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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

Primary Purpose

Chronic Hepatitis C Infection, Hepatitis C, Hepatitis C Virus

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ABT-450
ABT-333
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 Chronic Hepatitis C Infection

Eligibility Criteria

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

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

Sites / Locations

  • Site Reference ID/Investigator# 48263
  • Site Reference ID/Investigator# 48264
  • Site Reference ID/Investigator# 51282
  • Site Reference ID/Investigator# 50425
  • Site Reference ID/Investigator# 50423
  • Site Reference ID/Investigator# 48268
  • Site Reference ID/Investigator# 50428
  • Site Reference ID/Investigator# 48266
  • Site Reference ID/Investigator# 50427
  • Site Reference ID/Investigator# 48265
  • Site Reference ID/Investigator# 50424

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

ABT-450/r (250/100 mg) and ABT-333 plus RBV in treatment-naïve

ABT-450/r (150/100 mg) and ABT-333 plus RBV in treatment-naïve

ABT-450/r (150/100 mg) and ABT-333 plus RBV in non-responders

Arm Description

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.

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.

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.

Outcomes

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
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)
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
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
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 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
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
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
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
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
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.

Full Information

First Posted
February 28, 2011
Last Updated
December 29, 2014
Sponsor
AbbVie (prior sponsor, Abbott)
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1. Study Identification

Unique Protocol Identification Number
NCT01306617
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
October 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 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.
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.

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
ABT-450/r (250/100 mg) and ABT-333 plus RBV in treatment-naïve
Arm Type
Experimental
Arm Description
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.
Arm Title
ABT-450/r (150/100 mg) and ABT-333 plus RBV in treatment-naïve
Arm Type
Experimental
Arm Description
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.
Arm Title
ABT-450/r (150/100 mg) and ABT-333 plus RBV in non-responders
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ABT-450
Intervention Description
tablets
Intervention Type
Drug
Intervention Name(s)
ABT-333
Other Intervention Name(s)
dasabuvir
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 Detection (LLOD) 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 detection (< 15 IU/mL).
Time Frame
Week 4 through Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With HCV 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 HCV RNA Below the Lower Limit of Quantitation (LLOQ; <25 IU/mL) 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
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 Frame
Day 1 through Week 12
Title
Time to Virologic Relapse Post-treatment
Description
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.
Time Frame
Post-treatment Day 1 to post-treatment week 48
Title
Resistance-Associated Variants and Phenotypic Resistance
Description
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.
Time Frame
Day 1 to post-treatment week 48
Title
Pharmacokinetics (C Trough) of ABT 450 in HCV Infected Participants
Description
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.
Time Frame
Day 1 to Week 12
Title
Pharmacokinetics (C Trough) of ABT-333 in HCV Infected Participants
Description
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.
Time Frame
Day 1 to Week 12
Title
Pharmacokinetics (C Trough) of Ritonavir in HCV Infected Participants
Description
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.
Time Frame
Day 1 to Week 12
Title
Pharmacokinetics (C Trough) of Ribavirin in HCV Infected Participants
Description
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.
Time Frame
Day 1 to Week 12

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

12. IPD Sharing Statement

Citations:
PubMed Identifier
23281975
Citation
Poordad F, Lawitz E, Kowdley KV, Cohen DE, Podsadecki T, Siggelkow S, Heckaman M, Larsen L, Menon R, Koev G, Tripathi R, Pilot-Matias T, Bernstein B. Exploratory study of oral combination antiviral therapy for hepatitis C. N Engl J Med. 2013 Jan 3;368(1):45-53. doi: 10.1056/NEJMoa1208809.
Results Reference
derived
Links:
URL
http://rxabbvie.com
Description
Related Info

Learn more about this trial

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

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