An Open-label, Single Arm, Phase 2 Study to Evaluate ABT-450/r/ABT-267 and ABT-333 With Ribavirin (RBV) in Adults With Genotype 1 HCV Infection Taking Methadone or Buprenorphine

April 30, 2018 updated by: AbbVie

An Open-label, Single-Arm, Phase 2 Study to Evaluate the Combination of ABT-450/r/ABT-267 and ABT-333 Coadministered With Ribavirin (RBV) in Adults With Genotype 1 Hepatitis C Virus (HCV) Infection Taking Methadone or Buprenorphine

The purpose of this study is to evaluate the safety and efficacy of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267; ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) coadministered with ribavirin (RBV) in hepatitis C virus (HCV) genotype 1-infected adults taking methadone or buprenorphine ± naloxone.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study consisted of 2 periods: a 12-week treatment period and a 48-week post-treatment period (for all participants who received study drugs). All participants who received at least 1 dose of study drug were to be followed for 48 weeks post-treatment to monitor for safety, HCV RNA, the emergence and/or persistence of resistant viral variants, and assessment of patient-reported outcome (PRO) instruments.

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Females must be practicing specific forms of birth control on study treatment, or be postmenopausal for more than 2 years or surgically sterile.
  • Chronic HCV infection prior to study enrollment.
  • Screening laboratory result indicating HCV genotype 1-infection.
  • Subject must be treatment naive or previous pegylated interferon/ribavirin treatment experienced.
  • Subjects must be on a stable opioid replacement therapy of methadone or buprenorphine ± naloxone for at least 6 months prior to screening.

Exclusion Criteria:

  • Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency virus antibody (HIV Ab) at screening.
  • Prior therapy with direct acting antiviral agents for the treatment of HCV, including telaprevir and boceprevir.
  • Females who are pregnant or plan to become pregnant, or breastfeeding, or males whose partners are pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug.
  • Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis, e.g., a Metavir Score of >3 or Ishak score of > 4.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: ABT-450/r/ABT-267 and ABT-333, plus RBV
ABT-450/r/ABT-267 (150/100/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; 1,000 mg/day if <75 kg or 1,200 mg/day if ≥75 kg, divided twice daily) for 12 weeks
Drug: Ribavirin (RBV)
Tablet
Drug: ABT-450/r/ABT-267
Tablet; ABT-450 coformulated with ritonavir and ABT-267
Other Names:
  • ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir
Drug: ABT-333
Tablet
Other Names:
  • dasabuvir

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment
Time Frame: 12 weeks after the last actual dose of study drug
The percentage of participants with sustained virologic response (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.
12 weeks after the last actual dose of study drug

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Virologic Failure During Treatment
Time Frame: Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, and 12
Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log(subscript)10(subscript) IU/mL above the lowest value post baseline] at any time point during treatment) or fail to suppress (HCV RNA ≥ LLOQ) persistently during treatment with at least 6 weeks [≥ 36 days] of treatment.
Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, and 12
Percentage of Participants With Virologic Relapse Post-treatment
Time Frame: From the end of treatment through 12 weeks after the last actual dose of study drug
Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment. Completion of treatment was defined as a study drug duration ≥ 77 days.
From the end of treatment through 12 weeks after the last actual dose of study drug
Area Under the Plasma Concentration-time Curve (AUC) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
Time Frame: Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and were analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC24 in ng*hr/mL)] was estimated using noncompartmental analyses. For ABT-450, ritonavir, and ABT-267, the AUC from time 0 to the last measureable concentration (AUCt in ng*hr/mL) was calculated instead of AUC24 due to time deviations at 24 hours. The AUCt values are approximately equivalent to AUC24. For ABT-333, ABT-333 M1, and RBV, the AUC from time 0 to 12 hours (AUC12 in ng*hr/mL) after the morning dose was calculated using the 24-hour concentration as the 12-hour concentration as dosing was twice a day and a 12-hour sample was not collected in this study.
Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Maximum Plasma Concentration (Cmax) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
Time Frame: Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and were analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Maximum plasma concentration (Cmax; measured in ng/mL) was directly determined from the concentration-time data.
Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Time to Maximum Plasma Concentration (Tmax) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
Time Frame: Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. The time to maximum plasma concentration (Tmax; measured in hours) was directly determined from the concentration-time data.
Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Plasma Trough Concentration (Ctrough) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
Time Frame: Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Minimum plasma concentration (C trough; measured in ng/mL) was directly determined from the concentration-time data.
Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (ACTUAL)

December 1, 2013

Study Completion (ACTUAL)

September 1, 2014

Study Registration Dates

First Submitted

May 13, 2013

First Submitted That Met QC Criteria

July 29, 2013

First Posted (ESTIMATE)

July 30, 2013

Study Record Updates

Last Update Posted (ACTUAL)

May 30, 2018

Last Update Submitted That Met QC Criteria

April 30, 2018

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M14-103

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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