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

NCT00689390 | Terminated Phase 2 Results DMC

• 2 other identifiers: P050632006-006529-25
• Study Type: interventional
• Target: 1,954
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hepatitis C, Chronic; Hepacivirus

Outcome Measures

Primary Outcomes (5)

• 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.

  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)

• 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 \[for 1 year\].

  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)

• 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).

  From EOT in the previous treatment study to the last available date in the LTFU (up to 3.5 years)

• 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.

  From enrollment in the LTFU study to the last available date in the LTFU study (up to 3 years)

• 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.

  From enrollment in the LTFU study to the last available date in the LTFU study (up to 3 years)

Study Arms (2)

Participants from Boceprevir Studies

OTHER

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; Biological: Peginterferon alfa-2b; Drug: Ribavirin; Other: Blood/Plasma Collection

Participants from Narlaprevir Studies

OTHER

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; Biological: Peginterferon alfa-2b; Drug: Ribavirin; Other: Blood/Plasma Collection

Interventions

Boceprevir BIOLOGICAL

In previous treatment studies, boceprevir was administered as specified by the protocol. No treatment was administered on the current follow-up study (P05063, NCT00689390).

Also known as: SCH 503034

Participants from Boceprevir Studies

Narlaprevir BIOLOGICAL

In previous treatment studies, narlaprevir was administered as specified by the protocol. No treatment was administered on the current follow-up study (P05063, NCT00689390).

Also known as: SCH 900518

Participants from Narlaprevir Studies

Peginterferon alfa-2b BIOLOGICAL

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).

Also known as: PEG-Intron®, SCH 054031

Participants from Boceprevir Studies; Participants from Narlaprevir Studies

Ribavirin DRUG

In previous treatment studies, ribavirin was administered as specified by the protocol. No treatment was administered on the current follow-up study (P05063, NCT00689390).

Also known as: Rebetol®

Participants from Boceprevir Studies; Participants from Narlaprevir Studies

Blood/Plasma Collection OTHER

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 Boceprevir Studies; Participants from Narlaprevir Studies

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• 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.

  PMID: 25446895 BACKGROUND

• 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.

  PMID: 27219495 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; narlaprevir; peginterferon alfa-2b; Ribavirin; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2008
• First Posted: June 3, 2008
• Study Start: February 20, 2007
• Primary Completion: October 13, 2014
• Study Completion: October 13, 2014
• Last Updated: September 11, 2018
• Results First Posted: October 6, 2015

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share