An Open-Label Study to Evaluate the Safety and Efficacy of ABT-450/Ritonavir/ABT-267 (ABT 450/r/ABT-267) and ABT-333 Coadministered With Ribavirin (RBV) in Treatment-Naïve and Treatment-Experienced Asian Adults With GT1b Chronic Hepatitis C Virus (HCV) Infection and Compensated Cirrhosis
Phase: PHASE3
Conditions: Chronic Hepatitis C Virus (HCV)
Sponsor: AbbVie

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
1
1.0
Title Page
Clinical Study Protocol M14-491
An Open-Label Study to Evaluate the Safety and 
Efficacy of ABT-450/Ritonavir/ABT-267
(ABT-450/r/ABT-267) and ABT-333 Coadministered 
with Ribavirin (RBV) in Treatment-Naïve and 
Treatment-Experienced Asian Adults with 
Genotype 1b Chronic Hepatitis C Virus (HCV) 
Infection and Compensated Cirrhosis
AbbVie Investigational
  Product:
ABT-450/r/ABT-267, ABT-333
Date:
11 February 2015
Development Phase:
3
Study Design:
This is an open-label combination drug study.
Investigator:
Multicenter.  Investigator information is on file at AbbVie 
Sponsor:
AbbVie
Sponsor/Emergency
  Contact:
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
/$5

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
2
1.1
Synopsis
AbbVie Inc.
Protocol Number:  M14-491
Name of Study Drug:  ABT-450, ritonavir, 
ABT-267, ABT-333
Phase of Development:  3
Name of Active Ingredient:  
ABT-450
ritonavir
ABT-267
ABT-333 
Date of Protocol Synopsis:  11 February 2015
Protocol Title:  An Open-Label Study to Evaluate the Safety and Efficacy of ABT-450/Ritonavir/ 
ABT-267 (ABT-450/r/ABT-267) and ABT-333 Coadministered with Ribavirin (RBV) in 
Treatment-Naïve and Treatment-Experienced Asian Adults with Genotype 1b Chronic Hepatitis C Virus 
(HCV) Infection and Compensated Cirrhosis
Objectives:  
The primary objectives of this study are to assess the safety and to compare the percentage of subjects 
achieving SVR12 rate (the percentage of subjects achieving a 12 week sustained virologic response, 
SVR12, [HCV ribonucleic acid (RNA), < lower limit of quantification (LLOQ), 12 weeks following 
therapy] and the percentage of subjects achieving SVR24 [HCV RNA < LLOQ, 24 weeks following 
therapy] (SVR24 for China only) following 12 weeks of treatment with co-formulated ABT-450, ritonavir 
and ABT-267 (ABT-450/r/ABT-267) and ABT-333 coadministered with ribavirin to the historical SVR 
rate of telaprevir plus pegIFN and RBV therapy in HCV genotype 1b-infected cirrhotic adults.  
The secondary objectives of this study are to demonstrate the effect of the DAA combination regimen on 
HCV RNA levels during and after treatment as measured by on-treatment virologic failure and 
post-treatment relapse, respectively.
Investigator:  Multicenter trial:  Investigator information is on file at AbbVie.
Study Sites:  Approximately 18 sites.
Study Population:  Treatment-naïve and previous IFN (alpha, beta or pegIFN) with RBV therapy 
treatment-experienced HCV genotype 1b Chinese, Korean, and Taiwanese adults with compensated 
cirrhosis, aged 18 to 70 years of age, inclusive.
Number of Subjects to be Enrolled:  Approximately 100 subjects; 60 from China, 20 from South Korea 
and 20 from Taiwan.
Methodology:  
This is a Phase 3, open-label, multicenter study evaluating the efficacy and safety of ABT 450/r/ 
ABT-267 and ABT-333 coadministered with ribavirin for 12 weeks in HCV genotype 1b, 
treatment-naïve and IFN (alpha, beta or pegIFN) plus RBV treatment-experienced Asian adults with 
compensated cirrhosis.
Treatment will consist of:  ABT-450/r/ABT-267 150/100/25 mg once daily (QD) + ABT-333 250 mg 
twice daily (BID) + RBV* for 12 weeks.

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
3
Methodology (Continued):
*
RBV will be administered weight-based 1000 – 1200 mg divided to twice daily.
Subjects meeting the eligibility criteria will be enrolled and begin the 12-week treatment period.  
Approximately 100 subjects are will be enrolled.  A minimum of 35 treatment-naïve and 
35 treatment-experienced subjects will be enrolled.
The treatment-experienced subjects are defined as follows: 
!
Non-responder:  Received at least 12 weeks of IFN (alpha, beta or pegIFN) with RBV therapy 
for the treatment of HCV and failed to achieve undetectable HCV RNA (HCV RNA < LLOD) at 
the end of treatment, or 
!
Relapser:  Received IFN (alpha, beta or pegIFN) with RBV therapy for the treatment of HCV 
and was undetectable at or after the end of treatment, but subsequently had detectable HCV 
RNA within 24 weeks of treatment follow-up; or
!
IFN (alpha, beta or pegIFN) with RBV therapy Intolerant:  treatment of HCV was discontinued 
during the treatment period due to intolerance to any of the components of the IFN based 
therapy.
This study will consist of a Treatment Period and a Post-Treatment (PT) Period.  All subjects dosed with 
study drug who complete or prematurely discontinue study drug will be followed for 48 weeks in the 
Post-Treatment Period, to monitor safety, HCV RNA level, the emergence and persistence of viral 
variants and assessment of patient reported outcomes (PROs). 
Visits will occur during the treatment period at Day 1, Weeks 1, 2, 4, 6, 8, 10, and 12 and Post-Treatment 
Weeks 2, 4, 8, 12, 24, 36, and 48 for all subjects on study.
The safety data will be reviewed by the sponsor, as this is an open-label study, and by an independent 
Data Monitoring Committee (DMC) during the Treatment Period of the study.
Virologic Failure Criteria – The following criteria will be considered evidence of virologic failure.  
!
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;
!
Failure to achieve HCV RNA < LLOQ by Week 6; or
!
Confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) 
at any point after HCV RNA < LLOQ during treatment.
Confirmatory testing should be completed as soon as possible.  If any of the above criteria are met for a 
subject in the Treatment Period, study drug will be discontinued.
The Sponsor will evaluate efficacy throughout the Treatment and Post-Treatment Periods in this 
open-label study.
Diagnosis and Main Criteria for Inclusion/Exclusion:  
Main Inclusion:  
1.
Male or female of Chinese, South Korean, and Taiwanese descent with full Chinese, South Korean, 
and Taiwanese parentage between the ages of 18 and 70 years, inclusive, at the time of Screening.
2.
Chronic HCV-infection prior to study enrollment.  Chronic HCV-infection is defined as one of the 
following:

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
4
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):  
Main Inclusion (Continued):
!
Positive for anti-HCV antibody (Ab) or HCV RNA > 1000 IU/mL at least 6 months before 
Screening, and positive for HCV RNA and anti-HCV Ab at the time of Screening; or 
!
Positive for HCV RNA > 1000 IU/mL at the time of Screening with a liver biopsy consistent 
with chronic HCV-infection (or a liver biopsy performed prior to enrollment with evidence of 
chronic hepatitis C disease).
3.
Screening laboratory result indicating HCV genotype 1b-infection.
4.
Compensated cirrhosis defined as a Child-Pugh Score of ≤ 6 at Screening.
5.
Per local standard practice, documentation of cirrhosis by one of the following methods:  
!
Diagnosis on previous liver biopsy or liver biopsy conducted during screening e.g., Metavir 
Score of > 3 (including 3/4 or 3 – 4), Ishak score of > 4 or,
!
FibroScan score ≥ 14.6 kPa within 6 months of Screening or during the Screening Period.
Main Exclusion:  
1.
HCV genotype performed during screening indicating unable to genotype or infection with any other 
HCV genotype.
2.
Positive test result at Screening for Hepatitis B surface antigen (HBsAg), or HBV DNA > LLOQ if 
HBsAg negative, or anti-Human Immunodeficiency virus antibody (HIV Ab).
3.
Use of known strong inducers of cytochrome P450 3A (CYP3A) or strong inhibitors of CYP2C8 
within 2 weeks or within 10 half-lives, whichever is longer, of the respective medication/supplement 
prior to study drug administration.
4.
Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver 
decompensation including ascites (noted on physical exam), variceal bleeding, or hepatic 
encephalopathy.
5.
Serum Alpha-Fetoprotein (sAFP) > 100 ng/mL at Screening.
6.
Confirmed presence of hepatocellular carcinoma (HCC) indicated on imaging techniques such as 
computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months prior to 
Screening or on an ultrasound performed at Screening (a positive ultrasound result should be 
confirmed with CT scan or MRI.)
7.
Any primary 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
!
Drug-related liver disease
Steatosis and steatohepatitis on a liver biopsy coincident with HCV-related changes would not 
be considered exclusionary unless the steatohepatitis is considered to be the primary cause of the 
liver disease.

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
5
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):  
Main Exclusion (Continued):  
8.
Screening laboratory analyses showing any of the following abnormal laboratory results:
!
Alanine aminotransferase (ALT) > 7 × upper limit of normal (ULN)
!
Aspartate aminotransferase (AST) > 7 × ULN
!
Estimated Glomerular filtration rate adjusted for the Asian population (eGFR) 
< 50 mL/min/1.73m2 as estimated by the C-MDRD method, modified for the Asian population, 
according to the following formula:  eGFR = 175 × (Serum Creatinine) –1 234 × (Age) –0 179 × 
(0.79 if Female)
!
Albumin < 2.8 g/dL
!
International normalized ratio (INR) > 2.3.  Subjects with a known inherited blood disorder and 
INR > 2.3 may be enrolled with permission of the AbbVie Study Designated Physician
!
Hemoglobin < LLN
!
Platelets < 60,000 cells per mm3
!
Absolute neutrophil count (ANC) < 1200 cells/μL 
!
Total bilirubin ≥ 3.0 mg/dL
Investigational Products:
!
ABT-450/Ritonavir/ABT-267 75 mg/50 mg/12.5 mg tablet
!
ABT-333 250 mg tablet
!
Ribavirin 200 mg tablet (for Korea and Taiwan)
!
Ribavirin 100 mg tablet (for China)
Doses:
!
ABT-450/Ritonavir/ABT-267 150/100/25 mg QD
!
ABT-333 250 mg BID
!
Ribavirin weight-based dosing 1000 to 1200 mg divided twice daily
Mode of Administration:
Oral
Duration of Treatment:  
Subjects will receive ABT-450/Ritonavir/ABT-267 and ABT-333 co-administered with RBV for 
12 weeks.
Criteria for Evaluation:
Efficacy:  
Plasma HCV RNA (IU/mL) will be assessed at each Treatment and Post-Treatment Visit.
Patient Reported Outcomes (PROs):
The change in general and disease-specific Health Related Quality of Life (HRQoL) will be assessed 
using the SF-36v2 (Short Form 36-Version 2) and HCV Patient Reported Outcomes (HCVPRO) 
instruments, respectively.  Health State Utility will be measured using the EuroQol-5 Dimensions-5 
Level (EQ-5D-5L).

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
6
Criteria for Evaluation (Continued):  
Resistance:  
For subjects receiving study drugs who experience virologic failure, the amino acid variants at signature 
resistance-associated amino acid positions by population nucleotide sequencing at baseline compared to 
the prototypic reference sequence, the amino acid variants by population nucleotide sequencing at 
available post-baseline time points compared to baseline, and the amino acid variants at signature 
resistance-associated positions by population nucleotide sequencing compared to the prototypic reference 
sequence will be tabulated and summarized.  In addition, a listing of amino acid variants that emerge in 
isolates from at least 2 subjects will be provided, and the persistence of viral resistance-associated amino 
acid variants will be summarized.
Pharmacokinetic:  
Plasma concentrations for ABT-450, possible ABT-450 metabolites, ritonavir, ABT-267, ABT-267 
metabolites ABT-333, ABT-333 M1 metabolite, other possible ABT-333 metabolites and RBV will be 
determined at each study visit up to the end of treatment.
Values for the pharmacokinetic parameters of ABT-450, ABT-267, ritonavir, ABT-333, ABT-333 M1 
metabolite, and ribavirin including the Cmax, Tmax, Ctrough, and AUC will be determined by 
non-compartmental methods using data from subjects who participate in intensive pharmacokinetic 
sampling in the study.  Additional parameters or summaries may be determined if useful in the 
interpretation of the data.
Safety:  
Safety and tolerability will be assessed by monitoring adverse events, physical examinations, clinical 
laboratory tests, 12-Lead ECGs and vital signs.
Statistical Methods:  
Efficacy:  
For South Korea and Taiwan, the primary efficacy endpoint is:
A1. SVR12:  Superiority to the historical SVR rate for telaprevir plus pegIFN and RBV therapy –
lower confidence bound of 2-sided 95% confidence interval (LCB) for the percentage of 
subjects with SVR12 must exceed 67% to achieve superiority. 
For China, the primary efficacy endpoints are as follows.  In order to control the Type 1 error rate of 
0.05, a fixed-sequence testing procedure will be used to proceed through the primary endpoints in the 
order numbered below. 
B1.
SVR12:  Superiority to the historical SVR rate for telaprevir plus pegIFN and RBV therapy –
lower confidence bound of 2-sided 95% confidence interval (LCB) for the percentage of 
subjects with SVR12 must exceed 67% to achieve superiority.
B2.
SVR24:  Superiority to the historical SVR rate for telaprevir plus pegIFN and RBV therapy –
lower confidence bound of 2-sided 95% confidence interval (LCB) for the percentage of 
subjects with SVR24 must exceed 67% to achieve superiority.
To test each hypothesis that the percentage of treatment-naïve and IFN based treatment experienced HCV 
genotype 1b-infected Asian subjects with compensated cirrhosis treated with ABT 450/r/ABT 267 + 
ABT-333 + RBV for 12 weeks who achieve SVR12/SVR24 is superior to a clinically meaningful threshold 
based on historical SVR rates for the HCV genotype 1b-infected population treated with telaprevir plus 
pegIFN and RBV.

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
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Statistical Methods (Continued):  
Efficacy (Continued):  
The percentage of subjects with SVR12/SVR24 will be calculated with a 2-sided 95% CI using Wilson 
score method, and the LCB will be compared to the defined threshold.  The LCB of the 95% CI of 
SVR12/SVR24 must be greater than 67% in order for the regimen to be considered superior.
The secondary endpoints are:
!
The percentage of subjects with on treatment virologic failure (defined as confirmed HCV RNA 
≥ the lower limit of quantitation (LLOQ) (defined as 2 consecutive HCV RNA measurements 
≥LLOQ) at any point during treatment after HCV RNA < LLOQ, confirmed increase from 
nadir in HCV RNA (two consecutive HCV RNA measurements > 1 log10 IU/mL above nadir) at 
any time point during treatment or HCV RNA ≥ LLOQ persistently during treatment with at 
least 6 weeks (≥ 36 days) of treatment
!
The percentage of subjects with  relapse by Post-Treatment Week 12 (defined as confirmed 
HCV RNA ≥ LLOQ between end of treatment and 12 weeks after the last dose of study drugs 
among subjects completing treatment and with HCV RNA < LLOQ at the end of treatment) and,
!
The percentage of subjects with relapse by Post-Treatment Week 24 (defined as confirmed HCV 
RNA ≥ LLOQ between end of treatment and 24 weeks after the last dose of study drugs among 
subjects completing treatment and with HCV RNA < LLOQ at the end of treatment).
The percentages (with 2-sided 95% confidence intervals using the Wilson Score method to the binomial 
distribution) of the subjects with on treatment virologic failure and post-treatment relapse will be 
calculated and summarized.
Resistance:
The following resistance information will be provided for subjects receiving active study drugs who 
experience virologic failure (who have HCV RNA ≥ 1000 IU/mL):  1) the amino acid variants at baseline 
at signature resistance-associated positions identified by population nucleotide sequencing and 
comparison to the prototypic reference sequence, 2) the amino acid variants in available post-baseline 
samples identified by population nucleotide sequencing and comparison to the baseline sequence, and 
3) the amino acid variants in available post-baseline samples at signature resistance-associated positions 
identified by population nucleotide sequencing and comparison to the prototypic reference sequence.  
In addition, a listing of amino acid variants that emerge in isolates from at least 2 subjects will be 
provided, and the persistence of viral resistance-associated amino acid variants will be summarized.
Pharmacokinetic:  
Plasma concentrations for ABT-450, possible ABT-450 metabolites, ritonavir, ABT-267, ABT-267 
metabolites, ABT-333, ABT-333 M1 metabolite, other possible ABT-333 metabolites and RBV will be 
tabulated and summarized at each study visit through the end of the Treatment Period.
Values for the pharmacokinetic parameters of ABT-450, ABT-267, ritonavir, ABT-333, ABT-333 M1 
metabolite, and ribavirin including the Cmax, Tmax, Ctrough, and AUC will be summarized and tabulated.

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
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Statistical Methods (Continued):
Safety:  
The number and percentage of subjects reporting treatment-emergent adverse events will be tabulated by 
Medical Dictionary for Regulatory Activities (MedDRA) system organ class and preferred term.  The 
number and percentage of subjects with serious treatment-emergent adverse events and the number and 
percentage of subjects with treatment-emergent adverse events leading to study drug discontinuation will 
also be provided.
Tabulations will also be provided in which the number of subjects reporting an adverse event (MedDRA 
preferred term) is presented by grading and relationship to study drug(s). 
Change from baseline in laboratory tests and vital sign measurements to each time point of collection will 
be summarized descriptively.  Laboratory test and vital sign values that are potentially clinically 
significant, according to predefined criteria, will be identified and the number and percentage of subjects 
with potentially clinically significant values during treatment will be calculated.

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
9
1.2
List of Abbreviations and Definition of Terms
Abbreviations
Ab
Antibody
ABT-450/r/ABT-267
ABT-450 co-formulated with ritonavir and ABT-267
AE
Adverse event
ALT
Alanine aminotransferase
ANC
Absolute neutrophil count
aPTT
Activated partial thromboplastin time 
AST
Aspartate aminotransferase
AUC
Area Under the Concentration Curve
BID
Twice Daily
BMI
Body mass index
BOC
Boceprevir
BUN
Blood urea nitrogen
CL/F
Apparent Oral Clearance
CR/CL
Creatinine clearance
CRF
Case report form
CT
Computed Tomography
CYP2C8
Cytochrome P450 2C8
CYP3A
Cytochrome P450 3A
DAA
Direct-acting antiviral agent
D/C
Discontinuation
DMC
Data Monitoring Committee
DNA
Deoxyribonucleic acid
EC
Ethics Committee
ECG
Electrocardiogram
eCRF
Electronic case report form
EDC
Electronic data capture
EDTA
Edetic acid (ethylenediaminetetraacetic acid)
eGFR
Estimated Glomerular Filtration Rate
EOT
End of treatment
EOTR
End of treatment response
EU
European Union

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
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EQ-5D-5L
EuroQol 5 Dimensions 5 Levels Health State Instrument 
GCP
Good Clinical Practice
GCSF
granulocyte colony stimulating factor 
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
HCVPRO
Hepatitis C Virus Patient Reported Outcomes Instrument
Hemoglobin A1c
Glycated hemoglobin
HIV
Human immunodeficiency virus
HIV Ab
Human immunodeficiency virus antibody
HRQoL
Health Related Quality of Life
ICH
International Conference on Harmonization
IEC
Independent ethics committee
IFN
Interferon
IL28B
Interleukin 28B
IMP
Investigational Medical Product
INR
International normalized ratio
IP-10
Interferon gamma-induced protein 10
IRB
Institutional Review Board
IRT
Interactive Response Technology
ITT
Intent to Treat
IU
International units
IUD
Intrauterine device
LLN
Lower limit of normal
LLOD
Lower limit of detection
LLOQ
Lower limit of quantification
MCS
Mental Component Summary
MedDRA
Medical Dictionary for Regulatory Activities
MID
Minimally Important Difference
MRI
Magnetic Resonance Imaging

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
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NS3A
Nonstructural viral protein 3A
NS4A
Nonstructural viral protein 4A
NS5A
Nonstructural viral protein 5A
NS5B
Nonstructural viral protein 5B
PCR
Polymerase Chain Reaction
PCS
Physical Component Summary
PegIFN
Pegylated-interferon alfa-2a or alfa-2b
PK
Pharmacokinetic
POR
Proof of Receipt
PRO
Patient Reported Outcomes
PT
Post-Treatment
QD
Once daily
QTc
QT interval corrected for heart rate
QTcF
QTc using Fridericia's correction formula
RBC
Red blood cells
RBV
Ribavirin
RNA
Ribonucleic acid
ROC
Receiver Operating Characteristic
RT-PCR
Reverse transcriptase PCR
RVR
Rapid virologic response
SAE
Serious adverse event
sAFP
Serum Alpha-Fetoprotein
SAS
Statistical Analysis System
SD
Standard Deviation
SF-36 V2
Short Form 36-Version 2
SGOT
Serum glutamic oxaloacetic transaminase
SGPT
Serum glutamic pyruvic transaminase
SOC
System Organ Class
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
TP
Treatment Period

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M14-491 Protocol
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TVR
Telaprevir
ULN
Upper limit of normal
VAS
Visual analogue scale
V/F
Apparent Volume of distribution
WBC
White blood cells
Definition of Terms
Non-responder
Received at least 12 weeks of IFN (alpha, bet or pegIFN) with RBV 
therapy for the treatment of HCV and failed to achieve undetectable 
HCV RNA (HCV RNA < LLOD) at the end of treatment
Relapser
Received IFN-based therapy (IFN [alpha, beta or pegIFN] with RBV 
therapy) for the treatment of HCV and was undetectable at or after the 
end of treatment, but subsequently had detectable HCV RNA within 
24 weeks of treatment follow-up
IFN-based therapy (IFN 
[alpha, beta, or pegIFN] with 
RBV therapy) Intolerant
Treatment of HCV was discontinued during the treatment period due to 
intolerance to any of the components of the IFN RBV therapy.
Study Drug
ABT-450/r/ABT-267, ABT-333, RBV
Study Day 1
First day of study drug dosing 
Treatment Period
Baseline/Day 1 through the day of last dose of study drug
Post-Treatment Period
Day after the last dose of study drug through Post-Treatment Week 48 or 
the day of Post-Treatment Discontinuation

ABT-450/r/ABT-267, ABT-333
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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..........................................9
2.0
Table of Contents...................................................................13
3.0
Introduction ...........................................................................18
3.1
Differences Statement..............................................................................35
3.2
Benefits and Risks....................................................................................35
4.0
Study Objectives....................................................................36
4.1
Primary Objectives...................................................................................36
4.2
Secondary Objectives...............................................................................36
5.0
Investigational Plan...............................................................37
5.1
Overall Study Design and Plan:  Description ..........................................37
5.1.1
Screening..................................................................................................38
5.1.1.1
Rescreening..............................................................................................38
5.1.2
Treatment Period (TP) .............................................................................39
5.1.3
Post-Treatment (PT) Period .....................................................................41
5.2
Selection of Study Population..................................................................42
5.2.1
Inclusion Criteria .....................................................................................42
5.2.2
Exclusion Criteria ....................................................................................45
5.2.3
Prior and Concomitant Therapy...............................................................48
5.2.3.1
Prior HCV Therapy..................................................................................49
5.2.3.2
Concomitant Therapy...............................................................................49
5.2.3.3
Prohibited Therapy...................................................................................50
5.3
Efficacy, Pharmacokinetic, Optional Pharmacogenetic and Safety 
Assessments/Variables.............................................................................51
5.3.1
Efficacy and Safety Measurements Assessed and Flow Chart ................51
5.3.1.1
Study Procedures .....................................................................................58
5.3.1.2
Meals and Dietary Requirements.............................................................70
5.3.1.3
Blood Samples for Pharmacogenetic Analysis ........................................70
5.3.2
Drug Concentration Measurements .........................................................71
5.3.2.1
Collection of Samples for Analysis .........................................................71

