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

Phase 2

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: GLPG2222 300 mg q.d.; Drug: Placebo; Drug: GLPG2222 150 mg q.d.

• Registration Number: NCT03045523
• Lead Sponsor: Galapagos NV

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01
• Study First Submitted: 2017-01-26
• Study First Submitted QC: 2017-02-03
• Study First Posted: 2017-02-07
• Primary Completion: 2017-08-11
• Study Completion: 2017-08-11
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-20
• Last Update Posted: 2017-11-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

1. Male or female subject ≥ 18 years of age, on the day of signing the Informed Consent Form (ICF).
2. A confirmed clinical diagnosis of CF.
3. 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).
4. Weight ≥ 40 kg.
5. Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline (including physician prescribed ivacaftor (Kalydeco®) 150 mg b.i.d.).
6. Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening (pre- or postbronchodilator).

Exclusion Criteria

1. 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.
2. Unstable pulmonary status or respiratory tract infection (including rhinosinusitis) requiring a change in therapy within 4 weeks of baseline.
3. Need for supplemental oxygen during the day, and >2 liters per minute (LPM) while sleeping.
4. History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms of splenomegaly, esophageal varices, etc).
5. 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).
6. Estimated creatinine clearance < 60mL/min using the Cockroft-Gault formula at screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GLPG2222 Dose 2	GLPG2222 300 mg q.d.	-
Placebo	Placebo	-
GLPG2222 Dose 1	GLPG2222 150 mg q.d.	-

Primary Outcome Measures

Name	Time	Method
Changes in adverse events	at screening and at each study visit up to day 43 which is the final FU visit	To evaluate the safety and tolerability of GLPG2222 as compared to placebo in terms of adverse events
Changes in abnormal laboratory	at screening and at each study visit up to day 43 which is the final FU visit	To evaluate the safety and tolerability of GLPG2222 as compared to placebo in terms of laboratory
Changes in abnormal vital signs, ECG or physical examination	at screening and at each study visit up to day 43 which is the final FU visit	To evaluate the safety and tolerability of GLPG2222 as compared to placebo in terms of vital signs, ECG or physical examination

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (22)

Westmead Hospital; 🇦🇺 Westmead, Australia

UZ Leuven; 🇧🇪 Leuven, Belgium

The Prince Charles Hospital; 🇦🇺 Chermside, Australia

The Alfred; 🇦🇺 Melbourne, Australia

Sir Charles Gairdner Hospital; 🇦🇺 Nedlands, Australia

UZ Brussel; 🇧🇪 Brussels, Belgium

UZ Gent; 🇧🇪 Ghent, Belgium

Universitaetsklinikum Carl Gustav Carus TU Dresden; 🇩🇪 Dresden, Germany

Universitätsklinikum Erlangen; 🇩🇪 Erlangen, Germany

Fakultni nemocnice v Motole; 🇨🇿 Praha, Czechia

University Children´s Hospital; 🇩🇪 Tübingen, Germany

Beaumont Hospital; 🇮🇪 Dublin, Ireland

Cork University Hospital; 🇮🇪 Cork, Ireland

Birmingham Heartlands; 🇬🇧 Birmingham, United Kingdom

Royal Devon and Exeter; 🇬🇧 Exeter, United Kingdom

St Vincents University Hospital; 🇮🇪 Dublin, Ireland

St James's University; 🇬🇧 Leeds, United Kingdom

Liverpool Heart and Chest Hospital; 🇬🇧 Liverpool, United Kingdom

University Hospital of South Manchester; 🇬🇧 Manchester, United Kingdom

Royal Victoria Infirmary; 🇬🇧 Newcastle, United Kingdom

Southampton General Hospital; 🇬🇧 Southampton, United Kingdom

Royal Brompton Hospital; 🇬🇧 London, United Kingdom