A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of ABT-450 With Ritonavir (ABT-450/r) When Given Together With ABT-333 and Ribavirin (RBV) in Treatment-Naïve and Non-responder Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

December 29, 2014 updated by: AbbVie (prior sponsor, Abbott)

An Open-Label Pilot Study to Evaluate the Antiviral Activity, Safety and Pharmacokinetics of ABT-450 With Ritonavir (ABT-450/r) Dosed in Combination With ABT-333 and Ribavirin (RBV) in Treatment-Naive and Non-responder Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

The purpose of this study is to evaluate the antiviral activity, safety, and pharmacokinetics of ABT-450 with ritonavir (ABT-450/r) dosed in combination with ABT-333 (also known as dasabuvir) and ribavirin (RBV) in treatment-naïve and non responder participants with genotype 1 chronic hepatitis C virus (HCV) infection.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This was a phase 2a multicenter, open-label, sequential, 3-arm, combination treatment study of a regimen of ABT-450/r/ABT-333, and ribavirin (RBV) in hepatitis C virus (HCV) genotype 1-infected treatment-naïve participants and previous non-responders to pegylated interferon (pegIFN)/RBV treatment.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Site Reference ID/Investigator# 48263
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Site Reference ID/Investigator# 48264
    • Florida
      • Gainesville, Florida, United States, 32610
        • Site Reference ID/Investigator# 51282
    • Massachusetts
      • Springfield, Massachusetts, United States, 01105
        • Site Reference ID/Investigator# 50425
    • Missouri
      • Kansas City, Missouri, United States, 64131
        • Site Reference ID/Investigator# 50423
    • New York
      • New York, New York, United States, 10016
        • Site Reference ID/Investigator# 48268
    • North Carolina
      • Statesville, North Carolina, United States, 28677
        • Site Reference ID/Investigator# 50428
    • Texas
      • San Antonio, Texas, United States, 78215
        • Site Reference ID/Investigator# 48266
    • Virginia
      • Newport News, Virginia, United States, 23602
        • Site Reference ID/Investigator# 50427
    • Washington
      • Seattle, Washington, United States, 98101
        • Site Reference ID/Investigator# 48265
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Site Reference ID/Investigator# 50424

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 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Chronic hepatitis C virus (HCV)
  • Treatment naive, null or partial responders to previous treatment with peginterferon and ribavirin
  • Males and females 18-65 years old
  • Body mass index 18 to < 35 kg/m^2
  • Females must be postmenopausal for at least 2 years or surgically sterile

Exclusion Criteria:

  • Cirrhosis or extensive bridging fibrosis
  • History of cardiac disease
  • Positive screen for certain drugs or alcohol
  • Abnormal laboratory results
  • Significant sensitivity to any drug
  • Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody
  • Use of strong cytochrome P450 3A (CYP3A), cytochrome P450 2C8 (CYP2C8), and organic anion transporting polypeptide 1B1 (OATP1B1) enzyme inducers or inhibitors within 1 month of dosing

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ABT-450/r (250/100 mg) and ABT-333 plus RBV in treatment-naïve
ABT-450/r (250/100 mg) once daily (QD) and ABT-333 (400 mg) twice daily (BID) plus weight-based ribavirin (RBV) divided BID for 12 weeks in treatment-naïve participants.
Drug: ABT-450
tablets
Drug: ABT-333
tablets
Other Names:
  • dasabuvir
Drug: ribavirin
tablets
Drug: ritonavir
capsules
Other Names:
  • Norvir
Experimental: ABT-450/r (150/100 mg) and ABT-333 plus RBV in treatment-naïve
ABT-450/r (150/100 mg) once daily (QD) and ABT-333 (400 mg) twice daily (BID) plus weight-based ribavirin (RBV) divided BID for 12 weeks in treatment-naïve participants.
Drug: ABT-450
tablets
Drug: ABT-333
tablets
Other Names:
  • dasabuvir
Drug: ribavirin
tablets
Drug: ritonavir
capsules
Other Names:
  • Norvir
Experimental: ABT-450/r (150/100 mg) and ABT-333 plus RBV in non-responders
ABT-450/r (150/100 mg) once daily (QD) and ABT-333 (400 mg) twice daily (BID) plus weight-based ribavirin (RBV) divided BID in previous non-responders to pegylated interferon (pegIFN) and RBV.
Drug: ABT-450
tablets
Drug: ABT-333
tablets
Other Names:
  • dasabuvir
Drug: ribavirin
tablets
Drug: ritonavir
capsules
Other Names:
  • Norvir

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Detection (LLOD) From Week 4 Through Week 12
Time Frame: Week 4 through Week 12
Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of detection (< 15 IU/mL).
Week 4 through Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With HCV RNA < 1000 International Units Per Milliliter (IU/mL)
Time Frame: Week 2
Analysis of participants with HCV RNA levels below 1000 IU/mL at Week 2.
Week 2
Percentage of Participants With HCV RNA Below the Lower Limit of Quantitation (LLOQ; <25 IU/mL) at Week 4
Time Frame: Week 4
Analysis of percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (< 25 IU/mL).
Week 4
Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment
Time Frame: Post-treatment Day 1 to Post-treatment Week 12
Sustained virologic response 12 (SVR12) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; < 25 IU/mL) 12 weeks after the last dose of study drug.
Post-treatment Day 1 to Post-treatment Week 12
Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment
Time Frame: Post-treatment Day 1 to Post-treatment Week 24
Sustained virologic response 24 (SVR24) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; < 25 IU/mL) 24 weeks after the last dose of study drug.
Post-treatment Day 1 to Post-treatment Week 24
Time to Failure to Suppress or Rebound During Treatment
Time Frame: Day 1 through Week 12
Time to failure to achieve a 2 log10 IU/mL HCV RNA decrease at Week 1, failure to achieve HCV RNA < Lower Limit of Detection (LLOD) at Week 6, or a confirmed increase of at least 0.5 log10 IU/mL above nadir (local minimum value) or confirmed HCV RNA > lower limit of quantitation (LLOQ) for participants who previously achieved HCV RNA < LLOQ.
Day 1 through Week 12
Time to Virologic Relapse Post-treatment
Time Frame: Post-treatment Day 1 to post-treatment week 48
Time to the first of 2 consecutive measurements of confirmed HCV RNA ≥ lower limit of quantitation (LLOQ) at any point in the post-treatment period among participants with HCV RNA < LLOQ at the end of treatment.
Post-treatment Day 1 to post-treatment week 48
Resistance-Associated Variants and Phenotypic Resistance
Time Frame: Day 1 to post-treatment week 48
Baseline samples were analyzed for resistance-associated amino acid variants using population sequencing. Phenotypic resistance to ABT-450 or ABT-333 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Participants not achieving SVR12 were analyzed for resistance-associated variants at the time of failure using population sequencing and were compared with the baseline and appropriate reference sequences to assess amino acid changes. Phenotypic resistance to ABT-450 or ABT-333 at the time of failure was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance at baseline and at the time of failure are presented.
Day 1 to post-treatment week 48
Pharmacokinetics (C Trough) of ABT 450 in HCV Infected Participants
Time Frame: Day 1 to Week 12
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.
Day 1 to Week 12
Pharmacokinetics (C Trough) of ABT-333 in HCV Infected Participants
Time Frame: Day 1 to Week 12
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.
Day 1 to Week 12
Pharmacokinetics (C Trough) of Ritonavir in HCV Infected Participants
Time Frame: Day 1 to Week 12
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.
Day 1 to Week 12
Pharmacokinetics (C Trough) of Ribavirin in HCV Infected Participants
Time Frame: Day 1 to Week 12
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.
Day 1 to Week 12

Collaborators and Investigators

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

Sponsor

AbbVie (prior sponsor, Abbott)

Investigators

  • Study Director: Daniel Cohen, MD, 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

February 1, 2011

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

October 1, 2012

Study Registration Dates

First Submitted

February 28, 2011

First Submitted That Met QC Criteria

February 28, 2011

First Posted (Estimate)

March 2, 2011

Study Record Updates

Last Update Posted (Estimate)

January 8, 2015

Last Update Submitted That Met QC Criteria

December 29, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M12-746

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.

Clinical Trials on Hepatitis C

Clinical Trials on ABT-450

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ecuador

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe