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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)

Primary Purpose

Hepatitis C, HCV, Chronic Hepatitis C Infection

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ABT-450
ABT-072
Ribavirin
Ritonavir
Sponsored by
AbbVie (prior sponsor, Abbott)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Site Reference ID/Investigator# 41128
  • Site Reference ID/Investigator# 42262
  • Site Reference ID/Investigator# 41127
  • Site Reference ID/Investigator# 43182

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ABT-450/r and ABT-072, plus ribavirin (RBV)

Arm Description

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.

Outcomes

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
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)
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
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
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
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
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 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.

Full Information

First Posted
October 13, 2010
Last Updated
December 29, 2014
Sponsor
AbbVie (prior sponsor, Abbott)
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1. Study Identification

Unique Protocol Identification Number
NCT01221298
Brief Title
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)
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie (prior sponsor, Abbott)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, HCV, Chronic Hepatitis C Infection, Hepatitis C Genotype 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ABT-450/r and ABT-072, plus ribavirin (RBV)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ABT-450
Intervention Description
tablets
Intervention Type
Drug
Intervention Name(s)
ABT-072
Intervention Description
tablets
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Intervention Description
tablets
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Other Intervention Name(s)
Norvir
Intervention Description
capsules
Primary Outcome Measure Information:
Title
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
Description
Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (< 25 IU/mL).
Time Frame
Week 4 through Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) < 1000 International Units Per Milliliter (IU/mL)
Description
Analysis of participants with HCV RNA levels below 1000 IU/mL at Week 2.
Time Frame
Week 2
Title
Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Below the Lower Limit of Quantitation (LLOQ) at Week 4
Description
Analysis of percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (< 25 IU/mL).
Time Frame
Week 4
Title
Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment
Description
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.
Time Frame
Post-treatment Day 1 to Post-treatment Week 12
Title
Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment
Description
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 Frame
Post-treatment Day 1 to Post-treatment Week 24
Title
Time to Failure to Suppress or Rebound During Treatment
Description
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 Frame
Day 1 through Week 12
Title
Time to Virologic Relapse Through 24 Weeks Post-treatment
Description
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.
Time Frame
Post-treatment Day 1 to Post-treatment Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Cohen, MD
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Site Reference ID/Investigator# 41128
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Site Reference ID/Investigator# 42262
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Site Reference ID/Investigator# 41127
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Site Reference ID/Investigator# 43182
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23439262
Citation
Lawitz E, Poordad F, Kowdley KV, Cohen DE, Podsadecki T, Siggelkow S, Larsen L, Menon R, Koev G, Tripathi R, Pilot-Matias T, Bernstein B. A phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1. J Hepatol. 2013 Jul;59(1):18-23. doi: 10.1016/j.jhep.2013.02.009. Epub 2013 Feb 22.
Results Reference
derived
Links:
URL
http://rxabbvie.com
Description
Related Info

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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)

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