 
Studies M14-867 and M14-868 (Parts 1 and 2), the 300 mg dose of the ABT-493 and 
120 mg dose of ABT-530 in combination was proposed for global registrational studies.  
This dose had been demonstrated to be efficacious for the proposed Phase 3 study 
populations with the planned study durations and would reduce chances of virologic 
failures across GTs and difficult-to-treat patient populations to maximize the chance for 
SVR.  Importantly, ABT-493 and ABT-530 regimens including the proposed 
300 mg/120 mg ABT-493/ABT-530 QD regimen had been well-tolerated and safe across 


ABT-493, ABT-530
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all Phase 2b study arms including cirrhotic subjects.  All ABT-493 and ABT-530 doses 
studied had a similar safety profile.  The 300 mg ABT-493 and 120 mg ABT-530 dose 
were also supported by the exposure-response analyses and SVR simulations to achieve 
higher SVR rates than using lower doses of respective DAAs in the planned Phase 3 
populations.  Based on all current data available, AbbVie believes the combination of 
300 mg ABT-493 and 120 mg ABT-530 provides optimal balance for efficacy, safety, and 
regimen simplicity 
The 6 Global Phase 3 trials include a study in HCV GT1 – 6 in patients with Renal 
Impairment (Study M15-462), a study in HCV GT1 comparing 8 versus 12 weeks in 
subjects without cirrhosis (Study M13-590), a placebo controlled comparator trial in HCV 
GT2-infected subjects without cirrhosis (Study M15-464), an active comparator trial with 
daclatasvir plus sofosbuvir for 12 weeks in GT3 subjects without cirrhosis 
(Study M13-594), a dedicated GT4 – 6 non-cirrhotic trial for 12 weeks (Study M13-583) 
and a 12 week treatment duration Phase 3 trial evaluating subjects with HCV GT1, 2, 5 –
6 with compensated cirrhosis (Study M14-172).
Three additional Phase 3 studies were initiated in 2Q2016.  The objective of these studies 
is to assess the efficacy and safety of the combination of ABT-493 and ABT-530 in 
special populations and include:  HCV GT1 – 6 subjects who are status post liver 
transplantation (Study M13-596), HCV GT1 – 6 subjects with HIV/HCV co-infection 
(Study M14-730), and a study in HCV GT3 subjects without cirrhosis (expansion of 
Study M14-868).
Phase 2 Studies that were subsequently expanded (Studies M14-867 and M14-868) 
assessed efficacy, safety and pharmacokinetics of combination of ABT-493 and ABT-530 
in HCV GT1 (Study M14-867 Part 1) or GT2- or 3-infected (Study M14-868 Part 1) in 
treatment-naïve and PR-experienced non-cirrhotic subjects, respectively, GT4 – 6 
(Study M14-867 Part 2) or GT2- or 3-infected (Study M14-868 Parts 1, 2 and 3) 
treatment-naïve and PR-experienced subjects with and without cirrhosis.


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In Study M14-867 Part 1, HCV GT1-infected subjects received either 12 weeks of 
ABT-493 200 mg QD + ABT-530 120 mg QD (Arm A) or ABT-493 200 mg + ABT-530 
40 mg QD (Arm B).  One hundred percent (40/40) of subjects treated with ABT-493 
200 mg QD + ABT-530 120 mg QD for 12 weeks and 97% (38/39) of subjects treated 
with ABT-493 200 mg QD + ABT-530 40 mg QD for 12 weeks achieved SVR12.  
One subject in Arm B experienced relapse at Post-Treatment Week 4.
In Study M14-867 Part 2, HCV GT1-infected subjects without cirrhosis received 8 weeks 
of ABT-493 300 mg QD + ABT-530 120 mg, 100% (34/34) achieved SVR4 and 97% 
(33/34) achieved SVR12.  The one subject who did not achieve SVR12 died due to 
adenocarcinoma in the abdomen which was deemed not related to study drugs, but did 
have HCV RNA undetectable at last visit.  In Study M14-867 Part 2, treatment-naïve and 
PR-experienced HCV GT1-infected subjects with compensated cirrhosis received 
12 weeks of ABT-493 200 mg QD + ABT-530 120 mg, 96% (26/27) achieved SVR12
with one subject who relapsed at Week 4 post treatment completion.
In Study M14-867 Part 2, HCV GT4 – 6 infected treatment-naïve and PR-experienced 
non-cirrhotic subjects were treated with ABT-493 300 mg QD + ABT-530 120 mg QD for 
12 weeks.  All 34 subjects (22 with HCV GT4 infection, 1 with HCV GT5 infection, and 
11 with HCV GT6 infection) achieved SVR12.
In Study M14-868 Part 1, HCV GT2- and GT3 subjects were randomized to receive 
12 weeks of the combination regimen of ABT-493 (200 or 300 mg) and ABT-530 (40 or 
120 mg) with or without twice-daily, weight based RBV (1000 or 1200 mg total daily 
dose).
Among 74 subjects with HCV GT2 infection in Part 1 of Study M14-868, no subject has 
experienced on treatment virologic failure or post-treatment relapse.  Excluding 
one subject who was lost to follow-up, all 73 subjects with HCV GT2 infection achieved 
SVR12.  The SVR12 rates for each of the treatment regimens were 96% (24/25) (including 
a subject who was lost to follow-up) of subjects treated with ABT-493 300 mg QD + 
ABT-530 120 mg QD for 12 weeks, 100% (24/24) of subjects treated with ABT-493 


ABT-493, ABT-530
M15-592 Protocol
28
200 mg QD + ABT-530 120 mg QD for 12 weeks and 100% (25/25) of subjects treated 
with ABT-493 200 mg QD + ABT-530 120 mg QD + RBV for 12 weeks.
One hundred twenty-one (121) subjects with HCV GT3 infection were treated in Part 1 of 
Study M14-868.  Among all subjects receiving the regimen tested in this study, 
i.e., ABT-493 300 mg and ABT-530 120 mg without RBV for 12 weeks, 93% 
(28/30 subjects) achieved SVR12.  One subject in this arm had no data available (HCV 
RNA < LLOQ at most recent visit) through Post-Treatment Week 12 and was counted as 
an SVR12 non-responder.  One subject in this arm experienced relapse at Post-Treatment 
Week 4.
In Study M14-868 Part 2, among 29 treatment-naïve non-cirrhotic subjects with GT3 
infection treated for 8 weeks with ABT-493 300 mg QD + ABT-530 120 mg QD, no 
subject experienced on-treatment virologic failure or post-treatment relapse.  One of the 
29 subjects had missing SVR12 data.  Among 24 treatment-naïve cirrhotic subjects with 
GT3 infection treated for 12 weeks with ABT-493 300 mg QD + ABT-530 120 mg QD, 
no subject experienced on-treatment virologic failure or post-treatment relapse.
In Study M14-868 Part 3, GT3-infected subjects with treatment experience and/or 
cirrhosis were treated with ABT-493/ABT-530 300 mg/120 mg QD for 12 and/or 
16 weeks.  Treatment-naïve GT3-infected subjects with cirrhosis achieved a SVR12 rate of 
98% (39/40) and treatment-experienced subjects with cirrhosis achieved a SVR12 rate of 
96% (45/47) following 12 and 16 weeks of treatment with ABT-493/ABT-530 
300 mg/120 mg QD, respectively, with no virologic failures among treatment-naïve 
subjects with cirrhosis.  The relapse rate among treatment-experienced subjects with 
cirrhosis following 16 weeks of treatment was 2% (1/46).  Among treatment-experienced 
subjects without cirrhosis, the SVR12 rates for the 12-week and 16-week regimens were 
91% (20/22) and 96% (21/22), respectively.
To date, safety data across all Part 1 arms in Studies M14-867 and M14-868
encompassing 274 subjects treated with ABT-493 at doses 200 and 300 mg and ABT-530 
at doses 40 and 120 mg (with and without RBV in Study M14-868) for 12 weeks show 


ABT-493, ABT-530
M15-592 Protocol
29
that the most frequently reported adverse events were fatigue, nausea, and headache 
(occurring in > 5% of subjects).  Most of them were Grade 1 or 2 in severity.  There were 
no increases in the frequency or severity of any adverse event between the different 
regimens of ABT-493 200 mg plus 40 mg or 120 mg ABT-530, and ABT-493 300 mg 
plus 120 mg ABT-530.
Of the 274 subjects, there have been 4 (1.5%) treatment-emergent SAEs reported 
combined (all assessed as not related to ABT-493 or ABT-530):  pneumonia, atrial 
fibrillation, B-cell lymphoma, and metastatic prostate cancer.  Two subjects (0.7%; 2/274) 
had treatment-emergent adverse events leading to treatment discontinuation.  Both were 
GT3-infected subjects (ABT-493/ABT-530 [200 mg/120 mg] QD + RBV) of 
Study M14-868.  One subject with history of irritable bowel disease discontinued for 
Grade 2 AE of abdominal pain assessed as having a reasonable possibility of relatedness 
to both the DAAs and RBV.  Baseline ALT elevations for this subject normalized during 
treatment and there were no on-treatment ALT elevations above baseline; the subject had 
total bilirubin elevations that were primarily indirect.  The abdominal pain for this subject 
resolved after discontinuation from study drugs.  The other subject discontinued for the 
aforementioned Grade 4 SAE of B-cell lymphoma for the purpose of initiating 
chemotherapy.
In both Studies M14-867 and M14-868, in all subjects with baseline ALT elevations, the 
ALT levels showed a trend toward normal or became normal with DAA treatment, and 
there have been no on-treatment ALT elevations above baseline.  The ALT normalization 
pattern was similar across all arms (i.e., both ABT-493 and ABT-530 dose levels) in both 
studies.  Other laboratory abnormalities were infrequent and were primarily associated 
with well-described hemolytic effect of RBV, manifesting as Grade 1 anemia in total of 
4 subjects, all occurring in Study M14-868 RBV-containing arms.  Observed total 
bilirubin elevations were Grade 1 or 2 with predominantly indirect fraction, were mostly 
isolated occurrences, and normalized or stabilized with continued DAA therapy.  Total 
bilirubin elevations were primarily observed in the RBV-containing arms.


ABT-493, ABT-530
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The safety of the combination regimen of ABT-493 and ABT-530 in subjects with 
compensated cirrhosis is investigated in Study M14-867 Part 2 (ABT-493/ABT-530 
[200 mg/120 mg] QD for 12 weeks) and Study M14-868 Part 2 (ABT-493/ABT-530 
[300 mg/120 mg] QD for 12 weeks with and without ribavirin or for 16 weeks without 
ribavirin).  Based on 82 subjects with compensated cirrhosis enrolled in these arms who 
have received 4 weeks or more of treatment, the ABT-493 and ABT-530 regimen has 
demonstrated a favorable safety profile in this patient population.  The majority of adverse 
events have been Grade 1 or 2 and there have been no treatment discontinuations.
A detailed discussion of the preclinical pharmacology and toxicology, in vitro virology 
and metabolism, and clinical data for ABT-493, ABT-530 and the combination of 
ABT-493 and ABT-530 can be found in the ABT-493 and ABT-530 Fixed-Dose 
Combination Investigator's Brochure.
AbbVie evaluated the combination of ABT-493 (300 mg QD) + ABT-530 (120 mg QD) 
in healthy Western subjects in Phase 1 drug-drug interaction (DDI) studies and in Han 
Chinese, Japanese and Caucasians in Study M15-432.  Based on cross-study comparison, 
the exposures (Cmax and AUC24) in Japanese and Han Chinese subjects were comparable 
to the exposures observed in Western subjects.  Overall, results from these studies 
demonstrate similar pharmacokinetic profiles between Han Chinese and Caucasian 
subjects and support parallel approach in the proposed China development strategy 
utilizing the Global Phase 3 dose.
AbbVie's IFN-free combination regimen of ABT-493 and ABT-530 provides a 
compelling opportunity for improving the treatment of HCV-infected patients in China 
and meeting significant unmet medical needs of these patients.  The proposed regimen 
provides for an all oral, IFN-free treatment that is simpler, safer, shorter and more 
efficacious than currently available injection-based regimens for the treatment of HCV 
GT1 – 6.


ABT-493, ABT-530
M15-592 Protocol
31
Antiretroviral Therapy (ART) Drug-Drug Interaction (DDI) Studies with ABT-493 
and ABT-530
Phase 1 DDI studies of the ABT-493 + ABT-530 combination with HIV antiretroviral 
(ARV) drugs have been conducted in healthy volunteers and/or HIV-1 infected subjects.
The ABT-493 + ABT-530 combination had no clinically meaningful impact on the 
exposures (≤ 80%) of evaluated ARV regimens:  rilpivirine, raltegravir, dolutegravir, 
abacavir, lamivudine, ritonavir-boosted protease inhibitors (darunavir, lopinavir), 
elvitegravir, emtricitabine and tenofovir disoproxil fumarate (TDF).
Based on phase 1 DDI studies, the exposures of ABT-493 and ABT-530 were not affected 
by rilpivirine and raltegravir.
Dolutegravir, lamivudine and abacavir (Triumeq®) coadministered with ABT-493 + 
ABT-530 was evaluated in a DDI study (Study M15-584 Arm 2).  Coadministration was 
safe and well tolerated with mild adverse events reported.  The exposures of dolutegravir, 
lamivudine and abacavir were similar with and without coadministration with ABT-493 
and ABT-530 (≤ 13% difference).  ABT-493 and ABT-530 exposures were slightly lower 
(25% to 28%) when administered with dolutegravir, lamivudine and abacavir.
ABT-493 is a substrate of an organic anion transporting polypeptide (OATP), therefore 
OATP inhibitors may increase the exposures of ABT-493.  When ABT-493 + ABT-530 
was administered with cyclosporine (400 mg), an OATP inhibitor, ABT-493 exposure 
increased to 5.1-fold to that of DAAs administered alone.  The observed increase in 
exposure, however, was not associated with clinically significant safety findings.
Protease inhibitors as a class have potential to inhibit OATP, thus the larger exposure 
increases in ABT-493 with ritonavir boosted protease inhibitors than with ritonavir alone 
may result from interaction of ABT-493 with both the protease inhibitor and ritonavir 
components.  Cobicistat has been shown in vitro and in vivo to have similar cytochrome 
P-450 enzyme and transporter inhibition potential as ritonavir.


ABT-493, ABT-530
M15-592 Protocol
32
When ABT-493 was administered with ritonavir, exposure of ABT-493 was 2-fold of 
ABT-493 exposure alone.  Coadministration of ABT-493 + ABT-530 with ritonavir 
boosted protease inhibitors, darunavir QD or lopinavir BID, increased ABT-493 
exposures, AUC and Cmax to 3- to 5-fold and 2.6- to 4.4-fold, respectively while 
exposures of ABT-530 were similar with and without darunavir QD (≤ 16% change) and 
increased to 1.4- to 2.5-fold with lopinavir BID.  The exposures of lopinavir (≤ 24% 
increase) or darunavir (< 30% increase) were comparable with and without DAA 
coadministration.  Both the regimens (darunavir QD or lopinavir BID) tested were well 
tolerated with mild adverse events.  Therefore, coadministration of ritonavir-boosted PIs 
is not recommended with ABT-493/ABT-530.  Coadministration of ABT-493 + ABT-530 
with ritonavir boosted atazanavir was studied in a DDI study that was terminated early 
due to an increase in ABT-493 exposure up to 16-fold and ABT-530 exposure up to
3-fold with Grade 1 and 2 increases in ALT and Grade 2 to 3 increase in total bilirubin 
(predominately indirect).  Therefore, coadministration of atazanavir is contraindicated 
with ABT-493/ABT-530.
The combination of ABT-493 +ABT-530 was evaluated with Genvoya® (elvitegravir 
150 mg, cobicistat 150 mg, emtricitabine 200 mg, tenofovir alafenamide 10 mg QD).  
Coadministration was safe and well tolerated, with mild adverse events reported and 
one grade 3 neutropenia deemed related to the combination of Genvoya®, ABT-493 and 
ABT-530 in a black male subject with a low baseline ANC, leading to premature study 
drug discontinuation.  The ABT-493 exposure increased to 3-fold and the ABT-530 
exposure increased by 57%, with clinically insignificant increases in elvitegravir, 
cobicistat, tenofovir and emtricitabine exposures.  Thus, cobicistat boosted elvitegravir 
will be allowed in Study M15-592.
Efavirenz induces P-gp and exposures of ABT-493 and ABT-530 in the presence of 
efavirenz were approximately 3- and 2-fold lower, respectively, and thus coadministration 
of efavirenz and efavirenz-containing regimens is not recommended with 
ABT-493/ABT-530.


ABT-493, ABT-530
M15-592 Protocol
33
In summary, coadministration of HIV-PIs alone, ritonavir-boosted PIs and efavirenz is not 
recommended with ABT-493/ABT-530.  Based on the above information, cobicistat-
boosted elvitegravir, dolutegravir, abacavir, lamivudine, rilpivirine and raltegravir are 
allowed.
For a more detailed discussion of drug-drug interaction studies please refer to the 
ABT-493 and ABT-530 Fixed-Dose Combination Investigator's Brochures.32
3.1
Differences Statement
The current study (Study M15-592) is the Phase 3 study evaluating the efficacy, safety 
and pharmacokinetics of the combination of ABT-493/ABT-530 in approximately 
504 Asian subjects with chronic HCV GT1, 2, 3, 4, 5 or 6-infection who are HCV-
treatment naïve or -experienced, without cirrhosis and with or without HIV co-infection.  
The current study will evaluate the selected dose and regimen of ABT-493/ABT-530 
300 mg/120 mg QD using the co-formulated, fixed dose combination tablet intended for 
marketing for 8 or 16 (for GT3 treatment-experienced) weeks in Asian subjects.  The 
diverse subject population to be enrolled will be representative of the intended population 
of subjects infected with a broad range of HCV GTs and will allow evaluation of the 
safety and efficacy of ABT-493/ABT-530 in Asian subjects.
3.2
Benefits and Risks
Potential benefits of treatment with ABT-493/ABT-530 include:  Potent and pan-
genotypic antiviral activity in vitro, higher genetic barrier to development of drug 
resistance across GTs compared to first generation protease and NS5A inhibitors, no need 
for RBV, 8 or 16 weeks of treatment, and the convenience of a once-daily regimen.
Adverse events that are known, and those not previously described, may occur with 
ABT-493/ABT-530 as detailed in the informed consent of this study.  In addition, subjects 
may experience inconvenience or discomfort related to the study visits or study 
procedures.  Additional safety data for each DAA alone and the combination of ABT-530 


ABT-493, ABT-530
M15-592 Protocol
34
and ABT-493 are detailed in Section 3.0 and in the Investigator's Brochures for the 
respective compounds.
Risks associated with ABT-493 and ABT-530, including the risks of toxicity, virologic 
failure and development of resistant mutations (Section 5.3.4), appear to be limited and 
manageable based upon the available data.  Given the potential for SVR in this population 
of HCV GT1, 2, 3, 4, 5 and 6-infected subjects, the risk-benefit assessment is favorable.
4.0
Study Objective
4.1
Primary Objective
The primary objectives of this study are to compare, among the combined group of GT1 
to GT6-infected subjects, among the GT1-infected subjects, and among the GT2-infected 
subjects, the percentage of subjects achieving SVR12, (HCV RNA < lower limit of 
quantification [LLOQ] 12 weeks after the last actual dose of study drug) to a historical 
SVR12 rate and to assess the safety following 8 or 16 weeks of treatment with the 
ABT-493/ABT-530 combination regimen in treatment-naïve and treatment-experienced 
non-cirrhotic adults with chronic hepatitis C virus (HCV) GT1 to GT6 infection with or 
without human immunodeficiency virus (HIV) co-infection.
4.2
Secondary Objective
The secondary objectives are to assess:
●
The percentage of subjects with on-treatment HCV virologic failure;
●
The percentage of subjects with post-treatment relapse of HCV infection;
●
The percentage of HCV/HIV co-infected subjects achieving SVR12.
An additional objective is to assess the pharmacokinetics of ABT-493 and ABT-530 in 
Asian HCV-infected adults.


ABT-493, ABT-530
M15-592 Protocol
35
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study to 
evaluate the efficacy, safety and pharmacokinetics of ABT-493/ABT-530 in non-cirrhotic 
chronic HCV GT1 to GT6-infected Asian adult subjects with or without HIV co-infection 
who are HCV treatment-naïve or treatment-experienced with IFN (alpha, beta or pegIFN) 
with or without RBV OR sofosbuvir with RBV with or without IFN.
This study will consist of 3 periods as follows:
Double-Blind (DB) Treatment Period:  Eligible subjects will be randomized to receive 
ABT-493/ABT-530 300 mg/120 mg QD (Arm A) or placebo QD (Arm B) for either 8 
or 16 weeks.
Open-Label (OL) Treatment Period:  Subjects who are randomized to the placebo arm 
during the DB Treatment Period (Arm B) will receive open-label ABT-493/ABT-530 
300 mg/120 mg QD for either 8 or 16 weeks in the OL Treatment Period.
Treatment duration in both the DB and OL Treatment Periods will differ among 
subjects based on HCV GT and treatment-experience (8 weeks of treatment for GT1, 
2, 3, 4, 5 and 6-infected subjects with the exception of 16 weeks for treatment-
experienced GT3-infected subjects).
Post-Treatment Period:  Subjects randomized to active drug (Arm A) who complete or 
prematurely discontinue study drug during the DB Treatment Period and subjects 
randomized to placebo (Arm B) who complete the OL Treatment Period or prematurely 
discontinue study drug during the OL Treatment Period will be followed for 24 weeks to 
monitor safety and to evaluate efficacy and the emergence and/or persistence of HCV 
resistance-associated substitutions.


ABT-493, ABT-530
M15-592 Protocol
36
Figure 2.
Study Schematic
Chronic HCV GT1 – 6 infected adults without underlying cirrhosis will be enrolled into 
one of two treatment arms:
Arm A:
ABT-493/ABT-530 300 mg/120 mg for 8 or 16 weeks
Arm B:
Matching Placebo for 8 or 16 weeks followed by open-label 
ABT-493/ABT-530 300 mg/120 mg QD for 8 or 16 weeks
Approximately 504 subjects meeting the eligibility criteria will be enrolled.  A minimum 
of 150 GT1-infected subjects, a minimum of 150 GT2-infected subjects and 
approximately 60 GT3, 4, 5 or 6-infected subjects from China will be enrolled into this 
study.  Approximately 105 GT1-infected subjects and approximately
39 GT2-infected subjects will also be enrolled into this study from the regional Asian 
countries of South Korea and Singapore.  Of the approximately 504 subjects, a maximum 
of 50 HCV/HIV co-infected subjects will be enrolled.
In China, subjects will be randomized to receive active treatment (Arm A) or placebo 
(Arm B) in a 2:1 ratio for each of the GT1 and GT2-infected groups and the combined 


ABT-493, ABT-530
M15-592 Protocol
37
GT3 to GT6 infected group.  In each regional Asian country, each of the GT1 and GT2 
infected groups will be randomized in a 2:1 ratio to Arm A or Arm B.
Subjects who are randomized to Arm B will receive open-label ABT-493/ABT-530 
300 mg/120 mg QD for 8 or 16 weeks following the DB Treatment Period.
Randomization of subjects will be stratified by geographic region (China, South Korea 
and Singapore), genotype (GT1, GT2, combined GT3 – 6), and HCV/HIV co-infection 
status (yes, no).
The study is designed to enroll approximately 504 subjects to meet scientific and 
regulatory objectives without enrolling an undue number of subjects in alignment with 
scientific and ethical considerations.  Therefore, if the target number of subjects has been 
enrolled, there is a possibility that additional subjects in Screening will not be enrolled.
5.1.1
Screening
At the Screening Visit, subjects who provide written (signed and dated) informed consent 
prior to any study-specific procedures will receive a unique subject number via the 
Interactive Response Technology (IRT) system.  The investigator will evaluate whether 
the subject meets all of the eligibility criteria specified in Section 5.2.1 and Section 5.2.2
during the period from the Screening Visit through Study Day 1 prior to dosing, and will 
record the results of this assessment and the details of the informed consent process in the 
subject's medical records.  Eligible subjects have up to 35 days following the Screening 
Visit to enroll into the study.
5.1.1.1
Rescreening
Subjects who at Screening have any of the following are not eligible to rescreen or retest:
●
HCV GT does not meet Inclusion Criterion 4, Section 5.2.1, or meets 
Exclusion Criterion 4, Section 5.2.2.
Otherwise subjects may be retested or rescreened only once.


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Subjects who have exclusionary laboratory parameter(s) are allowed to retest on the 
related panel(s) (e.g., exclusionary ALT requires a repeat chemistry panel) within the 
same screening period and must meet all eligibility laboratory criteria on any panel that is 
repeated.  If the retest result(s) are also exclusionary, the subject may not be rescreened.
Subjects that are rescreened outside of the initial 35 day screening period must be 
rescreened for all laboratory and eligibility criteria, not just those that were exclusionary.
For subjects who rescreen or subjects that do not meet the study eligibility criteria, the site 
personnel must contact the IRT and identify the subject as a screen failure.
5.1.2
Double-Blind Treatment Period
After meeting the eligibility criteria, subjects will be randomized via IRT to a treatment 
arm.  Subjects will be administered study drug at the site on Study Day 1, with dosing 
instructions.
Study visits and procedures during the DB Treatment Period are detailed in Appendix C.  
Safety and tolerability will be assessed throughout the study.  Laboratory testing will 
include chemistry, hematology, and urinalysis as specified in Table 2.  Plasma samples for 
pharmacokinetic analysis (including optional samples for intensive PK analysis) and HCV 
RNA analysis will be collected as detailed in Section 5.3.2 and Section 5.3.1.1.
AbbVie, investigators and subjects will be blinded to drug assignment and HCV virologic 
results for the duration of the DB Treatment Period.  AbbVie, investigators and subjects 
will remain un-blinded to HIV virologic results for the duration of the study.  HCV 
virologic results will be reviewed and HCV virologic failure criteria will be assessed for 
those subjects randomized to active drugs by an un-blinded independent reviewer.  See 
Section 5.4.1.1 for further details.  Certain safety laboratory results which could 
potentially be un-blinding (such as AST, ALT, and total and indirect bilirubin) will also 
be blinded to AbbVie, investigators and subjects.  For the blinded laboratory tests, if pre-
specified toxicity thresholds are exceeded then the relevant un-blinded laboratory data 
will be provided to the investigator and AbbVie.  See Section 6.1.7 for further details.  In 


ABT-493, ABT-530
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39
addition, a subject's study drug assignment may be un-blinded as directed by the toxicity 
management guidelines or at the investigator's discretion, if deemed necessary for subject 
safety.
All subjects will continue to return to the site on an outpatient basis as outlined in 
Appendix C.  Sites should ensure that subjects adhere to all study visits.  Subjects who 
cannot complete their study visit per the visit schedule should ensure they do not run out 
of study drug prior to their next study visit.  Compliance is critical to ensure adequate 
drug exposure.
At the final scheduled DB Period visit (Week 8 or Week 16), the study drug will be un-
blinded and subjects randomized to placebo (Arm B) who complete the DB Treatment 
Period may enter the OL Treatment Period and receive 8 or 16 weeks of open-label 
ABT-493/ABT-530.
Subjects who prematurely discontinue from the DB Treatment Period should return for a 
Treatment Discontinuation (D/C) Visit and undergo the study procedures as outlined in 
Appendix C and as described in Section 5.4.1.  Ideally, this should occur on the day of 
study drug discontinuation, but is recommended to be no later than 2 days after their final 
dose of study drug in the DB Period and prior to the initiation of any other anti-HCV 
therapy.  At the Treatment D/C Visit, subjects will be un-blinded to study drug 
assignment.
Subjects who were randomized to active study drug (Arm A) will immediately start the 
PT Period and be monitored for virologic failure and resistance as detailed in 
Section 5.1.4.  Subjects who prematurely discontinue study drugs during the DB 
Treatment Period and who are found to be on placebo may elect to remain in the study (at 
the investigator's discretion) and receive active drug during the OL Treatment Period. 
However, the subject is expected to continue to attend all remaining DB Treatment Period 
study visits and perform all remaining study procedures through the final scheduled DB 
Treatment Period visit (Week 8 or Week 16) in order to be enrolled into the OL Treatment 
Period.


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Subjects who complete or prematurely discontinue from treatment will be monitored for 
safety, HCV RNA, and the emergence and/or persistence of HCV resistance-associated 
substitutions, plasma HIV-1 RNA, HIV resistance (as applicable) and PROs in the 
24-week PT Period as detailed in Section 5.1.4.
5.1.3
Open-Label Treatment Period
After completing the DB Treatment Period, subjects initially randomized to placebo 
(Arm B) at the beginning of the DB Treatment Period will receive 8 or 16 weeks of open-
label ABT-493/ABT-530.  Subjects will be provided dosing instructions and will be 
dispensed study drug at the final scheduled DB Treatment Period visit (Week 8 or 
Week 16).  Administration of ABT-493/ABT-530 will start the next day (OL Day 1).  The 
same type of bottles as used for placebo will be used for active study drug 
ABT-493/ABT-530.
Sites must call subjects within 4 days after the final scheduled DB Treatment Period visit 
(Week 8 or Week 16) to verify the first day of open-label, study drug administration and 
record this date on the eCRF and in the source documents.  Study drugs, virologic results 
and safety laboratory results will not be blinded during the OL Treatment Period.  
Virologic failure criteria and toxicity management will be evaluated and applied by the 
investigator (Section 5.4.1.1 and Section 6.1.7).
Subjects who prematurely discontinue from the OL Treatment Period should return for a 
Treatment D/C Visit and undergo the study procedures as defined in Appendix C and as 
described in Section 5.4.1.  Ideally, this should occur on the day of study drug 
discontinuation, but is recommended to be no later than 2 days after their final dose of 
study drugs and prior to the initiation of any other anti-HCV therapy.  Subjects who 
complete or discontinue the OL Treatment Period will be monitored for safety, HCV 
RNA, the emergence and persistence of resistant viral variants, plasma HIV-1 RNA and 
HIV resistance (as applicable) in the 24-week Post-Treatment Period as detailed in 
Section 5.1.4.


ABT-493, ABT-530
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41
5.1.4
Post-Treatment Period
All subjects who received at least one dose of active study drug and either complete 
treatment or prematurely discontinue the active study drug in either the DB or OL 
Treatment Periods will be monitored in the Post-Treatment Period for safety, HCV RNA 
and the emergence and persistence of resistant viral variants, plasma HIV-1 RNA and 
HIV resistance (as applicable) for an additional 24 weeks following the last dose of active 
study drug.  Subjects in Arm A who receive at least one dose of active study drug in the 
DB Treatment Period will also be monitored in the Post-Treatment Period for PROs for 
24 weeks following the last dose of active study drug.
The Post-Treatment Period will begin the day following the last dose of active study drugs 
(in either the DB Treatment Period for subjects who were randomized to Arm A or the OL 
Treatment Period for subjects who were randomized to Arm B).
Some of the Post-Treatment Period study visits and visit activities (including but not 
limited to vital signs, clinical laboratory tests and concomitant medication assessment) 
may be conducted in the home or non-hospital/clinic environment at the request of the 
investigator and with the agreement of the subject.
Subjects who prematurely discontinue the Post-Treatment Period should return to the site 
for a Post-Treatment D/C Visit as outlined in Appendix C.
5.2
Selection of Study Population
The study population consists of chronic HCV GT1, 2, 3, 4, 5 or 6-infected Asian, male 
and female adults, without cirrhosis, with or without HIV co-infection who are HCV 
treatment-naïve or treatment-experienced to IFN (alpha, beta or pegIFN) with or without 
RBV OR sofosbuvir with RBV with or without IFN.
5.2.1
Inclusion Criteria
1.
Male or female of Asian descent and at least 18 years of age at time of Screening.


ABT-493, ABT-530
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42
2.
If female, subject must be either (as defined in section 5.2.4)  postmenopausal, OR 
permanently surgically sterile OR for Women of Childbearing Potential (WOCBP) 
practicing at least one protocol specified method of birth control starting at Study 
Day 1 (or earlier) through at least 30 days after the last dose of study drug.
No male contraception is required if the male subject has a female partner who is 
postmenopausal or permanently sterile (bilateral oophorectomy, bilateral 
salpingectomy or hysterectomy).
3.
Females of childbearing potential must have a negative serum pregnancy test result 
at Screening, and a negative urine pregnancy test at Study Day 1.
Females of non-childbearing potential (either postmenopausal or permanently 
surgically sterile as defined in the protocol) at Screening do not require pregnancy 
testing.
4.
Screening laboratory result indicating HCV GT1, 2, 3, 4, 5 or 6-infection.
5.
Subject has positive HCV antibody (Ab) and plasma HCV RNA viral load 
≥1000 IU/mL at Screening Visit.
6.
Chronic HCV infection defined as one of the following:
●
Positive for HCV Ab or HCV RNA at least 6 months before Screening;
●
A liver biopsy consistent with chronic HCV infection.
7.
Subject must be HCV treatment-naïve (i.e., subject has not received any approved 
or investigational HCV treatment) or treatment-experienced (i.e., subject has failed 
prior HCV treatment with IFN [alpha, beta or pegIFN] with or without RBV OR 
sofosbuvir with RBV with or without IFN).  Previous HCV treatment must have 
been completed ≥ 8 weeks prior to screening.
8.
Body Mass Index (BMI) is ≥ 18.0 kg/m2 at the time of Screening.  BMI is 
calculated as weight measured in kilograms (kg) divided by the square of height 
measured in meters (m).


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43
9.
Subject must be documented as non-cirrhotic, defined as meeting one of the 
following criteria:
●
A liver biopsy within 24 months prior to or during screening demonstrating the 
absence of cirrhosis, e.g., a METAVIR, Batts-Ludwig, Knodell, IASL, 
Scheuer, or Laennec fibrosis score of ≤ 3, Ishak fibrosis score of ≤ 4; or
●
A FibroScan® score of < 12.5 kPa within 6 months of Screening or during the 
Screening Period; or
○
Subjects with indeterminate FibroScan® score (12.5 ≤ score < 14.6), must 
have a qualifying liver biopsy.
●
A screening FibroTest score of ≤ 0.48 and Aspartate Aminotransferase to 
Platelet Ratio Index (APRI) < 1.
○
Subjects with indeterminate FibroTest (0.48 < result < 0.75), or conflicting 
FibroTest and APRI results (e.g., FibroTest ≤ 0.48, but APRI ≥ 1) must 
have a qualifying liver FibroScan® or biopsy.
10.
Must voluntarily sign and date an informed consent form, approved by an 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) prior to the
initiation of any screening or study specific procedures.
11.
Subjects must be able to understand and adhere to the study visit schedule and all 
other protocol requirements.
In addition to Inclusion Criteria 1 through 11, subjects enrolled with HCV GT1 to 6 and 
HIV-1 co-infection, must also meet the following criteria per local standard practice:
12.
Positive test result for Human Immunodeficiency Virus antibody (HIV Ab) at 
Screening.
13.
Naïve to treatment with any ART (and have no plans to initiate ART treatment 
while participating in this study)
or


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On a stable, qualifying HIV-1 ART regimen (allowed regimens will be based on 
AbbVie approval) for at least 8 weeks prior to screening.
14.
Subjects naïve to ART must have CD4+ count ≥ 500 cells/mm3 (or CD4+ % 
≥29%) at Screening.
15.
Subjects on stable ART must have the following:
●
CD4+ count ≥ 200 cells/mm3 (or CD4+ % ≥ 14%) at Screening; and
●
Plasma HIV-1 RNA below LLOQ by an approved plasma HIV-1 RNA 
quantitative assay (including but not limited to Roche COBAS®
Ampliprep/COBAS® Taqman HIV-1 Test, v 2.0) at Screening and at least 
once during the 12 months prior to Screening.
Rationale for Inclusion Criteria
1, 4 – 7, 9,
12 – 15
In order to select the appropriate subject population with appropriate 
disease characteristics for evaluation
2, 3
The impact of ABT-493 and ABT-530 on pregnancies is unknown
8
For the safety of study subjects
10, 11
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.
Female subject who is pregnant, breastfeeding or is considering becoming pregnant 
during the study or for approximately 30 days after the last dose of study drug.
2.
Recent (within 6 months prior to study drug administration) history of drug or 
alcohol abuse that could preclude adherence to the protocol in the opinion of the 
investigator.


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3.
Positive test result at Screening for hepatitis B surface antigen (HBsAg) or 
hepatitis B virus (HBV) DNA > LLOQ if HBsAg is negative.
4.
HCV genotype performed during screening indicating co-infection with more than 
one HCV genotype.
5.
Requirement for and inability to safely discontinue contraindicated medications or 
supplements listed in Table 1 at least 2 weeks or 10 half-lives (whichever is longer) 
prior to the first dose of any study drug.
6.
Clinically significant abnormalities, other than HCV infection or HCV/HIV co-
infection, based upon the results of a medical history, physical examination, vital 
signs, laboratory profile, and a 12-lead electrocardiogram (ECG) that make the 
subject an unsuitable candidate for this study in the opinion of the investigator, 
including, but not limited to:
●
Uncontrolled diabetes as defined by a glycated hemoglobin (hemoglobin A1C) 
level > 8.5% at the Screening Visit.
●
Active or suspected malignancy or history of malignancy (other than basal cell 
skin cancer or cervical carcinoma in situ) in the past 5 years.
●
Uncontrolled cardiac, respiratory, gastrointestinal, hematologic, neurologic, 
psychiatric, or other medical disease or disorder, which is unrelated to the 
existing HCV infection.
7.
Any cause of liver disease other than chronic HCV-infection, including but not 
limited to the following:
●
Hemochromatosis
●
Alpha-1 antitrypsin deficiency
●
Wilson's disease
●
Autoimmune hepatitis
●
Alcoholic liver disease
●
Steatohepatitis on liver biopsy considered to be the primary cause of the liver 
disease rather than concomitant/incidental with HCV infection


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8.
Screening laboratory analyses showing any of the following abnormal laboratory 
results:
●
ALT > 10 × upper limit of normal (ULN)
●
AST > 10 × ULN
●
Estimated Glomerular filtration rate adjusted for the Chinese population 
(eGFR) < 50 mL/min/1.73 m2 as estimated by the MDRD method, modified 
for the Chinese population (C-MDRD), according to the following formula:
eGFR = 175 × (Serum Creatinine)–1.234 × (Age)–0.179 × (0.79 if Female)
●
Direct bilirubin > ULN
●
Albumin < lower limit of normal (LLN)
●
International normalized ratio (INR) > 1.5 × ULN, unless subject has known 
hemophilia or is on a stable anticoagulant regimen affecting INR
●
Hemoglobin < 11 g/dL for women; < 12 g/dL for men
●
Platelets < 90,000 cells per mm3
●
Absolute neutrophil count (ANC) < 1000 cells/μL
9.
History of solid organ transplantation.
10.
Receipt of any investigational product within a time period equal to 10 half-lives of 
the product, if known, or a minimum of 6 weeks (whichever is longer) prior to 
study drug administration.
11.
Any current or past clinical evidence of decompensated liver disease such as 
ascites noted on physical exam, use of diuretics for ascites, hepatic encephalopathy 
or esophageal variceal bleeding.
12.
Requirement for chronic use of systemic immunosuppressants including, but not 
limited to, corticosteroids (prednisone equivalent of > 10 mg/day for > 2 weeks), 
azathioprine, or monoclonal antibodies (e.g., infliximab).
13.
Chronic human immunodeficiency virus, type 2 (HIV-2) infection.
14.
Consideration by the investigator, for any reason, that the subject is an unsuitable 
candidate to receive ABT-493/ABT-530.


