GIFT I: Study to Evaluate the Efficacy and Safety of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) in Japanese Adults With Subgenotype 1b Chronic Hepatitis C Virus (HCV) Infection

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02023099
• Collaborator: (none)
• Enrollment: 363
• Arms: 3
• Duration (Months): 22

Study Details

Study Description

Brief Summary

This is a phase 3, double-blinded, multicenter study. The study will consist of 2 substudies:

Substudy 1 (SS1) will be double-blinded and enroll non-cirrhotic subjects and Substudy 2 (SS2) will be open label and enroll subjects with compensated cirrhosis.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 363 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) in Treatment-Naïve and Treatment-Experienced Japanese Adults With Subgenotype 1b Chronic Hepatitis C Virus (HCV) Infection With and Without Compensated Cirrhosis (GIFT I)
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Substudy 1, Arm A: DB 2-DAA Double-blind (DB) 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2 direct-acting antiviral agents [2-DAA]) once daily (QD) for 12 weeks in participants without cirrhosis	Drug: ABT-450/r/ABT-267; Tablet; ABT-450 coformulated with ritonavir and ABT-267; Other Names: ABT-267 also known as ombitasvir ABT-450 also known as paritaprevir ritonavir also known as Norvir VIEKIRAX Combination Tablets Qurevo Technivie VIEKIRA Combination Tablets
Placebo Comparator: Substudy 1, Arm B: DB Placebo, Followed by OL 2-DAA DB placebo QD for 12 weeks followed by open-label (OL) 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis	Drug: ABT-450/r/ABT-267; Tablet; ABT-450 coformulated with ritonavir and ABT-267; Other Names: ABT-267 also known as ombitasvir ABT-450 also known as paritaprevir ritonavir also known as Norvir VIEKIRAX Combination Tablets Qurevo Technivie VIEKIRA Combination Tablets ; Drug: Placebo; Tablet
Experimental: Substudy 2, Arm C: OL 2-DAA OL 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants with compensated cirrhosis	Drug: ABT-450/r/ABT-267; Tablet; ABT-450 coformulated with ritonavir and ABT-267; Other Names: ABT-267 also known as ombitasvir ABT-450 also known as paritaprevir ritonavir also known as Norvir VIEKIRAX Combination Tablets Qurevo Technivie VIEKIRA Combination Tablets

Outcome Measures

Primary Outcome Measures

1. Percentage of Non-cirrhotic Treatment-Naïve Participants Who Are Eligible for Interferon (IFN)-Based Therapy and Who Have High Viral Load in the DB Active Treatment Group With a Sustained Virologic Response 12 Weeks Post-treatment [12 weeks after the last dose of study drug]

   The percentage noncirrhotic treatment-naïve participants who were eligible for IFN-based therapy and who had high viral load at baseline (HCV RNA ≥ 100,000 IU/mL) in the DB active treatment group 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 active study drug (SVR12). Among noncirrhotic treatment-naïve participants who were eligible for IFN-based therapy and who had high viral load at baseline, superiority of Arm A to a clinically relevant threshold based on historical SVR rate with telaprevir plus pegylated interferon alpha/ribavirin (pegIFN/RBV) in treatment-naïve, non-cirrhotic patients with high viral load; the lower bound of 95% confidence interval (LCB) had to exceed 63% to achieve superiority. The 95% confidence interval was calculated using the normal approximation to the binomial distribution.

Secondary Outcome Measures

1. Percentage of Participants in the Active Treatment Group With On-treatment Virologic Failure During Treatment [up to 12 weeks]

   On-treatment virologic failure among all randomized non-cirrhotic participants who received at least one dose of DB ABT-450/r/ABT-267 and all enrolled participants with compensated cirrhosis who received at least one dose of OL ABT-450/r/ABT-267. On-treatment virologic failure is defined as the occurrence of at least one of the following: confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) at any point during treatment after HCV RNA < LLOQ (rebound), 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 (rebound), or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks (≥ 36 days) of treatment (failure to suppress). The 95% confidence interval was calculated using the Wilson's score method.

