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)

NCT ID: NCT02265237

Last Updated: 2017-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 184 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-28
• Study Completion Date: 2017-04-07

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.

Conditions

Hepatitis C Virus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

ombitasvir/paritaprevir/ritonavir

Intervention Type: DRUG

tablets

ribavirin

Intervention Type: DRUG

tablets

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.

Group Type: EXPERIMENTAL

ombitasvir/paritaprevir/ritonavir

Intervention Type: DRUG

tablets

ribavirin

Intervention Type: DRUG

tablets

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.

Group Type: EXPERIMENTAL

ombitasvir/paritaprevir/ritonavir

Intervention Type: DRUG

tablets

ribavirin

Intervention Type: DRUG

tablets

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.

Group Type: EXPERIMENTAL

ombitasvir/paritaprevir/ritonavir

Intervention Type: DRUG

tablets

ribavirin

Intervention Type: DRUG

tablets

Interventions

ombitasvir/paritaprevir/ritonavir

tablets

Intervention Type: DRUG

ribavirin

tablets

Intervention Type: DRUG

Other Intervention Names

norvir (ritonavir); paritaprevir (ABT-450); ombitasvir (ABT-267)

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

References

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.

Reference Type: DERIVED

PMID: 28404108 (View on PubMed)

Other Identifiers

2014-001496-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M11-665

Identifier Type: -

Identifier Source: org_study_id