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

This study has been terminated.
(The study was terminated due to satisfaction of post-marketing commitments)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00689390
First received: May 27, 2008
Last updated: November 30, 2015
Last verified: November 2015
  Purpose
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.

Condition Intervention Phase
Hepatitis C, Chronic
Hepacivirus
Biological: Boceprevir
Biological: Narlaprevir
Biological: Peginterferon alfa-2b
Drug: Ribavirin
Other: Blood/Plasma Collection
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

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) [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: From EOT in the previous treatment study to the last available date in the LTFU (up to 3.5 years) ] [ Designated as safety issue: No ]
    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 [ Time Frame: From enrollment in the LTFU study to the last available date in the LTFU study (up to 3 years) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: From enrollment in the LTFU study to the last available date in the LTFU study (up to 3 years) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 1954
Study Start Date: February 2007
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Participants from Boceprevir Studies
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.
Biological: Boceprevir
In previous treatment studies, boceprevir was administered as specified by the protocol. No treatment was administered on the current follow-up study (P05063, NCT00689390).
Other Name: SCH 503034
Biological: Peginterferon alfa-2b
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).
Other Names:
  • PEG-Intron®
  • SCH 054031
Drug: Ribavirin
In previous treatment studies, ribavirin was administered as specified by the protocol. No treatment was administered on the current follow-up study (P05063, NCT00689390).
Other Name: Rebetol®
Other: Blood/Plasma Collection
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.
Participants from Narlaprevir Studies
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.
Biological: Narlaprevir
In previous treatment studies, narlaprevir was administered as specified by the protocol. No treatment was administered on the current follow-up study (P05063, NCT00689390).
Other Name: SCH 900518
Biological: Peginterferon alfa-2b
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).
Other Names:
  • PEG-Intron®
  • SCH 054031
Drug: Ribavirin
In previous treatment studies, ribavirin was administered as specified by the protocol. No treatment was administered on the current follow-up study (P05063, NCT00689390).
Other Name: Rebetol®
Other: Blood/Plasma Collection
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00689390

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00689390     History of Changes
Other Study ID Numbers: P05063  2006-006529-25 
Study First Received: May 27, 2008
Results First Received: September 1, 2015
Last Updated: November 30, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Peginterferon alfa-2b
Interferon-alpha
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 25, 2016