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Vaniprevir Administered With Pegylated-interferon and Ribavirin in Japanese Treatment-Naïve Chronic Hepatitis C Participants (MK-7009-043)

Primary Purpose

Hepatitis C, Chronic

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
vaniprevir
Placebo to vaniprevir
Peg-IFN
ribavirin
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C, Chronic

Eligibility Criteria

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

Inclusion criteria:

  • Japanese participant diagnosed with compensated CHC GT 1
  • Absence of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease.
  • IFN treatment naive
  • No evidence of cirrhosis

Exclusion criteria:

  • Co-infection with human immunodeficiency virus (HIV)
  • Positive hepatitis B surface antigen or other evidence of active hepatitis B infection
  • Any other condition that is contraindicated or for which caution is required for treatment with peg-IFN or RBV
  • Any condition or pre-study laboratory abnormality, or history of any illness, that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs, peg-IFN and RBV, to the participant.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Active Comparator

    Arm Label

    Vaniprevir 12 Week Arm

    Vaniprevir 24 Week Arm

    Control Arm

    Arm Description

    Participants on this arm receive 12 weeks of vaniprevir (300 mg twice daily) and then 12 weeks of placebo to vaniprevir along with 24 weeks of treatment with peg-IFN and RBV.

    Participants on this arm receive 24 weeks of vaniprevir (300 mg twice daily) along with 24 weeks of treatment with peg-IFN and RBV.

    Participants on this arm receive 24 weeks of treatment with placebo to vaniprevir along with 48 weeks of treatment with peg-IFN and RBV.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completion of All Study Therapy (SVR24)
    SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy.
    Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study
    An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an adverse experience. For this study, safety parameters or AEs of special interest that were identified a priori constituted "Tier 1" safety endpoints that were subject to inferential testing for statistical significance. Tier 1 AEs on this study included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse (GI) experiences (vomiting, nausea, and diarrhea).
    Percentage of Participants Who Discontinued Study Drug Due to an AE
    An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an adverse experience.

    Secondary Outcome Measures

    Percentage of Participants Achieving SVR12
    SVR12 was defined as having an undetectable HCV RNA level 12 weeks after completion of all study therapy.
    Percentage of Participants Achieving Rapid Virologic Response (RVR)
    RVR was defined as having an undetectable HCV RNA level at Week 4.
    Percentage of Participants Achieving Complete Early Virologic Response (cEVR)
    cEVR was defined as having an undetectable HCV RNA level at Week 12.
    Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT)
    Participants were assessed for undetectable HCV RNA levels at the end of all study therapy.
    Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10)
    HCV RNA levels were assessed at baseline (BL) and during treatment weeks 2, 4, 8, 12, and 24 using the Roche TaqMan HCV assay, and transformed to Log 10 values. HCV RNA values below the limit of reliable quantification (LoQ) or the limit of detection (LoD) at any time point were handled as follows (imputations done for computational purposes): values below the LoQ but above the LoD were imputed with the LoQ minus 0.1; values below the LoD were imputed with the value of 0 Log IU/mL. HCV RNA levels below the LoD were considered "undetectable".

    Full Information

    First Posted
    June 8, 2011
    Last Updated
    September 21, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01370642
    Brief Title
    Vaniprevir Administered With Pegylated-interferon and Ribavirin in Japanese Treatment-Naïve Chronic Hepatitis C Participants (MK-7009-043)
    Official Title
    A Phase III Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of MK-7009 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Japanese Treatment-Naïve Patients With Chronic Hepatitis C Infection
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    June 27, 2011 (Actual)
    Primary Completion Date
    July 31, 2013 (Actual)
    Study Completion Date
    March 17, 2014 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the safety, tolerability, and efficacy of vaniprevir given in combination with pegylated interferon alfa-2b (peg-IFN) and ribavirin (RBV) versus treatment with peg-IFN and RBV alone in Japanese treatment-naïve participants with chronic hepatitis C (CHC) genotype (GT)1. The primary efficacy hypothesis is that the percentage of participants achieving sustained virologic response 24 weeks after completion of all study therapy (SVR24) in at least one of the vaniprevir arms is superior to the percentage of participants achieving SVR24 in the control arm.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatitis C, Chronic