ABT-450/r/ABT-267, ABT-333
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5.3.2.2
Handling/Processing of Samples .............................................................71
5.3.2.3
Disposition of Samples ............................................................................71
5.3.2.4
Measurement Methods.............................................................................72
5.3.3
Efficacy Variables....................................................................................72
5.3.3.1
Primary Variable......................................................................................72
5.3.3.2
Secondary Variable(s)..............................................................................72
5.3.3.3
Resistance Variables ................................................................................72
5.3.4
Safety Variables .......................................................................................73
5.3.5
Pharmacokinetic Variables ......................................................................73
5.3.6
Pharmacogenetic Variables......................................................................73
5.4
Removal of Subjects from Therapy or Assessment .................................74
5.4.1
Discontinuation of Individual Subjects....................................................74
5.4.1.1
Virologic Failure Criteria.........................................................................75
5.4.2
Discontinuation of Entire Study...............................................................76
5.5
Treatments................................................................................................76
5.5.1
Treatments Administered.........................................................................76
5.5.2
Identity of Investigational Product...........................................................78
5.5.2.1
Packaging and Labeling...........................................................................78
5.5.2.2
Storage and Disposition of Study Drugs..................................................79
5.5.3
Method of Assigning Subjects to Treatment ...........................................79
5.5.4
Selection and Timing of Dose for Each Subject......................................79
5.5.5
Blinding....................................................................................................80
5.5.5.1
Data Monitoring Committee ....................................................................80
5.5.6
Treatment Compliance.............................................................................80
5.5.7
Drug Accountability.................................................................................82
5.6
Discussion and Justification of Study Design..........................................83
5.6.1
Discussion of Study Design and Choice of Control Groups....................83
5.6.2
Appropriateness of Measurements...........................................................83
5.6.3
Justification of Primary Endpoint Success Criteria .................................83
5.6.4
Suitability of Subject Population .............................................................87
5.6.5
Selection of Doses in the Study ...............................................................87
6.0
Adverse Events.......................................................................92
6.1
Definitions................................................................................................92

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6.1.1
Adverse Event..........................................................................................92
6.1.2
Serious Adverse Events ...........................................................................93
6.2
Adverse Event Severity............................................................................94
6.3
Relationship to Study Drug......................................................................95
6.4
Adverse Event Collection Period.............................................................95
6.5
Adverse Event Reporting.........................................................................96
6.6
Pregnancy.................................................................................................98
6.7
Toxicity Management ..............................................................................99
6.7.1
Grades 1 or 2 Laboratory Abnormalities and Mild or Moderate 
Adverse Events ........................................................................................99
6.7.2
Grades 3 or 4 Laboratory Abnormalities and Severe or Serious 
Adverse Events ......................................................................................100
6.7.3
Management of Hemoglobin Decreases ................................................101
6.7.4
Management of Transaminase Elevations .............................................102
6.7.5
Management of eGFR Decreases...........................................................103
7.0
Protocol Deviations..............................................................104
8.0
Statistical Methods and Determination of Sample 
Size ........................................................................................105
8.1
Statistical and Analytical Plans..............................................................105
8.1.1
Demographics ........................................................................................107
8.1.2
Efficacy..................................................................................................107
8.1.2.1
Primary Efficacy Endpoints...................................................................108
8.1.2.2
Secondary Efficacy Endpoints...............................................................109
8.1.2.3
Sensitivity Analyses for the Primary Endpoint......................................110
8.1.2.4
Subgroup Analysis .................................................................................111
8.1.2.5
Additional Efficacy Endpoints...............................................................112
8.1.3
Patient Reported Outcomes....................................................................113
8.1.4
Resistance Analyses...............................................................................114
8.1.5
Safety .....................................................................................................116
8.1.5.1
Adverse Events ......................................................................................116
8.1.5.2
Clinical Laboratory Data........................................................................116
8.1.5.3
Vital Signs Data .....................................................................................117
8.1.6
Pharmacokinetic and Exposure-Response Analyses .............................117

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8.2
Determination of Sample Size ...............................................................119
9.0
Ethics.....................................................................................120
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) ...........................................................................................120
9.2
Ethical Conduct of the Study .................................................................121
9.3
Subject Information and Consent...........................................................121
10.0
Source Documents and Case Report Form 
Completion ...........................................................................121
10.1
Source Documents .................................................................................121
10.2
Case Report Forms.................................................................................122
11.0
Data Quality Assurance......................................................123
12.0
Use of Information...............................................................123
13.0
Completion of the Study .....................................................123
14.0
Investigator's Agreement....................................................125
15.0
References.............................................................................126
List of Tables
Table 1.
SVR12 Rates (Intent-to-Treat, Missing = Failure) in Phase 3 by 
Subpopulation of Subtype, Prior Treatment History, and Presence 
or Absence of Cirrhosis ...........................................................................27
Table 2.
Overview of Treatment-Emergent Adverse Events (AE)........................32
Table 3.
Treatment-Emergent Adverse Events with ≥ 10% Frequency in at 
Least One Arm of the Analysis and Rates of Key Post-Baseline 
Lab Abnormalities ...................................................................................33
Table 4.
Medications Contraindicated for Use with the Study Drug 
Regimen ...................................................................................................47
Table 5.
Study Activities – Treatment Period (TP)................................................52
Table 6.
Study Activities – Post-Treatment (PT) Period .......................................56
Table 7.
Clinical Laboratory Tests.........................................................................61
Table 8.
Child-Pugh Classification of Severity of Cirrhosis .................................65
Table 9.
Identity of Investigational Products .........................................................78
Table 10.
Estimated SVR Rates for Telaprevir Plus PegIFN and RBV in 
Cirrhotic Subjects.....................................................................................84

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Table 11.
SVR Rates for Telaprevir Plus pegIFN and RBV Therapy in 
Treatment-Naïve Subjects by Subgenotype.............................................85
Table 12.
Estimated SVR Rates for Telaprevir-Based Therapy in Treatment 
Experienced Subjects by Subgenoytpe ....................................................86
Table 13.
Ribavirin Dose Modification Guidelines in Management of 
Hemoglobin Decreases ..........................................................................102
Table 14.
Management of Confirmed ALT Elevations .........................................103
Table 15.
Dosing of RBV in Subjects with Renal Impairment..............................104
List of Figures
Figure 1.
Worldwide Distribution of HCV Genotypes ...........................................19
Figure 2.
HCV Genotypes Distributions in China ..................................................21
Figure 3.
Adverse Event Collection ........................................................................96
List of Appendices
Appendix A.
Responsibilities of the Clinical Investigator ..........................................133
Appendix B.
List of Protocol Signatories....................................................................135
Appendix C.
Clinical Toxicity Grades ........................................................................136

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3.0
Introduction
Hepatitis C viral (HCV) infection is a global health problem, with over 170 million 
individuals chronically infected worldwide.1  Cirrhosis is a common sequelae of HCV 
infection occurring in approximately 20% of patients.2  Complications of cirrhosis include 
hepatic decompensation (ascites, encephalopathy, variceal hemorrhage, hepatorenal 
syndrome, or hepatic synthetic dysfunction) and hepatocellular carcinoma ensue at a rate 
of about 3% per year.3-6  Without liver transplantation, decompensated cirrhosis leads to 
death in 50% to 72% of patients after 5 years.7  As a result of the high prevalence of HCV 
infection and resultant complications, HCV is the leading indication for liver
transplantation in the United States and the world as a whole.8
World Geographical Distribution of HCV Genotypes
HCV can be classified into 6 major genotypes based on sequence divergence of 30%.  In 
North America and Western Europe, HCV genotype 1 (subgenotypes 1a and 1b) is the 
most prevalent, causing > 75% of all infections in some countries (Figure 1).9  In Asia, 
genotypes 1 (subgenotype 1b), 2, 3, and 6 are the most common types of HCV 
infections.10

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Figure 1.
Worldwide Distribution of HCV Genotypes
Epidemiology of HCV in China
Chronic HCV infection is recognized as an important cause of chronic hepatitis, cirrhosis, 
and hepatocellular carcinoma in China.11  Epidemiological studies in the mid-1990s 
reported a national prevalence of 3.2%,12 but other reports suggested a prevalence ranging 
from 0.29% to 9.6%.13
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%).12  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.12  A study of individuals > 55 years old in the rural 

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Henan province found a prevalence of 9.6%,14 while Liu et al., documented a prevalence 
of 0.9% in persons 25 to 65 years old in Anyang.15
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.16  A recent study reported that 25 million Chinese were infected with HCV 
chronically and advance liver diseases were frequently detected.17  Among human 
immunodeficiency virus (HIV)-positive Chinese patients, it is estimated that 60% to 90% 
are coinfected with HCV.16  Among patients with chronic hepatitis B, it is estimated that 
11% to 15% are coinfected with HCV.18,19  In addition, 50% of the patients receiving
dialysis in China are reported to be infected with HCV.16  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 
genotypes (Figure 2).  HCV subgenotype 1b is the most common genotype in China with 
a prevalence of 66%,20 but it has been reported to be as high as 90% in some areas of 
southern China.16  HCV genotype 2 is the second most common genotype, with a 
prevalence of 14%,20 increasing gradually from southern to northern China (Figure 2).16  
Other HCV genotypes include genotype 6, which is detected in approximately 10% of 
cases, especially in the south region of China; and genotype 3 which is reported in 
approximately 4.3% of the cases in China (Study M14-491).20  Majority of these chronic 
HCV-infected patients in China have IL28B CC genotype.17

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Figure 2.
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 genotypes in the general 
population countrywide are HCV subgenotype 1b and genotype 2.  HCV genotypes 3 and 
6 are detected in the southern region of China, but their frequency is reported to be 
increasing in recent years.
Epidemiology of HCV in South Korea
South Korea is a relatively low prevalence area for HCV, while known as a high 
prevalence area for HBV infection.  For this reason less attention has been given to HCV 
related liver diseases and few studies have been focused in the analyses of clinical and 
epidemiological characteristics of HCV-infection in Korea.21  A recent nationwide 
seroprevalence survey showed that the age, sex, and area-adjusted prevalence of 

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anti-HCV antibody in Korean adults in 2009 was 0.78%,22 whereas the nationwide 
seroprevalence of HBsAg in persons aged > 10 years in 2009 was 3.2% according to the 
results of the National Health and Nutrition Examination Survey.23  In Korea, chronic 
liver disease is caused by HCV in approximately 10 – 15% of patients and by HBV in 
65% to 75% of patients.  Few studies have reported the prevalent HCV genotypes in 
Korea.24,25  An assessment of anti-HCV antibodies detection performed in blood donor
revealed that genotype 1b and 2a/c are dominant in Korea and genotypes 4 and 6 were 
identified in a small proportion of the tested population.26
However, after the launch of new therapeutics such as DAA in 2011, the importance of 
HCV infection as a cause of liver disease has been increasingly recognized in 
South Korea.
A recent evaluation of a large multicenter cohort of 1,173 anti-HCV antibody positive 
adult patients shown that the mean age of the HCV patients is around 55 years old, and 
half of the infected people were women.27  The large majority presented with chronic 
hepatitis (66%) as the clinical diagnosis, followed by cirrhosis of the liver (15%), and 
HCC (10%).  In patients with HCC, cirrhosis was present in 87% of the patients.  The 
proportion of patients with Child class B or C decompensated liver cirrhosis was 8.1%.  
Comparison of clinical and epidemiological characteristics between patients with 
subgenotype 1b and those with non-1b genotypes (genotypes 2, 3, 4, and 6) showed that 
advanced liver disease such as cirrhosis of the liver or HCC was more prevalent in the 
subgenotype 1b group than in non-1b genotypes (29.4% versus 22.5%, respectively; 
P = 0.02).27
Antiviral therapy was initiated in 43% of patients, which is a higher proportion than that 
reported in studies conducted in the US and Europe.27-29  The patients who had received
antiviral therapy included those with chronic hepatitis (73.2%), cirrhosis of the liver 
(15.2%), HCC (8.0%), and acute hepatitis (3.6%).  Currently, most HCV patients were 
treated with a combination of pegIFN/RBV (65%), and the remainder were treated with
conventional interferon (15%), or a combination of conventional interferon alpha and 
RBV (17%), or pegIFN alone (3%).  The duration of treatment is 48 weeks.27

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Epidemiology of HCV in Taiwan
Similar to the case in China, the frequency of HCV infection in Taiwan varied by 
geographical region within the country, age, and population groups.  There is a wide 
geographic variation in HCV seroprevalence in Taiwan.  The seroprevalence of anti-HCV 
varied from 1.7% to 57.9% in different townships in different studies reported over the 
period from 1992 to 2003.  In the HCV hyperendemic areas, transmission may partly be 
related to the iatrogenic routes.  People acquired HCV infection when they received 
medical or dental procedures, blood transfusion, medical injections, hemodialysis, 
acupuncture, and similar procedures.30,31
In Taiwan, the prevalence of HCV is estimated at 4% to 10% in the general 
population,30,32 however increases dramatically in some subpopulations.  The prevalence 
of HCV goes up to 30% to 56% in HIV-positive patients in studies that included different 
proportions of injecting drug users (IDUs)31,33,34 and up to 90% in hemophilic patients.35  
After an outbreak of HIV infection occurred among IDUs in Taiwan between 2003 and 
2007, HCV seropositivity was 95% to 97% among HIV-positive IDUs.36  A 
seroprevalence of anti-HCV positivity also increases gradually with age, from 4.3% in 
subjects with 60 to 69 years old, 6.3% in subjects with 70 to 79 years old, and 8.8% in 
subjects with > 80 years old group.30,37
In regards to HCV subtype distribution, a difference is observed between the north and 
south regions.  The most common subtype in the south are 1b and genotype 2, while 1b 
alone is the most common genotype observed in the north regions.38
HCV infection is highly associated to mortality due progressive liver diseases (liver 
cancer, and cirrhosis).  However, chronic hepatitis C has been also associated with an 
increased mortality from extra-hepatic diseases, including circulatory diseases renal 
diseases, and extra-hepatic cancers.39  Currently, the local standard of care treatment has 
been pegINF/RBV for 24 – 48 weeks pending on patients' clinical and virological 
characteristics.

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In summary, the prevalence of HCV in China, South Korea, and Taiwan varies depending 
on the research and region from less that 1% to 10%.  Most patients with Chronic HCV 
are middle-age.  Subgenotype 1b is the predominant serotype detected in more than 60% 
of the patients followed by genotype 2.  The current standard of care (SoC) for the 
treatment of chronic HCV infection in these countries is pegIFN combined with RBV.  
SVR rates vary from 50% to 70% among subgenotype 1b, however the pegIFN-RBV 
regimen carries a well described burden of toxicity (e.g., severe anemia, and depression) 
and cumbersome weekly injections.  Therefore, the treatment for chronic HCV in Asian 
could be improved by a regimen that requires shorter treatment duration, provides higher 
SVR rates and a convenient all oral PegIFN-free regimen.
Treatment in HCV Patients with Cirrhosis
Patients with compensated cirrhosis who receive treatment and achieve an SVR (sustained 
virologic response) essentially eliminate their subsequent risk of decompensation, may 
achieve histologic regression, and decrease their risk of hepatocellular carcinoma by 
two-thirds.40-42
While the introduction of the protease inhibitors, telaprevir (TVR) or boceprevir (BOC), 
have increased SVR rates, current treatment is less than optimal as the protease inhibitors 
must be used in combination with pegIFN/RBV, two agents with considerable treatment 
limiting toxicities and treatment may extend for up to 48 weeks.  Furthermore, regardless 
of a patient's treatment history, treatment of HCV infected patients with underlying 
cirrhosis with either telaprevir or boceprevir in combination with pegIFN/RBV results in 
lower rates of SVR when compared to overall response rates:  treatment-naïve patients 
treated with TVR (62% response rate in cirrhotics versus 79% overall response rate in the
ADVANCE study),43,44 prior partial responders treated with TVR (34% response rate in 
cirrhotics versus 59% overall response rate in the REALIZE study),45,46 prior null 
responders treated with TVR (14% response rate in cirrhotics versus 32% overall response 
rate in the REALIZE study),45,46 treatment-naïve patients treated with BOC (31% to 42% 
response rate in cirrhotics versus 62% to 66% overall response in the SPRINT-2 study),47

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and treatment-experienced patients treated with BOC (35% response in cirrhotics versus 
59% overall response rate in the RESPOND-2 study).47
Combinations of multiple DAAs (direct-acting antiviral agent) have the potential of 
further improving HCV treatment by increasing SVR rates, eliminating interferon (IFN), 
increasing the safety and tolerability of treatment, shortening duration of therapy and 
simplifying the treatment algorithm.  In addition, wider application of DAA therapy and 
better responses with combination DAA regimens could significantly reduce the public 
health burden of this disease.
Promising short-term antiviral efficacy results have been reported from IFN-free 
combinations (either with or without RBV) of a protease inhibitor with a nucleoside 
polymerase inhibitor,48 a non-nucleoside polymerase inhibitor,49 or a nonstructural protein 
5A (NS5A) inhibitor.50  Twelve-week SVR (SVR12) rates of 36% (4/11) in HCV genotype 
1-infected null responders and 90% (9/10) in HCV genotype 1b-infected null responders 
have been observed in subjects treated with the combination of a protease inhibitor and 
NS5A inhibitor (BMS 650032 and BMS-790052) for 24 weeks.51,52  Additionally, a recent 
descriptive sub-analysis from the SOUND-C2 study, a Phase 2b study evaluating IFN-free 
treatment with BI 201335 and BI 207127 plus RBV, reported SVR12 rates of 54% (20/37) 
in genotype 1, treatment-naive patients with compensated liver cirrhosis, regardless of IL 
28B allele status.53  Recently, preliminary data from ELECTRON Phase 2 study revealed 
that sofobuvir/ledipavir combination with or without ribavirin for 12 weeks delivered 
100% (11/11) and 70% (7/10) SVR12 in cirrhotic genotype 1 HCV patients respectively.54  
LONESTAR trial also demonstrated 100% (11/11) and 91% (11/11) SVR12 in 
sofobuvir/ledipavir with or without RBV in treatment-experienced cirrhotic HCV 
genotype 1 patients.55
Together, these safety and efficacy data suggest that interferon-free DAA combinations 
may address patient's needs and further advance HCV therapy by increasing SVR rates 
even in difficult-to-treat populations, improving safety and tolerability of treatment, 
reducing duration, and simplifying treatment.

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AbbVie IFN-Free Regimen
AbbVie's IFN-free regimen for the treatment of chronic HCV genotype 1 infection 
includes 3 DAAs targeting different steps in HCV replication.  ABT-450 is a 
nonstructural protein 3/nonstructural protein 4A (NS3/NS4A) protease inhibitor 
coadministered with the pharmacokinetic enhancer, ritonavir (ABT-450/r); ABT-267 is a 
NS5A inhibitor, and ABT-333 is a NS5B non-nucleoside polymerase inhibitor.  The 
3-DAA regimen has been studied with and without ribavirin in over 2,300 patients in 
Phase 3 trials across a variety of patient populations including compensated cirrhosis.  
Based on Phase 3 data, the regimen with or without RBV is safe, well tolerated and 
efficacious in treatment-naïve and treatment-experienced HCV genotype 1-infected 
subjects.  The overall efficacy results (intent-to-treat) from the Phase 3 studies are listed in 
Table 1.

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Table 1.
SVR12 Rates (Intent-to-Treat, Missing = Failure) in Phase 3 by 
Subpopulation of Subtype, Prior Treatment History, and Presence 
or Absence of Cirrhosis
Subpopulation
3-DAA
12 Weeks 
SVR12
3-DAA + RBV
12 Weeks
SVR12
3-DAA + RBV
24 Weeks
SVR12
Genotype 1b non-cirrhotics
     Naïve
99.0
98.0, 99.5
--
     Null
100
93.5, 94.9
--
     Partial
100
96.0, 100
--
     Relapser
100
97.2, 100
--
Genotype 1a non-cirrhotics
     Naïve
90.2
95.3, 97.0
--
     Null
--
95.4
--
     Partial
--
100
--
     Relapser
--
94.0
--
Genotype 1b cirrhotics
     Naïve
--
100
100
     Null
--
100
100
     Partial
--
85.7*
100
     Relapser
--
100
100
Genotype 1a cirrhotics
     Naïve
--
92.2
92.9
     Null
--
80.0
92.9
     Partial
--
100
100
     Relapser
--
93.3
100
*
Based on N = 7; 6/7 achieved SVR.
Phase 3 Placebo-Controlled Studies:  Studies M11-646 and M13-098 
Study M11-646 and Study M13-098 are randomized, placebo-controlled studies to assess 
the safety and efficacy of 12 weeks therapy with 3-DAA + RBV in HCV genotype 
1-infected treatment-naïve (Study M11-646) and prior pegIFN/RBV non-responders 
(Study M13 098) without cirrhosis.  ABT-450/r/ABT-267 with ABT-333 was given for 

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12 weeks of treatment in combination with RBV.  Subjects randomized to the placebo arm 
received placebo for 12 weeks, after which they received open-label ABT-450/r/ABT-267 
with ABT-333 in combination with RBV for 12 week. 
In Study M11-646, treated subjects (N = 631) had a median age of 52 years (range:  18 to 
70); 54.5% of the subjects were male; 5.4% were black and 5.1% were Hispanic or 
Latino; 16.2% had a body mass index (BMI) greater than or equal to 30 kg/m2; 79.1% had 
baseline HCV RNA levels ≥ 800,000 international units (IU)/mL; 8.7% had bridging 
fibrosis (F3); 67.7% had HCV GT1a; 32.3% had HCV GT1b, and 69.3% had IL28B 
non-CC genotype. 
The SVR12 rate for treatment-naïve subjects receiving 3-DAA + RBV for 12 weeks in 
Study M11-646 was 96.2%.  Virologic failure was noted in 7/322 (2.2%) GT1a subjects 
(on-treatment virologic failure:  n = 1; relapse:  n = 6) and 1/151 (0.7%) GT1b subjects 
(relapse).
In Study M13-098, treated subjects (N = 394) had a median age of 54 years (range:  19 to 
71); 57.6% of the subjects were male; 8.1% were black and 6.3% were Hispanic or 
Latino; 19.8% had a BMI greater than or equal to 30 kg/m2; 87.1% had baseline HCV 
RNA levels ≥ 800,000 IU/mL; 14.5% had bridging fibrosis; 58.4% had HCV GT1a; 
41.4% had HCV GT1b; 89.6% had IL28B non-CC genotype; 49.0% were prior 
pegIFN/RBV null responders; 21.9/% were prior pegIFN/RBV partial responders, and 
29.2% were prior pegIFN/RBV relapsers.  The SVR12 rate for treatment-experienced 
subjects receiving 3-DAA + RBV for 12 weeks was 96.3% in Study M13-098.  Virologic 
failure (all relapse) was noted in 5/173 (2.9%) GT1a subjects and 2/123 (1.6%) GT1b 
subjects.
Phase 3 Regimen-Controlled Studies:  Studies M13-389, M13-961, and M14-002
Studies M13-389, M13-961, and M14-002 are randomized, regimen-controlled studies to 
assess the safety and efficacy of 12 weeks of treatment with 3-DAA + RBV versus 
3-DAA without RBV.  Study M13-961 and Study M14-002 are placebo-controlled 

