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A Study to Evaluate the Safety and Antiviral Effect of Multiple Doses of ABT-493 and ABT-530 in Adults With Genotype 1 Hepatitis C Virus (HCV)

Primary Purpose

Chronic Hepatitis C, Hepatitis C Virus, Compensated Cirrhosis

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
ABT-493
ABT-530
ABT-450/r/ABT-267, ABT-333
Ribavirin (RBV)
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C focused on measuring Chronic Hepatitis C, Cirrhosis, Child Pugh A, Hepatitis C virus, Compensated Cirrhosis, Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, Cirrhotic

Eligibility Criteria

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

Inclusion Criteria:

  • Chronic HCV infection prior to study enrollment.
  • Screening laboratory result indicating HCV genotype 1-infection.
  • Subject has plasma HCV RNA level greater than 10,000 IU/mL at Screening.
  • Per local standard, subject is considered to be non-cirrhotic or to have compensated cirrhosis.

Exclusion Criteria:

  • History of severe, life-threatening or other significant sensitivity to any drug.
  • Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency Virus antibody (HIV Ab).
  • Prior therapy for the treatment of HCV.
  • Any current or past clinical evidence of Child Pugh B or C classification of clinical history of liver decompensation including ascites (noted on physical exam), variceal bleeding or hepatic encephalopathy.
  • Any cause of liver disease other than chronic HCV infection.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm 8

    Arm 9

    Arm 10

    Arm 11

    Arm 12

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Arm 1 Non-cirrhotic

    Arm 2 Non-cirrhotic

    Arm 3 Non-cirrhotic

    Arm 4 Non-cirrhotic

    Arm 5 Compensated cirrhotic

    Arm 6 Non-cirrhotic

    Arm 7 Non-cirrhotic

    Arm 8 Non-cirrhotic

    Arm 9 Non-cirrhotic

    Arm 10 Compensated cirrhotic

    Arm 11 Non-cirrhotic

    Arm 12 Non-cirrhotic

    Arm Description

    ABT-493 Dose A (100 mg once daily [QD]) for 3 days, followed by 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-493 Dose B (400 mg QD) for 3 days, followed by 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-493 Dose C (700 mg QD) for 3 days, followed by 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-493 Dose D (200 mg QD) for 3 days, followed by 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-493 Dose E (200 mg QD) for 3 days, followed by 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-530 Dose A (15 mg QD) for 3 days, followed by 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-530 Dose B (120 mg QD) for 3 days,followed by 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-530 Dose C (400 mg QD) for 3 days, followed by 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-530 Dose D (40 mg QD) for 3 days, followed by 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-530 Dose E (120 mg QD) for 3 days, followed by 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-493 Dose F (300 mg QD) for 3 days, followed by 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-530 Dose F (≤ 400 mg) for 3 days, followed by 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

    Outcomes

    Primary Outcome Measures

    Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment
    Maximal decrease from baseline in log10 HCV RNA levels during ABT-493 or ABT-530 monotherapy treatment. The baseline value was the last measurement before the first dose of monotherapy on Day 1.

    Secondary Outcome Measures

    Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
    SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of combination study drug.
    Percentage of Participants With On-treatment Virologic Failure
    On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during combination treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during combination treatment; or HCV RNA ≥ LLOQ at end of combination treatment with at least 6 weeks of combination treatment.
    Percentage of Participants With Post-treatment Relapse
    Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants completing combination treatment with HCV RNA levels < LLOQ at the end of treatment.

    Full Information

    First Posted
    November 21, 2013
    Last Updated
    July 8, 2021
    Sponsor
    AbbVie
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01995071
    Brief Title
    A Study to Evaluate the Safety and Antiviral Effect of Multiple Doses of ABT-493 and ABT-530 in Adults With Genotype 1 Hepatitis C Virus (HCV)
    Official Title
    A Randomized, Open-Label, Dose Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-493 and ABT-530 in Adult Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    November 2013 (undefined)
    Primary Completion Date
    June 2015 (Actual)
    Study Completion Date
    June 2015 (Actual)

    3. Sponsor/Collaborators

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

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the safety and antiviral effect of multiple doses of ABT-493 and ABT-530 in adults with genotype 1 HCV.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Hepatitis C, Hepatitis C Virus, Compensated Cirrhosis
    Keywords
    Chronic Hepatitis C, Cirrhosis, Child Pugh A, Hepatitis C virus, Compensated Cirrhosis, Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, Cirrhotic

