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

Phase 3

Completed

• Conditions: Chronic Hepatitis C Infection
• Interventions: Drug: ABT-450/r/ABT-267; Drug: Placebo

• Registration Number: NCT02023099
• Lead Sponsor: AbbVie

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12
• Study First Submitted: 2013-12-23
• Study First Submitted QC: 2013-12-23
• Study First Posted: 2013-12-30
• Primary Completion: 2014-10
• Study Completion: 2015-10
• Results First Submitted: 2015-10-27
• Results First Submitted QC: 2015-10-27
• Results First Posted: 2015-11-26
• Status Verified: 2016-09
• Last Update Submitted: 2018-05-02
• Last Update Posted: 2018-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 363

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Substudy 1, Arm B: DB Placebo, Followed by OL 2-DAA	Placebo	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
Substudy 1, Arm B: DB Placebo, Followed by OL 2-DAA	ABT-450/r/ABT-267	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
Substudy 1, Arm A: DB 2-DAA	ABT-450/r/ABT-267	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
Substudy 2, Arm C: OL 2-DAA	ABT-450/r/ABT-267	OL 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants with compensated cirrhosis

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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.
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.
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.
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.
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.