Efficacy and Safety of Boceprevir in Combination With Peginterferon Alfa-2b Plus Ribavirin in Pediatric Subjects With Chronic Hepatitis C Genotype 1 (P08034)

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT01590225

Collaborator

(none)

Enrollment

Arms

102.6

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a three-part (Part A, Part B, and Part C), open-label, multicenter study of boceprevir in pediatric participants with chronic hepatitis C (CHC) genotype 1 (GT1). In Part A and Part B, efficacy and safety will be evaluated in participants with CHC GT1 who are non-cirrhotic, treatment naïves (Part A) or who are non-cirrhotic, treatment failures to (peg)interferon/ribavirin or who are cirrhotics (whether treatment naïve or treatment failure) (Part B). Part C is long-term follow up and no study treatment will be administered during this period, but participants who do not achieve viral clearance will be allowed to receive other treatments for CHC.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: Boceprevir Drug: Peginterferon alpha-2b Drug: Ribavirin Drug: Boceprevir Drug: Peginterferon alfa-2b Drug: Ribavirin	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3 Study to Assess the Efficacy and Safety of Boceprevir in Combination With Peginterferon Alfa-2b Plus Ribavirin in Pediatric Subjects With Chronic Hepatitis C Genotype 1

Actual Study Start Date :

Jan 28, 2013

Anticipated Primary Completion Date :

Aug 18, 2021

Anticipated Study Completion Date :

Aug 18, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: boceprevir + peginterferon alpha-2b + ribavirin	Drug: Boceprevir Boceprevir will be administered orally at a dose of 11.4 mg/kg three-times daily (TID) for 24 weeks. The boceprevir dose will be calculated based on 11.4 mg/kg and will then be rounded to the nearest 200-mg value for subjects in the oldest age group, or to the nearest 100-mg or 200-mg value for the subjects in the two youngest age groups. Other Names: Victrelis® SCH 503034 Drug: Peginterferon alpha-2b Peginterferon alpha-2b will be administered subcutaneously at a dose of 60 μg/m^2 once weekly (QW) for 24 weeks. Other Names: Pegintron® Sylatron® Drug: Ribavirin The dose of ribavirin will be approximately 15 mg/kg/day administered orally in two divided doses (twice daily [BID]) for 24 weeks. Other Names: Copegus® Rebetol® RibaTab® Ribasphere®
Experimental: Part B: boceprevir + peginterferon alpha-2b + ribavirin	Drug: Boceprevir Boceprevir will be administered orally at a dose of 11.4 mg/kg three-times daily (TID) for up to 48 weeks. The boceprevir dose will be calculated based on 11.4 mg/kg and will then be rounded to the nearest 200-mg value for subjects in the oldest age group, or to the nearest 100-mg or 200-mg value for the subjects in the two youngest age groups. Drug: Peginterferon alfa-2b Peginterferon alpha-2b will be administered subcutaneously at a dose of 60 μg/m^2 once weekly (QW) for 48 weeks. Other Names: Pegintron® Sylatron® Drug: Ribavirin Drug: Ribavirin The dose of ribavirin will be approximately 15 mg/kg/day administered orally in two divided doses (twice daily [BID]) for 48 weeks. Other Names: Copegus® Rebetol® RibaTab® Ribasphere®

Arm

Intervention/Treatment

Experimental: Part A: boceprevir + peginterferon alpha-2b + ribavirin

Drug: Boceprevir

Boceprevir will be administered orally at a dose of 11.4 mg/kg three-times daily (TID) for 24 weeks. The boceprevir dose will be calculated based on 11.4 mg/kg and will then be rounded to the nearest 200-mg value for subjects in the oldest age group, or to the nearest 100-mg or 200-mg value for the subjects in the two youngest age groups.

Other Names:

Victrelis®

SCH 503034

Drug: Peginterferon alpha-2b

Peginterferon alpha-2b will be administered subcutaneously at a dose of 60 μg/m^2 once weekly (QW) for 24 weeks.

Other Names:

Pegintron®

Sylatron®

Drug: Ribavirin

The dose of ribavirin will be approximately 15 mg/kg/day administered orally in two divided doses (twice daily [BID]) for 24 weeks.

Other Names:

Copegus®

Rebetol®

RibaTab®

Ribasphere®

Experimental: Part B: boceprevir + peginterferon alpha-2b + ribavirin

Drug: Boceprevir

Boceprevir will be administered orally at a dose of 11.4 mg/kg three-times daily (TID) for up to 48 weeks. The boceprevir dose will be calculated based on 11.4 mg/kg and will then be rounded to the nearest 200-mg value for subjects in the oldest age group, or to the nearest 100-mg or 200-mg value for the subjects in the two youngest age groups.

Drug: Peginterferon alfa-2b

Peginterferon alpha-2b will be administered subcutaneously at a dose of 60 μg/m^2 once weekly (QW) for 48 weeks.

Other Names:

Pegintron®

Sylatron®

Drug: Ribavirin

Drug: Ribavirin The dose of ribavirin will be approximately 15 mg/kg/day administered orally in two divided doses (twice daily [BID]) for 48 weeks.

Other Names:

Copegus®

Rebetol®

RibaTab®

Ribasphere®

Outcome Measures

Primary Outcome Measures

Participants Achieving Sustained Viral Response (SVR) at Follow-Up Week 24 in Study Part A [Follow-Up Week 24]
Participants Achieving SVR at Follow-Up Week 24 in Study Part B [Follow-Up Week 24]
Time to Viral Relapse in Study Part C [Follow-Up Week 24 to 5 Years]

Secondary Outcome Measures

Proportion of Participants With Alanine Aminotransferase (ALT) Normalization in Study Part A [Week 2, Week 4, Week 8, Week 12]
Participants With Early Virologic Response in Study Part A [Week 2, Week 4, Week 8, Week 12]
Proportion of Participants With Undetectable Hepatitis C Virus Ribonucleic Acid (HCV-RNA) in Study Part A [Week 12, End of Treatment, Follow-Up Week 24]
Proportion of Participants With Undetectable HCV-RNA Who Also Achieved SVR in Study Part A [Follow-Up Week 12]
Proportion of Participants With Alanine Aminotransferase (ALT) Normalization in Study Part B [Week 2, Week 4, Week 8, Week 12]
Proportion of Participants With Undetectable HCV-RNA in Study Part B [Week 24, End of Treatment, Follow-Up Week 12]
Proportion of Participants With Undetectable HCV-RNA Who Also Achieved SVR in Study Part B [Follow-Up Week 12]
Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs) in Study Part A [Week 1 to Follow-Up Visit 24]
Number of Participants Experiencing Treatment-Emergent Treatment-Related AEs in Study Part A [Week 1 to Follow-Up Week 24]
Number of Participants Experiencing Serious AEs (SAEs) in Study Part A [Week 1 to Follow-Up Week 24]
Participants Discontinuing Treatment Due to AEs in Study Part A [Week 1 to Follow-Up Week 24]
Change from Baseline in Participant Laboratory Values in Study Part A [Baseline to Follow-Up Week 24]
Change From Baseline in Participant Vital Signs in Study Part A [Baseline to Follow-Up Week 24]
Number of Participants Experiencing AEs in Study Part B [Week 1 to Follow-Up Week 24]
Number of Participants Experiencing SAEs in Study Part B [Week 1 to Follow-Up Week 24]
Change from Baseline in Participant Laboratory Values in Study Part B [Week 1 to Follow-Up Week 24]
Change From Baseline in Participant Vital Signs in Study Part B [Week 1 to Follow-Up Week 24]
Number of Participants Discontinuing From Study Treatment Due to AEs in Study Part B [Week 1 to Follow-Up Week 24]

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

CHC GT1 infection for at least 6 months with with HCV-RNA ≥10,000 IU/mL.
Treatment naive, non-cirrhotic participants will be eligible for inclusion in Study Part A
Non-cirrhotic subjects who failed previous (peg)interferon/ribavirin treatment for CHC and cirrhotics, whether treatment naive or treatment failure, will be eligible for inclusion in Study Part B
To participate in Study Part C, participants must have completed the required post-treatment follow-up in Study Part A or Part B
Weight ≥ 10 kg to ≤ 125 kg
Body surface area (BSA) ≥0.46 m^{2 and ≤2.5 m}2
Previous liver biopsy with histology consistent with chronic hepatitis C and no other etiology within 2 years of the screening visit
Participants with bridging fibrosis or cirrhosis must have an ultrasound within 6 months of the screening visit or between the screening visit and Day 1 with no findings suspicious for hepatocellular carcinoma
Participant must be able to adhere to dose and visit schedules

Exclusion Criteria:

Known co-infection with the the human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive)
For Study Part A, participant received any prior hepatitis C treatment, including herbal remedies, with known hepatotoxicity
For Study Part B, participant received treatment with ribavirin within 90 days or any interferon alpha within 30 days prior to screening
For Study Part B, participant received previous treatment with a hepatitis C virus protease inhibitor (excepting participants in study P07614, Pharmacokinetics of Boceprevir in Pediatric Subjects With Chronic Hepatitis C Genotype 1)
For Study Part B, participant required discontinuation of previous (peg)interferon/ribavirin therapy for an adverse event considered by the investigator to be related to (peg)interferon and/or ribavirin
For Study Part B, participant is currently taking any antiviral/immunomodulatory treatment for hepatitis C
Participant has taken any investigational drugs, except boceprevir
Participant has received any of the following medication(s) within 2 weeks prior to the Day 1 visit: midazolam, pimozide, amiodarone, flecainide,

propafenone, quinidine, and ergot derivatives (dihydroergotamine, ergonovine,

ergotamine, methylergonovine)

Participation in any other clinical trial within 30 days of enrollment or

intent to participate in another clinical trial during participation in the current study

Evidence of decompensated liver disease
Child Pugh score >6 (class B and C)
History of diabetes or hypertension or was born prior to 32 weeks

of gestation and has clinically significant ocular examination findings

Pre-existing clinically significant psychiatric condition(s)
Clinical diagnosis of substance abuse
Any pre-existing medical condition that could interfere with participation in and completion of the study
Evidence of active or suspected malignancy
Females who are pregnant, nursing, or intend to become pregnant during

the study period