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

• Sponsor: Galapagos NV
• Information provided by (Responsible Party): Galapagos NV

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: GLPG2222 150 mg q.d.; Drug: GLPG2222 300 mg q.d.; Drug: Placebo	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	37 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	January 2017
Actual Primary Completion Date :	August 11, 2017
Actual Study Completion Date :	August 11, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: GLPG2222 Dose 1	Drug: GLPG2222 150 mg q.d.; GLPG2222 150 mg administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days
Experimental: GLPG2222 Dose 2	Drug: GLPG2222 300 mg q.d.; GLPG2222 300 mg administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days
Placebo Comparator: Placebo	Drug: Placebo; Placebo administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days

Outcome Measures

Primary Outcome Measures :

1. Changes in adverse events [ Time Frame: 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
2. Changes in abnormal laboratory [ Time Frame: 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
3. Changes in abnormal vital signs, ECG or physical examination [ Time Frame: 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 :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 99 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Locations

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Australia
The Prince Charles Hospital
Chermside, Australia
The Alfred
Melbourne, Australia
Sir Charles Gairdner Hospital
Nedlands, Australia
Westmead Hospital
Westmead, Australia
Belgium
UZ Brussel
Brussels, Belgium
UZ Gent
Ghent, Belgium
UZ Leuven
Leuven, Belgium
Czechia
Fakultni nemocnice v Motole
Praha, Czechia
Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
Dresden, Germany
Universitätsklinikum Erlangen
Erlangen, Germany
University Children´s Hospital
Tübingen, Germany
Ireland
Cork University Hospital
Cork, Ireland
Beaumont Hospital
Dublin, Ireland
St Vincents University Hospital
Dublin, Ireland
United Kingdom
Birmingham Heartlands
Birmingham, United Kingdom
Royal Devon and Exeter
Exeter, United Kingdom
St James's University
Leeds, United Kingdom
Liverpool Heart and Chest Hospital
Liverpool, United Kingdom
Royal Brompton Hospital
London, United Kingdom
University Hospital of South Manchester
Manchester, United Kingdom
Royal Victoria Infirmary
Newcastle, United Kingdom
Southampton General Hospital
Southampton, United Kingdom

Sponsors and Collaborators

Galapagos NV

Investigators

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Study Director:	Olivier Van Steen, MD, MBA	Galapagos NV

More Information

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Responsible Party:	Galapagos NV
ClinicalTrials.gov Identifier:	NCT03045523 History of Changes
Other Study ID Numbers:	GLPG2222-CL-201
First Posted:	February 7, 2017
Last Update Posted:	November 21, 2017
Last Verified:	November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Additional relevant MeSH terms:

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Fibrosis; Cystic Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases	Genetic Diseases, Inborn; Infant, Newborn, Diseases; Ivacaftor; Chloride Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action