43 Patient-reported outcomes in Phase 3 trials of ivacaftor in subjects with CF who have the G551D-CFTR mutation

Objectives: Two Phase 3 studies were conducted to evaluate the effect of ivacaftor in CF subjects with a G551D mutation. Change in Cystic Fibrosis Questionnairerevised (CFQ-R) scores was evaluated in both studies. Methods: Both were randomized, double-blind, placebo-controlled studies. Subjects received placebo or ivacaftor 150mg q12h for 48 weeks in addition to prescribed therapies. In STRIVE, 161 subjects 12 years were dosed. In ENVISION, 52 subjects 6−11 years were dosed. The CFQ-R is a patient-reported outcome measure with multiple domains each scored on a 100-point scale. Higher numbers indicate fewer symptoms. In the respiratory domain, a difference of at least 4 points is considered the minimal clinically important difference (MCID). MCIDs for other domains have not been established. Results: The treatment difference in the mean pooled CFQ-R Respiratory Symptoms scores for ivacaftor vs. placebo through Week 48 was 8.6 points (P < 0.0001) in STRIVE and 5.1 points (P = 0.1354) in ENVISION. Differences between groups were detected by Day 15 in both studies and were maintained at subsequent visits in STRIVE. In STRIVE, the treatment difference for ivacaftor was 4.4 points (P = 0.0055) for the Physical Functioning scale, 4.3 points (P = 0.0026) for Social Functioning scale, 3.3 points (P = 0.0021) for Eating Disturbances scale, and 3.3 points (P = 0.0419) for Treatment Burden scale. Conclusions: Both studies demonstrated clinically meaningful improvements in respiratory symptoms that were rapid, durable, and of comparable magnitude. There were statistically significant improvements in other domains, though the MCID for those domains has not been established. Sponsored by Vertex.