This is a Phase IIa, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate GLPG2737 administered orally b.i.d. for 28 days to adult male and female subjects with a confirmed diagnosis of cystic fibrosis homozygous for the F508del CFTR mutation and on stable treatment with Orkambi.

Inclusion Criteria:

• Male or female subject ≥18 years of age on the day of signing the ICF.
• A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation.
• Stable intake of physician prescribed Orkambi (lumacaftor 400 mg/ivacaftor 250 mg b.i.d.) for at least 12 weeks prior to the first study drug administration, and planned continuation of Orkambi for the duration of the study.
• FEV1 ≥40% of predicted normal for age, gender and height at screening (pre- or postbronchodilator).
• Sweat chloride concentration ≥60 mmol/L at screening.

Exclusion Criteria:

• History of serious allergic reaction to any drug as determined by the investigator (e.g., anaphylaxis requiring hospitalization) and/or known sensitivity to any component of the study drug.
• 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.
• Unstable pulmonary status or respiratory tract infection (including rhinosinusitis) requiring a change in therapy within 4 weeks prior to the first study drug administration.
• History of hepatic cirrhosis with portal hypertension (e.g.,signs/symptoms of splenomegaly, esophageal varices, etc.).
• Abnormal liver function test at screening, defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or alkaline phosphatase and/or gammaglutamyl transferase (GGT) ≥3 x the upper limit of normal (ULN), and/or total bilirubin ≥1.5 x the ULN at screening.