Clinical trial NCT03119649: A Study to Evaluate Multiple Doses of GLPG2222 in Adult Subjects With Cystic Fibrosis
Official title: A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate Multiple Doses of GLPG2222 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2017-04-18
Enrollment: 59
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 is a Phase IIa, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate 4 different doses of GLPG2222 administered for 4 weeks to adult subjects with a confirmed diagnosis of CF and homozygous for the F508del Cystic Fibrosis Transmembrane conductance Regulator (CFTR) mutation.


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 and homozygous for the F508del CFTR mutation
3. Weight ≥ 40 kg.
4. Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline
5. Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening

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 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. Use of CFTR modulator therapy (e.g. lumacaftor or ivacaftor) within 4 weeks prior to the first study drug administration.
5. History of hepatic cirrhosis with portal hypertension.
6. Abnormal liver function test at screening; defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/ or alkaline phosphatase and/or gamma-glutamyl transferase (GGT) ≥ 3x the upper limit of normal (ULN); and/or total bilirubin (\>1.5 times ULN)
7. Estimated creatinine clearance \< 60 mL/min using the Cockcroft-Gault formula at screening.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: First administration (Day 1) through Follow-up (Day 43)
Secondary outcomes:
measure: Mean Change From Baseline in Sweat Chloride Concentration at Day 29
timeFrame: Prior to dosing on Days 1 and 29, or at early discontinuation
measure: Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29
timeFrame: Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation
measure: Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29
timeFrame: Prior to dosing on Days 1 and 29, or at early discontinuation
measure: Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222
timeFrame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
measure: Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL)
timeFrame: Days 15 and 29 (predose)
measure: Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h])
timeFrame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
measure: Mean Area Under the Concentration-Time Curve From Time 0 up to 24 Hours Following Multiple Dosing (AUC[0-t]; ng.h/mL) of GLPG2222
timeFrame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Other outcomes:
Locations:
city: Chatom
country: United States
facility: Child Health Research Unit at UAB
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for medical Sciences
state: Arkansas
city: Orlando
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Glenview
country: United States
facility: Cystic Fibrosis Center of Chicago
state: Illinois
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: John Hopkins University School of Medicine
state: Maryland
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Antwerp
country: Belgium
facility: UZ Antwerpen
city: Brussels
country: Belgium
facility: UZ Brussel
city: Ghent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Amsterdam
country: Netherlands
facility: AMC Amsterdam
city: Rotterdam
country: Netherlands
facility: Erasmus medisch centrum
city: The Hague
country: Netherlands
facility: Haga Ziekenhuis
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Novi Beograd
country: Serbia
facility: Mother and child health institute of Serbia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Valencia
country: Spain
facility: Hospital Universitarii Plitecnic La Fe
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital
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: 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.