Back to resultsA Study to Evaluate Chronic Hepatitis C Infection in Adults With Genotype 1b Infection (PEARL-III)
Primary Purpose
Chronic Hepatitis C Infection
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ABT-450/r/ABT-267, ABT-333
Ribavirin
Placebo for ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis C Infection focused on measuring Interferon-Free, Hepatitis C Genotype 1b, Chronic Hepatitis C, Hepatitis C Virus, Hepatitis C, Treatment-Naive, Paritaprevir, Ombitasvir, Dasabuvir, Viekira PAK, Ribavirin
Eligibility Criteria
Inclusion Criteria:
- Females must be practicing specific forms of birth control on study treatment, or be post-menopausal for more than 2 years or surgically sterile
- Chronic hepatitis C, genotype 1b-infection (HCV RNA level greater than or equal to 10,000 IU/mL at screening)
- Subject has never received antiviral treatment for hepatitis C infection
- No evidence of liver cirrhosis
Exclusion Criteria:
- Significant liver disease with any cause other than HCV as the primary cause
- Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody
- Positive screen for drugs or alcohol
- Significant sensitivity to any drug
- Use of contraindicated medications within 2 weeks of dosing
- Abnormal laboratory tests
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
ABT-450/r/ABT-267 and ABT-333, Plus RBV
ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
Arm Description
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks
Outcomes
Primary Outcome Measures
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analyses of Each Treatment Arm Compared to Historical Rate
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL.
The primary efficacy endpoints were noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b infection treated with telaprevir and peginterferon/RBV (pegIFN).
Secondary Outcome Measures
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analysis of ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV Compared With ABT-450/r/ABT-267 and ABT-333, Plus RBV
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.
The secondary endpoint was the noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment who received ABT-450/r/ABT-267 and ABT-333, plus placebo RBV compared with those who received ABT-450/r/ABT-267 and ABT-333, plus RBV.
Percentage of Participants With Hemoglobin Decrease to Below the Lower Limit of Normal (LLN) At End of Treatment
The percentage of participants with a decrease in hemoglobin from greater than or equal to the lower limit of normal (≥ LLN) at baseline to < LLN at the end of treatment.
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Superiority Analyses of Each Treatment Arm Compared to Historical Rate
The percentage of participants with sustained virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.
The secondary efficacy endpoints were superiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b treated with telaprevir and pegIFN/RBV.
Percentage of Participants With Virologic Failure During Treatment
Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log10 IU/mL above the lowest value post baseline] at any time point during treatment), or failure to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks [≥ 36 days] of treatment).
Percentage of Participants With Virologic Relapse After Treatment
Participants who completed treatment with plasma HCV RNA less than the lower limit of quantification (<LLOQ) at the end of treatment were considered to have virologic relapse if they had confirmed HCV RNA ≥ LLOQ during the post-treatment period.
Full Information
NCT ID
NCT01767116
First Posted
November 30, 2012
Last Updated
July 8, 2021
Sponsor
AbbVie (prior sponsor, Abbott)
1. Study Identification
Unique Protocol Identification Number
NCT01767116
Brief Title
A Study to Evaluate Chronic Hepatitis C Infection in Adults With Genotype 1b Infection
Acronym
PEARL-III
Official Title
A Randomized, Double-blind, Controlled Study to Evaluate the Efficacy and Safety of the Combination of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With and Without Ribavirin (RBV) in Treatment-Naive Adults With Genotype 1b Chronic Hepatitis C Virus (HCV) Infection (PEARL-III)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
August 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie (prior sponsor, Abbott)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and antiviral activity of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267; ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) with and without ribavirin (RBV) in patients with chronic hepatitis C virus genotype 1b (HCV GT1b) infection without cirrhosis.
