Hepatitis C
Conditions
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.
Interventions
DRUGTelaprevir
100- and 250-mg chewable tablets or 375-mg film-coated tablets for oral administration
DRUGPeginterferon alfa-2b
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
DRUGRibavirin
200-mg capsules or 40-mg/mL solution for oral administration
Sponsors
Janssen Pharmaceuticals
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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). |
| 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. |
| 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. |
| 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. |
Countries
Belgium, Germany, Italy, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
The study was planned to be conducted in 2 parts (Part A and Part B), which would use separate groups of participants. However, the study was terminated early (12 weeks after last dose of study drug in Part A) and Part B was not conducted.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV Participants aged 13 to 17 years received telaprevir twice daily for 12 weeks either as a film coated tablet (15 mg/kg of body weight) or as a chewable tablet (14 mg/kg of body weight) in combination with Peg-IFN-alfa-2b 60 mcg/m\^2 subcutaneous injection weekly and RBV 200 mg capsules or 40 mg/mL solution orally twice daily with a maximum dose of 1200 mg per day. Peg-IFN-alfa-2b and RBV were administered for 24 weeks in participants who achieved eRVR or for 48 weeks in participants who did not achieve eRVR. eRVR was defined as undetectable HCV RNA levels at Week 4 and Week 12. | 13 |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV Participants aged 7 to 12 years received telaprevir twice daily for 12 weeks as a chewable tablet (16 mg/kg of body weight) in combination with Peg-IFN-alfa-2b 60 mcg/m\^2 subcutaneous injection weekly and RBV 200-mg capsules or 40 mg/mL solution orally twice daily with a maximum dose of 1200 mg per day. Peg-IFN-alfa-2b and RBV were administered for 24 weeks in participants who achieved eRVR or for 48 weeks in participants who did not achieve eRVR. eRVR was defined as undetectable HCV RNA levels at Week 4 and Week 12. | 19 |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV Participants aged 3 to 6 years received telaprevir twice daily for 12 weeks as a chewable tablet (18 mg/kg of body weight) in combination with Peg-IFN-alfa-2b 60 mcg/m\^2 subcutaneous injection weekly and RBV 200-mg capsules or 40 mg/mL solution orally twice daily with a maximum dose of 1200 mg per day. Peg-IFN-alfa-2b and RBV were administered for 24 weeks in participants who achieved eRVR or for 48 weeks in participants who did not achieve eRVR. eRVR was defined as undetectable HCV RNA levels at Week 4 and Week 12. | 10 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Total |
|---|---|---|---|---|
| Age, Continuous | 14.9 years STANDARD_DEVIATION 2.06 | 10.2 years STANDARD_DEVIATION 1.57 | 4.9 years STANDARD_DEVIATION 0.88 | 10.4 years STANDARD_DEVIATION 4.05 |
| Sex: Female, Male Female | 11 Participants | 13 Participants | 4 Participants | 28 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 6 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 13 | 18 / 19 | 10 / 10 |
| serious Total, serious adverse events | 0 / 13 | 0 / 19 | 1 / 10 |
Outcome results
Primary
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.
Time frame: Baseline up to Week 52
Population: Safety set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 participants |
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 13 participants |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 participants |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 18 participants |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 participants |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 10 participants |
Secondary
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.
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
Population: PK population. Here 'Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC 0-t last | 39900 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 11300 |
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC 0-12h | 39900 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 11300 |
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC 0-24h | 79900 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 22700 |
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC 0-24h_Adj | 95700 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 29800 |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC 0-24h_Adj | 88600 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 19200 |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC 0-t last | 43300 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 9480 |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC 0-24h | 88100 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 18000 |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC 0-12h | 44100 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 9020 |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC 0-24h_Adj | 76300 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 22800 |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC 0-12h | 35300 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 12000 |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC 0-24h | 70600 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 24100 |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir | AUC 0-t last | 35300 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 12000 |
Secondary
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.
