A Phase IIb, 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)
- Conditions
- Cystic FibrosisTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- CTIS2022-500410-26-01
- Lead Sponsor
- niversity Medical Center Utrecht
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 52
Male or female subjects who have completed the HIT-CF Organoid Study and are =18 years of age on the date of informed consent, Confirmed diagnosis of CF as follows: Sweat chloride value of =60 mmol/L based on quantitative pilocarpine iontophoresis (at screening) OR 2-CF causing mutations AND o chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities, Clinically stable CF disease in the opinion of the investigator with no significant changes in health status within 28 days prior to Day 1, FEV1 =40% to =90% predicted according to the Global Lung Function Initiative (GLI), Body mass index (BMI) =16 kg/m2 and =30 kg/m2, Non-smoker and non-tobacco user for a minimum of 30 days prior to screening, and subject agrees not to smoke or use tobacco for the duration of the study, Selected by an unblinded coordinating team based on organoid response or random selection
Key exclusion criteria include: • Any CF patient meeting either of the following two criteria is defined as having a ‘common’ CFTR mutation(s): o At least one of the following mutations: F508del, G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, R117H, A455E, 3849+10kbC>T; OR o A combination of any two of the following mutations: any nonsense mutation, 1717-1G>A, 621+1G>T, 3120+1G>A, 1898+1G->A, CFTRdele2,3, and 2183AA->G, Subject is currently taking or has taken a CFTR modulator within 28 days prior to Day 1
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of DIR/POS/NES after 8 weeks compared to placebo in (a) CF patients with rare CFTR mutations and a high organoid response to DIR/POS/NES and (b) CF patients with rare CFTR mutations not pre-selected on organoid response.;Secondary Objective: To evaluate the safety and tolerability and efficacy of DIR/POS/NES in CF patients with rare CFTR mutations and to evaluate PK of DIR/POS/NES and their respective metabolites, when relevant.;Primary end point(s): The primary endpoint in both groups is the mean percent predicted forced expiratory volume in 1 second (ppFEV1) of measurements taken after 4, 6 and 8 weeks of treatment. Period baseline values will be corrected for in the analysis.
- Secondary Outcome Measures
Name Time Method Secondary end point(s):The average of the sweat chloride measurements taken after 4, 6 and 8 weeks of treatment;Secondary end point(s):The average of the body weight measurements taken after 4, 6 and 8 weeks of treatment;Secondary end point(s):The average of the Cystic Fibrosis Questionnaire Revised (CFQ R) respiratory domain measurements taken after 4, 6 and 8 weeks of treatment;Secondary end point(s):Safety and tolerability assessments based on treatment-emergent Adverse Events (AEs) and Serious Adverse events (SAEs), clinical laboratory tests (ie, haematology, serum chemistry, coagulation studies, and urinalysis), physical examinations, electrocardiography (ECG), and vital signs;Secondary end point(s):PK parameter estimates and metabolites of DIR/POS/NES derived from plasma