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A Study to Evaluate the Safety and Effect of Co-administration of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Adults With Chronic Hepatitis C Virus Infection (PEARL-I)

Primary Purpose

Hepatitis C, Chronic

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
ABT-450/r
ABT-267
Ribavirin (RBV)
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, Chronic focused on measuring Hepatitis C Virus, Ribavirin-Free, Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, Chronic Hepatitis C, Compensated cirrhosis, Hepatitis C Genotype 4, Paritaprevir, Ombitasvir, Ritonavir, Ribavirin

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Females must be practicing specific forms of birth control on study treatment, or be postmenopausal for more than 2 years or surgically sterile

  • Subjects must meet one of the following:

    • Treatment-naive: Subject has never received antiviral treatment for hepatitis C infection OR
    • Treatment Experienced (Prior null responders, Partial responders or Relapsers to pegIFN/RBV);
  • Body mass index (BMI) is ≥ 18 to < 38 kg/m^2.
  • Chronic HCV genotype 1b infection/with or without cirrhosis or HCV genotype 4 infection/without cirrhosis for at least 6 months prior to study screening.
  • Subject has plasma HCV RNA level > 10,000 IU/mL at Screening

Exclusion Criteria:

  • History of severe, life-threatening or other significant sensitivity to any drug.
  • Females who were pregnant or planned to become pregnant, or breastfeeding, or GT4-infected males whose partners were pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug/RBV.
  • Recent history of drug or alcohol abuse that could preclude adherence to the protocol.
  • Positive test result for hepatitis B surface antigen or anti-Human Immunodeficiency Virus (HIV) antibodies.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm 8

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Group 1

    Group 2

    Group 3

    Group 4

    Group 5

    Group 6

    Group 7

    Group 8

    Arm Description

    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants

    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants

    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants

    ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants

    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-experienced, HCV GT4-infected participants

    ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants

    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis

    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis

    Outcomes

    Primary Outcome Measures

    Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment
    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.

    Secondary Outcome Measures

    Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment
    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]) 24 weeks after the last dose of study drug.
    Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure.
    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 log(subscript)10(subscript) IU/mL above the lowest value post baseline] at any time point during treatment), or fail to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks [≥ 36 days] of treatment).
    Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse.
    Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment.
    Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events
    Treatment-emergent adverse events were defined as any event that began or worsened in severity after initiation of study drug through 30 days after the last dose of study drug.

    Full Information

    First Posted
    September 12, 2012
    Last Updated
    July 28, 2021
    Sponsor
    AbbVie (prior sponsor, Abbott)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01685203
    Brief Title
    A Study to Evaluate the Safety and Effect of Co-administration of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Adults With Chronic Hepatitis C Virus Infection
    Acronym
    PEARL-I
    Official Title
    A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Coadministration of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Adults With Chronic Hepatitis C Virus Infection (PEARL-I)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    August 2012 (undefined)
    Primary Completion Date
    June 2014 (Actual)
    Study Completion Date
    February 2015 (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 and efficacy of co-administration of ABT-450 (also known as paritaprevir) with ritonavir (ABT-450/r) and ABT-267 (also known as ombitasvir) in adults with chronic hepatitis C virus infection.
    Detailed Description
    This was a Phase 2, randomized, open-label, combination treatment study of the 2-DAA regimen (ABT-450 150 mg QD + ritonavir 100 mg QD + ABT-267 25 mg QD) in adult HCV GT1b-infected treatment-naïve and Pegylated-interferon/ribavirin (pegIFN/RBV) treatment-experienced participants without cirrhosis and with compensated cirrhosis, and in adult GT4-infected treatment-naïve and pegIFN/RBV treatment-experienced participants without cirrhosis. Treatment Group 5 was not open to enrollment, based on a protocol-specified interim review of results from the treatment-naïve GT4 Groups 1 and 4 that indicated higher sustained virologic response (SVR) rates among participants receiving the 2-DAA regimen with RBV. All other groups completed the study.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatitis C, Chronic
    Keywords
    Hepatitis C Virus, Ribavirin-Free, Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, Chronic Hepatitis C, Compensated cirrhosis, Hepatitis C Genotype 4, Paritaprevir, Ombitasvir, Ritonavir, Ribavirin

