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

Phase 1

Terminated

• Conditions: Hepatitis C
• Interventions: Drug: Telaprevir; Drug: Peginterferon alfa-2b; Drug: Ribavirin

• Registration Number: NCT01701063
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-09-27
• Study First Submitted QC: 2012-10-02
• Study First Posted: 2012-10-04
• Study Start: 2013-01
• Primary Completion: 2015-04
• Study Completion: 2015-04
• Status Verified: 2016-04
• Results First Submitted: 2016-04-18
• Results First Submitted QC: 2016-06-07
• Last Update Submitted: 2016-06-07
• Results First Posted: 2016-07-20
• Last Update Posted: 2016-07-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 42

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment-Naive or Prior Partial/Null Response	Telaprevir	telaprevir + Peginterferon alfa-2b + Ribavirin
Treatment-Naive or Prior Partial/Null Response	Peginterferon alfa-2b	telaprevir + Peginterferon alfa-2b + Ribavirin
Treatment-Naive or Prior Partial/Null Response	Ribavirin	telaprevir + Peginterferon alfa-2b + Ribavirin

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to Week 52	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24)	24 weeks after last planned dose of study drug (up to Week 72)	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.
Percentage of Participants With Rapid Virologic Response (RVR)	Week 4	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.
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)	12 weeks after last planned dose of study drug (up to Week 60)	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).
Percentage of Participants With Extended Rapid Virologic Response (eRVR)	Week 4 and 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. 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.
Percentage of Participants With Undetectable HCV RNA at Week 12	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.
Percentage of Participants With On-treatment Virologic Failure	Baseline up to Week 48	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.
Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region	Baseline, On treatment (up to Week 48)	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.
Maximum Plasma Concentration (Cmax) of Telaprevir	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	Cmax was measured for telaprevir only.
Time to Reach Maximum Plasma Concentration (Tmax) of Telaprevir	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	Tmax was measured for telaprevir only.
Percentage of Participants With Virologic Relapse	12 weeks after planned EOT (up to Week 60)	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.
Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir	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	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.
Elimination Half-Life (T1/2) of Telaprevir	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	T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.