Study of GLPG1837 in Subjects With Cystic Fibrosis (G551D Mutation)

Lakefront Biotherapeutics NV26 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cystic Fibrosis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (16)

Royal Adelaide Hospital

Adelaide, Australia

The Prince Charles Hospital

Chermside, Australia

Monash Medical Centre

Clayton, Australia

Sir Charles Gairdner Hospital

Nedlands, Australia

Mater Adult Hospital

South Brisbane, Australia

Fakultni nemocnice v Motole

Prague, Czechia

Charité Universitätsmedizin Berlin

Berlin, Germany

Universitätsklinkikum Koeln

Cologne, Germany

Uniklinik Carl-Gustav-Carus

Dresden, Germany

Lungenheilkunde München-Pasing

München, Germany

...and 6 more locations

Outcomes

Primary Outcomes

Changes in adverse events

To evaluate the safety and tolerability of GLPG1837 in terms of adverse events at every visit

Time frame: Up to 9 weeks

Changes in laboratory parameters

To evaluate the safety and tolerability of GLPG1837 in terms of abnormal laboratory parameters at every visit

Time frame: Up to 7 weeks

Changes in vital signs - composite outcome measure

To evaluate the safety and tolerability of GLPG1837 in terms of abnormal vital signs as measured by temperature, blood pressure, heart rate and respiratory rate, at every visit

Time frame: Up to 9 weeks

Changes in physical examination - composite outcome measure

To evaluate the safety and tolerability of GLPG1837 in terms of abnormalities during physical examination at every visit

Time frame: Up to 9 weeks

Changes in electrocardiogram

To evaluate the safety and tolerability of GLPG1837 in terms of abnormal electrocardiogram at every visit

Time frame: Up to 7 weeks

Secondary Outcomes

Changes in sweat chloride concentration

To evaluate the effect of GLPG1837 in terms of change in sweat chloride concentration, a biomarker to measure cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function at every visit

Time frame: Up to 9 weeks

Changes in pulmonary function (forced expiratory volume in 1 second, FEV1) assessed by spirometry

To explore the effect of GLPG1837 in terms of change in pulmonary function (forced expiratory volume in 1 second, FEV1) assessed by spirometry at every visit

Time frame: Up to 9 weeks

Plasma levels of GLPG1837: Cmax, the maximum observed plasma concentration

To characterize the pharmacokinetics (PK) of GLPG1837 by measuring the amount in plasma between Day 8 and Day 29 at every visit; On Day 29, an 8-hour profile will determine the Cmax, the maximum observed plasma concentration

Time frame: Up to 3 weeks

Plasma levels of GLPG1837: tmax, the time of occurrence of Cmax

To characterize the pharmacokinetics (PK) of GLPG1837 by measuring the amount in plasma between Day 8 and Day 29 at every visit; On Day 29, an 8-hour profile will determine the tmax, the time of occurrence of Cmax

Time frame: Up to 3 weeks

Plasma levels of GLPG1837: AUC, the area under the plasma concentration-time curve

To characterize the pharmacokinetics (PK) of GLPG1837 by measuring the amount in plasma between Day 8 and Day 29 at every visit; On Day 29, an 8-hour profile will determine the AUC, the area under the plasma concentration-time curve

Time frame: Up to 3 weeks