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studies, while Study M13-389 is an open-label study.  The patient population was 
different in each of the 3 studies.  Study M13-389 enrolled G1b-infected subjects with 
prior non-response to PegIFN/RBV, Study M13-961 enrolled G1b-infected subjects who 
were treatment-naïve, and Study M14-002 enrolled G1a-infected subjects who were 
treatment naïve.  All three studies excluded subjects with cirrhosis.
In Study M13-389, treated subjects (N = 186) had a median age of 57 years (range:  26 to 
70); 54.8% of the subjects were male; 4.8% were black and 3.2% were Hispanic or 
Latino; 21.5% had a BMI greater than or equal to 30 kg/m2; 87.6% had baseline HCV 
RNA levels ≥ 800,000 IU/mL; 14.5% had bridging fibrosis; 90.9% had IL28B non-CC 
genotype; 34.9% were prior pegIFN/RBV null responders; 28.5% were prior 
pegIFN/RBV partial responders, and 36.6% were prior pegIFN/RBV relapsers. 
The SVR12 rates were 96.6% in the 3-DAA + RBV arm and 100% in the 3-DAA without 
RBV arm in Study M13-389.  The 3-DAA regimen without RBV demonstrated 
noninferiority in SVR12 rates compared to 3-DAA + RBV, as the lower bound of the 
95% confidence interval for the difference in response rates was 3.4%, which was above 
the prespecified noninferiority threshold of –10.5%.  No subject in either arm experienced 
on treatment virologic failure or post-treatment relapse. 
In Study M13-961, treated subjects (N = 419) had a median age of 50 years (range:  19 to 
70); 45.8% of the subjects were male; 4.8% were black and 1.7% were Hispanic or 
Latino; 16.5% had a BMI greater than or equal to 30 kg/m2; 73.3% had baseline HCV 
RNA ≥ 800,000 IU/mL; 10.0% had bridging fibrosis; and 79.0% had IL28B non-CC 
genotype. 
The SVR12 rates for treatment-naïve subjects with HCV GT1b infection who received 
either 3-DAA + RBV or 3-DAA without RBV for 12 weeks in Study M13-961 were 
99.5% and 99.0%, respectively.  The 3-DAA regimen demonstrated noninferiority in 
SVR12 rates compared to 3-DAA + RBV, as the lower bound of the 95% confidence 
interval for the difference in response rates was –2.1%, which was above the prespecified 

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noninferiority threshold of –10.5%.  One of the 419 treated subjects (3-DAA + RBV arm) 
experienced on-treatment virologic failure.  
In Study M14-002, treated subjects (N = 305) had a median age of 54 years (range:  19 to 
70); 65.2% of the subjects were male; 11.8% were black and 9.2% were Hispanic or 
Latino; 19.7% had a BMI greater than or equal to 30 kg/m2; 86.6% had baseline HCV 
RNA levels ≥ 800,000 IU/mL; 17.7% had bridging fibrosis; and 69.2% had IL28B 
non-CC genotype. 
The SVR12 rates for treatment-naïve subjects with HCV GT1a infection who received 
either 3-DAA + RBV or 3-DAA without RBV for 12 weeks in Study M14-002 were 
97.0% and 90.2%, respectively.  The SVR12 rate in the 3-DAA arm did not achieve 
noninferiority to the 3-DAA + RBV arm since the lower bound of the 95% confidence 
interval for the difference between arms was –12.0%, below the prespecified –10.5% 
noninferiority margin.  Virologic failure was noted in 2/100 (2.0%) subjects (on treatment 
virologic failure:  n = 1; relapse:  n = 1) in the RBV-containing regimen and 16/205 
(7.8%) subjects (on treatment virologic failure:  n = 6; relapse:  n = 10) in the RBV-free 
regimen.  The difference between arms demonstrates that RBV contributes to the efficacy 
in GT1a-infected patients and suggests that 3-DAA + RBV is the optimal regimen for 
these patients.
A Phase 3 Study in Cirrhotics:  Study M13-099
Study M13-099 is a randomized, multicenter, open-label trial in treatment-naïve subjects 
or subjects previously treated with pegIFN/RBV with chronic HCV GT1-infection with 
compensated (Child-Pugh A, score ≤ 6) cirrhosis.  ABT-450/r/ABT-267 with ABT-333 in 
combination with RBV was administered for either 12 or 24 weeks of treatment.
Treated subjects (N = 380) had a median age of 58 years (range:  21 to 71); 70.3% of the 
subjects were male; 3.2% were black and 11.8% were Hispanic or Latino; 28.4% had a 
BMI greater than or equal to 30 kg/m2; 14.7% had platelet counts of < 90,000 × 109/L, 
86.1% had baseline HCV RNA levels of 800,000 IU/mL or greater; 68.7% had HCV 

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GT1a, 31.3% had HCV GT1b, 81.8% had IL28B non-CC genotype; 42.1% were 
treatment-naïve, 36.1% were prior pegIFN/RBV null responders; 8.2% were prior 
pegIFN/RBV partial responders, and 13.7% were prior pegIFN/RBV relapsers. 
The SVR12 rates for subjects with compensated cirrhosis treated with 3-DAA + RBV for 
12 or 24 weeks were 91.8% and 95.9%, respectively.  Virologic failure was noted in 
13/208 (6.3%) subjects (on treatment virologic failure:  n = 1; relapse:  n = 12) receiving 
the 12-week regimen and 4/172 (2.3%) subjects (on treatment virologic failure:  n = 3; 
relapse:  n = 1) receiving the 24-week regimen.
Analyses of subgroups suggest that the overall difference in SVR12 rates was driven 
largely by lower SVR12 rate among genotype 1a prior null responders who received.  The 
SVR12 for the treatment-naïve and treatment-experienced genotype 1b patients were both 
99%.  Therefore, a 12-week treatment regimen is recommended for all patients with 
cirrhosis with the exception of GT1a prior null responders for whom 24 weeks of 
treatment provides a higher SVR.
Integrated Safety Results
A summary of treatment-emergent adverse events from the pooled analyses of data from 
the Phase 3 studies is presented in Table 2.  A majority of subjects experienced at least 
one event, but most subjects experienced events that were mild in severity.  Rates of 
severe adverse events and adverse events leading to discontinuation were low across 
studies but numerically higher in the study of subjects with cirrhosis.

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
32
Table 2.
Overview of Treatment-Emergent Adverse Events (AE)
Placebo-Controlled
Regimen-Controlled
Cirrhotics
12-Week 
3-DAA + 
RBV
12-Week 
PBO
12-Week 
3-DAA + 
RBV
12-Week 
3-DAA
12-Week 
3-DAA + 
RBV
24-Week 
3-DAA + 
RBV
Events, %
N = 770
N = 255
N = 401
N = 509
N = 208
N = 172
Subjects ≥ 1 AE
89.0
76.9
82.8
75.0
91.8
90.7
Severe AE
3.5
0.4
1.0
1.2
6.7
7.6
Grade 3 or 4 AE
3.9
0.8
3.0
2.0
7.7
8.1
Serious AE
2.1
0.4
2.2
1.4
6.3
4.7
AE leading to 
discontinuation 
0.8
0.4
0.5
0.4
1.9
2.3
Deaths 
0.1a
0
0
0
0.5b
0
PBO = Placebo
a.
Lung cancer.
b.
Metformin toxicity, lactic acidosis, multi-organ system failure.
The most common adverse events regardless of causality are listed in Table 3.  Adverse 
events that occurred at a ≥ 5% incidence in the 3-DAA + RBV regimen versus the placebo 
were considered to be adverse drug reactions related to the study treatment.  These include 
fatigue, nausea, pruritus, insomnia, asthenia, and anemia.  These events were mostly 
attributable to ribavirin as the rates were lower in the RBV-free arm, and were similar to 
the placebo rates observed in the placebo-controlled cohorts.  In general, rates of adverse 
events were similar in patients with cirrhosis versus patients without cirrhosis.  Patients 
with cirrhosis had a higher frequency of bilirubin elevations.

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
33
Table 3.
Treatment-Emergent Adverse Events with ≥ 10% Frequency in at 
Least One Arm of the Analysis and Rates of Key Post-Baseline Lab 
Abnormalities
Placebo-Controlled
Regimen-Controlled
Cirrhotics
12-Week 
3-DAA + 
RBV
12-Week 
PBO
12-Week 
3-DAA + 
RBV
12-Week 
3-DAA
12-Week 
3-DAA + 
RBV
24-Week 
3-DAA + 
RBV
Treatment-emergent 
Adverse Events, %
N = 770
N = 255
N = 401
N = 509
N = 208
N = 172
Headache
34.3
29.8
24.4
25.1
27.9
30.8
Fatigue
34.2
26.3
29.9
26.5
32.7
46.5
Nausea
22.3
14.9
15.7
8.4
17.8
20.3
Pruritus
15.7
4.3
12.0
6.1
18.3
19.2
Insomnia
14.0
7.5
12.2
5.1
15.4
18.0
Diarrhea
13.5
9.0
8.7
11.4
14.4
16.9
Asthenia
13.5
6.7
9.0
3.9
13.9
12.8
Rash
10.0
5.9
6.2
3.7
11.1
14.5
Cough
8.7
5.1
6.7
4.7
11.5
11.0
Irritability
5.3
4.7
3.2
3.1
7.2
12.2
Anemia
5.3
0
7.5
0.2
7.7
10.5
Dyspnea
9.7
5.5
4.7
2.2
5.8
12.2
Laboratory Events, %
N = 765
N = 254
N = 401
N = 509
N = 208
N = 172
Hemoglobin
     < 10 g/dL (Gr 2)
5.5
0
6.2
0
7.2
11.0
     < 8.0 g/dL (Gr 3)
0.1
0
0.5
0
1.4
0.6
ALT
     > 5 × ULN (Gr 3)
1.2
3.9
0.7
0.2
2.9
0
Bilirubin
     > 3 × ULN (Gr 3)
2.6
0
5.7
0.4
13.5
5.2
PBO = Placebo 
Note:
Percentages of laboratory events are based on the number of subjects with at least one post-baseline value.
Transient elevations in total (predominantly indirect) bilirubin may occur due ABT-450 
inhibition of OATP1B1, an enzyme involved in bilirubin transport, accentuated by 
RBV-induced hemolysis.  The elevations generally peaked by Weeks 1 – 2 and declined 

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
34
after wards.  Rates of hyperbilirubinemia were lower in subjects treated with 3-DAA 
without RBV.  Rates and degree of hyperbilirubinemia were higher in patients with 
cirrhosis, but the temporal pattern of elevation followed by resolution was similar and few 
were symptomatic (jaundice).  All bilirubin elevations resolved completely after treatment 
was discontinued.  
Rates of ≥ grade 2 hemoglobin reductions were 5% to 7% across the 12-week arms among 
subjects who received the RBV-containing regimen, and 11% with the 24-week arm.  
Grade 3 hemoglobin events were rare.  Anemia observed during the clinical trials was 
attributable to the presence of RBV as it was not observed when the 3-DAA regimen was 
administered without RBV.
Transient asymptomatic post baseline serum ALT elevations of > 5 × ULN occurred at a 
frequency of 1% across active treatment arms and were evaluated by an external hepatic 
panel.  The ALT elevations were asymptomatic, usually occurred within the first 4 weeks 
of treatment and typically declined with ongoing treatment.  A disproportionate number of 
the cases were in women on concurrent estrogen-containing therapy (i.e., contraceptives 
or hormone replacement) and discontinuation of the hormonal therapy with continuation 
or brief interruption of the DAA regimen led to resolution in serum ALT elevation.  
Among the cases of serum ALT elevation thought to be related to the DAA regimen, none 
resulted in hepatic dysfunction and they resolved or improved with ongoing treatment.  
All cases had resolved completely in the post-treatment follow-up.
Thirty Asian subjects were enrolled in these Phase 3 studies.  Overall, no data in the 
37 Asian subjects suggest a difference in efficacy or safety.
In summary, the 3-DAA regimen, with or without RBV, was well tolerated with a low 
discontinuation rate.  Adverse events were typically mild, and the main adverse events 
and laboratory abnormalities observed were mainly due to the presence of RBV.  
Transient, asymptomatic serum ALT elevations were observed at a low rate, were not 
associated with hepatic dysfunction and generally resolved with ongoing treatment.

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
35
Study M12-536 is an ongoing Phase 2, multicenter, randomized, dose and duration 
ranging, open-label study evaluating the antiviral activity, safety and pharmacokinetics of 
two doses of ABT450/r (100/100 mg or 150/100 mg) with ABT 267 25 mg for 12 or 
24 weeks for treatment-experienced HCV subgenotype 1b-infected Japanese subjects and 
for 12 weeks for treatment-experienced HCV genotype 2-infected Japanese subjects.  A 
preliminary analysis shows that among subjects infected with HCV subgenotype 1b, 
SVR24 rates from 88.9% to 100% were achieved in the 12 week treatment arms, and 
SVR12 rates of 100% were achieved in the 24-week treatment arms.  The most common 
treatment-emergent adverse events (AEs) were nasopharyngitis, headache, back pain, 
hypertension, gastroenteritis, pruritus, and rash.  One serious AE (fluid retention) was 
deemed as having a reasonable possibility of being related to study drug; this AE led to 
study drug discontinuation.
The current study is intended to examine the safety and efficacy of the combination of 
ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin for 12 weeks in 
treatment-naïve and pegIFN-containing regimen treatment experienced Asian adults with 
chronic HCV GT1b infection and compensated cirrhosis.
3.1
Differences Statement
The combination of ABT-450/r, ABT-267 and ABT-333 coadministered with RBV for 12 
and 24 weeks was explored in treatment-naïve and treatment-experienced genotype 1 
HCV subjects with compensated cirrhosis in Study M13-099 globally except in Asia.  
This is a study to evaluate ABT 450/r/ABT 267 and ABT-333 coadministered with RBV 
for 12 weeks in HCV genotype 1b-infected Asian subjects with compensated cirrhosis.
3.2
Benefits and Risks
This is a single arm study with ABT-450/r/ABT-267 and ABT-333 coadministered with 
RBV for 12 weeks to treat HCV genotype 1b-infected patients with compensated cirrhosis 
in an Asian population. 

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
36
The likelihood of successfully demonstrating high SVR12 in an Asian cirrhotic population 
in the current study is high.  Based on data from Study M13-099, the SVR12 rates for the 
same regimen in treatment-naïve and treatment-experience genotype 1b patients with 
compensated cirrhosis were 100% and 98%, respectively.  The regimen was well tolerated 
with < 2% treatment discontinuation rate due to adverse events. 
Risks associated with ABT-450/r/ABT-267 and ABT-333 co-administered with RBV, 
including the risks of toxicity and virologic failure, appear limited and manageable based 
on the results of the ongoing Phase 3 trials discussed above.  Given the potential high rate 
of cure in this population of HCV-infected subjects, the risk-benefit comparison is 
favorable.
4.0
Study Objectives
4.1
Primary Objectives
The primary objectives of this study are to assess the safety and to compare SVR 12 (the 
percentage of subjects achieving a 12-week sustained virologic response, SVR12, [HCV 
ribonucleic acid {RNA},< lower limit of quantification {LLOQ}, 12 weeks following 
therapy]) and SVR24 (the percentage of subjects achieving a 24-week sustained virologic 
response, SVR24 [HCV RNA < LLOQ, 24 weeks following therapy]) of 12 weeks of
treatment with co-formulated ABT-450, ritonavir and ABT-267 (ABT-450/r/ABT-267) 
and ABT-333 coadministered with ribavirin to the historical SVR rate of telaprevir plus 
pegIFN and RBV therapy in HCV genotype 1b-infected cirrhotic adults.
4.2
Secondary Objectives
The secondary objectives of this study are to demonstrate the effect of the DAA 
combination regimen on HCV RNA levels during and after treatment as measured by on 
treatment virologic failure and post-treatment relapse, respectively.

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
37
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
This is a Phase 3, open-label, multicenter study evaluating the efficacy and safety of 
ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin for 12 weeks in HCV 
genotype 1b, treatment-naïve and IFN based therapy (IFN [alpha, beta or pegIFN] with 
RBV) treatment-experienced adults with compensated cirrhosis.
Treatment will consist of:  ABT-450/r/ABT-267 150/100/25 mg once daily (QD) + 
ABT-333 250 mg twice daily (BID) + RBV* for 12 weeks.
*
RBV will be administered weight-based 1000 – 1200 mg divided to twice daily.
Approximately 100 subjects will be enrolled (approximately 60 subjects from sites in 
China and 20 subjects each from sites in S. Korea and Taiwan).  At least 
35 treatment-naïve and 35 treatment-experienced subjects will be enrolled.
This study will consist of a Treatment Period and a Post-Treatment (PT) Period.
During the Treatment Period, subjects will receive treatment with ABT-450/r/ABT-267 
and ABT-333 co-administered with RBV for 12 weeks.
Upon completing the Treatment Period or premature discontinuation of the Treatment 
Period, subjects will enter the 48-week Post-Treatment Period.  Safety evaluations will 
also occur by a Data Monitoring Committee (DMC); see Section 5.5.5.1. 
As this is an open-label study, safety and efficacy evaluations will occur throughout the 
Treatment and Post-Treatment Periods.  Safety evaluations will also occur by a Data 
Monitoring Committee (DMC); see Section 5.5.5.1.
A primary analysis will occur after all subjects have completed the Treatment Period 
through Post-Treatment Week 24 of the Post-Treatment Period or prematurely 
discontinued from the study.  An interim analysis will occur after all subjects at sites in 

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
38
South Korea and Taiwan have completed the Treatment Period through Post-Treatment 
Week 12 of the Post-Treatment Period or prematurely discontinued from the study.  This 
interim analysis is planned to also support regulatory submission activities in S. Korea 
and Taiwan.
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 and will undergo the study procedures 
identified in Section 5.3.1.1 associated with the Screening Visit.  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 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.
Subjects who meet all eligibility criteria with the exception of their initial non-invasive 
assessment of liver cirrhosis by FibroScan may undergo a liver biopsy.
Liver biopsy should only be performed during the Screening Period if all inclusion criteria 
and none of the exclusion criteria are met (see Section 5.3.1.1 for exception regarding 
FibroScan).
The study is designed to enroll approximately 100 subjects to meet scientific and 
regulatory objectives without enrolling an undue number of subjects in alignment with 
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.
5.1.1.1
Rescreening
Subjects who meet all eligibility criteria with the exception of up to three exclusionary 
laboratory parameters may rescreen once within the 35-day screening period without prior 

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
39
AbbVie approval.  However, subjects with any of the following exclusionary values will 
not be allowed to rescreen: exclusionary HCV genotype, a positive hepatitis B surface 
antigen, positive human immunodeficiency virus (HIV) antibody, confirmed pregnancy, 
or positive drug screening results without a prescription nor medical justification 
confirmed by the investigator on over the counter medication.  Subjects with more than 
three exclusionary laboratory results will require approval from the AbbVie Study 
Designated Physician prior to rescreening.  Subjects being rescreened because of 
exclusionary laboratory parameter(s) must have the related panel(s) repeated 
(e.g., exclusionary ALT requires a repeat chemistry panel) within the same screening 
period. 
Subjects who otherwise meet all eligibility criteria, but have a positive urine alcohol 
screen, may have only the urine alcohol screen repeated. If the repeat urine alcohol screen 
is negative, the subject may be considered eligible.
Subjects who fail to enroll within 35 days of Screening, regardless of the reason for 
falling outside the 35-day screening window, may be allowed to rescreen only once
without approval of the AbbVie Study Designated Physician.  These subjects must be 
rescreened for all laboratory and eligibility criteria, not just those that were exclusionary 
at the first screening attempt (with the exception of HCV genotype, IL28B genotype, 
FibroTest, FibroScan, liver biopsy, Follicle stimulating hormone [FSH], and hemoglobin 
Apolipoprotein A1 [AIC] which do not need to be repeated).
For subjects who do not meet the study eligibility criteria, the site personnel must register 
the subject as a screen failure in both IRT and electronic data capture (EDC) systems.
5.1.2
Treatment Period (TP)
After meeting the eligibility criteria, approximately 100 treatment-naïve and IFN based 
therapy (IFN [alpha, beta or pegIFN] with RBV) treatment-experienced subjects will be 
enrolled via IRT and assigned to 12 weeks of treatment.  Approximately 100 subjects will 
be enrolled (approximately 60 subjects at sites in China and 20 subjects each at sites in 

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
40
South Korea and Taiwan).  At least 35 treatment-naïve subjects and 
35 treatment-experienced subjects will be enrolled.  Subjects will be administered study 
drugs at the site on Study Day 1.  Subjects will receive instructions about the study drugs 
and the dosing schedule at the Day 1 Visit.  ABT-450/r/ABT-267 will be administered 
orally once daily and ABT-333 and RBV will be dosed orally twice daily as described in 
Section 5.5.1.  The doses are as follows:
●
ABT-450/r/ABT-267 150/100/25 mg QD
●
ABT-333 250 mg BID
●
RBV weight based, 1000 mg to 1200 mg daily divided BID per local label 
(e.g., < 75 kg = 1000 mg daily divided BID or ≥ 75 kg = 1200 mg daily 
divided BID)
Subjects will be administered the first doses of study drugs at the site on Study Day 1 
(ABT-450/r/ABT-267, ABT-333, and RBV).  Plasma samples for pharmacokinetic 
analysis and HCV RNA analysis will be collected on Study Day 1 prior to dose and at 
2 hours post dose and at the additional visits detailed in Table 5 and Table 6.
All subjects will continue to return to the site on an outpatient basis up to 12 weeks for the 
study procedures identified in Section 5.3.1.1.  Sites should ensure that subjects adhere to 
the study visits listed in Table 5.  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.
Safety and tolerability of the treatments will be assessed throughout the study.  Laboratory 
testing will include chemistry, hematology, and urinalysis (Section 5.3.1.1).  Blood 
samples for optional pharmacogenetic analysis, will be collected as detailed in 
Section 5.3.1.3.  Patient Reported Outcomes (PROs) will also be assessed at the visits 
listed in Table 5 and Table 6.  Virologic failure criteria will be evaluated and applied by 
the Investigator as detailed in Section 5.4.1.1 and ongoing review of the data is planned in 
order to determine if subjects meet the virologic failure criteria (Section 5.4.1.1).

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
41
Subjects who prematurely discontinue from the Treatment Period should return for a 
Treatment Discontinuation Visit and undergo the study procedures as outlined in and as 
described in Section 5.4.1.
Ideally, this should occur on the day of study drug discontinuation, but should be no later 
than 2 days after their final dose of study drug and prior to the initiation of any other 
anti-HCV therapy if applicable.  Subjects who complete or discontinue treatment will be 
monitored for safety, HCV RNA, the emergence and persistence of resistant viral variants 
and assessment of PROs in the 48-week Post-Treatment Period as detailed in 
Section 5.4.1.
5.1.3
Post-Treatment (PT) Period
All subjects who receive at least one dose of DAA in the Treatment Period and either 
complete treatment or prematurely discontinue study drug will be monitored in the 
Post-Treatment Period for safety, HCV RNA, the emergence and persistence of resistant 
viral variants and assessment of PROs for an additional 48 weeks following the last dose 
of study drug.
The Post-Treatment Period will begin the day following the last dose of study drug 
treatment.  Subjects with HCV RNA < LLOQ at the end of treatment and who have a 
confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements 
≥LLOQ) at any point in the Post-Treatment Period will be considered to have relapsed.  
Confirmation of an HCV RNA ≥ LLOQ in the Post-Treatment Period should be 
completed as soon as possible.
Subjects who prematurely discontinue the Post-Treatment Period should return to the site 
for a Post-Treatment discontinuation visit as outlined in Table 6.
All subjects who receive at least one dose of DAA and who do not achieve and maintain 
virologic suppression (HCV RNA < LLOQ), or who relapse post DAA therapy, should 
discuss the future treatment options with the investigators.

