A phase IIa, randomized, double-blind, placebo-controlled study to evaluate GLPG2222 in ivacaftor-treated subjects with Cystic Fibrosis harbouring one F508del CFTR mutation and a second gating (class III) mutation

INTERVENTION: Product Name: GLPG2222 Product Code: G957389 Pharmaceutical Form: Oral suspension INN or Proposed INN: Not Applicable Current Sponsor code: G957389 Other descriptive name: GLPG2222 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Oral suspension Route of administration of the placebo: Oral use Product Name: GLPG2222 Product Code: G957389 Pharmaceutical Form: Oral suspension INN or Proposed INN: Not Applicable Current Sponsor code: G957389 Other descriptive name: GLPG2222 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Oral suspension Route of administration of the placebo: Oral use CONDITION: Cystic Fibrosis ; MedDRA version: 19.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 ‐ Congenital, familial and genetic disorders Therapeutic area: Body processes [G] ‐ Genetic Phenomena [G05] PRIMARY OUTCOME: Main Objective: To evaluate the safety and tolerability of two doses of orally administered GLPG2222 in ivacaftor‐treated adult subjects with CF harbouring one F508del CFTR mutation and a second gating (class III) mutation Primary end point(s): Safety and tolerability will be assessed through:; Adverse events (AEs); Oxygen saturation by pulse oximetry; Physical examinations; Vital signs ; 12‐lead ECG; Spirometry; Safety laboratory assessments Secondary Objective: •To assess changes in sweat chloride as biomarker of CFTR ion channel function; •To assess changes in pulmonary function (FEV1); •To assess changes in Cystic Fibrosis Questionnaire – Revised (CFQ‐R); ; ; Timepoint(s) of evaluation of this end point: Various time points throughout the trial as specified in the protocol SECONDARY OUTCOME: Secondary end point(s): Efficacy will be assessed through: ; sweat Chloride Concentration Testing ; Spirometry ; Cystic Fibrosis Questionnaire – Revised (CFQ‐R) Timepoint(s) of evaluation of this end point: Various time points throughout the trial as specified in the protocol INCLUSION CRITERIA: 1.Male or female subject = 18 years of age, on the day of signing the Informed Consent Form (ICF). 2.A confirmed clinical diagnosis of CF. 3.One F508del mutation on one allele in the CFTR gene, a gating (class III) mutation (one of the following: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R) on the 2nd allele in the CFTR gene (documented in the subject’s medical record or CF registry). 4.Weight = 40 kg. 5.Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline (including physician prescribed ivacaftor (Kalydeco®) 150 mg b.i.d.). 6.Forced expiratory volume in 1 second (FEV1) = 40% of predicted normal for age, gender and height at screening (pre‐ or post‐bronchodilator). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 34 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of sub