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A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus (HCV) Genotype 2 Infection (ENDURANCE-2)

Primary Purpose

Chronic Hepatitis C Virus (HCV) Infection

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ABT-493/ABT-530
Placebo for ABT-493/ABT-530
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C Virus (HCV) Infection focused on measuring Treatment-Naive, Hepatitis C Virus Genotype 2, Sofosbuvir (SOF)-Experienced, Treatment-Experienced, Non-cirrhotic

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Screening laboratory result indicating hepatitis C virus (HCV) Genotype-2 (GT2) infection.
  • Chronic HCV infection.
  • Subject must be HCV treatment-naïve (subject had never received a single dose of any approved or investigational regimen) or had failed prior interferon (IFN) or pegylated-interferon (pegIFN) ± ribavirin (RBV) or sofosbuvir (SOF) + RBV ± pegIFN therapy.
  • Subject must be non-cirrhotic.

Exclusion Criteria:

  • History of severe, life-threatening or other significant sensitivity to any excipient of the study drugs.
  • Female who is pregnant, planning to become pregnant during the study, or breastfeeding; or male whose partner is 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 preclude 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 antibody (HIV Ab).
  • HCV genotype performed during screening indicating coinfection with more than 1 HCV genotype.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Arm A DB Active Drug

    Arm B DB Placebo

    Arm B OL Active Drug

    Arm Description

    ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind [DB] treatment period)

    Placebo for ABT-493/ABT-530 QD for 12 weeks (DB treatment period)

    ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (open-label [OL] treatment period)

    Outcomes

    Primary Outcome Measures

    Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Noninferiority Analysis
    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 active study drug. The primary efficacy endpoint was the noninferiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior sofosbuvir (SOF) + ribavirin (RBV) ± pegylatedinterferon (pegIFN) failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks).

    Secondary Outcome Measures

    Percentage of Participants With SVR12 in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Superiority Analysis
    SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. The secondary efficacy endpoint was the superiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior SOF + RBV ± pegIFN failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks). As pre-specified in the study protocol, the primary outcome measure and the secondary outcome measure are not tested independently from each other. Rather, the two measures are ranked in a fixed sequential testing procedure that only if success was demonstrated for the primary outcome (i.e. non-inferiority test of Arm A SVR12 rate to the standard of care) did we test the first secondary outcome (i.e. superiority test of Arm A SVR12 rate to the standard of care).
    Percentage of Participants With On-treatment Virologic Failure in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures
    On-treatment virologic failure was defined as confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value of post-baseline 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 in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures
    Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of DB treatment and 12 weeks after the last dose of active study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment, excluding reinfection.
    Percentage of Participants With SVR12 in Arm A DB Active Drug With Prior SOF + RBV ± pegIFN Failure
    SVR12 was defined as HCV RNA level <LLOQ 12 weeks after the last dose of active study drug.

    Full Information

    First Posted
    December 18, 2015
    Last Updated
    July 14, 2021
    Sponsor
    AbbVie
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02640482
    Brief Title
    A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus (HCV) Genotype 2 Infection
    Acronym
    ENDURANCE-2
    Official Title
    A Randomized, Double-Blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus Genotype 2 Infection (ENDURANCE-2)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    November 2015 (Actual)
    Primary Completion Date
    September 2016 (Actual)
    Study Completion Date
    February 2017 (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 efficacy of ABT-493/ABT-530 in adults with genotype 2 chronic hepatitis C virus (HCV) infection.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Hepatitis C Virus (HCV) Infection
    Keywords
    Treatment-Naive, Hepatitis C Virus Genotype 2, Sofosbuvir (SOF)-Experienced, Treatment-Experienced, Non-cirrhotic

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    304 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm A DB Active Drug
    Arm Type
    Experimental
    Arm Description
    ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind [DB] treatment period)
    Arm Title
    Arm B DB Placebo
    Arm Type
    Experimental
    Arm Description
    Placebo for ABT-493/ABT-530 QD for 12 weeks (DB treatment period)
    Arm Title
    Arm B OL Active Drug
    Arm Type
    Experimental
    Arm Description
    ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (open-label [OL] treatment period)
    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)
    Placebo for ABT-493/ABT-530
    Intervention Description
    tablet
    Primary Outcome Measure Information:
    Title
    Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Noninferiority Analysis
    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 active study drug. The primary efficacy endpoint was the noninferiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior sofosbuvir (SOF) + ribavirin (RBV) ± pegylatedinterferon (pegIFN) failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks).
    Time Frame
    12 weeks after the last actual dose of active study drug
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants With SVR12 in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Superiority Analysis
    Description
    SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. The secondary efficacy endpoint was the superiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior SOF + RBV ± pegIFN failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks). As pre-specified in the study protocol, the primary outcome measure and the secondary outcome measure are not tested independently from each other. Rather, the two measures are ranked in a fixed sequential testing procedure that only if success was demonstrated for the primary outcome (i.e. non-inferiority test of Arm A SVR12 rate to the standard of care) did we test the first secondary outcome (i.e. superiority test of Arm A SVR12 rate to the standard of care).
    Time Frame
    12 weeks after the last actual dose of active study drug
    Title
    Percentage of Participants With On-treatment Virologic Failure in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures
    Description
    On-treatment virologic failure was defined as confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value of post-baseline 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
    Up to Week 12 post baseline
    Title
    Percentage of Participants With Post-treatment Relapse in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures
    Description
    Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of DB treatment and 12 weeks after the last dose of active study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment, excluding reinfection.
    Time Frame
    Between End of Treatment (Week 12) and 12 weeks after the last dose of Arm A DB active drug (up to Week 24)
    Title
    Percentage of Participants With SVR12 in Arm A DB Active Drug With Prior SOF + RBV ± pegIFN Failure
    Description
    SVR12 was defined as HCV RNA level <LLOQ 12 weeks after the last dose of active study drug.
    Time Frame
    12 weeks after the last actual dose of active study drug