2. Percentage of Participants in the Substudy 1 Arm A Active Treatment Group With On-treatment Virologic Failure During Treatment, by Subpopulation [up to 12 weeks]

   On-treatment virologic failure among all randomized non-cirrhotic participants who received at least one dose of DB ABT-450/r/ABT-267 in the following subpopulations: noncirrhotic treatment-naïve (T-naïve) participants with a high baseline (BL) viral load (HCV RNA ≥ 100,000 IU/mL) who are eligible for IFN-based therapy (IFN-BT), a low viral load (HCV RNA < 100,000 IU/mL), or who are ineligible for IFN-BT; noncirrhotic treatment-experienced (T-exp) participants who relapsed after prior IFN-BT, who were nonresponders to prior IFN-BT, or who were intolerant to IFN-BT. On-treatment virologic failure is defined in Outcome measure 2. The 95% confidence interval was calculated using the Wilson's score method.

3. Percentage of Participants in the Active Treatment Group With Post-treatment Relapse [within 12 weeks after last dose of study drug]

   Post-treatment relapse among all randomized non-cirrhotic participants who received at least one dose of DB ABT-450/r/ABT-267 and completed treatment, and all enrolled participants with compensated cirrhosis who received at least one dose of OL ABT-450/r/ABT-267 and completed treatment. Relapse was defined as confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) between the final treatment visit and 12 weeks after the last dose of study drugs among participants completing treatment and with HCV RNA < LLOQ at the final treatment visit and at least one post-treatment HCV RNA value. The 95% confidence interval was calculated using the Wilson's score method.

4. Percentage of Participants in Substudy 1 Arm A Active Treatment Group With Post-treatment Relapse, by Subpopulation [within 12 weeks after last dose of study drug]

   Post-treatment relapse among all randomized non-cirrhotic participants who received at least one dose of DB ABT-450/r/ABT-267 and completed treatment, in the following subpopulations: noncirrhotic treatment-naïve (T-naïve) participants with a high baseline (BL) viral load (HCV RNA ≥ 100,000 IU/mL) who are eligible for IFN-based therapy (IFN-BT), a low BL viral load (HCV RNA < 100,000 IU/mL), or who are ineligible for IFN-BT; noncirrhotic treatment-experienced (T-exp) participants who relapsed after prior IFN-BT, who were nonresponders to prior IFN-BT, or who were intolerant to IFN-BT. Relapse was defined as confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) between the final treatment visit and 12 weeks after the last dose of study drugs among participants completing treatment and with HCV RNA < LLOQ at the final treatment visit and at least one post-treatment HCV RNA value. The 95% confidence interval was calculated using the Wilson's score method.

5. Percentage of Participants in the Active Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment [12 weeks after last dose of study drug]

   Sustained virologic response (plasma HCV RNA level < LLOQ) 12 weeks after the last dose of study drug for all randomized non-cirrhotic participants who received at least one dose of DB ABT-450/r/ABT-267 and for all enrolled participants with compensated cirrhosis who received at least one dose of open-label ABT-450/r/ABT-267. The 95% confidence interval was calculated using the Wilson's score method.

6. Percentage of Participants in Substudy 1 Arm A Active Treatment Group With Sustained Virologic Response 12 Weeks Post-Treatment, by Subpopulation [12 weeks after last dose of study drug]

   Sustained virologic response (plasma HCV RNA level < LLOQ) 12 weeks after the last dose of study drug for all randomized non-cirrhotic participants who received at least one dose of DB ABT-450/r/ABT-267 in the following subpopulations: noncirrhotic T-naïve participants with a high BL viral load (HCV RNA ≥ 100,000 IU/mL) who are eligible for IFN-BT; noncirrhotic T-naïve participants with low BL viral load (HCV RNA < 100,000 IU/mL); noncirrhotic T-naïve participants who are ineligible for IFN-BT; noncirrhotic T-exp participants who relapsed after prior IFN-BT; noncirrhotic T-exp participants who were nonresponders to prior IFN-BT; noncirrhotic T-exp participants who were intolerant to IFN-BT. The 95% confidence interval was calculated using the Wilson's score method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Chronic HCV-infection prior to study enrollment

