Back to resultsA Study to Evaluate the Safety and Effect of the Experimental Drugs ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 in Subjects With Chronic Hepatitis C (PEARL-II)
Primary Purpose
Chronic Hepatitis C Infection
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ABT-450/r/ABT-267, ABT-333
Ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis C Infection focused on measuring Hepatitis C virus, Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, Chronic Hepatitis C, Ombitasvir, Ribavirin, Viekira PAK, Dasabuvir, Paritaprevir
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's hepatitis C virus genotype is subgenotype 1b at Screening without co infection with any other genotype/subgenotype.
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
- Use of contraindicated medications within 2 weeks of dosing
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
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
Outcomes
Primary Outcome Measures
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Primary Analyses
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 with and without RBV) compared with the historical control rate for noncirrhotic, treatment-experienced participants with HCV GT1b infection treated with telaprevir and peginterferon (pegIFN)/RBV.
Secondary Outcome Measures
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; Secondary Analyses
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 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 with and without RBV) compared with the historical control rate for noncirrhotic, treatment-experienced participants with HCV GT1b treated with telaprevir and pegIFN/RBV; and 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 compared with those who received ABT-450/r/ABT-267 and ABT-333, plus 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. 95% CI was calculated using the Wilson score method for the single proportion because the point estimate was 0%.
Full Information
NCT ID
NCT01674725
First Posted
July 27, 2012
Last Updated
July 8, 2021
Sponsor
AbbVie (prior sponsor, Abbott)
1. Study Identification
Unique Protocol Identification Number
NCT01674725
Brief Title
A Study to Evaluate the Safety and Effect of the Experimental Drugs ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 in Subjects With Chronic Hepatitis C
Acronym
PEARL-II
Official Title
A Randomized, Open-Label, 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 in Treatment-Experienced Subjects With Genotype 1b Chronic Hepatitis C Virus (HCV) Infection (PEARL-II)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
October 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, open-label, 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-experienced, 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
Hepatitis C virus, Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, Chronic Hepatitis C, Ombitasvir, Ribavirin, Viekira PAK, Dasabuvir, Paritaprevir
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
187 (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
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
Intervention Type
Drug
Intervention Name(s)
ABT-450/r/ABT-267, ABT-333
Other Intervention Name(s)
ABT-450 also known as paritaprevir, ABT-267 also known as ombitasvir, 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
Tablet
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Primary Analyses
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 with and without RBV) compared with the historical control rate for noncirrhotic, treatment-experienced participants with HCV GT1b infection treated with telaprevir and peginterferon (pegIFN)/RBV.
Time Frame
12 weeks after last dose of study drug
Secondary Outcome Measure Information:
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; Secondary Analyses
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 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 with and without RBV) compared with the historical control rate for noncirrhotic, treatment-experienced participants with HCV GT1b treated with telaprevir and pegIFN/RBV; and 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 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 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. 95% CI was calculated using the Wilson score method for the single proportion because the point estimate was 0%.
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's hepatitis C virus genotype is subgenotype 1b at Screening without co infection with any other genotype/subgenotype.
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
Use of contraindicated medications within 2 weeks of dosing
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Enejosa, MD
Organizational Affiliation
AbbVie
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
24818763
Citation
Andreone P, Colombo MG, Enejosa JV, Koksal I, Ferenci P, Maieron A, Mullhaupt B, Horsmans Y, Weiland O, Reesink HW, Rodrigues L Jr, Hu YB, Podsadecki T, Bernstein B. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology. 2014 Aug;147(2):359-365.e1. doi: 10.1053/j.gastro.2014.04.045. Epub 2014 May 9.
Results Reference
result
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
Learn more about this trial
A Study to Evaluate the Safety and Effect of the Experimental Drugs ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 in Subjects With Chronic Hepatitis C
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