Cystic Fibrosis MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: GLPG3067
Product Code: G914167
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not applicable
Current Sponsor
Sponsors
Galapagos NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female subject =18 years of age - A confirmed clinical diagnosis of CF as documented in the subject’s medical records. - Eligible CFTR genotype (confirmed during screening period): Part I: homozygous for the F508del CFTR mutation Part II: heterozygous for the F508del CFTR mutation, i.e., a mutation on the second allele, which is non-responsive to potentiator. - Body mass index (BMI) =18 kg/m² during screening. - Stable concomitant medication for CF (including pulmonary CF, diabetes, pancreatic enzymes, as applicable) in the opinion of the investigator, for at least 4 weeks prior to the first IMP administration, and planned continuation of the same concomitant medication regimen for the duration of the study (including the follow-up visit). - Forced expiratory volume in 1 second (FEV1) =40% and =90% of predicted normal for age, sex and height (pre- or post-bronchodilator) during screening. - Sweat chloride concentration =60 mmol/L at screening. Reference is made to the protocol for a complete overview of the inclusion criteria. 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 140 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: - History of clinically meaningful unstable or uncontrolled chronic disease that makes the subject unsuitable for inclusion in the study in the opinion of the investigator. This includes CF pulmonary disease with frequent exacerbations and short periods of stability (e.g., 2 liter per minute while sleeping. - History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms of splenomegaly, esophageal varices). - Use of any moderate or strong inhibitor(s) or inducer(s) of cytochrome P450 (CYP) type 3A4 (CYP3A4) within 4 weeks prior to the first IMP administration (e.g., clarithromycin, itraconazole, ketoconazole, telithromycin, rifampin, carbamazepine) (see Appendix 2). - Use of CFTR modulator therapy (e.g., lumacaftor, tezacaftor and/or ivacaftor) within 4 weeks prior to the first IMP administration. - Abnormal liver function test during screening, defined as AST and/or ALT and/or alkaline phosphatase (ALP) and/or gamma-glutamyl transferase (GGT) =3x the upper limit of normal (ULN), and/or total bilirubin >1.5 times ULN. Reference is made to the protocol for a complete overview of the exclusion criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess changes in sweat chloride concentration as a biomarker of CFTR ion channel function for dual combination (GLPG3067 and GLPG2222) and triple combination (GLPG3067, GLPG2222, and GLPG2737) treatment, in adult CF subjects who are homozygous for CFTR mutation F508del, and in adult CF subjects who are heterozygous for CFTR mutation F508del (with a mutation on the second allele, which is non-responsive to potentiator).; Secondary Objective: - To assess changes in pulmonary function (ppFEV1) for dual combination (GLPG3067 and GLPG2222) and triple combination (GLPG3067, GLPG2222, and GLPG2737) treatment, in adult CF subjects who are homozygous for CFTR mutation F508del, and in adult CF subjects who are heterozygous for CFTR mutation F508del (with a mutation on the second allele, which is non-responsive to potentiator) - To assess safety and tolerability of dual combination (GLPG3067 and GLPG2222) and triple combination (GLPG3067, GLPG2222, and GLPG2737) treatment in adult CF subjects - To assess changes in the respiratory domain of the CFQ-R for dual combination (GLPG3067 and GLPG2222) and triple combination (GLPG3067, GLPG2222, and GLPG2737) treatment in adult CF subjects - To assess the PK of GLPG3067, GLPG2222, and GLPG2737 (including its active metabolite G1125498 [M4]), when administered in dual and triple combination. ;Primary end point(s): Absolute change from baseline (pre-morning dose on Day 1) in sweat chloride concentration, for the dual combination treatment (Day 15) and for each triple combination treatment (Days 29, 43, and 57).;Timepoint(s) of evaluation of this end point: Various timepoints during the trial as specified in the protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Various timepoints during the trial as specified in the protocol. ; Secondary end point(s): - Absolute change from baseline (pre-morning dose on Day 1) in ppFEV1 for the dual combination treatment (Day 15) and for each triple combination treatment (Days 29, 43, and 57). - Relative change from baseline (pre-morning dose on Day 1) in ppFEV1 for the dual combination treatment (Day 15) and for each triple combination treatment (Days 29, 43, and 57). - Safety and tolerability, assessed by the number of subjects with adverse events (AEs) and serious adverse events (SAEs) - Absolute change from baseline (pre-morning dose on Day 1) in the respiratory domain of the CFQ-R, for the dual combination treatment (Day 15) and for the triple combination treatment (Day 57) - Plasma concentrations of GLPG3067, GLPG2222, and GLPG2737 (including its active metabolite G1125498 [M4]). | — |
Countries
Australia, Belgium, Denmark, France, Germany, Ireland, Netherlands, New Zealand, Serbia, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Galapagos NV
Outcome results
None listed