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15.
History of severe, life-threatening or other significant sensitivity to any excipients 
of the study drugs.
16.
Patients who can't participate in study per local law.
Additional Exclusion Criteria for Subjects with HCV/HIV-1 Co-Infection:
17.
For subjects on stable ART, taking anti-retroviral agent(s) other than those 
permitted based on AbbVie approval.
18.
Treatment for an AIDS-associated opportunistic infection (OI) (see Appendix D) 
within 12 months of screening or prophylaxis for an AIDS-associated opportunistic 
infection within 6 months of screening.
19.
Diagnosis of any clinical AIDS-defining event within 12 months prior to screening.  
A list of these events may be found in Appendix D.
Rationale for Exclusion Criteria
1, 6, 8, 9, 
11, 14 – 19
In order to ensure safety of the subjects throughout the study
2, 5, 10,12, 
13
In order to avoid bias for the evaluation of efficacy and safety, including 
concomitant use of other medications
3, 4, 7
To exclude subjects with hepatitis B and liver diseases other than HCV
5.2.3
Prior and Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins and/or traditional Chinese medicine and/or herbal supplements) that the subject 
is receiving from the time of signing the consent through the DB and OL Treatment 
Periods and 30 days after study drugs are 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 interactions.


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Information regarding each subject's qualifying, stable HIV-1 ART medications (allowed 
regimens will be based on AbbVie approval) including start date, dose and frequency will 
be recorded into the eCRF at screening.  In addition, subjects will be requested to record 
information for the last two doses of their HIV-1 ART medications taken (dosing date, 
times, and number of pills) prior to the study visits detailed in Appendix C, and site 
personnel will record this information in the eCRF.
During the Post-Treatment Period, all medications taken will be recorded until 30 days 
following the last dose of study drugs.  Only medications taken for SAEs and for 
treatment of HCV and HIV will be recorded thereafter.
The AbbVie Primary Therapeutic Area Medical Director (TA MD) should be contacted if 
there are any questions regarding concomitant or prior therapies.
5.2.3.1
Prior HCV Therapy
Subjects will be considered treatment-experienced if they have failed prior HCV treatment 
with IFN [alpha, beta or pegIFN] with or without RBV OR sofosbuvir with RBV with or 
without IFN.  Previous HCV-treatment must have been completed ≥ 8 weeks prior to the 
Screening Visit.
Subjects will be categorized as follows:
●
Treatment-naïve:  subject never received any treatment for HCV infection.
●
Subjects with an allowed prior treatment will be categorized as follows:
●
Non-responder:  HCV RNA detected at the end of a prior treatment course 
(except for breakthrough, which is captured separately).  These subjects are 
further categorized as:
○
Null responder:  failed to achieve a 1 log10 IU/mL reduction in HCV RNA 
by Week 4 or a 2 log10 IU/mL reduction in HCV RNA by Week 12 during 
a prior treatment course;


ABT-493, ABT-530
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○
Partial responder:  achieved at least a 2 log10 IU/mL reduction in HCV 
RNA by Week 12 during a prior treatment course but failed to achieve 
HCV RNA undetectable at the end of treatment;
○
Unknown or Unable to Specify:  insufficient data to categorize as null or 
partial responder.
●
Breakthrough:  confirmed ≥ 1 log10 IU/mL increase from nadir or achieved 
HCV RNA undetectable (or unquantifiable) during a prior treatment course but 
HCV RNA was quantifiable during or at the end of treatment.
●
Relapse:  achieved HCV RNA undetectable at the end of a prior treatment 
course but HCV RNA was detectable following cessation of therapy.
●
Other:  subject received a prior treatment course and reason for not achieving 
SVR is other than above.
●
Unknown:  subject received a prior treatment course and reason for not 
achieving SVR is unknown.
Subjects must have discontinued prior HCV therapy at least 8 weeks prior to the 
Screening Visit in order to be eligible for the study.
5.2.3.2
Prior and Concomitant HIV-1 Therapy
Subjects with HCV/HIV co-infection who are not naïve to HIV ARTs must be on a stable, 
qualifying HIV-1 ART regimen (allowed regimens will be based on AbbVie approval) for 
at least 8 weeks prior to screening.
Information regarding each subject's qualifying, stable HIV-1 ART medications including 
start date, dose and frequency will be recorded into the eCRF at screening.  In addition, 
subjects will be requested to record information for the last two doses of their HIV-1 ART 
medications taken (dosing date, times, and number of pills) prior to the study visits during 
the DB and OL Treatment Periods and the Post-Treatment Period detailed in Appendix C, 
and site personnel will record this information in the eCRF.
Study participants should plan to remain on the same HIV-1 ART regimen for the entire 
study (both the DB and OL Treatment Periods and Post-Treatment Period).  Any change 


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in the HIV-1 ART regimen during the DB or OL Treatment Period must be discussed 
with the AbbVie TA MD prior to the change being made, unless the change is being made 
to address an immediate safety concern.
5.2.3.3
Concomitant Therapy
Subjects should be on stable doses of concomitant medications for at least 2 weeks prior 
to the initiation of study drugs (8 weeks prior to screening for HIV ARTs). The 
investigator should confirm that a concomitant medication/supplement can be safely 
administered with study drugs.  Some concomitant medications may require dose 
adjustments due to the potential for drug-drug interactions.  The investigator can also 
review the label(s) for the concomitant medication(s) for additional information.
The use of hepatoprotective medication (e.g., Sho-saiko-to, Milk thistle, ursodeoxycholic 
acid, glycyrrhizin acid, SAMe, etc.) is allowed, provided that the drug does not meet any 
other exclusion criterion.
A subject on a stable dose of a hepatoprotectant should have been on the same dose for at 
least 2 weeks prior to study entry which begins when the subject signs the informed 
consent.  In addition, the subject should maintain the hepatoprotectant at the same dose 
throughout the whole study until the end of the Post-Treatment Period.  If any change to 
hepatoprotectant dosing is needed, the investigator should contact the AbbVie TA MD to 
discuss prior to taking action.
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 after 30 days following 
discontinuation of active study drugs, as applicable.
5.2.3.4
Prohibited Therapy
Subjects must be able to safely discontinue any prohibited medications or supplements 
listed in Table 1 at least 2 weeks or 10 half-lives (whichever is longer) prior to the 


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first dose of any study drug and not use these during the entire DB or OL Treatment 
Periods and for 30 days following discontinuation of active study drugs.
Table 1.
Prohibited Medications and Supplements
Medication or Supplement Name
Red yeast rice (monacolin K), St. John's Wort
Carbamazepine, phenytoin, pentobarbital, phenobarbital, primidone, rifabutin, rifampin
Atorvastatin, lovastatin, simvastatin*
Astemizole, cisapride, terfenadine
Efavirenz containing regimens
*
Some HMG-CoA reductase inhibitors (including atorvastatin, lovastatin, or simvastatin) should not be taken with 
the study drugs.  Subjects receiving these statins should either switch to pravastatin or rosuvastatin prior to the 
first dose of study drugs or may interrupt statin therapy throughout the treatment period and until 30 days after the 
last dose of study drug, based on the investigator's judgment.  If switching to or continuing pravastatin or 
rosuvastatin, it is recommended to reduce the pravastatin dose by 50% or limit the rosuvastatin dose to 10 mg QD 
when taking with the study drugs.
Use of ethinyl estradiol containing oral contraceptives with ABT-493 and ABT-530 
combination was associated with ALT increases in some healthy female subjects.  
Hormonal contraceptives (including oral, topical [including vaginal rings], injectable, or 
implantable varieties) containing ethinyl estradiol may not be used from 2 weeks prior to 
the first dose of ABT-493/ABT-530 until 30 days after the end of ABT-493/ABT-530 
dosing.  Progestin-only contraceptives, such as those containing norethindrone, 
desogestrel, or levonorgestrel, without ethinyl estradiol, may be used with 
ABT-493/ABT-530.  Post-menopausal hormone replacement therapy, such as with 
esterified or conjugated estrogens, i.e., not containing ethinyl estradiol, may be used with 
ABT-493/ABT-530 at the discretion of the Investigator.
Anti-HCV medications other than those specified in the protocol will not be allowed 
anytime during any of the Treatment Periods.
The chronic use of systemic immuno-suppressants is prohibited from 2 weeks prior to the 
first dose of study drug and until 30 days after the last dose of study drug including, but 


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not limited to, corticosteroids (prednisone equivalent of > 10 mg/day for > 2 weeks), 
azathioprine, or monoclonal antibodies (e.g., infliximab).
For HCV/HIV-1 Co-Infected Subjects
The investigator must refer to the current package insert(s) or product label(s) of the 
subject's ART regimen for a complete list of prohibited medications.
5.2.4
Contraception Recommendations
If female, subject must be either –
●
Postmenopausal defined as:
○
Age ≥ 55 years with no menses for 12 or more months without an 
alternative medical cause.
○
Age < 55 years with no menses for 12 or more months without an 
alternative medical cause AND an FSH level > 40 IU/L.
OR
●
Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy 
or hysterectomy).
OR
●
Women of Childbearing Potential (WOCBP):
○
Practicing at least one of the following methods of birth control, on Study 
Day 1 (or earlier) through at least 30 days after the last dose of study drug–
●
Progestogen-only hormonal contraception (oral, injectable, 
implantable) associated with inhibition of ovulation, initiated at least 
1 month prior to Study Day 1.
●
Bilateral tubal occlusion/ligation.
●
Vasectomized partner(s), provided the vasectomized partner has 
received medical assessment of the surgical success and is the sole 
sexual partner of the WOCBP trial participant.
●
Intrauterine device (IUD).


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●
Intrauterine hormone-releasing system (IUS), excluding ethinyl 
estadiol.
●
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).
If required per local practices, male or female condom with or without spermicide OR 
cap, diaphragm or sponge with spermicide should be used in addition to one of the birth 
control methods listed above (excluding true abstinence).
If the male subject has a female partner who is postmenopausal or permanently sterile 
(bilateral oophorectomy, bilateral salpingectomy or hysterectomy), no contraception is 
required.
If the male subject is sexually active with female partner(s) of childbearing potential, he 
must agree from Study Day 1 through 90 days after the last dose of study drug to practice 
contraception with:
●
Condom use and female partner(s) using at least one of the contraceptive 
measures (as defined in the protocol for female study subjects of childbearing 
potential).
●
True abstinence:  Refraining from heterosexual intercourse-when this is in line 
with the preferred and usual lifestyle of the subject.  (Note:  Periodic 
abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] 
and withdrawal are not acceptable).
●
Additionally, male subject agrees not to donate sperm from Study Day 1 
through 90 days after the last dose of study drug.


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5.3
Efficacy, Pharmacokinetic, Pharmacogenetic and Safety 
Assessments/Variables
5.3.1
Efficacy and Safety Measurements Assessed and Flow 
Chart
Study procedures are described in the following section of this protocol and are 
summarized in tabular format in Appendix C.
5.3.1.1
Study Procedures
Informed Consent Information
Signed study-specific 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
A complete medical history, including history of alcohol, tobacco and nicotine-containing 
product use, will be taken at Screening.  The medical history will be updated on Study 
Day 1.  The medical history obtained prior to the first dose of study drug will serve as the 
baseline for clinical assessment.
Physical Examination
Physical examinations will be performed at visits specified in Appendix C, or upon 
subject discontinuation.  A symptom-directed physical examination will be performed 
when necessary.  The physical examination performed on DB Treatment Period Day 1 
will serve as the baseline physical examination for clinical assessment.  Any significant 
physical examination findings after dosing will be recorded as adverse events.
Height will be measured only at Screening.  Waist circumference will be measured at the 
Screening Visit, but if it is not measured at Screening, it may be measured on Day 1.


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Vital Signs and Weight
Body temperature, blood pressure, pulse and weight will be measured at each study visit 
as specified in Appendix C or upon subject discontinuation.  The subject will wear 
lightweight clothing and no shoes during weighing.  Blood pressure and pulse rate will be 
measured after the subject has been sitting for at least 3 minutes.  The vital signs 
measurements on Day 1 will serve as the baseline measurements for clinical assessment.
12-Lead Electrocardiogram (ECG)
A single 12-lead resting ECG will be obtained at the visits indicated in Appendix C or 
upon subject discontinuation.  The ECG obtained at Screening will serve as the baseline 
assessment in the DB and OL Treatment Periods.  The ECG should be performed prior to 
blood collection.
Each ECG will be evaluated by an appropriately qualified physician at the site ("local 
reader"), preferably a cardiologist.  This reading of the ECG will be used by the 
investigator for subject safety assessments, including adverse event determination and 
management, and decision on whether a subject will be discontinued from the study.
The local reader will sign and date all the ECGs collected in this study and provide a 
global interpretation for each ECG using the following categories:
●
Normal ECG
●
Abnormal ECG – Not clinically significant (NCS)
●
Abnormal ECG – Clinically significant (CS)
All local reader's evaluations of ECGs will be entered into the electronic source 
documents, electronic case report forms or paper case report forms.  All ECG source 
documentation will be retained at the study site.  The automatic cardiograph reading 
(i.e., cardiograph-generated measurements and interpretations) will not be collected for 
analysis.


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Clinical Laboratory Tests
Samples will be obtained at a minimum for the clinical laboratory tests listed in Table 2 at 
the visits indicated in Appendix C.
The blood samples for serum chemistry tests should be collected following a minimum 
8-hour fast prior to study drug intake (with the exception of the Screening Visit, which 
may be non-fasting).  Subjects whose visits occur prior to the morning dose of study drug 
should be instructed to fast after midnight until the blood sample is collected in the 
morning and thereafter take their study medications with food.  Subjects whose visits 
occur following the morning dose of study drug should be instructed to fast after breakfast 
until the study visit occurs.  At the Double-Blind Study Day 1 visit, a fasting blood 
sample should be collected prior to the first dose of study drug.  Blood samples should 
still be drawn if the subject did not fast for at least 8 hours.  Fasting or non-fasting status 
will be recorded in the source documents and on the laboratory requisition.  The baseline 
laboratory test results for clinical assessment for a particular test will be defined as the last 
measurement prior to the initial dose of study drug.
A central laboratory will be utilized to process and provide results for the clinical 
laboratory tests.
During the DB Treatment Period, measures to prevent implicit un-blinding by laboratory 
results will be used.  Specifically, the results of HCV RNA, ALT, AST, and bilirubin 
(indirect and total), will be blinded to the investigator, subject and AbbVie until the final 
scheduled DB Period visit (Week 8 or Week 16) or Premature D/C Visit, unless criteria 
for virologic failure or relevant predefined toxicity are met, in which case the relevant 
laboratory data will be un-blinded to the investigator, subject and AbbVie, see 
Section 5.4.1.1, Section 5.5.5 and Section 6.1.7.
Instructions regarding the collection, processing, and shipping of these samples can be 
found in the laboratory manual provided by the central laboratory chosen for this study.  
The certified laboratory chosen for this study is Covance.


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Table 2.
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Other Tests
Hematocrit
Hemoglobin
Red Blood Cell (RBC) 
count
White Blood Cell (WBC) 
count
Neutrophils
Bands, if detected
Lymphocytes
Monocytes
Basophils
Eosinophils
Platelet count (estimate not
acceptable)
Reticulocyte count
Prothrombin Time/INR
Activated partial 
thromboplastin time 
(aPTT)
Blood Urea Nitrogen (BUN)
Creatinine
Total bilirubin
Direct and indirect bilirubin
Alanine aminotransferase
(SGPT/ALT)
Aspartate aminotransferase 
(SGOT/AST)
Alkaline phosphatase
Sodium
Potassium
Calcium
Inorganic phosphorus
Uric Acid
Cholesterol
Total protein
Glucose
Triglycerides
Low Density Lipoproteins
(LDL)a,b
High Density Lipoprotein (HDL)b
Albumin
Chloride
Bicarbonate
Magnesium
Total insulin
Gamma-glutamyl transferase 
(GGT)
Creatinine clearance (Cockcroft 
Gault calculation)
Creatine phosphokinase (CPK)c
Follicle stimulating hormone
(FSH)d
eGFR (C-MDRD)e
HBsAgf
HBV DNA (if HBsAg is negative)f
HCV Abf
HIV Abf
Opiatesf
Barbituratesf
Amphetaminesf
Cocainef
Benzodiazepinesf
Alcoholf
Phencyclidinef
Propoxyphenef
Methadonef
Hemoglobin A1Cf
HCV genotype and sub-typef
Urine and Serum:
Human Chorionic
Gonadotropin (hCG) 
for femalesg
Hepatitis B Panelh
HCV RNA
Plasma HIV-1 RNAi
HIV-1 genotypic resistance
testing (as applicable)i
CD4,i CD4%i
CD8,i CD8%i
CD4:CD8i
IL28B
Alpha2-macroglobulinj
Haptoglobinj
Apolipoprotein A1j
Urinalysis
Specific gravity
Ketones
pH
Protein
Blood
Glucose 
Urobilinogen
Bilirubin
Leukocyte esterase
Microscopic (reflex)
a.
Directly Measured.
b.
Performed only at Baseline.
c.
Performed during the Double-Blind Treatment Period.
d.
FSH at Screening only for female subjects to assess postmenopausal state.
e.
eGFR calculated by the MDRD formula, modified for the Chinese population (C-MDRD).
f.
Performed only at Screening.
g.
Pregnancy testing is not required for females of non-childbearing potential.


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Table 2.
Clinical Laboratory Tests (Continued)
h.
Performed for management of transaminase elevations (Section 6.1.7.1).
i.
Only for HCV/HIV co-infected subjects.
j.
Component of FibroTest collected only if needed during the Screening Period.
For any laboratory test value outside the reference range that the investigator considers 
clinically significant:
●
The investigator will repeat the test to verify the out-of-range value.
●
The investigator will follow the out-of-range value to a satisfactory clinical 
resolution.
●
A laboratory test value that requires a subject to be discontinued from the 
study or study drug or requires a subject to receive treatment will be recorded 
as an adverse event.
The management of laboratory abnormalities that may occur during the study is described 
in Section 6.1.7.
Pregnancy Test
A serum pregnancy test will be performed for all female subjects of childbearing potential 
at Screening.  Subjects with borderline pregnancy tests at Screening must have a serum 
pregnancy test ≥ 3 days later to document continued lack of a positive result.  Additional 
urine pregnancy tests will be performed at all the visits indicated in Appendix C.  
Pregnancy testing is not required for females of non-childbearing potential.  
Determination of postmenopausal status will be made during the Screening period, based 
on the subject's history.
Concomitant Medication Assessment
Use of medications (prescription or over-the-counter, including vitamins, herbal 
supplements, and vaccines) from the time of signing the consent, through the DB (and 
OL, if applicable) Treatment Period, and 30 days after active study drugs are stopped 
must be recorded in the eCRF at each study visit indicated in Appendix C.  Thereafter, 


ABT-493, ABT-530
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only medications taken for SAEs and treatment of HCV and HIV will be recorded in the 
eCRF at each study visit indicated in Appendix C (Post-Treatment Period).
Hepatitis and HIV Screen
HBsAg (hepatitis B surface antigen), HBV DNA (if HBsAg is negative), HCV Ab and 
HIV Ab tests will be performed at Screening.  The tests will be performed by a certified 
laboratory.  The investigator must discuss any local reporting requirements to local health 
agencies with the subject.  The site will report these results per local regulations, if 
necessary.
Urine Screens for Drugs of Abuse
A urine screen for drugs of abuse will be performed at Screening.  The panel for drugs of 
abuse will minimally include drugs listed in Table 2.  Any positive result must be assessed 
for clinical significance.
These analyses will be performed by the certified central laboratory chosen for the study.
Liver Diagnostic Testing
Subjects who have not had a qualifying liver biopsy within the previous 24 months or 
who have not had a qualifying FibroScan® within the previous 6 months but otherwise 
meet all of the inclusion criteria and none of the exclusion criteria will undergo liver 
biopsy or non-invasive testing (FibroTest and APRI or FibroScan®) for assessment of 
cirrhosis prior to enrollment.  Selection of liver biopsy or non-invasive testing performed 
should be based on local standard practice.
Biopsy results as per METAVIR, Batts Ludwig, Knodell, IASL, Scheuer, or Laennec 
gradings with fibrosis score of ≤ 3, or Ishak grading with fibrosis score of ≤ 4 are 
acceptable for ascertaining absence of cirrhosis.  Subjects with historical liver FibroScan®
or biopsy results are acceptable if these were conducted within 6 or 24 months from 
Screening, respectively and the results are not exclusionary.  In a subject with an 
indeterminate FibroTest result (0.48 < result < 0.75), or conflicting FibroTest and APRI 


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results (e.g., FibroTest ≤ 0.48, but APRI ≥ 1) at Screening, liver FibroScan® or biopsy can 
be performed during Screening to ascertain the presence or absence of cirrhosis.  Subjects 
with indeterminate FibroScan® score (12.5 ≤ score < 14.6) may only be enrolled if they 
have a qualifying liver biopsy performed within 24 months prior to or during Screening.
Patient Reported Outcomes (PRO) Instruments (Questionnaires)
Subjects will complete the self-administered PRO instruments (where allowed per local 
regulatory guidelines) on the study days specified in Appendix C.  Subjects should be 
instructed to follow the instructions provided with each instrument and to provide the best 
possible response to each item.  Site personnel shall not provide interpretation or 
assistance to subjects other than encouragement to complete the tasks.  Subjects who are 
functionally unable to read any of the instruments may have site personnel read the 
questionnaires to them.  Site personnel should encourage completion of each instrument at 
all specified visits and should ensure that a response is entered for all items.
EuroQol-5 Dimensions-3 Level (EQ-5D-3L)
The EQ-5D-3L is a health state utility instrument that evaluates preference for health 
status (utility).  The 5 items in the EQ-5D-3L comprise 5 dimensions (mobility, self-
care, usual activities, pain/discomfort, and anxiety/depression) each of which are rated
on 3 levels of severity.  Responses to the 5 items encode a discrete health state which 
is mapped to a preference (utility) specific for different societies.  Subjects also rate 
their perception of their overall health on a separate visual analogue scale (VAS).  The 
EQ-5D-3L should require approximately 5 minutes to complete.
Fatigue Severity Scale (FSS)
The FSS measures the impact of fatigue over the past week on specific types of 
functioning (e.g., motivation, exercise, physical functioning, carrying out duties, 
interfering with work, family, or social life).  The survey consists of 9 questions using 
a 7-point Likert scale.  A total score is calculated as the average of the individual item 
responses.  The scale's psychometric properties have been confirmed in chronic 


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hepatitis C and other diseases.  The FSS should require approximately 5 minutes to 
complete.
PRO instruments should be completed prior to drug administration on Study Day 1 and 
prior to any discussion of adverse events or any review of laboratory findings, including 
HCV RNA levels.
Enrollment and Assignment of Subject Numbers
All screening activities must be completed and reviewed prior to enrollment.  Subjects 
who meet all the Inclusion Criteria and none of the Exclusion Criteria at Screening will 
proceed to randomization via the IRT system on DB Study Day 1.
Screening numbers will be unique 6-digit numbers and will begin with 100101 with the 
first three digits representing the investigative site, and the last three digits representing 
the subjects at that site.  Randomized subjects will keep their screening number as their 
subject number throughout the study.  Subjects will be enrolled at the DB Day 1 visit as 
described in Section 5.5.3 and will receive a separate unique 5-digit randomization 
number that will be recorded automatically in the eCRF through the IRT system.  The 
randomization number will be used only by AbbVie for loading the treatment schedule 
into the database.
Study Drug Compliance for Kits
Individual kits of ABT-493/ABT-530 or matching placebo will be provided for subject 
dosing to the site.  Each subject will have compliance documented by the site in the 
subject's source notes for ABT-493/ABT-530 or placebo.  At each Study Drug 
Accountability Visit, the overall number of tablets of ABT-493/ABT-530 or placebo 
remaining in each bottle will be recorded in the source and entered in the IRT system 
along with the date of reconciliation.


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HCV Genotype and Sub-Genotype
Plasma samples for HCV genotype and sub-genotype determination will be collected at 
Screening.  Genotype and sub-genotype will be assessed using the appropriate assay by 
the central laboratory.
HCV RNA Levels
Plasma samples for HCV RNA levels will be collected as indicated in Appendix C.  
Plasma HCV RNA levels will be determined by an approved HCV RNA quantitative 
assay for each sample collected by the central laboratory (including but not limited to 
Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Quantitative Test, v2.0).
HCV Resistance Testing Sample
A plasma sample for HCV resistance testing will be collected prior to dosing on Day 1 in 
the DB Treatment Period and at the study visits indicated in Appendix C.  Specific 
instructions for preparation and storage of HCV RNA and HCV resistance samples will 
be provided by the central laboratory, AbbVie, or its designee.
Flow Cytometry, HIV-1 RNA and HIV Resistance Testing Samples
Samples for plasma HIV-1 RNA levels and flow cytometry (including but not limited to 
CD4+ T-cell and CD8+ T-cell counts [absolute and percent]) will be obtained at the times 
specified in Appendix C.
If a subject who is on stable HIV-1 ART has an HIV-1 RNA level ≥ 200 copies/mL, the 
subject's HIV-1 RNA is to be repeated as noted in Section 5.4.1.2.  At the time the repeat 
plasma HIV-1 RNA is drawn, a sample may be obtained for HIV-1 genotypic resistance 
testing.  If the subject's repeat HIV-1 RNA is ≥ 500 copies/mL, the sample obtained for 
HIV-1 genotypic resistance testing may be analyzed as indicated by local standard of care.


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If the subject's repeat HIV-1 RNA is < 200 copies/mL, then the subject will resume 
routine plasma HIV-1 RNA assessments as shown in Appendix C and described in 
Section 5.4.1.2.
Specific instructions for preparation and storage of flow cytometry, plasma HIV-1 RNA, 
and HIV resistance samples, if applicable, will be provided by the central laboratory, 
AbbVie, or its designee.
Archive Plasma Sample
Archive plasma samples will be collected at the study visits, indicated in Appendix C.  
Archive plasma samples are being collected for possible additional analyses, including but 
not limited to, study drug or metabolite measurements, viral load, safety/efficacy 
assessments, HCV gene sequencing, HCV resistance testing, and other possible predictors 
of response, as determined by AbbVie.
Specific instructions for preparation and storage of archive samples will be provided by 
the central laboratory, AbbVie, or its designee.
5.3.1.2
Meals and Dietary Requirements
Study drugs, both ABT-493/ABT-530 and matching placebo should be taken with food.
5.3.1.3
Blood Samples for Pharmacogenetic Analysis
Specific instructions for collection, storage and shipment of pharmacogenetic samples will 
be provided by the central laboratory, AbbVie, or its designee.
IL28B Sample
One (required) whole blood sample for DNA isolation will be collected from each subject 
at Study Day 1 in the DB Treatment Period for Interleukin 28B (IL28B) pharmacogenetic 
analysis.  If the IL28B pharmacogenetic sample is not collected on DB Study Day 1, it 
may be collected at any other visit during the study.  This sample will not be used for any 
testing other than IL28B GTs.


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Optional Sample for Pharmacogenetic Analysis
A separate (optional) whole blood sample for DNA isolation will be collected at baseline 
on Study Day 1 from each subject who consents.  If the optional pharmacogenetic sample 
is not collected on Study Day 1, it may be collected at any other visit during the study.  
The procedure for obtaining and documenting informed consent is discussed in 
Section 9.3.  Samples collected in China will be shipped frozen to the central laboratory in 
China and then to an AbbVie designated laboratory in China for long-term storage.  
Samples collected outside of China will be sent to an AbbVie designated laboratory 
outside of China for long term storage.  All samples will be stored in a secure storage 
space with adequate measures to protect confidentiality.  The samples will be retained 
while research on ABT-493 and ABT-530 or drugs for the treatment of HCV continues 
but no longer than 5 years after completion of this study and all study endpoint data are 
analyzed.
5.3.2
Drug Concentration Measurements
5.3.2.1
Collection of Samples for Analysis
Blood samples for pharmacokinetic assay of ABT-493, possible ABT-493 metabolites, 
ABT-530, possible ABT-530 metabolites and HIV-1 ART regimens will be collected by 
venipuncture at each study visit during the DB or OL Treatment Periods as indicated in 
Appendix C.
Subjects who do not participate in Optional Intensive PK sampling:
●
At all DB and OL Treatment Period visits, except for Day 1, a single blood 
sample (3 mL) will be collected for ABT-493/ABT-530 without regard to the 
time of dosing.  For co-infected subjects only, an additional blood sample 
(4 mL) will be collected for possible HIV-1 ART assays.
●
The date and time of blood sample collection and the two previous doses of the 
study drug will be recorded to the nearest minute in the source documents.  
Additionally, the date and time of the two previous doses of the study drug 
will be recorded to the nearest minute on the eCRF.


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Subjects who consent to participate in Optional Intensive PK sampling:
●
On DB Day 1 and the DB and OL Week 4 visits, subjects will have their dose 
administered by study site personnel after food.  Blood samples (3 mL each) 
will be collected on DB Day 1 at 2, 4 and 6 hours post-dose and at the DB and 
OL Week 4 Visits immediately prior to dose (0 hour) and 2 and 4 hours post-
dose.  For co-infected subjects only, an additional blood sample (4 mL) will be 
collected at each timepoint for possible HIV-1 ART assays.
○
The date and time of site-administered dose, blood sample collection and 
the two previous doses of study drug (for Week 4 Visit only) will be 
recorded to the nearest minute in the source documents.  Additionally, the 
date and time of the site-administered dose and two previous doses (for 
Week 4 Visit only) will be recorded in the eCRF.
●
At all other DB and OL Treatment Period visits, a single blood sample (3 mL) 
will be collected for ABT-493/ABT-530 without regard to the time of dosing.  
For co-infected subjects only, an additional blood sample (4 mL) will be 
collected for possible HIV-1 ART assays.
○
The date and time of blood sample collection and the two previous doses 
of the study drug will be recorded to the nearest minute in the source 
documents.  Additionally, the date and time of the two previous doses of 
the study drug will be recorded to the nearest minute on the eCRF.
5.3.2.2
Handling/Processing of Samples
Specific instructions for collection of blood samples and subsequent preparation and 
storage of the plasma samples for the pharmacokinetic assays of ABT-493 and ABT-530 
(and their possible metabolites) and HIV-1 ART regimens will be provided by the central 
laboratory, AbbVie, or its designee.
5.3.2.3
Disposition of Samples
The frozen plasma samples for the pharmacokinetic assays of ABT-493 and ABT-530 
(and their possible metabolites), HIV-1 ART regimens and archive plasma samples will 


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be packed in dry ice sufficient to last during transport, and transferred from the study site 
to the central laboratory.
The central laboratory will then ship the ABT-493, ABT-530 and HIV-1 ART samples to 
the reference laboratories following separately provided instructions.
5.3.2.4
Measurement Methods
Plasma concentrations of ABT-493 and ABT-530 will be determined using validated 
assay methods under the supervision of the Drug Analysis Department at AbbVie.  
Plasma concentrations of possible metabolites of any analytes listed above may also be 
determined using either validated or non-validated methods.
Plasma concentrations of HIV-1 ART regimens for individual subjects, a group of 
subjects or for the whole study may be analyzed based on safety, HCV RNA and plasma 
HIV-1 RNA results.  The plasma concentrations of HIV-1 ART regimens will be 
determined, if necessary, under the supervision of the Drug Analysis Department at 
AbbVie.
5.3.3
Efficacy Variables
HCV virologic response will be assessed by plasma HCV RNA levels in IU/mL at various 
time points from Day 1 through 24 weeks after completion or discontinuation of active 
treatment in either DB Treatment Period (Arm A) or the OL Treatment Period (Arm B).
5.3.3.1
Primary Variable
The primary efficacy variable is SVR12 (HCV RNA < LLOQ 12 weeks after the last 
actual dose of study drug) for the subjects treated with ABT-493/ABT-530 in the DB 
Treatment Period (Arm A).


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5.3.3.2
Secondary Variables
The secondary efficacy variables are on-treatment HCV virologic failure and post-
treatment relapse of HCV infection (excluding re-infection) in Arm A subjects, and SVR12
for HCV/HIV co-infected Arm A subjects.
5.3.4
HCV Resistance Variables
For all subjects receiving active study drugs who experience virologic failure, the HCV 
amino acid variants at signature resistance-associated positions in NS3 and NS5A at 
baseline identified by population or deep sequencing and comparison to the appropriate 
prototypic reference sequence will be analyzed.
The following resistance information will be analyzed for subjects receiving active study 
drugs who experience virologic failure and who have an available post baseline sample 
with HCV RNA ≥ 1000 IU/mL:  1) the HCV amino acid variants in NS3 and NS5A 
identified by population or deep sequencing and comparison to the baseline sequence, 
2) the HCV amino acid variants at signature resistance-associated amino acid positions in 
NS3 and NS5A identified by population or deep sequencing and comparison to the 
appropriate prototypic reference sequence, and 3) the persistence of HCV viral amino acid 
variants in NS3 and NS5A by population or deep sequencing.
5.3.5
HIV Resistance Variables
If any subject on stable HIV-1 ART develops a confirmed, quantifiable plasma HIV-1 
RNA level (HIV-1 RNA ≥ 200 copies/mL at one assessment and ≥ 500 copies/mL on 
repeat testing) after starting the study, the HIV-1 protease, reverse transcriptase and 
integrase sequences may be analyzed as indicated by local standard of care practices.
5.3.6
Safety Variables
The following safety evaluations will be performed during the study:  adverse events, vital 
signs, physical examination, ECG, and laboratory tests assessments.


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HIV virologic response will be assessed by plasma HIV-1 RNA levels in copies/mL at 
various time points during the DB and OL Treatment Periods and the Post-Treatment 
Period.
5.3.7
Pharmacokinetic Variables
Individual plasma concentrations of ABT-493 and ABT-530 (and their possible 
metabolites) will be tabulated and summarized.  Plasma concentrations of HIV-1 ARTs 
for individual subjects, a group of subjects or for the whole study may be analyzed based 
on HCV RNA and/or plasma HIV-1 RNA results and summarized.
5.3.8
Pharmacogenetic Variables
IL28B status will be determined for each subject and analyzed as a factor contributing to 
the subject's response to study treatment.  These IL28B GT results may be analyzed as 
part of a multi-study assessment of IL28B and response to ABT-493, ABT-530, or drugs 
of these classes.  The results may also be used for the development of diagnostic tests 
related to IL28B and study treatment, or drugs of these classes.  The results of additional 
IL28B pharmacogenetic analyses may not be reported with the clinical study report.
DNA samples from subjects who separately consent for additional pharmacogenetic 
analysis may be sequenced and data analyzed for genetic factors contributing to the 
disease or to the subject's response to study treatment, in terms of pharmacokinetics, 
efficacy, tolerability and safety.  Such genetic factors may include genes for drug 
metabolizing enzymes, drug transport proteins, genes within the target pathway, or other 
genes believed to be related to drug response.  Some genes currently insufficiently 
characterized or unknown may be understood to be important at the time of analysis.  
Pharmacogenetic analyses will be limited to ABT-493 and ABT-530, drugs of this class, 
HCV and related conditions.  Pharmacogenetic analyses will not be done to determine a 
subject's predisposition to unrelated diseases.  Pharmacogenetic analyses will take place at 
an AbbVie designated laboratory in China and data will be exported to AbbVie in the 
United States.


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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 an adverse event or 
noncompliance with the protocol.
If, during the DB or OL Treatment Period, the subject prematurely discontinues, the 
procedures outlined for the applicable Premature D/C Visit should be completed as 
defined in Appendix C.  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 
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.  The last dose of any study drug and reason for discontinuation will be recorded 
in the EDC (electronic data capture) system.  The subject should then begin the Post-
Treatment Period where the subject will be monitored for 24 weeks for HCV RNA, the 
emergence and/or persistence of resistant viral variants, plasma HIV-1 RNA, HIV 
resistance (as applicable) and PROs (Arm A Only).
Subjects prematurely discontinuing from the DB period and who on un-blinding are found 
to have been randomized to placebo may elect to remain in the study (at the investigator's 
discretion) and receive active treatment during the Open-Label Period.  However, the 
subject is expected to continue to attend all remaining DB Treatment Period study visits 
and perform all remaining study procedures through the final scheduled DB visit (Week 8 
or Week 16), in order to be eligible to enter the OL Treatment Period and receive active 
open-label treatment.


