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Vaniprevir Plus PegIntron®/Ribavirin in Japanese Participants With Chronic Hepatitis C Who Are Non-responders to Previous Treatment (MK-7009-045)

Primary Purpose

Hepatitis C, Chronic

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
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
  • Has received and tolerated treatment with IFN-based therapy (IFN α, IFN β, or peg-IFN) with or without use of ribavirin, but failed to respond to the prior treatment (partial responder or null responder)
  • 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 Type

    Experimental

    Arm Label

    Vaniprevir 24 Week Arm

    Arm Description

    Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment

    Outcomes

    Primary Outcome Measures

    Percentage of Participants Achieving Sustained Virologic Response (SVR)24
    SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy. The percentage of participants achieving SVR24 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
    Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study
    An AE 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 AE. For this study, safety parameters or AEs of special interest that were identified a priori included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse experiences (vomiting, nausea, and diarrhea). The percentage of participants with ≥1 specific AEs were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
    Percentage of Participants Who Discontinued Study Drug Due to an AE
    An AE 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 AE.

    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. The percentage of participants achieving SVR12 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
    Percentage of Participants Achieving Rapid Virologic Response (RVR)
    RVR was defined as having an undetectable HCV RNA level at Week 4. The percentage of participants achieving RVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
    Percentage of Participants Achieving Complete Early Virologic Response (cEVR)
    cEVR was defined as having an undetectable HCV RNA level at Week 12. The percentage of participants achieving cEVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
    Percentage of Participants Achieving Undetectable HCV Ribonucleic Acid (RNA) at the End of Treatment (EOT)
    Participants were assessed for undetectable HCV RNA levels at the end of all study therapy. The percentage of participants with undetectable HCV RNA levels at EOT were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
    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
    July 28, 2011
    Last Updated
    September 21, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01405560
    Brief Title
    Vaniprevir Plus PegIntron®/Ribavirin in Japanese Participants With Chronic Hepatitis C Who Are Non-responders to Previous Treatment (MK-7009-045)
    Official Title
    A Phase III Study to Evaluate the Safety, Tolerability, and Efficacy of MK-7009 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Japanese Patients With Chronic Hepatitis C Infection Who Were Non-responders to Previous Treatment
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    September 2, 2011 (Actual)
    Primary Completion Date
    March 29, 2013 (Actual)
    Study Completion Date
    March 29, 2013 (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 (300 mg twice daily) given in combination with pegylated interferon alfa-2b (peg-IFN) and ribavirin (RBV) in Japanese participants with chronic hepatitis C (CHC) genotype (GT) 1 who have not responded to previous treatment. The primary efficacy objective is to estimate efficacy of vaniprevir, peg-IFN and RBV for 24 weeks as assessed by the percentage of participants achieving undetectable Hepatitis C Virus ribonucleic acid (HCV RNA) 24 weeks after completion of all study therapy (Sustained Viral Response 24 [SVR24]).

    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
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    42 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Vaniprevir 24 Week Arm
    Arm Type
    Experimental
    Arm Description
    Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
    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 24 weeks
    Intervention Type
    Biological
    Intervention Name(s)
    peg-IFN
    Other Intervention Name(s)
    PegIntron
    Intervention Description
    Open-label peg-IFN alfa-2b at 1.5 μg/kg once per week, administered subcutaneously (SC) for 24 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 weeks
    Primary Outcome Measure Information:
    Title
    Percentage of Participants Achieving Sustained Virologic Response (SVR)24
    Description
    SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy. The percentage of participants achieving SVR24 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
    Time Frame
    24 weeks after 24 weeks of study therapy (up to 48 weeks)
    Title
    Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study
    Description
    An AE 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 AE. For this study, safety parameters or AEs of special interest that were identified a priori included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse experiences (vomiting, nausea, and diarrhea). The percentage of participants with ≥1 specific AEs were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
    Time Frame
    From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
    Title
    Percentage of Participants Who Discontinued Study Drug Due to an AE
    Description
    An AE 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 AE.
    Time Frame
    From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 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. The percentage of participants achieving SVR12 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
    Time Frame
    12 weeks after 24 weeks of study therapy (up to 36 weeks)
    Title
    Percentage of Participants Achieving Rapid Virologic Response (RVR)
    Description
    RVR was defined as having an undetectable HCV RNA level at Week 4. The percentage of participants achieving RVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
    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. The percentage of participants achieving cEVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
    Time Frame
    At Week 12
    Title
    Percentage of Participants Achieving Undetectable HCV Ribonucleic Acid (RNA) at the End of Treatment (EOT)
    Description
    Participants were assessed for undetectable HCV RNA levels at the end of all study therapy. The percentage of participants with undetectable HCV RNA levels at EOT were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
    Time Frame
    At Week 24
    Title
    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 Has received and tolerated treatment with IFN-based therapy (IFN α, IFN β, or peg-IFN) with or without use of ribavirin, but failed to respond to the prior treatment (partial responder or null responder) 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
    26936417
    Citation
    Kumada H, Mochida S, Suzuki F, Chayama K, Karino Y, Nakamura K, Fujimoto G, Howe AY, Ludmerer SW, Mobashery N. Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 (GT1b) infection: Phase 3 studies. J Gastroenterol Hepatol. 2016 Oct;31(10):1674-1683. doi: 10.1111/jgh.13328.
    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=7009-045&kw=7009-045&tab=access

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    Vaniprevir Plus PegIntron®/Ribavirin in Japanese Participants With Chronic Hepatitis C Who Are Non-responders to Previous Treatment (MK-7009-045)

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