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A Study to Evaluate Chronic Hepatitis C Infection in Adults With Genotype 1a Infection (PEARL-IV)

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
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C Infection focused on measuring Chronic Hepatitis C, Hepatitis C Virus, Hepatitis C Genotype 1a, Hepatitis C, Treatment-Naïve, Interferon-Free, Paritaprevir, Ombitasvir, Dasabuvir, Ribavirin, Viekira PAK

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 post-menopausal for more than 2 years or surgically sterile
  • Chronic hepatitis C, genotype 1a-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; 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, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1a 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 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 GT1a infection 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, plus placebo RBV 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 calculated using the normal approximation to the binomial distribution.

    Full Information

    First Posted
    February 27, 2013
    Last Updated
    July 8, 2021
    Sponsor
    AbbVie
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01833533
    Brief Title
    A Study to Evaluate Chronic Hepatitis C Infection in Adults With Genotype 1a Infection
    Acronym
    PEARL-IV
    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-Naïve Adults With Genotype 1a Chronic Hepatitis C Virus (HCV) Infection (PEARL-IV)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    March 2013 (undefined)
    Primary Completion Date
    December 2013 (Actual)
    Study Completion Date
    September 2014 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    AbbVie

    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 1a (HCV GT1a) infection without cirrhosis.
    Detailed Description
    A randomized, double-blind, placebo-controlled, 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-naive, noncirrhotic participants with chronic hepatitis C virus genotype 1a (HCV GT1a) 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
    Chronic Hepatitis C, Hepatitis C Virus, Hepatitis C Genotype 1a, Hepatitis C, Treatment-Naïve, Interferon-Free, Paritaprevir, Ombitasvir, Dasabuvir, Ribavirin, Viekira PAK

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    305 (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; 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, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1a 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 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 GT1a infection 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, 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 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 calculated using the normal approximation to the binomial distribution.
    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 1a-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
    Yan Luo, 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
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    A Study to Evaluate Chronic Hepatitis C Infection in Adults With Genotype 1a Infection

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