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If a subject is discontinued from the Post Treatment Period, the subject should return for 
Post-Treatment Discontinuation procedures as defined in Appendix C.  The reason for 
discontinuation will also be recorded in the Study Discontinuation eCRF.
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.
In the event that a positive result is obtained on a pregnancy test for a subject or a subject 
reports becoming pregnant during the DB or OL Treatment Period, the administration of 
DAAs to that subject may be continued at the Principal Investigator's discretion after 
discussion with the subject, if the benefit of continuing DAAs is felt to outweigh the 
potential risk.  Specific instructions regarding subject pregnancy can be found in 
Section 6.1.6.  Subjects will be monitored for SVR in the Post-Treatment Period as 
described in Section 5.1.4.
5.4.1.1
HCV Virologic Stopping Criteria
During the DB Treatment Period of the study, the HCV virologic results will be reviewed 
and HCV virologic stopping criteria will be applied to those subjects randomized to active 
drugs by an un-blinded independent reviewer who will provide information to the 
investigators to assist with managing these subjects according to the criteria below.  No 
HCV virologic stopping criteria will be applied to subjects randomized to placebo during 
the DB Treatment Period.  During the OL Treatment Period, investigators will be un-
blinded to HCV virologic data and will manage subjects according to the criteria below.
HCV virologic stopping criteria are defined as follows: 
●
Confirmed increase from nadir in HCV RNA (defined as 2 consecutive HCV 
RNA measurements of > 1 log10 IU/mL above nadir) at any time point during 
treatment; or


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●
Confirmed HCV RNA ≥ 100 IU/mL (defined as 2 consecutive HCV RNA 
measurements ≥ 100 IU/mL) after HCV RNA < LLOQ during treatment.
When confirmatory testing is required it should be completed as soon as possible and the 
subject should remain on study treatment until the HCV virologic stopping criterion has 
been confirmed.  Subjects meeting a virologic stopping criterion 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, plasma HIV-1 RNA, HIV resistance 
(as applicable) and PROs (Arm A only) until 24 weeks post-treatment.
5.4.1.2
Failure to Maintain HIV Virologic Suppression
HIV-1 RNA will be assessed at each scheduled study visit during the DB Treatment 
Period, OL Treatment Period and PT Period, as detailed in Appendix C.
For HCV/HIV-1 Co-Infected Subjects on Stable ART
The criteria for failure to maintain HIV virologic suppression is as follows:
●
HIV-1 RNA ≥ 200 copies/mL confirmed on 2 consecutive tests at least 
2 weeks apart, in a subject compliant with their HIV ART therapy.
At the time a confirmatory HIV-1 RNA is drawn, a sample for HIV-1 genotypic resistance 
testing may also be obtained; this sample may be analyzed if the subject's repeat plasma 
HIV-1 RNA is ≥ 500 copies/mL.  A subject should remain on HCV study drug treatment 
and his/her current ART regimen while the failure to maintain HIV virologic suppression 
is being confirmed.  A confirmatory HIV-1 RNA and HIV-1 genotypic resistance blood 
draw can be done as an unscheduled visit.  However, if this blood draw falls on the date of 
a scheduled study visit (Appendix C), only a single HIV-1 RNA and HIV-1 genotypic 
resistance blood draw needs to be performed at this visit.  
Clinical management of failure to maintain HIV-1 virologic suppression during the study 
(DB and OL Treatment Periods and Post-Treatment Period) will be handled by the site 
investigator according to current HIV treatment guidelines and local standard of care.  


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If the investigator wishes to change the HIV-1 ART regimen for a subject, it must be 
discussed with the AbbVie TA MD prior to the change being made, unless the change is 
being made to address an immediate safety concern.
During the DB or OL Treatment Periods, subjects with confirmed failure to maintain 
HIV-1 RNA suppression should continue study drug (active or matching placebo) 
treatment unless there is a requirement for prohibited concomitant medications (see 
Section 5.2.3.2 and Section 5.2.3.4) to construct a new HIV ART regimen.
For HCV/HIV-1 Co-Infected Subjects Naïve to ART
Clinical management of ART-naïve co-infected subjects during the study (DB and OL 
Treatment Periods and Post-Treatment period) will be handled by the site investigator 
according to current HIV treatment guidelines and local standard of care.  During the DB 
and OL Treatment Periods, if an investigator deems it necessary to initiate HIV-1 ART for 
a subject, continuation of study drug treatment must be discussed with the AbbVie TA 
MD prior to ART initiation.
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.  If AbbVie terminates the study for safety reasons, AbbVie will immediately 
notify the investigator by telephone and subsequently provide written instructions for 
study termination.


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5.5
Treatments
5.5.1
Treatments Administered
Each dose of blinded or open-label study drugs (ABT-493/ABT-530 or placebo) will be 
dispensed in the form of film-coated co-formulated tablets at the visits listed in 
Appendix C.  Subjects will be instructed to take study drugs at the same time every day 
with food.  Prior to all visits with pharmacokinetic sampling, the date and time of the 
two previous doses will be recorded to the nearest minute in the source documents and the 
eCRF.  For subjects participating in Intensive PK sampling on Study Day 1 and at the 
Week 4 visit during the DB and OL treatment periods, they will have their dose 
administered by study site personnel after food and blood samples are collected for assay 
of study drugs.  The date and time of dosing and blood sample collection will be recorded 
to the nearest minute in the source document.
In Arm A, ABT-493/ABT-530 will be provided by AbbVie as 100 mg/40 mg film-coated 
tablets.  ABT-493/ABT-530 will be taken orally as 3 tablets QD with food, which 
corresponds to ABT-493 300 mg/ABT-530 120 mg QD.
In Arm B, placebo matching the ABT-493/530 will be provided by AbbVie.
Subjects in Arm B entering the OL Treatment Period will be given ABT-493/ABT-530 as 
100/40 mg film-coated tablets to be taken orally as 3 tablets QD with food at the final 
scheduled DB Treatment Period visit (Week 8 or Week 16) along with instructions to 
begin dosing the next day.  The site will call the subject within 4 days after the final 
scheduled DB Treatment Period visit to confirm dosing on OL Day 1 and record the date 
of the first dose in the source documents.
Study drugs (ABT-493/ABT-530 and matching placebo) should be taken with food. 
Study drug must not be dispensed without contacting the IRT system.  Study drug may 
only be dispensed to subjects enrolled in the study through the IRT system.  At the end of 
the DB and OL Treatment Periods or at the Premature D/C Visit from the DB or OL 


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Treatment Period, the site will contact the IRT system to provide visit date information 
and study drug return information for each kit (Section 5.5.7).
All subjects who receive at least one dose of active study drug, either in the DB or OL 
Treatment Period, and meet the HCV virologic stopping criteria or fail to maintain HIV 
virologic suppression should follow instructions in Section 5.4.1.1 and Section 5.4.1.2, 
respectively.
5.5.2
Identity of Investigational Product
Information about the study drugs to be used in this study is presented in Table 3.
Table 3.
Identity of Investigational Products
Investigational Product
Manufacturer
Mode of 
Administration
Dosage 
Form
Strength
ABT-493/ABT-530
AbbVie
Oral
Film 
Coated 
Tablet
100 mg/40 mg
Placebo for ABT-493/ABT-530
AbbVie
Oral
Film 
Coated 
Tablet
0 mg
5.5.2.1
Packaging and Labeling
All study drugs, including matching placebo, will be supplied in matching bottles.
Each bottle will be labeled as required per country requirements.
The labels must remain affixed to the bottles.  All blank spaces should be completed by 
site staff prior to dispensing to subject.


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5.5.2.2
Storage and Disposition of Study Drug
Study Drug
Storage Conditions
ABT-493/ABT-530 bottles
15° to 25°C (59° to 77°F)
Placebo for ABT-493/ABT-530
15° to 25°C (59° to 77°F)
The investigational products are for investigational use only and are to be used only 
within the context of this study.  The study drug supplied for this study must be 
maintained under adequate security and stored under the conditions specified on the label 
until dispensed for subject use or returned to AbbVie.
5.5.3
Method of Assigning Subjects to Treatment Groups
At the Screening Visit, all subjects will be assigned a unique subject number through the 
use of IRT.  For subjects who do not meet the study selection criteria, the site personnel 
must contact the IRT system and identify the subject as a screen failure.
Subjects who are enrolled will retain their subject number, assigned at the Screening Visit, 
throughout the study.  For enrollment of eligible subjects into the study, the site will 
utilize the IRT system in order to receive unique randomization numbers.  The 
randomization number will be used only by AbbVie for loading the treatment assignments 
into the database.  The randomization numbers will be assigned according to schedules 
computer-generated before the start of the study by the AbbVie Statistics Department.  
Upon receipt of study drug, the site will acknowledge receipt in the IRT system.
Contact information and user guidelines for IRT use will be provided to each site.
Subjects meeting the eligibility criteria will be randomized as described in Section 8.3.
5.5.4
Selection and Timing of Dose for Each Subject
Selection of the doses for this study is discussed in Section 5.6.4.  Study drug dosing will 
be initiated at the DB Day 1 Visit.


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All three tablets of ABT-493/ABT-530 or placebo will be dosed together QD.  All 
subjects should take all doses of study medications with food.
Subjects initially randomized to placebo in the DB Treatment Period will begin open-label 
ABT-493/ABT-530 on OL Day 1, the day after the final scheduled DB Period visit 
(Week 8 or Week 16).
5.5.5
Blinding
Investigators, study site personnel, AbbVie, and subjects will remain blinded to each 
subject's treatment during the DB Treatment Period.  ABT-493/ABT-530 and matching 
placebo will be provided as tablets.
During the DB Treatment Period, measures to prevent implicit un-blinding by laboratory 
results will be used.  Specifically, the results of HCV RNA, ALT, AST, and bilirubin 
(indirect and total), will be blinded to the investigator, subject and AbbVie until the final 
scheduled DB Period visit (Week 8 or Week 16) or Premature D/C Visit, unless criteria 
for HCV virologic failure or relevant predefined toxicity are met, in which case the 
relevant laboratory data will be un-blinded to the investigator, subject and AbbVie, see 
Section 5.4.1.1, and Section 6.1.7.  During the blinded period, an un-blinded independent 
reviewer will review HCV RNA data and provide guidance related to HCV virologic 
failure (Section 5.4.1.1).
A subject's study drug assignment may be un-blinded as part of toxicity management, at 
the investigator's or TA MD's discretion (if deemed necessary for subject safety), or at 
premature discontinuation. If a subject's treatment assignment is formally un-blinded 
during the DB Treatment Period then results of the previously blinded laboratory tests, 
i.e., HCV RNA levels, transaminases, and bilirubin (indirect and total) will be provided to 
the investigator and AbbVie.
In the setting of premature discontinuation of double-blind study drug for toxicity 
management or HCV virologic failure (for those subjects on active drug), the investigator, 
subject and AbbVie will be un-blinded to study drug assignment via IRT.  Subjects 


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prematurely discontinuing and who on un-blinding are found to have been randomized to 
placebo may elect to remain in the study (at the Investigator's and the TA MD's joint 
decision) and receive active treatment during the Open-Label Period.  However, the 
subject is expected to attend all remaining DB Treatment Period study visits and perform 
all remaining study procedures through the final scheduled DB Period visit (Week 8 or 
Week 16), in order to be eligible to enter the OL Treatment Period and receive active 
treatment.  During the OL Treatment Period, open-label ABT-493/ABT-530 will be 
supplied.  Subjects prematurely discontinuing and who on un-blinding are found to have 
been randomized to active study drugs will enter the PT Period at the time of 
discontinuation.
The IRT system will be programmed with blind-breaking capability.  The study blind may 
be broken if, in the opinion of the investigator, it is in the subject's best interest to know 
the study drug assignment.  The sponsor, AbbVie, MUST be notified before breaking the 
blind unless identification of the study drug is required for emergency therapeutic 
measures.  If an emergency situation warrants breaking the blind, AbbVie must be 
notified within 24 hours of the blind being broken.  The date and reason the blind was 
broken must be recorded in the source records and on the appropriate eCRF.  The study 
blind may also be broken by the appropriately delegated AbbVie employees for safety and 
pharmacokinetic sample analysis reasons.  Any employees of AbbVie who are un-blinded 
will not be involved in other aspects of the trial or its management.
5.5.5.1
Blinding of Investigational Product
In order to maintain the blind, the ABT-493/ABT-530 and placebo tablets provided for 
the study will be identical in appearance and will be supplied in matching bottles.
5.5.6
Treatment Compliance
The investigator or his/her designated and qualified representatives will 
administer/dispense study drug only to subjects enrolled in the study in accordance with 
the protocol.  The study drug must not be used for reasons other than that described in the 
protocol.


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At the start of the study, each subject should receive counseling regarding the importance 
of dosing adherence with the treatment regimen with regard to virologic response and 
potential development of resistance due to poor compliance.
At each study drug accountability visit during the DB and OL Treatment Periods (see 
Appendix C), subjects will be instructed to bring all bottles of study drug (full, partial or 
empty) for assessment of treatment compliance.  At post-baseline dispensing visits 
denoted in Appendix C, study site personnel will assess subject compliance by inspecting 
the contents of the bottles and record the status of each one, as well as the exact number of 
remaining tablets of ABT-493/ABT-530 or placebo in IRT.  Treatment compliance will be 
based on the number of tablets dispensed, as recorded in IRT, and the number of 
remaining tablets.  If poor compliance is noted, the subject should be counseled and this 
should be documented in the subject's source.
5.5.7
Drug Accountability
The investigator or his/her representative will verify that study drug supplies are received 
intact and in the correct amounts via the IRT system.  A current (running) and accurate 
inventory of study drug will be kept by the investigator and will include lot number, kit 
number, number of tablets dispensed, subject number, initials of person who dispensed 
study drug and date dispensed for each subject.  An overall accountability of the study 
drug will be performed and verified by the AbbVie monitor throughout the DB and OL 
Treatment Periods.  The monitor will review study drug accountability on an ongoing 
basis.  Final accountability will be verified by the monitor at the end of study drug 
treatment at the site.
During the study, should an enrolled subject misplace or damage a study drug bottle of 
ABT-493/ABT-530 or placebo, the IRT system must be contacted and informed of the 
misplaced or damaged study drug.  If the bottle is damaged, the subject will be requested 
to return the remaining study drug to the site.  Replacement study drug may only be 
dispensed to the subject by contacting the IRT system.  Study drug replacement(s) and an 
explanation of the reason for the misplaced or damaged study drug(s) will be documented 


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within the IRT system.  Study drug start dates for each drug and the last dose of the 
regimen will be documented in the subject's source documents and recorded on the 
appropriate eCRF.  The status of each bottle, number of tablets remaining in each one 
returned, and the date of reconciliation will be documented in the IRT system.  The 
monitor will review study drug accountability on an ongoing basis.
Upon completion of or discontinuation from the DB or OL Treatment Period, all original 
study drug bottles (containing unused study drugs) will be returned to AbbVie (or 
designee) or destroyed on site.  All destruction procedures will be according to 
instructions from AbbVie and according to local regulations following completion of drug 
accountability procedures.  The number of tablets of each type of study drug returned in 
each bottle will be noted in the IRT system or on a drug accountability log (if 
appropriate).  Labels must remain attached to the containers.
5.6
Discussion and Justification of Study Design
5.6.1
Discussion of Study Design and Choice of Control Groups
The selection of the treatment regimen is based on Phase 2 and Phase 3 studies which 
indicate that the combination of ABT-493/ABT-530 300/120 mg QD is generally safe and 
is optimal to achieve high SVR rates in HCV GT1 – 6 infected subjects.
The current study (Study M15-592) is a multicenter, randomized, double-blind, placebo-
controlled Phase 3 study to evaluate the safety and efficacy of ABT-493/ABT-530 
300/120 mg QD combination in treatment-naïve or treatment-experienced (i.e., alpha, beta 
or pegylated interferon [pegIFN]) with or without RBV OR sofosbuvir with RBV with or 
without IFN.  HCV GT1 – 6 infected Asian adult subjects without cirrhosis, with or 
without HIV-co-infection.  The treatment duration is 8 weeks in non-cirrhotic subjects, 
with the exception of treatment-experienced GT3 HCV non-cirrhotic subjects who will 
receive 16 weeks of treatment.
The Phase 2 and 3 Analysis Set (integrated) from the global clinical development program 
includes all subjects who received doses of ABT-493 300 mg QD and ABT-530 120 mg 


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QD either from registrational studies or in supportive Phase 2 studies.  Efficacy data 
through Post-Treatment Week 12 for all subjects in the Phase 2 and 3 Analysis Set were 
included for the primary (SVR12) and secondary (on-treatment virologic failure and post-
treatment relapse) endpoints.  The Phase 2 and 3 Analysis Set organized by subject 
population is displayed in Table 4.  Subjects were considered treatment-experienced if 
they had failed regimens containing interferon, pegylated interferon, ribavirin, and/or 
sofosbuvir (TE-PRS).


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Table 4.
Overview of Clinical Studies by Subject Population (Phase 2 and 3 
Analysis Set)
Genotype
Clinical Study
Summary of Study Design
TN and TE Subjects Without Cirrhosis
GT1
M13-590*
ABT-493/ABT-530 300 mg/120 mg QD for 8 (n = 351) or 12 weeks
(n = 352)
M14-867
ABT-493/ABT-530 300 mg/120 mg QD for 8 weeks (n = 34)
GT2
M15-464
ABT-493/ABT-530 300 mg/120 mg QD (n = 202) or placebo
(n = 100) for 12 weeks
M14-868
ABT-493/ABT-530 300 mg/120 mg QD for 8 weeks (n = 199) or 12 weeks 
(n = 25)
GT3
M13-594
ABT-493/ABT-530 300 mg/120 mg QD for 8 (n = 157) or 12 weeks
(n = 233) or SOF 400 mg + DCV 60 mg QD for 12 weeks (n = 115) (all 
subjects in study were TN)
M14-868
ABT-493/ABT-530 300 mg/120 mg QD for 8 weeks (n = 29; TN only), 
12 weeks (n = 76), or 16 weeks (n = 22; TE only)
GT4, GT5, GT6
M13-583
ABT-493/ABT-530 300 mg/120 mg QD for 12 weeks (n = 121)
M14-867
ABT-493/ABT-530 300 mg/120 mg QD for 12 weeks (n = 32)
M14-868
ABT-493/ABT-530 300 mg/120 mg QD for 8 weeks (n = 58)
TN and TE Subjects With Cirrhosis
GT1, GT2, 
GT4, GT5, GT6
M14-172
ABT-493/ABT-530 300 mg/120 mg QD for 12 weeks (n = 146)
GT3
M14-868
ABT-493/ABT-530 300 mg/120 mg QD for 12 weeks (n = 64; TN only) or 
16 weeks (n = 51; TE only)
Subjects With CKD Stages 4 – 5 With or Without Cirrhosis
GT1 – GT6
M15-462
ABT-493/ABT-530 300 mg/120 mg QD for 12 weeks (n = 104)
NS5A Inhibitor and/or PI-Experienced Subjects With or Without Cirrhosis
GT1, GT4
M15-410
ABT-493/ABT-530 300 mg/120 mg QD for 12 (n = 66) or 16 weeks (n = 47)
CKD = chronic kidney disease; DCV = daclatasvir; GT = genotype; NS5A = nonstructural viral protein 5A; 
PI = protease inhibitor; QD = once daily; SOF = sofosbuvir; TE = treatment-experienced; TN = treatment-naïve
*
HCV monoinfected or HIV-coinfected.
Treatment durations were selected based on Phase 2 and 3 Analysis Set from 8-week or 
12-week treatment groups receiving ABT-493/ABT-530 300/120 mg combinations in 
HCV GT1, GT2, GT3, GT4, GT5, and GT6-infected non-cirrhotic patients with or 
without previous treatment experience (Table 5, Table 6, and Table 7).


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Table 5.
Summary of SVR12, On-Treatment Virologic Failure, and Post-Treatment Relapse in TN and TE
Non-GT3-Infected Subjects by Cirrhosis Status (TN + TE-PRS Subjects, Phase 2 and 3 Analysis Set)
Endpoint
n/N (%)
GT1
GT2
GT4
GT5
GT6
8 
Weeks
12 
Weeks
Overall
8 Weeks
12 
Weeks
Overall
8 
Weeks
12 
Weeks
Overall
8 
Weeks
12 
Weeks
Overall
8 
Weeks
12 
Weeks
Overall
Subjects Without Cirrhosis
SVR12
383/387 
(99.0)
400/401 
(99.8)
783/788 
(99.4)
193/197 
(98.0)
232/234 
(99.1)
425/431 
(98.6)
43/46 
(93.5)
111/112 
(99.1)
154/158 
(97.5)
2/2 
(100)
28/28 
(100)
30/30 
(100)
9/10 
(90.0)
31/31 
(100)
40/41 
(97.6)
OTVF
1/387 
(0.3)
0/401
1/788 
(0.1)
0/197
0/234
0/431
0/46
0/112
0/158
0/2
0/28
0/30
0/10
0/31
0/41
Relapse12
0/384
0/400
0/784
2/195 
(1.0)
0/232
2/427 
(0.5)
0/45
0/111
0/156
0/2
0/27
0/29
0/10
0/30
0/40
Subjects With Cirrhosis
SVR12
N/A
98/101 
(97.0)
98/101 
(97.0)
N/A
35/35 
(100)
35/35 
(100)
N/A
20/20 
(100)
20/20 
(100)
N/A
2/2 
(100)
2/2 
(100)
N/A
7/7 
(100)
7/7 
(100)
OTVF
N/A
0/101
0/101
N/A
0/35
0/35
N/A
0/20
0/20
N/A
0/2
0/2
N/A
0/7
0/7
Relapse12
N/A
1/98 
(1.0)
1/98 
(1.0)
N/A
0/35
0/35
N/A
0/19
0/19
N/A
0/2
0/2
N/A
0/7
0/7
GT = genotype; HCV = hepatitis C virus; N/A = not applicable; OTVF = on-treatment virologic failure; PRS = regimens containing interferon, pegylated interferon, ribavirin, 
and/or sofosbuvir; Relapse12 = relapse before or during the SVR12 window; RNA = ribonucleic acid; SVR12 = sustained virologic response 12 weeks postdosing; TE = treatment-
experienced; TN = treatment-naïve


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Table 6.
SVR12 Rates by Prior Treatment Experience, HCV Genotype, and Duration for Non-GT3 Infected Subjects 
(ITT Population, Phase 2 and 3 Analysis Set)
Treatment 
Group
n/N (%)
GT1
GT2
GT4
GT5
GT6
8 Weeks
12 Weeks
8 Weeks
12 Weeks
8 Weeks
12 Weeks
8 Weeks
12 Weeks
8 Weeks
12 Weeks
TN
245/248 
(98.8)
310/313 
(99.0)
172/174 
(98.9)
193/195 
(99.0)
36/39 
(92.3)
83/83 
(100)
2/2 (100)
24/24 
(100)
7/8 (87.5)
33/33 
(100)
TE-PRS
138/139 
(99.3)
188/189 
(99.5)
21/23 
(91.3)
74/74 (100)
7/7 (100)
48/49 
(98.0)
N/A
6/6 (100)
2/2 (100)
5/5 (100)
TN + TE-PRS
All
383/387 
(99.0)
498/502 
(99.2)
193/197 
(98.0)
267/269 
(99.3)
43/46 
(93.5)
131/132 
(99.2)
2/2 (100)
30/30 
(100)
9/10 (90.0)
38/38 
(100)
Difference 
% (8-week –
12 week) 
95% CI
–0.7 (–2.1, 
0.6)
–1.4 (–4.4, 
1.7)
–5.6
(–14.1,
2.9)
0.0 (–73.3, 
73.3)
–10.5
(–37.8, 
16.9)
CI = confidence interval; GT = genotype; HCV = hepatitis C virus; ITT = intention-to-treat (all subjects who received at least 1 dose of study drug); N/A = not applicable; 
PRS = regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir; SVR12 = sustained virologic response 12 weeks postdosing; TE = treatment-experienced; 
TN = treatment-naïve


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Table 7.
Summary of SVR12, On-Treatment Virologic Failure, and Post-Treatment Relapse in TN and TE
GT3-Infected Subjects by Cirrhosis Status and Treatment Duration (ITT Population, Phase 2 and 3 Analysis 
Set)
Endpoint
n/N (%)
TN
TE-PRS
8 Weeks
12 Weeks
12 Weeks
16 Weeks
Subjects Without Cirrhosis
SVR12
177/186 (95.2)
258/270 (95.6)
44/49 (89.8)
21/22 (95.5)
OTVF
1/186 (0.5)
1/270 (0.4)
1/49 (2.0)
0/22
Relapse12
5/178 (2.8)
3/257 (1.2)
4/48 (8.3)
1/22 (4.5)
Subjects With Cirrhosis
SVR12
N/A
64/65 (98.5)
N/A
48/51 (94.1)
OTVF
N/A
0/65
N/A
1/51 (2.0)
Relapse12
N/A
0/64
N/A
2/50 (4.0)
GT = genotype; ITT = intention-to-treat (all subjects who received at least 1 dose of study drug); N/A = not applicable; OTVF = on-treatment virologic failure; PRS = regimens 
containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir; Relapse12 = relapse before or during the SVR12 window; SVR12 = sustained virologic response 12 weeks 
postdosing; TE = treatment-experienced; TN = treatment-naïve


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Treatment-experienced GT3-infected subjects with and without cirrhosis were evaluated 
for 12-week and 16-week durations of treatment.  Among TE GT3-infected subjects 
without cirrhosis, the SVR12 rates were higher in subjects treated for 16 weeks (95.5%) 
compared to 12 weeks (89.8%).  Subjects with cirrhosis treated for 16 weeks achieved a 
high (94.1%) SVR12 rate, similar to subjects without cirrhosis (95.5%).  These results in 
GT3-infected subjects support the use of 16 weeks of treatment in TE GT3-infected 
subjects with or without cirrhosis.
Based on the efficacy data presented above, the 8-week treatment duration is anticipated 
to achieve high SVR rates in GT 1, 2, 3, 4, 5 and 6 infected treatment-naïve 
and -experienced subjects without cirrhosis, with the exception of 16 weeks for treatment-
experienced GT3-infected subjects as depicted in Table 8.
Table 8.
Recommended Treatment Duration for Subjects Without Cirrhosis
Patient Population
Recommended Treatment Duration
Treatment-naïve
8 weeks
Treatment-Experienced*
8 weeks
(16 weeks for GT 3)
*
Treatment-experienced to interferon (IFN) (alpha, beta or pegylated interferon [pegIFN]) with or without ribavirin 
(RBV) OR sofosbuvir with RBV with or without IFN.
As SVR rates for the current therapies (e.g., ombitasvir/paritaprevir/ritonavir ± RBV or 
sofosbuvir/ledispavir) in non-cirrhotic subjects are well-established and very high 
(≥95%) in various GTs, historical control data will be used to provide a comparator for 
assessment of efficacy in this placebo-controlled study.
5.6.2
Appropriateness of Measurements
Standard pharmacokinetic, statistical, clinical, and laboratory procedures will be utilized 
in this study.  HCV RNA and HIV-1 RNA assays are standard and validated.


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5.6.3
Suitability of Subject Population
This study plans to enroll HCV GT1, 2, 3, 4, 5, and 6-infected subjects without cirrhosis 
who are treatment-naïve or treatment-experienced to prior HCV therapy with or without 
HIV co-infection in order to assess the safety, pharmacokinetics and antiviral activity of 
ABT-493/ABT-530.  Subjects who are treatment-naïve as well as those who received 
prior treatment with IFN (alpha, beta or pegylated interferon [pegIFN]) with or without 
RBV OR sofosbuvir with RBV with or without IFN for their HCV infection are included 
in the study in order to evaluate the efficacy of ABT-493/ABT-530 regimen in this 
diverse cohort of HCV GT1 – 6-infected subjects.  Subjects who have failed treatment 
with a PI or NS5A inhibitor alone or in combination with interferon (with or without 
RBV) will not be permitted to enroll.
HCV-infected subjects who are on stable opiate (methadone or buprenorphine/naloxone) 
maintenance therapy will be allowed to enroll in this study based on the results from 
Study M13-602 evaluating the pharmacokinetic, pharmacodynamic, safety and tolerability 
effects of the coadministration of buprenorphine/naloxone or methadone and the DAAs 
(ABT-493 + ABT-530) in adult subjects on stable opioid maintenance therapy showing 
acceptable safety and no relevant pharmacokinetic or pharmacodynamic interactions.
5.6.4
Selection of Doses in the Study
5.6.4.1
Rationale for Dose Selections
The doses of 300 mg ABT-493 and 120 mg ABT-530 were selected to optimize efficacy 
of the combination while maintaining an acceptable safety profile.
5.6.4.1.1
ABT-493 and ABT-530 Doses
Based on the results from the Phase 2b studies, Studies M14-867 and M14-868, the 
300 mg dose of ABT-493 and 120 mg dose of ABT-530 in combination has been selected 
for Phase 3 studies in HCV GT1 to 6 cirrhotic and non-cirrhotic populations and is also 
applicable for this Asian regional Phase 3 study.  This dose has been demonstrated 
efficacious for the proposed Phase 3 study populations with the planned study duration 


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and would reduce the chance of virologic failure across genotypes and difficult-to-treat 
patient populations to maximize the chance for SVR.  Importantly, ABT-493 and 
ABT-530 regimens including the proposed 300 mg/120 mg ABT-493/ABT-530 QD 
regimen have been well-tolerated and safe across all Phase 2b study arms including 
cirrhotic subjects.
Further detailed rationale is provided below:
●
In Phase 1 studies, no ethnic difference was observed in ABT-493 and 
ABT-530 exposures for, Han Chinese, Japanese and Caucasian subjects living 
in the United States.
●
Based on in vitro studies, both ABT-493 and ABT-530 demonstrated strong 
pan-genotypic anti-viral activity.  Given the potent in vitro efficacy across GTs 
and high SVR rates of 93% – 100% observed to date across dose groups in 
Phase 2 studies in GT1, GT2 and GT3-infected non-cirrhotic patients, the 
ABT-493/ABT-530 dose of 300 mg/120 mg are is expected to provide 
sufficient exposure to achieve significant antiviral potency in GT1-, GT2-, 
GT3-, GT4-, GT5- and GT6-infected non-cirrhotic subjects.
●
Maximization of SVR rate:  The ABT-493/ABT-530 combination has 
demonstrated SVR close to 100% in GT1 infected non-cirrhotic subjects with 
12-week treatment duration in Part 1 of Study M14-867.  All subjects in the 
120 mg ABT-530 arm achieved SVR12.  However, one subject in the 40 mg 
ABT-530 Arm had virologic relapse when coadministered with the same dose 
of 200 mg ABT-493.  Preliminary sequencing results indicate that the relapse 
subject developed treatment-emergent resistance associated substitutions in 
NS5A but not in NS3.  These results suggest that the 120 mg ABT-530 dose 
may decrease the incidence of relapse by reducing the emergence of NS5A 
RAVs and thus increase the chance of achieving SVR compared to 40 mg.
●
For GT2 and GT3 subjects, ABT-493 doses of 200 mg and 300 mg were 
evaluated in Part 1 of Study M14-868.  No virological breakthroughs and no 
relapses were observed in subjects with GT2 infection at either of the 
2 ABT-493 dose levels.  For GT3 arms, 2 subjects (1 TN and 1 PR-
experienced) had virological breakthrough before the completion of treatment 
in the 200 mg ABT-493 groups.  No subjects receiving 300 mg ABT-493 have 


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had breakthroughs before completion of treatment.  The results suggested that 
the 300 mg ABT-493 dose reduces the incidence of breakthroughs and 
increases the chance of achieving SVR.  Taken together, these data suggest 
that ABT-493/ABT-530 dose of 300/120 will maximize SVR rate compared to 
lower dose-combinations.
●
For other genotypes (GT4, 5 and 6), the 300 mg/120 mg ABT-493/ABT-530 
combination for 12 weeks achieved 100% SVR4.
●
ABT-493 and ABT-530 regimens including the proposed 300 mg/120 mg 
ABT-493/ABT-530 QD regimen have been well-tolerated and safe across all 
Phase 2b study arms including cirrhotic subjects.  All ABT-493 and ABT-530 
doses studied had a similar safety profile.  The most frequently reported 
adverse events were fatigue, nausea and headache and were mostly Grade 1 or 
2 in severity.  In all subjects with baseline ALT elevations, the ALT levels 
have normalized or trended toward normal with DAA treatment, and there 
have been no on treatment ALT elevations above baseline grade.
●
Based on the integrated pharmacokinetic exposures of ABT-493 and safety 
data in healthy subjects across 100 mg to 1200 mg dose range, ALT elevations 
≥ Grade 2 are only anticipated to occur when ABT-493 AUC is higher than 
190,000 ng•h/mL, which is 33× higher than the projected geometric mean 
AUC exposure at ABT-493 300 mg in non-cirrhotic subjects.
●
ABT-530 had shown to be safe and well tolerated at 600 mg QD multiple 
dosing and MTD was not achieved.  Although ABT-493 300 mg increases 
ABT-530 exposure at 120 mg by 4-fold, the increased ABT-530 exposure was 
still less than the exposures of ABT-530 600 mg QD in Study M13-356 and no 
significant safety signal was observed in healthy subjects and HCV infected 
patients.  No clinically meaningful adverse events or laboratory abnormalities 
were observed in any ABT-530 120 mg dose groups in Phase 2 
Studies M14-867 and M14-868.
●
For HIV-HCV co-infected patients, extensive drug-drug interaction studies 
have been conducted between HIV-1 ART regimens and ABT-493 + ABT-530 
combinations.  The allowed HIV-1 ART regimens in the study are not 
anticipated to significantly interact with ABT-493 and ABT-530.


ABT-493, ABT-530
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●
A film-coated co-formulated bilayer tablet of ABT-493 and ABT-530 will be 
used in this Phase 3 study.  Preliminary pharmacokinetic results of the Phase 3 
 bilayer tablet formulation administered under fasting conditions showed 
approximately 35% to 56% lower bioavailability compared to the Phase 2 
formulations at the ABT-493/ABT-530 dose of 300 mg/120 mg.  When the 
Phase 3 bilayer tablet was administered under non-fasting conditions, 
exposures became comparable to the Phase 2 formulation.  Hence, the Phase 3 
co-formulated ABT-493/ABT-530 bilayer tablet must be administered with 
food to provide desirable DAA exposures.
The maximum dose of ABT-493/ABT-530 will not exceed 300 mg/120 mg per day for 8 
or 16 weeks.
5.6.4.2
Rationale for Duration Selections
Treatment duration for this Asian regional Phase 3 study was determined based on study 
results from the Global program.  The treatment duration differs among subjects based on 
HCV GT and treatment experience (8 weeks of treatment for treatment-naïve and 
treatment-experienced GT1, 2, 3, 4, 5 and 6-infected subjects with the exception of 
16 weeks for treatment-experienced GT3-infected subjects).
Results from ABT-493 300 mg QD + ABT-530 120 mg QD for an 8-week treatment 
duration in HCV GT1- (Study M14-867 Part 2) and HCV GT2-infected subjects 
(Study M14-867 Part 2) showed 100% SVR12.  In Study M14-867 Part 2, ABT-493 
300 mg QD + ABT-530 120 mg QD for 12 weeks was evaluated in 34 DAA-naïve HCV 
GT4 (n = 22), GT5 (n = 1), and GT6 (n = 11)-infected non-cirrhotic subjects.  All 
34 subjects achieved SVR12.  Based on exposure-response analyses, simulations were 
conducted to predict SVR rates for ABT-493 and ABT-530 administered for 8 weeks in 
HCV GT4-infected subjects and showed > 95% SVR in this population.
Treatment-naïve HCV GT3-infected subjects treated for 12 weeks achieved high efficacy 
(SVR12 rate of 98%) with no virological failures observed.  Treatment-experienced HCV 
GT3-infected subjects with cirrhosis treated for 16 weeks achieved SVR12 rate of 96%, 


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with a low rate of relapse (2%).  Among treatment-experienced subjects without cirrhosis, 
the 16-week regimen appeared to have a slightly higher SVR12 rate (96%) and a slightly 
lower relapse rate (5%) than the 12-week regimen.  Treatment with the shorter duration of 
12 weeks resulted in a slightly lower SVR12 rate (91%) and a slightly higher relapse rate 
(9%) compared to the 16 week regimen.  There was a comparable safety profile for GT3 
treatment-experienced subjects regardless of duration of treatment with study drug (12 or 
16 weeks) and between subjects with or without cirrhosis.  
Overall, the SVR12 rates for the GT3-infected treatment-experienced cohort, with and 
without cirrhosis, in the 16-week arm (SVR12 of 96% [66/69]) demonstrates that 16 weeks 
of treatment maximizes efficacy and is the most appropriate duration for this hardest-to-
treat population.
5.6.4.3
Risk of Development of Resistance Mutations During 
Combination DAA Trials
In subjects treated with a DAA, variants with amino acid substitution(s) in the targeted 
protein conferring resistance to the DAA can be selected.  For example, in AbbVie HCV 
Phase 3 studies in which patients with GT1 infection were treated with the NS3/4A 
protease inhibitor paritaprevir and NS5A inhibitor ombitasvir, variants that conferred 
resistance to paritaprevir or ombitasvir were detected in patients experiencing virologic 
failure.  While resistance data from patients treated with the combination of ABT-530 and 
ABT-493 are limited, it is expected that ABT-530, an NS5A inhibitor, will be able to 
suppress the appearance of virus containing resistance-associated substitutions in NS3 that 
confer resistance to ABT-493, because there should not be any cross-resistance in variants 
resistant to DAAs targeting different proteins.  The converse is expected to be true as well 
– ABT-493 should be able to suppress the appearance of virus containing NS5A variants 
conferring resistance to ABT-530.  In addition, in vitro resistant colony selection studies 
in HCV replicon cells containing GT1 – 6 NS5A demonstrated that ABT-530 had a high 
genetic barrier to resistance – very few colonies were selected, and those that were 
selected contained NS5A variants that conferred only modest levels of resistance to 
ABT-530.  It remains to be seen whether the development of resistance in subjects treated 


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with ABT-530 resembles that seen in vitro.  Based on accumulated clinical and in vitro 
data to date, the risk of development of resistant variants during ABT-493 and ABT-530 
combination trials is reduced when compared to treatment with first generation protease 
and NS5A inhibitors.  For example, the combination of ABT-493 and ABT-530 achieved 
high SVR rates with few virologic failures in DAA-naïve patients with HCV genotype 1, 
2, 3, 4, 5, or 6 infection in the Phase 3 registrational studies.  These results support the 
prediction that the risk of development of resistance-associated substitutions with 
ABT-493 and ABT-530 combination treatment is low.
6.0
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/device after it is released for 
distribution.
Complaints associated with any component of this investigational product must be 
reported to AbbVie (Section 6.2.2).  For adverse events, please refer to Section 6.1
through 6.1.8.  For product complaints, please refer to Section 6.2.
6.1
Medical Complaints
The investigator will monitor each subject for clinical and laboratory evidence of adverse 
events on a routine basis throughout the study.  The investigator will assess and record 
any adverse event in detail including the date of onset, event diagnosis (if known) or 
sign/symptom, severity, time course (end date, ongoing, intermittent), relationship of the 
adverse event to study drug, and any action(s) taken.  For serious adverse events 
considered as having "no reasonable possibility" of being associated with study drug, the 
investigator will provide an "Other" cause of the event.  For adverse events to be 
considered intermittent, the events must be of similar nature and severity.  Adverse 
events, whether in response to a query, observed by site personnel, or reported 
spontaneously by the subject will be recorded.


