Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older With the G551D Mutation (STRIVE)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||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|
- Absolute Mean Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24 [ Time Frame: baseline through 24 weeks ] [ Designated as safety issue: No ]Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
- Absolute Mean Change From Baseline in Percent Predicted FEV1 Through Week 48 [ Time Frame: baseline through 48 weeks ] [ Designated as safety issue: No ]Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
- Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score Through Week 24 and Week 48 (Respiratory Domain Score, Pooled) [ Time Frame: baseline through 24 weeks and 48 weeks ] [ Designated as safety issue: No ]The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID).
- Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48 [ Time Frame: baseline through 24 weeks and 48 weeks ] [ Designated as safety issue: No ]The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.
- Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48 [ Time Frame: baseline through 24 weeks and 48 weeks ] [ Designated as safety issue: No ]Pulmonary exacerbation was defined as a change in antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of signs/symptoms such as change in sputum; new or increased hemoptysis; increased cough or dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees C; anorexia or weight loss; sinus pain/tenderness and discharge; change in physical examination of the chest; decreased pulmonary function by 10%; and radiographic changes indicative of pulmonary infection.
- Absolute Change From Baseline in Weight at Week 24 and Week 48 [ Time Frame: baseline to 24 weeks and 48 weeks ] [ Designated as safety issue: No ]As malnutrition is common in patients with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.
|Study Start Date:||June 2009|
|Study Completion Date:||November 2012|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Subjects who received placebo every 12 hours (q12h) for up to 48 weeks.
Tablet given orally q12h for up to 48 weeks
Experimental: 150 mg Ivacaftor q12h
Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.
150-mg tablets given orally q12h for up to 48 weeks
Other Name: VX-770
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.
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|Principal Investigator:||Bonnie W. Ramsey, MD||Children's Hospital and Regional Medical Center, Seattle, Washington, USA|
|Principal Investigator:||Stuart Elborn, MD||Respiratory Medicine Group, Queen's University of Belfast, Belfast, Northern Ireland, UK|