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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) (AGATE-1)

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ClinicalTrials.gov Identifier: NCT02265237
Recruitment Status : Completed
First Posted : October 15, 2014
Results First Posted : August 31, 2017
Last Update Posted : August 31, 2017
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE October 10, 2014
First Posted Date  ICMJE October 15, 2014
Results First Submitted Date April 26, 2017
Results First Posted Date August 31, 2017
Last Update Posted Date August 31, 2017
Study Start Date  ICMJE October 28, 2014
Actual Primary Completion Date July 28, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 1, 2017)
Percentage of Participants in Arms A, B and C With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [ Time Frame: 12 weeks after the last actual dose of study drug ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 10, 2014)
  • Percentage of subjects with sustained virologic response 12 (SVR12) weeks post treatment [ Time Frame: 12 weeks after the last actual dose of study drug ]
    Hepatitis C virus ribonucleic acid is less than the lower limit of quantification
  • Percentage of subjects with treatment-emergent adverse events [ Time Frame: Up to 30 days following end of treatment ]
    Percentage of subjects who develop treatment-emergent adverse events
Change History Complete list of historical versions of study NCT02265237 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2017)
  • Percentage of Participants With SVR12 in Participants Receiving 12 Weeks (Arm A) of Treatment Compared to Participants Receiving 16 Weeks of Treatment (Arm B) [ Time Frame: 12 weeks after the last actual dose of study drug ]
    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) [ Time Frame: 12 weeks after the last actual dose of study drug ]
    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 [ Time Frame: Up to Treatment Week 24 (end of treatment) or premature discontinuation from treatment ]
    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 [ Time Frame: From the end of treatment through 12 weeks after the last dose of study drug ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2014)
  • Percentage of subjects with SVR12 in subjects receiving 12 weeks of treatment compared to subjects receiving 16 weeks of treatment. [ Time Frame: 12 weeks after last actual dose of study drug ]
    Hepatitis C virus ribonucleic acid less than the lower limit of quantification
  • Percentage of subjects with on-treatment virologic failure [ Time Frame: Up to 16 weeks after first dose of study drug ]
    Hepatitis C virus ribonucleic acid greater than lower limit of quantification
  • Percentage of subjects with post-treatment relapse [ Time Frame: Within 12 weeks after the last dose of study drug ]
    Hepatitis C virus ribonucleic acid greater than lower limit of quantification
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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)
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.

Study Type  ICMJE Interventional
Study Phase Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C Virus
Intervention  ICMJE
  • Drug: ombitasvir/paritaprevir/ritonavir
    tablets
    Other Names:
    • norvir (ritonavir)
    • paritaprevir (ABT-450)
    • ombitasvir (ABT-267)
  • Drug: ribavirin
    tablets
Study Arms
  • Experimental: Arm A
    Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 12 weeks for genotype 4 treatment-naïve or treatment-experienced with IFN/RBV.
    Interventions:
    • Drug: ombitasvir/paritaprevir/ritonavir
    • Drug: ribavirin
  • Experimental: Arm B
    Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 16 weeks for genotype 4 treatment-naive or treatment-experienced with IFN/RBV.
    Interventions:
    • Drug: ombitasvir/paritaprevir/ritonavir
    • Drug: ribavirin
  • Experimental: Arm C
    Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 24 weeks for genotype 4 treatment-naive and treatment-experienced with IFN/RBV.
    Interventions:
    • Drug: ombitasvir/paritaprevir/ritonavir
    • Drug: ribavirin
  • Experimental: Arm D
    Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 24 weeks for genotype 4 SOF/pegIFN/RBV or SOF/RBV treatment-experienced.
    Interventions:
    • Drug: ombitasvir/paritaprevir/ritonavir
    • Drug: ribavirin
Publications * Asselah T, Hézode 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 1, 2017)
184
Original Estimated Enrollment  ICMJE
 (submitted: October 10, 2014)
160
Actual Study Completion Date April 7, 2017
Actual Primary Completion Date July 28, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Austria,   Belgium,   Canada,   France,   Germany,   Greece,   Italy,   Spain,   United States
 
Administrative Information
NCT Number  ICMJE NCT02265237
Other Study ID Numbers  ICMJE M11-665
2014-001496-31 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP