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

This study has been terminated.
Sponsor:
Collaborator:
Janssen Pharmaceuticals
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01701063
First received: September 27, 2012
Last updated: June 7, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Hepatitis C
Drug: Telaprevir
Drug: Peginterferon alfa-2b
Drug: Ribavirin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 52 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: 12 weeks after last planned dose of study drug (up to Week 60) ] [ Designated as safety issue: No ]
    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) [ Time Frame: 24 weeks after last planned dose of study drug (up to Week 72) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 4 and Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline up to Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks after planned EOT (up to Week 60) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, On treatment (up to Week 48) ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    Cmax was measured for telaprevir only.

  • Time to Reach Maximum Plasma Concentration (Tmax) of Telaprevir [ 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 ] [ Designated as safety issue: No ]
    Tmax was measured for telaprevir only.

  • Area Under the Plasma Concentration Versus Time Curve (AUC) of Telaprevir [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.


Enrollment: 42
Study Start Date: January 2013
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment-Naive or Prior Partial/Null Response
telaprevir + Peginterferon alfa-2b + Ribavirin
Drug: Telaprevir
100- and 250-mg chewable tablets or 375-mg film-coated tablets for oral administration
Drug: Peginterferon 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
Other Name: PegIntron®
Drug: Ribavirin
200-mg capsules or 40-mg/mL solution for oral administration
Other Name: Rebetol®

  Eligibility

Ages Eligible for Study:   3 Years to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01701063

  Hide Study Locations
Locations
United States, Arizona
Phoenix, Arizona, United States
United States, California
San Francisco, California, United States
United States, Colorado
Denver, Colorado, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Gainesville, Florida, United States
Miami, Florida, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Maryland
Baltimore, Maryland, United States
United States, New York
Bronx, New York, United States
New York, New York, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Texas
Houston, Texas, United States
United States, Washington
Seattle, Washington, United States
Belgium
Brussel, Belgium
Bruxelles, Belgium
Germany
Wuppertal, Germany
Italy
Milano, Italy
Padova, Italy
Pisa, Italy
Spain
Esplugues de Llobregat, Spain
Madrid, Spain
United Kingdom
Birmingham, United Kingdom
Leeds, United Kingdom
London, United Kingdom
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Janssen Pharmaceuticals
Investigators
Study Director: Medical Monitor Vertex Pharmaceuticals Incorporated
  More Information

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01701063     History of Changes
Other Study ID Numbers: VX11-950-118 
Study First Received: September 27, 2012
Results First Received: April 18, 2016
Last Updated: June 7, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Peginterferon alfa-2b
Interferon-alpha
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 24, 2016