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Vaniprevir 12 Week Arm
    Arm Type
    Experimental
    Arm Description
    Participants on this arm receive 12 weeks of vaniprevir (300 mg twice daily) and then 12 weeks of placebo to vaniprevir along with 24 weeks of treatment with peg-IFN and RBV.
    Arm Title
    Vaniprevir 24 Week Arm
    Arm Type
    Experimental
    Arm Description
    Participants on this arm receive 24 weeks of vaniprevir (300 mg twice daily) along with 24 weeks of treatment with peg-IFN and RBV.
    Arm Title
    Control Arm
    Arm Type
    Active Comparator
    Arm Description
    Participants on this arm receive 24 weeks of treatment with placebo to vaniprevir along with 48 weeks of treatment with peg-IFN and RBV.
    Intervention Type
    Drug
    Intervention Name(s)
    vaniprevir
    Other Intervention Name(s)
    MK-7009
    Intervention Description
    Capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 12 or 24 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to vaniprevir
    Intervention Description
    Placebo to vaniprevir, capsules, orally, twice daily for 12 weeks or 24 weeks
    Intervention Type
    Biological
    Intervention Name(s)
    Peg-IFN
    Other Intervention Name(s)
    PegIntron
    Intervention Description
    Peg-IFN 1.5 μg/kg once per week, subcutaneously (SC) for 24 or 48 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    ribavirin
    Other Intervention Name(s)
    REBETOL®
    Intervention Description
    Capsules containing 200 mg RBV orally, 3 to 5 capsules, dosage based on the participant's weight (600 mg/day to 1000 mg/day), for 24 or 48 weeks
    Primary Outcome Measure Information:
    Title
    Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completion of All Study Therapy (SVR24)
    Description
    SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy.
    Time Frame
    24 weeks after 24 or 48 weeks of study therapy (up to 72 weeks)
    Title
    Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study
    Description
    An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an adverse experience. For this study, safety parameters or AEs of special interest that were identified a priori constituted "Tier 1" safety endpoints that were subject to inferential testing for statistical significance. Tier 1 AEs on this study included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse (GI) experiences (vomiting, nausea, and diarrhea).
    Time Frame
    From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks)
    Title
    Percentage of Participants Who Discontinued Study Drug Due to an AE
    Description
    An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an adverse experience.
    Time Frame
    From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks)
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants Achieving SVR12
    Description
    SVR12 was defined as having an undetectable HCV RNA level 12 weeks after completion of all study therapy.
    Time Frame
    12 weeks after 24 or 48 weeks of study therapy (up to 60 weeks)
    Title
    Percentage of Participants Achieving Rapid Virologic Response (RVR)
    Description
    RVR was defined as having an undetectable HCV RNA level at Week 4.
    Time Frame
    At Week 4
    Title
    Percentage of Participants Achieving Complete Early Virologic Response (cEVR)
    Description
    cEVR was defined as having an undetectable HCV RNA level at Week 12.
    Time Frame
    At Week 12
    Title
    Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT)
    Description
    Participants were assessed for undetectable HCV RNA levels at the end of all study therapy.
    Time Frame
    At Week 24 or 48
    Title
    Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10)
    Description
    HCV RNA levels were assessed at baseline (BL) and during treatment weeks 2, 4, 8, 12, and 24 using the Roche TaqMan HCV assay, and transformed to Log 10 values. HCV RNA values below the limit of reliable quantification (LoQ) or the limit of detection (LoD) at any time point were handled as follows (imputations done for computational purposes): values below the LoQ but above the LoD were imputed with the LoQ minus 0.1; values below the LoD were imputed with the value of 0 Log IU/mL. HCV RNA levels below the LoD were considered "undetectable".
    Time Frame
    Baseline, Week 2, Week 4, Week 8, Week 12, Week 24

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    20 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion criteria: Japanese participant diagnosed with compensated CHC GT 1 Absence of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease. IFN treatment naive No evidence of cirrhosis Exclusion criteria: Co-infection with human immunodeficiency virus (HIV) Positive hepatitis B surface antigen or other evidence of active hepatitis B infection Any other condition that is contraindicated or for which caution is required for treatment with peg-IFN or RBV Any condition or pre-study laboratory abnormality, or history of any illness, that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs, peg-IFN and RBV, to the participant.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    26403160
    Citation
    Hayashi N, Nakamuta M, Takehara T, Kumada H, Takase A, Howe AY, Ludmerer SW, Mobashery N. Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-naive Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase III study. J Gastroenterol. 2016 Apr;51(4):390-403. doi: 10.1007/s00535-015-1120-x. Epub 2015 Sep 25.
    Results Reference
    result
    PubMed Identifier
    26947564
    Citation
    Ludmerer SW, Hirano T, Black S, Howe AY, Chang W, Takase A, Nakamura K, Tanaka Y, Kumada H, Hayashi N, Nickle D. HCV evolutionary genetics of SVR versus virologic failure assessed from the vaniprevir phase III registration trials. Antiviral Res. 2016 Jun;130:118-29. doi: 10.1016/j.antiviral.2016.03.004. Epub 2016 Mar 3.
    Results Reference
    derived
    Available IPD and Supporting Information:
    Available IPD/Information Type
    CSR Synopsis
    Available IPD/Information URL
    http://www.merck.com/clinical-trials/study.html?id=7009-043&kw=7009-043&tab=access

    Learn more about this trial

    Vaniprevir Administered With Pegylated-interferon and Ribavirin in Japanese Treatment-Naïve Chronic Hepatitis C Participants (MK-7009-043)

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