PEARL-III: A Study to Evaluate Chronic Hepatitis C Infection in Adults With Genotype 1b Infection

• Sponsor: AbbVie (prior sponsor, Abbott) (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01767116
• Collaborator: (none)
• Enrollment: 419
• Arms: 2
• Duration (Months): 20

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and antiviral activity of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267; ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) with and without ribavirin (RBV) in patients with chronic hepatitis C virus genotype 1b (HCV GT1b) infection without cirrhosis.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Infection	Drug: ABT-450/r/ABT-267, ABT-333; Drug: Ribavirin; Drug: Placebo for ribavirin	Phase 3

Detailed Description

A randomized, double-blind, multicenter study to evaluate the safety and antiviral activity of the combination of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 with and without ribavirin (RBV) in treatment-naïve, noncirrhotic participants with chronic hepatitis C virus genotype 1b (HCV GT1b) infection.

Study Design

• Study Type: Interventional
• Actual Enrollment: 419 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Controlled Study to Evaluate the Efficacy and Safety of the Combination of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With and Without Ribavirin (RBV) in Treatment-Naive Adults With Genotype 1b Chronic Hepatitis C Virus (HCV) Infection (PEARL-III)
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABT-450/r/ABT-267 and ABT-333, Plus RBV ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	Drug: ABT-450/r/ABT-267, ABT-333; Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet; Other Names: ABT-267 also known as ombitasvir ABT-450 also known as paritaprevir ABT-333 also known as dasabuvir Viekira PAK ; Drug: Ribavirin; Capsule
Experimental: ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks	Drug: ABT-450/r/ABT-267, ABT-333; Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet; Other Names: ABT-267 also known as ombitasvir ABT-450 also known as paritaprevir ABT-333 also known as dasabuvir Viekira PAK ; Drug: Placebo for ribavirin; Capsule

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analyses of Each Treatment Arm Compared to Historical Rate [12 weeks after last dose of study drug]

   The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL. The primary efficacy endpoints were noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b infection treated with telaprevir and peginterferon/RBV (pegIFN).

Secondary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analysis of ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV Compared With ABT-450/r/ABT-267 and ABT-333, Plus RBV [12 weeks after last dose of study drug]

   The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. The secondary endpoint was the noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment who received ABT-450/r/ABT-267 and ABT-333, plus placebo RBV compared with those who received ABT-450/r/ABT-267 and ABT-333, plus RBV.

2. Percentage of Participants With Hemoglobin Decrease to Below the Lower Limit of Normal (LLN) At End of Treatment [Baseline (Day 1) and Week 12 (End of Treatment)]

   The percentage of participants with a decrease in hemoglobin from greater than or equal to the lower limit of normal (≥ LLN) at baseline to < LLN at the end of treatment.

3. Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Superiority Analyses of Each Treatment Arm Compared to Historical Rate [12 weeks after last dose of study drug]

   The percentage of participants with sustained virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. The secondary efficacy endpoints were superiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b treated with telaprevir and pegIFN/RBV.

4. Percentage of Participants With Virologic Failure During Treatment [Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, and 12]

   Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log10 IU/mL above the lowest value post baseline] at any time point during treatment), or failure to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks [≥ 36 days] of treatment).

5. Percentage of Participants With Virologic Relapse After Treatment [Between End of Treatment (Week 12) and Post-treatment (up to Week 12 Post-treatment)]

   Participants who completed treatment with plasma HCV RNA less than the lower limit of quantification (<LLOQ) at the end of treatment were considered to have virologic relapse if they had confirmed HCV RNA ≥ LLOQ during the post-treatment period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Females must be practicing specific forms of birth control on study treatment, or be post-menopausal for more than 2 years or surgically sterile

• Chronic hepatitis C, genotype 1b-infection (HCV RNA level greater than or equal to 10,000 IU/mL at screening)

• Subject has never received antiviral treatment for hepatitis C infection

• No evidence of liver cirrhosis

Exclusion Criteria:

