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A Study Comparing Efficacy and Safety of ABT-493/ABT-530 to Sofosbuvir Dosed With Daclatasvir in Adults With HCV Genotype 3 Infection (ENDURANCE-3)

Primary Purpose

Chronic Hepatitis C, Hepatitis C Virus, Genotype 3 Hepatitis C Virus

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ABT-493/ABT-530
Sofosbuvir
Daclatasvir
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 interferon free, Hepatitis C, daclatasvir, Sovaldi, HCV, Hepatitis C Virus, Hepatitis C Genotype 3, Hep C, sofosbuvir, Chronic Hepatitis C, Daklinza

Eligibility Criteria

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

Inclusion Criteria:

  • Male or female (of nonchildbearing potential, practicing total abstinence, sexually active with female partners only, or using allowed contraceptive methods) at least 18 years of age at time of screening.
  • Screening laboratory result indicating HCV GT3 infection.

  • Chronic HCV infection, defined as one of the following:

    • Positive for anti-HCV antibody (Ab) or HCV RNA at least 6 months before screening; or
    • A liver biopsy consistent with chronic HCV infection; or
    • Abnormal alanine aminotransferase (ALT) levels for at least 6 months before screening.
  • Hepatitis C virus treatment-naïve (i.e., participant had never received any anti-HCV treatment).
  • Documented as noncirrhotic.

Exclusion Criteria:

  • Female who was pregnant, planning to become pregnant during the study, or breastfeeding; or male whose partner was pregnant or planning to become pregnant during the study.
  • Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could have precluded adherence to the protocol in the opinion of the investigator.
  • Positive test result at screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus Ab (HIV Ab).
  • Hepatitis C virus genotyping performed during screening indicated co-infection with more than one HCV genotype.
  • Any cause of liver disease other than chronic HCV infection.
  • Consideration by the investigator, for any reason, that the participant was an unsuitable candidate to receive ABT-493/ABT-530, SOF, or DCV.
  • History of severe, life-threatening, or other significant sensitivity to any excipients of the study drug.
  • Previous use of any anti-HCV treatment.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Active Comparator

    Experimental

    Arm Label

    Arm A

    Arm B

    Arm C

    Arm Description

    ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.

    Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg QD for 12 weeks.

    ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm A to Arm B
    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 study drug. The primary efficacy endpoint was noninferiority in the percentage of participants achieving SVR12 of the 12-week regimen (Arm A) to the standard of care (Arm B: 12 weeks of treatment with sofosbuvir [SOF] + daclatasvir [DCV]), defined as: a) the lower bound of the 95% confidence interval (CI) for the difference was above the non-inferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm A was greater than 92%; OR b) the lower bound of the 95% CI for the difference was below the non-inferiority margin of -6% and the lower bound of the 97.5% CI for the SVR12 rate within Arm A was greater than 92%; OR c) the lower bound of the 97.5% CI for the difference was above the non-inferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm A was below 92%.
    Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm C to Arm A
    SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. If the first primary efficacy objective (noninferiority of Arm A to Arm B) was achieved, then the second primary efficacy objective, noninferiority in the percentage of participants achieving SVR12 of the 8-week regimen (Arm C) to the 12-week regimen (Arm A) was to be tested. Noninferiority was defined as: a) the lower bound of the 95% CI for the difference was above the noninferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm C was greater than 92%, OR b) the lower bound of the 95% CI for the difference was below the noninferiority margin of -6% and the lower bound of the 97.5% CI for the SVR12 rate within Arm C was greater than 92%, OR c) the lower bound of the 97.5% CI for the difference was above the noninferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm C was below 92%.

    Secondary Outcome Measures

    Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Superiority of Arm A to Arm B
    SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. Per statistical analysis plan to adjust for multiplicity among the primary and first secondary hypothesis tests, the test for superiority of Arm A to Arm B was not conducted.
    Percentage of Participants With On-treatment Virologic Failure
    On-treatment virologic failure was defined as confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < LLOQ during treatment, or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of 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 who completed treatment with HCV RNA levels < LLOQ at the end of treatment, excluding reinfection.