Detailed Description
A randomized, double-blind, multicenter study to evaluate the safety and antiviral activity of the combination of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 with and without ribavirin (RBV) in treatment-naïve, noncirrhotic participants with chronic hepatitis C virus genotype 1b (HCV GT1b) infection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C Infection
Keywords
Interferon-Free, Hepatitis C Genotype 1b, Chronic Hepatitis C, Hepatitis C Virus, Hepatitis C, Treatment-Naive, Paritaprevir, Ombitasvir, Dasabuvir, Viekira PAK, Ribavirin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
419 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ABT-450/r/ABT-267 and ABT-333, Plus RBV
Arm Type
Experimental
Arm Description
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
Arm Title
ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
Arm Type
Experimental
Arm Description
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks
Intervention Type
Drug
Intervention Name(s)
ABT-450/r/ABT-267, ABT-333
Other Intervention Name(s)
ABT-267 also known as ombitasvir, ABT-450 also known as paritaprevir, ABT-333 also known as dasabuvir, Viekira PAK
Intervention Description
Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Intervention Description
Capsule
Intervention Type
Drug
Intervention Name(s)
Placebo for ribavirin
Intervention Description
Capsule
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analyses of Each Treatment Arm Compared to Historical Rate
Description
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL.
The primary efficacy endpoints were noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b infection treated with telaprevir and peginterferon/RBV (pegIFN).
Time Frame
12 weeks after last dose of study drug
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analysis of ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV Compared With ABT-450/r/ABT-267 and ABT-333, Plus RBV
Description
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.
The secondary endpoint was the noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment who received ABT-450/r/ABT-267 and ABT-333, plus placebo RBV compared with those who received ABT-450/r/ABT-267 and ABT-333, plus RBV.
Time Frame
12 weeks after last dose of study drug
Title
Percentage of Participants With Hemoglobin Decrease to Below the Lower Limit of Normal (LLN) At End of Treatment
Description
The percentage of participants with a decrease in hemoglobin from greater than or equal to the lower limit of normal (≥ LLN) at baseline to < LLN at the end of treatment.
Time Frame
Baseline (Day 1) and Week 12 (End of Treatment)
Title
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Superiority Analyses of Each Treatment Arm Compared to Historical Rate
Description
The percentage of participants with sustained virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.
The secondary efficacy endpoints were superiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b treated with telaprevir and pegIFN/RBV.
Time Frame
12 weeks after last dose of study drug
Title
Percentage of Participants With Virologic Failure During Treatment
Description
Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log10 IU/mL above the lowest value post baseline] at any time point during treatment), or failure to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks [≥ 36 days] of treatment).
Time Frame
Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, and 12
Title
Percentage of Participants With Virologic Relapse After Treatment
Description
Participants who completed treatment with plasma HCV RNA less than the lower limit of quantification (<LLOQ) at the end of treatment were considered to have virologic relapse if they had confirmed HCV RNA ≥ LLOQ during the post-treatment period.
Time Frame
Between End of Treatment (Week 12) and Post-treatment (up to Week 12 Post-treatment)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Females must be practicing specific forms of birth control on study treatment, or be post-menopausal for more than 2 years or surgically sterile
Chronic hepatitis C, genotype 1b-infection (HCV RNA level greater than or equal to 10,000 IU/mL at screening)
Subject has never received antiviral treatment for hepatitis C infection
No evidence of liver cirrhosis
Exclusion Criteria:
Significant liver disease with any cause other than HCV as the primary cause
Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody
Positive screen for drugs or alcohol
Significant sensitivity to any drug
Use of contraindicated medications within 2 weeks of dosing
Abnormal laboratory tests
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dan Cohen, MD
Organizational Affiliation
AbbVie
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
24795200
Citation
Ferenci P, Bernstein D, Lalezari J, Cohen D, Luo Y, Cooper C, Tam E, Marinho RT, Tsai N, Nyberg A, Box TD, Younes Z, Enayati P, Green S, Baruch Y, Bhandari BR, Caruntu FA, Sepe T, Chulanov V, Janczewska E, Rizzardini G, Gervain J, Planas R, Moreno C, Hassanein T, Xie W, King M, Podsadecki T, Reddy KR; PEARL-III Study; PEARL-IV Study. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014 May 22;370(21):1983-92. doi: 10.1056/NEJMoa1402338. Epub 2014 May 4.
Results Reference
background
PubMed Identifier
29377566
Citation
Feld JJ, Bernstein DE, Younes Z, Vlierberghe HV, Larsen L, Tatsch F, Ferenci P. Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin. Liver Int. 2018 Sep;38(9):1571-1575. doi: 10.1111/liv.13708. Epub 2018 Mar 14.
Results Reference
derived
Links:
URL
http://rxabbvie.com
Description
Related Info
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A Study to Evaluate Chronic Hepatitis C Infection in Adults With Genotype 1b Infection
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