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
42
5.2
Selection of Study Population
The study population consists of HCV genotype 1b-infected adult subjects with 
compensated cirrhosis who are either treatment-naïve or (IFN [alpha, beta or pegIFN] 
with RBV) based treatment-experienced adults.  Refer to Section 5.2.1 for details 
regarding required documentation for prior IFN-based treatment failures.
Subjects who meet the inclusion criteria and who do not meet any of the exclusion criteria 
will be eligible for enrollment into the study.
5.2.1
Inclusion Criteria
1.
Male or female of Chinese, South Korean, and Taiwanese descent with full 
Chinese, South Korean, and Taiwanese parentage between the ages of 18 and 
70 years of age, inclusive, at time of screening.
2.
Chronic HCV-infection prior to study enrollment.  Chronic HCV-infection is 
defined as one of the following:
●
Positive for anti-HCV antibody (Ab) or HCV RNA > 1000 IU/mL at least 
6 months before Screening, and positive for HCV RNA and anti-HCV Ab at 
the time of Screening; or
●
Positive HCV RNA > 1000 IU/mL at the time of Screening with a liver biopsy 
consistent with chronic HCV-infection (or a liver biopsy performed prior to 
enrollment with evidence of chronic hepatitis C disease).
3.
Screening laboratory result indicating HCV genotype 1b-infection.
4.
Per local standard practice, documentation of cirrhosis by one of the following 
methods:
●
Diagnosis on previous liver biopsy or liver biopsy conducted during screening, 
e.g., Metavir Score of > 3 (including 3/4 or 3-4), Ishak score of > 4 or,
●
FibroScan score ≥ 14.6 kPa within 6 months of Screening or during the 
Screening Period.
Subjects with a non-qualifying FibroScan result may only be enrolled if they have 
a qualifying liver biopsy diagnosis. 

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
43
5.
Compensated cirrhosis defined as Child-Pugh score of ≤ 6 at Screening.
6.
Subject has never received antiviral treatment including IFN based therapy (IFN 
[alpha, beta or pegIFN] with or without RBV) for hepatitis C infection 
(treatment-naïve subject), or subject must have documentation that they meet the 
definition of one of the following categories (treatment-experienced subject):
●
Non responder:  received at least 12 weeks of IFN based therapy (IFN [alpha, 
beta or pegIFN] with RBV) for the treatment of HCV and failed to achieve 
undetectable HCV RNA (HCV RNA < LLOD) at the end of treatment; or
●
Relapser:  Received IFN based therapy (IFN [alpha, beta or pegIFN] with 
RBV) for the treatment of HCV and was undetectable (HCV RNA < LLOD) at 
or after the end of treatment, but subsequently had detectable HCV RNA 
within 24 weeks of treatment follow-up; or 
●
IFN based therapy (IFN [alpha, beta or pegIFN] with RBV) Intolerant: 
treatment of HCV was discontinued during the treatment period due to 
intolerance to any of the components of the IFN based therapy (IFN [alpha, 
beta or pegIFN] with RBV) therapy.
HCV RNA levels that serve as documentation to support the type of prior 
non-response should have been obtained in relation to the previous IFN based 
therapy (IFN [alpha, beta or pegIFN] with RBV) treatment.  IFN based therapy 
(IFN [alpha, beta or pegIFN] with RBV) must have been completed no less than 
2 months prior to the Screening visit.
7.
Female who is:
●
practicing total abstinence from sexual intercourse (minimum 1 complete 
menstrual cycle)
●
sexually active with female partners only
●
not of childbearing potential and sexually active with male partner(s);
○
postmenopausal for at least 2 years prior to screening (defined as 
amenorrheic for longer than 2 years, age appropriate, and confirmed by a 
follicle stimulating hormone [FSH] level indicating a postmenopausal 
state) or

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
44
○
surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy 
or hysterectomy) or has a vasectomized partner(s)
●
of childbearing potential and sexually active with male partner(s):
○
currently using at least one effective method of birth control at the time of 
screening and 
○
agree to using two effective methods of birth control while receiving study 
drugs (as outlined in the subject information and consent form or other 
subject information documents), starting with Study Day 1 and for 
7 months after stopping study drug or as directed by the local ribavirin 
label.  
8.
Males who are not surgically sterile who are sexually active with female partner(s) 
of childbearing potential must agree to practice two effective forms of birth control 
(as outlined in the subject informed consent or other subject information 
documents) throughout the course of the study, starting with Day 1 and for 
7 months after stopping study drug or as directed by the local ribavirin label.  
9.
Body Mass Index (BMI) is from ≥ 18 to < 38 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).
10.
Subjects must be able to understand and adhere to the study visit schedule and all 
other protocol requirements and 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.
Rationale for Inclusion Criteria
1 – 6
To select the appropriate subject population with sufficient disease 
severity for evaluation
7, 8
For the safety of study subjects
10
In accordance with harmonized Good Clinical Practice (GCP)

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
45
5.2.2
Exclusion Criteria
1.
HCV genotype performed during screening indicating unable to genotype or 
subtype infection with any other HCV genotype or subtype.
2.
Positive test result at Screening for hepatitis B surface antigen (HBsAg), or 
HBV-DNA > LLOQ if HBsAg negative, or anti-human immunodeficiency virus 
antibody (HIV Ab).
3.
Any current or past clinical evidence of Child-Pugh B or C Classification or 
clinical history of liver decompensation including ascites (noted on physical exam), 
variceal bleeding or hepatic encephalopathy.
4.
Serum Alpha-Fetoprotein (sAFP) > 100 ng/mL at Screening.
5.
Confirmed presence of hepatocellular carcinoma indicated on imaging techniques 
such as computed tomography (CT) scan or magnetic resonance imaging (MRI) 
within 3 months prior to Screening or on an ultrasound performed at Screening (a 
positive ultrasound result should be confirmed with CT scan or MRI.)
6.
Any primary 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
●
Drug-related liver disease
Steatosis and steatohepatitis on a liver biopsy coincident with HCV-related 
changes would not be considered exclusionary unless the steatohepatitis is 
considered to be the primary cause of the liver disease.
7.
Screening laboratory 
●
ALT > 7 × upper limit of normal (ULN)

ABT-450/r/ABT-267, ABT-333
M14-491 Protocol
46
●
Aspartate aminotransferase (AST) > 7 × ULN
●
Estimated Glomerular filtration rate adjusted for the Asian population (eGFR) 
< 50 mL/min/1.73 m2 as estimated by the C-MDRD method, modified for the 
Asian population, according to the following formula:  eGFR = 175 × (Serum 
Creatinine) –1.234 × (Age) –0.179 × (0.79 if female)
●
Albumin < 2.8 g/dL
●
International normalized ratio (INR) > 2.3.  Subjects with a known inherited 
blood disorder and INR > 2.3 may be enrolled with permission of the AbbVie 
Study Designated Physician
●
Hemoglobin < LLN
●
Platelets < 60,000 cells per mm3
●
Absolute neutrophil count (ANC) < 1200 cells/μL
●
Total bilirubin ≥ 3.0 mg/dL
8.
Females who are pregnant or plan to become pregnant, or breastfeeding, or males 
whose partners are pregnant or planning to become pregnant within 7 months (or 
per local RBV label) after their last dose of study drug/RBV.
●
Female subjects with a borderline hCG at Screening and/or Day 1 may enroll 
into the study if they either:
○
Have a documented history of bilateral tubal ligation, hysterectomy, 
bilateral oophorectomy; or
○
Are confirmed to be postmenopausal defined as amenorrheic for longer 
than 2 years, age appropriate, and confirmed by a follicle-stimulating 
hormone (FSH) level indicating a postmenopausal state at Screening.
9.
Use of known strong inducers of cytochrome P450 3A (CYP3A) 
(e.g.,phenobarbital, rifampin, carbamazepine, St. John's Wort), or strong CYP2C8 
inhibitors within 2 weeks or within 10 half-lives, whichever is longer, of the 
respective medication/supplement, prior to the initial dose of study drug.  
10.
Use of any medication listed below, as well as those that are contraindicated for 
ritonavir and RBV, within 2 weeks or 10 half-lives of the medication whichever is 
longer, to study drug administration including but not limited to:

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Table 4.
Medications Contraindicated for Use with the Study Drug Regimen
Alfuzosin
Amiodarone
Astemizole
Bepredil
Carbamazepine 
Cisapride
Clorazepate
Clozapine
Diazepam
Efavirenz
Encainide Ergot
Derivatives
(ergotamine, dihydroergotamine, 
ergonovine, methylergonovine)
Estazolam
Flecainide
Flurazepam
Fusidic acid
Gemfibrozil
Hormonal contraceptives
Lovastatin
Midazolam (oral)
Pethidine
Phenobarbital
Phenytoin
Pimozide
Piroxicam
Propafenone
Propoxyphene
Quindine
Rifabutin
Rifampin
Sildenafil*
Simvastatin
St. John's Wort
Terfenadine
Triazolam
Voriconazole
*
When used for the treatment of pulmonary arterial hypertension.
Note:
Not all medications contraindicated with ritonavir and ribavirin are listed above.  Refer to the most current 
package inserts or product labeling of ritonavir and ribavirin for a complete list of contraindicated 
medications.
11.
History of uncontrolled seizures, 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 
carcinoma in situ) in the past 5 years.
12.
History of solid organ transplant.
13.
Clinical significant abnormal ECG, or ECG with QT interval corrected for heart 
rate (QTc) using Fridericia's correction formula (QTcF) > 470 msec at Screening or 
Study Day 1 (Baseline, prior to dosing).
14.
Clinically significant abnormalities or comorbidities, other than HCV-infection, 
that make the subject an unsuitable candidate for this study in the opinion of the 
investigator.
15.
Recent (within 6 months prior to study drug administration) history of drug or 
alcohol abuse that could preclude adherence to the protocol.

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16.
Positive result of a urine drug screen at the Screening Visit for opiates, barbiturates, 
amphetamines, cocaine, benzodiazepines, phencyclidine, propoxyphene, or 
alcohol, with the exception of a positive result associated with documented short 
term use or chronic stable use of a prescribed or over-the-counter medication.  In 
the case of a positive urine drug screen attributed to an over-the-counter 
medication, there must be documented medical justification for its use confirmed 
by the Investigator.  Single positive results on urine screen for alcohol are 
discussed in Section 5.1.1.1, Rescreening.
17.
Current enrollment in another interventional clinical study, previous enrollment in 
this study, or previous use of any protease inhibitor, non-nucleoside polymerase 
inhibitor, or Ns5A inhibitor, either investigational or experimental (including 
previous exposure to ABT-450, ABT-267 or ABT333).  Receipt of any 
investigational produce within 6 weeks prior to study drug administration. 
Rationale for Exclusion Criteria
1 – 8, 11 – 13, 15
To ensure safety of the subjects throughout the study
9, 10, 16
To avoid bias for the evaluation of efficacy and safety by 
concomitant use of other medications
14, 17
To avoid bias for the evaluation of efficacy and safety
5.2.3
Prior and Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, traditional medicines, and/or herbal supplements) that the subject is receiving 
from the time of signing the consent through the Treatment Period 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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During the Post-Treatment Period, all medications will be collected until 30 days 
following the last dose of study drugs.  Only medications associated with HCV treatment 
or a serious adverse event (SAE) will be collected thereafter.
The AbbVie Study Designated Physician should be contacted if there are any questions 
regarding concomitant or prior therapy(ies).
5.2.3.1
Prior HCV Therapy
Treatment-naïve subjects must not have prior or current use of any investigational or 
commercially available anti-HCV agents, including IFN, pegIFN, telaprevir, boceprevir or 
RBV.  Subjects who previously participated in trials of direct-acting antiviral agents for 
treatment of HCV may be enrolled with the approval of the AbbVie Study Designated 
Physician if they can provide documentation that they received placebo.
Treatment-experienced subjects must have previously received IFN based therapy (IFN 
[alpha, beta or pegIFN] with RBV) and failed treatment.  These subjects should have 
documentation of IFN based therapy (IFN [alpha, beta or pegIFN] with RBV) treatment 
history, including start and stop dates and HCV RNA levels to document the type of 
non-response or the reason for discontinuation of therapy to document intolerance in the 
source document.
Treatment-experienced subjects must have discontinued IFN based therapy (IFN [alpha, 
beta or pegIFN] with RBV) at least 2 months prior to the Screening Visit and IFN based 
therapy (IFN [alpha, beta or pegIFN] with RBV) was the last therapy received in order to 
be eligible for the study.
5.2.3.2
Concomitant Therapy
The investigator should confirm that concomitant medication can be administered with 
DAAs (including ritonavir).  Some medications may require dose adjustments due to 
potential for drug-drug interactions.  The investigator should also review the label(s) for 
the concomitant medication(s) for additional information.

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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.  While the subject is using hepatoprotective medication, the 
dose should be kept stable.
During the Post-Treatment Period, investigators should reassess concomitant medications 
and subjects may resume previously prohibited medications or revert to pre-study doses, 
2 weeks following discontinuation of study drugs, if applicable.
5.2.3.3
Prohibited Therapy
In addition to the medications listed above in Table 4, use of known strong inducers of 
CYP3A or strong inhibitors of CYP2C8 are prohibited within 2 weeks or within 
10 half-lives, whichever is longer, prior to the initial dose of study drugs and through the 
first 2 weeks after the subject has completed active study drugs in the Treatment Period.
Refer to the ritonavir and RBV labeling for a list of prohibited medications.  Anti-HCV 
medications other than those specified in the protocol will not be allowed during the 
Treatment Period of the study.
Hormonal contraceptives (including oral, topical, injectable or implantable varieties) may 
not be used from 2 weeks prior to the first dose of study drug until 2 weeks after the end 
of study drug dosing.  Post-menopausal hormone replacement therapy may be used at the 
discretion of the Investigator.
Management of hematologic growth factor therapy is the responsibility of the 
Investigator; growth factors will not be provided by AbbVie, and AbbVie will not 
reimburse for the expense of growth factors or their use.
Investigators should refer to the package inserts for erythropoiesis stimulating agents for 
additional information regarding their use.

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5.3
Efficacy, Pharmacokinetic, Optional Pharmacogenetic and 
Safety Assessments/Variables
5.3.1
Efficacy and Safety Measurements Assessed and Flow 
Chart

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Table 5.
Study Activities – Treatment Period (TP)
Activity
Treatment Period (TP)
Treatment Visits – All Subjects
Screening
Day1/ 
Baselinea
Wk 1
Wk 2
Wk 4
Wk 6
Wk 8
Wk 10
Wk 12 
(EOT)b
Premature 
D/Cb
Informed Consentc
X
Provide RBV Medication Guided and 
Partner Risk Fact Sheet 
X
Medical History
X
Xe
Physical Exam
X
X
X
X
Vital Signs, Weight, Height
Xf
X
X
X
X
X
X
X
X
X
ECG
X
Xg
X
X
Hematology/Chemistry/Urinalysis/ 
Coagulation Panel
X
X
X
X
X
X
X
X
X
X
Pregnancy Test (serum [s] urine [u])h
X (s, u)
X (s, u)
X (u)
X (u)
X (u)
X (u)
Urine Albumini
X
FSH (all females), HbA1c 
X
HBsAg, Anti-HCV Ab, Anti-HIV Ab, 
HBV-DNA if HBsAg Negative
X
Drug/Alcohol Screen
X
Total Insulin
X
X
X
HCV Genotype and Subgenotype
X
IL28B Sample
X

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Table 5.
Study Activities – Treatment Period (TP) (Continued)
Activity
Treatment Period (TP)
Treatment Visits – All Subjects
Screening
Day1/ 
Baselinea
Wk 1
Wk 2
Wk 4
Wk 6
Wk 8
Wk 10
Wk 12 
(EOT)b
Premature 
D/Cb
Screening:  Liver Biopsy or Fibroscanj
X
Longitudinal FibroTest  
Xk
Child-Pugh Score
X
X
X
Clinical Assessment of Hepatic 
Decompensation
Xl
HCC Screening: Liver Ultrasound and 
Alpha Fetoproteinm
X
Concomitant Medication Assessment
X
X
X
X
X
X
X
X
X
X
Patient Reported Outcomes 
Instruments (PROs)n
X
X
X
X
X
Adverse Event Assessment
X
X
X
X
X
X
X
X
X
X
Study Drugs Dispensed
X
X
X
HCV RNA Samples
X
Xo
X
X
X
X
X
X
X
X
HCV Resistance Sample
X
X
X
X
X
X
X
X
X
Pharmacokinetic Sample
Xp
X
X
X
X
X
X
X
X
Archive Plasma Sample
X
X
X
X
X
X
X
X
X
X

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Table 5.
Study Activities – Treatment Period (TP) (Continued)
Activity
Treatment Period (TP)
Treatment Visits – All Subjects
Screening
Day1/ 
Baselinea
Wk 1
Wk 2
Wk 4
Wk 6
Wk 8
Wk 10
Wk 12 
(EOT)b
Premature 
D/Cb
Archive Serum Sample
X
X
X
X
X
X
X
X
X
X
Interferon Gamma-Induced Protein 
10 (IP-10) Sample
X
X
X
X
X
Pharmacogenetic Sample (optional)q
X
Wk = Week; EOT = End of treatment; D/C = Discontinuation
a.
All procedures, including pharmacokinetic sample collection, to be performed prior to first dose with the exception of the 2-hour post-dose pharmacokinetic and HCV RNA 
samples.
b.
Subjects should begin the Post-Treatment Period after the subject completes study drug treatment or prematurely discontinues Treatment Period.
c.
Subjects will need to sign an informed consent for the study (prior to performing any screening or study-specific procedures) and the optional Pharmacogenetic sample(s), if 
applicable.
d.
Where applicable/locally available.
e.
Medical history will be updated at the Day 1 Visit.  This updated medical history will serve as the Baseline for clinical assessment.
f.
Height will be measured at Screening only.
g.
Evaluate the Day 1 ECG prior to dosing to determine eligibility.
h.
Urine pregnancy testing is not required after the Screening Visit for female subjects with a documented history of bilateral tubal ligation, bilateral oophorectomy or 
hysterectomy or who are confirmed to be post-menopausal. A positive urine pregnancy test requires a confirmatory serum test.  (Refer to Section 5.3.1.1 [Pregnancy Test] for 
additional details.) 
i.
Done at Day 1/Baseline and collected for decrease in eGFR as defined in Section 5.3.1.1.
j.
Subjects who do not have a qualifying historical liver biopsy, but who otherwise meet all of the inclusion criteria and none of the exclusion criteria will undergo a liver 
biopsy.  
k.
Longitudinal FibroTest measured for exploratory analysis of fibrosis over time.  Day 1 results will be blinded to the investigator/site.

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Table 5.
Study Activities – Treatment Period (TP) (Continued)
l.
Clinical assessment of Hepatic encephalopathy and ascites at Day 1 prior to dosing. 
m.
Liver Ultrasound and alpha fetoprotein to be performed at Screening.  Subjects with a historical negative Liver Ultrasound, CT or MRI (within 3 months prior to screening) 
are not required to have a screening Ultrasound performed.  If additional Liver Ultrasound testing is required it should be completed as an unscheduled visit.  A positive 
Ultrasound result suspicious for HCC will be confirmed with CT scan or MRI.
n.
SF-36v2, EuroQol 5 Dimensions 5 Levels Health State Instrument (EQ-5D-5L), and Hepatitis C Virus Patient Reported Outcomes Instrument (HCVPRO), should be 
administered before any study procedures and in the following order:  SF-36v2, EQ-5D-5L and HCVPRO.
o.
HCV RNA will be collected at 0-hour (immediately prior to the morning dose) and at 2 hours post-dose.
p.
Blood Sample(s) for pharmacokinetic assay as described in Section 5.3.2.1 will be collected as follows:
!
Day 1:  0-hr (immediately prior to the morning dose), and at 2 hours post-dose.
!
A single pharmacokinetic sample will be collected at all other Treatment Study Visits without regard to the time of dosing asdetailed in Section 5.3.2.1 above.  
Additional intensive PK samples will be collected at a single visit on or after the Week 2 study visit.  Samples will be collected at predose and approximately 2, 4, 6 and 
at 24 hours post DAA dose.  Subjects may opt out of intensive PK sampling. On the day of intensive blood sampling, subjects will take their morning dose of DAAs and 
ribavirin onsite in the presence of study site personnel and the time of administration will be noted.
q.
If the optional pharmacogenetic sample is not collected at Day 1, it may be collected at any other visit during the study.

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Table 6.
Study Activities – Post-Treatment (PT) Period
Activity
PT Wk 2
PT Wk 4
PT Wk 8
PT Wk 12
PT Wk 24
PT Wk 36
PT Wk 48 
or PT D/Ca
Vital Signs and Weight
X
X
X
X
X
X
X
Hematology/Chemistry/Urinalysis/Coagulation Panel
X
X
X
X
X
X
X
Monthly Pregnancy Test (females)b
X
X
(Weeks 12, 16, 20, 24, 28)
Longitudinal FibroTest
X
X
Child-Pugh Score
X
HCC Screening: Liver Ultrasound and Alpha 
Fetoproteinc
X
X
PRO Instrumentsd
X
X
X
X
Concomitant Medication Assessmente
X
X
X
X
X
X
X
Adverse Event Assessmentf
X
X
X
X
X
X
X
HCV RNAg
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
Archive Serum Sample
X
X
X
X
X
X
X
IP-10 Sample
X
X
Wk = Week; PT D/C = Post-Treatment Discontinuation
a.
Subjects who prematurely discontinue from the Post-Treatment Period should return to the site to complete the PT D/C Visit 
b.
Urine pregnancy testing is not required after TP Day 1 visit for female subjects with a documented history of bilateral tubal ligation, hysterectomy, bilateral oophorectomy, or 
who are confirmed post-menopausal.  At PT Weeks 16, 20 and 28, subjects may have an unscheduled office visit for pregnancy testing or elect to perform the tests at home 
with test kits provided by the site.  Additional testing may be required per local RBV label.

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Table 6.
Study Activities – Post-Treatment (PT) Period (Continued)
c.
Liver ultrasound and alpha fetoprotein to be performed at PT Week 12 and PT Week 36.  A positive Ultrasound result suspicious for HCC will be confirmed with CT scan or 
MRI.
d.
PRO instruments should be administered before any study procedures and in the order listed below. 
!
PT Week 4:  SF-36v2, EQ-5D-5L and HCVPRO
!
PT Week 12:  SF-36v2, EQ-5D-5L and HCVPRO
!
PT Week 24:  SF-36v2, EQ-5D-5L and HCVPRO
!
PT Week 48 or D/C:  SF-36v2, EQ-5D-5L and HCVPRO
e.
Only medications related to the treatment of HCV and medications prescribed in association with a SAE will be collected after 30 days post-dosing.
f.
Only SAEs will be collected after 30 days post-dosing.
g.
Confirmation of an HCV RNA ≥ LLOQ in the post-treatment period should be completed as soon as possible per Section 5.1.3.