• Screening laboratory result indicating HCV subgenotype 1b infection

• Subject has plasma HCV RNA level greater than 10,000 IU/mL at Screening

• Voluntarily sign an informed consent

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

Exclusion Criteria:

• Co-infection of Hepatitis B Virus (HBV), human immunodeficiency virus (HIV) or any HCV genotype other than subgenotype 1b

• Prior therapy with direct acting antiviral agents for the treatment of HCV, including telaprevir, simeprevir and boceprevir

• Any cause of liver disease other than chronic HCV-infection, including but not limited to the following: hemochromatosis; alpha-1 antitrypsin deficiency; Wilson's disease; autoimmune hepatitis; alcoholic liver disease; drug-related liver disease; clinically significant laboratory abnormalities; uncontrolled clinically significant disease, disorder or medical illness

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: Nori Yachi, AbbVie GK.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02023099
• Other Study ID Numbers: M13-004
• First Posted: Dec 30, 2013
• Last Update Posted: Jun 6, 2018
• Last Verified: Sep 1, 2016

• Keywords provided by AbbVie: Hepatitis C; Genotype 1b; Cirrhotic; Treatment Experienced; Treatment Naive; Japanese; ombitasvir; paritaprevir; ritonavir; VIEKIRAX Combination Tablets
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir

Study Results

Participant Flow

Arm/Group Title	Substudy 1, Arm A: DB 2-DAA	Substudy 1, Arm B: DB Placebo, Followed by OL 2-DAA	Substudy 2, Arm C: OL 2-DAA
Arm/Group Description	Double-blind (DB) 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2 direct-acting antiviral agents [2-DAA]) once daily (QD) for 12 weeks in participants without cirrhosis	DB placebo QD for 12 weeks followed by open-label (OL) 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis	OL 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants with compensated cirrhosis
Period Title: Overall Study
STARTED	215	106	42
COMPLETED	212	106	39
NOT COMPLETED	3	0	3

Baseline Characteristics

Arm/Group Title	Substudy 1, Arm A: DB 2-DAA	Substudy 1, Arm B: DB Placebo, Followed by OL 2-DAA	Substudy 2, Arm C: OL 2-DAA	Total
Arm/Group Description	DB 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis	DB placebo QD for 12 weeks followed by OL 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis	OL 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants with compensated cirrhosis	Total of all reporting groups
Overall Participants	215	106	42	363
Age, Customized (participants) [Number]
< 65 years	129 60%	59 55.7%	21 50%	209 57.6%
≥ 65 years	86 40%	47 44.3%	21 50%	154 42.4%
Sex: Female, Male (Count of Participants)
Female	135 62.8%	59 55.7%	22 52.4%	216 59.5%
Male	80 37.2%	47 44.3%	20 47.6%	147 40.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Non-cirrhotic Treatment-Naïve Participants Who Are Eligible for Interferon (IFN)-Based Therapy and Who Have High Viral Load in the DB Active Treatment Group With a Sustained Virologic Response 12 Weeks Post-treatment
Description	The percentage noncirrhotic treatment-naïve participants who were eligible for IFN-based therapy and who had high viral load at baseline (HCV RNA ≥ 100,000 IU/mL) in the DB active treatment group 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 active study drug (SVR12). Among noncirrhotic treatment-naïve participants who were eligible for IFN-based therapy and who had high viral load at baseline, superiority of Arm A to a clinically relevant threshold based on historical SVR rate with telaprevir plus pegylated interferon alpha/ribavirin (pegIFN/RBV) in treatment-naïve, non-cirrhotic patients with high viral load; the lower bound of 95% confidence interval (LCB) had to exceed 63% to achieve superiority. The 95% confidence interval was calculated using the normal approximation to the binomial distribution.
Time Frame	12 weeks after the last dose of study drug

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population: randomized non-cirrhotic treatment-naïve participants who are eligible for interferon-based therapy and who have high viral load and received at least one dose of double-blind ABT-450/r/ABT-267.

