Randomised controlled studies: VX17-659-102, VX17-445-102, VX17-659-103 and VX17-445-103 |
Primary end-point |
F508del/MF genotypes (VX17-659-102 and VX17-445-102): absolute change in FEV1 % pred from baseline at week 4 (global protocol); through week 24 (European protocol) |
F508del/F508del genotype (VX17-659-103 and VX17-445-103): absolute change in FEV1 % pred from baseline at week 4 |
Key secondary end-points |
Absolute change in FEV1 % pred from baseline through week 24 (global protocol) and at week 4 (European protocol)# |
Number of pulmonary exacerbation events through week 24# |
Absolute change in sweat chloride concentration from baseline through week 24# |
Absolute change in CFQ-R respiratory domain score from baseline through week 24# |
Absolute change in BMI from baseline at week 24# |
Absolute change in sweat chloride concentration from baseline at week 4 |
Absolute change in CFQ-R respiratory domain score from baseline at week 4 |
Other secondary end-points |
Safety and tolerability based on AEs, clinical laboratory values, ECG findings, vital signs and pulse oximetry |
Pharmacokinetics parameters of VX-659 or VX-445, TEZ, M1-TEZ and IVA |
Time to first pulmonary exacerbation event through week 24# |
Absolute change in BMI z-score from baseline at week 24# |
Absolute change in body weight from baseline at week 24# |
Open-label extension studies: VX17-659-105 and VX17-445-105 |
Primary end-point |
Safety and tolerability based on AEs, clinical laboratory values, ECG findings, vital signs and pulse oximetry |
Secondary end-points |
Absolute change from baseline in FEV1 % pred |
Absolute change from baseline in sweat chloride concentration |
Number of pulmonary exacerbation events |
Time to first pulmonary exacerbation event |
Absolute change from baseline in BMI |
Absolute change from baseline in BMI z-score |
Absolute change from baseline in body weight |
Absolute change from baseline in CFQ-R respiratory domain score |
MF: minimal function; FEV1: forced expiratory volume in 1 s; CFQ-R: Cystic Fibrosis Questionnaire-Revised; BMI: body mass index; AE: adverse event; TEZ: tezacaftor; M1-TEZ: metabolite of tezacaftor; IVA: ivacaftor. #: patients with F508del/MF genotypes only (VX17-659-102 and VX17-445-102).