TABLE 4

Study end-points

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).