Arm/Group Title	Substudy 1, Arm A: DB 2-DAA
Arm/Group Description	DB 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis
Measure Participants	112
Number (95% Confidence Interval) [percentage of participants]	94.6 44%

2. Secondary Outcome

Title	Percentage of Participants in the Active Treatment Group With On-treatment Virologic Failure During Treatment
Description	On-treatment virologic failure among all randomized non-cirrhotic participants who received at least one dose of DB ABT-450/r/ABT-267 and all enrolled participants with compensated cirrhosis who received at least one dose of OL ABT-450/r/ABT-267. On-treatment virologic failure is defined as the occurrence of at least one of the following: confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) at any point during treatment after HCV RNA < LLOQ (rebound), 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 (rebound), or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks (≥ 36 days) of treatment (failure to suppress). The 95% confidence interval was calculated using the Wilson's score method.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: randomized/enrolled participants who received at least 1 dose of DB study drugs in Substudy 1 (Substudy 1 ITT population) and completed treatment; n=number of participants in the given subpopulation (among noncirrhotic participants, a single participant could potentially be included in more than 1 subpopulation).

Arm/Group Title	Substudy 1, Arm A: DB 2-DAA	Substudy 2, Arm C: OL 2-DAA
Arm/Group Description	DB 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis	OL 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants with compensated cirrhosis
Measure Participants	215	42
Number (95% Confidence Interval) [percentage of participants]	0.5 0.2%	2.4 2.3%

3. Secondary Outcome

Title	Percentage of Participants in the Substudy 1 Arm A Active Treatment Group With On-treatment Virologic Failure During Treatment, by Subpopulation
Description	On-treatment virologic failure among all randomized non-cirrhotic participants who received at least one dose of DB ABT-450/r/ABT-267 in the following subpopulations: noncirrhotic treatment-naïve (T-naïve) participants with a high baseline (BL) viral load (HCV RNA ≥ 100,000 IU/mL) who are eligible for IFN-based therapy (IFN-BT), a low viral load (HCV RNA < 100,000 IU/mL), or who are ineligible for IFN-BT; noncirrhotic treatment-experienced (T-exp) participants who relapsed after prior IFN-BT, who were nonresponders to prior IFN-BT, or who were intolerant to IFN-BT. On-treatment virologic failure is defined in Outcome measure 2. The 95% confidence interval was calculated using the Wilson's score method.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

ITT population: all randomized/enrolled participants who received at least 1 dose of active DB study drugs in Substudy 1 (Substudy 1 ITT population, Arm A).

Arm/Group Title	Substudy 1, Arm A: DB 2-DAA
Arm/Group Description	DB 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis
Measure Participants	215
T-naïve: high BL viral load, IFN-eligible; n=112	0 0%
T-naïve: low BL viral load; n=6	0 0%
T-naïve: IFN-ineligible; n=23	0 0%
T-exp. w/prior IFN-BT: relapser; n=22	0 0%
T-exp. w/prior IFN-BT: nonresponder; n=28	0 0%
T-exp. w/prior IFN-BT: IFN-intolerant; n=26	3.8 1.8%

4. Secondary Outcome

Title	Percentage of Participants in the Active Treatment Group With Post-treatment Relapse
Description	Post-treatment relapse among all randomized non-cirrhotic participants who received at least one dose of DB ABT-450/r/ABT-267 and completed treatment, and all enrolled participants with compensated cirrhosis who received at least one dose of OL ABT-450/r/ABT-267 and completed treatment. Relapse was defined as confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) between the final treatment visit and 12 weeks after the last dose of study drugs among participants completing treatment and with HCV RNA < LLOQ at the final treatment visit and at least one post-treatment HCV RNA value. The 95% confidence interval was calculated using the Wilson's score method.
Time Frame	within 12 weeks after last dose of study drug

Outcome Measure Data

Analysis Population Description

ITT population: all randomized/enrolled participants who received at least 1 dose of active DB study drugs in Substudy 1 (Substudy 1 ITT population, Arm A) or at least 1 dose of OL study drugs in Substudy 2 (Substudy 2 ITT population).

Arm/Group Title	Substudy 1, Arm A: DB 2-DAA	Substudy 2, Arm C: OL 2-DAA
Arm/Group Description	DB 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis	OL 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants with compensated cirrhosis
Measure Participants	209	40
Number (95% Confidence Interval) [percentage of participants]	2.4 1.1%	5.0 4.7%

5. Secondary Outcome

Title	Percentage of Participants in Substudy 1 Arm A Active Treatment Group With Post-treatment Relapse, by Subpopulation
Description	Post-treatment relapse among all randomized non-cirrhotic participants who received at least one dose of DB ABT-450/r/ABT-267 and completed treatment, in the following subpopulations: noncirrhotic treatment-naïve (T-naïve) participants with a high baseline (BL) viral load (HCV RNA ≥ 100,000 IU/mL) who are eligible for IFN-based therapy (IFN-BT), a low BL viral load (HCV RNA < 100,000 IU/mL), or who are ineligible for IFN-BT; noncirrhotic treatment-experienced (T-exp) participants who relapsed after prior IFN-BT, who were nonresponders to prior IFN-BT, or who were intolerant to IFN-BT. Relapse was defined as confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) between the final treatment visit and 12 weeks after the last dose of study drugs among participants completing treatment and with HCV RNA < LLOQ at the final treatment visit and at least one post-treatment HCV RNA value. The 95% confidence interval was calculated using the Wilson's score method.
Time Frame	within 12 weeks after last dose of study drug

Outcome Measure Data

Analysis Population Description

ITT population: all randomized/enrolled participants who received at least 1 dose of active DB study drugs in Substudy 1 (Substudy 1 ITT population, Arm A) and completed treatment; n=number of participants in the given subpopulation (among noncirrhotic participants, a single participant could potentially be included in more than 1 subpopulation).

Arm/Group Title	Substudy 1, Arm A: DB 2-DAA
Arm/Group Description	DB 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis
Measure Participants	209
T-naïve: high BL viral load, IFN-eligible; n=109	2.8 1.3%
T-naïve: low BL viral load; n=6	0 0%
T-naïve: IFN-ineligible; n=22	4.5 2.1%
T-exp. w/prior IFN-BT: relapser; n=21	0 0%
T-exp. w/prior IFN-BT: nonresponder; n=28	0 0%
T-exp. w/prior IFN-BT: IFN-intolerant; n=25	4.0 1.9%

6. Secondary Outcome

Title	Percentage of Participants in the Active Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment
Description	Sustained virologic response (plasma HCV RNA level < LLOQ) 12 weeks after the last dose of study drug for all randomized non-cirrhotic participants who received at least one dose of DB ABT-450/r/ABT-267 and for all enrolled participants with compensated cirrhosis who received at least one dose of open-label ABT-450/r/ABT-267. The 95% confidence interval was calculated using the Wilson's score method.
Time Frame	12 weeks after last dose of study drug

Outcome Measure Data

Analysis Population Description

ITT population: all randomized/enrolled participants who received at least 1 dose of DB study drugs in Substudy 1 (Substudy 1 ITT population) or at least 1 dose of OL study drugs in Substudy 2 (Substudy 2 ITT population).

Arm/Group Title	Substudy 1, Arm A: DB 2-DAA	Substudy 2, Arm C: OL 2-DAA
Arm/Group Description	DB 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis	OL 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants with compensated cirrhosis
Measure Participants	215	42
Number (95% Confidence Interval) [percentage of participants]	94.9 44.1%	90.5 85.4%

7. Secondary Outcome

Title	Percentage of Participants in Substudy 1 Arm A Active Treatment Group With Sustained Virologic Response 12 Weeks Post-Treatment, by Subpopulation
Description	Sustained virologic response (plasma HCV RNA level < LLOQ) 12 weeks after the last dose of study drug for all randomized non-cirrhotic participants who received at least one dose of DB ABT-450/r/ABT-267 in the following subpopulations: noncirrhotic T-naïve participants with a high BL viral load (HCV RNA ≥ 100,000 IU/mL) who are eligible for IFN-BT; noncirrhotic T-naïve participants with low BL viral load (HCV RNA < 100,000 IU/mL); noncirrhotic T-naïve participants who are ineligible for IFN-BT; noncirrhotic T-exp participants who relapsed after prior IFN-BT; noncirrhotic T-exp participants who were nonresponders to prior IFN-BT; noncirrhotic T-exp participants who were intolerant to IFN-BT. The 95% confidence interval was calculated using the Wilson's score method.
Time Frame	12 weeks after last dose of study drug

