Back to resultsA Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/ABT-450/Ritonavir Co-administered With Ribavirin (RBV) in Adults With Genotype 4 Chronic Hepatitis C Virus (HCV) Infection and Cirrhosis (AGATE-1) (AGATE-1)
Primary Purpose
Hepatitis C Virus
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ombitasvir/paritaprevir/ritonavir
ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C Virus focused on measuring Compensated Cirrhosis, Hepatitis C, Hepatitis C Genotype 4, Chronic Hepatitis C
Eligibility Criteria
Inclusion Criteria:
For Arms A, B and C:
- Participants must meet one of the following:
- Treatment-naive: Participant has never received antiviral treatment for hepatitis C infection OR
- Treatment Experienced (Prior null responders, Partial responders or Relapsers to IFN/RBV);
For Arm D:
- Participant must have prior treatment experience with SOF/pegIFN/RBV or SOF/RBV and meet one of the following categories:
- Prior SOF breakthrough/non-responder: HCV RNA detectable at the end of treatment with SOF/pegIFN/RBV or SOF/RBV;
- Prior SOF relapser: achieved HCV RNA undetectable at end of a prior treatment course SOF/pegIFN/RBV or SOF/RBV, but HCV RNA was detectable within 52 weeks following completion of therapy.
For Arms A, B, C and D:
- Chronic HCV genotype 4 infection with cirrhosis.
- Participant has plasma HCV RNA level > 1,000 IU/mL at Screening
Exclusion Criteria:
- Positive test result at Screening for Hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab).
- Current enrollment in another interventional clinical study, previous enrollment in this study, or previous use of any protease inhibitor, non-nucleoside polymerase inhibitor, or Nonstructural viral protein (NS) 5A inhibitor, either investigational or commercially available (including previous exposure to paritaprevir or ombitasvir), or receipt of any investigational product within 6 weeks prior to study drug administration. Prior use of any direct-acting antiviral will not be allowed, except for Arm D where prior experience with the nucleoside polymerase inhibitor, sofosbuvir with pegIFN/RBV or SOF with RBV is required.
- Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation including ascites, variceal bleeding, or hepatic encephalopathy.
- Confirmed presence of hepatocellular carcinoma.
- Any cause of liver disease other than chronic HCV infection.
- Abnormal laboratory tests.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Arm A
Arm B
Arm C
Arm D
Arm Description
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 12 weeks for genotype 4 treatment-naïve or treatment-experienced with IFN/RBV.
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 16 weeks for genotype 4 treatment-naive or treatment-experienced with IFN/RBV.
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 24 weeks for genotype 4 treatment-naive and treatment-experienced with IFN/RBV.
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 24 weeks for genotype 4 SOF/pegIFN/RBV or SOF/RBV treatment-experienced.
Outcomes
Primary Outcome Measures
Percentage of Participants in Arms A, B and C With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (<LLOQ) 12 weeks after the last dose of study drug.
Secondary Outcome Measures
Percentage of Participants With SVR12 in Participants Receiving 12 Weeks (Arm A) of Treatment Compared to Participants Receiving 16 Weeks of Treatment (Arm B)
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of study drug.
Percentage of Participants With SVR12 in Participants Receiving 16 Weeks (Arm B) of Treatment Compared to Participants Receiving 24 Weeks of Treatment (Arm C)
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of study drug.
Percentage of Participants in Arms A, B and C With On-treatment Virologic Failure
On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or all on-treatment values of HCV RNA >= LLOQ with at least 6 weeks of treatment.
Percentage of Participants in Arms A, B and C With Post-treatment Relapse
Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants with HCV RNA levels < LLOQ at the end of treatment.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02265237
Brief Title
A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/ABT-450/Ritonavir Co-administered With Ribavirin (RBV) in Adults With Genotype 4 Chronic Hepatitis C Virus (HCV) Infection and Cirrhosis (AGATE-1)
Acronym
AGATE-1
Official Title
A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/ABT-450/Ritonavir Co-administered With Ribavirin (RBV) in Adults With Genotype 4 Chronic Hepatitis C Virus (HCV) Infection and Cirrhosis (AGATE-1)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
October 28, 2014 (undefined)
Primary Completion Date
July 28, 2016 (Actual)
Study Completion Date
April 7, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study in HCV genotype 4-infected participants with compensated cirrhosis is to assess the safety and to compare the percentage of participants achieving a 12-week sustained virologic response (SVR12), [HCV ribonucleic acid (RNA) < lower limit of quantification (LLOQ) 12 weeks following treatment], to a clinically relevant threshold [based on SVR rates for HCV genotype 4-infected participants treated with pegylated interferon (pegIFN)/RBV].
Detailed Description
This is a Phase 3, randomized, open-label, multicenter study evaluating the safety and efficacy of ombitasvir/paritaprevir/ritonavir coadministered with RBV for 12, 16, or 24 weeks in HCV genotype 4 (GT4)-infected participants with compensated cirrhosis who are either treatment-naïve or who had previously received only IFN/RBV treatment for HCV.
The study also enrolled HCV GT4-infected participants with compensated cirrhosis who had previously experienced virologic failure with either SOF/pegIFN/RBV or sofosbuvir (SOF)/RBV treatment. These participants were treated with ombitasvir/paritaprevir/ritonavir coadministered with RBV for 24 weeks in this study.