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5.3.1.1
Study Procedures
The study procedures outlined in Table 5 and Table 6 are discussed in detail in this 
section with the exception of the assessment of concomitant medications (Section 5.2.3.3), 
the collection of blood samples for optional pharmacogenetic analysis (Section 5.3), the 
collection of blood samples for pharmacokinetic analysis (Section 5.3.2), the monitoring 
of treatment compliance (Section 5.5.6), and the collection of adverse event information 
(Section 6.0).  All study data will be recorded in the subject's source documentation and 
then on the appropriate eCRFs, with the exception of laboratory data which will be 
provided to the Sponsor electronically from the individual laboratorie(s).
Informed Consent and RBV Information
Signed study-specific informed consent will be obtained from the subject before any study 
procedures are performed.  All subjects will be given the RBV Medication Guide (where 
applicable/locally available).  Male subjects will be given an additional copy of the RBV 
Medication Guide (where applicable/locally available) and a RBV Partner Risk Fact Sheet 
to share with their female partner(s).  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 tobacco, alcohol use and injection drug 
use will be taken from each subject during the Screening Visit.  The subject's medical 
history will be updated at the Day 1 Visit (Treatment Period).  This updated medical 
history will serve as the baseline for clinical assessment.
Physical Examination
A complete physical examination will be performed at visits indicated in Table 5, or upon 
subject discontinuation.  A symptom-directed physical examination may be performed at 
any other visit, when necessary.

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The physical examination performed on Day 1 of the Treatment Period will serve as the 
baseline physical examination for clinical assessment.  Any significant physical 
examination findings after the first dose will be recorded as adverse events.
Vital Signs, Weight, Height
Body temperature (oral or tympanic), blood pressure, pulse, and body weight will be 
measured at the visits indicated in Table 5 and Table 6.  Blood pressure and pulse rate will 
be measured after the subject has been sitting for at least 3 minutes.  The vital signs 
performed on Day 1 will serve as the baseline for clinical assessment.  The subject should 
wear lightweight clothing and no shoes during weighing.  Height will only be measured at 
Screening; the subject will not wear shoes.
12-lead Electrocardiogram
A 12-lead resting ECG will be obtained at the visits indicated in Table 5 or upon subject 
discontinuation from the Treatment Period (or as clinically needed).  The Day 1 
(Treatment Period) reading will serve as the baseline assessment.  The ECG should be 
performed prior to blood collection.
The ECGs will be evaluated by an appropriately trained physician at the site ("local 
reader").  The local reader from the site will sign, and date all ECG tracings and will 
provide his/her global interpretation as a written comment on the tracing using the 
following categories:
●
Normal ECG
●
Abnormal ECG – not clinically significant
●
Abnormal ECG – clinically significant
Only the local reader's evaluation of the ECG will be collected and documented in the 
subject's source.  The automatic machine reading (i.e., machine-generated measurements 
and interpretation that are automatically printed on the ECG tracing) will not be collected.  

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The QT interval measurement (corrected by Fridericia formula, QTcF) will be 
documented in the eCRF only if the local reader's assessment is "prolonged QT."
Clinical Laboratory Tests
Samples will be obtained at a minimum for the clinical laboratory tests outlined in Table 7
at the visits indicated in Table 5 and Table 6.
Blood samples for serum chemistry tests should be collected following a minimum 8-hour 
fast (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.  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 Day 1 study 
visit, a fasting blood sample is to be collected prior to the first dose of study drug which is 
administered at the Day 1 study visit.  Subjects should be reminded to eat prior to their 
first dose of study drug (e.g., suggest they bring a light snack).  Blood samples should still 
be drawn if the subject did not fast for at least 8 hours.  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.
Instructions regarding the collection, processing, and shipping of these samples will be 
provided by the central laboratory chosen for this study.  The certified laboratory chosen 
for this study is Covance.  Information on the location of the lab where samples will be 
sent will be found in the lab manual.

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Table 7.
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Additional 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)
ANC
Prothrombin Time/INRa
Activated partial thromboplastin 
time (aPTT)
Reticulocyte count
Blood Urea Nitrogen (BUN)
Creatinine
Total bilirubina,b
Direct and indirect bilirubin
Serum glutamic-pyruvic 
transaminase (SGPT/ALT) 
Serum glutamic-oxaloacetic
transaminase (SGOT/AST)
Alkaline phosphatase
Sodium
Potassium
Calcium
Inorganic phosphorus
Uric acid
Cholesterol
Total protein
Glucose
Triglycerides
Albumina
Chloride
Bicarbonate
Magnesium
Gamma-glutamyl transferase 
(GGT)b
Creatinine clearance (Cockcroft 
Gault calculation)
eGFRe
Alpha2-macroglobulinb
Haptoglobinb
Apolipoprotein A1b
Alpha fetoprotein
HBV DNAg
HBsAgc
Anti-HCV Abc
Anti-HIV Abc
FSH (all females)c
Opiatesc
Barbituratesc
Amphetaminesc
Cocainec
Benzodiazepinesc
Alcoholc
Phencyclidinec
Propoxyphenec
Methadonec
Urine and Serum 
Human Chorionic 
Gonadotropin (hCG) females)d
Total insulin
HCV RNA
Hepatitis B Panelf
Hepatitis A Antibody, Totalf
Hepatitis E Virus IgGf
Hepatitis E Virus IgMf
Hemoglobin A1Cc
IP-10
IL28Bc
HCV genotype and subtypec
Pharmacogenetic sample (optional)
Urinalysis
Specific gravity
Ketones
pH
Protein
Blood
Glucose 
Urobilinogen
Bilirubin
Leukocyte esterase
Microscopic (reflex)
Albumini
Urine Archive Specimenh
a.
Also a component of the Child-Pugh Assessment.
b.
Also a component of FibroTest.
c.
Performed only at Screening.
d.
Urine pregnancy testing is not required after Day 1 of the Treatment Period for female subjects who are confirmed 
to be post-menopausal or who have a documented history of prior bilateral tubal ligation, bilateral oophorectomy or 
hysterectomy.
e.
eGFR calculated by the MDRD formula, modified for the Chinese population.
f.
Performed for management of transaminase elevations.  See Section 6.7.4 for details.
g.
Only performed if HBsAg is negative.
h,
Performed if eGFR level is < 50 mL/minute.  See Section 6.7.5 Management of eGFR decreases for details.
i.
Collected at Day 1 and if eGFR level < 50 mL/minute.  See Section 6.7.5 Management of eGFR decreases for 
details.

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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 6.7. 
Pregnancy Test
A urine pregnancy test will be performed for all female subjects at all the visits indicated 
in Table 5 and Table 6 except for those female subjects with a documented history of 
bilateral tubal ligation, bilateral oophorectomy or hysterectomy or who are confirmed to 
be post-menopausal.  In addition, a serum pregnancy test will be performed at Screening 
and Day 1 and analyzed by the central laboratory.  All urine pregnancy tests will be 
performed on-site during the study visit if there is a scheduled visit, as indicated in 
Table 5 and Table 6 and monthly for a minimum of 7 months after the discontinuation of 
RBV, or according to the local RBV label and/or local treatment guidelines for RBV.  A 
positive urine pregnancy test requires a confirmatory serum test.  Urine pregnancy tests 
are not required after Day 1 for female subjects with a documented history of bilateral 
tubal ligation, hysterectomy, bilateral oophorectomy, or for subjects who are confirmed to 
be postmenopausal.  Confirmation of postmenopausal status will be determined during the 
Screening period, based on the subject's history and on the FSH level.
During post-treatment where there is not a scheduled study visit, female subjects of 
childbearing potential may either have pregnancy testing performed at the site as an 
unscheduled study visit using an unscheduled test kit or a urine pregnancy test may be 
conducted by the subject at home with a pregnancy test kit provided by the site; site 

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personnel should contact these female study subjects to capture the results of any study 
related pregnancy tests performed at home.  The at home pregnancy test results will only 
be recorded in the subject's source records.
If the subject elects to return to the study site for an unscheduled visit for pregnancy 
testing, the results of the urine pregnancy test will be captured in the eCRF, unless serum 
pregnancy is elected.  Serum pregnancy testing will be completed by the central 
laboratory.
Hepatitis and HIV Screen
HBsAg (hepatitis B surface antigen), anti-HCV Ab, anti-HIV Ab and HBV-DNA (only if 
HBsAg is negative) will be performed at Screening.  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.  The HBsAg and/or HBV DNA results 
will be reported by the central laboratory to the clinical database.
Urine Screens for Drugs of Abuse
Urine specimens will be tested at the Screening Visit for the presence of drugs of abuse.  
The panel for drugs of abuse will minimally include the drugs listed in Table 7.  A 
positive screen is exclusionary, with the exception of a positive screen associated with 
documented short-term use or chronic stable use of a prescribed medication in that class.
Subjects who otherwise meet all eligibility criteria, but have a positive urine alcohol 
screen, may have only the urine alcohol screen repeated as described in Section 5.1.1.  If 
the repeat urine screen is negative, and all other eligibility criteria have been met, the 
subject may be considered eligible for study participation.
These analyses will be performed by the certified central laboratory chosen for the study.

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Screening:  Liver Biopsy or FibroScan
To be eligible, subjects must have a diagnosis of cirrhosis by one of the following 
methods, per local standard practice:
●
Diagnosis on liver biopsy, e.g., Metavir Score of > 3 (including 3/4), Ishak 
score of > 4; or
●
FibroScan score ≥ 14.6 kPa within 6 months of Screening or during the 
Screening Period;
●
Subjects with a non-qualifying FibroScan result may only be enrolled if they 
have a qualifying liver biopsy.
Longitudinal FibroTest 
In addition to the assessments of cirrhosis performed during the Screening Period, all 
subjects will have FibroTest performed at baseline (Day 1) and throughout the 
Post-Treatment Period as indicated in Table 5 and Table 6 for the purpose of assessing 
changes in liver fibrosis over time.  Day 1 results will be blinded to the investigator/site.
Child-Pugh Score and Category
The Child-Pugh score uses five clinical measures of liver disease (3 laboratory parameters 
and 2 clinical assessments).  Child-Pugh score will be determined at the visits indicated in 
Table 8.

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Table 8.
Child-Pugh Classification of Severity of Cirrhosis
Parameter
Points Assigned for Observed Findings
1
2
3
Total bilirubin, μmol/L (mg/dL)
< 34.2 (< 2)
34.2 – 51.3 (2 – 3)
> 51.3 (> 3)
Serum albumin, g/L (g/dL)
> 35 (> 3.5)
28 – 35 (2.8 – 3.5)
< 28 (< 2.8)
INR
< 1.7
1.7 – 2.3
> 2.3
Ascites*
None
Slight
Moderate to severe
Hepatic encephalopathy**
None
Grade 1 or 2
(or suppressed with 
medication)
Grade 3 or 4
(or refractory)
*
None.
Slight ascites = Ascites detectable only by ultrasound examination.
Moderate ascites = Ascites manifested by moderate symmetrical distension of the abdomen.
Severe ascites = Large or gross ascites with marked abdominal distension.
**
Grade 0:  normal consciousness, personality, neurological examination, electroencephalogram.
Grade 1:  restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cps waves.
Grade 2:  lethargic, time-disoriented, inappropriate behavior, asterixis, ataxia, slow triphasic waves.
Grade 3:  somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves.
Grade 4:  unarousable coma, no personality/behavior, decerebrate, slow 2 to 3 cps delta activity.
Clinical Assessment of Hepatic Decompensation
A clinical assessment of hepatic encephalopathy and ascites will be performed at Day 1 
prior to dosing to confirm the subject has not progressed to hepatic decompensation since 
Screening.
Hepatocellular Carcinoma Screening:  Liver Ultrasound and Alpha Fetoprotein
In order to monitor for the presence of hepatocellular carcinoma (HCC), alpha fetoprotein 
will be assayed and an ultrasound of the liver will be performed as indicated in Table 5
and Table 6.
A positive Ultrasound result suspicious for HCC at screening will be confirmed with CT 
scan or MRI during the screening period.  Suspicious ultrasound lesions confirmed by CT 
or MRI are exclusionary.

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A positive Ultrasound result suspicious for HCC during the treatment or Post-Treatment 
Period will be confirmed with CT scan or MRI.  Confirmatory results should be discussed 
with the AbbVie Study Designated Physician as appropriate.
Concomitant Medication Assessment
Use of medications (prescription or over-the-counter, including vitamins and herbal 
supplements) from the time of signing the consent through 30 days after last dose of study 
drug will be recorded in the eCRF at each study visit indicated in Table 5.
During the Post-Treatment Period, antiviral therapies related to the treatment of HCV and 
medications prescribed in association with an SAE will be recorded in the eCRF at the 
visits indicated in Table 6.
Assignment of Subject Numbers
All screening activities must be completed and reviewed prior to enrollment.  Subjects 
who meet the eligibility criteria will proceed to enrollment via the IRT system on Day 1 
(Treatment Period).
Subject numbers will be unique 4-digit numbers and will begin with 1001 with the 
first two digits representing the investigative site, and the last two digits representing the 
subjects at that site.  Enrolled subjects will keep their subject number assigned at the 
Screening Visit.
Study Drug Diary
Subjects will be provided self-administration instructions and study drug diaries to record 
the exact date, time and number of tablets of study drug administration.  On Study Day 1,
the time of dosing will be recorded to the nearest minute by the site staff.  The exact date, 
time and number of tablets of study drug taken will be recorded daily by the subjects 
between study visits.  In the event the study drug diary is not available, the site may 
obtain dosing information via patient interview and record this information in the source 
notes.

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Patient Reported Outcomes (PRO) Instruments (Questionnaires)
Subjects will complete the self-administered PRO instruments (where allowed per local 
regulatory guidelines) on the study days indicated in Table 5 and Table 6.  Subjects will 
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 or understand any of the instruments may have site personnel 
read the questionnaires to them.  Site personnel will encourage completion of each 
instrument at all visits and will ensure that a response is entered for all items.
In this study, PRO instruments should be consistently presented so that subjects complete 
the SF-36v2 instrument first, followed by the EQ-5D-5L and followed by the HCVPRO.  
PRO instruments should be completed prior to drug administration (on Day 1) and prior to 
any discussion of adverse events or any review of laboratory findings, including HCV 
RNA levels.
Short Form 36 – Version 2 Health Status Survey
The SF-36v2 is a general Health Related Quality of Live (HRQoL) instrument with 
extensive use in multiple disease states.  The SF-36v2 instrument comprises 36 total items 
(questions) targeting a subject's functional health and well-being in 8 dimensions 
(physical functioning, role physical, bodily pain, general health, vitality, social 
functioning, role emotional and mental health).  Scoring is totaled into a Physical 
Component Summary and a Mental Component Summary.  Higher SF-36v2 scores 
indicate a better state of health.  Completion of the SF-36v2 should require approximately 
10 minutes to complete.
EuroQol-5 Dimensions-5 Level (EQ-5D-5L)
The EQ-5D-5L is a health state utility instrument that evaluates preference for health 
status (utility).  The 5 items in the EQ-5D-5L comprise 5 dimensions (mobility, self-care, 
usual activities, pain/discomfort, and anxiety/depression) each of which are rated on 

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5 levels of severity.  Responses to the 5 items encode a discrete health state which is 
mapped to a preference (utility) using country-specific based weights, where available.  
Subjects also rate their perception of their overall health on a separate visual analogue 
scale (VAS).  The EQ-5D-5L should require approximately 5 minutes to complete.
HCV Patient Report Outcomes (HCVPRO) Instrument
The HCVPRO has been developed specifically to capture the function and wellbeing 
impact of HCV conditions and treatment.  This instrument has been preliminarily 
validated and further validation is ongoing.  The HCVPRO contains 16 items important to 
HCV patients; items are totaled to a summary score.  Higher HCVPRO score indicates a 
better state of health.  Completion of the HCVPRO should require approximately 
5 minutes.
Study Drug Compliance for Kits
Study drug compliance will be recorded per kit in the IRT system.  Study drugs will be 
collected at each drug dispensation visit after Day 1, as indicated Section 5.5.6.  The 
number of tablets of ABT-450/r/ABT-267, ABT-333, and of RBV remaining in each 
bottle will be recorded in the source and transferred to the IRT system along with the date 
of reconciliation.
HCV Genotype and Subgenotype 
Plasma samples for HCV genotype and subgenotype will be collected at Screening.  
Genotype and subgenotype will be assessed using the Versant® HCV Genotype Inno 
LiPA Assay, Version 2.0 or higher (LiPA; Siemens Healthcare Diagnostics, Tarrytown, 
NY).
HCV RNA Levels
Plasma samples for HCV RNA levels will be collected as indicated in Table 5 and 
Table 6.  Plasma HCV RNA levels will be determined for each sample collected by the 

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central laboratory using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test 
v. 2.0. For this assay, the lower limit of quantification (LLOQ) is 15 IU/mL.
HCV Resistance Testing Sample
A plasma sample for HCV resistance testing will be collected at 0-hour (prior to dose) and 
2 hours post dose on Day 1 and at the study visits, indicated in Table 5 and Table 6.  
Specific instructions for preparation and storage of HCV RNA and HCV resistance 
samples will be provided by the central laboratory, the Sponsor, or its designee.
Archive Plasma Sample
Archive plasma samples will be collected at the study visits, indicated in Table 5 and 
Table 6.  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 the Sponsor.
Specific instructions for preparation and storage of archive samples will be provided by
the central laboratory, the Sponsor, or its designee.
Archive Serum Sample 
Archive serum samples will be collected at the study visits, indicated in Table 5 and 
Table 6.  Archive serum 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 the Sponsor.
Specific instructions for preparation and storage of archive samples will be provided by 
the central laboratory, the Sponsor, or its designee.

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Interferon Gamma-Induced Protein 10 (IP-10) Levels
A plasma sample for IP-10 testing will be collected at the study visits indicated in Table 5
and Table 6.  Specific instructions for preparation and storage of IP-10 samples will be 
provided by the central laboratory, the Sponsor, or its designee.
5.3.1.2
Meals and Dietary Requirements
All study drugs should be dosed together and administered with food, i.e., the AM dose of 
ABT-450/r/ABT-267, ABT-333 and RBV should be taken together with food and the PM 
dose of ABT-333 and RBV should be taken together with food. 
5.3.1.3
Blood Samples for Pharmacogenetic Analysis
IL28B Sample
One (required) whole blood sample for DNA isolation will be collected from each subject 
Day 1 for Interleuken 28B (IL28B) pharmacogenetic analysis.  This sample will not be 
used for any testing other than IL28B genotypes.
Optional Sample for Pharmacogenetic Analysis
A separate (optional) whole blood sample for DNA isolation will be collected on Day 1 
(Treatment Period) from each subject who consents to provide the optional sample for 
pharmacogenetic analysis.  If the optional pharmacogenetic sample is not collected at 
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.
Specific instructions for preparation and storage of archive samples will be provided by 
the central laboratory, the Sponsor, or its designee.
Samples will be stored in a secure storage space with adequate measures to protect 
confidentiality.  The samples will be retained while research on ABT-450, ABT-267 and 
ABT-333 (or drugs for the treatment of HCV) continues but no longer than 10 years.

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5.3.2
Drug Concentration Measurements
5.3.2.1
Collection of Samples for Analysis
Blood samples for pharmacokinetic assay of ABT-450, possible ABT-450 metabolites, 
ABT-267, possible ABT-267 metabolites, ABT-333, ABT-333 M1 metabolite, other 
possible ABT-333 metabolites, as well as ritonavir and RBV will be collected by 
venipuncture at each study visit, including at Day 1, for the 0-hour and 2-hour PK sample 
collection.  Intensive PK samples will be collected from at least 30 subjects at a visit on or 
after 2 weeks of the beginning of the treatment with DAAs.  Samples will be collected at 
predose and approximately 2, 4, 6, and at 24 hours post DDA dose.  Subjects may opt out 
of intensive PK sampling. 
The date and time of the first dose of each drug will be recorded in the source documents 
and the eCRF.  The time that each blood sample is collected will be recorded to the 
nearest minute.
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-450, possible 
ABT-450 metabolites, ABT-267, possible ABT-267 metabolites, ABT-333, ABT-333 
M1 metabolite, other possible ABT-333 metabolites, ritonavir and RBV will be provided 
by the central laboratory, the Sponsor, or its designee.
5.3.2.3
Disposition of Samples
The frozen plasma samples for the pharmacokinetic assays of ABT-450, possible 
ABT-450 metabolites, ABT-267, possible ABT-267 metabolites, ABT-333, ABT-333 
M1 metabolite, other possible ABT-333 metabolites, ritonavir, RBV and archive plasma 
samples will be packed in dry ice sufficient to last during transport, and transferred from 
the study site to the central laboratory.  Specific instructions for shipping to the analytical 
lab from the central laboratory will be provided by the central laboratory, the Sponsor, or 
its designee. 

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5.3.2.4
Measurement Methods
Plasma concentrations of ABT-450, ritonavir, ABT-267, ABT-333, ABT-333 
M1 metabolite, and RBV will be determined using validated assay methods under the 
supervision of the Drug Analysis Department at AbbVie.  Plasma concentrations of 
possible metabolites of ABT-450 and ABT-267, and other metabolites of ABT-333 may 
also be determined using non-validated methods.
5.3.3
Efficacy Variables
Virologic response will be assessed by HCV RNA in IU/mL at various time points from 
Day 1 through 48 weeks after completion of treatment.
5.3.3.1
Primary Variable
The primary endpoints are the percentage of subjects with SVR12 (HCV RNA < LLOQ 
12 weeks after the last actual dose of study drug) and the percentage of subjects with 
SVR24 (HCV RNA < LLOQ 24 weeks after the last actual dose of study drug).
5.3.3.2
Secondary Variable(s)
The secondary endpoints are: 
●
The percentage of subjects with on-treatment virologic failure;
●
The percentage of subjects with relapse by post treatment Week 12;
●
The percentage of subjects with relapse by post treatment Week 24.
5.3.3.3
Resistance Variables
The following resistance analyses will be performed for subjects receiving study drugs 
who experience virologic failure (who have HCV RNA ≥ 1000 IU/mL):  
1.
the amino acid variants at baseline at signature resistance-associated positions 
identified by population nucleotide sequencing and comparison to the prototypic 
reference sequence,

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2.
the amino acid variants in available post-baseline samples identified by population 
nucleotide sequencing and comparison to the baseline sequence, 
3.
the amino acid variants in available post-baseline samples at signature resistance 
associated positions identified by population nucleotide sequencing and 
comparison to the prototypic reference.
5.3.4
Safety Variables
The following safety evaluations will be analyzed during the study:  adverse event 
monitoring and vital signs, physical examination, ECG, and laboratory tests assessments.  
5.3.5
Pharmacokinetic Variables
Values for the pharmacokinetic parameters of ABT-450, ABT-267, ritonavir, ABT-333, 
ABT-333 M1 metabolite, and RBV including the Cmax, Tmax, Ctrough, and AUC will be 
determined by noncompartmental methods using data from subjects who participate in the 
intensive pharmacokinetic sampling.  Additional parameters or summaries may be 
determined if useful in the interpretation of the data.
Individual plasma concentrations and pharmacokinetic parameters of ABT-450, 
ABT-267, ritonavir, ABT-333, ABT-333 M1 metabolite, ribavirin and possible 
metabolites of ABT-450, ABT-267, and ABT-333 (other than ABT-333 M1) will be 
tabulated and summarized.
5.3.6
Pharmacogenetic Variables
IL28B genotypes are associated with response to pegIFN/RBV.  IL28B status will be 
determined for each subject and analyzed as a factor contributing to the subject's response 
to study treatment.  These IL28B genotype results may be analyzed as part of a 
multi-study assessment of IL28B and response to ABT-450, ABT-267, ABT-333, or 
drugs of these classes.  The results may also be used for the development of diagnostic 

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tests related to IL28B and study treatment, or drugs of these classes.  The results of 
additional pharmacogenetic analyses may not be reported with the clinical study report.
Additional parameters or summaries may be determined if useful in the interpretation of 
the data.
DNA samples from subjects who separately consent for additional pharmacogenetic 
analysis may be analyzed for genetic factors contributing to the subject's response to study 
treatment, in terms of pharmacokinetics, pharmacodynamics, 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 (including IL28B).  Some genes currently insufficiently characterized or 
unknown may be understood to be important at the time of analysis.  Pharmacogenetic 
analyses will be limited to studying response to HCV therapy; no other analyses will be 
performed.
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 course of study drug administration, the subject prematurely discontinues 
during the Treatment Period or the Post-Treatment Period, the procedures outlined for the 
applicable Premature D/C Visit should be completed as defined in Table 5 and Table 6.  
  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 

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accordance with the Investigator's best clinical judgment.  The last dose of any study drug 
and reason for discontinuation from the Treatment Period 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 48 weeks for safety, HCV RNA, the emergence 
and persistence of resistant viral variants and PROs.
If a subject is discontinued from study drug (Treatment Period) 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 Treatment Period, the administration of study drug 
(including RBV) to that subject must be discontinued immediately.  Specific instructions 
regarding subject pregnancy can be found in Section 6.6.  Subjects will be monitored for 
SVR in the Post-Treatment Period as described in Section 5.1.3.  The Investigator is also 
encouraged to report the pregnancy information to the voluntary RBV Pregnancy 
Registry.
5.4.1.1
Virologic Failure Criteria
The following criteria will be considered evidence of virologic failure.  Subjects 
demonstrating any of the following will be discontinued from study drug:
●
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;
●
Failure to achieve HCV RNA < LLOQ by Week 6 (≥36 days of treatment); or
●
Confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA 
measurements ≥ LLOQ) at any point after HCV RNA < LLOQ during 
treatment.

