A Pilot Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of ABT-450 With Ritonavir (ABT-450/r) Dosed in Combination With ABT-072 and Ribavirin (RBV)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01221298
First received: October 13, 2010
Last updated: December 29, 2014
Last verified: December 2014
  Purpose
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of ABT-450 with ritonavir (ABT-450/r) dosed in combination with ABT-072 and ribavirin (RBV) in treatment-naïve participants with genotype 1 chronic hepatitis C virus (HCV) infection.

Condition Intervention Phase
Hepatitis C
HCV
Chronic Hepatitis C Infection
Hepatitis C Genotype 1
Drug: ABT-450
Drug: ABT-072
Drug: Ribavirin
Drug: Ritonavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Pilot Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of ABT-450 With Ritonavir (ABT-450/r) Dosed in Combination With ABT-072 and Ribavirin (RBV) in Treatment-Naive 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 Quantitation (LLOQ) 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 quantitation (< 25 IU/mL).


Secondary Outcome Measures:
  • Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (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 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Below the Lower Limit of Quantitation (LLOQ) 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 ]
    The time to failure to suppress was defined as first day a participant met any virologic stopping criteria during treatment. The virologic stopping criteria also includes failure to achieve a 2 log10 IU/mL decrease in HCV RNA by Week 1, failure to achieve HCV RNA <LLOQ by Week 6, or rebound, defined as first day of 2 consecutive increases of at least 0.5 log10 IU/mL above nadir (local minimum value) or confirmed HCV RNA > lower limit of detection (LLOD) for participants who previously achieved HCV RNA < LLOD.

  • Time to Virologic Relapse Through 24 Weeks Post-treatment [ Time Frame: Post-treatment Day 1 to Post-treatment Week 24 ] [ Designated as safety issue: No ]
    Time to confirmed hepatitis C virus (HCV) ribonucleic acid (RNA) ≥ lower limit of quantitation (LLOQ) (2 consecutive measurements ≥ LLOQ) at any point in the post-treatment period among participants with HCV RNA < LLOQ at the end of treatment.


Enrollment: 11
Study Start Date: October 2010
Study Completion Date: April 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ABT-450/r and ABT-072, plus ribavirin (RBV)
ABT-450/r (150/100 mg) once daily (QD) and ABT-072 (400 mg) QD plus weight-based RBV divided twice daily (BID) for 12 weeks.
Drug: ABT-450
tablets
Drug: ABT-072
tablets
Drug: Ribavirin
tablets
Drug: Ritonavir
capsules
Other Name: Norvir

Detailed Description:
This was a Phase 2a multicenter, open-label, single arm, combination treatment study of a regimen of ABT-450/r/ABT-072, and ribavirin (RBV) in hepatitis C virus (HCV) genotype 1-(1a or 1b) infected treatment-naïve participants.
  Eligibility

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

Inclusion Criteria:

  • Chronic hepatitis C, genotype 1 infection with interleukin 28B (IL28B) rs12979860 genotype C/C.
  • Liver biopsy within 3 years with histology consistent with hepatitis C virus (HCV) - induced liver damage, with no evidence of cirrhosis or liver pathology due to any cause other than chronic HCV.
  • Treatment naïve male or female between the ages of 18 and 65.
  • Females must be postmenopausal for at least 2 years or surgically sterile.
  • Be in a condition of general good health, as perceived by the investigator, other than hepatitis C virus infection.
  • Body mass index 18 to < 35 kg/m^2 .

Exclusion Criteria:

  • Significant sensitivity to any drug.
  • Use of herbal supplements within 2 weeks prior to study drug dosing.
  • Positive screen for certain drugs or alcohol.
  • Positive hepatitis B surface antigen or anti-human immunodeficiency virus (HIV) 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.
  • Prior treatment with any investigational or commercially available anti-hepatitis C virus agents.
  • Abnormal laboratory tests.
  • Cirrhosis or extensive bridging fibrosis.
  • History of cardiac disease.
  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: NCT01221298

Locations
United States, California
Site Reference ID/Investigator# 41128
Los Angeles, California, United States, 90048
United States, Illinois
Site Reference ID/Investigator# 42262
Chicago, Illinois, United States, 60637
United States, Texas
Site Reference ID/Investigator# 41127
San Antonio, Texas, United States, 78215
United States, Washington
Site Reference ID/Investigator# 43182
Seattle, Washington, United States, 98101
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Daniel Cohen, MD AbbVie
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AbbVie (prior sponsor, Abbott)
ClinicalTrials.gov Identifier: NCT01221298     History of Changes
Other Study ID Numbers: M12-267 
Study First Received: October 13, 2010
Results First Received: December 29, 2014
Last Updated: December 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Infection
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Ritonavir
Antiviral Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 27, 2016