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 (GIFT I)

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)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C Infection
• Intervention / Treatment: Drug: Placebo; Drug: ABT-450/r/ABT-267

• Study Type: Interventional
• Enrollment (Actual): 363
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / 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; Technivie; ritonavir also known as Norvir; VIEKIRAX Combination Tablets; Qurevo; 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: Placebo; Tablet; 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; Technivie; ritonavir also known as Norvir; VIEKIRAX Combination Tablets; Qurevo; VIEKIRA Combination Tablets
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; Technivie; ritonavir also known as Norvir; VIEKIRAX Combination Tablets; Qurevo; VIEKIRA Combination Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	12 weeks after the last dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants in the Active Treatment Group With On-treatment Virologic Failure During Treatment	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.	up to 12 weeks
Percentage of Participants in the Substudy 1 Arm A Active Treatment Group With On-treatment Virologic Failure During Treatment, by Subpopulation	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.	up to 12 weeks
Percentage of Participants in the Active Treatment Group With Post-treatment Relapse	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.	within 12 weeks after last dose of study drug
Percentage of Participants in Substudy 1 Arm A Active Treatment Group With Post-treatment Relapse, by Subpopulation	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.	within 12 weeks after last dose of study drug
Percentage of Participants in the Active Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment	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.	12 weeks after last dose of study drug
Percentage of Participants in Substudy 1 Arm A Active Treatment Group With Sustained Virologic Response 12 Weeks Post-Treatment, by Subpopulation	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.	12 weeks after last dose of study drug

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: Nori Yachi, AbbVie GK.

Publications and helpful links

General Publications

• Kumada H, Chayama K, Rodrigues L Jr, Suzuki F, Ikeda K, Toyoda H, Sato K, Karino Y, Matsuzaki Y, Kioka K, Setze C, Pilot-Matias T, Patwardhan M, Vilchez RA, Burroughs M, Redman R. Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis. Hepatology. 2015 Oct;62(4):1037-46. doi: 10.1002/hep.27972. Epub 2015 Aug 25.
• Gopalakrishnan S, Khatri A, Mensing S, Redman R, Menon R, Zha J. Exposure-Response Relationship for Ombitasvir and Paritaprevir/Ritonavir in Hepatitis C Virus Subgenotype 1b-Infected Japanese Patients in the Phase 3 Randomized GIFT-I Study. Adv Ther. 2016 Apr;33(4):670-83. doi: 10.1007/s12325-016-0320-y. Epub 2016 Mar 21.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: December 23, 2013
• First Submitted That Met QC Criteria: December 23, 2013
• First Posted (Estimate): December 30, 2013

Study Record Updates

• Last Update Posted (Actual): June 6, 2018
• Last Update Submitted That Met QC Criteria: May 2, 2018
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Treatment Experienced; Japanese; Hepatitis C; Cirrhotic; Treatment Naive; ritonavir; ombitasvir; paritaprevir; Genotype 1b; VIEKIRAX Combination Tablets
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Infections; Communicable Diseases; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir
• Other Study ID Numbers: M13-004