A Phase 3 Study of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
- Registration Number
- NCT03447249
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
This study will evaluate the efficacy of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 385
- Heterozygous for F508del and an MF mutation (as defined in the protocol)
- Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
Key
- Clinically significant cirrhosis with or without portal hypertension
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- Solid organ or hematological transplantation
Other protocol defined Inclusion/Exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants who received placebo matched to VX-659/TEZ/IVA for 24 weeks in the TC treatment period. VX-659/TEZ/IVA TC VX-659/TEZ/IVA Participants who received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period. VX-659/TEZ/IVA TC IVA Participants who received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.
- Primary Outcome Measures
Name Time Method Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline at Week 4 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
- Secondary Outcome Measures
Name Time Method Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline through Week 24 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Number of Pulmonary Exacerbations (PEx) From Baseline through Week 24 Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Absolute Change in Sweat Chloride (SwCl) From Baseline through Week 24 Sweat samples were collected using an approved collection device.
Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score From Baseline at Week 4 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 in Body Mass Index (BMI) From Baseline at Week 24 BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).
Absolute Change in Sweat Chloride From Baseline at Week 4 Sweat samples were collected using an approved collection device.
Time-to-first Pulmonary Exacerbation (PEx) From Baseline through Week 24 Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline From Baseline at Week 24 BMI was defined as weight in kg divided by height in m\^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI.
Absolute Change in Body Weight From Baseline at Week 24 Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 28 weeks) Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, and IVA Pre-dose on Week 4, 8, 12, and 16
Trial Locations
- Locations (101)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Stanford University
🇺🇸Palo Alto, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Hartford Health
🇺🇸Hartford, Connecticut, United States
Yale New Haven Medical Center
🇺🇸New Haven, Connecticut, United States
University of Miami/ Miller School of Medicine
🇺🇸Miami, Florida, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Arnold Palmer Hospital
🇺🇸Orlando, Florida, United States
Johns Hopkins All Children's Hospital Outpatient Care Center
🇺🇸Saint Petersburg, Florida, United States
St. Luke's CF Center of Idaho
🇺🇸Boise, Idaho, United States
Scroll for more (91 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States