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Three-year Follow-up of Participants After Administration of Boceprevir or Narlaprevir for the Treatment of Chronic Hepatitis C (P05063)

Primary Purpose

Hepatitis C, Chronic, Hepacivirus

Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Boceprevir
Narlaprevir
Peginterferon alfa-2b
Ribavirin
Blood/Plasma Collection
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Hepatitis C, Chronic

Eligibility Criteria

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

Inclusion Criteria:

  • Participant must be willing to give written informed consent and be able to adhere to the visit schedule.
  • Participant must have received at least one dose of boceprevir or narlaprevir in a previous Phase 1, 2, or 3 clinical study.

Exclusion Criteria:

  • Concurrent participation in any other clinical study for the treatment of chronic hepatitis C.
  • Retreatment with any antiviral or immunomodulatory drug for chronic hepatitis C after completion of, or discontinuation from, the SPRI Phase 1, 2, or 3 clinical study in which the participant previously participated.
  • Any condition which in the opinion of the Investigator would make the participant unsuitable for enrollment.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Other

    Other

    Arm Label

    Participants from Boceprevir Studies

    Participants from Narlaprevir Studies

    Arm Description

    Participants who previously participated in treatment studies in which boceprevir was administered were subsequently enrolled in Part 1 of the current follow-up study P05063 (NCT00689390). Participants may have received boceprevir or control peginterferon plus ribavirin (PR) in the previous treatment study. No treatment was administered in the current follow-up study.

    Participants who previously participated in treatment studies in which narlaprevir was administered were subsequently enrolled in Part 2 of the current follow-up study P05063 (NCT00689390). Participants may have received narlaprevir or control PR in the previous treatment study. No treatment was administered in the current follow-up study.

    Outcomes

    Primary Outcome Measures

    Number of Participants With Relapse During the LTFU Among Sustained Responders From Previous Treatment Studies With Boceprevir or Narlaprevir (Durability of Virologic Response)
    Durability of response was assessed by the number of participants who relapsed during the LTFU among those that had achieved sustained virologic response (SVR) by 24 weeks after treatment with boceprevir or narlaprevir in a previous Phase 1, 2, or 3 treatment study. In the current LTFU, participants were classified based on the last Hepatitis C Virus ribonucleic acid (HCV-RNA) result available at the time of the data cut-off date as follows: A participant was classified as a sustained virologic responder at a given time point if serum HCV-RNA was undetectable at that time point and there had not been a positive HCV-RNA since the participant was determined to have achieved SVR in the previous study. A participant was classified as a relapser if they were a sustained virologic responder in the previous treatment study and became serum HCV-RNA positive with no subsequent negative results during LTFU.
    Kaplan-Meier Exposure-adjusted Relapse Rate
    The distribution of time to relapse was summarized using Kaplan-Meier estimates for all participants who were sustained responders at 24 weeks post-treatment in the previous study. Exposure Adjusted Relapse Rate = 1000 × (number of relapses) / (Total exposure time in years). Total exposure time in years = [(total number of days from last day of treatment to the last follow-up day for all subjects who did not relapse) + (total number of days from last day of treatment to the day of relapse for those who relapsed)] / 365.25 days [for 1 year].
    Number of Participants With HCV Treatment-Emergent Resistance Associated Variants (TE-RAVs) of NS3/4A Protease Loci
    Plasma samples of all participants receiving at least one dose of study medication in a previous treatment protocol were evaluated by population sequencing and analyzed to detect amino acid variants in the NS3/4A protease known to be associated with reduced susceptibility to boceprevir and narlaprevir. RAVs in the NS3/4A protease gene were evaluated at 12 loci (V36, Q41, F43, T54, V55, V107, R155, A156, V158, D168, I/V170 and M175) on the basis of in vitro studies. A TE-RAV was defined as a RAV not present at baseline and that had not returned to wild type (WT) while the participant was still on treatment. The number of participants with TE-RAVS detected at the EOT in the previous treatment study are reported below, followed by those participants with TE-RAVS that returned to WT during the LTFU (among those with detected TE-RAVS).
    Number of Participants With Serious Adverse Events (SAEs) Reported During the LTFU
    Long-term safety was assessed based on the SAEs reported during the LTFU period. An SAE was any adverse drug or biologic or device experience occurring at any dose that resulted in any of the following outcomes: death, life-threatening AE, persistent or significant disability/incapacity, required in-patient hospitalization or prolongs hospitalization, congenital anomaly or birth defect. Important medical events that did not result in any of these outcomes could still be considered SAEs if they jeopardized the participant and/or required medical/surgical intervention, based on appropriate medical judgment. Grade 4 laboratory abnormalities and out of normal range liver function tests that were not accompanied by clinical manifestations were NOT considered SAEs.
    Number of Participants That Discontinued the LTFU Due to SAEs
    An SAE was any adverse drug or biologic or device experience occurring at any dose that resulted in any of the following outcomes: death, life-threatening AE, persistent or significant disability/incapacity, required in-patient hospitalization or prolongs hospitalization, congenital anomaly or birth defect. Important medical events that did not result in any of these outcomes could still be considered SAEs if they jeopardized the participant and/or required medical/surgical intervention, based on appropriate medical judgment. Grade 4 laboratory abnormalities and out of normal range liver function tests that were not accompanied by clinical manifestations were NOT considered SAEs.

