WS05.03 A phase 3b study of the effects of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on glucose tolerance in people with cystic fibrosis (CF) and abnormal glucose metabolism

Objectives: We assessed the impact of ELX/TEZ/IVA treatment on glucose tolerance in people with CF and either impaired (IGT) or CF-related diabetes (CFRD) over a 48-week period. Methods: VX19-445-117 (NCT04599465) was Phase 3b, single-arm, open-label study aged ≥12 years heterozygous for F508del minimal function mutation who had abnormal as determined by oral testing (OGTT), IGT CFRD at screening. Primary endpoint change 2-hour OGTT blood levels from baseline to average Week 36 48. Secondary endpoints were proportion participants improved dysglycemia categorization 48 (defined normal tolerance), safety tolerability. Results: Sixty-nine enrolled received ≥1 dose (mean [SD] age 25.1 [9.5] years; BMI 20.54 [2.60]; 217.6 [73.1] mg/dL); 29 40 Three discontinued (commercial drug availability [n = 2]; physician decision 1]). Mean –35.0 mg/dL (95% CI: –49.2, –20.7; P < 0.0001). Overall, 37.7% 24.8, 52.1) 48; 35.5% compared 13.0% baseline. Safety tolerability generally consistent established profile ELX/TEZ/IVA. Conclusion: In this largest trial date CFTR modulator metabolism, led clinically meaningful benefits regulation statistically significant within-group decreases categorization.