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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03045523
• Other study ID #: GLPG2222-CL-201
• Status: Completed
• Phase: Phase 2
• First received: January 26, 2017
• Last updated: November 20, 2017
• Start date: January 2017
• Est. completion date: August 11, 2017

Study information

• Verified date: November 2017
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: August 11, 2017
• Est. primary completion date: August 11, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• GLPG2222 150 mg q.d.
GLPG2222 150 mg administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days
• GLPG2222 300 mg q.d.
GLPG2222 300 mg administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days
• Placebo
Placebo administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Chermside
Australia	The Alfred	Melbourne
Australia	Sir Charles Gairdner Hospital	Nedlands
Australia	Westmead Hospital	Westmead
Belgium	UZ Brussel	Brussels
Belgium	UZ Gent	Ghent
Belgium	UZ Leuven	Leuven
Czechia	Fakultni nemocnice v Motole	Praha
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	University Children´s Hospital	Tübingen
Ireland	Cork University Hospital	Cork
Ireland	Beaumont Hospital	Dublin
Ireland	St Vincents University Hospital	Dublin
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

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Countries where clinical trial is conducted

Australia,  Belgium,  Czechia,  Germany,  Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Change from baseline of Sweat chloride concentration		at screening and at each study visit up to day 43 which is the final FU visit
Secondary	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
Secondary	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