This study was divided into 2 parts with approximately 184 total participants. Part I included participants who were randomized to receive either 12 or 16 weeks of treatment and Part II included participants who received 24 weeks of treatment. Enrollment into Part II opened once randomization in Part I was completed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Virus
Keywords
Compensated Cirrhosis, Hepatitis C, Hepatitis C Genotype 4, Chronic Hepatitis C
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
184 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 12 weeks for genotype 4 treatment-naïve or treatment-experienced with IFN/RBV.
Arm Title
Arm B
Arm Type
Experimental
Arm Description
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 16 weeks for genotype 4 treatment-naive or treatment-experienced with IFN/RBV.
Arm Title
Arm C
Arm Type
Experimental
Arm Description
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 24 weeks for genotype 4 treatment-naive and treatment-experienced with IFN/RBV.
Arm Title
Arm D
Arm Type
Experimental
Arm Description
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 24 weeks for genotype 4 SOF/pegIFN/RBV or SOF/RBV treatment-experienced.
Intervention Type
Drug
Intervention Name(s)
ombitasvir/paritaprevir/ritonavir
Other Intervention Name(s)
norvir (ritonavir), paritaprevir (ABT-450), ombitasvir (ABT-267)
Intervention Description
tablets
Intervention Type
Drug
Intervention Name(s)
ribavirin
Intervention Description
tablets
Primary Outcome Measure Information:
Title
Percentage of Participants in Arms A, B and C With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
Description
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (<LLOQ) 12 weeks after the last dose of study drug.
Time Frame
12 weeks after the last actual dose of study drug
Secondary Outcome Measure Information:
Title
Percentage of Participants With SVR12 in Participants Receiving 12 Weeks (Arm A) of Treatment Compared to Participants Receiving 16 Weeks of Treatment (Arm B)
Description
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of study drug.
Time Frame
12 weeks after the last actual dose of study drug
Title
Percentage of Participants With SVR12 in Participants Receiving 16 Weeks (Arm B) of Treatment Compared to Participants Receiving 24 Weeks of Treatment (Arm C)
Description
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of study drug.
Time Frame
12 weeks after the last actual dose of study drug
Title
Percentage of Participants in Arms A, B and C With On-treatment Virologic Failure
Description
On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or all on-treatment values of HCV RNA >= LLOQ with at least 6 weeks of treatment.
Time Frame
Up to Treatment Week 24 (end of treatment) or premature discontinuation from treatment
Title
Percentage of Participants in Arms A, B and C With Post-treatment Relapse
Description
Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants with HCV RNA levels < LLOQ at the end of treatment.
Time Frame
From the end of treatment through 12 weeks after the last dose of study drug
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
For Arms A, B and C:
- Participants must meet one of the following:
Treatment-naive: Participant has never received antiviral treatment for hepatitis C infection OR
Treatment Experienced (Prior null responders, Partial responders or Relapsers to IFN/RBV);
For Arm D:
- Participant must have prior treatment experience with SOF/pegIFN/RBV or SOF/RBV and meet one of the following categories:
Prior SOF breakthrough/non-responder: HCV RNA detectable at the end of treatment with SOF/pegIFN/RBV or SOF/RBV;
Prior SOF relapser: achieved HCV RNA undetectable at end of a prior treatment course SOF/pegIFN/RBV or SOF/RBV, but HCV RNA was detectable within 52 weeks following completion of therapy.
For Arms A, B, C and D:
Chronic HCV genotype 4 infection with cirrhosis.
Participant has plasma HCV RNA level > 1,000 IU/mL at Screening
Exclusion Criteria:
Positive test result at Screening for Hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab).
Current enrollment in another interventional clinical study, previous enrollment in this study, or previous use of any protease inhibitor, non-nucleoside polymerase inhibitor, or Nonstructural viral protein (NS) 5A inhibitor, either investigational or commercially available (including previous exposure to paritaprevir or ombitasvir), or receipt of any investigational product within 6 weeks prior to study drug administration. Prior use of any direct-acting antiviral will not be allowed, except for Arm D where prior experience with the nucleoside polymerase inhibitor, sofosbuvir with pegIFN/RBV or SOF with RBV is required.
Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation including ascites, variceal bleeding, or hepatic encephalopathy.
Confirmed presence of hepatocellular carcinoma.
Any cause of liver disease other than chronic HCV infection.
Abnormal laboratory tests.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AbbVie Inc.
Organizational Affiliation
AbbVie
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
28404108
Citation
Asselah T, Hezode C, Qaqish RB, ElKhashab M, Hassanein T, Papatheodoridis G, Feld JJ, Moreno C, Zeuzem S, Ferenci P, Yu Y, Redman R, Pilot-Matias T, Mobashery N. Ombitasvir, paritaprevir, and ritonavir plus ribavirin in adults with hepatitis C virus genotype 4 infection and cirrhosis (AGATE-I): a multicentre, phase 3, randomised open-label trial. Lancet Gastroenterol Hepatol. 2016 Sep;1(1):25-35. doi: 10.1016/S2468-1253(16)30001-2. Epub 2016 Jun 16.
Results Reference
derived
Learn more about this trial
A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/ABT-450/Ritonavir Co-administered With Ribavirin (RBV) in Adults With Genotype 4 Chronic Hepatitis C Virus (HCV) Infection and Cirrhosis (AGATE-1)
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