CHOICES
Research type
Research Study
Full title
A Phase III, Multicentre, Randomised, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy and Safety of Dirocaftor/Posenacaftor/Nesolicaftor in Subjects with Cystic Fibrosis Aged 18 Years or Older (CHOICES)
IRAS ID
1005882
Contact name
Kors van der Ent
Contact email
Sponsor organisation
University Medical Center Utrecht
Eudract number
2022-500410-26
Research summary
CHOICES consists of two randomised, double-blind, placebo-controlled, cross-over trials with a 16-week extension. The trials are identical in design, but enrol a different population: For both trials, the study population is comprised of subjects with a diagnosis of CF who are ≥18 years of age (at the time of informed consent) and have completed organoid screening (conducted by the HIT-CF consortium; HIT-CF Organoid Study [NTR7520]) prior to screening for this study. The study population of the HIT-CF Organoid Study consisted of patients with the highest organoid response to the combination of DIR/POS/NES, whereas for the second trial no such pre-selection is performed (i.e., a simple random sample is drawn instead). This approach allows for independent evaluation of the treatment effect in both populations, as well as for exploratory assessment of a possible difference in treatment effects. An unblinded coordinating team will be responsible for subject selection based on a subject’s organoid response (52 participants in total).\n\nActive and placebo study drugs will be supplied as capsules for oral administration. \nDirocaftor, posenacaftor and nesolicaftor is given as a triple therapy with the following dosing 300mg/dayg, 600mg/day and 10mg/day, respectively. \n \nEligible subjects will be randomised at a 1:1 randomisation ratio into one of 2 treatment sequences: Either DIR/POS/NES once daily for 8 weeks followed by placebo once daily for 8 weeks plus 16 weeks, or placebo once daily for 8 weeks followed by DIR/POS/NES once daily for 8 weeks plus 16 weeks. Subjects will visit the study site several times during each treatment period for a total of 12 times.\nBlood, sweat and urine samples will be collected at screening, TP1, TP2, TP3 and the follow-up visit. A single 12-lead electrocardiogram (ECG) and pulmonary tests will be completed prior to collection of blood samples. The CFQ R and Q-Life scores will be completed during each visit.
REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
22/EM/0192
Date of REC Opinion
16 Nov 2022
REC opinion
Further Information Favourable Opinion