    Secondary Outcome Measures

    Full Information

    First Posted
    May 27, 2008
    Last Updated
    August 13, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00689390
    Brief Title
    Three-year Follow-up of Participants After Administration of Boceprevir or Narlaprevir for the Treatment of Chronic Hepatitis C (P05063)
    Official Title
    Long-Term Follow-Up of Subjects in a Phase 1, 2, or 3 Clinical Trial in Which Boceprevir or Narlaprevir Was Administered for the Treatment of Chronic Hepatitis C
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2018
    Overall Recruitment Status
    Terminated
    Why Stopped
    The study was terminated due to satisfaction of post-marketing commitments
    Study Start Date
    February 20, 2007 (Actual)
    Primary Completion Date
    October 13, 2014 (Actual)
    Study Completion Date
    October 13, 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
    Study P05063 is a 3-year long-term follow-up (LTFU) study in participants previously treated with boceprevir (BOC) or narlaprevir (NAR) in a Phase 1, 2, or 3 clinical study. Participants will be followed for up to 3.5 years after the end of their participation in the treatment protocol to document maintenance of the antiviral response (for sustained responders) and to characterize the long-term safety after use of this therapeutic regimen. LTFU procedures include collection of plasma samples for measuring Hepatitis C Virus ribonucleic acid (HCV-RNA) by polymerase chain reaction (PCR) and HCV sequence analysis. No drug therapy will be administered as part of this study.
    Detailed Description
    In Part 1, participants who previously participated in one of nine boceprevir studies (P03523 [NCT00423670], P03659 [NCT00160251], P04487 [No NCT], P05101 [NCT00708500], P05216 [NCT00705432], P05411 [NCT00959699], P05514 [NCT00910624], P05685 [NCT00845065], and P06086 [NCT01023035]) were followed for response. In Part 2, participants who previously participated in one narlaprevir study (P05104 [NCT00797745]) were followed for response.