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All adverse events will be followed to a satisfactory conclusion.
6.1.1
Definitions
6.1.1.1
Adverse Event
An adverse event (AE) is defined as any untoward medical occurrence in a patient 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.
Such an event 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 adverse events only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, meet 
protocol specific criteria (see Section 6.1.7 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.
6.1.1.2
Serious Adverse Events
If an AE meets any of the following criteria, it is to be reported to AbbVie as a serious 
adverse event (SAE) within 24 hours of the site being made aware of the SAE.


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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).
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 SAEs with the outcome of death, the date and cause of death will be recorded on the 
appropriate case report form.


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6.1.2
Adverse Event Severity
The investigator will rate the severity of each AE 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 AEs.  Below are the 
general grading categories.  However, the investigator should always search NCI CTCAE 
for a given diagnostic/symptomatic AE term to identify and apply specific grading details 
for that AE entity.
Grading system for AEs (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.
6.1.3
Relationship to Study Drug
The investigator will use the following definitions to assess the relationship of the AE to 
the use of study drug:


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Reasonable Possibility
An AE where there is evidence to suggest a causal 
relationship between the study drug and the AE.
No Reasonable Possibility
An AE where there is no evidence to suggest a causal 
relationship between the study drug and the AE.
For causality assessments, events assessed as having a reasonable possibility of being 
related to the study drug will be considered "associated."  Events assessed as having no 
reasonable possibility of being related to study drug will be considered "not associated."  
In addition, when the investigator has not reported a causality or deemed it not assessable, 
AbbVie will consider the event associated.
If an investigator's opinion of no reasonable possibility of being related to study drug is 
given, an "Other" cause of the event must be provided by the investigator for the serious 
adverse event.
6.1.4
Adverse Event Collection Period
All SAEs as well as protocol-related nonserious AEs (e.g., infection at liver biopsy site) 
will be collected from the time the subject signed the study-specific informed consent 
until study drug administration.  From the time of study drug administration until 30 days 
following discontinuation of study treatment has elapsed, all AEs will be collected, 
whether solicited or spontaneously reported by the subject.  After 30 days following 
completion of study treatment, and throughout the Post-Treatment Period, all 
spontaneously reported SAEs will be collected (nonserious AEs will not be collected).
Adverse event information will be collected as shown in Figure 3.


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Figure 3.
Adverse Event Collection
6.1.5
Adverse Event Reporting
In the event of an SAE, whether associated with study drug or not, the Investigator will 
notify Clinical Pharmacovigilance within 24 hours of the site being made aware of the 
SAE by entering the SAE data into the electronic data capture (EDC) system.  SAEs that 
occur prior to the site having access to the RAVE® system, or if RAVE is not operable, 
should be documented on the SAE Non-CRF forms and emailed (preferred route) or faxed 
to Clinical Pharmacovigilance within 24 hours of the site being made aware of the SAE.
Email:
FAX to:  
For safety concerns, contact the Antiviral Safety Team at:
Antiviral Safety Team
1 North Waukegan Road
North Chicago, IL  60064
Office:
Fax:
Email:


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For any subject safety concerns, please contact the physician listed below:
Primary Therapeutic Area Medical Director:
In emergency situations involving study subjects when the primary TA MD is not 
available by phone, please contact the 24-hour AbbVie Medical Escalation Hotline where 
your call will be re-directed to a designated backup AbbVie TA MD:
Phone:  
AbbVie 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.
6.1.6
Pregnancy
Pregnancy in a study subject must be reported to AbbVie within 1 working day of the site 
becoming aware of the pregnancy.  Female subjects who report a positive pregnancy test 
during the DB or OL Treatment Period may be continued at the investigator's discretion 
after discussion with the subject, if the benefits of continuing therapy are felt to outweigh 
the risk (Section 5.4.1).  Subjects who discontinued and received active drug either in the 
DB or OL Treatment Period will be monitored for SVR in the Post-Treatment Period as 
described in Section 5.1.4.


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Information regarding a pregnancy occurrence in a study subject and the outcome of the 
pregnancy will be collected for pregnancies occurring up to 30 days after the end of 
treatment.
Pregnancy in a study subject is not considered an AE.  However, 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.
6.1.7
Toxicity Management
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 will be managed and followed to a satisfactory clinical resolution.  A 
toxicity is deemed "clinically significant" based on the medical judgment of the 
investigator.  The table of clinical toxicity grades "National Cancer Institute Common 
Terminology Criteria for Adverse Events, Version 4" is to be used in the grading of AEs 
and laboratory abnormalities and is available on the Cancer Therapy Evaluation Program 
(CTEP) website at:  http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf.
Specific toxicity management guidelines apply to the instances of increases in ALT 
(Section 6.1.7.1).
6.1.7.1
Management of Increases in ALT
If a subject experiences a post-baseline increase in ALT to > 5 × ULN which is also
> 2 × the 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 × the baseline value, the 
recommendations below should be followed:


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●
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 additional testing as appropriate 
(e.g., hepatitis B panel, etc.).
●
Manage the subject as medically appropriate.
●
Repeat ALT, AST, total and fractionated bilirubin, alkaline phosphatase and 
INR within 1 week.  Repeat liver chemistries as indicated until resolution.
●
Discontinue study drugs 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 TA 
MD.
During the DB Treatment Period, if confirmed ALT values meet or exceed predefined 
toxicity thresholds, refer to Section 5.1.2.
6.1.8
Collection of Data Regarding Known AIDS-Associated 
Opportunistic Infections
HIV-1 infected subjects participating in clinical trials may develop infections typically 
associated with AIDS.  Appendix D contains a list of these known AIDS-associated 
opportunistic infections (OI).  The events listed in Appendix D will be summarized as 
HIV-related events, not as AEs.  These OIs will be collected from the time of study drug 
administration until 30 days following discontinuation of study drug.
6.2
Product Complaint
6.2.1
Definition
A Product Complaint is any Complaint (see Section 6.0 for the definition) related to the 
biologic or drug component of the product(s).


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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.
Any information available to help in the determination of causality to the events outlined 
directly above should be captured.
6.2.2
Reporting
Product Complaints concerning the investigational product must be reported to AbbVie 
within 24 hours of the study site's knowledge of the event via the Product Complaint 
form.  Product Complaints occurring during the study will be followed-up to a satisfactory 
conclusion.  All follow-up information is to be reported to AbbVie (or an authorized 
representative) and documented in source as required by AbbVie.  Product Complaints 
associated with AEs will be reported in the study summary.  All other complaints will be 
monitored on an ongoing basis.
Product Complaints may require return of the product with the alleged complaint 
condition.  In instances where a return is requested, every effort should be made by the 
investigator to return the product within 30 days.  If returns cannot be accommodated 
within 30 days, the site will need to provide justification and an estimated date of return.
The description of the complaint is important for AbbVie in order to enable AbbVie to 
investigate and determine if any corrective actions are required.
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 


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Independent Ethics Committee (IEC)/Independent Review Board (IRB) regulatory 
authorities (as applicable), their assigned Site Monitor and the following AbbVie Clinical 
Team Members:
Primary Contact:
Alternate Contact:
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.  Any significant 
protocol deviations affecting subject eligibility and/or safety must be reviewed and/or 
approved by the IEC/IRB and regulatory authorities, as applicable, prior to 
implementation.
8.0
Statistical Methods and Determination of Sample 
Size
8.1
Statistical and Analytical Plans
The primary analysis will occur after all subjects in Arm A have completed the PT 
Week 12 Visit or prematurely discontinued the study.  The primary analysis will 
summarize data through PT Week 12 for Arm A subjects and data through the DB 
Treatment Period for Arm B subjects.  The data for the primary analysis will be locked 
after data cleaning, and data collected after this lock will be added to a new version of the 
database.  Results from the primary analysis will be described in the primary clinical 
study report (CSR) and submitted to regulatory agencies as part of an NDA submission.  
An interim analysis will occur after all Arm A subjects have completed the PT Week 24 
Visit or prematurely discontinued the study and all Arm B subjects have completed the PT 


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Week 12 Visit or prematurely discontinued the study.  The data for the interim analysis 
will be locked after data cleaning.  Data collected after this lock will be added to a new 
version of the database which will be cleaned and locked at the end of the study.  
SAS® (SAS Institute, Inc., Cary, NC) for the UNIX operating system will be used for all 
analyses.  All statistical tests and confidence intervals will be two-sided with an alpha 
level of 0.05.  Descriptive statistics will be provided, such as the number of observations 
(N), mean, and standard deviation (SD) for continuous variables and counts and 
percentages for categorical variables.
Analyses will be performed on the intent-to-treat (ITT) population defined as all 
randomized subjects who receive at least one dose of study drug in the DB Treatment 
Period, unless otherwise specified.  The primary and secondary efficacy endpoints will be 
analyzed on the ITT population treated with active study drug in the DB Treatment Period 
(Arm A).  Sensitivity analyses of the primary efficacy endpoint, when applicable, will be 
performed on the ITT population modified to exclude subjects of multiple GTs according 
to the central laboratory or phylogenetic analyses (mITT-GT), and on the mITT-GT 
population modified to exclude subjects who did not achieve SVR12 for reasons other than 
virologic failure (mITT-GT-VF).  In addition, some analyses will be performed on the OL 
Population defined as all subjects who receive at least one dose of study drug during the 
OL Treatment Period.
No data will be imputed for any efficacy or safety analysis except for analyses of SVR 
endpoints (HCV RNA data), and PRO questionnaires.  HCV RNA values will be selected 
for the analyses of all SVR endpoints (e.g., SVR4, SVR12, and SVR24) based on defined 
visit windows.  A backward imputation method will be used to impute missing responses 
for SVR analyses.  Imputation of missing responses on PRO questionnaires is described in 
Section 8.1.3.


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8.1.1
Demographics
DB Treatment Period
Demographics, baseline characteristics, study drug exposure, and compliance will be 
summarized by treatment arm for the set of all subjects in the ITT and mITT population(s) 
and for each of the GT1-infected and GT2-infected groups.  Demographics include age 
(continuous; < 65 or ≥ 65 years; < 75 or ≥ 75 years), weight, height, waist circumference, 
BMI (continuous; < 25, ≥ 25 to < 30, or ≥ 30 kg/m2), sex, race, ethnicity, type of Asian 
descent, and geographic region.  Baseline characteristics will be summarized as 
continuous variables (where appropriate) and as categorical variables, including all 
subgroup variables defined in Section 8.1.2.4, and include HCV GT and available 
subtype, prior HCV treatment history, baseline HIV co-infection status, HIV ART at 
baseline, IL28B genotype (CC, CT, or TT; CC or non-CC), baseline HCV RNA level, 
baseline homeostasis model of assessment – insulin resistance (HOMA-IR), fibrosis stage 
(F0 – F1, F2, F3, F4 [if applicable]), tobacco (user, ex-user, or non-user) and alcohol use 
(drinker, ex-drinker, or non-drinker) status, injection drug user, (yes, within last 
12 months; yes, more than 12 months ago; or no) use of stable opiate substitution, history 
of diabetes, baseline metabolic syndrome, history of bleeding disorders, history of 
depression or bipolar disorder, history of cardiovascular disease, and use of 
hepatoprotectants at baseline.
Summary statistics (N, mean, median, SD, and range) will be generated for continuous 
variables (e.g., age and BMI), and the number and percentage of subjects will be 
presented for categorical variables (e.g., sex and race).  Treatment arms will be compared 
using a chi-square test for categorical variables and using a one-way analysis of variance 
(ANOVA) with treatment arm as the factor for continuous variables.  
Study drug exposure and compliance during the DB Treatment Period will be 
summarized.  Treatment compliance to study drug will be calculated based on the 
percentage of tablets taken relative to the total tablets expected to be taken.  A subject will 
be considered compliant if the percentage is between 80% and 120%.  Compliance will be 


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calculated for each subject and summarized by treatment arm with the mean, median, 
standard deviation, minimum, and maximum.  The percentage of compliant subjects will 
be calculated for each treatment arm, based on data as observed.  An additional summary 
of the percentage of compliant subjects will be provided where subjects who are missing 
study drug accountability records will be imputed as non-compliant.
The summaries described above will also be performed for each geographic region.
OL Treatment Period
Demographics, baseline characteristics, study drug exposure, and compliance will be 
summarized for the set of all subjects in the OL Population and for each of the GT1-
infected and GT2-infected groups of the OL Population.  Summary statistics will be 
presented for continuous variables and the number and percentage of subjects will be 
presented for categorical variables.
Study drug exposure and compliance for the OL Population during the OL Treatment 
Period will be summarized using methods similar to those used for the DB Treatment 
Period.
The summaries described above will also be performed for each geographic region.
8.1.2
Efficacy
All efficacy analyses will be performed on the ITT population, unless otherwise specified.
Plasma HCV RNA levels will be determined by an approved HCV RNA quantitative
assay for each sample collected by the central laboratory (including but not limited to 
Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Quantitative Test, v2.0).
8.1.2.1
Primary Efficacy Endpoint
The primary efficacy endpoint variable is SVR12 (HCV RNA < LLOQ 12 weeks after the 
last actual dose of study drug) for the subjects treated with ABT-493/ABT-530 in the DB 
Treatment Period (Arm A).  In order to control the Type I error rate, a fixed sequence 


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testing procedure will be used for the ranked primary efficacy endpoints.  Only if success 
has been demonstrated for the first primary endpoint will the testing proceed to the 
second primary endpoint.  Similarly, only if success has been demonstrated for the 
second primary endpoint will the testing proceed to the third primary endpoint.
The three ranked primary efficacy endpoints are:
1.
The percentage of Arm A subjects from the combined group of GT1 to 6-infected 
subjects achieving SVR12.  The percentage of these subjects with SVR12 will be 
non-inferior to the historical SVR12 rate of 96% if the lower confidence bound 
(LCB) of the 2-sided 95% confidence interval (CI) for the percentage is > 90%.
2.
The percentage of Arm A subjects from the group of GT1-infected subjects 
achieving SVR12.  The percentage of these subjects with SVR12 will be non-inferior 
to the historical SVR12 rate of 97% if the LCB of the 2-sided 95% CI for the 
percentage is > 91%.
3.
The percentage of Arm A subjects from the group of GT2-infected subjects 
achieving SVR12.  The percentage of these subjects with SVR12 will be non-inferior 
to the historical SVR12 rate of 95% if the LCB of the 2-sided 95% CI for the 
percentage is > 89%.
The normal approximation to the binomial distribution will be used to calculate each CI 
unless the rate for the primary endpoint is 100%, in which case the Wilson's score method 
will be used for the calculation of the CI.
8.1.2.2
Secondary Efficacy Endpoints
The secondary efficacy endpoints are: 
●
the percentage of Arm A subjects with on-treatment HCV virologic failure 
(defined as confirmed increase of > 1 log10 IU/mL above nadir during 
treatment, confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < LLOQ 


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during treatment, or HCV RNA ≥ LLOQ at the end of treatment with at least 
6 weeks of treatment), and
●
the percentage of Arm A subjects with post-treatment relapse (defined as 
confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after 
the last dose of study drug among subjects who completed treatment as 
planned with HCV RNA < LLOQ at the end of treatment, excluding re-
infection), and
●
the percentage of Arm A HCV/HIV co-infected subjects (determined at 
Screening) achieving SVR12.
For the analysis of relapse, a subject enrolled to receive 8 weeks of treatment is 
considered to have completed treatment if study drug duration is 52 days or more, and a 
subject enrolled to receive 16 weeks of treatment is considered to have completed 
treatment if study drug duration is 105 days or more.
The percentages of subjects with on-treatment HCV virologic failure, post-treatment 
relapse, and SVR12 will be calculated along with two-sided 95% Wilson score confidence 
intervals.
In addition, a summary of reason for SVR12 non-response (e.g., on-treatment virologic 
failure, relapse, re-infection) will be provided for the set of all Arm A subjects and for the 
set of HCV/HIV co-infected Arm A subjects.
The secondary endpoints will be summarized for the set of all Arm A subjects in the ITT 
population and for the Arm A subjects in each of the GT1-infected and GT2-infected 
groups.
8.1.2.3
Sensitivity Analysis
The analyses of the primary endpoints will also be performed on Arm A of the mITT-GT 
and mITT-GT-VF populations.  Comparisons of the SVR12 rates may also be made to 
geographic region-specific SVR rates.


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The number and percentage of subjects with SVR12 and the corresponding 95% 
confidence interval will be provided for each randomization stratum:
●
China/GT1-infected/HIV co-infected
●
China/GT1-infected/non-HIV co-infected 
●
China/GT2-infected/HIV co-infected
●
China/GT2-infected/non-HIV co-infected 
●
China/GT3 – 6-infected/HIV co-infected
●
China/GT3 – 6-infected/non-HIV co-infected 
●
Singapore/GT1-infected/HIV co-infected
●
Singapore/GT1-infected/non-HIV co-infected 
●
Singapore/GT2-infected/HIV co-infected  
●
Singapore/GT2-infected/non-HIV co-infected  
●
South Korea/GT1-infected/HIV co-infected
●
South Korea/GT1-infected/non-HIV co-infected 
●
South Korea/GT2-infected/HIV co-infected
●
South Korea/GT2-infected/non-HIV co-infected
8.1.2.4
Subgroup Analysis
The percentage of Arm A subjects with SVR12 will be calculated, as will the 
corresponding two-sided 95% Wilson score CIs, for subgroups based on the following 
factors for the set of all subjects in the ITT and mITT population(s) and for each of the 
GT1-infected and GT2-infected groups:
●
Geographic region;
●
HCV genotype and available subtype;
●
Prior HCV treatment history;
●
For treatment-experienced subjects, type of prior treatment experience;
●
For treatment-experienced subjects, type of non-response to previous 
treatment;


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●
Baseline HIV co-infection status;
●
IL28B genotype;
●
Sex;
●
Age;
●
Type of Asian descent;
●
Baseline BMI;
●
Baseline HCV RNA level;
●
Baseline HOMA-IR;
●
Baseline fibrosis stage;
●
Baseline platelet count;
●
Baseline albumin;
●
Baseline GGT;
●
Baseline LDL;
●
Baseline APRI;
●
Baseline FIB-4;
●
Baseline AST/ALT ratio;
●
History of diabetes;
●
History of bleeding disorders;
●
History of depression or bipolar disorder;
●
Baseline metabolic syndrome;
●
History of cardiovascular disease;
●
Injection drug use; 
●
Baseline stable opiate substitution use;
●
Baseline hepatoprotectant medication use;
●
Study drug compliance.
Further details about subgroup analyses will be described in the Statistical Analysis Plan 
(SAP).


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8.1.2.5
Additional Efficacy Endpoints
The following additional efficacy endpoints will be summarized for the set of all Arm A 
subjects in the ITT and mITT population(s) and for each of the GT1-infected and GT2-
infected groups:
●
The percentage of subjects with HCV RNA < LLOQ at each post-baseline visit 
in the DB Treatment Period (using data as observed);
●
The percentage of subjects with SVR4;
●
A summary of reason for SVR4 non-response (e.g., on-treatment virologic 
failure, relapse, re-infection);
●
The percentage of subjects with SVR24;
●
A summary of reason for SVR24 non-response (e.g., on-treatment virologic 
failure, relapse, re-infection);
●
The percentage of subjects who relapsed after achieving SVR12.
The following additional endpoints will be summarized for the set of all subjects in the 
OL Population and for each of the GT1-infected and GT2-infected groups of the OL 
Population:
●
The percentage of subjects with SVR12;
●
A summary of reason for SVR12 non-response (e.g., on-treatment virologic 
failure, relapse, other);
●
The percentage of subjects with SVR12 by HCV genotype and available 
subtype;
●
The percentage of subjects with SVR12 by HIV co-infection status;
●
The percentage of subjects with SVR12 by prior HCV treatment history 
(treatment-naïve and treatment-experienced, with further breakdown by type of 
prior HCV treatment experience);
●
The percentage of subjects with SVR24;
●
A summary of reason for SVR24 non-response (e.g., on-treatment virologic 
failure, relapse, re-infection);


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●
The percentage of subjects who relapsed after achieving SVR12;
●
The percentage of subjects with HCV RNA < LLOQ at each post-baseline visit 
in the OL Treatment Period (using data as observed);
●
The percentage of subjects with SVR4;
●
A summary of reason for SVR4 non-response (e.g., on-treatment virologic 
failure, relapse, re-infection).
In the above analyses for SVR and relapse, the percentage of subjects with each endpoint 
among those receiving active treatment during the DB or the OL Treatment Period, as 
applicable, will be calculated along with a two-sided 95% Wilson score CI.  The 
summaries listed above will also be presented by geographic region.
Additionally, the secondary endpoints will be summarized by geographic region, and the 
subgroup and sensitivity analyses will be performed separately for each geographic 
region.
The additional endpoints along with the secondary endpoints of on-treatment virologic 
failure and post-treatment relapse will also be summarized for the HCV/HIV co-infected 
subjects.  The sensitivity analyses will also be performed for the HCV/HIV co-infected 
population.
8.1.3
Patient Reported Outcomes
The handling of missing data for patient reported outcomes (PROs) will be as follows.  
The missing items of the FSS questionnaire will be imputed with the average score of the 
answered items as long as more than 50% of the items on the FSS are answered.  For EQ-
5D-3L index and VAS scores, no imputation will be performed for missing items.  
The mean change from baseline will be summarized descriptively for the FSS total score 
and the EQ-5D-3L health index score and VAS score for each treatment arm.  For each of 
these scores, mean change from Baseline to the final scheduled DB Treatment Period 
Visit (Week 8 or Week 16) will be compared between treatment arms using an analysis of 


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covariance (ANCOVA) model with treatment arm as a factor and baseline score as a 
covariate.
The cumulative number and percentage of subjects who have ever experienced an 
increase from baseline in the FSS total score of greater than or equal to 0.7 through each 
applicable timepoint will also be calculated for each treatment arm.
The analyses described above will also be performed separately for each geographic 
region.  Additional analyses of PROs will be performed as useful and appropriate.
8.1.4
HCV and HIV Resistance Analyses
For subjects who, experience HCV virologic failure (on treatment virologic failure or 
post-treatment relapse), full length NS3/4A and NS5A genes from their available baseline 
samples will be sequenced by population or deep sequencing.  For each DAA target, 
resistance associated signature amino acid variants will be identified by AbbVie Clinical 
Virology.  An appropriate prototypic reference sequence will be used for comparison with 
sequences from samples.
Only samples with an HCV RNA level of ≥ 1000 IU/mL will undergo sequence analysis 
in order to allow accurate assessment of products of amplification.  Therefore, if the HCV 
RNA level at the time of virologic failure or treatment discontinuation is < 1000 IU/mL, 
the sample closest in time after failure/discontinuation with an HCV RNA level 
≥1000 IU/mL will be used.  Included time points for analyses on available samples from 
subjects who do not achieve SVR12 are 1) the sample closest in time after 
failure/discontinuation with an HCV RNA level of ≥ 1000 IU/mL, and 2) 24 weeks post-
DAA treatment, provided that resistance-associated substitutions were detected by either 
population or deep sequencing at the time of failure/discontinuation.
The following definitions will be used in the HCV resistance analyses:
●
Baseline variant:  a variant (by population or deep sequencing) in a baseline 
sample determined by comparison of the amino acid sequence of the baseline 


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sample to the appropriate prototypic reference amino acid sequence for a given 
DAA target.
●
Post-baseline variant by population or deep sequencing:  an amino acid variant 
detected by population or deep sequencing in a post-baseline time point sample 
that was not detected by population or deep sequencing at baseline in the 
subject.
●
Emerged variant by population or deep sequencing:  a post-baseline variant 
that is observed in 2 or more subjects of the same HCV subgenotype by 
population or deep sequencing.
The following analyses will be performed for all subjects in Arm A who experience 
virologic failure and for subjects in Arm B who experience virologic failure during or 
after the OL Treatment Period:
The HCV amino acid sequence as determined by population or deep sequencing of 
available baseline samples will be compared to the appropriate prototypic reference 
amino acid sequence.  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 NS5A).
The following analyses will be performed for subjects who experience virologic failure 
and have post-baseline resistance data available:
The HCV amino acid sequence as determined by population or deep sequencing on 
the sample closest in time after virologic failure with an HCV RNA level of 
≥1000 IU/mL will be compared to the baseline and appropriate prototypic reference 
amino acid sequence.  Listings by subject of all post-baseline amino acid variants 
detected by population or deep sequencing relative to the baseline amino acid 
sequences will be provided for each DAA target (NS3 and NS5A).  Listings by 
subject of all emerged variants by population or deep sequencing, by amino acid 
position and variants within a DAA target in a post baseline sample relative to the 
baseline amino acid sequence will be provided for each DAA target.  In addition, 


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listings by subject of all post-baseline amino acid variants (by population or deep 
sequencing) at signature resistance-associated positions relative to the appropriate 
prototypic reference amino acid sequence will be provided for each DAA target (NS3 
and NS5A).
The persistence of post-baseline variants at signature resistance-associated amino acid 
positions for each target (NS3 and NS5A) will be assessed by population or deep 
sequencing at Post-Treatment Week 24.  Listings by subject and time point of all post-
baseline variants relative to the baseline amino acid sequence will be provided for 
each DAA target (NS3 and NS5A).
If resistance-associated substitutions are not detected a given target for a subject at the 
time of failure, then that target may not be sequenced in subsequent samples from that 
subject.
HIV-1 drug resistance genotyping for protease, reverse transcriptase and integrase 
sequences may be performed for protocol-defined eligible specimens.
8.1.5
Safety
All subjects who receive at least one dose of study drug will be included in the safety 
analyses.  Safety data will be summarized for the set of all subjects and for each of the 
GT1-infected and GT2-infected groups; these summaries will also be performed 
separately for each geographic region.  Safety data will also be summarized for the set of 
HCV/HIV co-infected subjects.  For safety analyses, data from the active (Arm A) and 
placebo (Arm B) treatment arms during the DB Treatment Period will be summarized, 
and comparisons between Arms A and B will be performed, as appropriate.  The data 
from the OL Treatment Period and PT Period will also be summarized, but no 
comparisons will be performed.


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8.1.5.1
Adverse Events
Adverse events (AEs) will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA).  AE data will be summarized and presented using primary 
MedDRA system organ classes (SOCs) and preferred terms according to the version of 
the MedDRA coding dictionary used for the study at the time of database lock. 
AEs will be presented for the following treatment groups:  (1) double-blind active (Arm A 
in the DB Treatment Period), (2) double-blind placebo (Arm B in the DB Treatment 
Period), and (3) open-label active (OL Population Arm B).  Treatment group comparisons 
refer to comparisons of events between double-blind active and double-blind placebo 
during the DB Treatment Period of the study.  For the active treatment arm during the DB 
Treatment Period (Arm A), treatment emergent AEs are defined as any event that begins 
or worsens in severity after initiation of active study drug through 30 days after the last 
dose of active study drug. For the placebo arm (Arm B), treatment-emergent AEs during 
the DB Treatment Period are defined as any event that begins or worsens in severity after 
initiation of placebo through 30 days after the last dose of placebo and prior to OL Day 1 
(if applicable).  For subjects in the OL Population, treatment-emergent AEs are defined as 
any event that begins or worsens in severity after initiation of open-label study drug 
through 30 days after the last dose of open-label study drug.
The number and percentage of subjects in each treatment group with treatment-emergent 
AEs will be tabulated by primary MedDRA SOC and preferred term; comparisons 
between arms will be made using Fisher's exact test.  The tabulation of the number of 
subjects with treatment-emergent AEs by severity grade and relationship to study drug 
DAAs also will be provided.  Subjects reporting more than one AE for a given MedDRA 
preferred term will be counted only once for that term using the event with the most 
severe grade for the severity grade tables and the most related event for the relationship to 
study drug tables.  Subjects reporting more than one type of event within a SOC will be 
counted only once for that SOC.


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8.1.5.2
Clinical Laboratory Data
Clinical laboratory test values will be summarized by treatment group at each visit during 
the DB Treatment Period and separately for subjects treated in the OL Treatment Period.  
The baseline value will be the last measurement on or before the day of the first dose of 
double-blind study drug.  This same baseline value will be used for all summary tables in 
the DB, OL, and Post-Treatment Periods.
Change from baseline to each post-baseline visit, including Final DB and OL Treatment 
Visits and applicable post-treatment visits, will be summarized for each protocol-specified 
laboratory parameter by treatment group; the baseline and visit means will be calculated 
along with the mean, standard deviation, and median for the change from baseline.  The 
differences between the active and placebo arms in the DB Treatment Period will be 
analyzed using an ANOVA model with treatment arm as the factor.  Separate tables will 
be used to summarize the changes from baseline to the DB Treatment Period visits 
(Arms A and B), the OL Treatment Period visits (Arm B), and the Post-Treatment Period 
visits (Arms A and B).
During the DB and OL Treatment periods, laboratory test values will be categorized as 
low, normal, or high based on reference ranges of the laboratory used in this study.  Shift 
tables from baseline to minimum value and from baseline to maximum value during the 
DB and OL Treatment periods will be created.  The shift tables will cross-tabulate, by 
treatment arm, the frequency of subjects with baseline values below/within/above the 
normal range versus minimum/maximum values below/within/above the normal range.
In addition, the number and percentage of subjects with post-baseline values during the 
DB and OL Treatment periods meeting pre-specified criteria for potentially clinically 
significant laboratory values or toxicity grades will be presented by treatment arm.  
Comparisons between arms will be performed on the percentage of subjects with 
laboratory abnormalities (by potentially clinically significant criterion or toxicity grade) 
during the DB Treatment Period for each parameter using Fisher's exact tests.


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8.1.5.3
HIV-1 RNA Data
For the HCV/HIV co-infected subjects who were on stable HIV-1 ART at initiation of 
double-blind study drug, the numbers and percentages of subjects with 2 consecutive 
HIV-1 RNA values ≥ 200 copies/mL during the DB and OL Treatment Periods will be 
calculated for each treatment arm.
8.1.5.4
Vital Signs Data
Vital signs will be summarized by treatment group (DB active and DB placebo) at each 
visit during the DB Treatment Period and separately for subjects treated in the OL
Treatment Period.  The baseline value will be the last measurement on or before the day 
of the first dose of double-blind study drug.  This same baseline value will be used for all 
summary tables in the DB, OL, and Post-Treatment Periods.
Mean changes in temperature, systolic and diastolic blood pressure, pulse, and weight 
from baseline to each post-baseline visit, including Final DB and OL Treatment Visits, 
will be summarized descriptively by arm.  The differences between the active and placebo 
arms in the DB Treatment Period will be analyzed using contrasts within an ANOVA 
model with treatment arm as the factor.  Frequencies and percentages of subjects with 
post-baseline values meeting pre-defined criteria for potentially clinically significant vital 
sign values will be summarized by treatment arm, separately for the DB and OL 
Treatment Periods.  Comparisons between arms will be performed on the percentage of 
subjects experiencing a value meeting the criteria during the DB Treatment Period for 
each parameter using Fisher's exact tests.
8.1.6
Pharmacokinetic and Exposure-Response Analyses
Plasma concentrations of ABT-530 and ABT-493 and possible metabolites and 
pharmacokinetic parameter values for ABT-493 and ABT-530 will be tabulated for each 
subject and group.  Summary statistics will be computed for each time and visit.


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Plasma concentration data from this study may be combined with data from other studies 
and analyzed using the following general methodology:
Population pharmacokinetic analyses will be performed using the actual sampling time 
relative to dosing.  Pharmacokinetic models will be built using a non-linear mixed-effect 
modeling approach with the NONMEM software (version VII, or higher version).  The 
structure of the starting pharmacokinetic model will be based on the pharmacokinetic 
analysis of data from previous studies.  Apparent oral clearance (CL/F) and apparent 
volume of distribution (V/F) of the PK analytes will be the pharmacokinetic parameters of 
major interest in the NONMEM analyses.  If necessary, other parameters, including the 
parameters describing absorption characteristics, may be fixed if useful in the analysis.  
The evaluation criteria described below will be used to examine the performance of 
different models.
●
The objective function of the best model is significantly smaller than the 
alternative model(s).
●
The observed and predicted concentrations from the preferred model are more 
randomly distributed across the line of unity (a straight line with zero intercept 
and a slope of one) than the alternative model(s).
●
Visual inspection of model fits, standard errors of model parameters and 
change in inter-subject and intra-subject error.
Once an appropriate base pharmacokinetic model (including inter- and intra-subject error 
structure) is developed, empirical Bayesian estimates of individual model parameters will 
be calculated by the posterior conditional estimation technique using NONMEM.  The 
relationship between these conditional estimates CL/F and V/F values with only 
potentially physiologically relevant or clinically meaningful covariates (such as subject 
age, sex, body weight, concomitant medications, laboratory markers of hepatic or renal 
function, etc.) will be explored using either stepwise forward selection method, or 
generalized additive method (GAM) or another suitable regression/smoothing method at a 
significance level of 0.05.  After identification of all relevant covariates, a stepwise 
backward elimination of covariates from the full model will be employed to evaluate the 


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significance (at P < 0.005, corresponding to an increase in objective function > 7.88 for 
one degree of freedom) of each covariate in the full model.
In general, all continuous covariates will be entered in the model, initially in a linear 
fashion, with continuous covariates centered around the median value.  Linear or non-
linear relationships of primary pharmacokinetic parameters with various covariates may 
also be explored.  For example:
TVCLi = Theta(1) + Theta(2) (Comedication [1,2,…]) + Theta(3) (WTi-median value) + 
Theta(4) (AGEi – median value).
Where TVCLi = Typical value of clearance for an individual, Theta(1) is the intercept and 
Theta(2) – (4) are regression parameters relating the fixed effects (weight and age 
centered on the median value) to clearance.
Relationship between exposure and clinical observations (antiviral activity) will be 
explored.  Exposure-response relationships for primary and secondary efficacy variables 
and/or some safety measures of interest may also be explored.
The relationship between exposure (e.g., population pharmacokinetic model predicted 
concentrations over time or average concentrations or AUC or trough concentrations of 
the individual model-predicted pharmacokinetic profiles, or some other appropriate 
measure of exposure) and antiviral activity will be explored.  
Logistic regression analyses will explore the relationship between exposure and one or 
more virologic endpoints (e.g., SVR12, relapse following end of treatment and 
breakthrough on treatment).
Additionally, relationship between exposure and safety endpoints of interest may also be 
explored.  Additional analyses will be performed if useful and appropriate.


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8.2
Determination of Sample Size
It is planned to enroll a total of approximately 504 subjects.  In China, approximately 
150 GT1-infected subjects will be randomized to receive active treatment (Arm A) or 
placebo (Arm B) in a 2:1 ratio; approximately 150 GT2-infected subjects will be 
randomized in a 2:1 ratio; and approximately 60 GT3, 4, 5, or 6-infected subjects will be 
randomized in a 2:1 ratio.  Across Singapore and South Korea, approximately 
105 GT1-infected subjects and approximately 39 GT2-infected subjects will be 
randomized to Arm A and Arm B; randomization will occur within each regional country 
in a 2:1 ratio.  A maximum of 50 of the 504 subjects will have HCV/HIV co-infection.  
The expected approximate number of subjects by subpopulation is presented is Table 9.
For the first primary endpoint, with a sample size of 336 GT1 – 6-infected subjects in the 
active treatment arm (Arm A) and assuming that 97% of these subjects will achieve 
SVR12, this study has greater than 95% power to show non-inferiority to a historical 
control regimen, using a threshold of 90%, based on a 1-sample test for superiority using 
EAST 6.3.  The threshold of 90% was based on a historical SVR12 rate of 96% and a 6% 
non-inferiority margin.  To establish efficacy, the lower bound of a 2-sided 95% CI for the 
SVR12 rate must be greater than 90% (based on a normal approximation of a single 
binomial proportion CI).  No adjustment for dropouts is applicable because subjects who 
do not have data at Post Treatment Week 12 (after imputing) are counted as failures for 
SVR12.
For the second primary endpoint, with a sample size of 170 GT1-infected subjects in the 
active treatment arm (Arm A) and assuming that 97% of these subjects will achieve 
SVR12, this study has 90% power to show non-inferiority to a historical control regimen, 
using a threshold of 91%, based on a 1-sample test for superiority using EAST 6.3.  The 
threshold of 91% was based on a historical SVR12 rate of 97% and a 6% non-inferiority 
margin.  To establish efficacy, the lower bound of a 2-sided 95% CI for the SVR12 rate 
must be greater than 91% (based on a normal approximation of a single binomial 
proportion CI).  No adjustment for dropouts is applicable because subjects who do not 
have data at Post Treatment Week 12 (after imputing) are counted as failures for SVR12.


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For the third primary endpoint, with a sample size of 126 GT2-infected subjects in the 
active treatment arm (Arm A) and assuming that 96% of these subjects will achieve 
SVR12, this study has greater than 80% power to show non-inferiority to a historical 
control regimen, using a threshold of 89%, based on a 1-sample test for superiority using 
EAST 6.3.  The threshold of 89% was based on a historical SVR12 rate of 95% and a 6% 
non-inferiority margin.  To establish efficacy, the lower bound of a 2-sided 95% CI for the 
SVR12 rate must be greater than 89% (based on a normal approximation of a single 
binomial proportion CI).  No adjustment for dropouts is applicable because subjects who 
do not have data at Post Treatment Week 12 (after imputing) are counted as failures for 
SVR12.