• Significant liver disease with any cause other than HCV as the primary cause

• Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody

• Positive screen for drugs or alcohol

• Significant sensitivity to any drug

• Use of contraindicated medications within 2 weeks of dosing

• Abnormal laboratory tests

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie (prior sponsor, Abbott)

Investigators

• Study Director: Dan Cohen, MD, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

• Ferenci P, Bernstein D, Lalezari J, Cohen D, Luo Y, Cooper C, Tam E, Marinho RT, Tsai N, Nyberg A, Box TD, Younes Z, Enayati P, Green S, Baruch Y, Bhandari BR, Caruntu FA, Sepe T, Chulanov V, Janczewska E, Rizzardini G, Gervain J, Planas R, Moreno C, Hassanein T, Xie W, King M, Podsadecki T, Reddy KR; PEARL-III Study; PEARL-IV Study. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014 May 22;370(21):1983-92. doi: 10.1056/NEJMoa1402338. Epub 2014 May 4.

• Responsible Party: AbbVie (prior sponsor, Abbott)
• ClinicalTrials.gov Identifier: NCT01767116
• Other Study ID Numbers: M13-961; 2012-003687-52
• First Posted: Jan 14, 2013
• Last Update Posted: Jul 12, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by AbbVie (prior sponsor, Abbott): Interferon-Free; Hepatitis C Genotype 1b; Chronic Hepatitis C; Hepatitis C Virus; Hepatitis C; Treatment-Naive; Paritaprevir; Ombitasvir; Dasabuvir; Viekira PAK; Ribavirin
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ribavirin

Study Results

Participant Flow

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV	ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
Arm/Group Description	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks
Period Title: Overall Study
STARTED	210	209
COMPLETED	208	207
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV	ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV	Total
Arm/Group Description	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks	Total of all reporting groups
Overall Participants	210	209	419
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.4 (11.94)	49.2 (12.03)	48.8 (11.98)
Sex: Female, Male (Count of Participants)
Female	104 49.5%	123 58.9%	227 54.2%
Male	106 50.5%	86 41.1%	192 45.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analyses of Each Treatment Arm Compared to Historical Rate
Description	The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL. The primary efficacy endpoints were noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b infection treated with telaprevir and peginterferon/RBV (pegIFN).
Time Frame	12 weeks after last dose of study drug

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug (intent-to-treat [ITT] population); participants with missing data were counted as non-responders.

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV	ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
Arm/Group Description	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks
Measure Participants	210	209
Number [percentage of participants]	99.5 47.4%	100.0 47.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
	Comments	For the primary efficacy endpoint of sustained virologic response at 12 weeks after treatment, based on a 2-sided significance level of 0.05 and an underlying rate of 92% or higher in each arm, a sample size of 200 participants per treatment arm provides >95% power to demonstrate noninferiority of each regimen to the historical rate for telaprevir plus pegIFN and RBV therapy (84%) (based on the normal approximation of a single binomial proportion in a one-sample test for superiority).
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The noninferiority of the rate of sustained virologic response at 12 weeks after treatment for the ABT-450/r/ABT-267 and ABT-333, plus placebo RBV treatment group as compared with the historical rate for telaprevir plus pegIFN-RBV was analyzed; the lower confidence bound of the 2-sided 95% confidence interval (95% CI) for the percentage of participants with sustained virologic response at 12 weeks after treatment must exceed 73% to achieve noninferiority.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	100
	Confidence Interval	(2-Sided) 95%; 98.2 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI was calculated using the Wilson score method for the single proportion because the point estimate was 100%..

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ABT-450/r/ABT-267 and ABT-333, Plus RBV
	Comments	For the primary efficacy endpoint of sustained virologic response at 12 weeks after treatment, based on a 2-sided significance level of 0.05 and an underlying rate of 92% or higher in each arm, a sample size of 200 participants per treatment arm provides >95% power to demonstrate noninferiority of each regimen to the historical rate for telaprevir plus pegIFN and RBV therapy (84%) (based on the normal approximation of a single binomial proportion in a one-sample test for superiority).
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The noninferiority of the rate of sustained virologic response at 12 weeks after treatment for the ABT-450/r/ABT-267 and ABT-333, plus RBV treatment group as compared with the historical rate for telaprevir plus pegIFN-RBV was analyzed; the lower confidence bound of the 2-sided 95% CI for the percentage of participants with sustained virologic response at 12 weeks after treatment must exceed 73% to achieve noninferiority.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	99.5
	Confidence Interval	(2-Sided) 95%; 98.6 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI was calculated using the normal approximation to the binomial distribution.

2. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analysis of ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV Compared With ABT-450/r/ABT-267 and ABT-333, Plus RBV
Description	The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. The secondary endpoint was the noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment who received ABT-450/r/ABT-267 and ABT-333, plus placebo RBV compared with those who received ABT-450/r/ABT-267 and ABT-333, plus RBV.
Time Frame	12 weeks after last dose of study drug

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug (ITT population); participants with missing data were counted as non-responders.

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV	ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
Arm/Group Description	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks
Measure Participants	210	209
Number [percentage of participants]	99.5 47.4%	100 47.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-450/r/ABT-267 and ABT-333, Plus RBV, ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
	Comments	For the secondary efficacy endpoint of sustained virologic response at 12 weeks after treatment, based on a -10% margin, a 2-sided significance level of 0.05 and an underlying rate of 92% or higher in each arm, a sample size of 200 participants per arm provides >95% power to demonstrate noninferiority of ABT-450/r/ABT-267 and ABT-333, plus Placebo RBV compared with ABT-450/r/ABT-267 and ABT-333, plus RBV (normal approximation of a single binomial proportion in a 1-sample test for superiority).
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Noninferiority of the rate of sustained virologic response at 12 weeks after treatment for the ABT-450/r/ABT-267 and ABT-333, plus placebo RBV treatment group as compared with the ABT-450/r/ABT-267 and ABT-333, plus RBV treatment group was analyzed using a noninferiority margin of -10.5%. The lower confidence bound of the 2-sided 95% CI for the difference in percentage of participants with sustained virologic response at 12 weeks after treatment must exceed -10.5% to achieve noninferiority.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage of Participants
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -0.5 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI was calculated using the normal approximation to the binomial distribution.

3. Secondary Outcome

Title	Percentage of Participants With Hemoglobin Decrease to Below the Lower Limit of Normal (LLN) At End of Treatment
Description	The percentage of participants with a decrease in hemoglobin from greater than or equal to the lower limit of normal (≥ LLN) at baseline to < LLN at the end of treatment.
Time Frame	Baseline (Day 1) and Week 12 (End of Treatment)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug (ITT population) and had hemoglobin ≥ LLN reference range at baseline.

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV	ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
Arm/Group Description	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks
Measure Participants	207	205
Number [percentage of participants]	51.2 24.4%	3.4 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-450/r/ABT-267 and ABT-333, Plus RBV, ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Superiority Analyses of Each Treatment Arm Compared to Historical Rate
Description	The percentage of participants with sustained virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. The secondary efficacy endpoints were superiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b treated with telaprevir and pegIFN/RBV.
Time Frame	12 weeks after last dose of study drug

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug (ITT population); participants with missing data were counted as non-responders.

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV	ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
Arm/Group Description	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks
Measure Participants	210	209
Number [percentage of particpants]	99.5	100

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
	Comments	For the secondary efficacy endpoint of sustained virologic response at 12 weeks after treatment, based on a 2-sided significance level of 0.05 and an underlying rate of 92% or higher in each arm, a sample size of 200 participants per treatment arm provides >90% power to demonstrate superiority of each regimen to the historical rate for telaprevir plus pegIFN and RBV therapy (84%) (based on the normal approximation of a single binomial proportion in a one-sample test for superiority).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	100
	Confidence Interval	(2-Sided) 95%; 98.2 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI calculated using the Wilson score method for the single proportion; the lower confidence bound for the percentage of participants with sustained virologic response at 12 weeks after treatment must exceed 84% to achieve superiority.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ABT-450/r/ABT-267 and ABT-333, Plus RBV
	Comments	For the secondary efficacy endpoint of sustained virologic response at 12 weeks after treatment, based on a 2-sided significance level of 0.05 and an underlying rate of 92% or higher in each arm, a sample size of 200 participants per treatment arm provides >90% power to demonstrate superiority of each regimen to the historical rate for telaprevir plus pegIFN and RBV therapy (84%) (based on the normal approximation of a single binomial proportion in a one-sample test for superiority).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	99.5
	Confidence Interval	(2-Sided) 95%; 98.6 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI calculated using the normal approximation to the binomial distribution; the lower confidence bound for the percentage of participants with sustained virologic response at 12 weeks after treatment must exceed 84% to achieve superiority.

