A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of VX-770 in Subjects With Cystic Fibrosis and the G551D Mutation
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Cystic Fibrosis
- Sponsor
- Vertex Pharmaceuticals Incorporated
- Enrollment
- 167
- Locations
- 65
- Primary Endpoint
- Absolute Mean Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
The purpose of this study was to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis aged 12 years and older who have the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a potent and selective CFTR 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 AMP-dependent protein kinase A (PKA) activation.
Detailed Description
This was a phase 3 study in subjects with cystic fibrosis (CF) age 12 years and older who have a G551D-CFTR mutation and percent predicted forced expiratory volumn in 1 second (FEV1) between 40% and 90%. 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 function of the CFTR protein, and the most prevalent mutation with a gating defect in CF is the G551D mutation. This study was designed to further evaluate the efficacy of ivacaftor in subjects with CF who have a G551D-CFTR gene mutation and to evaluate safety in this population over a longer period than previously studied.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele
- •Forced expiratory volume in 1 second (FEV1) of 40% to 90% (inclusive) of predicted normal for age, gender, and height at Screening.
- •No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator
- •Willing to use highly effective birth control methods during the study
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
- •History of alcohol, medication or illicit drug abuse within one year prior to Day 1
- •Abnormal liver function ≥ 3x the upper limit of normal
- •Abnormal renal function at Screening
- •History of solid organ or hematological transplantation
- •Pregnant, planning a pregnancy, breast-feeding, or unwilling to follow contraception requirements
- •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)
Arms & Interventions
Placebo
Subjects who received placebo every 12 hours (q12h) for up to 48 weeks.
Intervention: Placebo
150 mg Ivacaftor q12h
Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.
Intervention: Ivacaftor
Outcomes
Primary Outcomes
Absolute Mean Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
Time Frame: baseline through 24 weeks
Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
Secondary Outcomes
- Absolute Mean Change From Baseline in Percent Predicted FEV1 Through Week 48(baseline through 48 weeks)
- Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score Through Week 24 and Week 48 (Respiratory Domain Score, Pooled)(baseline through 24 weeks and 48 weeks)
- Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48(baseline through 24 weeks and 48 weeks)
- Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48(baseline through 24 weeks and 48 weeks)
- Absolute Change From Baseline in Weight at Week 24 and Week 48(baseline to 24 weeks and 48 weeks)