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Confirmatory testing should be completed as soon as possible.  Subjects should remain on 
study treatment until the virologic failure has been confirmed.
If any of the above criteria are met for subjects on DAA therapy, the subject will 
discontinue study treatment (Section 5.4.1).  Subjects with HCV RNA < LLOQ at the end 
of treatment and who have a confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive 
HCV RNA measurements ≥ LLOQ) at any point in the Post-Treatment Period will be 
considered to have relapsed.  Confirmation of an HCV RNA ≥ LLOQ in the 
Post-Treatment Period should be completed as soon as possible.
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.
5.5
Treatments
5.5.1
Treatments Administered
Each dose of study drug (ABT-450/r/ABT-267, ABT-333 and RBV) will be dispensed in 
the form of tablets at the visits listed in Table 6. 
ABT-450/r/ABT-267 will be provided by the Sponsor as 75 mg/50 mg/12.5 mg tablets.  
ABT 450/r/ABT-267 will be taken orally as 2 tablets once daily which corresponds to a 
150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 dose QD.
ABT-333 will be provided by the Sponsor as 250 mg tablets.  ABT-333 will be taken 
orally as 1 tablet twice daily, which corresponds to a 250 mg dose BID.

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RBV will also be provided by the Sponsor to the Investigator for use in this study.  RBV 
will be provided as 200 mg tablets for Korea and Taiwan sites.  RBV will be provided as 
100 mg tablets for China sites.  RBV has weight-based dosing 1000 to 1200 mg divided 
twice daily per local label.  (For example, for Korea and Taiwan subjects weighing less 
than 75 kg, 200 mg RBV may be taken orally as 2 tablets in the morning and 3 tablets in 
the evening which corresponds to a 1000 mg total daily dose.  Or for subjects weighing 
75 kg or more, 200 mg RBV may be taken orally as 3 tablets in the morning and 3 tablets 
in the evening which corresponds to a 1200 mg total daily dose.  For example, for Chinese 
subjects weighing less than 75 kg, RBV 100 mg tablets may be taken orally as 
five 100 mg tablets in the morning and five 100 mg tablets in the evening which 
corresponds to a 1000 mg total daily dose.  Or for Chinese subjects weighing 75 kg or 
more, RBV 100 mg tablets may be taken orally as six 100 mg tablets in the morning and 
six 100 mg tablets in the evening which corresponds to a 1200 mg total daily dose.)
At Day 1 subjects will be administered study drugs by the study site personnel and receive 
instructions for self-administration of all study drugs from Study Day 2 through Study 
Week 12 of the Treatment Period.  
On the day of intensive PK subjects will take their morning dose of DAAs and RBV 
onsite in the presence of study site personnel and the time of administration will be noted.
Subjects will be instructed to take study medication at the same time(s) every day.  All 
compounds should be taken with food.
Following enrollment, the site will use the IRT system to obtain the study drug kit 
numbers to dispense at the study visits indicated in Section 5.5.7.  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 Treatment Period 
or at the Premature D/C Visit from the 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).

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All subjects who receive at least one dose of DAA and who fail to achieve virologic 
suppression, or who experience virologic breakthrough on DAA therapy will be 
discontinued from treatment.  Resistance monitoring will continue in the Post-Treatment 
Period regardless whether subjects opt for alternative post-study treatment.
5.5.2
Identity of Investigational Product
Information about the study drugs to be used in this study is presented in Table 9.
Table 9.
Identity of Investigational Products
Investigational Product
Manufacturer
Mode of 
Administration
Dosage Form
Strength
ABT-450/ 
Ritonavir/ABT-267
AbbVie
Oral
Tablet
75 mg/50 mg/ 
12.5 mg
ABT-333
AbbVie
Oral
Tablet
250 mg
Ribavirin for Korea and 
Taiwan
Roche or Generic 
Manufacturer
Oral
Tablet
200 mg
Ribavirin for China
Shanghai Sine 
Tianping 
Pharmaceutical 
Co., Ltd.
Oral
Tablet
100 mg
5.5.2.1
Packaging and Labeling
ABT-450/r/ABT-267 tablets will be supplied in bottles containing 64 tablets.  ABT-333 
will be supplied in bottles containing 64 tablets.  Ribavirin 200 mg will be supplied in 
bottles containing 168 tablets each for Korea and Taiwan.  Ribavirin 100 mg will be 
supplied in cartons for China.  Each Ribavirin 100 mg carton will contain a blister pack of 
24 tablets for China.
Each bottle or carton will be labeled as required per country requirements.  
The labels must remain affixed to the bottles or cartons.  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 Drugs
Study Drug
Storage Conditions
ABT-450/Ritonavir/ABT-267 bottles
15° to 25°C (59° to 77°F)
ABT-333 bottles
15° to 25°C (59° to 77°F)
Ribavirin 200 mg bottles 
Ribavirin 100 mg cartons 
15° to 25°C (59° to 77°F) 
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 the Sponsor.  Upon receipt of study drugs, 
the site will acknowledge receipt within the IRT system.
5.5.3
Method of Assigning Subjects to Treatment 
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 study drug kit numbers.  The study drug 
kit 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. 
5.5.4
Selection and Timing of Dose for Each Subject
Selection of the doses for this study is discussed in Section 5.6.5.  Study drug dosing will 
be initiated at the Study Day 1 Visit.  

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ABT-450/r/ABT-267 will be dosed QD; ABT-333 and RBV will be dosed BID.  Thus 
with normal dosing, 2 ABT-450/r/ABT-267 tablets, 1 ABT-333 tablet, should be taken in 
the morning, and 1 ABT-333 tablet should be taken in the evening. 
RBV should be dosed BID, e.g., 2 to 3 tablets taken in the morning, and 3 RBV tablets 
taken in the evening for subjects in Korea and Taiwan, or 5 to 6 tablets taken in the 
morning and 5 to 6 tablets taken in the evening for subjects in China.
All study drugs should be dosed together and administered with food i.e., the AM dose of 
ABT-450/r/ABT-267, ABT-333 and RBV should be taken together with food and the PM 
dose of ABT-333 and RBV should be taken together and with food.
5.5.5
Blinding
This is an open-label study.
5.5.5.1
Data Monitoring Committee 
An independent DMC will review safety data and provide recommendations to the 
Sponsor as per the DMC charter.  The charter also describes DMC membership, which 
will include individuals with experience in the management of patients with chronic HCV 
infection, and member responsibilities.  The DMC will receive interim summaries of 
safety data according to a schedule and format specified in the charter.  After each review, 
the DMC will communicate its recommendations to the Sponsor.  The Sponsor will retain 
sole responsibility for study management, communication with study sites and regulatory 
authorities.
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.  All study drugs will be dispensed to subjects by study-site personnel under the 
direction of the Investigator.

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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.  Subjects will be administered study drugs at the site 
at the Day 1 Visit.  The start and stop dates of all study drugs will be recorded in the 
source documents and eCRFs.  Subjects will be provided self-administration instructions 
and study drug diaries to record the exact date, time and number of tablets of study drug 
administration each day between study visits. 
Subjects will be instructed to return all bottles of ABT-450/r/ABT-267 and ABT 333 (full, 
partial, or empty) and bottles and/or blister packs or cartons of RBV (full, partial or 
empty) to the study site at each visit indicated in Table 3.  At every study visit, during the 
Treatment Period, study site personnel will inspect the contents of the bottles and record 
the status of each one as well as the exact number of remaining tablets of 
ABT-450/r/ABT-267 and ABT-333 or tablets of RBV in IRT at the dispensing visits and 
in the source at all other Treatment Period visits (Weeks 1, 2, 6, and 10).  Study drugs 
may be re-dispensed at Treatment Period Weeks 1, 2, 6 and 10 therefore, Reconciliation 
in IRT should occur only when the bottles are returned to the site at the dispensation visits 
during the Treatment Period in Table 2.  If poor adherence is noted, the subject should be 
counseled and this should be documented in the subject's source.
Study drugs should not be interrupted for toxicity management or any other reason for 
more than 7 days consecutively.  If study drugs need to be interrupted for more than 
7 days consecutively, the Study Designated Physician should be contacted and 
consideration should be given to discontinue the subject.
At Day 1, for the 0-hour and 2-hour PK sample collection, the date and time of the 
first dose of each drug will be recorded in the source documents and the eCRF.  The date 
of last dose of all study drugs will be recorded in the source documents and the 
appropriate eCRF. 

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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.  This will be documented by signing and dating the 
Proof of Receipt (POR) or similar document and via recording in the IRT system.  A 
current (running) and accurate inventory of study drug will be kept by the Investigator and 
will include lot number, POR 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 Treatment Period.  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, 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 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 bottle, 
number of each type 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 Treatment Period, all original study drug 
bottles (containing unused study drugs) will be returned to the Sponsor (or designee) or 
destroyed on site.  All destruction procedures will be according to instructions from the 
Sponsor 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.

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5.6
Discussion and Justification of Study Design
5.6.1
Discussion of Study Design and Choice of Control Groups
The Phase 3 Study M13-099 demonstrated a high SVR12 of 99% with ABT-450/r/ 
ABT-267 + ABT-333 with ribavirin for 12 weeks treatment in subjects infected with 
HCV genotype 1 and with compensated cirrhosis except those with HCV genotype 1a 
who were prior null responders.  Study M13-099 was conducted globally except Asia.  
The current single arm study is evaluating the safety and efficacy of the same regimen in 
Asian subjects infected with HCV genotype 1b and with compensated cirrhosis.  No 
control arm is required per design.
The regulatory requirements for the primary endpoint differ for countries participating in 
this trial.  Currently SVR12 is accepted as the primary endpoint by health authorities in 
S. Korea and Taiwan but not in China.  Therefore, for S. Korea and Taiwan, superiority of 
the SVR12 rate to the historical SVR rate for telaprevir plus pegIFN/RBV therapy is 
specified as a primary endpoint.  For China, superiority of the SVR 12 and SVR24 rates to 
the historical SVR rate for telaprevir plus pegIFN/RBV therapy in genotype 1 HCV
infected patients with cirrhosis is specified as the primary endpoints.  
5.6.2
Appropriateness of Measurements
Standard pharmacokinetic, statistical, clinical, and laboratory procedures will be utilized 
in this study.  HCV RNA assays are standard and validated.  Clonal and population 
sequencing methods are experimental.  The SF-36v2 and EQ 5D 5L instruments are 
standard in the literature and thoroughly validated.  The HCVPRO is preliminarily 
validated and has demonstrated excellent responsiveness in patients with HCV.
5.6.3
Justification of Primary Endpoint Success Criteria
The current study is a Asian study examining the combination of ABT-450/r/ABT-267 
and ABT-333 administered with RBV for 12 weeks in treatment-naïve and IFN based 
therapy (IFN [alpha, beta or pegIFN] with RBV) treatment-experienced HCV genotype 
1-infected subjects with compensated cirrhosis.  This is a similar trial design as in AbbVie 

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Study M13-099.  In Study M13-099, the SVR12 rate for each treatment arm was compared 
to an historical SVR rate for telaprevir plus pegIFN and RBV (54%, see Table 10).  A 
weighted average of the corresponding SVR rates among treatment-naïve and 
treatment-experienced (prior relapsers, partial responders and null responders) in HCV 
genotype 1 infected cirrhotic subjects was calculated to reflect the population expected to 
enroll in Study M13-099.  The historical rate of 54% was defined conservatively as the 
upper bound of the 95% confidence interval for the telaprevir-based rate. 
Table 10.
Estimated SVR Rates for Telaprevir Plus PegIFN and RBV in 
Cirrhotic Subjects
Telaprevir-Treated 
Subjects with 
Cirrhosis n/N (%)
Projected Enrollment 
in Study M13-099 (%)
Population-Based 
Weighted Average % 
[95% CI]
Meta Analysis of ADVANCE57 and ILLUMINATE57 Studies
Naïve Subjects
(56)
53
REALIZE57
Prior relapsers
48/57 (84)
12
47 [41, 54]
Prior partial responders
11/32 (34)
12
Prior null responders
7/50 (14)
23
Consistent with Study M13-099, the SVR12 and SVR24 rates from the current study will 
be compared to a clinically relevant threshold based on historical SVR rates for telaprevir 
plus pegIFN/RBV.  However, since the historical SVR rate used in Study M13-099 is 
based on a population that included HCV genotype 1a-infected cirrhotic subjects as well 
as HCV genotype 1b-infected cirrhotic subjects, a higher threshold will be used in this 
study to account for a genotype 1b only population.  
Because data are not available on the subpopulation of HCV genotype 1b-infected 
subjects with cirrhosis treated with telaprevir plus pegIFN/ RBV, the SVR rates in HCV 
genotype 1a and genotype 1b-infected, non-cirrhotic subjects treated with telaprevir plus 
pegIFN/RBV were used to determine an appropriate adjustment factor to increase the 
historical rate used in Study M13-099.  An appropriate adjustment factor was determined 
based on the relative failure rate between the HCV genotype 1b and genotype 1a 

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populations in the telaprevir ADVANCE, ILLUMINATE, and REALIZE studies Table 11
and Table 12).  For treatment-naïve subjects, the SVR failure rate in genotype 1b subjects 
was reduced by a relative 29% (from 28% to 20%) from the SVR rate for genotype 1a 
subjects (Table 11).  For treatment-experienced subjects, the SVR failure rate in genotype 
1b was also reduced by a relative 29% (from 41% to 29%) from the SVR rate for 
genotype 1a subjects (Table 12).  Since the SVR rate for the genotype 1a cirrhotic 
subjects is not available and SVR rate for all cirrhotic patients would be higher than that 
for genotype 1a cirrhotic subjects, it would be more conservative to estimate the SVR rate 
for the genotype 1b cirrhotic subjects by taking 29% reduction from the combined data 
from genotype 1a + genotype 1b cirrhotic subjects together.  Therefore, to account for the 
exclusion of HCV genotype 1a-infected subjects in the current study, the historical SVR 
failure rate of 46% used in Study M13-099 for genotype 1 was reduced by a relative 29%, 
resulting in a 33% failure rate (or 67% SVR rate) for genotype 1b.  The rate of 67% 
should be conservative because the 54% was based on a population that was a mix of 
genotype 1a and 1b and the expectation is that the SRV rate for genotype 1a subjects 
would be lower than the SVR rate for the mix population of genotype 1a and 1b subjects.
Hence, for this current study, for a regimen to be considered superior to a clinically 
meaningful threshold based on SVR rates for telaprevir plus pegIFN/RBV, the lower 
confidence bound of the SVR rate must exceed 67%.  The value of 67% used for the 
superiority comparison represents the 54% historical genotype 1 SVR rate plus a relative 
29% adjustment factor for the exclusion of genotype 1a subjects.
Table 11.
SVR Rates for Telaprevir Plus pegIFN and RBV Therapy in 
Treatment-Naïve Subjects by Subgenotype
Telaprevir Studies
ADVANCE
ILLUMINATE
Meta Analysis
T12/PR n/N (%)
T12/PR n/N (%)
T12/PR % [95% CI]
Treatment-naïve GT1a 
subjects 
162/217 (75)57
273/388 (70)58
72 [68, 75]
Treatment-naïve GT1b 
subjects
119/142 (84)57
112/149 (75)59
80 [75, 84]
GT1a = genotype 1a; GT1b = genotype 1b

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Table 12.
Estimated SVR Rates for Telaprevir-Based Therapy in Treatment Experienced Subjects by Subgenoytpe
REALIZE†‡
GT1a 
(Pooled T12/PR48) 
n/N (%)
With Increase for 
Excluding Cirrhotics 
(%)
GT1b
(Pooled T12/PR48) 
n/N (%)
With Increase for 
Excluding Cirrhotics 
(%)
Population-Based 
Weighted Average* % 
[95% CI]
Relapsers
119/142 (83.8)
84.3
123/140 (87.9)
88.4
GT1a
59 [53, 65]
GT1b
71 [64, 77]
Partial responders
26/55 (47.3)
59.3
27/40 (67.5)
79.5
Null responders
24/88 (27.3)
36.5
22/59 (37.3)
46.5
GT1a = genotype 1a; GT1b = genotype 1b
†
US Prescribing Information for INCIVEK™ (telaprevir).  Vertex Pharmaceuticals Incorporated; Cambridge, MA.
‡
Zeuzem S, Andreone P, Pol S, et al.  REALIZE trial final results:  telaprevir-based regimen for GT1 hepatitis c virus infection in patients with prior null response, partial 
response or relapse to peginterferon/ribavirin.  J Hepatol.  2011;54Suppl:S3.
*
Based on a population of 30% relapsers, 35% partial responders, 35% null responders.

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5.6.4
Suitability of Subject Population 
This study plans to enroll both HCV treatment-naïve and treatment-experienced 
(pegIFN/RBV) subjects with genotype 1b chronic HCV and compensated cirrhosis.
The selection of subject population is based on the results from the Phase 3 trial 
Study M13-099.  Study M13-099 demonstrated high SVR12 100% and 98% with a 
12-week regimen of ABT-450/r/ABT-267 + ABT-333 with ribavirin in the treatment of 
naïve and treatment-experienced subjects infected with HCV genotype 1b and with 
compensated cirrhosis.  Study M13-099 was conducted globally except Asia and Russia.  
The goal of the current study is to confirm the results form Study M13-099 in Asian 
subjects infected with genotype 1b chronic HCV and compensated cirrhosis.
5.6.5
Selection of Doses in the Study
Doses of the three DAAs to be used in this study have shown significant antiviral activity 
and have been shown to be generally safe and well tolerated both as monotherapy, in 
combination with pegIFN + RBV, and in combination with each other and RBV in 
western studies.  Of note, coadministration of ABT-450/r, ABT-267 and ABT-333 at the 
doses planned for use in this study do not clinically significantly impact plasma exposures 
compared to administration as single agents thus dose adjustments based on drug 
interactions are not required.
ABT-450/r
An ABT-450 dose of 150 mg QD using the ABT-450/r/ABT-267 co-formulated tablet has 
been selected to for Phase 3 studies.  The same dose and formulation was used in western 
Phase 3 studies.
The ABT-450/r doses of 100/100 and 150/100 mg evaluated in the western Phase 2 
studies using the ABT-450 SDD tablet provided high ITT SVR12 rates in treatment-naïve 
(100% and 95%, respectively) and treatment-experienced (91% and 95.5%, respectively) 
subjects when dosed with ABT-333 and ABT-267 + RBV.  The higher ABT-450 dose of 
150 mg, administered with 100 mg ritonavir has been selected to advance into western 

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Phase 3 studies as it provides an optimal balance between safety and suppression of 
resistant variants.
In combination with other DAAs ± RBV, the highly fit, moderately resistant R155K viral 
variant was observed in a lower fraction of patients who had virologic failure at the 
150/100 and 200/100 mg ABT-450/r dose (SDD tablet of ABT-450) compared to the 
100/100 mg ABT-450/r dose.  This finding is consistent with monotherapy data for 
ABT-450/r where the higher 200/100 mg dose of ABT-450/r selected fewer resistant 
variants including R155K as compared to the lower 50/100 and 100/100 mg doses of 
ABT-450/r.  Higher doses were also associated with higher SVR24 rates when combined 
with pegIFN and RBV.  Thus based on resistance profile and SVR24 data with pegIFN + 
RBV, higher doses provide better efficacy.  However, ABT-450 doses of 200/100 and 
250/100 mg (SDD tablet) were associated with a greater incidence of grade 3+ ALT 
elevations (4% to 5% at doses ≥ 200/100 versus 0.3% to 0.5% at lower doses) suggesting 
that doses ≤ 200/100 mg SDD tablet might have a more favorable safety profile.  In 
western subjects, the ABT-450 150 mg dose from the ABT-450/r/ABT-267 co-formulated 
tablets planned for this study has a ~60% higher exposure compared to the 150/100 mg 
SDD tablet but the exposure is ~50% lower than that from the 200/100 mg SDD 
formulation.  The 150 mg ABT-450 dose from the co-formulation will hence provide a 
good balance between minimize the incidence of asymptomatic, transient grade 3 ALT 
elevations while maximizing virologic suppression.
ABT-450 exposures from the ABT-450/r/ABT-267 co-formulated tablets are comparable 
between Chinese and Western subjects.  Thus, same dose of ABT-450 is hence 
recommended in Western and Chinese subjects.
ABT-333
An ABT-333 dose of 250 mg BID using the optimized tablet formulation that is expected 
to provide exposures comparable to the 400 mg BID dose used in Phase 2 studies has 
been selected to for Phase 3 studies.  The same dose and formulation was used in western 
Phase 3 studies.  This is based on comparable efficacy and better safety profile compared 

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to exposures at higher ABT-333 doses.  Comparable viral load decline following 
monotherapy (approximately 1 log10 IU/mL) was observed at exposures greater than that 
achieved with the 400 mg BID dose evaluated in western Phase 2 studies.  Additionally, 
the 400 and 800 mg BID doses resulted in identical SVR rates (63%) when combined 
with pegIFN and RBV for 12 weeks followed by 36 weeks of pegIFN + RBV, indicating 
that increasing ABT-333 dose > 400 mg BID did not improve efficacy.  Furthermore, 
available data from the Phase 2b study indicates that when ABT-333 400 mg BID dose is 
combined with ABT-450, ABT-267 and RBV for 12 weeks, very high SVR12 rates were 
observed in treatment-naïve and treatment-experienced subjects (> 90%).  While both the 
400 mg BID and 800 mg BID doses of ABT-333 in combination with pegIFN and RBV 
were well tolerated by HCV-infected subjects for 12 weeks, the 800 mg BID dose was 
associated with a greater mean hemoglobin reduction compared to the 400 mg BID dose 
and compared to placebo plus pegIFN and RBV.  Therefore, 400 mg ABT-333 in tablet 
formulation is favored.
In the western subjects, the 250 mg optimized tablet used in the current study has 
comparable bioavailability to the 400 mg tablet formulation used in western Phase 2 
studies.  Hence, the ABT-333 250 mg optimized tablet dosed BID was selected as the 
Phase 3 formulation as it provides exposures that maximizes efficacy and a superior safety 
profile compared to higher ABT-333 doses.
The ABT-333 250 mg optimized tablet, alone or in combination, has not been evaluated 
in Chinese subjects.  However, ABT-333 400 mg tablet (which is bioequivalent to the 
ABT-333 250 mg optimized tablet) was evaluated as a part of the 3-DAA regimen, 
ABT-450/r + AB-267 + ABT-333, in Chinese and Western subjects (Study M12-221).  
Following administration of the 3-DAA combination (ABT-450/r 150/100 mg QD + 
ABT-267 25 mg QD + ABT-333 400 mg BID) for 21 day, ABT-333 exposures in Chinese 
subjects were comparable to Caucasian subjects with this 400mg tablet formulation.  
Thus, same dose of ABT-333, 250 mg optimized tablet, can be used in Chinese and 
Western subjects.

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ABT-267
An ABT-267 dose of 25 mg QD using the ABT-450/r/ABT-267 co-formulated tablet has 
been selected to for Phase 3 studies.  The same dose and formulation was used in Western 
Phase 3 studies.
Compared to higher doses, the 25 mg QD dose provided comparable viral load decline 
following monotherapy and lower potential to decrease ABT-450 exposures.  In Western 
subjects, following 2 to 3 days of ABT-267 monotherapy at doses of 1.5 mg to 200 mg 
QD, the 25 mg dose of ABT-267 showed viral load decline comparable to higher doses 
with none of the rebound between doses seen at lower doses.  Resistance analysis 
following monotherapy suggests that doses significantly greater than 25 mg would be 
needed to improve the resistance profile as a variety of NS5A resistant mutants were 
observed following monotherapy with doses of 5 mg to 200 mg.  In addition, higher 
ABT-267 doses have been associated with decreases in ABT-450 exposures; the ABT-267 
200 mg dose resulted in ~80% lower ABT-450 exposures when ABT-450 250 mg was 
dosed with 100 mg ritonavir.  Hence, doses > 25 mg could decrease the exposures of the 
"anchor" molecule ABT-450, without providing significant benefit in terms of improved 
efficacy.  Additionally, available data from the Phase 2b study indicates that when 
ABT-267 25 mg QD dose is combined with ABT-450, ABT-333 and RBV for 12 weeks, 
very high SVR12 rates were observed in treatment-naïve and treatment experienced 
subjects (> 90%).
In Western subjects, the co-formulated ABT-450/r/ABT-267 formulation used in the 
current study has ABT-267 bioavailability comparable to the ABT-267 25 mg tablet used 
in Phase 2 studies.  In addition, ABT-450 exposures from the ABT-450/r/ABT-267 
co-formulated tablets are comparable between Chinese and Western subjects.  Thus, same 
dose of ABT-450 can be used in Chinese and Western subjects.
Hence, the ABT-267 dose in the current study is the 25 mg dose, as it provides exposures 
that maximizes efficacy without compromising ABT-450 exposures.

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RBV
The daily dose of RBV selected in Western Phase 2 and 3 studies is 1000 mg to 1200 mg, 
divided twice daily, and based on subject weight.  This dose was chosen as it was the 
approved dose for treatment of adult patients with chronic hepatitis C infection in 
combination with pegIFN.  The same dose is selected for this study because its safety 
profile has been well characterized when administered with pegIFN, including the 
incidence of hemolytic anemia, and there are well-defined dose reduction criteria in the 
event of RBV-induced anemia.  In addition, this dose was studied in the absence of 
pegIFN in subjects with chronic hepatitis C infection in Studies M12-267, M12-746, 
M12-998 and M11-652 and was found to be generally safe and well-tolerated and resulted 
in high SVR rates.
In Chinese subjects, the recommended dose of RBV with an IFN-based regimen is weight 
based, 1000 mg daily in subjects with a body weight of less than 75 kg, and 1200 mg 
daily in subjects with a body weight of greater than or equal to 75 kg, per the Chinese 
HCV Treatment Guidelines.59  Hence, for the Regional Phase 3 studies, the proposed 
RBV dose is weight-based 1000 mg or 1200 mg.
Doses comparable to, and higher than, the DAA doses to be administered in this study 
have been studied in single- and multiple-dose healthy volunteer studies and administered 
to western HCV-infected subjects as monotherapy or in combination with pegIFN/RBV 
and found to be generally safe and well tolerated.  In addition, the pharmacokinetics of 
ABT-450, ABT-267 and ritonavir when given in combination to western subjects with 
mild hepatic impairment were comparable to or slightly lower than in subjects with 
normal hepatic function.  The area under the concentration curve (AUC) of ABT-450 and 
ABT-267 were comparable (≤ 30% change) in subjects with mild hepatic impairment 
compared to healthy controls.  The AUC for ritonavir was 34% lower in subjects with 
mild hepatic impairment.  Additionally, based on the package insert for RBV, dose 
adjustments are not required in subjects with mild hepatic impairment.

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Based on these data, no dose adjustment is required for Chinese subjects with 
compensated cirrhosis taking the DAA combination in this study.  The doses of ABT-267, 
ABT-333 and ABT-450/r chosen for this study in compensated cirrhotic subjects are the 
same that was used in Phase 3 studies for the IFN-free 3-DAA Study in Western subjects 
(Study M13-099).
The maximum dose of ABT-450/r/ABT-267 75 mg/50 mg/12.5 mg tablets will not exceed 
150 mg/100 mg/25 mg per day for 12 weeks.  The maximum dose of ABT-333 250 mg 
tablets administered in this study will not exceed 500 mg per day for 12 weeks.  The 
maximum RBV dose administered in this study will not exceed 1200 mg, divided 
twice daily for 12 weeks.
6.0
Adverse Events
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.
All adverse events will be followed to a satisfactory conclusion.
6.1
Definitions
6.1.1
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 

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necessarily have a causal relationship with this treatment.  An adverse event 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 adverse event.  
Worsening in severity of a reported adverse event should be reported as a new adverse 
event.  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, meets protocol specific criteria (see Section 6.7 regarding toxicity 
management) and/or if the investigator considers them to be adverse events.
An elective surgery/procedure scheduled to occur during a study will not be considered an 
adverse event 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 adverse event.
6.1.2
Serious Adverse Events
If an adverse event 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 serious 
adverse event.
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would have 
resulted in immediate fatality if medical intervention had not 
been taken.  This does not include an event that would have 
been fatal if it had occurred in a more severe form.

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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 serious adverse events with the outcome of death, the date and cause of death will be 
recorded on the appropriate case report form.
6.2
Adverse Event Severity
The investigator will use the following definitions to rate the severity of each adverse 
event:

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Mild
The adverse event is transient and easily tolerated by the subject.
Moderate
The adverse event causes the subject discomfort and interrupts the 
subject's usual activities.
Severe
The adverse event causes considerable interference with the subject's 
usual activities and may be incapacitating or life-threatening.
6.3
Relationship to Study Drug
The investigator will use the following definitions to assess the relationship of the adverse 
event to the use of DAAs (ABT-450/r/ABT-267 and ABT-333), and RBV:
Reasonable 
Possibility
An adverse event where there is evidence to suggest a causal 
relationship between the study drug and the adverse event.
No Reasonable 
Possibility
An adverse event where there is no evidence to suggest a causal 
relationship between the study drug and the adverse event.
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, another cause of the event must be provided by the investigator for the serious 
adverse event.
6.4
Adverse Event Collection Period
All serious adverse events as well as protocol-related nonserious adverse events 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 after last 
administration AEs and SAEs will be collected whether solicited or spontaneously 

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reported by the subject. From 30 days after last dose until the end of study, SAEs will be 
collected.  
Adverse event information will be collected as shown in Figure 3.
Figure 3.
Adverse Event Collection
6.5
Adverse Event Reporting
In the event of a serious adverse event, whether associated with study drug or not, the 
Investigator will notify Clinical Pharmacovigilance within 24 hours of the site being made 
aware of the serious adverse event by entering the serious adverse event data into the 
electronic data capture (EDC) system.  Serious adverse events that occur prior to the site 
having access to the RAVE® system or if RAVE is not operable s should use the SAE 
non-CRF paper forms and send them to Clinical Pharmacovigilance within 24 hours of 
the site being aware of the serious adverse event.
FAX to:  
Email:  

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For safety concerns, contact the Antiviral Safety Team at:
For any subject safety concerns, please contact the Primary Study Designated Physician 
listed below:
In case of subject safety concerns or medical emergencies when the Primary Study 
Designated Physician is unavailable, please call the following central back-up number:
Phone:  

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The sponsor will be responsible for Suspected Unexpected Serious Adverse Reactions 
(SUSAR) reporting for the Investigational Medicinal Product (IMP) in accordance with 
Directive 2001/20/EC.  The reference document used for SUSAR reporting in the EU 
countries will be the most current version of the Investigator's Brochure.  
6.6
Pregnancy
Subjects and their partners should avoid pregnancy and males should avoid sperm 
donation throughout the course of the study, starting with Day 1 and for 7 months after 
the last dose of RBV (or per local RBV label) and/or consistent with local treatment 
guidelines for RBV.
Pregnancy in a study subject must be reported to AbbVie within 1 working day of the site 
becoming aware of the pregnancy.  Subjects who report a positive pregnancy test during 
the Treatment Period must be notified to stop RBV immediately.  Subjects will be 
monitored for SVR in the Post-Treatment Period as described in Section 5.1.3.  
Administration of DAAs may be continued at the investigator's discretion, if the benefit of 
continuing therapy is felt to outweigh the risk.
Information regarding a pregnancy occurrence in a study subject and the outcome of the 
pregnancy will be collected for pregnancies occurring up to 7 months (or per local RBV 
label) after the last dose of RBV for treatment with DAAs plus RBV.  The investigator is 
encouraged to report the pregnancy information to the voluntary RBV Pregnancy 
Registry, if RBV is included within the regimen.
Subjects who discontinue study medications due to pregnancy will be monitored for SVR 
in the Post-Treatment Period as described in Section 5.1.3.
Pregnancy in a study subject is not considered an adverse event.  However, the medical 
outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered a serious adverse event and must be reported to the Sponsor within 24 hours of 
the site becoming aware of the event.

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6.7
Toxicity Management
For the purpose of medical management, all adverse events and laboratory abnormalities 
that occur during the study must be evaluated by the Investigator.  A table of Clinical 
Toxicity Grades for evaluating laboratory abnormalities is provided in Appendix C.  This 
table should be used in determination of the appropriate toxicity management as discussed 
in  Section 6.7.1 and Section 6.7.5.
A drug-related toxicity is an adverse event or laboratory value outside of the reference 
range that is judged by the Investigator or the Sponsor as having a "reasonable possibility"
of being related to the study drug (Section 6.3).  A toxicity is deemed "clinically 
significant" based on the medical judgment of the Investigator.  Laboratory abnormalities 
will be managed as deemed clinically appropriate by the investigator until resolved.
Investigators should avoid interrupting study drugs for more than 7 consecutive days.  The 
Investigator should ensure that any study drug interruptions or RBV dose modifications 
and associated adverse events are promptly entered into the appropriate eCRFs.
The toxicity management guidelines below should be followed throughout the Treatment 
Period of the study.
6.7.1
Grades 1 or 2 Laboratory Abnormalities and Mild or 
Moderate Adverse Events
Subjects who develop a mild or moderate adverse event or Grade 1 or 2 laboratory 
abnormality, other than those discussed separately in Section 6.7.4 and Section 6.7.5, may 
continue study drugs with follow-up per study protocol and in accordance with local 
standard of care.

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6.7.2
Grades 3 or 4 Laboratory Abnormalities and Severe or 
Serious Adverse Events
Grade 3 – 4 Laboratory Abnormalities
With the exception of Grade 3 or higher abnormalities of total bilirubin, uric acid, 
phosphorus, total cholesterol, triglycerides, or glucose (in subjects with a history of 
diabetes), if a subject experiences a Grade 3 or greater abnormal laboratory parameter 
during the Treatment Period, the abnormal laboratory test should be repeated.  If the 
Grade 3 or greater abnormality is confirmed, the investigator should assess whether the 
abnormality can be managed medically without interruption of study drug, or whether 
study drugs should be interrupted and the laboratory parameter followed until it improves.  
If study drugs are interrupted and restarted and the abnormality recurs, then study drugs 
should be permanently discontinued. 
Decreases in serum hemoglobin or elevations of serum ALT should be managed 
according to the guidance in Section 6.7.4 and Section 6.7.5 below.  Grade 3 or greater 
abnormalities of total bilirubin, uric acid, phosphorus, total cholesterol, triglycerides or 
glucose (in subjects with a history of diabetes) should be managed medically as 
appropriate and do not require confirmation or study drug interruption unless deemed 
necessary by the investigator.
Severe Adverse Event or Serious Adverse Events
If a subject experiences a severe adverse event or a serious adverse event that the 
investigator considers to be a reasonable possibility of relationship to study drug, 
investigator should assess whether the adverse event can be managed medically without 
interruption of study drug, or whether study drugs should be interrupted until it improves, 
or study drugs should be permanently discontinued.  If study drugs are interrupted and 
restarted and the adverse event recurs, then study drugs should be permanently 
discontinued. 

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If a subject experiences a severe adverse event or serious adverse event that is considered 
unrelated (no reasonable possibility) to the study drugs, it is not necessary to interrupt 
study drugs unless an interruption is required because of the nature of the event 
(e.g., unable to take oral medications).  If an interruption is required, it should not exceed 
7 days.
The investigator should ensure that all serious adverse events are reported to AbbVie 
within 24 hours of awareness.  Serious adverse event follow-up information, including 
associated dose interruptions (or discontinuations), must be reported to AbbVie within 
24 hours of awareness by entering updated SAE information into the appropriate eCRFs. 
Severe adverse events and any associated dose interruptions (or discontinuations) should 
be entered into the appropriate eCRFs.
6.7.3
Management of Hemoglobin Decreases
Reductions in hemoglobin are a well characterized side effect of ribavirin exposure.  If a 
subject experiences a hemoglobin decrease meeting one of the criteria outlined in 
Table 13, a confirmatory test should be performed.  If the hemoglobin decrease is 
confirmed, the management guidelines in Table 13 should be followed.  Management will 
be different for subjects without a history of known cardiac disease and subjects with 
known cardiac disease. 
Use of hematologic growth factors (such as erythropoietin or filgrastim) or blood 
transfusions are permitted at the discretion of the Investigator.  Management of 
hematologic growth factor therapy is the responsibility of the Investigator, and growth 
factors will not be provided by AbbVie.
Alternate management of hemoglobin decreases outside of these criteria requires approval 
of the AbbVie Study Designated Physician.

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Table 13.
Ribavirin Dose Modification Guidelines in Management of 
Hemoglobin Decreases
Hemoglobin Value
Intervention
All subjects
< 10 g/L and ≥ 8.5 g/dL for 
subjects without cardiac disease
< 12 g/L and ≥ 8.5 g/dL for 
subjects with cardiac disease
Reduce RBV dose*.  Study drugs may be continued.  If hemoglobin 
increases to ≥ 10 g/dL for subjects without cardiac disease or to 
12g/dL for subjects with cardiac disease.  RBV dose may be 
increased gradually in 200 mg increments towards original dose.
< 8.5 g/dL
Interrupt ribavirin.  Manage the subject as medically appropriate.
Investigator should evaluate if RBV discontinuation is warranted.
If subsequent hemoglobin results are improved to ≥ 10 g/dL for 
subjects without cardiac disease or 12 g/dL for subjects with cardiac 
disease RBV, may be restarted.
Additional guidance for subjects with history of stable cardiac disease
Hemoglobin decrease of ≥ 2 g/dL 
during any 4-week treatment 
period
Reduce RBV dose*.  If a subsequent hemoglobin result is greater 
than the level that triggered the dose reduction, RBV dose may be 
increased gradually in 200 mg increments 
< 12 g/dL after a 4-week RBV 
dose reduction
Interrupt ribavirin.  Manage the subject as medically appropriate.
Investigator should evaluate if RBV discontinuation is warranted.
If subsequent hemoglobin results are improved to ≥ 12g/dL, RBV 
may be restarted.
*
1st dose reduction of ribavirin is to 600 mg/day.  If needed, 2nd dose reduction of ribavirin is by an additional 
200 mg/day.  Subjects whose dose of ribavirin is reduced to 600 mg daily receive one 200 mg tablet in the morning 
and two 200 mg tablets in the evening.
6.7.4
Management of Transaminase Elevations
Transient asymptomatic Grades 3 – 4 ALT elevations have been observed in 
approximately 1% of subjects receiving ABT-450/r-containing regimens.  If a subject 
experiences an increase in ALT to > 10 × ULN, or to > 5 × ULN which was increased 
from previous measurement, the subject should have a confirmatory ALT measurement 
performed in a timely fashion.  If the ALT increase is confirmed, the management 
guidelines in Table 14 should be followed.  Subjects using an estrogen-containing product 
should discontinue use of that product.  Alternate management of ALT increases is 
permitted with approval of the AbbVie Study Designated Physician.

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Table 14.
Management of Confirmed ALT Elevations
ALT ≥ 20 × ULN
!
Permanently discontinue study drugs.
!
Manage the subject as medically appropriate.
ALT ≥ 10 × ULN 
or
ALT ≥ 5 × ULN and increased 
from previous measurement with 
symptoms and signs of hepatitis 
present
!
If using an estrogen-containing product:  Discontinue 
estrogen-containing product and repeat ALT testing, 
preferably within 1 week. 
!
Repeat ALT, AST, total and fractionated bilirubin, alkaline 
phosphatase and INR, preferably within 1 week.
!
Evaluate for alternative etiology of ALT elevation:  update 
medical history and concomitant medications eCRF (if 
applicable), and obtain additional testing as appropriate.
!
Manage the subject as medically appropriate.
!
Permanently discontinue study drugs for any of the following:  
ALT level increases to 20 × ULN, increasing direct bilirubin, 
increasing INR, or new symptoms/signs of hepatitis.
ALT ≥ 5 × ULN and increased 
from previous measurement but 
< 10 × ULN and without 
symptoms or signs of hepatitis
!
Continue study drugs.
!
As soon as possible, measure ALT, AST, total and 
fractionated bilirubin, alkaline phosphatase and INR.  Repeat 
liver chemistries as indicated until resolution. Evaluate for 
alternative etiology of ALT elevation:  update medical history 
and concomitant medications eCRF (if applicable), and obtain 
additional testing as appropriate.
!
Manage the subject as medically appropriate.
!
Permanently discontinue study drugs for any of the following:  
ALT level increases to 20 × ULN, increasing direct bilirubin, 
increasing INR, or symptoms/signs of hepatitis.
6.7.5
Management of eGFR Decreases
If calculated eGFR is confirmed to have decreased to < 50 mL/minute, medical evaluation 
should include a full review of current medications, including those taken on an as needed 
basis, those which are sold over the counter and any dietary and herbal supplements, and 
appropriate dose reduction or discontinuation based on impaired renal function should be 
done (if applicable).  Ribavirin dose should be adjusted as in Table 15.  Alternative 
management of RBV dose in the setting of reduced renal function will require approval of 
the AbbVie Study Designated Physician.

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The investigator should also consider whether drug-drug interactions with concomitant 
medications may have contributed to the decrease in eGFR, and whether discontinuation 
of substitution of the possible interacting drug should be considered.  For example, drug 
interactions between DAAs and some antihypertensive medications could potentially 
increase exposures of the antihypertensive and may reduce renal function.  If 
anti-hypertensive medications are adjusted, vital signs must be monitored to ensure 
appropriate blood pressure control.  Refer to Section 5.2.3.3 for additional information 
regarding drug-drug interactions.
If eGFR improves, the site should perform all necessary readjustment of any dose 
modifications that have been made. 
The Investigator should ensure that any concomitant medication changes, RBV dose 
reductions, and study drug discontinuations, as well as consequent related adverse events 
are entered into the appropriate eCRFs.
Table 15.
Dosing of RBV in Subjects with Renal Impairment
eGFR Value
RBV Dose
30 – 50 mL/min
Alternating doses of 200 mg with 400 mg every other day
< 30 mL/min
200 mg daily
Hemodialysis
200 mg daily
7.0
Protocol Deviations
The investigator should not implement any deviation from the protocol without prior 
review and agreement by the Sponsor and in accordance with the Independent Ethics 
Committee (IEC)/Independent Review Board (IRB) and local regulations, except when 
necessary to eliminate an immediate hazard to study subjects.  When a deviation from the 
protocol is deemed necessary for an individual subject, the investigator must contact the 
following AbbVie personnel:

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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
An interim analysis will occur after all enrolled subjects from S. Korea and Taiwan have 
completed the Treatment Period through Post-Treatment Week 12 of the Post-Treatment 
Period or prematurely discontinued from the study.  This interim analysis is planned to 
support regulatory submission activities in S. Korea and Taiwan.  The primary analysis 
will occur after all subjects have completed PT Week 24 or prematurely discontinued the 
study.  All remaining data through PT Week 48 will be summarized in the end of study 
analysis.
SAS® (SAS Institute, Inc., Cary, NC) for the UNIX operating system will be used for all 
analyses.  All confidence intervals will be 2-sided with an α 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 discrete variables.  

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Efficacy, safety, and demographic analyses will be performed on the intent-to-treat (ITT) 
population which will consist of all enrolled subjects who receive at least one dose of 
study drug.  Additional summaries will be provided by geographic region (China, 
S. Korea, Taiwan).
No data will be imputed for any efficacy or safety analyses except for the PRO 
questionnaires and for analyses of the HCV RNA endpoints of RVR, EOTR, and all SVR 
endpoints.  If a respondent answers at least 50% of the items in a multi-item scale of the 
SF-36v2, the missing items will be imputed with the average score of the answered items 
in the same scale.  In cases where the respondent did not answer at least 50% of the items, 
the score for that domain will be considered missing.  The Mental and Physical 
Component Summary measures will not be computed if any domain is missing.  If a 
respondent answers at least 12 of the 16 items on the HCVPRO, the missing items will be 
imputed with the mean score of the answered items.  In cases where the respondent did 
not answer five or more items, the HCVPRO total score will be considered missing.  For 
EQ-5D-5L index and VAS scores, no imputation will be performed for missing items.
HCV RNA values will be selected for the analyses of HCV RNA endpoints of RVR, 
EOTR, and all SVR endpoints based on the defined visit windows.  When there is no 
HCV RNA value in a visit window based on defined visit windows, the closest values 
before and after the window, regardless of the value chosen for the subsequent and 
preceding window, will be used for the flanking imputation described below. 
If a subject has a missing HCV RNA value at a post-baseline visit but with undetectable 
or unquantifiable HCV RNA levels at both the preceding value and succeeding value, the 
HCV RNA level will be considered undetectable or unquantifiable, respectively, at this 
visit for this subject.  Subsequent to this flanking imputation, if a subject is missing a 
value for the visit window associated with the analysis, the subject will be imputed as a 
visit failure (i.e., not undetectable or unquantifiable).  For SVR analyses (e.g., SVR4, 
SVR12, SVR24) if after performing the flanking imputation there is no value in the 
appropriate window but there is an HCV RNA value after the window, then it will be 
imputed into the SVR window.