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Table 9.
Summary of Approximate Subject Numbers Expected by 
Subpopulation
Sub-Population
DB Active
DB Placebo
Total
GT1
170
85
255
China
100
50
150
HCV/HIV Co-infected
10
5
15
Not HCV/HIV Co-infected 
90
45
135
Asian Regional Country(ies)
70
35
105
HCV/HIV Co-infected
6
3
9
Not HCV/HIV Co-infected
64
32
96
GT2
126
63
189
China
100
50
150
HCV/HIV Co-infected
10
5
15
Not HCV/HIV Co-infected 
90
45
135
Asian Regional Country(ies)
26
13
39
HCV/HIV Co-infected
2
1
3
Not HCV/HIV Co-infected 
24
12
36
GT3 – 6
40
20
60
China
40
20
60
HCV/HIV Co-infected
4
2
6
Not HCV/HIV Co-infected 
36
18
54
Total GT1 – 6
336
168
504
China
240
120
360
HCV/HIV Co-infected
24
12
36
Not HCV/HIV Co-infected 
216
108
324
Asian Regional Country(ies)
96
48
144
HCV/HIV Co-infected
8
4
12
Not HCV/HIV Co-infected 
88
44
132


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8.2.1
Justification of Success Criteria for Primary Endpoints
For the first, second, and third primary endpoints, SVR12 thresholds of 90%, 91%, and 
89%, respectively were chosen to align with the historical control rates (and 
corresponding non-inferiority margins) to be used in the Global Phase 3 studies.
In the Global Phase 3 study of GT1-infected subjects without cirrhosis (Study M13-590), 
a historical control rate of 97% is being used with a non-inferiority margin of 6%, 
resulting in a threshold of 91%.  The historical control SVR12 rate for non-cirrhotic 
subjects receiving 3-DAA ± RBV in the Phase 3 trials among subjects dosed according to 
USPI and SmPC recommendations was 97% (870/894 patients),21 with no difference 
between treatment-naïve and treatment-experienced subjects.  Of note, the historical 
SVR12 rate of 97% for the 3-DAA ± RBV regimen is identical to that of SOF/ledipasvir 
for 12 weeks in GT1-infected non-cirrhotic subjects (ION-1, ION-2, and ION-3).20
In the Global Phase 3 study of GT2-infected subjects without cirrhosis (Study M15-464), 
a historical control rate of 95% is being used with a non-inferiority margin of 6%, 
resulting in a threshold of 89%.  This historical control rate is based on the regimen of 
SOF + RBV for 12 weeks of treatment (Table 10).
Table 10.
Historical Data for SOF + RBV for 12 Weeks, GT2-Infected
Non-Cirrhotic Patients
Study
SVR12 n/N (%)
FISSION
59/61 (97%)
POSITRON
85/92 (92%)
FUSION
26/29 (90%)
VALENCE
59/63 (95%)
GS-US-334-01181233
132/136 (97%)
Total
361/381 (95%)
GT = genotype; RBV = ribavirin; SOF = sofosbuvir; SVR12 = sustained virologic response 12 weeks postdosing
Note:
SVR12 rates from Sovaldi® (sofosbuvir) Tablets United States Package Insert.25


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The Global Phase 3 study of GT3-infected subjects without cirrhosis (Study M13-594) is 
a randomized, active-controlled study, with the active control of SOF + daclatasvir (DCV) 
for 12 weeks.  The assumption of an SVR12 rate of 98% for the active control arm was 
based on the ALLY-3 study.26  Among non-cirrhotic subjects in the ALLY-3 trial, 98% of 
treatment-naïve subjects and 92% of treatment-experienced subjects achieved SVR12 after 
12 weeks of SOF + DCV treatment.  Only treatment-naïve subjects will be enrolled in 
Study M13-594.  A 6% non-inferiority margin will be used in Study M13-594.
The Global study of non-cirrhotic subjects which includes GT6 as well as GT4 and GT5 
patients (Study M13-583) is an open-label single-arm study.  The analysis of the primary 
endpoint (SVR12) is descriptive only.
The historical SVR12 rate for the first primary endpoint of the current study was calculated 
as a weighted average of the historical rates from the Global Phase 3 studies using the 
expected percentage of subjects for each GT, as indicated in Table 11.  The expected 
SVR12 rate for the first primary endpoint was calculated similarly, using the expected 
rates for the test regimens in the Global Phase 3 studies.  To align with the non-inferiority 
margin used in the Global studies, a non-inferiority margin of 6% was chosen for this 
study.  Therefore, the percentage of subjects with SVR12 will be non-inferior to the 
historical SVR12 rate of 96% if the lower confidence bound of the 2-sided 95% CI for the 
percentage is > 90%.
The historical and expected SVR12 rates for the second primary endpoint of the current 
study align with those from the Global Phase 3 Study M13-590.  To align with the non-
inferiority margin used in the Global studies, a non-inferiority margin of 6% was chosen 
for this study.  Therefore, the percentage of subjects with SVR12 will be non-inferior to 
the historical SVR12 rate of 97% if the lower confidence bound of the 2-sided 95% CI for 
the percentage is > 91%.
The historical and expected SVR12 rates for the third primary endpoint of the current 
study align with those from the Global Phase 3 Study M15-464.  To align with the non-
inferiority margin used in the Global studies, a non-inferiority margin of 6% was chosen 


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for this study.  Therefore, the percentage of subjects with SVR12 will be non-inferior to 
the historical SVR12 rate of 95% if the lower confidence bound of the 2-sided 95% CI for 
the percentage is > 89%.
Table 11.
SVR12 Rates for Calculation of Historical and Expected SVR12
Rates
GT1
GT2
GT3
GT4 – 6
Overall
Historical SVR12
97%
95%
98%
95%a
96%
Expected ABT-493/ABT-530 SVR12
97%
96%
97%
95%a
97%
Weight
51%
37%
7%
5%
--
GT = genotype; SVR12 = sustained virologic response 12 weeks postdosing
a.
Global Study M13-583 did not provide estimates of these rates; 95% was chosen as a conservative estimate.
8.3
Randomization Methods
The randomization will be stratified by geographic region (China, Singapore, South 
Korea), genotype (GT1, GT2, combined GT3 – 6), and HCV/HIV co-infection status (co-
infected, not co-infected).  In China, eligible subjects will be randomized to Arm A or 
Arm B in the following ratios:  2:1 for GT1, 2:1 for GT2, and 2:1 for combined GT3 – 6.  
In Singapore and South Korea, eligible subjects will be randomized to Arm A or Arm B 
in the following ratios:  2:1 for GT1 and 2:1 for GT2.
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 


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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 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.
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.


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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.
Optional pharmacogenetic and optional intensive PK samples will only be collected if the 
subject has voluntarily signed and dated a separate informed consent, approved by an 
IRB/IEC, after the nature of the testing has been explained and the subject has had an 
opportunity to ask questions.  The separate pharmacogenetic and intensive PK informed 
consents must be signed before the samples are collected and testing is performed.  If the 
subject does not consent to either pharmacogenetic or intensive PK testing, it will not 
impact the subject's participation in the study.
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.
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 


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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 
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.


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12.0
Use of Information
Any optional pharmacogenetic research that may be done using DNA samples from this 
study will be experimental in nature and the results will not be suitable for clinical 
decision making or patient management.  Hence, neither the investigator, nor the subject, 
will be informed of individual results, should analyses be performed, nor will anyone not 
directly involved in this research.  Correspondingly, researchers will have no access to 
subject identifiers.  Individual results will not be reported to anyone not directly involved 
in this research other than for regulatory purposes.  Aggregate data from optional 
pharmacogenetic research may be used in scientific publications or presented at medical 
conventions.  Optional pharmacogenetic research information will be published or 
presented only in a way that does not identify any individual subject.
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.
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 the European Agency for the Evaluation of Medicinal Products (EMEA) 
Guidance on Investigator's Signature for Study Reports.


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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 Randomized, Double-Blind, Placebo-Controlled, Multicenter 
Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in 
Treatment-Naïve and Treatment-Experienced, Non-Cirrhotic Asian 
Adults with Chronic Hepatitis C Virus Genotype (GT) 1 to GT6 
Infection With or Without Human Immunodeficiency Virus 
Co-Infection
Protocol Date:
03 April 2017
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)


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15.0
Reference List
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.
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.
Smith DB, Bukh J, Kuiken C, et al.  Expanded classification of hepatitis C virus 
into 7 genotypes and 67 subtypes:  updated criteria and genotype assignment web 
resource.  Hepatology.  2014;59(1):318-27.
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.e1.
9.
Tao QM, Wang Y, Wang H, et al.  Seroepidemiology of HCV and HBV infection 
in northern China.  Gastroenterol Jpn.  1991;26 (Suppl 3):156-8.
10.
Expert Committee on Chronic Hepatitis C Antiviral Therapy.  Expert consensus for 
antiviral therapy for chronic hepatitis C.  (Electronic Edition) Chin J Clin Infect 
Dis.  2009;3(3):343-52.


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11.
Zhao SM, Jiang TL, Li RQ, et al.  HCV infection in voluntary donors and its 
influence on recruitment of donors in Chongqing area.  Zhongguo Shi Yan Xue Ye 
Xue Za Zhi.  2008;16(3):676-80.
12.
Zhang M, Sun XD, Mark SD, et al.  Hepatitis C virus infection, Linxian, China.  
Emerg Infect Dis.  2005;11(1):17-21.
13.
Liu F, Chen K, He Z, et al.  Hepatitis C seroprevalence and associated risk factors, 
Anyang, China.  Emerg Infect Dis.  2009;15(11):1819-22.
14.
Zhuo H, Lu S, Wang T.  Chronic hepatitis C and progress of anti-viral drugs 
research.  Chemical Drugs, Division II-CDE/SFDA.  2012.
15.
Wei L, Lopez-Talavera JC, Rao H, et al.  Prevalence of HCV viral and host IL28B 
genotypes in China.  Poster Presented at:  62nd Annual Meeting of the American 
Association for the Study of Liver Disease (AASLD 2011); November 4-8, 2011; 
San Francisco, CA.  Poster 412.
16.
Li W, Zhu Y, Hua Z.  [Exploration on the association between the pattern of HBV 
markers and infection of HCV among population].  Zhonghua Liu Xing Bing Xue 
Za Zhi.  1994;15(4):212-4.
17.
Chen X, Xuan M, Wu D.  [Study of superinfection of HBV and HCV].  Zhonghua 
Liu Xing Bing Xue Za Zhi.  1999;20(3):141-3.
18.
Lu L, Nakano T, He Y, et al.  Hepatitis C virus genotype distribution in China; 
predominance of closely related subtype 1b isolates and existence of new 
genotype 6 variants.  J Med Virol.  2005;75(4):538-49.
19.
COPEGUS (ribavirin) [US prescribing information].  South San Francisco, CA; 
Genentech USA, Inc., 2013.
20.
HARVONI® (ledipasvir and sofosbuvir) tablets [package insert].  Foster City, CA; 
Gilead Sciences, Inc., 2015.
21.
Viekira Pak™ (ombitasvir, paritaprevir and ritonavir tablets; dasabuvir tablets) 
[Summary of Product Characteristics].  North Chicago, IL; AbbVie Inc., 2015.
22.
VIEKIRAX™ tablets (ombitasvir/paritaprevir/ritonavir) [Summary of Product 
Characteristics].  Maidenhead, UK; AbbVie Ltd., 2015.


ABT-493, ABT-530
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23.
Technivie (ombitasvir, paritaprevir and ritonavir) [US prescribing information].  
North Chicago, IL; AbbVie Inc., 2015.
24.
Asselah T, Hassanein TI, Qaqish RB.  Efficacy and safety of 
ombitasvir/paritaprevir/ritonavir co-administered with ribavirin in adults with 
genotype 4 chronic hepatitis C infection and cirrhosis (AGATE-I).  Paper presented 
at:  66th Annual Meeting of the American Association for the Study of Liver 
Diseases.  November 13-17, 2015.  Abstract 714.
25.
Sovaldi® (sofosbuvir) Tablets [package insert].  Foster City, CA; Gilead Sciences, 
Inc., 2014.
26.
DAKLINZA™ (daclatasvir) [package insert].  Princeton, NJ; Bristol-Myers Squibb 
Company, 2015.
27.
American Association for the Study of Liver Diseases.  Recommendations for 
testing, managing, and treating hepatitis C.  August 2015.
28.
European Association for the Study of the Liver:  EASL recommendations on 
treatment of hepatitis C.  April 2015.
29.
AbbVie.  ABT-493 Investigator's Brochure Edition 4.  14 September 2015.
30.
AbbVie.  ABT-530 Investigator's Brochure Edition 4.  16 September 2015.
31.
AbbVie.  R&D/13/030.  Combination of ABT-530 and ABT-493 in HCV replicon 
cells.  2013.
32.
AbbVie.  ABT-493 and ABT-530 Dose Combination Investigator's Brochure 
Edition 2.  06 September 2016.
33.
Omata M, Nishiguchi S, Ueno Y, et al.  Sofosbuvir plus ribavirin in Japanese 
patients with chronic genotype 2 HCV infection:  an open-label, phase 3 trial.  J 
Viral Hepat.  2014;21(11):762-8.
34.
http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm.


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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
Clinical
Clinical
CPPM
Statistics
Bioanalysis
Clinical Drug Supply 
Management


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Appendix C.
Study Activities
Double-Blind Treatment Period
Activity
Screening
Day 1a
Week 
1
Week 
2
Week 
4
Week 
8*
Week 
12#
Week 8 
EOT/Week 16 
EOT or 
Premature 
D/C from 
Treatmentb
Informed Consentc
X
Medical Historyd
X
X
Physical Examination 
X
X
X
Vital Signs, Weight, Waist Circumference,e Heighte
X
X
X
X
X
X
X
X
12-lead ECG
X
X
Hematology/Chemistry/Urinalysis/Coagulation Panel, FSHf
X
X
X
X
X
X
X
X
Pregnancy Test (serum [s] urine [u])g
X (s)
X (u)
X (u)
X (u)
X (u)
X (u)
HBsAg, HBV DNA,h HCV Ab, HIV Ab Tests
X
Drug/Alcohol Screen
X
HbA1ci
X
HCV Genotype and Sub-genotype
X
FibroTest and APRI, FibroScan®j or Liver Biopsyj
X
IL28B Samplek
X
Optional Pharmacogenetic Samplec,k
X
Total Insulin
X


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Activity
Screening
Day 1a
Week 
1
Week 
2
Week 
4
Week 
8*
Week 
12#
Week 8 
EOT/Week 16 
EOT or 
Premature 
D/C from 
Treatmentb
Concomitant Medication Assessment
X
X
X
X
X
X
X
X
Adverse Event Assessmentl
X
X
X
X
X
X
X
X
Patient Reported Outcomes Instruments (PROs)m
X
X
X
X
Dispense Study Drug
X
X
Xn
Xn
Xo
Study Drug Accountabilityp and Review of Study Drug 
Adherence
X
X
Xp
Xp
Xp
Xp
HCV RNA Sample
X
X
X
X
X
X
X
X
HIV-1 RNAq,r
X
X
X
X
X
X
X
HCV Resistance Sample
X
X
X
X
X
X
X
Archive Plasma Sample
X
X
X
X
X
X
X
X
Flow Cytometry Sampleq
X
X
X
X
X
Pharmacokinetic Samples for subjects who do not participate in 
the Optional Intensive PK samplings
X
X
X
X
X
X
Pharmacokinetic Samples for subjects who do participate in the 
Optional Intensive PK samplingc,s
Xt
X
X
Xt
X
X
X
EOT = End of treatment; D/C = Discontinuation
*
The EOT visit can be at Week 8 or Week 16 depending on treatment assigned.
#
Applicable only to those subjects enrolled into a 16-week treatment.
a.
All procedures to be performed prior to first dose, with exception of the additional (optional) post-dose pharmacokinetic samples (Section 5.3.2.1).


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b.
Subjects who prematurely discontinue the Treatment Period should return to the site to complete the Premature Discontinuation Visit Procedures (preferably prior to the 
initiation of any other anti-HCV therapy).
c.
Subjects need to sign an IRB/IEC approved informed consent for the study (prior to performing any screening or study-specific procedures) and the optional Pharmacogenetic 
Sample and Intensive PK sample(s), if applicable.
d.
A complete medical history will be taken at Screening and will be updated at the Study Day 1 Visit.
e.
Height will be measured at the Screening Visit only.  Waist circumference will be measured at the Screening Visit, but if it is not measured at Screening, it may be measured 
on Day 1.
f.
Only at Screening, for female subjects to assess postmenopausal state.
g.
Pregnancy testing is not required for females of non-childbearing potential as defined in Inclusion Criterion 3. 
h.
Perform the test for HBV DNA if HBsAg is negative. 
i.
For those with history of diabetes mellitus. 
j.
For subjects who have not had a qualifying liver biopsy within the previous 24 months or a qualifying FibroScan® within the previous 6 months. 
k.
If the sample is not collected at Study Day 1, it may be collected at any other visit during the study.
l.
See specific information regarding adverse event collection in Section 6.1.4.
m.
PROs should be administered before any study procedures.  EOT PROs are at Week 8 EOT or Week 16 EOT, as applicable. 
n.
Applicable only to those subjects enrolled into a 16-week treatment. 
o.
Open-Label study drug will be dispensed to those subjects randomized to Arm B in the DB Treatment Period.
p.
Subjects should bring all the study drug to the study drug accountability visits at Weeks 4, 8, 12, EOT or Premature D/C.  The site will record the number of tablets returned at 
these visits.
q.
HCV/HIV co-infected subjects only.
r.
For HCV/HIV co-infected subjects on stable ART:  As detailed in Section 5.4.1.2, a repeat HIV-1 RNA blood draw to confirm a HIV-1 RNA result of ≥ 200 copies/mL can 
be done as an unscheduled visit, but must be performed at least 2 weeks apart from the prior HIV-1 RNA result.  At the time the repeat plasma HIV-1 RNA is drawn, a sample 
may be obtained for HIV-1 resistance testing.  If the confirmatory HIV-1 RNA lab draw falls on the date of a scheduled study visit, only a single HIV-1 RNA and HIV-1 
resistance blood draw is needed at the visit.
s.
Details regarding timing of PK samples are provided in Section 5.3.2.1.
t.
For subjects participating in Optional Intensive PK sampling, additional PK samples will be drawn on Study Day 1 at 2, 4 and 6 hours post-dose and on Week 4 visit 
immediately prior to dose (0 hour) and 2 and 4 hours post-dose during the visit.


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Open-Label Treatment Period
Activity
Day 1
Week 1
Week 2
Week 4
Week 8*
Week 12#
Week 8 EOT/Week 16 
EOT or Premature D/C 
from Treatmenta
First Dose of Active Drug
Xb
Physical Examination
X
Vital Signs, Weight
X
X
X
X
X
X
12-lead ECG
X
Hematology/Chemistry/Urinalysis/Coagulation Panel
X
X
X
X
X
X
Pregnancy Test (urine [u])c
X (u)
X (u)
X (u)
X (u)
Concomitant Medication Assessment
X
X
X
X
X
X
Adverse Event Assessmentd
X
X
X
X
X
X
Dispense Study Drug
X
Xe
X
Study Drug Accountabilityf and Review of Study Drug Adherence
X
X
Xf
Xf
Xf
Xf
HCV RNA Sample
X
X
X
X
X
X
HIV-1 RNAg,h
X
X
X
X
X
X
HCV Resistance Sample
X
X
X
X
X
X
Archive Plasma Sample
X
X
X
X
X
X
Flow Cytometry Sampleg
X
X
X
Pharmacokinetic Samples for subjects who do not participate in the 
Optional Intensive PK samplingi
X
X
X
X
X
X
Pharmacokinetic Samples for subjects who do participate in the 
Optional Intensive PK samplingi
X
X
Xj
X
X
X
EOT = End of treatment; D/C = Discontinuation
*
The EOT visit can be at Week 8 or Week 16 depending on treatment assigned.


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#
Applicable only to those subjects enrolled into a 16-week treatment.
a.
Subjects who prematurely discontinue the OL Treatment Period should return to the site to complete the Premature D/C Visit Procedures (preferably prior to the initiation of 
any other anti-HCV therapy).
b.
Subjects will take the first dose of Open-Label study drugs the day after the last day of the DB Treatment Period.  The site will call the subject and record the study drug start 
date in the EDC system and source documents.  The study drug end date of drug will be recorded in EDC and the source at OL Week 8 EOT/Week 16 EOT or Premature D/C 
from treatment.
c.
Pregnancy testing is not required for females of non-childbearing potential as defined in Inclusion Criterion 3.
d.
See specific information regarding adverse event collection in Section 6.1.4.
e.
Applicable only to those subjects enrolled into a 16-week treatment. 
f.
Subjects should bring all the study drug to the study drug accountability visits at Weeks 4, 8, 12, EOT or Premature D/C.  The site will record the number of tablets returned at 
these visits.
g.
HCV/HIV co-infected subjects only. 
h.
For HCV/HIV co-infected subjects on stable ART:  As detailed in Section 5.4.1.2, a repeat HIV-1 RNA blood draw to confirm a HIV-1 RNA result of ≥ 200 copies/mL can 
be done as an unscheduled visit, but must be performed at least 2 weeks apart from the prior HIV-1 RNA result.  At the time the repeat plasma HIV-1 RNA is drawn, a sample 
may be obtained for HIV-1 resistance testing.  If the confirmatory HIV-1 RNA lab draw falls on the date of a scheduled study visit, only a single HIV-1 RNA and HIV-1 
resistance blood draw is needed at the visit.
i.
Details regarding timing of PK samples are provided in Section 5.3.2.1.
j.
For subjects participating in Optional Intensive PK sampling, additional PK samples will be drawn on the Week 4 visit immediately prior to dose (0 hour) and 2 and 4 hours 
post-dose during the visit.


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Post Treatment Period
Activity
PT Week 4
PT Week 12
PT Week 24 or PT D/Ca
Vital Signs and Weight
X
X
X
Hematology/Chemistry/Urinalysis/Coagulation Panel
X
Xb
Pregnancy Test (urine)c
X (u)
X (u)b
Concomitant Medication Assessmentd
X
X
X
PRO Instrumentse
X
X
Adverse Event Assessmentf,g
X
X
X
HCV RNA Sample
X
X
X
HIV-1 RNAh,i
X
X
X
HCV Resistance Sample
X
X
X
Flow Cytometry Sampleh
X
X
X
Archive Plasma Sample
X
X
X
PT = Post Treatment
a.
Subjects who prematurely discontinue from the Post-Treatment Period should return to the site to complete the PT Discontinuation Visit procedures.
b.
Hematology/Chemistry/Urinalysis/Coagulation Panel and Pregnancy Test are not required at PT Week 24, but only at PT D/C if subject discontinued prior to PT Week 4.
c.
Urine Pregnancy testing is not required in the PT Period for women that are not of childbearing potential.
d.
Only medications taken for SAEs and treatment of HCV and HIV will be collected after 30 days post-dosing.
e.
PROs should be administered before any study procedures.  PROs at PT WK 12 and PT WK 24 only required for subjects randomized to Arm A.
f.
All AEs (whether solicited or spontaneously reported by the subject) will be collected until 30 days post dosing.
g.
After 30 days following completion of study treatment, and throughout the Post-Treatment Period, all spontaneously reported SAEs will be collected (nonserious AEs will not 
be collected) (Section 6.1.4).
h.
HCV/HIV co-infected subjects only.


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i.
For HCV/HIV co-infected subjects on stable ART:  As detailed in Section 5.4.1.2, a repeat HIV-1 RNA blood draw to confirm a HIV-a RNA result of ≥ 200 copies/mL can 
be done as an unscheduled visit, but must be performed at least 2 weeks apart from the prior HIV-1 RNA result.  At the time the repeat plasma HIV-1 RNA is drawn, a sample 
should be obtained for HIV-1 resistance testing.  If the confirmatory HIV-1 RNA lab draw falls on the date of a scheduled study visit, only a single HIV-1 RNA and HIV-1 
resistance blood draw is needed at the visit.
Note:
Day 1 of the Post-Treatment Period will be defined as the day after the last dose of study drug.


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Appendix D.
List of AIDS-Associated Opportunistic Infections
Collection of data regarding known AIDS-associated opportunistic infections is covered 
in Section 6.1.8.
●
Aspergillosis
●
Bartonellosis
●
Candidiasis (*Bronchi; *Esophagus; *Lungs; Oropharyngeal [Thrush]; 
*Trachea; Vulvovaginal [Persistent, Frequent, or Poorly Responsive to 
Therapy])
●
*Coccidioidomycosis
●
*Cryptococcosis
●
*Cryptosporidiosis
●
Cytomegalovirus (*Retinitis; *Cytomegalovirus Disease [other than liver, 
spleen or nodes])
●
Enteric infections, Recurrent (Bacterial)
●
Herpes Simplex Virus (*Bronchitis; *Esophagitis; *Pneumonitis; *Chronic 
Ulcer(s) [> 1 month in duration])
●
*Histoplasmosis
●
Human Herpesvirus-8 Disease (Kaposi Sarcoma, Primary Effusion 
Lymphoma, Multicentric Castleman's Disease)
●
Human Papilloma Virus Infections
●
*Isosporiasis (Cystoisosporiasis)
●
Microsporidiosis
●
*Mycobacterium avium – Complex Disease (Disseminated)
●
*Mycobacterium tuberculosis – Infection and Disease
●
*Pneumonia
●
*Pneumonia, recurrent bacterial (and/or other respiratory infections including 
sinusitis, bronchitis, otitis)
●
*Progressive multifocal leukoencephalopathy (JC Virus Infection)
●
Syphilis


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●
*Toxoplasma Gondii Encephalitis
●
Varicella Zoster Virus Diseases
*
AIDS-defining event as described by CDC Surveillance Case Definition of 1993.34



SAP_000.pdf: 
ABT-493/ABT-530
M15-592 – Statistical Analysis Plan
Version 1.0 – 15 Jan 2018
1
1.0
Title Page
Statistical Analysis Plan
Study M15-592
A Randomized, Double-Blind, Placebo-Controlled, 
Multicenter Study to Evaluate the Efficacy and 
Safety of ABT-493/ABT-530 in Treatment-Naïve and 
Treatment-Experienced, Non-Cirrhotic Asian Adults 
with Chronic Hepatitis C Virus Genotype (GT) 1 to 
GT6 Infection With or Without Human 
Immunodeficiency Virus Co-Infection
Date:  15 Jan 2018
Version 1.0
NCT03222583


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M15-592 – Statistical Analysis Plan
Version 1.0 – 15 Jan 2018
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2.0
Table of Contents
1.0
Title Page ...............................................................................1
2.0
Table of Contents ..................................................................2
3.0
Introduction...........................................................................6
4.0
Study Objectives, Design and Procedures............................6
4.1
Objectives .............................................................................................. 6
4.2
Design Diagram ..................................................................................... 7
4.3
Sample Size............................................................................................ 9
4.3.1
Justification of Success Criteria for Primary Endpoints......................... 12
4.4
Planned Analyses ................................................................................. 14
5.0
Analysis Populations ........................................................... 15
5.1
Definitions of Analysis Populations...................................................... 15
5.1.1
Intention-to-Treat (ITT) Population ...................................................... 15
5.1.2
Modified Intention-to-Treat (mITT) Populations .................................. 15
5.1.3
Safety Population ................................................................................. 16
5.1.4
Open-Label (OL) Population ................................................................ 16
5.2
Variables Used for Stratification of Randomization .............................. 16
6.0
Analysis Conventions .......................................................... 17
6.1
Definition of Baseline, Final Treatment, and Final Post-Treatment 
Assessments ......................................................................................... 17
6.1.1
Baseline................................................................................................ 17
6.1.2
Study Days........................................................................................... 17
6.2
Definition of Analysis Windows........................................................... 19
6.3
Missing Data Imputation ...................................................................... 25
7.0
Demographics, Baseline Characteristics, Medical 
History, and Other Medications.........................................27
7.1
Demographic and Baseline Characteristics ........................................... 27
7.2
Medical History.................................................................................... 35
7.3
Prior, Concomitant and Post-Treatment Medications ............................ 35
8.0
Subject Disposition..............................................................36
8.1
Disposition of Safety Population .......................................................... 36
9.0
Study Drug Exposure and Compliance..............................37


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9.1
Exposure .............................................................................................. 37
9.2
Compliance .......................................................................................... 38
10.0
Efficacy Analysis .................................................................39
10.1
General Considerations......................................................................... 39
10.2
Handling of Multiplicity....................................................................... 44
10.3
Primary Efficacy Analysis.................................................................... 44
10.4
Secondary Efficacy Analyses ............................................................... 45
10.5
Sensitivity Analyses for SVR12............................................................. 46
10.5.1
Imputation Approaches......................................................................... 47
10.5.2
Assessment of Homogeneity Across Stratification Variables ................ 47
10.6
Efficacy Subgroup Analysis ................................................................. 48
10.7
Additional Efficacy Analyses ............................................................... 50
10.8
HCV and HIV Resistance Analyses...................................................... 53
10.9
Patient Reported Outcomes .................................................................. 60
11.0
Safety Analysis.....................................................................61
11.1
General Considerations......................................................................... 61
11.2
Analysis of Adverse Events.................................................................. 61
11.2.1
Treatment-Emergent Adverse Events.................................................... 62
11.2.2
Tabulations of Treatment-Emergent Adverse Events ............................ 62
11.2.3
Listings of Adverse Events................................................................... 67
11.3
Analysis of Laboratory Data................................................................. 68
11.3.1
Variables and Criteria Defining Abnormality........................................ 68
11.3.2
Statistical Methods ............................................................................... 71
11.4
Analysis of Vital Signs and Weight ...................................................... 73
11.4.1
Variables and Criteria Defining Abnormality........................................ 73
11.4.2
Statistical Methods ............................................................................... 74
11.5
Analysis of HIV-1 RNA and Flow Cytometry Data .............................. 75
12.0
Summary of Changes .......................................................... 76
12.1
Summary of Changes Between the Latest Version of the Protocol 
and SAP ............................................................................................... 76
13.0
References............................................................................78


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List of Tables
Table 1.
Summary of Approximate Subject Numbers Expected by 
Subpopulation ...................................................................................... 11
Table 2.
Historical Data for SOF + RBV for 12 Weeks, GT2-Infected  
Non-Cirrhotic Patients.......................................................................... 12
Table 3.
SVR12 Rates for Calculation of Historical and Expected SVR12
Rates .................................................................................................... 14
Table 4.
Analysis Time Windows for HCV RNA and Resistance 
Endpoints, Safety Laboratory and Vital Sign Measurements, and 
PRO Instruments (DB Treatment Period).............................................. 21
Table 5.
Analysis Time Windows for HCV RNA and Resistance Endpoints 
and Safety Laboratory and Vital Sign Measurements (OL 
Treatment Period)................................................................................. 22
Table 6.
Analysis Time Windows for HCV RNA and Resistance Endpoints 
(Post-Treatment Period) ....................................................................... 23
Table 7.
Analysis Time Windows for Safety Laboratory and Vital Sign 
Measurements and PRO Instruments (Post-Treatment Period).............. 23
Table 8.
Analysis Time Windows for HIV-1 RNA and Flow Cytometry 
Measurements (DB Treatment Period).................................................. 24
Table 9.
Analysis Time Windows for HIV-1 RNA and Flow Cytometry 
Measurements (OL Treatment Period).................................................. 24
Table 10.
Analysis Time Windows for HIV-1 RNA and Flow Cytometry 
Measurements (Post-Treatment Period)................................................ 25
Table 11.
Baseline Fibrosis Stage......................................................................... 30
Table 12.
Clinical Identification of Metabolic Syndrome ..................................... 32
Table 13.
Medical History Categories .................................................................. 33
Table 14.
List of Signature Amino Acid Positions and a Key Subset of 
Amino Acid Positions........................................................................... 55
Table 15.
Definitions of Toxicity Grades 1, 2, 3, and 4 for Laboratory 
Values .................................................................................................. 69
Table 16.
Criteria for Potentially Clinically Significant Vital Sign Values............ 74


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List of Figures
Figure 1.
Study Schematic..................................................................................... 8


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3.0
Introduction
This statistical analysis plan (SAP) describes the statistical analyses to be completed by 
the AbbVie Statistics and Statistical Programming Departments for Study M15-592.  
Study M15-592 evaluates the efficacy, safety, and pharmacokinetics of 
ABT-493/ABT-530 in non-cirrhotic, chronic hepatitis C virus (HCV) genotype (GT) 1 to 
GT6-infected Asian adult subjects with or without human immunodeficiency virus (HIV) 
co-infection who are HCV treatment-naïve or treatment-experienced with interferon (IFN) 
(alpha, beta or pegylated-IFN [pegIFN]) with or without ribavirin (RBV) OR sofosbuvir 
(SOF) with RBV with or without IFN.
This SAP provides details to further elaborate statistical methods as outlined in Clinical 
Study Protocol M15-592 incorporating Administrative Change No. 1 dated 
02 October 2017 and describes analysis conventions to guide the statistical programming.  
Analyses will be performed using SAS® Version 9.3 (SAS Institute, Inc., Cary, NC) or 
later under the UNIX operating system.
This SAP does not include the analysis plan for the pharmacokinetic data.
4.0
Study Objectives, Design and Procedures
4.1
Objectives
The primary objectives of this study are to compare, among the combined group of GT1 
to GT6-infected subjects, among the GT1-infected subjects, and among the GT2-infected 
subjects, the percentage of subjects achieving SVR12, (HCV RNA < lower limit of 
quantification [LLOQ] 12 weeks after the last actual dose of study drug) to a historical 
SVR12 rate and to assess the safety following 8 or 16 weeks of treatment with the 
ABT-493/ABT-530 combination regimen in treatment-naïve and treatment-experienced 
non-cirrhotic adults with chronic HCV GT1 to GT6 infection with or without HIV co-
infection.
The secondary objectives are to assess:


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●
The percentage of subjects with on-treatment HCV virologic failure;
●
The percentage of subjects with post treatment relapse of HCV infection;
●
The percentage of HCV/HIV co-infected subjects achieving SVR12.
An additional objective is to assess the pharmacokinetics of ABT-493 and ABT-530 in 
Asian HCV-infected adults.
4.2
Design Diagram
This is a Phase 3, randomized, double-blind, placebo-controlled multicenter study to 
evaluate the efficacy and safety of ABT-493/ABT-530 in non-cirrhotic chronic HCV GT1 
to GT6-infected Asian adult subjects with or without HIV co-infection who are HCV 
treatment-naïve or treatment-experienced with IFN (alpha, beta or pegIFN) with or 
without RBV OR sofosbuvir with RBV with or without IFN.  This study consists of a 
Double-Blind (DB) Treatment Period, an Open-Label (OL) Treatment Period, and a Post-
Treatment (PT) Period.  The study schematic is presented in Figure 1.
The study is designed to enroll approximately 504 subjects to meet scientific and 
regulatory objectives without enrolling an undue number of subjects in alignment with 
scientific and ethical considerations.  A minimum of 150 GT1-infected subjects, a 
minimum of 150 GT2-infected subjects and approximately 60 GT3, 4, 5 or 6-infected 
subjects from China will be enrolled into this study.  Approximately 105 GT1-infected 
subjects and approximately 39 GT2-infected subjects will also be enrolled into this study 
from the regional Asian countries of South Korea and Singapore.  Of the approximately 
504 subjects, a maximum of 50 HCV/HIV co-infected subjects will be enrolled.


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Figure 1.
Study Schematic
Chronic HCV GT1 – 6 infected adults without underlying cirrhosis will be enrolled into 
one of two treatment arms:
Arm A:  ABT-493/ABT-530 300 mg/120 mg QD for 8 or 16 weeks
Arm B:  Matching Placebo for 8 or 16 weeks followed by open-label 
ABT-493/ABT-530 300 mg/120 mg QD for 8 or 16 weeks
All subjects in this study are to be non-cirrhotic.  Treatment experienced GT3-infected 
subjects will receive 16 weeks of treatment in the DB and/or OL Treatment Period; all 
other subjects will receive 8 weeks of treatment in the DB and/or OL Treatment Period.
In China, subjects will be randomized to receive active treatment (Arm A) or placebo 
(Arm B) in a 2:1 ratio for each of the GT1 and GT2-infected groups and the combined 
GT3 to GT6 infected group.  In each regional Asian country, each of the GT1 and GT2 
infected groups will be randomized in a 2:1 ratio.
Subjects who are randomized to Arm B will receive open-label ABT-493/ABT-530 
300 mg/120 mg QD for 8 or 16 weeks following the DB Treatment Period.


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Randomization of subjects will be stratified by geographic region (China, Singapore and 
South Korea), genotype (GT1, GT2, combined GT3 – 6), and HCV/HIV co-infection 
status (yes, no).
4.3
Sample Size
It is planned to enroll a total of approximately 504 subjects.  In China, approximately 
150 GT1-infected subjects will be randomized to receive active treatment (Arm A) or 
placebo (Arm B) in a 2:1 ratio; approximately 150 GT2-infected subjects will be 
randomized in a 2:1 ratio; and approximately 60 GT3, 4, 5, or 6-infected subjects will be 
randomized in a 2:1 ratio.  Across Singapore and South Korea, approximately 
105 GT1-infected subjects and approximately 39 GT2-infected subjects will be 
randomized to Arm A and Arm B; randomization will occur within each regional country 
in a 2:1 ratio.  A maximum of 50 of the 504 subjects will have HCV/HIV co-infection 
across all countries.  The expected approximate number of subjects by subpopulation is 
presented in Table 1.
For the first primary endpoint, with a sample size of 336 GT1 – 6-infected subjects in the 
active treatment arm (Arm A) and assuming that 97% of these subjects will achieve 
SVR12, this study has greater than 95% power to show non-inferiority to a historical 
control regimen, using a threshold of 90%, based on a 1-sample test for superiority using 
EAST 6.3.  The threshold of 90% was based on a historical SVR12 rate of 96% and a 6% 
non-inferiority margin (see Section 4.3.1).  To establish efficacy, the lower bound of a 
2-sided 95% confidence interval (CI) for the SVR12 rate must be greater than 90% (based 
on a normal approximation of a single binomial proportion CI).  No adjustment for 
dropouts is applicable because subjects who do not have data at PT Week 12 (after 
imputing) are counted as failures for SVR12.
For the second primary endpoint, with a sample size of 170 GT1-infected subjects in the 
active treatment arm (Arm A) and assuming that 97% of these subjects will achieve 
SVR12, this study has 90% power to show non-inferiority to a historical control regimen, 
using a threshold of 91%, based on a 1-sample test for superiority using EAST 6.3.  The 


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threshold of 91% was based on a historical SVR12 rate of 97% and a 6% non-inferiority 
margin (see Section 4.3.1).  To establish efficacy, the lower bound of a 2-sided 95% CI 
for the SVR12 rate must be greater than 91% (based on a normal approximation of a single 
binomial proportion CI).  No adjustment for dropouts is applicable because subjects who 
do not have data at PT Week 12 (after imputing) are counted as failures for SVR12.
For the third primary endpoint, with a sample size of 126 GT2-infected subjects in the 
active treatment arm (Arm A) and assuming that 96% of these subjects will achieve 
SVR12, this study has greater than 80% power to show non-inferiority to a historical 
control regimen, using a threshold of 89%, based on a 1-sample test for superiority using 
EAST 6.3.  The threshold of 89% was based on a historical SVR12 rate of 95% and a 6% 
non-inferiority margin (see Section 4.3.1).  To establish efficacy, the lower bound of a 
2-sided 95% CI for the SVR12 rate must be greater than 89% (based on a normal 
approximation of a single binomial proportion CI).  No adjustment for dropouts is 
applicable because subjects who do not have data at PT Week 12 (after imputing) are 
counted as failures for SVR12.