    Full Information

    First Posted
    December 22, 2015
    Last Updated
    July 9, 2021
    Sponsor
    AbbVie
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02640157
    Brief Title
    A Study Comparing Efficacy and Safety of ABT-493/ABT-530 to Sofosbuvir Dosed With Daclatasvir in Adults With HCV Genotype 3 Infection
    Acronym
    ENDURANCE-3
    Official Title
    A Randomized, Open-Label, Active-Controlled, Multicenter Study to Compare Efficacy and Safety of ABT-493/ABT-530 to Sofosbuvir Co-Administered With Daclatasvir in Adults With Chronic Hepatitis C Virus Genotype 3 Infection (ENDURANCE-3)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    December 2015 (undefined)
    Primary Completion Date
    October 2016 (Actual)
    Study Completion Date
    February 2017 (Actual)

    3. Sponsor/Collaborators

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

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study was to compare the safety and efficacy of ABT-493/ABT-530 to the combination of sofosbuvir (SOF) and daclatasvir (DCV) in adults with genotype 3 (GT3) chronic hepatitis C virus (HCV) infection.
    Detailed Description
    This study was a Phase 3, randomized, open-label, active-controlled multicenter study to compare efficacy and safety of ABT-493/ABT-530 to SOF and DCV in treatment-naïve chronic HCV GT3-infected participants without cirrhosis. The study consisted of 2 periods, a treatment period (participants received 8 or 12 weeks of ABT-493/ABT-530 or 12 weeks of SOF with DCV) and a post-treatment period (participants who completed or prematurely discontinued the treatment period were followed for 24 weeks after their last dose of study drug to evaluate efficacy and to monitor HCV RNA and the emergence and persistence of viral variants).

    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, Genotype 3 Hepatitis C Virus
    Keywords
    interferon free, Hepatitis C, daclatasvir, Sovaldi, HCV, Hepatitis C Virus, Hepatitis C Genotype 3, Hep C, sofosbuvir, Chronic Hepatitis C, Daklinza

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    506 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm A
    Arm Type
    Experimental
    Arm Description
    ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
    Arm Title
    Arm B
    Arm Type
    Active Comparator
    Arm Description
    Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg QD for 12 weeks.
    Arm Title
    Arm C
    Arm Type
    Experimental
    Arm Description
    ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    ABT-493/ABT-530
    Other Intervention Name(s)
    ABT-493 also known as glecaprevir, ABT-530 also known as pibrentasvir, MAVYRET
    Intervention Description
    Tablet; ABT-493 coformulated with ABT-530
    Intervention Type
    Drug
    Intervention Name(s)
    Sofosbuvir
    Other Intervention Name(s)
    Sovaldi
    Intervention Description
    Tablet
    Intervention Type
    Drug
    Intervention Name(s)
    Daclatasvir
    Other Intervention Name(s)
    Daklinza
    Intervention Description
    Tablet
    Primary Outcome Measure Information:
    Title
    Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm A to Arm B
    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 study drug. The primary efficacy endpoint was noninferiority in the percentage of participants achieving SVR12 of the 12-week regimen (Arm A) to the standard of care (Arm B: 12 weeks of treatment with sofosbuvir [SOF] + daclatasvir [DCV]), defined as: a) the lower bound of the 95% confidence interval (CI) for the difference was above the non-inferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm A was greater than 92%; OR b) the lower bound of the 95% CI for the difference was below the non-inferiority margin of -6% and the lower bound of the 97.5% CI for the SVR12 rate within Arm A was greater than 92%; OR c) the lower bound of the 97.5% CI for the difference was above the non-inferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm A was below 92%.
    Time Frame
    12 weeks after the last actual dose of study drug
    Title
    Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm C to Arm A
    Description
    SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. If the first primary efficacy objective (noninferiority of Arm A to Arm B) was achieved, then the second primary efficacy objective, noninferiority in the percentage of participants achieving SVR12 of the 8-week regimen (Arm C) to the 12-week regimen (Arm A) was to be tested. Noninferiority was defined as: a) the lower bound of the 95% CI for the difference was above the noninferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm C was greater than 92%, OR b) the lower bound of the 95% CI for the difference was below the noninferiority margin of -6% and the lower bound of the 97.5% CI for the SVR12 rate within Arm C was greater than 92%, OR c) the lower bound of the 97.5% CI for the difference was above the noninferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm C was below 92%.
    Time Frame
    12 weeks after the last actual dose of study drug
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Superiority of Arm A to Arm B
    Description
    SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. Per statistical analysis plan to adjust for multiplicity among the primary and first secondary hypothesis tests, the test for superiority of Arm A to Arm B was not conducted.
    Time Frame
    12 weeks after the last actual dose of study drug
    Title
    Percentage of Participants With On-treatment Virologic Failure
    Description
    On-treatment virologic failure was defined as confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < LLOQ during treatment, or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment.
    Time Frame
    Treatment weeks 1, 2, 4, 8 (end of treatment for Arm C), and 12 (end of treatment for Arms A and B) or premature discontinuation from treatment
    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 who completed treatment with HCV RNA levels < LLOQ at the end of treatment, excluding reinfection.
    Time Frame
    From the end of treatment through 12 weeks after the last dose of study drug

