Study of Ivacaftor in Cystic Fibrosis Subjects Aged 6 to 11 Years With the G551D Mutation

NCT ID: NCT00909727

Last Updated: 2012-08-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-08-31

Study Completion Date

2011-04-30

Brief Summary

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The purpose of this study was to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis aged 6 to 11 years who have the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a potent and selective potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. Potentiators are pharmacological agents that increase the chloride ion transport properties of the channel in the presence of cyclic adenosine monophosphate (AMP)-dependent protein kinase A (PKA) activation.

Detailed Description

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This is a Phase 3, 2-part, randomized, double-blind, placebo-controlled, parallel group multicenter study of orally administered ivacaftor in subjects with cystic fibrosis (CF) 6 to 11 years of age who have the G551D-CFTR mutation and a forced expiratory volume in 1 second (FEV1) between 90% and 105% predicted (using Knudson standards).

Based on in vitro studies and pharmacologic, pharmacokinetic (PK), and safety profiles, ivacaftor was selected for clinical development as a possible treatment for patients with CF. Patients with the G551D mutation were the targeted population for this study because ivacaftor is a potentiator of the gating effect of the CFTR protein, and the most prevalent mutation with a gating defect in CF is the G551D mutation.

This study was conducted in 2 parts. Part A was conducted to analyze the PK properties of ivacaftor and to determine the most appropriate dose to administer to subjects in Part B of this study. Part B explored the safety and efficacy of ivacaftor over long-term treatment in subjects 6 to 11 years of age.

Conditions

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Cystic Fibrosis

Keywords

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Fibrosis Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Pathologic Processes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Subjects who received placebo every 12 hours (q12h) for up to 48 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Tablet given orally q12h for up to 48 weeks

150 mg Ivacaftor q12h

Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.

Group Type EXPERIMENTAL

Ivacaftor

Intervention Type DRUG

150-mg tablet given orally q12h for up to 48 weeks

Interventions

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Ivacaftor

150-mg tablet given orally q12h for up to 48 weeks

Intervention Type DRUG

Placebo

Tablet given orally q12h for up to 48 weeks

Intervention Type DRUG

Other Intervention Names

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VX-770

Eligibility Criteria

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Inclusion Criteria

* Weighing at least 15 kg
* Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele
* Forced expiratory volume in 1 second (FEV1) of 40% to 105% (inclusive) of predicted normal for age, gender, and height (Knudson standards) at Screening
* Able to swallow tablets
* As judged by the investigator, parent or legal guardian and subject must have been able to understand protocol requirements, restrictions, and instructions, and the parent or legal guardian should have been able to ensure that the subject complied with, and was likely to complete, the study as planned
* Parent or legal guardian must have signed the informed consent form and corresponding assent must be obtained from the subject
* Willing to use at least 1 highly effective birth control method during the study
* No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator

Exclusion Criteria

* History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject
* Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1 of the study
* Abnormal liver function ≥ 3x the upper limit of normal
* Abnormal renal function at Screening
* History of solid organ or hematological transplantation
* Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to Screening
* Use of inhaled hypertonic saline treatment
* Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4)
Minimum Eligible Age

6 Years

Maximum Eligible Age

11 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cystic Fibrosis Foundation

OTHER

Sponsor Role collaborator

Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Richard Ahrens, MD

Role: PRINCIPAL_INVESTIGATOR

Roy A. & Lucille A. Carver College of Medicine

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Emory Cystic Fibrosis Center

Atlanta, Georgia, United States

Site Status

Children's Memorial Hospital

Chicago, Illinois, United States

Site Status

The Cystic Fibrosis Center of Chicago

Glenview, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

University of Iowa Department of Pediatrics

Iowa City, Iowa, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Children's Hospital Boston

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

Helen DeVos Children's Hospital Spectrum Health Hospitals

Grand Rapids, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

The Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

University of Nebraska Medical Center Pediatric Pulmonary/ CF

Omaha, Nebraska, United States

Site Status

East Tennessee Children's Hospital Pediatric Pulmonary and Respiratory Care

Knoxville, Tennessee, United States

Site Status

University of Utah Pediatric Pulmonology

Salt Lake City, Utah, United States

Site Status

University of Virginia Pediatric Respiratory Medicine

Charlottesville, Virginia, United States

Site Status

The Children's Hospital Westmead

Westmead, New South Wales, Australia

Site Status

Royal Children's Hospital Brisbane

Herston, Queensland, Australia

Site Status

Royal Children's Hospital Melbourne

Parkville, Victoria, Australia

Site Status

Princess Margaret Hospital for Children

Subiaco, Western Australia, Australia

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

Hospital for Sick Children CF Center

Toronto, Ontario, Canada

Site Status

Hôpital Robert Debré - Service de gastro-entérologiemucoviscidose et nutrition

Paris, , France

Site Status

Kinder- und Jugendklinik Universitätsklinikum Erlangen

Erlangen, , Germany

Site Status

Mukoviszidose-Zentrum am Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Kinder- und Jugendmedizin

Jena, , Germany

Site Status

Our Lady's Children's Hospital

Dublin, , Ireland

Site Status

The National Children's Hospital

Dublin, , Ireland

Site Status

Dept of Gene Therapy, Imperial College London

London, , United Kingdom

Site Status

Countries

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United States Australia Canada France Germany Ireland United Kingdom

References

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Davies JC, Wainwright CE, Canny GJ, Chilvers MA, Howenstine MS, Munck A, Mainz JG, Rodriguez S, Li H, Yen K, Ordonez CL, Ahrens R; VX08-770-103 (ENVISION) Study Group. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med. 2013 Jun 1;187(11):1219-25. doi: 10.1164/rccm.201301-0153OC.

Reference Type DERIVED
PMID: 23590265 (View on PubMed)

Related Links

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Other Identifiers

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VX08-770-103

Identifier Type: -

Identifier Source: org_study_id