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Table 1.
Summary of Approximate Subject Numbers Expected by 
Subpopulation
Sub-Population
DB Active
DB Placebo
Total
GT1
170
85
255
China
100
50
150
HCV/HIV Co-infected
10
5
15
Not HCV/HIV Co-infected 
90
45
135
Asian Regional Countries
70
35
105
HCV/HIV Co-infected
6
3
9
Not HCV/HIV Co-infected
64
32
96
GT2
126
63
189
China
100
50
150
HCV/HIV Co-infected
10
5
15
Not HCV/HIV Co-infected 
90
45
135
Asian Regional Countries
26
13
39
HCV/HIV Co-infected
2
1
3
Not HCV/HIV Co-infected 
24
12
36
GT3 – 6
40
20
60
China
40
20
60
HCV/HIV Co-infected
4
2
6
Not HCV/HIV Co-infected 
36
18
54
Total GT1 – 6
336
168
504
China
240
120
360
HCV/HIV Co-infected
24
12
36
Not HCV/HIV Co-infected 
216
108
324
Asian Regional Countries
96
48
144
HCV/HIV Co-infected
8
4
12
Not HCV/HIV Co-infected 
88
44
132


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4.3.1
Justification of Success Criteria for Primary Endpoints
For the first, second, and third primary endpoints, SVR12 thresholds of 90%, 91%, and 
89%, respectively were chosen to align with the historical control rates (and 
corresponding non-inferiority margins) used in the Global Phase 3 studies.
In the Global Phase 3 study of GT1-infected subjects without cirrhosis (Study M13-590), 
a historical control rate of 97% was used with a non-inferiority margin of 6%, resulting in 
a threshold of 91%.  The historical control SVR12 rate for non-cirrhotic subjects receiving 
ombitasvir/paritaprevir/ritonavir and dasabuvir (3-DAA) ± RBV in the 3-DAA Phase 3 
trials among subjects dosed according to the United States Package Insert (USPI) and the 
Summary of Product Characteristics (SmPC) recommendations was 97% 
(870/894 patients),1 with no difference between treatment-naïve and treatment-
experienced subjects.  Of note, the historical SVR12 rate of 97% for the 3-DAA ± RBV 
regimen is identical to that of SOF/ledipasvir for 12 weeks in GT1-infected non-cirrhotic 
subjects (ION-1, ION-2, and ION-3).2
In the Global Phase 3 study of GT2-infected subjects without cirrhosis (Study M15-464), 
a historical control rate of 95% was used with a non-inferiority margin of 6%, resulting in 
a threshold of 89%.  This historical control rate was based on the regimen of SOF + RBV 
for 12 weeks of treatment (Table 2).
Table 2.
Historical Data for SOF + RBV for 12 Weeks, GT2-Infected 
Non-Cirrhotic Patients
Study
SVR12 n/N (%)
FISSION
59/61 (97%)
POSITRON
85/92 (92%)
FUSION
26/29 (90%)
VALENCE
59/63 (95%)
GS-US-334-0118123
132/136 (97%)
Total
361/381 (95%)
GT = genotype; RBV = ribavirin; SOF = sofosbuvir; SVR12 = sustained virologic response 12 weeks postdosing
Note:
SVR12 rates from Sovaldi® (sofosbuvir) Tablets United States Package Insert.4


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The Global Phase 3 study of GT3-infected subjects without cirrhosis (Study M13-594) 
was a randomized, active-controlled study, with the active control of SOF + daclatasvir 
(DCV) for 12 weeks.  The assumption of an SVR12 rate of 98% for the active control arm 
was based on the ALLY-3 study.5  Among non-cirrhotic subjects in the ALLY-3 trial, 
98% of treatment-naïve subjects and 92% of treatment-experienced subjects achieved 
SVR12 after 12 weeks of SOF + DCV treatment.  Only treatment-naïve subjects were 
enrolled in Study M13-594.  A 6% non-inferiority margin was used in Study M13-594.
The Global study of non-cirrhotic subjects which includes GT6 as well as GT4 and GT5 
patients (Study M13-583) was an open-label single-arm study.  The analysis of the 
primary endpoint (SVR12) was descriptive only.
The historical SVR12 rate for the first primary endpoint of the current study was calculated 
as a weighted average of the historical rates from the Global Phase 3 studies using the 
expected percentage of subjects for each GT, as indicated in Table 3.  The expected 
SVR12 rate for the first primary endpoint was calculated similarly, using the expected 
rates for the test regimens in the Global Phase 3 studies.  To align with the non-inferiority 
margin used in the Global studies, a non-inferiority margin of 6% was chosen for this 
study.  Therefore, the percentage of subjects with SVR12 will be non-inferior to the 
historical SVR12 rate of 96% if the lower confidence bound of the 2-sided 95% CI for the 
percentage is > 90%.
The historical and expected SVR12 rates for the second primary endpoint of the current 
study align with those from the Global Phase 3 Study M13-590.  To align with the 
non-inferiority margin used in the Global studies, a non-inferiority margin of 6% was 
chosen for this study.  Therefore, the percentage of subjects with SVR12 will be 
non-inferior to the historical SVR12 rate of 97% if the lower confidence bound of the 
2 sided 95% CI for the percentage is > 91%.
The historical and expected SVR12 rates for the third primary endpoint of the current 
study align with those from the Global Phase 3 Study M15-464.  To align with the 
non-inferiority margin used in the Global studies, a non-inferiority margin of 6% was 


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chosen for this study.  Therefore, the percentage of subjects with SVR12 will be 
non-inferior to the historical SVR12 rate of 95% if the lower confidence bound of the 
2-sided 95% CI for the percentage is > 89%.
Table 3.
SVR12 Rates for Calculation of Historical and Expected SVR12
Rates
GT1
GT2
GT3
GT4 – 6
Overall
Historical SVR12
97%
95%
98%
95%a
96%
Expected ABT-493/ABT-530 SVR12
97%
96%
97%
95%a
97%
Weight
51%
37%
7%
5%
--
GT = genotype; SVR12 = sustained virologic response 12 weeks postdosing
a.
Global Study M13-583 did not provide estimates of these rates; 95% was chosen as a conservative estimate.
4.4
Planned Analyses
The primary analysis will occur after all subjects in Arm A have completed the PT 
Week 12 Visit or prematurely discontinued the study.  The primary analysis will 
summarize data through PT Week 12 for Arm A subjects and data through the DB 
Treatment Period for Arm B subjects.  The data for the primary analysis will be locked 
after data cleaning, and data collected after this lock will be added to a new version of the 
database.  Results from the primary analysis will be described in the primary clinical 
study report (CSR) and submitted to regulatory agencies as part of an NDA submission.  
An interim analysis will occur after all Arm A subjects have completed the PT Week 24 
Visit or prematurely discontinued the study and all Arm B subjects have completed the PT 
Week 12 Visit or prematurely discontinued the study.  The data for the interim analysis 
will be locked after data cleaning, and data collected after this lock will be added to a new 
version of the database.    
The final analysis will be conducted after all subjects enrolled in the study have 
completed the PT Week 24 Visit or prematurely discontinued the study.  The data for the 
final analysis will be cleaned and locked at the end of the study and included in the final 
CSR.


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All analyses will be conducted by statisticians and programmers at AbbVie (or their 
designees) according to the methodologies specified in this SAP.  There is no intention of 
shortening the follow-up time of subjects based on efficacy findings from the primary or 
interim analyses.  All subjects who receive active study drug will be followed for 
24 weeks following treatment.  Therefore, no statistical adjustment will be employed due 
to the primary or interim analysis.
5.0
Analysis Populations
5.1
Definitions of Analysis Populations
Within each of the populations defined below, subjects who are GT1-infected and GT2-
infected will be categorized as such.  The categorization of these 2 groups will be based 
on the latest determination of genotype from the baseline sample (by the central 
laboratory or by phylogenetic analysis, with preference given to the phylogenetic analysis 
results) at the time of the primary SVR12 analysis.
5.1.1
Intention-to-Treat (ITT) Population
All randomized subjects who receive at least one dose of study drug in the DB Treatment 
Period will be included in the ITT population.  The data from the ITT population will be 
presented by the treatment arm assigned at the time of randomization (Arm A or Arm B).
Efficacy analyses and analyses of compliance data will be performed on the ITT 
population, unless otherwise specified.  If the ITT population differs from the safety 
population (as described in Section 5.1.3), analyses of demographics and baseline 
characteristics will also be performed on the ITT population by treatment arm.
5.1.2
Modified Intention-to-Treat (mITT) Populations
Sensitivity analyses of SVR12 as described in Section 10.5, when applicable, will be 
performed on the ITT population modified to exclude subjects who have multiple GTs 
according to the central laboratory or phylogenetic analyses of the baseline sample or 
subjects who received an incorrect duration of treatment due to incorrect classification of 


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GT or treatment experience at randomization (mITT-GT), and on the mITT-GT 
population modified to exclude subjects who did not achieve SVR12 for reasons other than 
virologic failure (i.e., subjects with reasons other than on-treatment HCV virologic failure 
and relapse) (mITT-GT-VF).  
5.1.3
Safety Population
All subjects who receive at least one dose of study drug in the DB Treatment Period will 
be included in the safety population.  Analyses of safety; demographics; baseline 
characteristics; medical history; prior, concomitant, and post-treatment medications; and 
study drug exposure will be performed on the safety population according to actual 
treatment received during the DB Treatment Period even if this differs from the 
randomized treatment assignment; i.e., subject grouping will be based on the actual 
treatment received, not the arm to which the subject was randomized.  If all subjects take 
the treatment to which they were randomly assigned, the safety population will be 
presented in the same way as the ITT population.
5.1.4
Open-Label (OL) Population
All subjects randomized to Arm B who receive at least one dose of active, OL study drug 
during the OL Treatment Period will be included in the OL population.  All analyses of 
data collected for subjects in Arm B during and after the OL Treatment Period will be 
performed on the OL population.
5.2
Variables Used for Stratification of Randomization
Randomization of subjects will be stratified by geographic region (China, Singapore and 
South Korea), genotype (GT1, GT2, combined GT3 – 6), and HCV/HIV co-infection 
status (yes, no). 
If a subject was randomized based on incorrect stratification information, the correct 
stratification information (if known at the time of the primary SVR12 analysis) will be 
used to define subpopulations for analyses.


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6.0
Analysis Conventions
6.1
Definition of Baseline, Final Treatment, and Final
Post-Treatment Assessments
6.1.1
Baseline
The baseline value refers to the last non-missing measurement collected before the 
first dose of study drug is received.  The protocol specifies that all Day 1 assessments 
(other than intensive PK samples) are to be performed prior to administering the first dose 
of study drug.  Therefore, all Day 1 assessments for which time is not collected will be 
assumed to be pre-dose and the baseline value will be the last non-missing measurement 
collected on or before the first day of study drug administration.
All Day 1 assessments with time available must be before the time of first dose to be 
considered baseline, and the last non-missing measurement collected before the date and 
time of the first dose of study drug will be considered the baseline value.  Only for 
resistance analyses, the last sample collected before OL Day 1 will be considered the 
baseline value for Arm B subjects.  If multiple measurements that are prior to dosing are 
recorded on the same date and with the same time or if time is not available, then the 
average of these measurements will be considered the baseline value.  The same baseline 
value will be used for analyses of the Treatment and PT Periods.
Safety assessments that are related to a serious adverse event that occurred on the 
first dose day are excluded when applying this algorithm.
6.1.2
Study Days
DB Study Days (Days Relative to the First Dose of DB Study Drug)
DB study days are calculated for each time point in the DB Treatment Period relative to 
the first dose of DB (active or placebo) study drug.  Study days are negative values when 
the time point of interest is prior to the first DB study drug dose day.  Study days are 
positive values when the time point of interest is after the first DB study drug dose day.  


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There is no DB Study Day 0.  DB Study Day 1 is the day of the first dose of DB study 
drug in the DB Treatment Period.
DB Study Drug End Days (Days Relative to the Last Dose of DB Study Drug)
Study drug end days are calculated for each time point relative to the last dose of DB 
study drug.  The last day of DB study drug dosing is defined as DB Study Drug End 
Day 0.  Days before it have negative study drug end days and days after it have positive 
study drug end days.
Active Study Days (Days Relative to the First Dose of Active Study Drug)
Active Study Days will be defined for all subjects who receive at least one dose of 
ABT-493/ABT-530 (DB or OL) study drug.  
Active Study Day 1 is the day of the first dose of active study drug.  For subjects 
randomized to Arm A, DB Study Days and Active Study Days are equivalent.  For 
subjects randomized to placebo (Arm B) and in the OL population, Active Study Days are 
based on the first dose of OL active study drug.
Active Study Drug End Days (Days Relative to the Last Dose of Active Study Drug)
Active study drug end days are calculated for each time point relative to the last dose of 
ABT-493/ABT-530 (DB or OL) study drug.  The last day of active study drug dosing is 
defined as Active Study Drug End Day 0.  Days before it have negative study drug end 
days and days after it have positive study drug end days.
For subjects randomized to Arm A, DB Study Drug End Days and Active Study Drug End 
Days are equivalent.  For subjects randomized to placebo (Arm B) and in the OL 
population, Active Study Drug End Days are based on the last dose of OL active study 
drug.


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Final Treatment Value
The final treatment value is defined as the last non-missing measurement collected after 
Study Day 1 dosing time within a treatment period as defined below.
During the DB Treatment Period, the Final DB Treatment Value is defined separately for 
placebo and active subjects.  Subjects randomized to placebo (Arm B) should take the 
first dose of OL study drugs the day immediately after the last day of the DB Treatment 
Period.  Therefore, for Arm B subjects, the Final DB Treatment Value is defined as the 
last non-missing measurement collected after DB Study Day 1 and no more than 2 days 
after the last dose of placebo and before OL Day 1 (if applicable).  For subjects 
randomized to active study drug (Arm A), the Final DB Treatment Value is defined as the 
last non-missing measurement collected after DB Study Day 1 and within 2 days of the 
last dose of active study drug (i.e., on or before Active Study Drug End Day 2).
During the OL Treatment Period, for subjects randomized to placebo who receive OL 
study drug, the Final OL Treatment Value is defined as the last non-missing measurement 
collected after OL Day 1 and on or before Active Study Drug End Day 2.
Final Post-Treatment Value
The final PT value for each subject is the last non-missing measurement collected after 
Active Study Drug End Day 2 and on or before Active Study Drug End Day 999.
6.2
Definition of Analysis Windows
For efficacy analyses of HCV RNA and resistance, the time windows specified in Table 4, 
Table 5 and Table 6 describe how efficacy data are assigned to protocol-specified time 
points during the DB Treatment, OL Treatment, and PT Periods, respectively.  All time 
points and corresponding time windows are defined based on the date/time of blood 
sample collection.


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For safety laboratory data, vital signs, and PRO instruments, the time windows specified 
in Table 4, Table 5 and Table 7 describe how data are assigned to protocol-specified time 
points.
For samples of plasma HIV-1 RNA and flow cytometry (including but not limited to 
CD4+ T-cell and CD8+ T-cell counts [absolute and percent]), the time windows specified 
in Table 8, Table 9, and Table 10 describe how data are assigned to protocol-specified 
time points.
If more than one assessment is included in a time window, the assessment closest (except 
in analyses of SVR) to the nominal time will be used.  If there are two observations 
equally distant to the nominal time, the latest one will be used in analyses.  For analyses 
of SVR (e.g., SVR12), the last value in the window will be used.
If multiple measurements are made on the same day for a safety laboratory parameter, a 
vital sign parameter, or a flow cytometry parameter, the average of the values will be used 
to calculate descriptive statistics and in analyses of the mean change from baseline.  For 
summaries of shifts from baseline, graded laboratory values and potentially clinically 
significant values, multiple values on the same day will not be averaged; all values will be 
considered for these analyses.


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Table 4.
Analysis Time Windows for HCV RNA and Resistance Endpoints, 
Safety Laboratory and Vital Sign Measurements, and PRO 
Instruments (DB Treatment Period)
Scheduled Visit
Nominal Day
(DB Study Day)
Time Window
(DB Study Day Range)
DB Day 1/Baselinea
1a
≤ 1a
DB Week 1
7
2 to 10
DB Week 2
14
11 to 21
DB Week 4
28
22 to 42
DB Week 8
56
43 to 70
DB Week 12b
84
71 to 98
DB Week 16b
112
99 to 126
Final DB Treatment Visitc
2 to ≤ 2 days after last dose of DB study drug
a.
Day of first dose of DB study drug.
b.
For 16-week treatment only. 
c.
The last value within the window will be used to define the Final DB Treatment Visit value.  For Arm A subjects, 
the upper bound of this Final window is DB Study Drug End Day 2.  For Arm B subjects, it is the earlier of DB 
Study Drug End Day 2 and the day of first dose of OL active study drug.  DB Study Drug End Day 0 is defined as 
the day of the last dose of DB study drug.
Note:
For all windows, data must be on or before DB Study Drug End Day 2, and for Arm B subjects data must also 
be on or before the day of first dose of OL active study drug.  The result closest to the scheduled time point 
will be used.  PRO instruments are collected at DB Day 1, DB Week 4, DB Week 12 (if 16-week treatment), 
and DB End of Treatment Visit.


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Table 5.
Analysis Time Windows for HCV RNA and Resistance Endpoints 
and Safety Laboratory and Vital Sign Measurements (OL 
Treatment Period)
Scheduled Visita
Nominal Day
(Active Study Day)
Time Window
(Active Study Day Range)
OL Day 1b
1
OL Week 1
7
2 to 10
OL Week 2
14
11 to 21
OL Week 4
28
22 to 42
OL Week 8
56
43 to 70
OL Week 12c
84
71 to 98
OL Week 16c
112
99 to 126
Final OL Treatment Visitd
2 to ≤ 2 days after last dose of OL study drug
a.
OL visits are applicable for subjects randomized to Arm B (placebo) who received at least one dose of OL active 
study drug.
b.
Day of first dose of OL active study drug.  For resistance analyses only, baseline value for Arm B subjects will use 
the last sample collected before OL Day 1.
c.
For 16-week treatment only. 
d.
The last value within the window will be used to define the Final OL Treatment Visit value.  The upper bound of 
this Final window is Active Study Drug End Day 2.  Active Study Drug End Day 0 is defined as the day of the last 
dose of active study drug.
Note:
For all windows, data must be on or before Active Study Drug End Day 2.  The result closest to the scheduled 
time point will be used.  PRO instruments are not collected for Arm B subjects during the OL Treatment 
Period.
Analyses of these data will not be included in the primary CSR.


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Table 6.
Analysis Time Windows for HCV RNA and Resistance Endpoints 
(Post-Treatment Period)
Scheduled Visita
Nominal Day
(Active Study Drug End Day)
Time Window
(Active Study Drug End Day Range)
Post-Treatment Week 4
28
3 to 56
Post-Treatment Week 12
84
57 to 126
Post-Treatment Week 24b
168
127 to 999
SVR4
c
28
3 to 56
SVR12
c
84
57 to 126
SVR24
b,c
168
127 to 210
a.
PT Visits are applicable for subjects who received at least one dose of active (DB or OL) study drug.
b.
Not included in primary CSR; for Arm B, included only in final CSR.
c.
For SVR windows, the last value in the window will be used.
Note:
The result closest to the scheduled time point will be used, except for SVR4, SVR12, and SVR24.  For all 
windows, data must occur after Active Study Drug End Day 2.  Active Study Drug End Day 0 is defined as 
the day of the last dose of active study drug.
Analyses of these data for Arm B will not be included in the primary CSR.
Table 7.
Analysis Time Windows for Safety Laboratory and Vital Sign 
Measurements and PRO Instruments (Post-Treatment Period)
Scheduled Visita
Nominal Day
(Active Study Drug End Day)
Time Window 
(Active Study Drug End Day Range)
Post-Treatment Week 4
28
3 to 56
Post-Treatment Week 12
84
57 to 126
Post-Treatment Week 24b
168
127 to 999
Final Post-Treatment Visitc
> 2 days after last dose of active study drug
a.
PT Visits are applicable for subjects who received at least one dose of active (DB or OL) study drug.
b.
Not included in primary CSR; for Arm B, included only in final CSR.
c.
The last value within the PT Period window will be used to define the Final PT Visit value.  The lower bound of 
this Final window is Active Study Drug End Day 3.  Active Study Drug End Day 0 is defined as the day of the last 
dose of active study drug.
Note:
The result closest to the scheduled time point will be used.  For all windows, data must occur after Active 
Study Drug End Day 2.  Vital signs are collected at every PT visit; hematology, chemistry, urinalysis, and 
coagulation panels are collected at PT Week 4 or PT D/C (if subject discontinued prior to PT Week 4); PRO 
instruments are collected for Arm A subjects only and only at PT Week 12 and PT Week 24 (or PT D/C).
Analyses of these data for Arm B will not be included in the primary CSR.


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Table 8.
Analysis Time Windows for HIV-1 RNA and Flow Cytometry 
Measurements (DB Treatment Period)
Scheduled Visit
Nominal Day
(DB Study Day)
Time Window
(DB Study Day Range)
DB Day 1/Baselinea
1a
≤ 1a
DB Week 2
14
2 to 21
DB Week 4
28
22 to 42
DB Week 8
56
43 to 70
DB Week 12b
84
71 to 98
DB Week 16b
112
99 to 126
Final DB Treatment Visitc
2 to ≤ 2 days after last dose of DB study drug
a.
Day of first dose of DB study drug.
b.
For 16-week treatment only. 
c.
The last value within the window will be used to define the Final DB Treatment Visit value.  For Arm A subjects, 
the upper bound of this Final window is DB Study Drug End Day 2.  For Arm B subjects, it is the earlier of DB 
Study Drug End Day 2 and the day of first dose of OL active study drug.  DB Study Drug End Day 0 is defined as 
the day of the last dose of DB study drug.
Note:
Time windows specified in this table are for HCV/HIV co-infected subjects only.  For all windows, data must 
be on or before DB Study Drug End Day 2, and for Arm B subjects, data must also be on or before the day of 
first dose of OL active study drug.  The result closest to the scheduled time point will be used.  Flow 
cytometry samples are collected at DB Day 1, DB Week 4, DB Week 12 (if 16-week treatment), and DB End 
of Treatment Visit.
Table 9.
Analysis Time Windows for HIV-1 RNA and Flow Cytometry 
Measurements (OL Treatment Period)
Scheduled Visita
Nominal Day
(Active Study Day)
Time Window
(Active Study Day Range)
OL Week 1
7
2 to 10
OL Week 2
14
11 to 21
OL Week 4
28
22 to 42
OL Week 8
56
43 to 70
OL Week 12b
84
71 to 98
OL Week 16b
112
99 to 126
Final OL Treatment Visitc
2 to ≤ 2 days after last dose of OL study drug
a.
OL visits are applicable for subjects randomized to Arm B (placebo) who received at least one dose of OL active 
study drug.
b.
For 16-week treatment only. 


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Table 9.
Analysis Time Windows for HIV-1 RNA and Flow Cytometry 
Measurements (OL Treatment Period) (Continued)
c.
The last value within the window will be used to define the Final OL Treatment Visit value.  The upper bound of 
this Final window is Active Study Drug End Day 2.  Active Study Drug End Day 0 is defined as the day of the last 
dose of active study drug.
Note:
Time windows specified in this table are for HCV/HIV co-infected subjects only.  For all windows, data must 
be on or before Active Study Drug End Day 2.  The result closest to the scheduled time point will be used.  
Flow cytometry samples are collected at OL Week 4, OL Week 12 (if 16-week treatment), and OL End of 
Treatment Visit.
Analyses of these data will not be included in the primary CSR.
Table 10.
Analysis Time Windows for HIV-1 RNA and Flow Cytometry 
Measurements (Post-Treatment Period)
Scheduled Visita
Nominal Day
(Active Study Drug End Day)
Time Window
(Active Study Drug End
Days Range)
Post-Treatment Week 4
28
3 to 56
Post-Treatment Week 12
84
57 to 126
Post-Treatment Week 24b
168
127 to 999
Final Post-Treatment Visitc
> 2 days after last dose of active study drug
a.
PT Visits are applicable for subjects who received at least one dose of active (DB or OL) study drug.
b.
Not included in primary CSR; for Arm B, included only in final CSR.
c.
The last value within the PT Period window will be used to define the Final PT Visit value.  The lower bound of 
this Final window is Active Study Drug End Day 3.  Active Study Drug End Day 0 is defined as the day of the last 
dose of active study drug.
Note:
Time windows specified in this table are for HCV/HIV co-infected subjects only.  The result closest to the 
scheduled time point will be used.  For all windows, data must occur after Active Study Drug End Day 2.  
Analyses of these data for Arm B will not be included in the primary CSR.
6.3
Missing Data Imputation
Missing Data Imputation for SVR
HCV RNA values will be selected for analysis based on the analysis windows defined in 
Section 6.2.


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For analyses of SVR, subjects missing visit values will have backward imputation 
applied, if possible.  For backward imputation, if the nearest HCV RNA value after the 
SVR window is unquantifiable or undetectable, then it will be used to impute the HCV 
RNA value in the SVR window.  If a subject is missing an HCV RNA value within the 
appropriate SVR window after performing backward imputation, then this value will be 
imputed with an HCV RNA value from a local laboratory if present; otherwise, the HCV 
RNA value will be missing.  A subject with missing HCV RNA data in the analysis 
window, after imputations, will be imputed as a failure.
Regardless of the imputation method described above, if a subject starts another treatment 
for HCV, then all HCV RNA values for this subject measured on or after the start date of 
the new HCV treatment will be excluded from analyses.  The subject will be considered a 
failure for summaries of viral response at all time points after the start of the new HCV 
treatment.
Missing Data Imputation for Virologic Failure
If HCV RNA values from the central laboratory are missing but a local laboratory value is 
present in the appropriate time period, then the local laboratory value will be used to 
assess PT relapse and on-treatment virologic failure.
Missing Data Imputation for PRO Questionnaires
The handling of missing data for patient reported outcomes (PROs) will be as follows.  
The missing items of the FSS questionnaire will be imputed with the average score of the 
answered items as long as more than 50% of the items on the FSS are answered.  For 
EQ-5D-3L index and VAS scores, no imputation will be performed for missing items.
If a subject starts another treatment for HCV, then all PRO assessment values for this 
subject measured on or after the start date of the new HCV treatment will be excluded 
from analyses.


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7.0
Demographics, Baseline Characteristics, Medical 
History, and Other Medications
The safety population (and ITT population if it differs from the safety population) will be 
used to summarize demographics and baseline characteristics by treatment arm (Arm A 
and Arm B) and across the treatment arms for the set of all subjects, for each of the GT1-
infected and GT2-infected groups, and for the geographic region of China during the DB 
Treatment Period.  In addition, demographics and baseline characteristics will be 
summarized for the geographic region of China for each of the GT1-infected and 
GT2-infected groups.
The safety population will be used to summarize medical history and previous, 
concomitant, and PT medications by treatment arm and across the treatment arms for the 
set of all subjects and for the geographic region of China.
7.1
Demographic and Baseline Characteristics
Categorical demographic and baseline characteristic variables will be summarized with 
the number and percentage of subjects in each category and proportions will be compared 
between the treatment arms with a chi-square test.  Continuous variables will be 
summarized with descriptive statistics (number of non-missing observations, mean, 
standard deviation, median, maximum and minimum), and means will be compared 
between the treatment arms with a one-way analysis of variance (ANOVA).
Continuous demographic variables include age, weight, height, waist circumference, and 
body mass index (BMI).  Categorical demographic variables include sex, age category 
(< 65 or ≥ 65 years; < 75 or ≥ 75 years), BMI category (< 25, ≥ 25 to < 30, or 
≥30 kg/m2), race, ethnicity, type of Asian descent (Chinese, Korean, Malay or Other), 
and geographic region.
Continuous baseline characteristics include baseline log10 HCV RNA level, homeostasis 
model of assessment – insulin resistance (HOMA-IR), platelet count, albumin, GGT, 
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(by Cockcroft-Gault formula, defined below), eGFR (using the modification of diet in 
renal disease [MDRD] formula modified for the Chinese population [C-MDRD], defined 
below), total, direct, and indirect bilirubin, total international normalized ratio (INR).
Categorical baseline characteristics include:
●
HCV genotype (1, 2, 3, 4, 5, or 6) and available subtype (as determined by the 
central laboratory);
●
HCV genotype (1, 2, 3, 4, 5, or 6) and available subtype (final HCV genotype 
and subtype as defined in Section 10.8);
●
Prior HCV treatment history (naïve or experienced);
●
HCV genotype (1, 2, 3, 4, 5, or 6) (as determined by the central laboratory)
and prior HCV treatment history;
●
HCV genotype (final HCV genotype as defined in Section 10.8) and prior 
HCV treatment history;
●
For treatment-experienced subjects, type of prior treatment experience (IFN-
based or SOF-based; subjects who received SOF will be categorized as SOF-
based);
●
For treatment-experienced subjects, type of non-response to previous treatment 
(on-treatment nonresponder or breakthrough, post-treatment relapse, or 
unknown/other);
●
Screening HIV co-infection status (HCV mono-infected or HCV/HIV co-
infected);
●
IL28B genotype (CC, CT, or TT; CC or non-CC);
●
Baseline HCV RNA level (< 1,000,000 or ≥ 1,000,000 IU/mL; < 6,000,000 or 
≥6,000,000 IU/mL; < 10,000,000 or ≥ 10,000,000 IU/mL);
●
Baseline HOMA-IR (< 2 or ≥ 2 mU × mmol/L2);
●
Baseline fibrosis stage (equivalent to Metavir F0 – F1, F2, F3, F4 [if 
applicable]);
●
Baseline platelet count (< 100 or ≥ 100 × 109/L);
●
Baseline albumin (< 35 or ≥ 35 g/L);


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●
Baseline creatinine clearance (Cockcroft-Gault) (< 60, ≥ 60 to < 90, or 
≥90 mL/min);
●
Baseline eGFR (C-MDRD) (< 60, ≥ 60 to < 90, or ≥ 90 mL/min/1.73 m2);
●
Baseline total bilirubin (< 34.2 or ≥ 34.2 umol/L);
●
Baseline total INR (continuous and < 1.7 or ≥ 1.7);
●
History of diabetes (yes/no);
●
History of bleeding disorders (yes/no);
●
History of depression or bipolar disorder (yes/no);
●
History of cardiovascular disease (yes/no);
●
Baseline metabolic syndrome (yes/no);
●
Injection drug use (yes, within last 12 months; yes, more than 12 months ago; 
or no);
●
Baseline stable opiate substitution use (yes/no);
●
Baseline hepato-protectant medication use (as determined by investigator on 
concomitant medication eCRF, yes/no);
●
Tobacco use (user, ex-user, or non-user);
●
Alcohol use (drinker, ex-drinker, or non-drinker);
●
Concomitant use of Proton Pump Inhibitors (PPIs) (yes/no).
The demographic and baseline characteristics specified above, along with the following, 
will be summarized for subjects with HCV/HIV co-infection at Screening for the overall 
safety population and for the geographic region of China:
●
HIV-1 treatment status (antiretroviral therapy [ART]-Naïve, ART-Treated), 
●
HIV-1 ART regimen (e.g., raltegravir [RAL], dolutegravir [DTG], rilpivirine 
[RPV]) for those receiving ART (as determined by investigator on 
concomitant medication eCRF) at baseline,
●
Baseline CD4+ T-cell count (continuous; and < 200, 200 to < 350, 350 to 
< 500, or ≥ 500 cells/mm3).


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Any concomitant medication coded to the WHO Drug Dictionary ATC code of A02BC 
will be counted as a PPI.
If the IL28B genotype result is not available from a sample collected during the Screening 
period, then a result available from a sample collected at any time during the study will be 
used to summarize IL28B genotype.
HOMA-IR is defined as fasting glucose (mmol/L) × fasting insulin (μIU/mL) ÷ 22.5.  
Subjects who do not have concurrent fasting glucose and fasting insulin values at baseline 
will be excluded from the summary of baseline HOMA-IR.
Baseline fibrosis stage is defined for subjects with non-missing liver biopsy scores, 
FibroScan scores, or FibroTest scores.  Only one score will be used to categorize each 
subject even if a subject has more than one score recorded.  If a biopsy score is present, 
then it will be used to categorize the subject, regardless of the FibroScan/FibroTest score.  
Similarly, if a FibroScan score is present along with a FibroTest score, then the FibroScan 
score will be used to categorize the subject.  If biopsy and FibroScan scores are not 
present and more than one FibroTest result is available, then the baseline FibroTest result 
(i.e., last non-missing FibroTest result on or before DB Day 1) will be used to categorize 
the subject.  Subjects will be categorized as F0 – F1, F2, F3 or F4 according to Table 11.
All subjects in this study will be categorized as not having cirrhosis (cirrhosis = no) since 
this study excludes subjects with cirrhosis.
Table 11.
Baseline Fibrosis Stage
Baseline Fibrosis 
Stage, Metavir 
Equivalents
Liver Biopsy Metavir, Batts 
Ludwig, Knodell, IASL, 
Scheuer, or Laennec Score
Liver Biopsy 
Ishak Score
FibroScan (kPa)
FibroTest
F0 – F1
0 or 1
0, 1, or 2
< 8.8
≤ 0.48
F2 
2
3
≥ 8.8 to < 9.6
0.49 to 0.58
F3
3
4
≥ 9.6 to < 14.6
0.59 to 0.72
F4
4
≥ 5
≥ 14.6
≥ 0.73


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Baseline APRI and FIB-4 are calculated by the equations below.  Subjects who do not 
have concurrent AST and platelet values at baseline will be excluded from the summary 
of baseline APRI.  Age is defined in years at baseline.  Subjects who do not have 
concurrent values of AST, ALT and platelet count at baseline or subjects who are missing 
age will be excluded from the summary of FIB-4.
The central laboratory calculates the estimated creatinine clearance (CrCl) based on the 
following Cockcroft-Gault formula:
CrCl (mL/min) = [(140 – age) × (weight in kg) × (0.85 if female)]/[serum 
creatinine (mg/dL) × 72].
The central laboratory calculates eGFR by C-MDRD using the following equation, where 
serum creatinine is measured in mg/dL and age is measured in years:
eGFR (mL/min/1.73 m2) = 175 × (Serum Creatinine)–1.234 × (Age)–0.179 × (0.79 if 
female).
Subjects will be classified as having metabolic syndrome if at least 3 of the 
5 characteristics in Table 12 are present.


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Table 12.
Clinical Identification of Metabolic Syndrome
Risk Factor
Defining Level in Conventional Units
Defining Level in SI Units
Abdominal obesity, given 
as waist circumference
Men
> 40 in
> 102 cm
Women
> 35 in
> 88 cm
Triglycerides
≥ 150 mg/dL
≥ 1.695 mmol/L
HDL cholesterol
Men
< 40 mg/dL
< 1.03452 mmol/L
Women
< 50 mg/dL
< 1.29315 mmol/L
Blood pressure (BP)
Systolic BP ≥ 130 mm Hg or Diastolic BP ≥ 85 mm Hg
Fasting glucose
≥ 100 mg/dL
≥ 5.5507 mmol/L
Cross reference:  Grundy 20046
Medical history data will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA); the actual version of the MedDRA coding dictionary will be noted in the 
clinical study report.  Histories of diabetes, bleeding disorders, depression or bipolar 
disorder, and cardiovascular disease will be defined by a subject having medical history 
coded to at least 1 preferred term within any of the high level terms specified for the 
category in Table 13.