Outcome Measure Data

Analysis Population Description

ITT population: all randomized/enrolled participants who received at least 1 dose of active DB study drugs in Substudy 1 (Substudy 1 ITT population, Arm A); n=number of participants in the given subpopulation (among noncirrhotic participants, a single participant could potentially be included in more than 1 subpopulation).

Arm/Group Title	Substudy 1, Arm A: DB 2-DAA
Arm/Group Description	DB 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis
Measure Participants	215
T-naïve: all; n=139	94.2 43.8%
T-naïve: high BL viral load, IFN-eligible; n=112	94.6 44%
T-naïve: low BL viral load; n=6	100 46.5%
T-naïve: IFN-ineligible; n=23	91.3 42.5%
T-exp. w/prior IFN-BT: all; n=76	96.1 44.7%
T-exp. w/prior IFN-BT: relapser; n=22	95.5 44.4%
T-exp. w/prior IFN-BT: nonresponder; n=28	100 46.5%
T-exp. w/prior IFN-BT: IFN-intolerant; n=26	92.3 42.9%

Adverse Events

Time Frame	AEs collected from time of informed consent through 30 days post-study drug dosing (dosing period was 12 or 24 weeks [12 weeks of placebo followed by 12 weeks of DAAs]); Serious AEs collected up to post-treatment Week 48.
Arm/Group Title	Substudy 1, Arm A: DB 2-DAA		Substudy 1, Arm B: DB Placebo		Substudy 1, Arm B: OL 2-DAA		Substudy 2, Arm C: OL 2-DAA
Arm/Group Description	DB 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2 direct-acting antiviral agents [2-DAA]) once daily (QD) for 12 weeks in participants without cirrhosis.		DB placebo QD for 12 weeks in participants without cirrhosis		OL 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis		OL 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants with compensated cirrhosis
All Cause Mortality
	Substudy 1, Arm A: DB 2-DAA		Substudy 1, Arm B: DB Placebo		Substudy 1, Arm B: OL 2-DAA		Substudy 2, Arm C: OL 2-DAA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Substudy 1, Arm A: DB 2-DAA		Substudy 1, Arm B: DB Placebo		Substudy 1, Arm B: OL 2-DAA		Substudy 2, Arm C: OL 2-DAA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/215 (3.3%)		2/106 (1.9%)		3/106 (2.8%)		2/42 (4.8%)
Eye disorders
NECROTISING RETINITIS	0/215 (0%)		0/106 (0%)		1/106 (0.9%)		0/42 (0%)
Gastrointestinal disorders
LARGE INTESTINE POLYP	0/215 (0%)		0/106 (0%)		1/106 (0.9%)		0/42 (0%)
Infections and infestations
ANAL ABSCESS	1/215 (0.5%)		0/106 (0%)		0/106 (0%)		0/42 (0%)
Injury, poisoning and procedural complications
TENDON RUPTURE	1/215 (0.5%)		0/106 (0%)		0/106 (0%)		0/42 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER	0/215 (0%)		0/106 (0%)		1/106 (0.9%)		0/42 (0%)
COLON ADENOMA	0/215 (0%)		1/106 (0.9%)		0/106 (0%)		0/42 (0%)
GASTRIC CANCER STAGE IV	1/215 (0.5%)		0/106 (0%)		0/106 (0%)		0/42 (0%)
HEPATOCELLULAR CARCINOMA	1/215 (0.5%)		0/106 (0%)		0/106 (0%)		0/42 (0%)
METASTASES TO BONE	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
RECTOSIGMOID CANCER	0/215 (0%)		1/106 (0.9%)		0/106 (0%)		0/42 (0%)
Nervous system disorders