    6. Conditions and Keywords

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

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    1954 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Participants from Boceprevir Studies
    Arm Type
    Other
    Arm Description
    Participants who previously participated in treatment studies in which boceprevir was administered were subsequently enrolled in Part 1 of the current follow-up study P05063 (NCT00689390). Participants may have received boceprevir or control peginterferon plus ribavirin (PR) in the previous treatment study. No treatment was administered in the current follow-up study.
    Arm Title
    Participants from Narlaprevir Studies
    Arm Type
    Other
    Arm Description
    Participants who previously participated in treatment studies in which narlaprevir was administered were subsequently enrolled in Part 2 of the current follow-up study P05063 (NCT00689390). Participants may have received narlaprevir or control PR in the previous treatment study. No treatment was administered in the current follow-up study.
    Intervention Type
    Biological
    Intervention Name(s)
    Boceprevir
    Other Intervention Name(s)
    SCH 503034
    Intervention Description
    In previous treatment studies, boceprevir was administered as specified by the protocol. No treatment was administered on the current follow-up study (P05063, NCT00689390).
    Intervention Type
    Biological
    Intervention Name(s)
    Narlaprevir
    Other Intervention Name(s)
    SCH 900518
    Intervention Description
    In previous treatment studies, narlaprevir was administered as specified by the protocol. No treatment was administered on the current follow-up study (P05063, NCT00689390).
    Intervention Type
    Biological
    Intervention Name(s)
    Peginterferon alfa-2b
    Other Intervention Name(s)
    PEG-Intron®, SCH 054031
    Intervention Description
    In previous treatment studies, peginterferon alfa-2b was administered as specified by the protocol. No treatment was administered on the current follow-up study (P05063, NCT00689390).
    Intervention Type
    Drug
    Intervention Name(s)
    Ribavirin
    Other Intervention Name(s)
    Rebetol®
    Intervention Description
    In previous treatment studies, ribavirin was administered as specified by the protocol. No treatment was administered on the current follow-up study (P05063, NCT00689390).
    Intervention Type
    Other
    Intervention Name(s)
    Blood/Plasma Collection
    Intervention Description
    Blood samples were collected at all visits during the LTFU for blood chemistry and hematology. Plasma samples were collected at all visits as appropriate from participants who were sustained responders at the end of FU in the previous treatment protocol for HCV-RNA PCR and HCV sequence analysis.
    Primary Outcome Measure Information:
    Title
    Number of Participants With Relapse During the LTFU Among Sustained Responders From Previous Treatment Studies With Boceprevir or Narlaprevir (Durability of Virologic Response)
    Description
    Durability of response was assessed by the number of participants who relapsed during the LTFU among those that had achieved sustained virologic response (SVR) by 24 weeks after treatment with boceprevir or narlaprevir in a previous Phase 1, 2, or 3 treatment study. In the current LTFU, participants were classified based on the last Hepatitis C Virus ribonucleic acid (HCV-RNA) result available at the time of the data cut-off date as follows: A participant was classified as a sustained virologic responder at a given time point if serum HCV-RNA was undetectable at that time point and there had not been a positive HCV-RNA since the participant was determined to have achieved SVR in the previous study. A participant was classified as a relapser if they were a sustained virologic responder in the previous treatment study and became serum HCV-RNA positive with no subsequent negative results during LTFU.
    Time Frame
    From End Of Treatment (EOT) date in the previous treatment study to the first date of a positive HCV RNA result for relapsers or the last contact date for non-relapsers in the LTFU (up to 3.5 years)
    Title
    Kaplan-Meier Exposure-adjusted Relapse Rate
    Description
    The distribution of time to relapse was summarized using Kaplan-Meier estimates for all participants who were sustained responders at 24 weeks post-treatment in the previous study. Exposure Adjusted Relapse Rate = 1000 × (number of relapses) / (Total exposure time in years). Total exposure time in years = [(total number of days from last day of treatment to the last follow-up day for all subjects who did not relapse) + (total number of days from last day of treatment to the day of relapse for those who relapsed)] / 365.25 days [for 1 year].
    Time Frame