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Table 13.
Medical History Categories
Category
MedDRA High Level Term Name
Diabetes
Diabetic complications cardiovascular
Diabetic complications dermal
Diabetic complications gastrointestinal
Diabetic complications NEC
Diabetic complications neurological
Diabetic complications ophthalmic
Diabetic complications renal
Diabetes mellitus (incl subtypes)
Hyperglycaemic conditions NEC
Bleeding disorders
Coagulation factor deficiencies
Coagulopathies
Platelet disorders NEC
Thrombocytopenias
Coagulation disorders congenital
Depression or bipolar disorder
Depressive disorders
Bipolar disorders
Mood alterations with manic symptoms


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Table 13.
Medical History Categories (Continued)
Category
MedDRA High Level Term Name
Cardiovascular disease
Coronary artery disorders NEC
Ischaemic coronary artery disorders
Cardiac conduction disorders
Rate and rhythm disorders NEC
Supraventricular arrhythmias
Ventricular arrhythmias and cardiac arrest
Congenital cardiac malpositions and transpositions
Congenital cardiac structural defects NEC
Congenital cardiovascular disorders NEC
Cardiac disorders congenital NEC
Cardiac hypoplasias congenital
Cardiac malpositions congenital
Cardiac septal defects congenital
Cardiac valve disorders congenital
Cardiovascular disorders congenital NEC
Great vessel disorders congenital
Multiple cardiac abnormalities congenital
Persistent foetal circulation disorders
Heart failure signs and symptoms
Heart failures NEC
Left ventricular failures
Right ventricular failures
Accelerated and malignant hypertension
Renal hypertensions
Vascular hypertensive disorders NEC
Coronary necrosis and vascular insufficiency
Infectious myocarditis
Noninfectious myocarditis
Peripheral vasoconstriction, necrosis and vascular insufficiency
Aortic valvular disorders
Cardiac valve disorders NEC
Mitral valvular disorders
Pulmonary valvular disorders
Tricuspid valvular disorders
Aortic inflammatory disorders
Arterial inflammations
Vasculitides NEC


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7.2
Medical History
Medical history data will be coded using the MedDRA coding dictionary; the actual 
version of the MedDRA coding dictionary will be noted in the clinical study report.  
Medical history data will be summarized and presented using MedDRA System Organ 
Class (SOC) and preferred term.  The SOCs will be presented in alphabetical order, and 
the preferred term will be presented in alphabetical order within each SOC.  The number 
and percentage of subjects with a particular preferred term will be summarized for each 
treatment arm.  Subjects reporting more than one preferred term within each SOC will be 
counted only once for that SOC.
7.3
Prior, Concomitant and Post-Treatment Medications
A prior medication is defined as any medication taken prior to the date of the first dose of 
DB study drug (ABT-493/ABT-530 or placebo).  A concomitant medication is defined as 
any medication that started prior to the date of the first dose of DB study drug and 
continued to be taken on or after the first dose of DB study drug or any medication that 
started on or after the date of the first dose of DB study drug, but not after the date of the 
last dose of study drug (DB or OL).  A post-treatment medication for the treatment of 
HCV is defined as any medication taken on or after the last dose of study drug and entered 
as "Post-treatment HCV medications" on the eCRF.
Hepatoprotective medications taken at baseline will be summarized by generic drug name 
for each treatment arm.
Prior medications will be divided into the following categories:
●
Prior HCV medications taken by treatment-experienced subjects;
●
Prior HIV medications taken by HCV/HIV co-infected subjects receiving 
ART (as determined by investigator on concomitant medication eCRF) at 
baseline;
●
All other prior medications for all treated subjects.


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Concomitant medications will be divided into the following categories:
●
Concomitant HIV medications taken by HCV/HIV co-infected subjects;
●
All other concomitant medications for all treated subjects.
The number and percentage of subjects taking prior medications, concomitant 
medications, and post-treatment HCV medications will be summarized for each treatment 
arm by generic drug name based on the WHO Drug Dictionary.  
8.0
Subject Disposition
The number and percentage of subjects who screen failed for any reason, and for each 
screen fail reason, will be summarized for all subjects who screen failed and for subjects 
who screen failed within each geographic region (China, Singapore and South Korea).  
8.1
Disposition of Safety Population
The number of subjects in each of the following categories will be summarized by 
investigator and across investigators for each treatment arm and across treatment arms for 
the set of all subjects and for the GT1-infected and GT2-infected groups; within these 
3 groups of subjects, summaries will also be performed for each geographic region 
(China, Singapore and South Korea):
●
Randomized subjects;
●
Subjects who took at least one dose of DB study drug;
●
Subjects who completed DB study drug;
●
Subjects who prematurely discontinued DB study drug;
●
Subjects who took at least one dose of OL study drug;
●
Subjects who completed OL study drug;
●
Subjects who prematurely discontinued OL study drug;
●
Subjects who completed the study;
●
Subjects who prematurely discontinued from the study;


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●
Subjects ongoing in the Post-Treatment Period (if applicable at the time of 
analysis).
Note that subjects randomized to placebo may prematurely discontinue DB study drug but 
upon unblinding at the DB Premature Discontinuation visit find that they are on placebo 
and elect to continue to attend all remaining DB Treatment Period study visits in order to 
receive OL, active study drug in the OL Treatment Period.  For these placebo subjects, 
reasons for discontinuation from DB study drug will be collected on the DB Study Drug 
Completion eCRF.  If such a placebo subject chooses to continue the DB Treatment 
Period in order to enter the OL Treatment Period, but then prematurely discontinues from 
the DB Period, they will be discontinued from the study entirely.
The number and percentage of subjects who discontinued (DB or OL) study drug will be 
summarized by reason (all reasons) and by primary reason (per eCRF) for each treatment 
arm and overall for the set of all subjects and for the geographic region of China.  Similar 
summaries will be provided for discontinuations from the study.
The number and percentage of subjects with reported study drug interruptions will be 
summarized by treatment arm and overall during the DB and OL Treatment Periods for 
the set of all subjects and for the geographic region of China.
Reasons for study drug interruptions will be presented in the CSR listings.
9.0
Study Drug Exposure and Compliance
The summaries described below will be performed for the set of all subjects and for the 
geographic region of China.
9.1
Exposure
The duration of exposure to study drug will be summarized separately for the DB 
Treatment Period (for each treatment arm and overall in the safety population) and the OL 
Treatment Period (for the OL population).  For each of the treatment periods, duration of 


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exposure is defined for each subject as the last study drug dose date minus the first study 
drug dose date plus 1 day.
Descriptive statistics (mean, standard deviation, median, minimum, and maximum) will 
be presented for exposure during each treatment period.  Study drug duration will also be 
summarized with frequencies and percentages using the following categories:
●
1 to 15 days
●
16 to 30 days
●
31 to 45 days
●
46 to 60 days
●
61 to 75 days
●
76 to 90 days
●
91 to 105 days
●
> 105 days
In addition, the number and percentage of subjects during the DB Treatment Period (for 
each treatment arm and overall in the safety population) and the OL Treatment Period (for 
the OL population) with a study drug duration of ≥ 52 days or ≥ 105 days will be 
summarized.
9.2
Compliance
During the DB and OL Treatment Periods, at each Study Drug Dispensation visit the 
number of tablets dispensed is automatically calculated according to the number of bottles 
dispensed, and at each Study Drug Accountability visit (starting with the Week 4 visit), 
the total number of tablets returned is recorded.  The compliance for each study drug 
(ABT-493/ABT-530 or matching placebo) during the DB Treatment Period will be 
calculated as the percentage of tablets taken relative to the total tablets expected to be 
taken.  The total number of tablets expected to be taken will be equal to the total number 
of tablets that should have been taken per the protocol for the duration that the subject was 
in the DB Treatment Period (date of last dose of study drug – date of first dose of study 


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drug + 1).  DB study drug interruptions recorded on the eCRF will not be subtracted from 
the duration.  
A subject is considered to be compliant if the percentage is between 80% and 120%.  
Compliance will be calculated for each subject and summarized with the mean, median, 
standard deviation, minimum, and maximum by treatment arm.  The percentage of 
compliant subjects will be summarized for each study drug and each treatment arm, based 
on data as observed.  An additional summary of the percentage of compliant subjects will 
be provided where subjects who are missing study drug accountability records will be 
imputed as non-compliant.
The summaries described above will be performed on the ITT population; similar 
summaries of the compliance for the active study drug (ABT-493/ABT-530) during the 
OL Treatment Period will be provided for the OL population.
10.0
Efficacy Analysis
10.1
General Considerations
General Considerations
Treatment effects will be evaluated based on a 2-sided significance level of 0.050 (when 
rounded to three decimal places), and all efficacy analyses will be performed on the ITT 
population randomized to Arm A, unless otherwise specified.
Missing data will be imputed as described in Section 6.3 for analyses of the HCV RNA 
endpoints of SVR.
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.  The lower limit of detection (LLOD) and lower limit of quantification 
(LLOQ) for this assay (regardless of genotype) are both 15 IU/mL.


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HCV RNA results that are detectable but not quantifiable are reported as "< 15 IU/ML 
HCV RNA DETECTED" and those that are undetectable are reported as "HCV RNA 
NOT DETECTED" in the database.
The notation "HCV RNA < LLOQ" is used to represent all HCV RNA values 
< 15 IU/mL, including values reported as "HCV RNA NOT DETECTED" or 
"< 15 IU/ML HCV RNA DETECTED."  HCV RNA ≥ LLOQ are all quantifiable values 
of 15 IU/mL or greater.
IL28B rs12979860 will be resulted as C/C, C/T, or T/T by the central laboratory.
Definitions for Efficacy Endpoints
A confirmed quantifiable value during treatment is defined as any two consecutive HCV 
RNA measurements ≥ LLOQ (or 100 IU/mL for Breakthrough), either both during 
treatment or at the final treatment measurement and the next consecutive post-treatment 
measurement.  A confirmed quantifiable post-treatment value is defined as any 
two consecutive post-treatment HCV RNA measurements ≥ LLOQ.
Breakthrough = confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < LLOQ during 
the Treatment Period; or confirmed increase from nadir in HCV RNA (two consecutive 
HCV RNA measurements > 1 log10 IU/mL above nadir) at any time point during the 
Treatment Period.  A single breakthrough value (≥ 100 IU/mL or > 1 log10 above nadir) 
followed by lost to follow-up also will be considered a breakthrough (i.e., will not require 
confirmation).
EOT failure = HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment, 
where the HCV RNA value must be collected on or after Study Drug Day 36 and study 
drug duration ≥ 36 days.
On-treatment HCV virologic failure = Breakthrough or EOT failure; if a subject 
meets both definitions of Breakthrough and EOT failure, he or she will be categorized 
as Breakthrough only. 


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SVR4 = HCV RNA < LLOQ in the SVR4 window (4 weeks after the last actual dose of 
active study drug) without any confirmed quantifiable (≥ LLOQ) post-treatment value 
before or during that SVR window.
SVR12 = HCV RNA < LLOQ in the SVR12 window (12 weeks after the last actual dose of 
active study drug) without any confirmed quantifiable (≥ LLOQ) post-treatment value 
before or during that SVR window.
SVR24 = HCV RNA < LLOQ in the SVR24 window (24 weeks after the last actual dose of 
active study drug) without any confirmed quantifiable (≥ LLOQ) post-treatment value 
before or during that SVR window.
Relapse12 = confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after 
last actual dose of active study drug (up to and including the SVR12 assessment time 
point) for a subject with HCV RNA < LLOQ at Final Treatment Visit who completed 
treatment and has post-treatment HCV RNA data available, excluding reinfection as 
described below.
Relapse24 = confirmed HCV RNA ≥ LLOQ within the SVR24 window for a subject who 
achieved SVR12 and has HCV RNA data available in the SVR24 window, excluding 
reinfection.
Relapseoverall = confirmed HCV RNA ≥ LLOQ between end of treatment and up to and 
including the last HCV RNA measurement collected in the PT Period for a subject with 
HCV RNA < LLOQ at Final Treatment Visit who completed treatment and has post 
treatment HCV RNA data available, excluding reinfection.
Only subjects who have at least one post-treatment HCV RNA value will be included in 
analyses of relapse.  For the analyses of relapse, completion of treatment is defined as a 
study drug duration of 52 days or greater for subjects assigned to 8 weeks of treatment 
and 105 days or greater for subjects assigned to 16 weeks of treatment.  If the last 
available post-treatment value is ≥ LLOQ, then the subject will be considered a relapse 
(i.e., will not require confirmation).


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HCV reinfection is defined as confirmed HCV RNA ≥ LLOQ after the end of active 
treatment in a subject who had HCV RNA < LLOQ at Final Treatment Visit, along with 
the post treatment detection of a different HCV genotype, subtype, or clade compared 
with baseline, as determined by phylogenetic analysis of the NS3 or NS5A, and/or NS5B 
gene sequences.  Reinfection in the case of the same HCV subtype is defined as a clade 
switch, as indicated by the lack of clustering between the baseline and post-treatment 
sequences by phylogenetic analysis.  If phylogenetic analysis is not possible due to 
technical difficulties, HCV reinfection may be determined with a confirmed HCV 
genotype or subgenotype switch by the Versant HCV Genotype Inno-LiPA Assay v2.0 or 
Sanger assay.
Post-treatment relapse is defined as described earlier (Relapse12, Relapse24, 
Relapseoverall), and no genotype, subtype, or clade switch compared with baseline as 
determined by phylogenetic analysis of the NS3 or NS5A gene sequences.  If 
phylogenetic analysis is not possible due to technical difficulties, the subject will be 
defined as having a post-treatment relapse unless an HCV genotype or subgenotype 
switch is confirmed by the Versant HCV Genotype Inno-LiPA Assay v2.0 or Sanger 
assay.
Reasons for SVR12 Non-Response
Subjects who do not achieve SVR12 (SVR12 non-responders) will be categorized as 
having:
1.
On-treatment HCV virologic failure (see On-treatment HCV virologic failure
definition; if a subject meets both definitions of Breakthrough and EOT failure, 
he or she will be categorized as Breakthrough only);
2.
Relapse12;
3.
Prematurely discontinued study drug with no on-treatment virologic failure 
(defined as any SVR12 non-responder who prematurely discontinued study drug 
[study drug duration < 52 days for subjects assigned to 8 weeks of treatment, and 


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< 105 days for subjects assigned to 16 weeks of treatment] and did not meet the 
On-treatment HCV virologic failure definition);
4.
HCV reinfection (see definition described earlier);
5.
Missing follow-up data in the SVR12 window (defined as any subject who 
completed study drug without data in the SVR12 window after applying the 
imputation rules and not meeting the definitions of [1], [2], [3], or [4]);
6.
Other (defined as any SVR12 non-responder not meeting the definitions of 
[1] – [5]).
Reasons for SVR24 Non-Response
Subjects who do not achieve SVR24 (SVR24 non-responders) will be categorized as 
having:
1.
On-treatment HCV virologic failure (see On-treatment HCV virologic failure
definition, if a subject meets both definitions of Breakthrough and EOT failure, 
he or she will be categorized as Breakthrough only);
2.
Relapse12;
3.
Relapse24;
4.
Prematurely discontinued study drug with no on-treatment virologic failure and no 
relapse after achieving SVR12 (defined as any SVR24 non-responder who 
prematurely discontinued study drug [study drug duration < 52 days for subjects 
assigned to 8 weeks of treatment, and < 105 days for subjects assigned to 16 weeks 
of treatment] and did not meet the On-treatment HCV virologic failure or 
Relapse24 definitions);
5.
HCV reinfection (see definition described earlier);


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6.
Missing follow-up data in the SVR24 window (defined as any subject who 
completed study drug without data in the SVR24 window after applying the 
imputation rules and not meeting the definitions of [1], [2], [3], [4], or [5]);
7.
Other (defined as any SVR24 non-responder not meeting the definitions of 
[1] – [6]).
For the reasons for SVR12 and SVR24 nonresponse defined above, subjects are only 
to be counted in 1 category.  For example, the categories of premature 
discontinuation and reinfection are mutually exclusive.  Thus, subjects who are 
SVR12 or SVR24 nonresponders meeting the definition of HCV reinfection will be 
counted in the reinfection category and will not be counted in any other category 
(as in the example, even if such a subject appears to meet the definition of 
prematurely discontinued study drug with no on-treatment HCV virologic failure, 
the subject would be counted in the reinfection category only).
10.2
Handling of Multiplicity
In order to control the Type I error rate at 0.05, a fixed sequence testing procedure7 will be 
used for the ranked primary efficacy endpoints.  That is, only if success has been 
demonstrated for the first primary endpoint will the testing proceed to the 
second primary endpoint.  Similarly, only if success has been demonstrated for the 
second primary endpoint will the testing proceed to the third primary endpoint.
10.3
Primary Efficacy Analysis
The primary efficacy endpoint is the percentage of Arm A subjects achieving SVR12.  The 
three ranked primary efficacy endpoints are:
1.
The percentage of Arm A subjects from the combined group of GT1 to 6-infected 
subjects in the ITT population achieving SVR12.  The percentage of these subjects 
with SVR12 will be non-inferior to the historical SVR12 rate of 96% if the lower 
confidence bound (LCB) of the 2-sided 95% CI for the percentage is > 90%.


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2.
The percentage of Arm A subjects from the group of GT1-infected subjects in the 
ITT population achieving SVR12.  The percentage of these subjects with SVR12 will 
be non-inferior to the historical SVR12 rate of 97% if the LCB of the 2-sided 95% 
CI for the percentage is > 91%.
3.
The percentage of Arm A subjects from the group of GT2-infected subjects in the 
ITT population achieving SVR12. The percentage of these subjects with SVR12 will 
be non-inferior to the historical SVR12 rate of 95% if the LCB of the 2-sided 95% 
CI for the percentage is > 89%.
The normal approximation to the binomial distribution will be used to calculate 
each CI unless the rate for the primary endpoint is 100%, in which case the 
Wilson's score method will be used for the calculation of the CI.8  
10.4
Secondary Efficacy Analyses
The secondary efficacy endpoints are: 
●
the percentage of Arm A subjects with on-treatment HCV virologic failure 
(defined as On-treatment HCV virologic failure);
●
the percentage of Arm A subjects with post-treatment relapse (defined as 
Relapse12; subjects with reinfection will be summarized separately);
●
the percentage of Arm A HCV/HIV co-infected subjects (determined at 
Screening) achieving SVR12.
The numbers and percentages of subjects with on-treatment HCV virologic failure, post-
treatment relapse (Relapse12), and SVR12 will be calculated along with two-sided 95% 
Wilson score CIs.8
In addition, a summary of reason for SVR12 non-response (e.g., on-treatment HCV 
virologic failure, relapse, re-infection, other) will be provided for the set of all Arm A 
subjects and for the set of HCV/HIV co-infected Arm A subjects.  Listings of subject 
numbers with reason for non-response will be prepared.  


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The secondary endpoints will be summarized for the set of all Arm A subjects in the ITT 
population and for the Arm A subjects in each of the GT1-infected and GT2-infected 
groups.
10.5
Sensitivity Analyses for SVR12
Two-sided 95% CIs for the SVR12 rates of the primary endpoints will be calculated using 
both the normal approximation to the binomial distribution and the Wilson score method.8
The analyses of the primary endpoints will also be performed on Arm A of the mITT-GT 
and mITT-GT-VF populations.  Both two-sided 95% normal approximation and Wilson 
score CIs will be provided for each of these sensitivity analyses.  
The analyses described above will also be performed for the geographic region of China 
within the overall set of Arm A subjects and the Arm A subjects in each of the 
GT1-infected and GT2-infected groups for the populations specified above.
The number and percentage of subjects with SVR12 and the corresponding 95% Wilson 
score CI will be provided for each randomization stratum:
●
China/GT1-infected/HIV co-infected
●
China/GT1-infected/non-HIV co-infected 
●
China/GT2-infected/HIV co-infected
●
China/GT2-infected/non-HIV co-infected 
●
China/GT3 – 6-infected/HIV co-infected
●
China/GT3 – 6-infected/non-HIV co-infected 
●
Singapore/GT1-infected/HIV co-infected
●
Singapore/GT1-infected/non-HIV co-infected 
●
Singapore/GT2-infected/HIV co-infected  
●
Singapore/GT2-infected/non-HIV co-infected  
●
South Korea/GT1-infected/HIV co-infected
●
South Korea/GT1-infected/non-HIV co-infected 


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●
South Korea/GT2-infected/HIV co-infected
●
South Korea/GT2-infected/non-HIV co-infected 
For each sensitivity analysis, a two-sided 95% CI will be produced only if there are at 
least 10 subjects in the summary.
Listings of subjects excluded from the mITT-GT and mITT-GT-VF populations will be 
provided, as applicable.
10.5.1
Imputation Approaches
In addition to imputing SVR12 as described in Section 6.3, SVR12 will be presented for the 
overall set of Arm A subjects and the Arm A subjects in each of the GT1-infected and 
GT2-infected groups in the ITT population using the following other methods to impute 
missing HCV RNA values:
●
impute any missing HCV RNA values in the SVR12 window by carrying 
forward the last non-missing (post-baseline) HCV RNA value prior to the 
SVR12 window;
●
impute as described in Section 6.3 but treat SVR12 non-responders who were 
categorized as "prematurely discontinued study drug with no on-treatment 
virologic failure" or "missing follow-up data in the SVR12 window" as 
successes.
For each of these, the number and percentage of Arm A subjects with SVR12 will be 
presented along with two-sided 95% CIs using both the normal approximation to the 
binomial distribution and the Wilson score method.  Within the 3 groups of subjects 
specified above, these analyses will also be performed for the geographic region of China.
10.5.2
Assessment of Homogeneity Across Stratification Variables
Heterogeneity across the randomization stratification variables of geographic region, 
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endpoint of SVR12 in Arm A using the chi-square test of homogeneity.  The 14 strata are 
presented in Section 10.5. 
If heterogeneity across the randomization stratification is detected, a confidence interval 
for the primary endpoint based on the 14 strata will be created using a stratum weighted 
variance calculated using the equations below.  The variance of ps will be estimated by:
and the 2-sided 95% CI will be calculated as ps ± z
)
(
sp
Var
, where z is the 1-α/2 point 
of the standard normal distribution.  Note that n represents the number of subjects in 
Arm A within the ITT population, nh represents the number of subjects in stratum h, wh
will be estimated by nh/n, ph = the proportion of subjects achieving SVR12 in stratum h, 
and ps = the proportion of subjects with SVR12 among n subjects which can be defined as:
Using the equations above, a confidence interval for the SVR12 rate across all 14 strata 
will be presented, along with the number and percentage (ph) of subjects achieving SVR12 
within each of the 14 strata.
10.6
Efficacy Subgroup Analysis
Subgroup analyses will be performed for the primary efficacy endpoint of SVR12.
Within each subgroup, the number and percentage of Arm A subjects achieving SVR12
will be calculated for the set of all subjects in the ITT population and for each of the GT1-


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infected and GT2-infected groups.  The 2-sided 95% Wilson score CI will be produced if 
there are at least 10 subjects in the subgroup.
The following subgroups will be analyzed:
●
HCV genotype and available subtype (based on the latest determination of 
genotype from the baseline sample [by the central laboratory or by 
phylogenetic analysis, with preference given to the phylogenetic analysis 
results] at the time of the primary SVR12 analysis);
●
Prior HCV treatment history (naïve or experienced);
●
For treatment-experienced subjects, type of prior treatment experience (IFN-
or SOF-based);
●
For treatment-experienced subjects, type of non-response to previous treatment 
(on-treatment nonresponder or breakthrough, post-treatment relapse, or 
unknown/other);
●
Screening HIV co-infection status (HCV mono-infected or HCV/HIV co-
infected);
●
IL28B genotype (CC or non-CC);
●
Sex (male or female);
●
Age (< 65 or ≥ 65 years) and (< 75 or ≥ 75 years);
●
Geographic region (China, Singapore, or South Korea);
●
Type of Asian descent (Chinese, Korean, Malay, or Other);
●
Baseline BMI (< 30 or ≥ 30 kg/m2);
●
Baseline HCV RNA level (< 1,000,000 or ≥ 1,000,000 IU/mL; < 6,000,000 or 
≥6,000,000 IU/mL; < 10,000,000 or ≥ 10,000,000 IU/mL);
●
Baseline HOMA-IR (< 2 or ≥ 2 mU × mmol/L2);
●
Baseline fibrosis stage (equivalent to Metavir F0 – F1, F2, F3, F4 [if 
applicable]);
●
Baseline platelet count (< 100 or ≥ 100 × 109/L);
●
Baseline albumin (< 35 or ≥ 35 g/L);
●
Baseline creatinine clearance (< 60, ≥ 60 to < 90, or ≥ 90 mL/min);


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●
Baseline eGFR (C-MDRD) (< 60, ≥ 60 to < 90, or ≥ 90 mL/min/1.73 m2);
●
History of diabetes (yes/no);
●
History of bleeding disorders (yes/no);
●
History of depression or bipolar disorder (yes/no);
●
History of cardiovascular disease (yes/no);
●
Baseline metabolic syndrome (yes/no);
●
Injection drug use (yes, within last 12 months; yes, more than 12 months ago; 
or no);
●
Baseline stable opiate substitution use (yes/no);
●
Baseline hepato-protectant medication use (yes/no);
●
Study drug compliance (yes/no);
●
Concomitant use of PPIs (yes/no).
The summaries described above will also be performed for the geographic region of China 
within the overall set of Arm A subjects and the Arm A subjects in each of the GT1-
infected and GT2-infected groups.
A logistic regression model will be used to explore the associations between each of the 
subgroup variables and SVR12 by fitting a logistic regression model on all subjects in the 
mITT-GT-VF population.  Among all candidate predictors, continuous measurements will 
be used where possible (e.g., continuous baseline log10 HCV RNA level, continuous age, 
continuous BMI) in the logistic regression model.  A stepwise logistic regression 
approach will be used to assess the strength of each subgroup variable in predicting 
SVR12, with a significance level of 0.10 to enter and remain in the model.
10.7
Additional Efficacy Analyses
The following additional efficacy endpoints will be summarized for the set of all Arm A 
subjects in the ITT population and in each of the GT1-infected and GT2-infected groups 
of the ITT population; within theses 3 groups of subjects, the endpoints will also be 
summarized for the geographic region of China:


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●
The percentage of subjects with HCV RNA < LLOQ at each post-baseline visit 
in the DB Treatment Period (using data as observed);
●
The percentage of subjects with SVR4;
●
A summary of reasons for SVR4 non-response (e.g., on-treatment virologic 
failure, relapse, re-infection, other);
●
The percentage of subjects with HCV virologic failure through PT Week 12
(i.e., the SVR12 non-responders due to on-treatment virologic failure or 
Relapse12);
●
The percentage of subjects with SVR24*;
●
A summary of reasons for SVR24 non-response (e.g., on-treatment virologic 
failure, relapse, re-infection, other)*;
●
The percentage of subjects who relapsed after achieving SVR12 (Relapse24).
*
These endpoints will be summarized for the HCV/HIV co-infected subjects 
(determined at Screening) within the populations/groups identified above.
The following additional endpoints will be summarized for the set of all subjects in the 
OL Population and for each of the GT1-infected and GT2-infected groups of the OL 
Population; within theses 3 groups of subjects, the endpoints will also be summarized for 
the geographic region of China:
●
The percentage of subjects with HCV RNA < LLOQ at each post-baseline visit 
in the OL Treatment Period (using data as observed);
●
The percentage of subjects with SVR4;
●
A summary of reason for SVR4 non-response (e.g., on-treatment virologic 
failure, relapse, re-infection, other);
●
The percentage of subjects with SVR12*;
●
A summary of reason for SVR12 non-response (e.g., on-treatment virologic 
failure, relapse, re-infection, other)*;
●
The percentage of subjects with SVR12 by HCV genotype and available 
subtype;


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●
The percentage of subjects with SVR12 by prior HCV treatment history 
(treatment-naïve and treatment-experienced, with further breakdown by type of 
prior HCV treatment experience);
●
The percentage of subjects with SVR12 by geographic region;
●
The percentage of subjects with HCV virologic failure through PT Week 12;
●
The percentage of subjects with SVR24*;
●
A summary of reason for SVR24 non-response (e.g., on-treatment virologic 
failure, relapse, re-infection, other)*;
●
The percentage of subjects who relapsed after achieving SVR12 (Relapse24).
*
These endpoints will be summarized for the HCV/HIV co-infected subjects 
(determined at Screening) within the populations/groups identified above.
In the above analyses for SVR, HCV virologic failure, and relapse, the number and 
percentage of subjects with each endpoint among those receiving active treatment during 
the DB or the OL Treatment Period, as applicable, will be calculated along with a 
two-sided 95% Wilson score CI.  Imputations for missing data will be performed as 
described in Section 6.3 for analysis of SVR, HCV virologic failure, and relapse.  All 
other endpoints will be presented using data as observed.
As additional endpoints, the secondary endpoints will be summarized for the geographic 
region of China within the set of Arm A subjects in the ITT population and in each of the 
GT1-infected and GT2-infected groups of the ITT population.
A summary of the subjects who completed treatment and relapsed (defined as 
Relapseoverall) will be prepared displaying the number of subjects relapsing overall and by 
SVR visit window (within the SVR4, SVR12, SVR24 windows or after SVR24 window), 
including the subject number and the SVR visit window corresponding to the first HCV 
RNA value of those indicating the occurrence of relapse.  A similar listing will be 
prepared for subjects who prematurely discontinued treatment and relapsed after having 
HCV RNA < LLOQ at their Final Treatment Visit.  These summaries will be presented 
across geographic regions and for the geographic region of China within the set of Arm A 


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subjects in the ITT population and in each of the GT1-infected and GT2-infected groups 
of the ITT population as well as within the overall OL population and the GT1-infected 
and GT2-infected groups in the OL population.
Listings of subject numbers with reason for non-response will be prepared for the SVR 
endpoints.
The concordance between SVR12 and SVR24 will be assessed by the agreement between 
SVR12 and SVR24 and the positive predictive value (PPV) and negative predictive value 
(NPV) of SVR12 on SVR24.  The agreement between SVR12 and SVR24 is a percentage 
defined as the number of subjects achieving both SVR12 and SVR24 and the number of 
subjects where both SVR12 and SVR24 are not achieved.  The PPV of SVR12 on SVR24 is 
the proportion of subjects who achieve SVR24 out of all subjects who achieved SVR12.  
The NPV of SVR12 on SVR24 is the proportion of subjects who do not achieve SVR24 out 
of all subjects who did not achieve SVR12.  Similarly, the concordance between SVR4 and 
SVR12 will be summarized.  These summaries will be presented across geographic regions 
and for the geographic region of China within the set of Arm A subjects in the ITT 
population and in each of the GT1-infected and GT2-infected groups of the ITT 
population as well as within the overall OL population and the GT1-infected and GT2-
infected groups in the OL population. 
For each additional analysis, a two-sided 95% CI will be produced only if there are at 
least 10 subjects in the summary.
10.8
HCV and HIV Resistance Analyses
For subjects who enroll in South Korea or Singapore, full length NS3/4A and NS5A from 
baseline samples will be sequenced by next generation sequencing (NGS).  For subjects 
who enroll in South Korea or Singapore who experience HCV virologic failure (on-
treatment HCV virologic failure or post-treatment relapse as defined in Section 10.1), full 
length NS3/4A and NS5A genes from the first sample after virologic failure with HCV 
RNA ≥ 1000 IU/mL will be sequenced by NGS.  For resistance analysis only, the last 


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sample collected before OL Day 1 will be considered the baseline sample for Arm B 
subjects.  For genotype 1-infected subjects experiencing virologic failure who enroll in 
China, amino acids 1 – 181 in NS3 and 1 – 215 in NS5A from the baseline sample and the 
first sample after virologic failure with HCV RNA ≥ 1000 IU/mL will be sequenced by 
population sequencing.  An appropriate subtype-specific prototypic reference sequence 
will be used for comparison with sequences from samples.  Subjects who experience HCV 
virologic failure will be referred to as subjects in the primary virologic failure (PVF) 
population, and a listing by subject that includes HCV subtype, IL28B genotype, reason 
for SVR12 non-response, time point(s) sequenced as closest to time of HCV virologic 
failure, and HCV RNA value at the HCV virologic failure time point(s) will be produced 
for these subjects.  In addition, all listings described below will display HCV subtype, and 
reason for SVR12 non-response in the subject identifier for each subject.  A separate 
listing will delineate all subjects in the PVF population for whom no sequencing was 
performed (e.g., lost to follow-up while HCV RNA ≤1000 IU/mL).
Subjects from South Korea and Singapore and GT1-infected subjects from China treated 
with active study drug who do not achieve SVR12 and who do not meet the above criteria 
for the PVF population (i.e., prematurely discontinue study drug with no on-treatment 
HCV virologic failure, have HCV reinfection, are missing SVR12 data or have other 
reasons as described in Section 10.1, Reasons for SVR12 Non-Response), but have a time 
point with HCV RNA ≥ 1000 IU/mL after treatment discontinuation, will have the sample 
at that time point sequenced.  For subjects from South Korea and Singapore and GT1-
infected subjects from China who are lost to follow-up with less than 6 weeks of therapy 
while not virally suppressed (e.g., HCV RNA never < LLOQ or have increase in viral 
load post-nadir), the sample at the latest available time point with HCV RNA 
≥1000 IU/mL and the corresponding baseline sample will be sequenced.  These subjects 
will be referred to as the non-PVF population.  A listing of all subjects in the non-PVF 
population with post-baseline sequencing available will be created that is similar to the 
listing of subjects in the PVF population with post-baseline sequencing.  For each DAA 
target, signature amino acid positions and a key subset of amino acid positions are shown 


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in Table 14.  Appropriate subtype-specific prototypic reference sequences will be used for 
comparison with sequences from samples.
Table 14.
List of Signature Amino Acid Positions and a Key Subset of Amino 
Acid Positions
Target
Signature Amino Acid Positions
Key Subset of Amino Acid Positions
GT1, NS3
36, 43 (GT1a only), 54, 55, 56, 80, 107, 
122, 132 (GT1a only), 155, 156, 158, 
168, 170, 175 (GT1b only)
155, 156, 168
GT1, NS5A
24, 28, 29, 30, 31, 32, 54 (GT1b only), 
58, 62, 92, 93
24, 28, 30, 31, 58, 92, 93
GT2, 4 – 6, NS3
36, 43, 54, 55, 56, 80, 155, 156, 168
155, 156, 168
GT2, 4 – 6, NS5A
24, 28, 29, 30, 31, 32, 58, 62, 92, 93
24, 28, 30, 31, 58, 92, 93
GT3, NS3/4A
36, 43, 54, 55, 56, 80, 155, 156, 166, 
168
155, 156, 168
GT3, NS5A
24, 28, 29, 30, 31, 32, 58, 92, and 93
24, 28, 30, 31, 58, 92, 93
Only samples with an HCV RNA level of ≥ 1000 IU/mL will undergo sequence analysis 
in order to allow accurate assessment of products of amplification.  Therefore, if the HCV 
RNA level at the time of virologic failure or treatment discontinuation is < 1000 IU/mL, 
the sample closest in time after failure/discontinuation with an HCV RNA level 
≥1000 IU/mL will be used.  Included time points for analyses on samples from subjects 
who do not achieve SVR12 are 1) the sample closest in time after failure/discontinuation 
with an HCV RNA level of ≥ 1000 IU/mL, and 2) 24 weeks post-DAA treatment, 
provided that resistance-associated substitutions were detected at the time of 
failure/discontinuation.
The following definitions will be used in the resistance analyses by population 
sequencing:
!
Baseline polymorphism:  a polymorphism in a 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. 


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!
Post-baseline substitution:  an amino acid substitution in a post-baseline time point 
sample that was not detected at baseline in the subject.
The following definitions will be used in the resistance analyses by NGS:
●
Baseline polymorphism:  a polymorphism in a baseline sample (≥ 2% or 
≥15% prevalence within a subject's viral population depending on frequency 
threshold utilized) that was not present in the appropriate prototypic reference 
amino acid sequence for a given DAA target (NS3/4A or NS5A).
●
Substitution at signature amino acid position:  substitution (relative to 
reference) present at a detection threshold of ≥ 2% or ≥ 15% (depending on 
frequency threshold utilized) within a subject's viral population in a baseline or 
a post-baseline sample at a signature amino acid position.
●
Post-baseline substitution:  an amino acid substitution in a post-baseline time 
point sample that was not detected at baseline (< 2%) in the subject and is 
detectable in ≥ 2% of the sequences from the sample.
●
Enriched substitution:  substitution present at both baseline and in a post-
baseline sample whose prevalence in the post-baseline sample is at least 
20 percentage points greater than the prevalence in the baseline sample [(post 
baseline % – baseline %) ≥ 20]. 
●
Treatment-emergent substitution by NGS:  a post-baseline substitution or an 
enriched substitution.
Analysis will be performed separately for each HCV subtype and treatment duration 
within each listing.
Analysis 1:  The following analyses will be performed for all subjects who enroll in 
South Korea or Singapore:
●
A listing of all baseline polymorphisms (≥ 2% detection threshold) at signature 
amino acid positions for each DAA target (NS3 and NS5A) for subjects in the 
ITT population. 
●
The number and percentage of subjects with baseline polymorphisms at 
detection-thresholds of ≥ 2% and ≥ 15% at signature amino acid positions (ITT 


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population).  This table includes prevalence of each baseline polymorphisms 
and a summary of number of subjects with polymorphisms in NS3 only, in 
NS5A only, any in NS3, any in NS5A, any in NS3 or NS5A, any in NS3 and 
NS5A.
●
Total number and percentage of subjects with baseline polymorphisms at the
key subset of amino acid positions in NS3 only, in NS5A only, any in NS3, 
any in NS5A, any in NS3 or NS5A, any in NS3 and NS5A (ITT population) 
by genotype, subtype, and total.
Analysis 2:  The impact of baseline polymorphisms on treatment outcome will be 
assessed for mITT-GT-VF population for subjects who enroll in South Korea or 
Singapore as follows:  for each polymorphism, the SVR12 rate will be calculated for 
subjects with and without the polymorphisms and the 2 rates will be compared using 
Fisher's exact test.  Analysis will be grouped by HCV subtype, treatment duration, and 
DAA target (NS3 or NS5A).  The following will be included in the analyses of impact of 
baseline polymorphisms on treatment outcome:
●
Polymorphisms at signature amino acid positions (vs no polymorphisms at that 
position), using detection thresholds of ≥ 2% and ≥ 15%.  The analysis will 
include the number of subjects with polymorphisms in NS3 only, in NS5A 
only, any in NS3, any in NS5A, any in NS3 or NS5A, any in NS3 + NS5A. 
●
Each polymorphism at signature amino acid position (vs not that variant) using 
detection thresholds of ≥ 2% and ≥ 15%.  The analysis will include the number 
of subjects with polymorphisms in NS3 only, in NS5A only, any in NS3, any 
in NS5A, any in NS3 or NS5A, any in NS3 + NS5A.
Analysis 3:  In subjects who enroll in South Korea or Singapore, the SVR12 rate will be 
calculated and compared using Fisher's exact test between subjects with or without 
polymorphisms at 15% detection threshold in NS3 only, in NS5A only, any in NS3, any 
in NS5A, any in NS3 or NS5A, any in NS3 and NS5A at the key subset of amino acid 
positions.  Analysis will be performed by HCV genotype, subtype, and overall on the 
mITT-GT-VF population.


