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.
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
Categories
Completion Date
Completion Date Type
Actual
Conditions
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Maximum Age
17 Years
Minimum Age
3 Years
NCT Id
NCT01701063
Org Class
Industry
Org Full Name
Vertex Pharmaceuticals Incorporated
Org Study Id
VX11-950-118
Overall Status
Terminated
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome 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.
Outcome Measure
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Outcome Time Frame
Baseline up to Week 52
Secondary Outcomes
Outcome 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).
Outcome Time Frame
12 weeks after last planned dose of study drug (up to Week 60)
Outcome Measure
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)
Outcome 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.
Outcome Time Frame
24 weeks after last planned dose of study drug (up to Week 72)
Outcome Measure
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24)
Outcome 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.
Outcome Time Frame
Week 4
Outcome Measure
Percentage of Participants With Rapid Virologic Response (RVR)
Outcome 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.
Outcome Time Frame
Week 4 and Week 12
Outcome Measure
Percentage of Participants With Extended Rapid Virologic Response (eRVR)
Outcome 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.
Outcome Time Frame
Week 12
Outcome Measure
Percentage of Participants With Undetectable HCV RNA at Week 12
Outcome 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.
Outcome Time Frame
Baseline up to Week 48
Outcome Measure
Percentage of Participants With On-treatment Virologic Failure
Outcome 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.
Outcome Time Frame
12 weeks after planned EOT (up to Week 60)
Outcome Measure
Percentage of Participants With Virologic Relapse
Outcome 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.
Outcome Time Frame
Baseline, On treatment (up to Week 48)
Outcome Measure
Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region
Outcome Description
Cmax was measured for telaprevir only.
Outcome 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
Outcome Measure
Maximum Plasma Concentration (Cmax) of Telaprevir
Outcome Description
Tmax was measured for telaprevir only.
Outcome 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
Outcome Measure
Time to Reach Maximum Plasma Concentration (Tmax) of Telaprevir
Outcome 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.
Outcome 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
Outcome Measure
Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir
Outcome 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.
Outcome 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
Outcome Measure
Elimination Half-Life (T1/2) of Telaprevir
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
3
Investigators
Investigator Type
Principal Investigator
Investigator Name
Debra Pan
Investigator Email
dpan@montefiore.org
Investigator Phone
718-741-2332