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Group 1
    Arm Type
    Experimental
    Arm Description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants
    Arm Title
    Group 2
    Arm Type
    Experimental
    Arm Description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants
    Arm Title
    Group 3
    Arm Type
    Experimental
    Arm Description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants
    Arm Title
    Group 4
    Arm Type
    Experimental
    Arm Description
    ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants
    Arm Title
    Group 5
    Arm Type
    Experimental
    Arm Description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-experienced, HCV GT4-infected participants
    Arm Title
    Group 6
    Arm Type
    Experimental
    Arm Description
    ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants
    Arm Title
    Group 7
    Arm Type
    Experimental
    Arm Description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis
    Arm Title
    Group 8
    Arm Type
    Experimental
    Arm Description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis
    Intervention Type
    Drug
    Intervention Name(s)
    ABT-450/r
    Other Intervention Name(s)
    ABT-450 also known as paritaprevir
    Intervention Description
    Tablet; ABT-450; Capsule; ritonavir
    Intervention Type
    Drug
    Intervention Name(s)
    ABT-267
    Other Intervention Name(s)
    ABT-267 also known as ombitasvir
    Intervention Description
    Tablet
    Intervention Type
    Drug
    Intervention Name(s)
    Ribavirin (RBV)
    Intervention Description
    Tablet
    Primary Outcome Measure Information:
    Title
    Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment
    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.
    Time Frame
    12 weeks after the last actual dose of study drug
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment
    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]) 24 weeks after the last dose of study drug.
    Time Frame
    24 weeks after the last actual dose of study drug
    Title
    Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure.
    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 log(subscript)10(subscript) IU/mL above the lowest value post baseline] at any time point during treatment), or fail to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks [≥ 36 days] of treatment).
    Time Frame
    Baseline (Day 1), Day 3, and Treatment Weeks 1, 2 ,3 ,4, 6, 8, 10, and 12 for all participants and Treatment Weeks 16, 20 and 24 for Groups 7 and 8
    Title
    Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse.
    Description
    Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment.
    Time Frame
    Within 12 weeks after the last dose of study drug
    Title
    Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events
    Description
    Treatment-emergent adverse events were defined as any event that began or worsened in severity after initiation of study drug through 30 days after the last dose of study drug.
    Time Frame
    From the start of study drug administration until 30 days after the last dose,16 weeks for Groups 1, 2, 3, 4, and 6, and 28 weeks for Groups 7 and 8.

    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 postmenopausal for more than 2 years or surgically sterile Subjects must meet one of the following: Treatment-naive: Subject has never received antiviral treatment for hepatitis C infection OR Treatment Experienced (Prior null responders, Partial responders or Relapsers to pegIFN/RBV); Body mass index (BMI) is ≥ 18 to < 38 kg/m^2. Chronic HCV genotype 1b infection/with or without cirrhosis or HCV genotype 4 infection/without cirrhosis for at least 6 months prior to study screening. Subject has plasma HCV RNA level > 10,000 IU/mL at Screening Exclusion Criteria: History of severe, life-threatening or other significant sensitivity to any drug. Females who were pregnant or planned to become pregnant, or breastfeeding, or GT4-infected males whose partners were pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug/RBV. Recent history of drug or alcohol abuse that could preclude adherence to the protocol. Positive test result for hepatitis B surface antigen or anti-Human Immunodeficiency Virus (HIV) antibodies.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Nilou Mobashery, MD
    Organizational Affiliation
    AbbVie
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    25837829
    Citation
    Hezode C, Asselah T, Reddy KR, Hassanein T, Berenguer M, Fleischer-Stepniewska K, Marcellin P, Hall C, Schnell G, Pilot-Matias T, Mobashery N, Redman R, Vilchez RA, Pol S. Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial. Lancet. 2015 Jun 20;385(9986):2502-9. doi: 10.1016/S0140-6736(15)60159-3. Epub 2015 Mar 31.
    Results Reference
    background
    PubMed Identifier
    26170136
    Citation
    Lawitz E, Makara M, Akarca US, Thuluvath PJ, Preotescu LL, Varunok P, Morillas RM, Hall C, Mobashery N, Redman R, Pilot-Matias T, Vilchez RA, Hezode C. Efficacy and Safety of Ombitasvir, Paritaprevir, and Ritonavir in an Open-Label Study of Patients With Genotype 1b Chronic Hepatitis C Virus Infection With and Without Cirrhosis. Gastroenterology. 2015 Oct;149(4):971-80.e1. doi: 10.1053/j.gastro.2015.07.001. Epub 2015 Jul 11.
    Results Reference
    background
    Links:
    URL
    http://www.rxabbvie.com
    Description
    Related Info

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    A Study to Evaluate the Safety and Effect of Co-administration of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Adults With Chronic Hepatitis C Virus Infection

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