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Analysis 4:  The following analyses will be performed for subjects who enroll in South 
Korea or Singapore who do not achieve SVR12 (with separate summaries for subjects in 
PVF and non-PVF populations) and have post-baseline resistance data available:
●
Listings by subject of all treatment-emergent substitutions relative to the 
baseline amino acid sequences will be provided for each DAA target (NS3 and 
NS5A).
●
Listings by subject of all substitutions at signature amino acid positions in a 
post-baseline time point for each DAA target (NS3 and NS5A).
Analysis 5:  For subjects who enroll in China who experience virologic failure and have 
sequence data available, the following analyses will be conducted:
●
A listing of all baseline polymorphisms at signature amino acid positions for 
each DAA target (NS3 and NS5A). 
●
Listings by subject of all post-baseline substitutions relative to the baseline 
amino acid sequence will be provided for each DAA target (NS3 and NS5A). 
●
Listings by subject of all emerged substitutions, by amino acid position and 
substitution within a DAA target in a post-baseline sample relative to the 
baseline amino acid sequence will be provided for each DAA target (NS3 and 
NS5A).  
●
Listings by subject of all post-baseline substitutions at signature amino acid 
positions relative to the appropriate prototypic reference amino acid sequence 
will be provided for each DAA target (NS3 and NS5A).
If resistance-associated substitutions are not detected in a given target for a subject at the 
time of failure/discontinuation, then that target may not be sequenced in subsequent 
samples from that subject.
HCV Genotype/Subtype
Phylogenetic analysis will be conducted on HCV sequence from all available baseline 
samples from subjects who enroll in South Korea or Singapore and genotype 1-infected 


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subjects experiencing virologic failure who enroll in China in order to accurately 
determine subtype.
Subjects' HCV genotype and subtype may be assessed based on the Inno-LiPA 2.0 Assay 
used by the Central lab (Covance), the HCV genotype determination by Sanger 
sequencing a region of NS5B by the Central lab (Covance) and/or from phylogenetic
analysis of the full length NS3/4A, and/or NS5A sequences performed by AbbVie.  If the 
phylogenetic analysis is available, then it will be used to determine the subject's HCV 
genotype and subtype.  If it is not available, then the Sanger sequencing assay result will 
be used to determine the subject's HCV genotype and subtype, if available.  Finally, if 
neither the phylogenetic analysis result nor the Sanger sequencing assay results is 
available, then the Inno-LIPA assay results will be used to categorize the subject.  This 
subtype information will be presented in summaries of efficacy subgroup analyses.  The 
baseline characteristic summary will use the results from the central laboratory (Sanger 
sequencing or Inno-LiPA 2.0 Assay [if Sanger sequencing not available]).
A summary of HCV genotype subtype as provided by the central laboratory (Sanger 
sequencing or Inno-LiPA 2.0 Assay [if Sanger sequencing not available]) versus 
phylogenetic analysis also will be provided.
HIV Drug-Resistance Analyses
If any subject on stable HIV-1 ART develops a confirmed, quantifiable plasma HIV-1 
RNA level (HIV-1 RNA ≥ 200 copies/mL at one assessment and ≥ 500 copies/mL on 
repeat testing) after starting the study, the HIV-1 protease, reverse transcriptase and/or 
integrase sequences, as applicable, will be analyzed by Monogram Biosciences using the 
GenoSure® Prime drug resistance assays for subjects from South Korea and Singapore.  
The number of subjects who demonstrate HIV genotypic resistance and the genotypic 
resistant mutations detected in the samples obtained from these subjects will be tabulated 
and summarized in the final CSR, as applicable.  Resistance will be defined as described 
by the IAS-USA Panel.9


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10.9
Patient Reported Outcomes
The following instruments will be used to collect patient reported outcomes (PROs):  
EuroQol-5 Dimensions-3 Level (EQ-5D-3L) and Fatigue Severity Scale (FSS).
Subject's responses to the EQ-5D-3L will be combined into a unique health state using a 
5-digit code with 1 digit from each of the 5 dimensions.  The EQ-5D-3L states will be 
converted into a single preference-weighted health utility index score by applying
weights.10,11  The VAS score will be analyzed separately.  For EQ-5D-3L index and VAS 
scores, no imputation will be performed for missing items. 
The FSS measures the impact of fatigue over the past week on specific types of 
functioning.  The survey consists of 9 questions using a 7-point Likert scale.  A total score 
is calculated as the average of the individual item responses (adding up all the answers 
and dividing by nine).  Higher FSS scores indicate a higher degree of impact of fatigue.  
Imputation will be applied to the total score as described in Section 6.3.
Summary statistics (n and mean,) at each protocol-specified visit and for change from 
baseline (n, mean, SD, minimum and maximum) to each protocol-specified visit will be 
provided for the EQ-5D-3L health index score and VAS score and for the FSS total score 
for each treatment arm in the ITT population (as applicable).  For each of these scores, 
mean change from Baseline to the final scheduled DB Treatment Period Visit (Week 8 or 
Week 16) will be compared between treatment arms using an analysis of covariance 
(ANCOVA) model with treatment arm as a factor and baseline score as a covariate. 
The number and percentage of subjects who have ever experienced an increase from 
baseline up through each applicable time point of greater than or equal to 0.7 in the FSS 
total score will also be calculated for each treatment arm in the ITT population (as 
applicable), along with two-sided 95% CIs based on the normal approximation to the 
binomial distribution.  In addition, percentages of subjects meeting the criteria at each 
applicable time point during the DB Treatment Period will be compared between Arm A 
and Arm B using Fisher's Exact Test.


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If a subject starts another treatment for HCV, then all PRO values for this subject 
measured on or after the start date of the new HCV treatment will be excluded from 
analyses.  
The analyses described above will also be performed for the geographic region of China.  
11.0
Safety Analysis
11.1
General Considerations
Safety analyses will be performed on the safety population for data corresponding to DB 
treatment and on the OL population for data corresponding to OL treatment.  Safety data 
will be summarized for the set of all subjects and for the geographic region of China.  
For safety analyses, data from the active (Arm A) and placebo (Arm B) treatment arms 
during the DB Treatment Period will be summarized, and comparisons between Arms A 
and B will be performed, as appropriate.  Data from the PT Period for Arm A through PT 
Week 4 will also be summarized for the change from baseline analyses of laboratory 
parameters, and through PT Week 24 for the change from baseline analyses of vital sign 
parameters.  
Data from the OL Treatment Period and PT Period for Arm B will be not be summarized 
in the primary CSR, except listings of any serious adverse events and deaths from the OL 
Treatment Period for Arm B will be included in the primary CSR; these data will be 
summarized in the interim analysis (following the primary CSR) and in the final CSR.
11.2
Analysis of Adverse Events
Adverse events (AEs) will be coded using the MedDRA coding dictionary.  The actual 
version of the MedDRA coding dictionary will be noted in the CSR.
HIV-1-infected subjects participating in clinical trials may develop infections typically 
associated with AIDS.  A list of these known AIDS-associated opportunistic infections 
(OIs) is contained in Appendix D of the study protocol.  AEs that are identified by the 


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investigators as AIDS-associated OIs will not be included in any analyses of AEs, but will 
be summarized separately for the HCV/HIV co-infected subjects.
11.2.1
Treatment-Emergent Adverse Events
Treatment-emergent AEs are defined below for the DB and OL Treatment Periods 
separately.  
Treatment-Emergent AEs in DB Treatment Period 
For the active arm (Arm A), treatment-emergent AEs are defined as any event with an 
onset date that is after the first dose of active study drug and no more than 30 days after 
the last dose of study drug.  For the placebo arm (Arm B), treatment-emergent AEs are 
defined as any event with an onset date that is after the first dose of placebo through 
30 days after the last dose of placebo and prior to OL Day 1 (if applicable).  Events where 
the onset date is the same as the study drug start date are assumed to be treatment-
emergent.  If an incomplete onset date was collected for an AE, the event will be assumed 
to be treatment-emergent, unless there is other evidence that confirms that the event was 
not treatment-emergent (e.g., the event end date was prior to the study drug start date).
Treatment-Emergent AEs in OL Treatment Period
For subjects in the OL Population, treatment-emergent AEs are defined as any event with 
an onset date that is after the first dose of OL study drug and no more than 30 days after 
the last dose of OL study drug.  Events where the onset date is the same as the OL study 
drug start date are assumed to be treatment-emergent.  If an incomplete onset date was 
collected for an AE, the event will be assumed to be treatment-emergent, unless there is 
other evidence that confirms that the event was not treatment-emergent (e.g., the event 
end date was prior to the OL study drug start date).
11.2.2
Tabulations of Treatment-Emergent Adverse Events
The number and percentage of subjects with treatment-emergent AEs will be tabulated by 
primary MedDRA System Organ Class (SOC) and preferred term.  The SOCs will be 


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presented in alphabetical order, and the preferred terms will be presented in alphabetical 
order within each SOC.
Subjects reporting more than one AE for a given preferred term will be counted only once 
for that term (most severe/highest grade incident for the severity tables and most related
incident for the relationship tables).  Subjects reporting more than one AE within a SOC 
will be counted only once for that SOC.  Subjects reporting more than one AE will be 
counted only once in the overall total.
AEs will be presented for the following 3 groups, separately:  1) DB active (Arm A during 
the DB Treatment period), 2) DB placebo (Arm B during the DB Treatment Period), and 
3) OL active (Arm B during the OL period).
Adverse Event Overview
An overview of AEs will be presented consisting of the number and percentage of 
subjects experiencing at least one event for each of the following AE categories; this 
overview will also be presented for the set of HCV/HIV co-infected subjects within the 
populations/groups specified in Section 11.1:
●
Any treatment-emergent AE;
●
Treatment-emergent AEs with a "reasonable possibility" of being related to 
DAAs (ABT-493/ABT-530);
●
Treatment-emergent AEs of Grade 3 or higher;
●
Treatment-emergent AEs of Grade 3 or higher with a "reasonable possibility" 
of being related to DAAs (ABT-493/ABT-530);
●
Serious treatment-emergent AEs;
●
Serious treatment-emergent AEs with a "reasonable possibility" of being 
related to DAAs (ABT-493/ABT-530);
●
Treatment-emergent AEs leading to discontinuation of study drug;
●
DAA-related treatment-emergent AEs leading to discontinuation of study 
drug;
●
Serious treatment-emergent AEs leading to discontinuation of study drug;


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●
Treatment-emergent AEs leading to interruption of study drug;
●
Treatment-emergent AEs leading to death;
●
Deaths.
Adverse Events by SOC and Preferred Term
The following summaries of AEs by SOC and preferred term will be generated:
●
Treatment-emergent AEs (will also be presented for the set of HCV/HIV co-
infected subjects within the populations/groups specified in Section 11.1);
●
Treatment-emergent AEs with a "reasonable possibility" of being related to 
DAAs (ABT-493/ABT-530);
●
Serious treatment-emergent AEs;
●
Serious treatment-emergent AEs with a "reasonable possibility" of being 
related to DAAs (ABT-493/ABT-530);
●
Treatment-emergent AEs of Grade 3 or higher;
●
Treatment-emergent AEs of Grade 3 or higher with a "reasonable possibility" 
of being related to DAAs (ABT-493/ABT-530);
●
Treatment-emergent AEs leading to discontinuation of study drug;
●
DAA-related treatment-emergent AEs leading to discontinuation of study 
drug;
●
Serious treatment-emergent AEs leading to discontinuation of study drug;
●
Treatment-emergent AEs leading to interruption of study drug;
●
Treatment-emergent AEs leading to death.
For all treatment-emergent AEs (at the SOC and preferred term level), risk differences 
will be calculated for the DB active arm (Arm A) versus placebo (Arm B).  The risk 
difference will be calculated as the percentage of subjects in Arm A with the event minus 
the percentage of subjects in Arm B with the event.  The risk differences will be included 
on the summaries of AEs during the DB Treatment Period.


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A listing of treatment-emergent adverse events grouped by SOC and preferred term with 
subject numbers will be created.
Adverse Events by Preferred Term
The following summaries of AEs tabulated according to preferred term and sorted by 
overall frequency in Arm A for the DB active and DB placebo groups and by frequency 
for the OL active group will be generated:
●
Treatment-emergent AEs (will also be presented for the set of HCV/HIV co-
infected subjects within the populations/groups specified in Section 11.1);
●
Treatment-emergent AEs with a "reasonable possibility" of being related to 
DAAs (ABT-493/ABT-530);
●
Serious treatment-emergent AEs;
●
Serious treatment-emergent AEs with a "reasonable possibility" of being 
related to DAAs (ABT-493/ABT-530);
●
Treatment-emergent AEs of Grade 3 or higher;
●
Treatment-emergent AEs of Grade 3 or higher with a "reasonable possibility" 
of being related to DAAs (ABT-493/ABT-530).
These summaries also will include the risk difference defined earlier and the 2-sided 95% 
CI on the risk difference using the Wilson score method for a difference in proportions.12
Adverse Events by Maximum Severity Grade Level
Treatment-emergent AEs and DAA-related treatment-emergent AEs will be summarized 
by maximum severity grade level of each preferred term.  Each AE will be assigned a 
grade level (Grade 1, 2, 3, 4, or 5) by the investigator.  If a subject has an AE with 
unknown severity, then the subject will be counted in the severity grade level category of 
"unknown," even if the subject has another occurrence of the same event with a severity 
present.  The only exception is if the subject has another occurrence of the same AE with 
the highest grade level (Grade 5).  In this case, the subject will be counted under the 
"Grade 5" category.


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Adverse Events by Maximum Relationship
Treatment-emergent AEs also will be summarized by maximum relationship of each 
preferred term to study drug (DAAs), as assessed by the investigator.  If a subject has an 
AE with unknown relationship, then the subject will be counted in the relationship 
category of "unknown," even if the subject has another occurrence of the same event with 
a relationship present.  The only exception is if the subject has another occurrence of the 
same AE with a relationship assessment of "Reasonable Possibility."  In this case, the 
subject will be counted under the "Reasonable Possibility" category.
Adverse Events of Special Interest
The AEs of special interest include the following:
"Hepatic Decompensation and Hepatic Failure" defined by the Product MedDRA 
Query (PMQ);
"Hepatocellular Carcinoma" defined by the MedDRA preferred terms of 
hepatocellular carcinoma, hepatic neoplasm, hepatic cancer, hepatic cancer 
recurrent, and hepatic cancer metastatic.
For the hepatic decompensation/hepatic failure AE of special interest, the number and 
percentage of subjects experiencing at least one treatment-emergent AE in the search will 
be presented by SOC and preferred term and across all SOCs/preferred terms.  In addition, 
a by-subject listing of treatment-emergent AEs meeting the search criterion will be 
provided.
For the hepatocellular carcinoma AE of special interest, a by-subject listing of all post-
baseline (i.e., including both treatment-emergent and non-treatment emergent) AEs 
meeting the search criterion will be provided.


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Adverse Events by HIV-1 ART Regimen 
For the HCV/HIV co-infected subjects who were on HIV-1 ART at initiation of DB study 
drug, treatment-emergent AEs also will be summarized for the subgroups defined by the 
HIV-1 ART regimen (e.g., RAL, DTG, RPV) the subjects were receiving at DB study 
drug initiation.  For each HIV-1 ART regimen, the number and percentage of subjects 
experiencing treatment-emergent AEs will be tabulated according to SOC and preferred 
term. 
AIDS-Associated Opportunistic Infections
The number and percentage of subjects experiencing treatment-emergent AIDS-associated 
OIs will be tabulated according to SOC and preferred term for the HCV/HIV co-infected 
subjects (determined at Screening).  Subjects reporting more than one AIDS-associated OI 
for a given preferred term will be counted only once for that term.  Subjects reporting 
more than one AIDS-associated OI within a SOC will be counted only once for that SOC.  
Subjects reporting more than one AIDS-associated OI will be counted only once in the 
overall total.
11.2.3
Listings of Adverse Events
The following listings of AEs will be prepared:
●
All serious AEs (from the time the subject signed the study-specific informed 
consent through the end of the study),
●
Treatment-emergent serious AEs,
●
Treatment-emergent AEs leading to death,
●
Treatment-emergent AEs leading to discontinuation of study drug,
●
Treatment-emergent AEs leading to study drug interruption,
●
AEs (treatment-emergent or all, as applicable) in each of the AEs of special 
interest categories,
●
Treatment-emergent AIDS-associated OIs.


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11.3
Analysis of Laboratory Data
Data collected from the central and local laboratories, including additional laboratory 
testing due to a serious AE, will be used in all analyses.
11.3.1
Variables and Criteria Defining Abnormality
Hematology variables to be summarized include:  hematocrit, hemoglobin, red blood cell 
(RBC) count, white blood cell (WBC) count, neutrophils, bands, lymphocytes, 
monocytes, basophils, eosinophils, platelet count, reticulocyte count, prothrombin time 
(PT), international normalized ratio (INR), and activated partial thromboplastin time 
(aPTT).
Chemistry variables to be summarized include:  blood urea nitrogen (BUN), creatinine, 
total bilirubin, direct and indirect bilirubin, alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), alkaline phosphatase, sodium, potassium, calcium, inorganic 
phosphorus, uric acid, cholesterol, total protein, glucose, triglycerides, albumin, chloride, 
bicarbonate, magnesium, total insulin, gamma-glutamyl transferase (GGT), creatinine 
clearance (calculated using Cockcroft-Gault), estimated glomerular filtration rate (eGFR) 
calculated using the modification of diet in renal disease (MDRD) equation modified for 
the Chinese population (C-MDRD), and creatinine phosphokinase (CPK).
Urinalysis variables to be summarized include:  specific gravity and pH.
The definitions of toxicity grades for laboratory parameters are presented in Table 15.


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Table 15.
Definitions of Toxicity Grades 1, 2, 3, and 4 for Laboratory Values
Test
Grade 1
Grade 2
Grade 3
Grade 4
ALT 
> ULN – 3 × ULN
> 3 – 5 × ULN
> 5 – 20 × ULN
> 20 × ULN
AST 
> ULN – 3 × ULN
> 3 – 5 × ULN
> 5 – 20 × ULN
> 20 × ULN
Alkaline 
Phosphatase
> ULN – 2.5 × ULN
> 2.5 – 5 × ULN
> 5 – 20 × ULN
> 20 × ULN
GGT
> ULN – 2.5 × ULN
> 2.5 – 5 × ULN
> 5 – 20 × ULN
> 20 × ULN
Total 
Bilirubin
> ULN – 1.5 × ULN
> 1.5 – 3 × ULN
> 3 – 10 × ULN
> 10 × ULN
Hemoglobin
< LLN – 100 g/L
< 100 – 80 g/L
< 80 g/L
--
White blood 
cells
< LLN – 3.0 × 109/L
< 3.0 – 2.0 × 109/L
< 2.0 – 1.0 × 109/L
< 1.0 × 109/L
Absolute 
Neutrophil 
Count
< LLN – 1.5 × 109/L
< 1.5 – 1.0 × 109/L
< 1.0 – 0.5 × 109/L
< 0.5 × 109/L
Platelet count
< LLN – 75.0 × 109/L
< 75.0 – 50.0 × 
109/L
< 50.0 – 25.0 × 109/L
< 25.0 × 109/L
INR
> 1 – 1.5 × ULN
> 1.5 – 2.5 × ULN
> 2.5 × ULN
--
Glucose 
(high)
> ULN – 8.9 mmol/L
> 8.9 – 13.9 mmol/L
> 13.9 – 27.8 mmol/L
> 27.8 mmol/L
Glucose (low)
< LLN – 3.0 mmol/L
< 3.0 – 2.2 mmol/L
< 2.2 – 1.7 mmol/L
< 1.7 mmol/L
Creatinine
> ULN – 1.5 × ULN
> 1.5 – 3 × ULN
> 3 – 6 × ULN
> 6 × ULN
Creatinine 
clearance
< LLN – 60 mL/min
< 60 – 30 mL/min
< 30 – 15 mL/min
< 15 mL/min
eGFR 
(C-MDRD)
< LLN –
60 mL/min/1.73 m2
< 60 –
30 mL/min/1.73 m2
< 30 –
15 mL/min/1.73 m2
< 15 mL/min/1.73 m2
Cholesterol
> ULN – 7.75 mmol/L
> 7.75 –
10.34 mmol/L
> 10.34 –12.92 mmol/L
> 12.92 mmol/L
Albumin
< LLN – 30 g/L
< 30 – 20 g/L
< 20 g/L
--
Lymphocyte
< LLN – 0.8 × 109/L
< 0.8 – 0.5 × 109/L
< 0.5 – 0.2 × 109/L
< 0.2 × 109/L
aPTT
> ULN – 1.5 × ULN
> 1.5 – 2.5 × ULN
> 2.5 × ULN
--
Sodium (low)
< LLN – 130 mmol/L
--
< 130 – 120 mmol/L
< 120 mmol/L
Sodium (high)
> ULN – 150 mmol/L
> 150 – 155 mmol/L
> 155 – 160 mmol/L
> 160 mmol/L
Potassium 
(low)
< LLN – 3.0 mmol/L
--
< 3.0 – 2.5 mmol/L
< 2.5 mmol/L
Potassium 
(high)
> ULN – 5.5 mmol/L
> 5.5 – 6.0 mmol/L
> 6.0 – 7.0 mmol/L
> 7.0 mmol/L


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Table 15.
Definitions of Toxicity Grades 1, 2, 3, and 4 for Laboratory Values 
(Continued)
Test
Grade 1
Grade 2
Grade 3
Grade 4
Triglycerides
> 1.71 – 3.42 mmol/L
> 3.42 – 5.7 mmol/L
> 5.7 – 11.4 mmol/L
> 11.4 mmol/L
Magnesium 
(low)
< LLN – 0.5 mmol/L
< 0.5 – 0.4 mmol/L
< 0.4 – 0.3 mmol/L
< 0.3 mmol/L
Magnesium 
(high)
> ULN – 1.23 mmol/L
--
> 1.23 – 3.30 mmol/L
> 3.30 mmol/L
CPK
> ULN – 2.5 × ULN
> 2.5 – 5 × ULN
> 5 – 10 × ULN
> 10 × ULN
Assessments of hepatotoxicity will be made based on a single laboratory parameter 
collected at any post-baseline visit through the Final Treatment visit using the following 
criteria:
●
ALT > 5 × ULN and ≥ 2 × baseline;
●
Total bilirubin ≥2 × ULN and > baseline;
●
Total bilirubin ≥ 2 × ULN and > baseline and direct/total bilirubin ratio > 0.4;
●
Increase from nadir by grade in ALT: 
○
ALT > 3 – 5 × ULN (Grade 2);
○
> 5 – 20 × ULN (Grade 3);
○
> 20 × ULN (Grade 4).
The direct/total bilirubin ratio will be calculated using the same date/time sample 
corresponding to the total bilirubin elevation.  For the summary of increase from nadir by 
grade in ALT, the post-baseline value must represent an increase from the first nadir 
(including baseline) to be counted, where the grade of the post-baseline value must be 
more extreme than the grade of the nadir value.  First nadir is defined as the last value 
prior to the first increase.  The maximum ratio relative to the ULN will be used to 
determine if subjects meet the criteria listed above.
Assessments of hepatotoxicity will also be made based on multiple laboratory parameters 
collected at any post-baseline visit through the Final Treatment visit using the following 
criterion:


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●
ALT > 3 × ULN (Grade 2 + and increase from nadir grade) and total bilirubin 
≥2 × ULN.
For the criterion based on multiple laboratory parameters, the analysis will check to see if 
the subject meets the ALT and total bilirubin portions of the criterion at any time within 
the Treatment Period (i.e., draw dates do not need to be concurrent).  The maximum ratio 
relative to the ULN for each parameter will be used to determine if the subject meets the 
criterion listed above.  For ALT, the post-baseline value must represent an increase from 
the first nadir (including baseline) to be counted.  First nadir is defined as the last value 
prior to the first increase.  The grade of the post-baseline ALT value must be at least 
Grade 2 and more extreme than the grade of the nadir value.  For total bilirubin, a subject 
or event will be counted if the post-baseline laboratory values meet the above criteria 
regardless of the baseline laboratory value (i.e., the post-baseline laboratory value does 
not need to be worse than the baseline laboratory value).
11.3.2
Statistical Methods
Clinical laboratory tests will be summarized by treatment arm (A and B) at each visit 
during the DB Treatment Period and separately for Arm B subjects during the OL 
Treatment Period.  Also, summaries of clinical laboratory data collected during the Post-
Treatment Period will be presented for Arm A of the safety population and separately for 
the OL population.
The baseline value for clinical laboratory tests will be the last non-missing measurement 
on or before the day of the first dose of DB study drug.  Values on Day 1 must also be 
before the time of first dose if time is available.  The same baseline value will be used for 
all summaries of the data from the DB, OL, and Post-Treatment Period visits.
Changes from baseline to each post-baseline visit, including applicable post-treatment 
visits, will be summarized.  For DB Treatment Period visits and for Post-Treatment visits 
for Arm A, each protocol-specified laboratory parameter will be summarized with the 
sample size; baseline mean; visit mean; and change from baseline mean, standard 


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deviation, and median.  The differences between the active and placebo arms in the DB 
Treatment Period will be analyzed using an ANOVA model with treatment arm as the 
factor.  The difference between the treatment arms (Arm A minus Arm B) in mean change 
from baseline along with the corresponding 95% CI, standard error, and P value will be 
presented.  For OL Treatment Period visits and Post-Treatment visits for Arm B, each 
protocol-specified laboratory parameter will be summarized with the sample size; baseline 
mean; visit mean; and change from baseline mean, standard deviation, minimum, median, 
and maximum.  
Plots of mean change (± standard error) from baseline to each visit will be presented by 
treatment arm for ALT and bilirubin (total, direct, and indirect).  For each parameter, 
mean changes at visits during the DB Treatment Period for Arms A and B along with 
mean changes at post-treatment visits for Arm A will be presented on the same plot, and 
mean changes at visits during the OL Treatment Period will be provided for Arm B on a 
separate plot.
Hematology and chemistry data values will be categorized as low, normal, or high based 
on the normal ranges of the laboratory used for each sample.  Shift tables from baseline to 
minimum value and from baseline to maximum value during the DB and OL Treatment 
Periods will be created for each treatment arm.  The shift tables will cross-tabulate the 
frequency of subjects with baseline values below/within/above the normal range versus 
minimum/maximum post-baseline values below/within/above the normal range.
The laboratory parameters listed in Table 15 will be categorized according to the toxicity 
grades defined in the table.  The number and percentage of subjects with a maximum 
toxicity grade of 1, 2, 3 or 4 during treatment (DB treatment and OL treatment 
summarized separately) will be calculated for each treatment arm.  To be counted, the 
post-baseline value must have a toxicity grade that is more extreme than the toxicity grade 
corresponding to the baseline value.  For each laboratory parameter in Table 15, the 
summary will also include the number and percentage of subjects with a maximum of at 
least Grade 3 for each treatment arm.  For summaries of data collected during the DB 
Treatment Period, the difference in rates between the 2 arms (Arm A minus Arm B), and 


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the 2-sided 95% CI for the rate difference using the Wilson score method for a difference 
in proportions will be presented.12  These summaries will also be presented for the set of 
HCV/HIV co-infected subjects (determined at Screening) within the populations/groups 
specified in Section 11.1.  
A listing of all relevant laboratory parameters will be provided for each subject who had 
an increase to Grade 2 or higher for any laboratory variable in Table 15.
For the assessments of hepatotoxicity based on single and multiple laboratory parameters, 
the number and percentage of subjects meeting the criterion during treatment will be 
calculated for each criterion.  A listing of all ALT, AST, total, indirect and direct 
bilirubin, ratio of direct to total bilirubin, and alkaline phosphatase values will be provided 
for each subject who met any of the single or multiple criteria defined above.  The listings 
will be reviewed to assess bilirubin (e.g., mixed or direct predominance) and temporal 
relationships for subjects with ALT > 3 × ULN (or ALT Grade 2 +) and total bilirubin 
≥2 × ULN.
11.4
Analysis of Vital Signs and Weight
11.4.1
Variables and Criteria Defining Abnormality
Vital sign variables are body temperature, sitting systolic blood pressure, sitting diastolic 
blood pressure, sitting pulse rate, and body weight.
The criteria for potentially clinically significant (PCS) vital sign findings are presented in 
Table 16.


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Table 16.
Criteria for Potentially Clinically Significant Vital Sign Values
Test/Measurement
Very Low (VL)
Very High (VH)
Systolic Blood Pressure
≤ 90 mmHg AND A decrease of 
≥ 20 mmHg from baseline
≥ 180 mmHg AND An increase of 
≥ 20 mmHg from baseline
Diastolic Blood Pressure
≤ 50 mmHg AND A decrease of 
≥ 15 mmHg from baseline
≥ 105 mmHg AND An increase of 
≥ 15 mmHg from baseline
Pulse Rate
≤ 50 bpm AND A decrease of 
≥ 15 bpm from baseline
≥ 120 bpm AND An increase of 
≥ 15 bpm from baseline
Weight
A decrease of ≥ 15% from baseline
An increase of ≥ 15% from baseline
Body Temperature
> 38.3°C AND An increase of 
≥ 1.1°C from baseline
11.4.2
Statistical Methods
Vital signs will be summarized by treatment arm at each visit during the DB Treatment 
Period and separately for Arm B subjects in the OL Treatment Period.  Also, vital signs 
collected during the Post-Treatment Period will be presented for Arm A of the safety 
population and separately for the OL population.
The baseline value for vital signs will be the last measurement on or before the day of the 
first dose of DB study drug.  The same baseline value will be used for all summaries of 
the data from the DB, OL, and Post-Treatment Period visits.
Changes from baseline to each post-baseline visit, including applicable post-treatment 
visits, will be summarized.  For DB Treatment Period visits and for Post-Treatment visits 
for Arm A, each vital sign parameter will be summarized with the sample size; baseline 
mean; visit mean; and change from baseline mean, standard deviation, and median.  The 
differences between the active and placebo arms in the DB Treatment Period will be 
analyzed using an ANOVA model with treatment arm as the factor.  The difference 
between the treatment arms (Arm A minus Arm B) in mean change from baseline along 
with the corresponding 95% CI, standard error, and P value will be presented.  For OL 
Treatment Period visits and Post-Treatment visits for Arm B, each vital sign parameter 


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will be summarized with the sample size; baseline mean; visit mean; and change from 
baseline mean, standard deviation, minimum, median, and maximum.
The number and percentage of subjects with on-treatment values (DB treatment and OL 
treatment summarized separately) meeting the specified criteria for PCS vital sign values 
(Table 16) will be calculated for each treatment arm.  A post-baseline value must be more 
extreme than the baseline value to be considered a PCS finding.  A separate listing will be 
provided that presents all vital sign values for the subjects meeting PCS criteria during 
treatment.
11.5
Analysis of HIV-1 RNA and Flow Cytometry Data
Plasma HIV-1 RNA will be measured by the central laboratory using the Roche COBAS 
AmpliPrep/COBAS TaqMan HIV-1 Test, version 2.0.  For specimens with HIV-1 RNA 
results that are detectable but not quantifiable, the results are reported as "< 20 CP/ML 
HIV-1 RNA DETECTED;" for specimens with no HIV RNA detected, the results are 
reported as "NO HIV-1 RNA DETECTED."  Subjects will also have blood samples 
drawn and archived.  These samples may be used for other analyses including drug 
resistance testing.  These samples may be tested at the discretion of AbbVie.
For the HCV/HIV co-infected subjects (determined at Screening) who are on HIV-1 ART 
at initiation of DB study drug, the numbers and percentages of subjects with 2 consecutive 
HIV-1 RNA values ≥ 200 copies/mL during the DB and OL Treatment Periods will be 
calculated for each treatment arm; only data from the central laboratory will be included 
in these analyses.  A listing of subjects with a plasma HIV-1 RNA value ≥ 200 copies/mL 
at any baseline or post-baseline visit during the study will be provided.  Data from the 
central and local laboratory will be included in the listing.
For the HCV/HIV co-infected subjects (determined at Screening), changes from baseline 
to each post-baseline visit, including applicable post treatment visits, in CD4+ T-cell 
count (absolute and percentage), CD8+ T-cell count (absolute and percentage), and 
lymphocytes (count) will be summarized for each treatment arm.  For DB Treatment 


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Period visits, for Post-Treatment visits for Arm A, and for OL Treatment Period visits and 
Post-Treatment visits for Arm B, each protocol-specified laboratory parameter will be 
summarized with the sample size; baseline mean; visit mean; and change from baseline 
mean, standard deviation, minimum, median, and maximum.
12.0
Summary of Changes
12.1
Summary of Changes Between the Latest Version of the 
Protocol and SAP
1.
Modified the definitions of the mITT populations to also exclude subjects who 
received incorrect duration of treatment due to incorrect classification of GT or 
treatment experience at randomization.
2.
Removed the analyses of demographics, baseline characteristics, study drug 
exposure and compliance for the mITT populations because it is expected that 
these populations will be very similar to the ITT population.
3.
Removed the analyses of demographics and baseline characteristics for the OL 
population because it is expected that this population will be very similar to the 
Arm B safety population.
4.
Removed the analyses of study drug exposure and compliance for the GT1-infected 
and GT2-infected groups because these variables are expected to be similar 
between the set of all subjects and the GT1-infected and GT2-infected groups.
5.
Replaced analyses by geographic region with analyses for the geographic region of 
China because analyses for the subset of subjects from China, rather than analyses 
by geographic region, are required by the regulatory agency.  Certain analyses of 
subject disposition and SVR12 will be performed by geographic region.
6.
Added additional analyses of categorical baseline characteristics for subjects with 
HCV/HIV co-infection at Screening to provide additional information for the 
HCV/HIV co-infected population.


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7.
Added analyses of SVR12 for Arm A for the geographic region of China to the 
sensitivity analysis to address regulatory requirements for China-specific analyses.
8.
Added additional imputation approaches and assessment of homogeneity across 
stratification variables to the sensitivity analysis of the primary endpoints to align 
with the HCV ABT-493/ABT-530 program.
9.
Removed the subgroup analysis of the primary endpoints for the mITT populations 
to align with the HCV ABT-493/ABT-530 program.
10.
Added the additional efficacy analysis of the percentage of subjects with HCV 
virologic failure through PT Week 12 to align with the HCV ABT-493/ABT-530 
program.
11.
Removed several of the additional efficacy analyses to be performed on the 
HCV/HIV co-infected population because the number of HCV/HIV co-infected 
subjects is anticipated to be lower than had been expected at the time the protocol 
was written.
12.
The PRO analysis as defined in the protocol:
●
Cumulative number and percentage of subjects who have ever experienced an 
increase from baseline in the FSS total score of greater than or equal to 0.7 
through each applicable timepoint;
Has been changed to below to align with the HCV ABT-493/ABT-530 program:
●
Number and percentage of subjects who have ever experienced an increase 
from baseline up through each applicable time point of greater than or equal to 
0.7 in the FSS total score.
13.
Specified the assays used by the central laboratory for the HCV RNA and HIV-1 
RNA samples and the HIV-1 resistance testing, along with the LLOD and LLOQ 
for the HCV RNA assay.  This information was not known at the time of protocol 
development.
14.
Removed the analyses of safety data for the GT1-infected and GT2-infected groups 
because GT is not expected to have an impact on safety.


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15.
Removed several of the safety analyses to be performed on the HCV/HIV co-
infected population because the number of HCV/HIV co-infected subjects is 
anticipated to be lower than had been expected at the time the protocol was written.
16.
Added calculation of the between-arm risk difference to all AE summaries at the 
SOC and preferred term level during the DB Treatment Period and removed 
comparisons using Fisher's exact test to align with the HCV ABT-493/ABT-530 
program.
17.
Added calculation of the between-arm risk difference and 95% CI using Wilson's 
score method to AE summaries by preferred term and clinical laboratory 
summaries by maximum toxicity grade and removed comparisons using Fisher's 
exact test to align with the HCV ABT-493/ABT-530 program.
18.
Added analysis of laboratory assessments of hepatotoxicity to align with the HCV 
ABT-493/ABT-530 program.
19.
Added plots of mean change (± standard error) from baseline for ALT and bilirubin 
(total, direct, and indirect) to align with the HCV ABT-493/ABT-530 program.  
20.
Removed comparisons between arms using Fisher's exact test from PCS vital sign 
summaries during the DB Treatment Period to align with the HCV 
ABT-493/ABT-530 program.
21.
Added analyses of CD4+ T-cell count, CD8+ T-cell count, and lymphocytes for the 
HCV/HIV co-infected population to align with the HCV ABT-493/ABT-530 
program.
13.0
References
1.
Viekira Pak™(ombitasvir, paritaprevir and ritonavir tablets; dasabuvir tablets) 
[Summary of Product Characteristics].  North Chicago, IL; AbbVie Inc., 2015.
2.
HARVONI® (ledipasvir and sofosbuvir) tablets [package insert].  Foster City, CA; 
Gilead Sciences, Inc., 2015.


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3.
Omata M, Nishiguchi S, Ueno Y, et al.  Sofosbuvir plus ribavirin in Japanese 
patients with chronic genotype 2 HCV infection:  an open-label, phase 3 trial.  J 
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4.
Sovaldi® (sofosbuvir) Tablets [package insert].  Foster City, CA; Gilead Sciences, 
Inc., 2014.
5.
DAKLINZA™(daclatasvir) [package insert].  Princeton, NJ; Bristol-Myers Squibb 
Company, 2015.
6.
Grundy SM, Brewer HB Jr, Cleeman JI, et al.  Definition of metabolic syndrome:  
report of the National Heart, Lung, and Blood Institute/American Heart 
Association conference on scientific issues related to definition.  Circulation.  
2004;109(3):433-8.
7.
Westfall PH, Krishen A.  Optimally weighted, fixed sequence and gatekeeper 
multiple testing procedures.  J Stat Plan Inference.  2001;99:25-40.
8.
Newcombe RG.  Two-sided confidence intervals for the single proportion:  
comparison of seven methods.  Stat Med.  1998;17(8):857-72.
9.
2017 update of the drug resistance mutations in HIV-1.  Top Antivir Med.  2017; 
24(4):132-141.  Available from:  https://www.iasusa.org/sites/default/files/tam/24-
4-132.pdf.
10.
Szende A, Williams A.  Measuring self-reported population health:  an 
international perspective based on EQ-5D.  EuroQol Group Monographs 
Volume 1.  SpringMed Publishing; 2004.
11.
Rabin R, Oemar M, Oppe M, et al.  EQ-5D-5L user guide:  basic information on 
how to use the EQ-5D-5L instrument, Version 1.0.  Rotterdam, the Netherlands:  
EuroQol Group; 2011.
12.
Newcombe RG.  Interval estimation for the difference between independent 
proportions:  comparison of eleven methods.  Stat Med.  1998;17(8):873-90.