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    99 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Screening laboratory result indicating hepatitis C virus (HCV) Genotype-2 (GT2) infection. Chronic HCV infection. Subject must be HCV treatment-naïve (subject had never received a single dose of any approved or investigational regimen) or had failed prior interferon (IFN) or pegylated-interferon (pegIFN) ± ribavirin (RBV) or sofosbuvir (SOF) + RBV ± pegIFN therapy. Subject must be non-cirrhotic. Exclusion Criteria: History of severe, life-threatening or other significant sensitivity to any excipient of the study drugs. Female who is pregnant, planning to become pregnant during the study, or breastfeeding; or male whose partner is 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 preclude 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 antibody (HIV Ab). HCV genotype performed during screening indicating coinfection with more than 1 HCV genotype.
    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
    28951228
    Citation
    Asselah T, Kowdley KV, Zadeikis N, Wang S, Hassanein T, Horsmans Y, Colombo M, Calinas F, Aguilar H, de Ledinghen V, Mantry PS, Hezode C, Marinho RT, Agarwal K, Nevens F, Elkhashab M, Kort J, Liu R, Ng TI, Krishnan P, Lin CW, Mensa FJ. Efficacy of Glecaprevir/Pibrentasvir for 8 or 12 Weeks in Patients With Hepatitis C Virus Genotype 2, 4, 5, or 6 Infection Without Cirrhosis. Clin Gastroenterol Hepatol. 2018 Mar;16(3):417-426. doi: 10.1016/j.cgh.2017.09.027. Epub 2017 Sep 22.
    Results Reference
    background
    PubMed Identifier
    31568620
    Citation
    Brown A, Welzel TM, Conway B, Negro F, Brau N, Grebely J, Puoti M, Aghemo A, Kleine H, Pugatch D, Mensa FJ, Chen YJ, Lei Y, Lawitz E, Asselah T. Adherence to pan-genotypic glecaprevir/pibrentasvir and efficacy in HCV-infected patients: A pooled analysis of clinical trials. Liver Int. 2020 Apr;40(4):778-786. doi: 10.1111/liv.14266. Epub 2019 Oct 18.
    Results Reference
    derived
    PubMed Identifier
    30977945
    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.
    Results Reference
    derived
    PubMed Identifier
    30923816
    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.
    Results Reference
    derived
    PubMed Identifier
    30529905
    Citation
    Foster GR, Dore GJ, Wang S, Grebely J, Sherman KE, Baumgarten A, Conway B, Jackson D, Asselah T, Gschwantler M, Tomasiewicz K, Aguilar H, Asatryan A, Hu Y, Mensa FJ. Glecaprevir/pibrentasvir in patients with chronic HCV and recent drug use: An integrated analysis of 7 phase III studies. Drug Alcohol Depend. 2019 Jan 1;194:487-494. doi: 10.1016/j.drugalcdep.2018.11.007. Epub 2018 Nov 24.
    Results Reference
    derived
    PubMed Identifier
    30012435
    Citation
    Flamm S, Reddy KR, Zadeikis N, Hassanein T, Bacon BR, Maieron A, Zeuzem S, Bourliere M, Calleja JL, Kosloski MP, Oberoi RK, Lin CW, Yu Y, Lovell S, Semizarov D, Mensa FJ. Efficacy and Pharmacokinetics of Glecaprevir and Pibrentasvir With Concurrent Use of Acid-Reducing Agents in Patients With Chronic HCV Infection. Clin Gastroenterol Hepatol. 2019 Feb;17(3):527-535.e6. doi: 10.1016/j.cgh.2018.07.003. Epub 2018 Sep 10.
    Results Reference
    derived
    Links:
    URL
    http://rxabbvie.com
    Description
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    A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus (HCV) Genotype 2 Infection

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