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Arm 1 Non-cirrhotic
    Arm Type
    Experimental
    Arm Description
    ABT-493 Dose A (100 mg once daily [QD]) for 3 days, followed by 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
    Arm 2 Non-cirrhotic
    Arm Type
    Experimental
    Arm Description
    ABT-493 Dose B (400 mg QD) for 3 days, followed by 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
    Arm 3 Non-cirrhotic
    Arm Type
    Experimental
    Arm Description
    ABT-493 Dose C (700 mg QD) for 3 days, followed by 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
    Arm 4 Non-cirrhotic
    Arm Type
    Experimental
    Arm Description
    ABT-493 Dose D (200 mg QD) for 3 days, followed by 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
    Arm 5 Compensated cirrhotic
    Arm Type
    Experimental
    Arm Description
    ABT-493 Dose E (200 mg QD) for 3 days, followed by 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
    Arm 6 Non-cirrhotic
    Arm Type
    Experimental
    Arm Description
    ABT-530 Dose A (15 mg QD) for 3 days, followed by 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
    Arm 7 Non-cirrhotic
    Arm Type
    Experimental
    Arm Description
    ABT-530 Dose B (120 mg QD) for 3 days,followed by 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
    Arm 8 Non-cirrhotic
    Arm Type
    Experimental
    Arm Description
    ABT-530 Dose C (400 mg QD) for 3 days, followed by 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
    Arm 9 Non-cirrhotic
    Arm Type
    Experimental
    Arm Description
    ABT-530 Dose D (40 mg QD) for 3 days, followed by 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
    Arm 10 Compensated cirrhotic
    Arm Type
    Experimental
    Arm Description
    ABT-530 Dose E (120 mg QD) for 3 days, followed by 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
    Arm 11 Non-cirrhotic
    Arm Type
    Experimental
    Arm Description
    ABT-493 Dose F (300 mg QD) for 3 days, followed by 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
    Arm 12 Non-cirrhotic
    Arm Type
    Experimental
    Arm Description
    ABT-530 Dose F (≤ 400 mg) for 3 days, followed by 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
    Intervention Type
    Drug
    Intervention Name(s)
    ABT-493
    Other Intervention Name(s)
    glecaprevir
    Intervention Description
    Tablet
    Intervention Type
    Drug
    Intervention Name(s)
    ABT-530
    Other Intervention Name(s)
    pibrentasvir
    Intervention Description
    Tablet
    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 (RBV)
    Intervention Description
    Tablet
    Primary Outcome Measure Information:
    Title
    Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment
    Description
    Maximal decrease from baseline in log10 HCV RNA levels during ABT-493 or ABT-530 monotherapy treatment. The baseline value was the last measurement before the first dose of monotherapy on Day 1.
    Time Frame
    Day 1 through prior to first dose of the combination regimen on Study Day 4
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
    Description
    SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of combination study drug.
    Time Frame
    12 weeks after last actual dose of combination study drug
    Title
    Percentage of Participants With On-treatment Virologic Failure
    Description
    On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during combination treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during combination treatment; or HCV RNA ≥ LLOQ at end of combination treatment with at least 6 weeks of combination treatment.
    Time Frame
    Up to 87 days
    Title
    Percentage of Participants With Post-treatment Relapse
    Description
    Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants completing combination treatment with HCV RNA levels < LLOQ at the end of treatment.
    Time Frame
    From the end of treatment through 12 weeks after the last dose of combination study drug

    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: Chronic HCV infection prior to study enrollment. Screening laboratory result indicating HCV genotype 1-infection. Subject has plasma HCV RNA level greater than 10,000 IU/mL at Screening. Per local standard, subject is considered to be non-cirrhotic or to have compensated cirrhosis. Exclusion Criteria: History of severe, life-threatening or other significant sensitivity to any drug. Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency Virus antibody (HIV Ab). Prior therapy for the treatment of HCV. Any current or past clinical evidence of Child Pugh B or C classification of clinical history of liver decompensation including ascites (noted on physical exam), variceal bleeding or hepatic encephalopathy. Any cause of liver disease other than chronic HCV infection.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    AbbVie Inc
    Organizational Affiliation
    AbbVie
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    26183611
    Citation
    Lawitz E, Freilich B, Link J, German P, Mo H, Han L, Brainard DM, McNally J, Marbury T, Rodriguez-Torres M. A phase 1, randomized, dose-ranging study of GS-5816, a once-daily NS5A inhibitor, in patients with genotype 1-4 hepatitis C virus. J Viral Hepat. 2015 Dec;22(12):1011-9. doi: 10.1111/jvh.12435. Epub 2015 Jul 16.
    Results Reference
    background
    PubMed Identifier
    26711747
    Citation
    Lawitz EJ, O'Riordan WD, Asatryan A, Freilich BL, Box TD, Overcash JS, Lovell S, Ng TI, Liu W, Campbell A, Lin CW, Yao B, Kort J. Potent Antiviral Activities of the Direct-Acting Antivirals ABT-493 and ABT-530 with Three-Day Monotherapy for Hepatitis C Virus Genotype 1 Infection. Antimicrob Agents Chemother. 2015 Dec 28;60(3):1546-55. doi: 10.1128/AAC.02264-15.
    Results Reference
    derived
    Links:
    URL
    http://rxabbvie.com
    Description
    Related Info

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    A Study to Evaluate the Safety and Antiviral Effect of Multiple Doses of ABT-493 and ABT-530 in Adults With Genotype 1 Hepatitis C Virus (HCV)

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