A Study to Evaluate GLPG2222 in Ivacaftor-treated Subjects With Cystic Fibrosis

Study Overview
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Brief Summary
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This clinical study is a phase IIa, multi-center, randomized, double-blind, placebo-controlled, parallel group study to evaluate two doses of orally administered GLPG2222 in adult subjects with a confirmed diagnosis of CF harbouring one F508del CFTR mutation and a second gating (class III) mutation and on stable treatment with ivacaftor. Up to 35 evaluable subjects are planned to be included in the study. Eligible subjects must be on stable treatment with physician prescribed ivacaftor (Kalydeco®) for at least 28 days at the baseline visit. They will be randomized in a 2:2:1 ratio to receive one of two active doses of GLPG2222 (150 mg q.d. or 300 mg q.d.) or placebo q.d. administered for 29 days. Subjects will be in the study for a minimum of 6 weeks and a maximum of 10 weeks, from screening until the follow-up visit.

Official Title
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A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate GLPG2222 in Ivacaftor-treated Subjects With Cystic Fibrosis Harbouring One F508del CFTR Mutation and a Second Gating (Class III) Mutation

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: GLPG2222 150 mg q.d.
* Drug: GLPG2222 300 mg q.d.
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject ≥ 18 years of age, on the day of signing the Informed Consent Form (ICF). A confirmed clinical diagnosis of CF. One F508del mutation on one allele in the CFTR gene, a gating (class III) mutation (one of the following: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R) on the 2nd allele in the CFTR gene (documented in the subject's medical record or CF registry). Weight ≥ 40 kg. Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline (including physician prescribed ivacaftor (Kalydeco®) 150 mg b.i.d.). Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening (pre- or postbronchodilator). Exclusion Criteria: 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. Unstable pulmonary status or respiratory tract infection (including rhinosinusitis) requiring a change in therapy within 4 weeks of baseline. Need for supplemental oxygen during the day, and >2 liters per minute (LPM) while sleeping. History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms of splenomegaly, esophageal varices, etc). Abnormal liver function test at screening; defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or alkaline phosphatase and/or total bilirubin (>1.5 times ULN (CTCAE Grade 2) and/or gamma-glutamyl transferase (GGT) ≥ 3x the upper limit of normal (ULN), and/or total bilirubin (>1.5 times ULN (CTCAE Grade 2). Estimated creatinine clearance < 60mL/min using the Cockroft-Gault formula at screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLPG2222 Dose 1<br> | Drug: GLPG2222 150 mg q.d.<br>* GLPG2222 150 mg administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days<br>|
| Experimental: GLPG2222 Dose 2<br> | Drug: GLPG2222 300 mg q.d.<br>* GLPG2222 300 mg administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days<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 GLPG2222 as compared to placebo in terms of adverse events | at screening and at each study visit up to day 43 which is the final FU visit | 
| Changes in abnormal laboratory | To evaluate the safety and tolerability of GLPG2222 as compared to placebo in terms of laboratory | at screening and at each study visit up to day 43 which is the final FU visit | 
| Changes in abnormal vital signs, ECG or physical examination | To evaluate the safety and tolerability of GLPG2222 as compared to placebo in terms of vital signs, ECG or physical examination | at screening and at each study visit up to day 43 which is the final FU visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of Sweat chloride concentration |  | at screening and at each study visit up to day 43 which is the final FU visit | 
| Change from baseline of FEV1 (L) and percent predicted FEV1 for age, gender and height as assessed by spirometry |  | at screening and at each study visit up to day 43 which is the final FU visit | 
| Change from baseline on the respiratory domain of Revised Cystic Fibrosis Questionnaire (CFQ-R) |  | at screening and at each study visit up to day 43 which is the final FU visit |