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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase IIa, Open-label Study of Multiple Doses of GLPG1837 in Subjects With Cystic Fibrosis and the G551D Mutation

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: GLPG1837 dose 1
* Drug: GLPG1837 dose 2
* Drug: GLPG1837 dose 3


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLPG1837 dose 1, GLPG1837 dose 2, GLPG1837 dose 3<br>GLPG1837 twice daily oral dosing - morning and evening, for 4 weeks | Drug: GLPG1837 dose 1<br>* two GLPG1837 tablets in the morning and two GLPG1837 tablets in the evening, for one week<br>Drug: GLPG1837 dose 2<br>* two GLPG1837 tablets in the morning and two GLPG1837 tablets in the evening, for one week<br>Drug: GLPG1837 dose 3<br>* two GLPG1837 tablets in the morning and two GLPG1837 tablets in the evening, for two weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in adverse events | To evaluate the safety and tolerability of GLPG1837 in terms of adverse events at every visit | 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 | 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 | 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 | Up to 9 weeks | 
| Changes in electrocardiogram | To evaluate the safety and tolerability of GLPG1837 in terms of abnormal electrocardiogram at every visit | Up to 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 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 | 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 | 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 | Up to 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic fibrosis G551D mutation, GLPG1837