A Study Looking at the Safety, Tolerability and Efficacy of the Combination of the Study Drugs GLPG2451 and GLPG2222 With or Without GLPG2737 in Patients With Cystic Fibrosis.

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03540524
• Date of registration: 27/04/2018
• Prospective Registration: Yes
• Primary sponsor: Galapagos NV
• Public title: A Study Looking at the Safety, Tolerability and Efficacy of the Combination of the Study Drugs GLPG2451 and GLPG2222 With or Without GLPG2737 in Patients With Cystic Fibrosis. FALCON
• Scientific title: Assessment of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Oral Doses of the Combination of GLPG2451 and GLPG2222, With or Without GLPG2737, in Adult Subjects With Cystic Fibrosis
• Date of first enrolment: May 31, 2018
• Target sample size: 10
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03540524
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Belgium, Bulgaria, Germany, Greece, Netherlands, Serbia, Sweden, United Kingdom

Contacts

• Name: Olivier Van de Steen, MD MBA
• Affiliation: Galapagos NV

Key inclusion & exclusion criteria

Inclusion Criteria:

- Female or male subject =18 years of age, on the day of signing the Informed Consent
Form (ICF)

- Confirmed clinical diagnosis of cystic fibrosis (CF) (documented in the subject's
medical record).

- Eligible cystic fibrosis transmembrane conductance regulator (CFTR) genotype at
screening:

- Cohort A: Homozygous for the F508del CFTR mutation

- Cohort B: Heterozygous for the F508del CFTR mutation with a potentiator
non-responsive mutation on the second allele

- Cohort C: Homozygous for the F508del CFTR mutation

- A body weight of =40 kg at screening.

- Stable concomitant medication for pulmonary health for CF for at least 4 weeks prior
to the first study drug administration and planned continuation of the same
concomitant medication for the duration of the dosing period of the study. Subjects
with diabetes mellitus and/or pancreatic insufficiency are eligible for the study
provided they are on stable treatment (e.g. medication, diet, pancreatic enzyme
replacement therapy) for at least 4 weeks prior to the first study drug administration
in the opinion of the investigator.

- Forced expiratory volume in 1 second (FEV1): 40% = FEV1 = 90% of predicted normal for
age, sex, and height at screening (pre- or post bronchodilator) at screening.

- Sweat chloride concentration =60 mmol/L at screening.

- Non-smoker and non-user of any nicotine and or cannabis containing products. A
non-smoker is defined as an individual who has abstained from smoking for at least 1
year prior to the screening. A non-user is defined as an individual who has abstained
from any nicotine containing products for at least 1 year prior to the screening.

Exclusion Criteria:

- History of or ongoing allergic bronchopulmonary aspergillosis.

- Medical history of cataract (or lens opacity) and/or glaucoma.

- Cataract (or lens opacity) and/or glaucoma determined by an ophthalmologist during the
screening period.

- 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 clinically meaningful unstable or uncontrolled chronic disease that makes
the subject unsuitable for inclusion in the study in the opinion of the investigator.

- Need for supplemental oxygen during the day, and >2 L/minute while sleeping.

- History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms of
splenomegaly, esophageal varices).

- History of malignancy within the past 5 years (except for basal cell carcinoma of the
skin with no evidence of recurrence and/or carcinoma in situ of the cervix that has
been treated with no evidence of recurrence).

- Use of any moderate and strong inhibitor(s) or inducer(s) of CYP3A4 within 4 weeks
prior to the first study drug administration (e.g., clarithromycin, itraconazole,
ketoconazole, telithromycin, rifampin, carbamazepine).

- Use of CFTR modulator therapy (e.g., lumacaftor and/or ivacaftor) within 4 weeks prior
to the first study drug administration.

- Use of any oral corticosteroid within 3 months of screening; or history of oral
corticosteroid use for =30 days (cumulative) within 2 years of screening.

- Abnormal liver function test at screening; defined as aspartate aminotransferase (AST)
and/or alanine aminotransferase (ALT) and/or alkaline phosphatase and/or
gamma-glutamyl transferase (GGT) =3× the upper limit of normal (ULN); and/or total
bilirubin =1.5× the ULN.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: GLPG2451 dose regimen B

Drug: GLPG2737

Drug: GLPG2222

Drug: GLPG2451 dose regimen A

Primary Outcome(s)

Change from baseline in percent predicted FEV1. [Time Frame: Between Day 1 pre-dose and Day 28]

Area under the plasma concentration-time curve from time zero until 24 hours (AUC0-24h). [Time Frame: Day 28]

Area under the plasma concentration-time curve from time zero until 24 hours (AUC0-24h). [Time Frame: Day 14]

Maximum observed plasma concentration (Cmax). [Time Frame: Day 14]

Maximum observed plasma concentration (Cmax). [Time Frame: Day 28]

Change from baseline in sweat chloride concentration. [Time Frame: Between Day 1 pre-dose and Day 28]

Number of subjects with adverse events. [Time Frame: Up to 24 weeks after the last dose]

Trough plasma concentration observed at the end of the dosing interval (24 hours post-dose) (Ctrough). [Time Frame: Between Day 2 and Day 28]

Secondary Outcome(s)

Change from baseline in percent predicted FEV1. [Time Frame: Between Day 1 pre-dose and Day 28]

Change from baseline in sweat chloride concentration. [Time Frame: Between Day 1 pre-dose and Day 28]

Secondary ID(s)

GLPG2737-CL-105

2017-001067-20

Source(s) of Monetary Support

Please refer to primary and secondary sponsors