MULTIPLE SCLEROSIS	1/215 (0.5%)		0/106 (0%)		0/106 (0%)		0/42 (0%)
Renal and urinary disorders
ANURIA	1/215 (0.5%)		0/106 (0%)		0/106 (0%)		0/42 (0%)
Respiratory, thoracic and mediastinal disorders
PULMONARY OEDEMA	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
Vascular disorders
HYPOTENSION	1/215 (0.5%)		0/106 (0%)		0/106 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	Substudy 1, Arm A: DB 2-DAA		Substudy 1, Arm B: DB Placebo		Substudy 1, Arm B: OL 2-DAA		Substudy 2, Arm C: OL 2-DAA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	116/215 (54%)		48/106 (45.3%)		47/106 (44.3%)		31/42 (73.8%)
Blood and lymphatic system disorders
ANAEMIA	3/215 (1.4%)		0/106 (0%)		1/106 (0.9%)		1/42 (2.4%)
Eye disorders
EYE DISCHARGE	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
Gastrointestinal disorders
ABDOMINAL DISCOMFORT	4/215 (1.9%)		0/106 (0%)		3/106 (2.8%)		1/42 (2.4%)
ABDOMINAL PAIN UPPER	3/215 (1.4%)		0/106 (0%)		1/106 (0.9%)		2/42 (4.8%)
CONSTIPATION	2/215 (0.9%)		2/106 (1.9%)		1/106 (0.9%)		2/42 (4.8%)
DIARRHOEA	8/215 (3.7%)		3/106 (2.8%)		5/106 (4.7%)		1/42 (2.4%)
GLOSSODYNIA	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
HAEMATOCHEZIA	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
NAUSEA	9/215 (4.2%)		4/106 (3.8%)		1/106 (0.9%)		3/42 (7.1%)
STOMATITIS	6/215 (2.8%)		3/106 (2.8%)		3/106 (2.8%)		0/42 (0%)
VOMITING	2/215 (0.9%)		2/106 (1.9%)		1/106 (0.9%)		2/42 (4.8%)
General disorders
FACE OEDEMA	2/215 (0.9%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
FATIGUE	6/215 (2.8%)		1/106 (0.9%)		1/106 (0.9%)		1/42 (2.4%)
FEELING HOT	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
LOCAL SWELLING	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
MALAISE	9/215 (4.2%)		3/106 (2.8%)		0/106 (0%)		2/42 (4.8%)
OEDEMA PERIPHERAL	11/215 (5.1%)		0/106 (0%)		4/106 (3.8%)		3/42 (7.1%)
PYREXIA	4/215 (1.9%)		1/106 (0.9%)		1/106 (0.9%)		4/42 (9.5%)
THIRST	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
Infections and infestations
CELLULITIS	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
CYSTITIS	2/215 (0.9%)		4/106 (3.8%)		2/106 (1.9%)		1/42 (2.4%)
FOLLICULITIS	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
NASOPHARYNGITIS	36/215 (16.7%)		14/106 (13.2%)		8/106 (7.5%)		6/42 (14.3%)
PHARYNGITIS	1/215 (0.5%)		1/106 (0.9%)		3/106 (2.8%)		1/42 (2.4%)
URINARY TRACT INFECTION	0/215 (0%)		2/106 (1.9%)		3/106 (2.8%)		0/42 (0%)
Injury, poisoning and procedural complications
ARTHROPOD BITE	0/215 (0%)		0/106 (0%)		2/106 (1.9%)		1/42 (2.4%)
CONTUSION	2/215 (0.9%)		0/106 (0%)		3/106 (2.8%)		1/42 (2.4%)
LIGAMENT SPRAIN	1/215 (0.5%)		1/106 (0.9%)		0/106 (0%)		1/42 (2.4%)
THERMAL BURN	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/215 (0.5%)		0/106 (0%)		1/106 (0.9%)		1/42 (2.4%)
ALPHA-2 MACROGLOBULIN INCREASED	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
APOLIPOPROTEIN A-I DECREASED	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