    From EOT date in the previous treatment study to the first date of a positive HCV RNA result for relapsers or the last contact date for non-relapsers in the LTFU (up to 3.5 years)
    Title
    Number of Participants With HCV Treatment-Emergent Resistance Associated Variants (TE-RAVs) of NS3/4A Protease Loci
    Description
    Plasma samples of all participants receiving at least one dose of study medication in a previous treatment protocol were evaluated by population sequencing and analyzed to detect amino acid variants in the NS3/4A protease known to be associated with reduced susceptibility to boceprevir and narlaprevir. RAVs in the NS3/4A protease gene were evaluated at 12 loci (V36, Q41, F43, T54, V55, V107, R155, A156, V158, D168, I/V170 and M175) on the basis of in vitro studies. A TE-RAV was defined as a RAV not present at baseline and that had not returned to wild type (WT) while the participant was still on treatment. The number of participants with TE-RAVS detected at the EOT in the previous treatment study are reported below, followed by those participants with TE-RAVS that returned to WT during the LTFU (among those with detected TE-RAVS).
    Time Frame
    From EOT in the previous treatment study to the last available date in the LTFU (up to 3.5 years)
    Title
    Number of Participants With Serious Adverse Events (SAEs) Reported During the LTFU
    Description
    Long-term safety was assessed based on the SAEs reported during the LTFU period. An SAE was any adverse drug or biologic or device experience occurring at any dose that resulted in any of the following outcomes: death, life-threatening AE, persistent or significant disability/incapacity, required in-patient hospitalization or prolongs hospitalization, congenital anomaly or birth defect. Important medical events that did not result in any of these outcomes could still be considered SAEs if they jeopardized the participant and/or required medical/surgical intervention, based on appropriate medical judgment. Grade 4 laboratory abnormalities and out of normal range liver function tests that were not accompanied by clinical manifestations were NOT considered SAEs.
    Time Frame
    From enrollment in the LTFU study to the last available date in the LTFU study (up to 3 years)
    Title
    Number of Participants That Discontinued the LTFU Due to SAEs
    Description
    An SAE was any adverse drug or biologic or device experience occurring at any dose that resulted in any of the following outcomes: death, life-threatening AE, persistent or significant disability/incapacity, required in-patient hospitalization or prolongs hospitalization, congenital anomaly or birth defect. Important medical events that did not result in any of these outcomes could still be considered SAEs if they jeopardized the participant and/or required medical/surgical intervention, based on appropriate medical judgment. Grade 4 laboratory abnormalities and out of normal range liver function tests that were not accompanied by clinical manifestations were NOT considered SAEs.
    Time Frame
    From enrollment in the LTFU study to the last available date in the LTFU study (up to 3 years)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Participant must be willing to give written informed consent and be able to adhere to the visit schedule. Participant must have received at least one dose of boceprevir or narlaprevir in a previous Phase 1, 2, or 3 clinical study. Exclusion Criteria: Concurrent participation in any other clinical study for the treatment of chronic hepatitis C. Retreatment with any antiviral or immunomodulatory drug for chronic hepatitis C after completion of, or discontinuation from, the SPRI Phase 1, 2, or 3 clinical study in which the participant previously participated. Any condition which in the opinion of the Investigator would make the participant unsuitable for enrollment.
    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
    25446895
    Citation
    Howe AY, Long J, Nickle D, Barnard R, Thompson S, Howe J, Alves K, Wahl J. Long-term follow-up of patients receiving boceprevir for treatment of chronic hepatitis C. Antiviral Res. 2015 Jan;113:71-8. doi: 10.1016/j.antiviral.2014.10.010. Epub 2014 Oct 24.
    Results Reference
    background
    PubMed Identifier
    27219495
    Citation
    Barnard R, Chopra A, James I, Blinco J, Watson MW, Jabara CB, Hazuda D, Lemon SM, Mallal S, Gaudieri S. Primer ID ultra-deep sequencing reveals dynamics of drug resistance-associated variants in breakthrough hepatitis C viruses: relevance to treatment outcome and resistance screening. Antivir Ther. 2016;21(7):567-577. doi: 10.3851/IMP3056. Epub 2016 May 24.
    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=P05063&kw=P05063&tab=access

    Learn more about this trial

    Three-year Follow-up of Participants After Administration of Boceprevir or Narlaprevir for the Treatment of Chronic Hepatitis C (P05063)

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