Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate GLPG2737 in Orkambi-treated Subjects With Cystic Fibrosis Homozygous for the F508del Mutation
Brief Summary: 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.


Options:
A: Inclusion Criteria:

* Confirmed diagnosis of CF with ∆F508-CFTR mutation in both alleles
* Forced expiratory volume in 1 second (FEV1) greater than or equal to (\>=) 40 percent (%) of predicted normal for age, gender, and height
* Weight \>=40 kilograms (kg) and body mass index greater than or equal to 18.5 kilogram per square meter (kg/m\^2)
* Screening laboratory values, tests, and physical examination within acceptable ranges
* Negative pregnancy test (for women of child-bearing potential)
* Able and willing to follow contraceptive requirements
* Willing to remain on a stable medication regimen for the duration of study participation

Exclusion Criteria:

* History of any illness, or any ongoing acute illness, that could impact the safety of the study participant or may confound results of study
* Pulmonary exacerbation or changes in therapy for pulmonary disease within 14 days before receiving the first dose of study drug
* Impaired hepatic or renal function
* History of organ or hematological transplant
B: Inclusion Criteria:

* Homozygous for the F508del CFTR mutation, genotype to be confirmed at the Screening Visit
* Confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis
* Forced expiratory volume at one second (FEV1) ≥40% and ≤90% of predicted normal for age, sex, and height during screening
* Stable CF disease as judged by the investigator
* Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit

Exclusion Criteria:

* History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant.
* An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug)
* Pregnant or nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Day 1)
* Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
C: Inclusion Criteria:

* Signed informed consent available before any study specific tests or procedures are performed
* Patients must be at least 18 years of age at time of inclusion (i.e. upon signature of informed consent)
* Patient diagnosed with Cystic Fibrosis according to standard criteria (i.e. either elevated sweat chloride content above 60 mmol/ L and/ or genetic testing)
* Patient is homozygous for the deltaF508 mutation
* Patient has a mild-to-moderate stage of lung disease as determined by FEV1 (FEV1 between 40 and 100% predicted)
* Patient has a stable condition of lung disease (no ongoing or recent pulmonary exacerbation and no change in current treatment) within the last 4 weeks prior to screening
* Ability and willingness to understand and follow study procedures for the entire study
* Patients do not smoke. Patients with a history of smoking can be included, if they have refrained from smoking for the last 3 months. If a patients starts smoking during the study participation, he/ she needs to be excluded and considered to be a drop out
* Body mass index (BMI): ≥ 16 kg/ m² (calculated by dividing the patient's weight by the square of his/ her height \[kg/ m2\])

Inclusion criterion valid for study part 1 only:

- Women of childbearing potential must agree to use adequate contraception when sexually active. 'Adequate contraception' is defined as one highly effective form of contraception (intrauterine devices \[IUD\], contraceptive implants or tubal sterilization) or a combination of methods (hormone method with a barrier method ). If a partner's vasectomy is the chosen method of contraception or if a partner has documented azoospermia, a hormone or barrier method must be used in combination. Adequate contraception is required from the signing of the informed consent form up until 4 weeks after the last study drug administration

Inclusion criteria valid for study part 2 only:

* Women of childbearing potential must agree to use adequate contraception when sexually active. 'Adequate contraception' is defined as one highly effective form of contraception (intrauterine devices \[IUD\], contraceptive implants or tubal sterilization) or a combination of methods (hormone method with a barrier method). For patients on Orkambi hormonal methods (including hormonal oral contraceptives) cannot be accepted in this study. They need to choose non-hormonal methods. If a partner's vasectomy is the chosen method of contraception or if a partner has documented azoospermia, a hormone or barrier method must be used in combination. Adequate contraception is required from the signing of the informed consent form up until 4 weeks after the last study drug administration
* Patients receiving Orkambi (Lumcaftor + Ivacaftor) as part of their standard care need to be on stable Orkambi treatment for at least 3 months prior to screening (patients on Lumacaftor and/or Ivacaftor are excluded in part 1)

Exclusion Criteria:

* Patients with Cystic Fibrosis with any background other than homozygous deltaF508 mutation
* Exclusion criterion only valid for study part 1: Patients receiving treatment with Lumacaftor and/ or Ivacaftor
* Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization. Also any history of moderate hemoptysis within the 3 months prior to inclusion
* Any history of pneumothorax, bronchial artery embolization or massive hemoptysis. Massive hemoptysis being defined as acute bleeding \>240 mL in a 24-hour period or recurrent bleeding \>100 mL/ d over several days
* A positive sputum culture for Burkholderia cenocepacia, Burkholderia dolosa, and/ or Mycobacterium abscessus either currently or within the previous year
* Active allergic broncho-pulmonary aspergillosis
* Current pulmonary exacerbation
* Known history of solid organ transplantation
* Known history of any form of pulmonary hypertension
* Clinically relevant deviations of the screened laboratory parameters from reference ranges outside of expected changes for Cystic Fibrosis patients, especially a hemoglobin value below 110 g/L or a creatinine clearance based on the Cockcroft-Gault formula \< 15 ml/ min
D: 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.

Answer: D