ASPARTATE AMINOTRANSFERASE INCREASED	2/215 (0.9%)		0/106 (0%)		1/106 (0.9%)		1/42 (2.4%)
BLOOD BILIRUBIN INCREASED	1/215 (0.5%)		0/106 (0%)		1/106 (0.9%)		1/42 (2.4%)
BLOOD PRESSURE INCREASED	1/215 (0.5%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
BLOOD TRIGLYCERIDES INCREASED	0/215 (0%)		0/106 (0%)		1/106 (0.9%)		2/42 (4.8%)
HAEMATOCRIT DECREASED	1/215 (0.5%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
HAEMOGLOBIN DECREASED	2/215 (0.9%)		0/106 (0%)		1/106 (0.9%)		2/42 (4.8%)
LYMPHOCYTE MORPHOLOGY ABNORMAL	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
PLATELET COUNT DECREASED	0/215 (0%)		0/106 (0%)		0/106 (0%)		3/42 (7.1%)
RED BLOOD CELL COUNT DECREASED	2/215 (0.9%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
TRANSAMINASES INCREASED	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
WHITE BLOOD CELL COUNT DECREASED	1/215 (0.5%)		1/106 (0.9%)		0/106 (0%)		1/42 (2.4%)
Metabolism and nutrition disorders
DECREASED APPETITE	2/215 (0.9%)		1/106 (0.9%)		1/106 (0.9%)		2/42 (4.8%)
DIABETES MELLITUS	2/215 (0.9%)		0/106 (0%)		1/106 (0.9%)		1/42 (2.4%)
HYPOKALAEMIA	0/215 (0%)		1/106 (0.9%)		1/106 (0.9%)		1/42 (2.4%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	3/215 (1.4%)		1/106 (0.9%)		1/106 (0.9%)		2/42 (4.8%)
BACK PAIN	7/215 (3.3%)		2/106 (1.9%)		1/106 (0.9%)		0/42 (0%)
MUSCLE SPASMS	1/215 (0.5%)		1/106 (0.9%)		0/106 (0%)		1/42 (2.4%)
MUSCULOSKELETAL STIFFNESS	6/215 (2.8%)		1/106 (0.9%)		1/106 (0.9%)		0/42 (0%)
PERIARTHRITIS	0/215 (0%)		0/106 (0%)		1/106 (0.9%)		1/42 (2.4%)
Nervous system disorders
DIZZINESS	6/215 (2.8%)		2/106 (1.9%)		0/106 (0%)		2/42 (4.8%)
HEADACHE	19/215 (8.8%)		10/106 (9.4%)		7/106 (6.6%)		3/42 (7.1%)
NERVOUS SYSTEM DISORDER	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
SOMNOLENCE	3/215 (1.4%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
Psychiatric disorders
INSOMNIA	4/215 (1.9%)		2/106 (1.9%)		1/106 (0.9%)		2/42 (4.8%)
Respiratory, thoracic and mediastinal disorders
SPUTUM RETENTION	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
UPPER RESPIRATORY TRACT INFLAMMATION	4/215 (1.9%)		2/106 (1.9%)		1/106 (0.9%)		2/42 (4.8%)
Skin and subcutaneous tissue disorders
DERMAL CYST	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
DERMATITIS ACNEIFORM	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
DRUG ERUPTION	0/215 (0%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
ECZEMA	3/215 (1.4%)		0/106 (0%)		3/106 (2.8%)		3/42 (7.1%)
ECZEMA ASTEATOTIC	2/215 (0.9%)		0/106 (0%)		0/106 (0%)		1/42 (2.4%)
PRURITUS	10/215 (4.7%)		4/106 (3.8%)		4/106 (3.8%)		0/42 (0%)
PRURITUS GENERALISED	0/215 (0%)		0/106 (0%)		0/106 (0%)		2/42 (4.8%)
RASH	4/215 (1.9%)		2/106 (1.9%)		4/106 (3.8%)		2/42 (4.8%)
Vascular disorders
HYPERTENSION	2/215 (0.9%)		2/106 (1.9%)		1/106 (0.9%)		1/42 (2.4%)
HYPOTENSION	1/215 (0.5%)		0/106 (0%)		0/106 (0%)		2/42 (4.8%)

Limitations/Caveats

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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.