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

Vertex Pharmaceuticals

Status and phase

Completed

Phase 3

Conditions

Cystic Fibrosis

Treatments

Drug: Ivacaftor

Drug: Placebo

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00909727

VX08-770-103

Details and patient eligibility

About

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.

Full description

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.

Enrollment

52 patients

Sex

All

Ages

6 to 11 years old

Volunteers

No Healthy Volunteers

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)