EPS6.05 A phase 3b study of the effects of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on cough and physical activity in people with cystic fibrosis (CF)

Objectives: We assessed the impact of ELX/TEZ/IVA treatment on cough frequency and physical activity using wearable devices in people with CF. Methods: VX20-445-126 (NCT04969224) was a Phase 3b, open-label, hybrid, decentralized study of ELX/TEZ/IVA in CFTR modulator-naïve people with CF aged ≥12 years heterozygous for F508del and a minimal function mutation. A wrist-worn actigraphy sensor (worn continuously during the study period) and an ambulatory cough-monitoring device (worn once/week for 24 continuous hours) were used for monitoring. Primary endpoint was percent reduction from baseline in cough frequency/day to the average of Week 8 through Week 12. Secondary endpoint was absolute change from baseline in total step count/day to the average of Week 8 through Week 12. Results: Eighty-one participants enrolled and received ≥1 dose of ELX/TEZ/IVA (mean [SD] age 25.7 [9.6] years; ppFEV1 67.8 [14.3]). Two participants discontinued treatment due to adverse events (AEs). Mean cough frequency/day was reduced by 91.7% (95% CI: 89.2, 93.6), from 241.3 coughs/day at baseline to 20.3 coughs/day at the average of Week 8 through Week 12. Cough frequency/day was reduced by 80.6% at Week 2. Mean step count increased by 638 steps/day (95% CI: 298, 977), from 5,279 (SD: 2,132) steps/day at baseline to 5,907 (SD: 1,909) steps/day at the average of Week 8 through Week 12. Time above sedentary, time in moderate to vigorous physical activity, and total activity improved. Most AEs were consistent with common manifestations of CF. Conclusion: In participants with CF receiving ELX/TEZ/IVA, mean cough frequency/day decreased rapidly and by 91.7% to 20.3 coughs/day, which is similar to cough frequency in healthy people without CF. Activity level, as measured by steps/day, increased in a clinically important manner compared to baseline. These results show ELX/TEZ/IVA has a clinically meaningful impact on cough frequency and activity levels in people with CF.