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
Population: Half life was not calculated because the calculation required the slope of terminal elimination phase and the PK sampling was relatively sparse and did not yield a terminal elimination phase from which half-life can be accurately estimated.
Secondary
Maximum Plasma Concentration (Cmax) of Telaprevir
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
Population: Pharmacokinetic (PK) population included all participants who received at least a single dose of telaprevir, whether the participant completed all treatments or not. Here 'Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Maximum Plasma Concentration (Cmax) of Telaprevir | 4310 nanogram per milliliter (ng/mL) | Standard Deviation 1160 |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Maximum Plasma Concentration (Cmax) of Telaprevir | 5050 nanogram per milliliter (ng/mL) | Standard Deviation 884 |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Maximum Plasma Concentration (Cmax) of Telaprevir | 4060 nanogram per milliliter (ng/mL) | Standard Deviation 1500 |
Secondary
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.
Time frame: Baseline, On treatment (up to Week 48)
Population: FAS. Here 'Number of Participants Analyzed' signifies those participants who were evaluable for this outcome and 'n' signifies those who were evaluable at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region | Baseline (n = 41) | 2 participants |
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region | On treatment (n = 6) | 6 participants |
Secondary
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.
Time frame: Week 4 and Week 12
Population: FAS included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Extended Rapid Virologic Response (eRVR) | 61.5 percentage of participants |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Extended Rapid Virologic Response (eRVR) | 73.7 percentage of participants |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Extended Rapid Virologic Response (eRVR) | 60.0 percentage of participants |
Secondary
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.
Time frame: Baseline up to Week 48
Population: FAS included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With On-treatment Virologic Failure | 15.4 percentage of participants |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With On-treatment Virologic Failure | 5.3 percentage of participants |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With On-treatment Virologic Failure | 30.0 percentage of participants |
Secondary
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.
Time frame: Week 4
Population: FAS included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Rapid Virologic Response (RVR) | 69.2 percentage of participants |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Rapid Virologic Response (RVR) | 73.7 percentage of participants |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Rapid Virologic Response (RVR) | 70.0 percentage of participants |
Secondary
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).
Time frame: 12 weeks after last planned dose of study drug (up to Week 60)
Population: Full analysis set (FAS) included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | 69.2 percentage of participants |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | 89.5 percentage of participants |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | 40.0 percentage of participants |
Secondary
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.
Time frame: 24 weeks after last planned dose of study drug (up to Week 72)
Population: SVR24 was not analyzed because study was terminated early and follow-up was conducted only up to 12 weeks after planned end of treatment (EOT).
Secondary
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.
Time frame: Week 12
Population: FAS included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Undetectable HCV RNA at Week 12 | 69.2 percentage of participants |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Undetectable HCV RNA at Week 12 | 89.5 percentage of participants |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Undetectable HCV RNA at Week 12 | 70.0 percentage of participants |
Secondary
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.
Time frame: 12 weeks after planned EOT (up to Week 60)
Population: FAS included all enrolled participants who received at least 1 dose of study drug. Here 'Number of Participants Analyzed' signifies those participants who completed the assigned treatment period and had undetectable HCV RNA at EOT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Virologic Relapse | 0 percentage of participants |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Virologic Relapse | 0 percentage of participants |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Percentage of Participants With Virologic Relapse | 0 percentage of participants |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Telaprevir
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
Population: PK population. Here 'Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (13-17 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Time to Reach Maximum Plasma Concentration (Tmax) of Telaprevir | 4.00 hours (h) |
| Cohort 2 (7-12 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Time to Reach Maximum Plasma Concentration (Tmax) of Telaprevir | 4.00 hours (h) |
| Cohort 3 (3-6 Years): Telaprevir + Peg-IFN-alfa-2b + RBV | Time to Reach Maximum Plasma Concentration (Tmax) of Telaprevir | 4.00 hours (h) |