Clinical trial NCT03045523: A Study to Evaluate GLPG2222 in Ivacaftor-treated Subjects With Cystic Fibrosis
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2017-02-07
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Changes in adverse events
timeFrame: at screening and at each study visit up to day 43 which is the final FU visit
measure: Changes in abnormal laboratory
timeFrame: at screening and at each study visit up to day 43 which is the final FU visit
measure: Changes in abnormal vital signs, ECG or physical examination
timeFrame: at screening and at each study visit up to day 43 which is the final FU visit
Secondary outcomes:
measure: Change from baseline of Sweat chloride concentration
timeFrame: at screening and at each study visit up to day 43 which is the final FU visit
measure: Change from baseline of FEV1 (L) and percent predicted FEV1 for age, gender and height as assessed by spirometry
timeFrame: at screening and at each study visit up to day 43 which is the final FU visit
measure: Change from baseline on the respiratory domain of Revised Cystic Fibrosis Questionnaire (CFQ-R)
timeFrame: at screening and at each study visit up to day 43 which is the final FU visit
Other outcomes:
Locations:
city: Chermside
country: Australia
facility: The Prince Charles Hospital
city: Melbourne
country: Australia
facility: The Alfred
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Brussels
country: Belgium
facility: UZ Brussel
city: Ghent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Praha
country: Czechia
facility: Fakultni nemocnice v Motole
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Tübingen
country: Germany
facility: University Children´s Hospital
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: St Vincents University Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter
city: Leeds
country: United Kingdom
facility: St James's University
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Galapagos NV
name: Olivier Van Steen, MD, MBA
role: STUDY_DIRECTOR
References:
citation: Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
citation: Bell SC, Barry PJ, De Boeck K, Drevinek P, Elborn JS, Plant BJ, Minic P, Van Braeckel E, Verhulst S, Muller K, Kanters D, Bellaire S, de Kock H, Geller DE, Conrath K, Van de Steen O, van der Ent K. CFTR activity is enhanced by the novel corrector GLPG2222, given with and without ivacaftor in two randomized trials. J Cyst Fibros. 2019 Sep;18(5):700-707. doi: 10.1016/j.jcf.2019.04.014. Epub 2019 May 3.