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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AbbVie (prior sponsor, Abbott)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 28, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 2, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 8, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 29, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings