Clinical trial NCT03540524: 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.
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cystic Fibrosis
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2018-05-30
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase Ib, multi-center, open-label, nonrandomized multiple cohorts study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of a combination treatment of GLPG2451 and GLPG2222, with and without GLPG2737, in adult subjects with Cystic Fibrosis.


Eligibility 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.

Primary outcomes:
measure: Number of subjects with adverse events.
timeFrame: Up to 24 weeks after the last dose
measure: Maximum observed plasma concentration (Cmax).
timeFrame: Day 14
measure: Maximum observed plasma concentration (Cmax).
timeFrame: Day 28
measure: Area under the plasma concentration-time curve from time zero until 24 hours (AUC0-24h).
timeFrame: Day 14
measure: Area under the plasma concentration-time curve from time zero until 24 hours (AUC0-24h).
timeFrame: Day 28
measure: Trough plasma concentration observed at the end of the dosing interval (24 hours post-dose) (Ctrough).
timeFrame: Between Day 2 and Day 28
measure: Change from baseline in sweat chloride concentration.
timeFrame: Between Day 1 pre-dose and Day 28
measure: Change from baseline in percent predicted FEV1.
timeFrame: Between Day 1 pre-dose and Day 28
Secondary outcomes:
measure: Change from baseline in sweat chloride concentration.
timeFrame: Between Day 1 pre-dose and Day 28
measure: Change from baseline in percent predicted FEV1.
timeFrame: Between Day 1 pre-dose and Day 28
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Study Site BEL004
city: Brussels
country: Belgium
facility: Study Site BEL003
city: Gent
country: Belgium
facility: Study Site BEL002
city: Leuven
country: Belgium
facility: Study Site BEL001
city: Sofia
country: Bulgaria
facility: Study Site BGR001
city: Berlin
country: Germany
facility: Study Site DEU001
city: Essen
country: Germany
facility: Study Site DEU002
city: Thessaloníki
country: Greece
facility: Study Site GRC001
city: Amsterdam
country: Netherlands
facility: Study Site NLD002
city: Utrecht
country: Netherlands
facility: Study Site NLD001
city: Belgrade
country: Serbia
facility: Study Site SRB001
city: Göteborg
country: Sweden
facility: Study Site SWE001
city: Stockholm
country: Sweden
facility: Study Site SWE002
city: Birmingham
country: United Kingdom
facility: Study Site GBR003
city: Glasgow
country: United Kingdom
facility: Study Site GBR004
city: Liverpool
country: United Kingdom
facility: Study Site GBR005
city: London
country: United Kingdom
facility: Study Site GBR007
city: Newcastle
country: United Kingdom
facility: Study Site GBR006
city: Papworth Everard
country: United Kingdom
facility: Study Site GBR001
city: Wythenshawe
country: United Kingdom
facility: Study Site GBR002
Study officials:
affiliation: Galapagos NV
name: Olivier Van de Steen, MD MBA
role: STUDY_DIRECTOR
References: