Back to resultsAn Open-Label Study of the Effect of Telaprevir in Combination With Peginterferon Alfa-2b and Ribavirin in Pediatric Subjects Infected With Hepatitis C Virus
Primary Purpose
Hepatitis C
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Telaprevir
Peginterferon alfa-2b
Ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment-Naive or Prior Partial/Null Response
Arm Description
telaprevir + Peginterferon alfa-2b + Ribavirin
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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.
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.
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.
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.
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.
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.
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.
Maximum Plasma Concentration (Cmax) of Telaprevir
Cmax was measured for telaprevir only.
Time to Reach Maximum Plasma Concentration (Tmax) of Telaprevir
Tmax was measured for telaprevir only.
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.
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.
Full Information
NCT ID
NCT01701063
First Posted
September 27, 2012
Last Updated
June 7, 2016
Sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
Janssen Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01701063
Brief Title
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
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Terminated
Study Start Date
January 2013 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
April 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
Janssen Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment-Naive or Prior Partial/Null Response
Arm Type
Experimental
Arm Description
telaprevir + Peginterferon alfa-2b + Ribavirin
Intervention Type
Drug
Intervention Name(s)
Telaprevir
Intervention Description
100- and 250-mg chewable tablets or 375-mg film-coated tablets for oral administration
Intervention Type
Drug
Intervention Name(s)
Peginterferon alfa-2b
Other Intervention Name(s)
PegIntron®
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Other Intervention Name(s)
Rebetol®
Intervention Description
200-mg capsules or 40-mg/mL solution for oral administration
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
Baseline up to Week 52
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)
Description
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).
Time Frame
12 weeks after last planned dose of study drug (up to Week 60)
Title
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24)
Description
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.
Time Frame
24 weeks after last planned dose of study drug (up to Week 72)
Title
Percentage of Participants With Rapid Virologic Response (RVR)
Description
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.
Time Frame
Week 4
Title
Percentage of Participants With Extended Rapid Virologic Response (eRVR)
Description
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.
Time Frame
Week 4 and Week 12
Title
Percentage of Participants With Undetectable HCV RNA at Week 12
Description
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.
Time Frame
Week 12
Title
Percentage of Participants With On-treatment Virologic Failure
Description
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.
Time Frame
Baseline up to Week 48
Title
Percentage of Participants With Virologic Relapse
Description
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.
Time Frame
12 weeks after planned EOT (up to Week 60)
Title
Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region
Description
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.
Time Frame
Baseline, On treatment (up to Week 48)
Title
Maximum Plasma Concentration (Cmax) of Telaprevir
Description
Cmax was measured for telaprevir only.
Time Frame
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
Title
Time to Reach Maximum Plasma Concentration (Tmax) of Telaprevir
Description
Tmax was measured for telaprevir only.
Time Frame
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
Title
Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir
Description
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.
Time Frame
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
Title
Elimination Half-Life (T1/2) of Telaprevir
Description
T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Vertex Pharmaceuticals Incorporated
Official's Role
Study Director
Facility Information:
City
Phoenix
State/Province
Arizona
Country
United States
City
San Francisco
State/Province
California
Country
United States
City
Denver
State/Province
Colorado
Country
United States
City
Washington
State/Province
District of Columbia
Country
United States
City
Gainesville
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Bronx
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Brussel
Country
Belgium
City
Bruxelles
Country
Belgium
City
Wuppertal
Country
Germany
City
Milano
Country
Italy
City
Padova
Country
Italy
City
Pisa
Country
Italy
City
Esplugues de Llobregat
Country
Spain
City
Madrid
Country
Spain
City
Birmingham
Country
United Kingdom
City
Leeds
Country
United Kingdom
City
London
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
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
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