An Open-Label Study of the Effect of Telaprevir in Combination With Peginterferon Alfa-2b and Ribavirin in Pediatric Subjects Infected With Hepatitis C Virus

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, efficacy, and pharmacokinetics in a carefully monitored cohort of pediatric subjects infected with hepatitis C virus (HCV) on a telaprevir-based regimen in Part A and with dose adjustments if needed before Part B.

Official Title
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A Two-Part, Open-Label, Single-Arm Phase 1/2 Study of Safety, Pharmacokinetics, and Efficacy of Telaprevir in Combination With Peginterferon Alfa-2b and Ribavirin in Pediatric Subjects Aged 3 to 17 Infected With Genotype 1 Hepatitis C Virus

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Telaprevir
* Drug: Peginterferon alfa-2b
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ages 3 to 17 years of age Chronic hepatitis C Hepatitis C virus genotype 1a or b at the Screening Visit Subject is judged to be in good health (besides HCV infection) in the opinion of the investigator. Signed informed consent form (ICF), and where appropriate, signed Assent Form Exclusion Criteria: History of or prior evidence of a medical condition associated with chronic liver disease other than HCV Body weight <15 kg or >90 kg Prior evidence of hepatic decompensation Contraindications to pegylated interferon/ribavirin (Peg-IFN/RBV) History or other evidence of severe retinopathy or clinically significant ophthalmological disorder History of non-genotype 1 HCV Participation in investigational drug study as described in Study Protocol Use of prohibited drugs within 7 days or 5 half-lives before the first dose of study drug

