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

• ClinicalTrials.gov Identifier: NCT01701063
• Recruitment Status: Terminated
• First Posted: October 4, 2012
• Results First Posted: July 20, 2016
• Last Update Posted: July 20, 2016
• Sponsor: Vertex Pharmaceuticals Incorporated
• Collaborator: Janssen Pharmaceuticals
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis C	Drug: Telaprevir; Drug: Peginterferon alfa-2b; Drug: Ribavirin	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: January 2013
• Actual Primary Completion Date: April 2015
• Actual Study Completion Date: April 2015

Arms and Interventions

Arm	Intervention/treatment
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®

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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 :

1. 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) ]
   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).
2. 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) ]
   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.
3. Percentage of Participants With Rapid Virologic Response (RVR) [ Time Frame: 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.
4. Percentage of Participants With Extended Rapid Virologic Response (eRVR) [ Time Frame: 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.
5. Percentage of Participants With Undetectable HCV RNA at Week 12 [ Time Frame: 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.
6. Percentage of Participants With On-treatment Virologic Failure [ Time Frame: 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.
7. Percentage of Participants With Virologic Relapse [ Time Frame: 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.
8. 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) ]
   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.
9. 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 ]
   Cmax was measured for telaprevir only.
10. 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 ]
    Tmax was measured for telaprevir only.
11. 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 ]
    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.
12. 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 ]
    T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• 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

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
• Other Study ID Numbers: VX11-950-118
• First Posted: October 4, 2012
• Results First Posted: July 20, 2016
• Last Update Posted: July 20, 2016
• Last Verified: April 2016

Additional relevant MeSH terms:

Hepatitis A; Hepatitis C; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; Flaviviridae Infections; Ribavirin; Peginterferon alfa-2b; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents