Clinical trial NCT02707562: Study of GLPG1837 in Subjects With Cystic Fibrosis (G551D Mutation)
Official title: A Phase IIa, Open-label Study of Multiple Doses of GLPG1837 in Subjects With Cystic Fibrosis and the G551D Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic fibrosis G551D mutation
GLPG1837
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2016-03-14
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 32 cystic fibrosis patients with the G551D mutation will be treated for 4 weeks, consisting of three consecutive treatment periods: two 1-week periods followed by one 2-week period, evaluating one dose of GLPG1837 each. After the treatment period, there is a 7-10 days follow-up period.

During the course of the study, subjects will be examined for any side effects that may occur (safety and tolerability).

Changes in sweat chloride will be assessed as biomarker from baseline onwards, and changes in pulmonary function (efficacy) will be explored throughout the study. The amount of GLPG1837 present in the blood (pharmacokinetics) will also be determined.


Eligibility criteria: Inclusion Criteria:

* Male or female subjects ≥ 18 years of age, with a confirmed diagnosis of cystic fibrosis
* Subjects with gating G551D CFTR mutation on at least one allele in the CFTR gene
* Subjects currently receiving treatment with ivacaftor on a stable regimen or not on a treatment regimen with ivacaftor, for at least 2 weeks prior to screening
* Weight ≥ 40.0 kg
* Subjects on stable concomitant treatment regimen for at least 4 weeks prior to baseline (excluding ivacaftor)
* Pre- or post-bronchodilator FEV1 ≥ 40% of predicted normal
* Subject will have to use highly effective contraceptive methods

Exclusion Criteria:

* On an ivacaftor-containing treatment regimen and unable or unwilling to discontinue ivacaftor for the washout and treatment periods of the study
* Concomitant use of antifungal drugs within 4 weeks of baseline
* A history of a clinically meaningful unstable or uncontrolled chronic disease
* Liver cirrhosis and portal hypertension
* Any significant change in the medical regimen for pulmonary health within 4 weeks of baseline
* Unstable pulmonary status or respiratory tract infection or changes in therapy for pulmonary disease within 4 weeks of baseline
* Abnormal liver function
* Clinically significant abnormalities on ECG
* History of malignancy, solid organ/haematological transplantation
* Abnormal renal function
* Participation in another experimental therapy study within 30 days or 5 times halflife

Primary outcomes:
measure: Changes in adverse events
timeFrame: Up to 9 weeks
measure: Changes in laboratory parameters
timeFrame: Up to 7 weeks
measure: Changes in vital signs - composite outcome measure
timeFrame: Up to 9 weeks
measure: Changes in physical examination - composite outcome measure
timeFrame: Up to 9 weeks
measure: Changes in electrocardiogram
timeFrame: Up to 7 weeks
Secondary outcomes:
measure: Changes in sweat chloride concentration
timeFrame: Up to 9 weeks
measure: Changes in pulmonary function (forced expiratory volume in 1 second, FEV1) assessed by spirometry
timeFrame: Up to 9 weeks
measure: Plasma levels of GLPG1837: Cmax, the maximum observed plasma concentration
timeFrame: Up to 3 weeks
measure: Plasma levels of GLPG1837: tmax, the time of occurrence of Cmax
timeFrame: Up to 3 weeks
measure: Plasma levels of GLPG1837: AUC, the area under the plasma concentration-time curve
timeFrame: Up to 3 weeks
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Chermside
country: Australia
facility: The Prince Charles Hospital
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
city: Praha 5
country: Czech Republic
facility: Fakultni nemocnice v Motole
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Cologne
country: Germany
facility: Universitätsklinkikum Koeln
city: Dresden
country: Germany
facility: Uniklinik Carl-Gustav-Carus
city: München
country: Germany
facility: Lungenheilkunde München-Pasing
city: Dublin
country: Ireland
facility: Beamont Hospital
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Manchester
country: United Kingdom
facility: The Medicines Evaluation Unit Ltd
Study officials:
affiliation: Galapagos NV
name: Olivier Van de Steen, MD, MBA
role: STUDY_DIRECTOR
References:
citation: Davies JC, Van de Steen O, van Koningsbruggen-Rietschel S, Drevinek P, Derichs N, McKone EF, Kanters D, Allamassey L, Namour F, de Kock H, Conrath K. GLPG1837, a CFTR potentiator, in p.Gly551Asp (G551D)-CF patients: An open-label, single-arm, phase 2a study (SAPHIRA1). J Cyst Fibros. 2019 Sep;18(5):693-699. doi: 10.1016/j.jcf.2019.05.006. Epub 2019 May 27.