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Male or female (of nonchildbearing potential, practicing total abstinence, sexually active with female partners only, or using allowed contraceptive methods) at least 18 years of age at time of screening. Screening laboratory result indicating HCV GT3 infection. Chronic HCV infection, defined as one of the following: Positive for anti-HCV antibody (Ab) or HCV RNA at least 6 months before screening; or A liver biopsy consistent with chronic HCV infection; or Abnormal alanine aminotransferase (ALT) levels for at least 6 months before screening. Hepatitis C virus treatment-naïve (i.e., participant had never received any anti-HCV treatment). Documented as noncirrhotic. Exclusion Criteria: Female who was pregnant, planning to become pregnant during the study, or breastfeeding; or male whose partner was pregnant or planning to become pregnant during the study. Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could have precluded adherence to the protocol in the opinion of the investigator. Positive test result at screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus Ab (HIV Ab). Hepatitis C virus genotyping performed during screening indicated co-infection with more than one HCV genotype. Any cause of liver disease other than chronic HCV infection. Consideration by the investigator, for any reason, that the participant was an unsuitable candidate to receive ABT-493/ABT-530, SOF, or DCV. History of severe, life-threatening, or other significant sensitivity to any excipients of the study drug. Previous use of any anti-HCV treatment.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    AbbVie Inc
    Organizational Affiliation
    AbbVie
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
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    Citation
    Back D, Belperio P, Bondin M, Negro F, Talal AH, Park C, Zhang Z, Pinsky B, Crown E, Mensa FJ, Marra F. Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic HCV infection and psychiatric disorders: An integrated analysis. J Viral Hepat. 2019 Aug;26(8):951-960. doi: 10.1111/jvh.13110. Epub 2019 May 20.
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    PubMed Identifier
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    Citation
    Gane E, Poordad F, Zadeikis N, Valdes J, Lin CW, Liu W, Asatryan A, Wang S, Stedman C, Greenbloom S, Nguyen T, Elkhashab M, Worns MA, Tran A, Mulkay JP, Setze C, Yu Y, Pilot-Matias T, Porcalla A, Mensa FJ. Safety and Pharmacokinetics of Glecaprevir/Pibrentasvir in Adults With Chronic Genotype 1-6 Hepatitis C Virus Infections and Compensated Liver Disease. Clin Infect Dis. 2019 Oct 30;69(10):1657-1664. doi: 10.1093/cid/ciz022.
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    Links:
    URL
    http://rxabbvie.com/
    Description
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    A Study Comparing Efficacy and Safety of ABT-493/ABT-530 to Sofosbuvir Dosed With Daclatasvir in Adults With HCV Genotype 3 Infection

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