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8.1.1
Demographics
Demographics and baseline characteristics will be summarized for the ITT population.  
Demographics include age, weight, and BMI, and the frequency of gender, race, ethnicity, 
age category ([< 55 years or ≥ 55 years] and [< 65 or ≥ 65 years]) and BMI category 
(< 30 kg/m2 or ≥ 30 kg/m2).  Baseline characteristics will include IL28B genotype ([CC, 
CT, or TT] and [CC or non-CC]), IFN based therapy (IFN [alpha, beta or pegIFN] with 
RBV) treatment history (treatment-naïve or treatment-experienced) non-responder {null 
responder, partial responder, or other non-responder} or relapser or IFN based therapy 
intolerant, baseline HCV RNA levels ([continuous] and [< 800,000 IU/mL or 
≥800,000 IU/mL]), baseline IP-10 ([continuous] and [< 600 pg/mL or ≥ 600 pg/mL]), 
baseline HOMA-IR (< 3 mU × mmol/L2 or ≥ 3 mU × mmol/L2), Child-Pugh score at 
Screening (5 or 6), baseline Child-Pugh score (5, 6, or > 6), baseline longitudinal 
FibroTest score (continuous), baseline platelet counts [(continuous) and (< 60, 60 to < 90, 
90 to < 120, or ≥ 120 × 109/L)],baseline albumin [(continuous) and (< 28, 28 to < 33, 
33 to < 40, 40 to 49, and > 49 g/L), baseline alpha fetoprotein (continuous), presence of 
hepatic steatosis at baseline (yes, no), hepatoprotective drug use at baseline (yes, no), 
tobacco (user, ex-user, or non-user) and alcohol use (drinker, ex-drinker, or non-drinker) 
status, former injection drug user (yes, no, unknown), history of bleeding disorders (yes, 
no), history of diabetes (yes, no), history of depression or bipolar disorder (yes, no), and 
geographic region (China, S. Korea and Taiwan).  Summary statistics (N, mean, median, 
Standard Deviation [SD], and range) will be generated for continuous variables (e.g., age 
and BMI).  The number and percentage of subjects will be presented for categorical 
variables (e.g., gender and race). 
8.1.2
Efficacy
All efficacy analyses will be performed on the ITT population. 
Plasma HCV RNA levels will be determined for each sample collected by the central 
laboratory using the Roche COBAS TaqMan® real-time reverse transcriptase-PCR (RT 
PCR) assay version 2.0.  For this assay, the lower limit of detection (LLOD) is 15 IU/mL 

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and lower limit of quantification (LLOQ) is 25 IU/mL.  HCV RNA results that are 
detectable but not quantifiable are reported as "< 25 IU/ML HCV RNA detected" and 
those that are undetectable are reported as "HCV RNA not detected" in the database.
8.1.2.1
Primary Efficacy Endpoints
For South Korea and Taiwan the primary endpoint is: 
A1.
SVR12:  Superiority to the historical SVR rate for telaprevir plus pegIFN/RBV 
therapy; the LCB of the 95% CI for the percentage of subjects with SVR12
must exceed 67% to achieve superiority.
For China, the primary endpoints are:
B1.
SVR12:  Superiority to the historical SVR rate for telaprevir plus pegIFN/RBV 
therapy; the LCB of the 95% CI for the percentage of subjects with SVR12 
must exceed 67% to achieve superiority.
B2.
SVR24:  Superiority to the historical SVR rate for telaprevir plus pegIFN/RBV 
therapy; the LCB of the 95% CI for the percentage of subjects with SVR24
must exceed 67% to achieve superiority.
For China, in order to control the Type I error rate at 0.05, a fixed-sequence testing 
procedure will be used to proceed through the primary efficacy endpoints.  That is, only if 
success has been demonstrated for the primary endpoint of superiority of SVR12 rate to 
the historical rate for telaprevir plus pegIFN and RBV therapy (B1) will the testing 
continue to the second primary endpoint of superiority of the SVR24 rate to the historical 
rate for telaprevir plus pegIFN and RBV therapy (B2).
To test the hypothesis that the percentage of treatment-naïve and IFN based therapy (IFN 
[alpha, beta or pegIFN] with RBV) treatment-experienced HCV genotype 1b infected 
Asian subjects with compensated cirrhosis treated with ABT-450/r/ABT-267 + ABT-333 
+ RBV for 12 weeks who achieve SVR12 is superior to a clinically meaningful threshold 

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based on the historical SVR rates for the HCV genotype 1 infected population treated with 
telaprevir plus pegIFN/RBV, the percentage of subjects with SVR12 will be calculated 
with a 2-sided 95% CI using Wilson score method, and the LCB will be compared to the 
defined threshold.  The LCB of the 95% CI of SVR12 must be greater than 67% in order 
for the regimen to be considered superior.
Similarly, to test the hypothesis that the percentage of treatment-naïve and IFN based 
therapy (IFN [alpha, beta or pegIFN] with RBV) treatment-experienced HCV genotype 1b 
infected Asian subjects with compensated cirrhosis treated with ABT-450/r/ABT-267 + 
ABT-333 + RBV for 12 weeks who achieve SVR24 is superior to a clinically meaningful 
threshold based on historical SVR rates for the HCV genotype 1 infected population 
treated with telaprevir plus pegIFN and RBV, the percentage of subjects with SVR24 will 
be calculated with a 2-sided 95% CI using Wilson score method, and the LCB will be 
compared to the defined threshold.  The LCB of the 95% CI of SVR24 must be greater 
than 67% in order for the regimen to be considered superior.
The value of 67% used in the endpoints as the historical SVR rate for telaprevir plus 
pegIFN/RBV is described in Section 5.6.3.
8.1.2.2
Secondary Efficacy Endpoints
The secondary efficacy endpoints are:
●
The percentage of subjects with on-treatment virologic failure defined as the 
occurrence of at least one of the following:
○
confirmed HCV RNA ≥ the lower limit of quantitation (LLOQ) (defined as 
2 consecutive HCV RNA measurements ≥ LLOQ) at any point during 
treatment after HCV RNA < LLOQ, or
○
confirmed increase from nadir in HCV RNA (defined as 2 consecutive 
HCV RNA measurements > 1 log10 IU/mL above nadir) at any time point 
during treatment, or
○
Failure to achieve HCV RNA < LLOQ by Week 6 with ≥ 36 days of 
treatment.

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●
The percentage of subjects with  relapse by Post-Treatment Week 12 
(confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after 
the last dose of study drug among subjects completing treatment and with 
HCV RNA < LLOQ at the end of treatment).  
●
The percentage of subjects with relapse by Post-Treatment Week 24 
(confirmed HCV RNA ≥ LLOQ between end of treatment and 24 weeks after 
the last dose of study drug among subjects completing treatment and with 
HCV RNA < LLOQ at the end of treatment).  
The percentages (with 2-sided 95% confidence intervals using the Wilson Score method 
to the binomial distribution) of the subjects with on treatment virologic failure and 
post-treatment relapse will be calculated and summarized.
8.1.2.3
Sensitivity Analyses for the Primary Endpoint
In addition to presenting the primary efficacy endpoints with HCV RNA and SVR 12 and 
SVR24 imputed as described in Section 8.1, SVR12 and SVR24 will be presented using the 
following other methods to impute missing post-treatment virologic results:
●
Imputing any missing HCV RNA values in the SVR12/SVR24 window by 
carrying forward the last non-missing (post-baseline) HCV RNA value prior to 
the SVR12/SVR24 window;
●
Imputing as described in Section 8.1 but exclude the subjects who were 
categorized as "prematurely discontinued study drug with no on-treatment 
virologic failure" and "missing follow-up data in the PT Period."
For each of these, the simple percentage of subjects with SVR12/SVR24 will be presented 
along with a 2-sided 95% CI using Wilson score method.
As a sensitivity analysis, comparisons of the SVR12 and SVR24 rates may be made to 
geographic region-specific SVR rates with IFN based therapy (IFN [alpha, beta or 
pegIFN] with RBV) treatment.

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8.1.2.4
Subgroup Analysis
The percentage (with 2-sided 95% confidence intervals) of subjects with SVR12 and 
SVR24 will be presented for the following subgroups:
●
Treatment-naïve versus previous IFN based therapy (IFN [alpha, beta or 
pegIFN] with RBV) treatment-experienced subjects;
○
For treatment-experienced subjects, type of response to previous IFN based 
therapy (non-responder, relapser, or (IFN based therapy intolerant);
○
For non-responders to previous IFN based therapy, type of response (null 
responder, partial responder, or other non-responder);
○
Geographic region/previous HCV treatment status (China/treatment-naïve, 
China/treatment-experienced, S. Korea/treatment-naïve, 
S. Korea/treatment-experienced, Taiwan/treatment-naïve, 
Taiwan/treatment-experienced). 
●
IL28B genotype (CC or non-CC), (CC, CT, or TT);
●
Baseline HCV RNA level (< 800,000 IU/mL or ≥ 800,000 IU/mL);
●
Baseline IP-10 (< 600 pg/mL or ≥ 600 pg/mL);
●
Baseline HOMA-IR (< 3 or ≥ 3 mU × mmol/L2);
●
Sex (male versus female);
●
Age (< 55 versus ≥ 55 years), (< 65 versus ≥ 65 years);
●
BMI (< 30 or ≥ 30 kg/m2);
●
Subjects with RBV dose modifications (yes/no);
●
Presence of hepatic steatosis at Baseline (yes/no);
●
Hepatoprotective drug use at baseline (yes/no);
●
History of Diabetes (yes/no);
●
History of Bleeding Disorders (yes/no);
●
History of Depression or Bipolar Disorder (yes/no);
●
Former injection drug user (yes/no);
●
Baseline Child-Pugh Score ( 5, 6, or > 6);
●
Baseline platelets (< 90 or ≥ 90 × 109cells/L);

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●
Baseline albumin (< 35 or ≥ 35 g/L);
●
Baseline alpha fetoprotein [AFP] (< 20 or ≥ 20 ng/mL).
8.1.2.5
Additional Efficacy Endpoints
The following additional efficacy endpoints will be summarized and analyzed, as 
specified:
●
The percentage of subjects with rapid virologic response (RVR) (HCV RNA 
< LLOQ at Week 4);
●
The percentage of subjects with end of treatment response (EOTR) (HCV 
RNA < LLOQ at Week 12;
●
The percentage of subjects with HCV RNA < LLOQ at each post-baseline visit 
in the Treatment Period (using only subjects with data in each visit window, 
i.e., no imputation for missing data);
●
The number of subjects with virologic rebound at each protocol-specified visit 
(confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment, or 
confirmed increase from nadir in HCV RNA (two consecutive HCV RNA 
measurements > 1 log10 IU/mL above nadir) at any time point during 
treatment.  A single rebound value (≥ LLOQ or >1 log10 IU/mL above nadir) 
followed by lost to follow-up will be considered a rebound);
●
The percentage of subjects who failed to have confirmed suppression of HCV 
RNA (never achieving HCV RNA < LLOQ) during the Treatment Period and 
have received at least 6 weeks of treatment (study drug duration ≥ 36 days);
●
Time to suppression of HCV RNA (defined as the study day of the 
first occurrence of HCV RNA < LLOQ) during the Treatment Period;
●
the percentage of subjects achieving SVR4;
●
The percentage of subjects who complete treatment (defined as a study drug 
duration ≥ 77 days) with HCV RNA < LLOQ at Final Treatment Visit who 
relapsed post-treatment within 4 weeks after the last actual dose of study drug 
(up to and including the SVR4 assessment time point);
●
The percentage of subjects who complete treatment (defined as a study drug 
duration ≥ 77 days) with HCV RNA < LLOQ at Final Treatment Visit who 

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relapsed between end of treatment and up to and including the last HCV RNA 
measurement collected in the PT Period; 
●
The percentage of subjects who achieved SVR24 who subsequently relapsed;
●
Time to relapse at any time post-treatment for subjects who complete treatment 
with HCV RNA < LLOQ at Final Treatment Visit;
●
The percentage of subjects with SVR12 weeks after the last planned dose of 
study drug (SVR12planned);
●
The percentage of subjects with SVR24 (South Korea and Taiwan);
●
The percentage of subjects with SVR24 weeks after the last planned dose of 
study drug (SVR24planned);
●
Mean change from baseline in liver function tests (e.g., PT/INR, Fibrotest) to 
each applicable post-baseline time point.
In the above analyses for RVR, EOTR, and SVR, the percentage of responders and 
2-sided 95% confidence intervals using Wilson score method will be calculated.  From 
HCV RNA levels, the time to suppression on treatment and time to relapse post-treatment 
will be displayed graphically using Kaplan-Meier curves.
8.1.3
Patient Reported Outcomes
The following exploratory analyses of patient reported outcomes (PROs) will be 
performed:
●
mean change from baseline in HCVPRO total score to each applicable 
post-baseline time point;
●
mean change from baseline in EQ-5D-5L health index score and VAS score to 
each applicable post-baseline time point;
●
mean change from baseline in the SF-36v2 Mental Component Summary 
(MCS) and Physical Component Summary (PCS) scores to each applicable 
post-baseline time point.

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Summary statistics (n, mean, SD, median, minimum and maximum) at each visit and for 
change from baseline to each visit will be provided for the HCVPRO total score, the 
EQ-5D-5L health index and VAS scores, and the SF-36v2 PCS and MCS scores.
For HCVPRO total score, a continuous plot by treatment arm will be provided with 
percent change from baseline on the horizontal axis and the cumulative percent of subjects 
experiencing up to that change on the vertical axis.  These plots will be used to show 
change from Baseline to Final Treatment Visit, and change from Baseline to 
Post-Treatment Week 12 and change from Baseline to Post-Treatment Week 24.
Additional analyses of PROs will be performed as useful and appropriate.
8.1.4
Resistance Analyses
Only samples with an HCV RNA level of ≥ 1000 IU/mL will undergo population 
sequence analysis in order to allow accurate assessment of the products of amplification.  
For subjects who experience virologic failure, the sample closest in time after failure with 
an HCV RNA level ≥ 1000 IU/mL will be used if the HCV RNA level at the time of 
failure is < 1000 IU/mL.  The prototypic reference strain with its associated GenBank 
Accession ID for sequence analyses is 1b-Con1 (AJ238799).
For each DAA target, resistance-associated signature amino acid variants will be 
identified by AbbVie Clinical Virology.  Amino acid positions where 
resistance-associated variants have been identified in vitro and/or in vivo in genotype 1b 
are 1) for ABT-450:  56, 155, 156, and 168 in NS3; 2) for ABT-267:  28, 29, 30, 31, 32, 
58, and 93 in NS5A; and 3) for ABT-333:  316, 368, 411, 414, 445, 448, 553, 556, 558, 
and 559 in NS5B.
The following definitions will be used in the resistance analyses:
●
Baseline sample:  sample collected before the first dose of DAA study drug.
●
Baseline variant:  a variant (by population sequencing) in a baseline sample 
determined by comparison of the amino acid sequence of the baseline sample 

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to the appropriate prototypic reference amino acid sequence for a given DAA 
target (NS3, NS5A, or NS5B).
●
Post-baseline variant by population sequencing:  an amino acid variant in a 
post-baseline time point sample that was not detected at baseline in the subject 
and is detectable by population sequencing.
●
Emerged variant by population sequencing:  a post-baseline variant that is 
observed in 2 or more subjects of the same subgenotype by population 
sequencing.
●
Linked variant by population sequencing:  2 or more signature or emerged 
amino acid variants identified within a sample by population sequencing where 
at least one of the variants is at a signature position, and no mixture of amino 
acids is detected at either position.
For those samples evaluated, a listing by subject of all baseline variants relative to the 
prototypic reference sequence at signature resistance-associated amino acid positions will 
be provided for each DAA target (NS3, NS5A, and/or NS5B).  Furthermore, the HCV 
amino acid sequence at post-baseline time points with an HCV RNA level of 
≥1000 IU/mL that are analyzed will be compared to the baseline and prototypic reference 
amino acid sequences.  A listing by subject and time point of all post-baseline variants 
relative to the baseline amino acid sequences will be provided for each DAA target (NS3, 
NS5A, and/or NS5B).  In addition, a listing by subject and time point of all post-baseline 
variants at signature resistance-associated amino acid positions relative to the prototypic 
reference amino acid sequences will be provided.  Furthermore, the number and 
percentage of subjects with emerged variants by amino acid position and variant within a 
DAA target as compared to baseline will be summarized.
The number and percentage of subjects with linked variants by population sequencing 
within a DAA target will be summarized.  In addition a listing of linked variants by 
subject and time point will be provided for each DAA target (NS3, NS5A, and NS5B).
The persistence of resistance-associated substitutions that emerged for each target (NS3, 
NS5A, and NS5B) will be assessed by population sequencing at selected post-treatment 

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time points.  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, NS5A, and 
NS5B). 
8.1.5
Safety
All subjects who receive at least one dose of study drug will be included in the safety 
analyses.
8.1.5.1
Adverse Events
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA).  The number and percentage of subjects with treatment-emergent adverse 
events (defined as any event that begins or worsens in severity after initiation of active 
study drugs through 30 days after the last dose of study drugs) will be tabulated by 
primary MedDRA System Organ Class (SOC) and preferred term (PT).  The tabulation of 
the number of subjects with treatment-emergent adverse events by severity rating and 
relationship to study drug will be provided.  In addition, the number and percentage of 
subjects with serious treatment-emergent adverse events and the number and percentage 
of subjects with treatment-emergent adverse events leading to study drug discontinuation 
will also be provided.  
Subjects reporting more than one adverse event for a given MedDRA preferred term will 
be counted only once for that term using the most severe incident for the severity rating 
table and the most related for the relationship to study drug table.  Subjects reporting more 
than one type of event within a SOC will be counted only once for that SOC.
Additional analyses will be performed if useful and appropriate.
8.1.5.2
Clinical Laboratory Data
Clinical laboratory tests will be summarized at each visit.  The baseline value will be the 
last measurement prior to the initial dose of study drug.  Mean changes from baseline to 
each Post-Baseline Visit will be summarized. 

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Laboratory data values collected during the Treatment Period will be categorized as low, 
normal, or high based on reference ranges of the laboratory used in this study.  The 
number and percent of subjects who experience post-baseline shifts during treatment in 
clinical laboratory values from low/normal to high and high/normal to low based on the 
normal range will be summarized.
In addition, the number and percentage of subjects with post-baseline values meeting pre 
specified criteria for Potentially Clinically Significant laboratory values during treatment 
will be summarized.
Additional analyses will be performed if useful and appropriate.
8.1.5.3
Vital Signs Data
Mean changes in temperature, systolic and diastolic blood pressure, pulse, and weight 
from baseline to each Post-Baseline Visit will be summarized.  Frequencies and 
percentages of subjects with post-baseline values meeting pre-defined criteria for 
Potentially Clinically Significant vital signs values during treatment will be summarized.
8.1.6
Pharmacokinetic and Exposure-Response Analyses
Plasma concentrations and pharmacokinetic parameters of ABT-450, possible ABT-450 
metabolites, ABT-267, possible ABT-267 metabolites, ABT-333, ABT-333 M1 
metabolite, other possible ABT-333 metabolites, ritonavir and ribavirin will be tabulated 
and summarized and summary statistics will be computed for each time and visit.
In addition, 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 VI, 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 

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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 
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:

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TVCLi = + Theta(2) (Comedication [1,2,…] + Theta(3) (WTi-median value) + Theta(4) 
(AGEi – median value).
Where TVCLi = Typical value of clearance for an individual i1, 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.  Exposure response 
relationships will be explored using a semi-mechanistic viral dynamic model and/or 
logistic regression analyses. 
Logistic regression analyses will explore the relationship between exposure and one or 
more virologic endpoints (e.g., RVR, EVR, SVR4, 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.
8.2
Determination of Sample Size
It is planned to enroll approximately 100 subjects (60 from China, 20 from South Korea 
and 20 from Taiwan).  All subjects will receive ABT-450/r/ABT-267 + ABT-333 
coadministered with RBV for 12 weeks.  With a total sample size of about 100 subjects 
and assuming that 94% of the subjects will achieve SVR12, this study has greater than 

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90% power to demonstrate SVR12 superiority with a 2-sided 95% lower confidence bound 
greater than 67% (based on the normal approximation of a single binomial proportion in a 
one-sample test for superiority using EAST 6.2).  The SVR24 rate is anticipated to be very 
similar to the SVR12 rate and thus the power should still be at least 90%.  No adjustment 
for dropout is applicable because subjects who do not have data at Post-Treatment 
Week 12 (after imputing) are counted as failures for SVR12 and SVR24.
9.0
Ethics
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB)
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigator's Brochure, the informed consent and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and 
any other necessary documents be reviewed by an IEC/IRB.  The IEC/IRB will review the 
ethical, scientific and medical appropriateness of the study before it is conducted.  
IEC/IRB approval of the protocol, informed consent and subject information and/or 
advertising, as relevant, will be obtained prior to the authorization of drug shipment to a 
study site.
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  The investigator will be required to submit, 
maintain and archive study essential documents according to ICH GCP.
Any serious adverse events that meet the reporting criteria, as dictated by local 
regulations, will be reported to both responsible Ethics Committees and Regulatory 
Agencies, as required by local regulations.  During the conduct of the study, the 
investigator should promptly provide written reports (e.g., ICH Expedited Reports, and 
any additional reports required by local regulations) to the IEC/IRB of any changes that 
affect the conduct of the study and/or increase the risk to subjects.  Written documentation 
of the submission to the IEC/IRB should also be provided to AbbVie.

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9.2
Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) guidelines, applicable regulations and guidelines governing clinical 
study conduct and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical investigator are specified in Appendix A.
9.3
Subject Information and Consent
The investigator or his/her representative will explain the nature of the study to the 
subject, and answer all questions regarding this study.  Prior to any study-related 
screening procedures being performed on the subject, the informed consent statement will 
be reviewed and signed and dated by the subject, the person who administered the 
informed consent, and any other signatories according to local requirements.  A copy of 
the informed consent form will be given to the subject and the original will be placed in 
the subject's medical record.  An entry must also be made in the subject's dated source 
documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy.
Additional pharmacogenetic analyses will only be performed if the subject has voluntarily 
signed and dated the IRB/IEC approved pharmacogenetic informed consent after the 
nature of the testing has been explained and the subject has had an opportunity to ask 
questions.  The subject must provide consent specific to pharmacogenetic before the 
pharmacogenetic testing is performed.  If the subject does not consent to the additional 
pharmacogenetic 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 

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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 
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 

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principal investigator will review the eCRFs for completeness and accuracy and provide 
his or her electronic signature and date to eCRFs as evidence thereof.
11.0
Data Quality Assurance
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.  
Computer logic and manual checks will be created to identify items such as inconsistent 
study dates.  Any necessary corrections will be made to the eCRF.
12.0
Use of Information
Any 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, the subject, nor the subject's 
physician (if different from the investigator) will be informed of individual subject 
pharmacogenetic results, should analyses be performed, nor will anyone not directly 
involved in this research.  Correspondingly, genetic 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 pharmacogenetic 
information from this study may be used in scientific publications or presented at medical 
conventions.  Pharmacogenetic 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.  

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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.
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-450, ABT-267, 
ABT-333 and the product labeling for ritonavir and RBV.
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: 
An Open-Label Study to Evaluate the Safety and Efficacy of 
ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 
Coadministered with Ribavirin (RBV) in Treatment-Naïve and 
Treatment-Experienced Asian Adults with Genotype 1b Chronic 
Hepatitis C Virus (HCV) Infection and Compensated Cirrhosis
Protocol Date:
11 February 2015
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)

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15.0
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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
Pharmacokinetics
Statistics
Global Drug Supply Management

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Appendix C.
Clinical Toxicity Grades

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