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment-Naive or Prior Partial/Null Response<br>telaprevir + Peginterferon alfa-2b + Ribavirin | Drug: Telaprevir<br>* 100- and 250-mg chewable tablets or 375-mg film-coated tablets for oral administration<br>Drug: Peginterferon alfa-2b<br>* 50 μg/0.5 mL, 80 μg/0.5 mL, 120 μg/0.5 mL, or 150 μg/0.5 mL for subcutaneous (SC) injection<br>* Other names: PegIntron®;Drug: Ribavirin<br>* 200-mg capsules or 40-mg/mL solution for oral administration<br>* Other names: Rebetol®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE: any adverse change from the participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Study drug includes all investigational agents administered during the course of the study. | Baseline up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | SVR12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (less than [<] lower limit of quantification) at 12 weeks after last planned dose of study drug. The plasma HCV RNA level was measured using Roche COBAS TaqMan HCV/High Pure System (HPS) RNA assay version 2.0. The lower limit of quantification was 25 international units per milliliter (IU/mL). | 12 weeks after last planned dose of study drug (up to Week 60) | 
| Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) | SVR24 was defined as an undetectable HCV RNA Levels (< lower limit of quantification) at 24 weeks after last planned dose of study drug. The plasma HCV RNA level was measured using Roche COBAS TaqMan HCV/HPS RNA assay version 2.0. The lower limit of quantification was 25 IU/mL. | 24 weeks after last planned dose of study drug (up to Week 72) | 
| Percentage of Participants With Rapid Virologic Response (RVR) | The plasma HCV RNA level was measured using Roche COBAS TaqMan HCV/HPS RNA assay version 2.0. The lower limit of quantification was 25 IU/mL. RVR was defined as an undetectable HCV RNA (<lower limit of quantification) 4 weeks after the start of study treatment. | Week 4 | 
| Percentage of Participants With Extended Rapid Virologic Response (eRVR) | The plasma HCV RNA level was measured using Roche COBAS TaqMan HCV/HPS RNA assay version 2.0. The lower limit of quantification was 25 IU/mL. eRVR was defined as an undetectable HCV RNA (<lower limit of quantification) at both 4 weeks and 12 weeks after the start of study treatment. | Week 4 and Week 12 | 
| Percentage of Participants With Undetectable HCV RNA at Week 12 | The plasma HCV RNA level was measured using Roche COBAS TaqMan HCV/HPS RNA assay version 2.0. The lower limit of quantification was 25 IU/mL. | Week 12 | 
| Percentage of Participants With On-treatment Virologic Failure | On treatment virologic failure was defined as meeting any futility rule or completing assigned treatment duration and having detectable HCV RNA at EOT. The plasma HCV RNA level was measured using Roche COBAS TaqMan HCV/HPS RNA assay Version 2.0. The lower limit of quantification was 25 IU/mL. Futility rules: 1) HCV RNA >1000 IU/mL at Week 4; 2) HCV RNA >1000 IU/mL at Week 12; 3) Detectable HCV RNA after Week 12 to end of treatment. | Baseline up to Week 48 | 
| Percentage of Participants With Virologic Relapse | The plasma HCV RNA level was measured using Roche COBAS TaqMan HCV/HPS RNA assay Version 2.0. The lower limit of quantification was 25 IU/mL. Viral relapse was defined as having detectable HCV at follow-up in participants who had HCV RNA less than (<) lower limit of quantification (LLOQ) at planned EOT. | 12 weeks after planned EOT (up to Week 60) | 
| Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region | Sequence analysis of the HCV NS3-4A region was performed to monitor telaprevir-resistant variants. HCV RNA was isolated from the plasma, amplified by reverse transcription-polymerase chain reaction (RT-PCR), and sequenced (sequencing assay limit of detection HCV RNA >=1000 IU/mL). Results of this outcome measure were to be reported for overall participants instead of by age. | Baseline, On treatment (up to Week 48) | 
| Maximum Plasma Concentration (Cmax) of Telaprevir | Cmax was measured for telaprevir only. | Cohort 1: Pre-dose and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, and 8.0 hours post-dose on Day 7, Cohort 2: Pre-dose and 0.5, 2.0, 4.0, 5.0, 6.0, and 8.0 hours post-dose on Day 7, Cohort 3: Pre-dose and 1.5, 4.0, and 8.0 hours post-dose on Day 7 | 
| Time to Reach Maximum Plasma Concentration (Tmax) of Telaprevir | Tmax was measured for telaprevir only. | Cohort 1: Pre-dose and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, and 8.0 hours post-dose on Day 7, Cohort 2: Pre-dose and 0.5, 2.0, 4.0, 5.0, 6.0, and 8.0 hours post-dose on Day 7, Cohort 3: Pre-dose and 1.5, 4.0, and 8.0 hours post-dose on Day 7 | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC was measured for telaprevir only. AUC 0-t last was defined as the area under the concentration-time curve from the time of dosing to the last measurable concentration. AUC 0-12 hour (AUC 0-12h) was calculated by respecifying predose concentrations as 12 hour concentrations. AUC 0-24h was calculated as AUC 0-12h multiplied by 2. Dose adjusted AUC (AUC 0-24h_Adj) was calculated by multiplying AUC 0-24h by the dose adjustment factor to obtain projected exposures in participants who were misdosed. Data were presented for AUC 0-t last, AUC 0-12h, AUC 0-24h, AUC 0-24h_Adj. | Cohort 1: Pre-dose and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, and 8.0 hours post-dose on Day 7, Cohort 2: Pre-dose and 0.5, 2.0, 4.0, 5.0, 6.0, and 8.0 hours post-dose on Day 7, Cohort 3: Pre-dose and 1.5, 4.0, and 8.0 hours post-dose on Day 7 | 
| Elimination Half-Life (T1/2) of Telaprevir | T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. | Cohort 1: Pre-dose and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, and 8.0 hours post-dose on Day 7, Cohort 2: Pre-dose and 0.5, 2.0, 4.0, 5.0, 6.0, and 8.0 hours post-dose on Day 7, Cohort 3: Pre-dose and 1.5, 4.0, and 8.0 hours post-dose on Day 7 |