5. Secondary Outcome

Title	Percentage of Participants With Virologic Failure During Treatment
Description	Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log10 IU/mL above the lowest value post baseline] at any time point during treatment), or failure to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks [≥ 36 days] of treatment).
Time Frame	Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug (ITT population).

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV	ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
Arm/Group Description	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks
Measure Participants	210	209
Rebound	0.5 0.2%	0 0%
Failure to suppress	0 0%	0 0%

6. Secondary Outcome

Title	Percentage of Participants With Virologic Relapse After Treatment
Description	Participants who completed treatment with plasma HCV RNA less than the lower limit of quantification (<LLOQ) at the end of treatment were considered to have virologic relapse if they had confirmed HCV RNA ≥ LLOQ during the post-treatment period.
Time Frame	Between End of Treatment (Week 12) and Post-treatment (up to Week 12 Post-treatment)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug (ITT population) with HCV RNA < LLOQ at the final treatment visit and completed treatment.

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV	ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
Arm/Group Description	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks
Measure Participants	208	207
Number [percentage of participants]	0 0%	0 0%

Adverse Events

Time Frame	AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of participation in the study (up to 65 weeks)
Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV		ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
Arm/Group Description	ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks		ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks
All Cause Mortality
	ABT-450/r/ABT-267 and ABT-333, Plus RBV		ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ABT-450/r/ABT-267 and ABT-333, Plus RBV		ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/210 (1.9%)		4/209 (1.9%)
Cardiac disorders
ATRIAL FIBRILLATION	1/210 (0.5%)		0/209 (0%)
CORONARY ARTERY DISEASE	1/210 (0.5%)		0/209 (0%)
Musculoskeletal and connective tissue disorders
ARTHRITIS	0/210 (0%)		1/209 (0.5%)
MYALGIA	0/210 (0%)		1/209 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
INTRADUCTAL PROLIFERATIVE BREAST LESION	0/210 (0%)		1/209 (0.5%)
Renal and urinary disorders
NEPHROLITHIASIS	1/210 (0.5%)		0/209 (0%)
Reproductive system and breast disorders
EPIDIDYMITIS	1/210 (0.5%)		0/209 (0%)
UTERINE POLYP	0/210 (0%)		1/209 (0.5%)
Other (Not Including Serious) Adverse Events
	ABT-450/r/ABT-267 and ABT-333, Plus RBV		ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	133/210 (63.3%)		97/209 (46.4%)
Blood and lymphatic system disorders
ANAEMIA	14/210 (6.7%)		1/209 (0.5%)
Gastrointestinal disorders
ABDOMINAL PAIN UPPER	11/210 (5.2%)		6/209 (2.9%)
DIARRHOEA	9/210 (4.3%)		13/209 (6.2%)
DYSPEPSIA	14/210 (6.7%)		9/209 (4.3%)
NAUSEA	23/210 (11%)		9/209 (4.3%)
General disorders
ASTHENIA	22/210 (10.5%)		12/209 (5.7%)
FATIGUE	45/210 (21.4%)		49/209 (23.4%)
Nervous system disorders
HEADACHE	51/210 (24.3%)		49/209 (23.4%)
Psychiatric disorders
INSOMNIA	19/210 (9%)		7/209 (3.3%)
Respiratory, thoracic and mediastinal disorders
COUGH	19/210 (9%)		5/209 (2.4%)
Skin and subcutaneous tissue disorders
PRURITUS	25/210 (11.9%)		11/209 (5.3%)
RASH	12/210 (5.7%)		8/209 (3.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.