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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: Boceprevir; Drug: Peginterferon alpha-2b; Drug: Ribavirin; Drug: Boceprevir; Drug: Ribavirin; Drug: Peginterferon alfa-2b

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

• Allergy or sensitivity to the investigational products or excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: SCH 503034; Victrelis®; 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: Ribasphere®; Copegus®; Rebetol®; RibaTab®; 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: 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: Ribasphere®; Copegus®; Rebetol®; RibaTab®
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 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: SCH 503034; Victrelis®; 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: Ribasphere®; Copegus®; Rebetol®; RibaTab®; 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: 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: Ribasphere®; Copegus®; Rebetol®; RibaTab®; 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®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2013
• Primary Completion (Anticipated): August 18, 2021
• Study Completion (Anticipated): August 18, 2021

Study Registration Dates

• First Submitted: May 1, 2012
• First Submitted That Met QC Criteria: May 1, 2012
• First Posted (Estimate): May 2, 2012

Study Record Updates

• Last Update Posted (Actual): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Immunologic Factors; Interferon-alpha; Ribavirin; Peginterferon alfa-2b
• Other Study ID Numbers: P08034; 2010-024260-17 (EudraCT Number)