Back to resultsStudy 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)
Primary Purpose
Chronic Hepatitis C Infection
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ABT-450/r/ABT-267
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis C Infection focused on measuring Hepatitis C, Genotype 1b, Cirrhotic, Treatment Experienced, Treatment Naive, Japanese, ombitasvir, paritaprevir, ritonavir, VIEKIRAX Combination Tablets
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
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 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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02023099
Brief Title
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
Acronym
GIFT I
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 Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C Infection
Keywords
Hepatitis C, Genotype 1b, Cirrhotic, Treatment Experienced, Treatment Naive, Japanese, ombitasvir, paritaprevir, ritonavir, VIEKIRAX Combination Tablets
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
363 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Substudy 1, Arm A: DB 2-DAA
Arm Type
Experimental
Arm 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
Arm Title
Substudy 1, Arm B: DB Placebo, Followed by OL 2-DAA
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
Substudy 2, Arm C: OL 2-DAA
Arm Type
Experimental
Arm Description
OL 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants with compensated cirrhosis
Intervention Type
Drug
Intervention Name(s)
ABT-450/r/ABT-267
Other Intervention Name(s)
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
Intervention Description
Tablet; ABT-450 coformulated with ritonavir and ABT-267
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablet
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nori Yachi
Organizational Affiliation
AbbVie GK.
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
26147154
Citation
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.
Results Reference
result
PubMed Identifier
27084721
Citation
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.
Results Reference
derived
Links:
URL
http://rxabbvie.com
Description
Related Info
Learn more about this trial
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
We'll reach out to this number within 24 hrs