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

Study at a glance

From the registry record, last updated by the sponsor on 11 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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

ClinicalTrials.gov ID

NCT00689390

Acronym / sponsor ID

P05063

Conditions

Hepatitis C, Chronic, Hepacivirus

Phase

Phase 2/3

Study type

Interventional

Recruitment status

TerminatedReason stopped: The study was terminated due to satisfaction of post-marketing commitments

Enrolment

1,954 participants (actual)

Lead sponsor

Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)

Study start

20 Feb 2007 (actual)

Primary completion

13 Oct 2014 (actual)

Study completion

13 Oct 2014 (actual)

First posted

3 Jun 2008 (estimated)

Results

Posted 6 Oct 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Other

Allocation

Non-randomised

Intervention model

Parallel groups

Masking

None (open label)

Number of arms

2

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. 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)

   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.

2. 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)

   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].

3. 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)

   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).

4. 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)

   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.

5. 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)

   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.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2018.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Background: PubMed 25446895Howe 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.
• Derived from this study: PubMed 27219495Barnard 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.
• Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.