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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01306617
First received: February 28, 2011
Last updated: December 29, 2014
Last verified: December 2014
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C Infection
Hepatitis C
Hepatitis C Virus
Drug: ABT-450
Drug: ABT-333
Drug: ribavirin
Drug: ritonavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of detection (< 15 IU/mL).


Secondary Outcome Measures:
  • Percentage of Participants With HCV RNA < 1000 International Units Per Milliliter (IU/mL) [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Analysis of participants with HCV RNA levels below 1000 IU/mL at 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 ] [ Designated as safety issue: No ]
    Analysis of percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (< 25 IU/mL).

  • Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment [ Time Frame: Post-treatment Day 1 to Post-treatment Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment [ Time Frame: Post-treatment Day 1 to Post-treatment Week 24 ] [ Designated as safety issue: No ]
    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.

  • Time to Failure to Suppress or Rebound During Treatment [ Time Frame: Day 1 through Week 12 ] [ Designated as safety issue: No ]
    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.

  • Time to Virologic Relapse Post-treatment [ Time Frame: Post-treatment Day 1 to post-treatment week 48 ] [ Designated as safety issue: No ]
    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.

  • Resistance-Associated Variants and Phenotypic Resistance [ Time Frame: Day 1 to post-treatment week 48 ] [ Designated as safety issue: No ]
    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.

  • Pharmacokinetics (C Trough) of ABT 450 in HCV Infected Participants [ Time Frame: Day 1 to Week 12 ] [ Designated as safety issue: No ]
    Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.

  • Pharmacokinetics (C Trough) of ABT-333 in HCV Infected Participants [ Time Frame: Day 1 to Week 12 ] [ Designated as safety issue: No ]
    Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.

  • Pharmacokinetics (C Trough) of Ritonavir in HCV Infected Participants [ Time Frame: Day 1 to Week 12 ] [ Designated as safety issue: No ]
    Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.

  • Pharmacokinetics (C Trough) of Ribavirin in HCV Infected Participants [ Time Frame: Day 1 to Week 12 ] [ Designated as safety issue: No ]
    Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.


Enrollment: 50
Study Start Date: February 2011
Study Completion Date: October 2012
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: dasabuvir
Drug: ribavirin
tablets
Drug: ritonavir
capsules
Other Name: 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 Name: dasabuvir
Drug: ribavirin
tablets
Drug: ritonavir
capsules
Other Name: 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 Name: dasabuvir
Drug: ribavirin
tablets
Drug: ritonavir
capsules
Other Name: Norvir

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01306617

Locations
United States, California
Site Reference ID/Investigator# 48263
Los Angeles, California, United States, 90048
United States, Colorado
Site Reference ID/Investigator# 48264
Aurora, Colorado, United States, 80045
United States, Florida
Site Reference ID/Investigator# 51282
Gainesville, Florida, United States, 32610
United States, Massachusetts
Site Reference ID/Investigator# 50425
Springfield, Massachusetts, United States, 01105
United States, Missouri
Site Reference ID/Investigator# 50423
Kansas City, Missouri, United States, 64131
United States, New York
Site Reference ID/Investigator# 48268
New York, New York, United States, 10016
United States, North Carolina
Site Reference ID/Investigator# 50428
Statesville, North Carolina, United States, 28677
United States, Texas
Site Reference ID/Investigator# 48266
San Antonio, Texas, United States, 78215
United States, Virginia
Site Reference ID/Investigator# 50427
Newport News, Virginia, United States, 23602
United States, Washington
Site Reference ID/Investigator# 48265
Seattle, Washington, United States, 98101
United States, Wisconsin
Site Reference ID/Investigator# 50424
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Daniel Cohen, MD AbbVie
  More Information

Additional Information:
No publications provided by AbbVie

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01306617     History of Changes
Other Study ID Numbers: M12-746
Study First Received: February 28, 2011
Results First Received: December 29, 2014
Last Updated: December 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Hepatitis A
Hepatitis, Chronic
Infection
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Ribavirin
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on May 29, 2015