A Phase 3 Study of Tezacaftor (VX-661) in Combination With Ivacaftor (VX-770) in Subjects Aged 12 Years and Older With Cystic Fibrosis (CF), Who Have One F508del-CFTR Mutation and a Second Mutation That Has Been Demonstrated to be Clinically Responsive to Ivacaftor
- Registration Number
- NCT02412111
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
This is a Phase 3, randomized, double-blind, ivacaftor-controlled, parallel-group, multicenter study of tezacaftor in combination with ivacaftor in subjects aged 12 years and older with CF who are heterozygous for the F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 156
- Heterozygous for F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive
- FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height during screening
- Stable CF disease as judged by the investigator.
- History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.
- Pregnant and nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Week -4 Visits).
- Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description VX-661 + Ivacaftor (Active comparator period) Tezacaftor/Ivacaftor VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks. Ivacaftor (Run-in Period) Ivacaftor Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks. VX-661 + Ivacaftor (Active comparator period) Ivacaftor VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks. Ivacaftor monotherapy (Active comparator period) Ivacaftor Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
- Primary Outcome Measures
Name Time Method Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 Baseline, Through Week 8 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
- Secondary Outcome Measures
Name Time Method Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 Baseline, Through Week 8 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline Through Week 8 Baseline, Through Week 8 The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Absolute Change From Baseline in Sweat Chloride Through Week 8 Baseline, Through Week 8 Sweat samples were collected using an approved collection device.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline up to Week 16 Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA) Predose on Week -2 for Run-in period; Pre-dose on Week 2 for Active comparator period