Study of GLPG1837 in Subjects With Cystic Fibrosis (S1251N Mutation)

Study Overview
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Brief Summary
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At least 6 cystic fibrosis patients with the S1251N mutation will be treated for 4 weeks, consisting of two consecutive treatment periods of two weeks 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 Two Doses of GLPG1837 in Subjects With Cystic Fibrosis and the S1251N Mutation

Conditions
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Cystic Fibrosis

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


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 S1251N 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 half-life

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 and GLPG1837 dose 2<br>GLPG1837 twice daily oral dosing - morning and evening, for 4 weeks | Drug: GLPG1837 dose 1<br>* one GLPG1837 tablet in the morning and one GLPG1837 tablet in the evening, for 2 weeks<br>Drug: GLPG1837 dose 2<br>* one GLPG1837 tablet in the morning and one GLPG1837 tablet in the evening, for 2 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 | To evaluate the safety and tolerability of GLPG1837 in terms of abnormal vital signs at every visit | Up to 9 weeks | 
| Changes in physical examination | To evaluate the safety and tolerability of GLPG1837 in terms of abnormal 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 | To characterize the pharmacokinetics (PK) of GLPG1837 by measuring the amount in plasma between Day 1 and Day 29 at every visit | Up to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic fibrosis S1251N mutation, GLPG1837