A Study to Evaluate Multiple Doses of GLPG2222 in Adult Subjects With Cystic Fibrosis

Phase 2

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: GLPG2222 50 mg; Drug: GLPG2222 100 mg; Drug: GLPG2222 400 mg; Drug: Placebo; Drug: GLPG2222 200 mg

• Registration Number: NCT03119649
• Lead Sponsor: Galapagos NV

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-03-18
• Study First Submitted: 2017-04-11
• Study First Submitted QC: 2017-04-17
• Study First Posted: 2017-04-18
• Primary Completion: 2017-10-19
• Study Completion: 2017-10-19
• Status Verified: 2018-10
• Results First Submitted: 2018-10-19
• Results First Submitted QC: 2018-10-19
• Last Update Submitted: 2018-10-19
• Results First Posted: 2018-11-16
• Last Update Posted: 2018-11-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A: GLPG2222 50 mg once daily (QD)	GLPG2222 50 mg	Participants received a single GLPG2222 50 mg tablet and two matching placebo tablets orally, QD for 29 days.
Cohort B: GLPG2222 400 mg QD	GLPG2222 400 mg	Participants received two GLPG2222 150 mg tablets and one GLPG2222 100 mg tablet orally, QD for 29 days.
Cohort A: GLPG2222 50 mg once daily (QD)	Placebo	Participants received a single GLPG2222 50 mg tablet and two matching placebo tablets orally, QD for 29 days.
Cohort B: GLPG2222 200 mg QD	Placebo	Participants received two GLPG2222 100 mg tablets and one matching placebo tablet orally, QD for 29 days.
Cohort B: GLPG2222 200 mg QD	GLPG2222 200 mg	Participants received two GLPG2222 100 mg tablets and one matching placebo tablet orally, QD for 29 days.
Cohort B: GLPG2222 400 mg QD	Placebo	Participants received two GLPG2222 150 mg tablets and one GLPG2222 100 mg tablet orally, QD for 29 days.
Cohort A: GLPG2222 100 mg QD	Placebo	Participants received a single GLPG2222 100 mg tablet and two matching placebo tablets orally, QD for 29 days.
Cohort A: GLPG2222 100 mg QD	GLPG2222 100 mg	Participants received a single GLPG2222 100 mg tablet and two matching placebo tablets orally, QD for 29 days.
Cohort A Placebo	Placebo	Participants received three matching placebo tablets, orally, QD for 29 days.
Cohort B Placebo	Placebo	Participants received three matching placebo tablets, orally, QD for 29 days.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events	First administration (Day 1) through Follow-up (Day 43)	Number of participants with any treatment-emergent adverse events (TEAEs) and serious or treatment-related TEAEs, as well as number of patients with TEAEs by worst intensity reported (mild, moderate, or severe).

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Sweat Chloride Concentration at Day 29	Prior to dosing on Days 1 and 29, or at early discontinuation	Two sweat collections, one from each arm, were obtained. Mean sweat chloride concentration was determined from both arms and measured as millimoles per liter (mmol/L). Baseline was defined as the predose value on Day 1 (or the last non-missing predose measurement).
Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222	Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29	Maximum concentration of GLPG2222 after multiple dosing (ng/ML), obtained directly from the observed concentration versus time data. All pharmacokinetic (PK) parameters were determined from Day 15; Day 29 data were determined if the participant was not available for full PK profiling on Day 15.
Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29	Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation	Percent predicted FEV1 for age, gender, and height was determined from standardized spirometry assessments and estimated using the 2012 Global Lungs Initiative equation. Baseline was defined as the last non-missing predose assessment on Day 1.
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	Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29	Area under the concentration-time curve from time 0 up to 24 hours following multiple dosing (ng.h/mL), calculated by linear up/log down trapezoidal summation. All PK parameters were determined from Day 15; Day 29 data were determined if the participant was not available for full PK profiling on Day 15.
Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h])	Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29	Time of occurrence of maximum concentration of GLPG2222 after multiple dosing (h), obtained directly from the observed concentration versus time data. All PK parameters were determined from Day 15; Day 29 data were determined if the participant was not available for full PK profiling on Day 15.
Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29	Prior to dosing on Days 1 and 29, or at early discontinuation	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. The respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), derived from Questions 40, 41, 42, 45, and 46 if at least 50% of the questions had non-missing data. The scale score ranged from 0-100; higher scores indicated fewer symptoms and better health-related quality of life with a negative change indicating a worsening of symptoms. A change of 4 is considered clinically relevant.
Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL)	Days 15 and 29 (predose)	Plasma concentration of GLPG2222 observed at pre-dose (ng/mL), obtained directly from the observed concentration versus time data. Ctrough was calculated using both Day 15 and Day 29 PK data.

Trial Locations

Locations (23)

University of Arkansas for medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Maine Medical Center; 🇺🇸 Portland, Maine, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

UZ Brussel; 🇧🇪 Brussels, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

Mother and child health institute of Serbia; 🇷🇸 Novi Beograd, Serbia

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitarii Plitecnic La Fe; 🇪🇸 Valencia, Spain

Papworth Hospital; 🇬🇧 Cambridge, United Kingdom

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

St James University Hospital; 🇬🇧 Leeds, United Kingdom

Southampton general Hospital; 🇬🇧 Southampton, United Kingdom

Child Health Research Unit at UAB; 🇺🇸 Chatom, Alabama, United States

Cystic Fibrosis Center of Chicago; 🇺🇸 Glenview, Illinois, United States

UZ Antwerpen; 🇧🇪 Antwerp, Belgium

AMC Amsterdam; 🇳🇱 Amsterdam, Netherlands

John Hopkins University School of Medicine; 🇺🇸 Baltimore, Maryland, United States

Haga Ziekenhuis; 🇳🇱 The Hague, Netherlands

UZ Gent; 🇧🇪 Ghent, Belgium

UMC Utrecht; 🇳🇱 Utrecht, Netherlands

Central Florida Pulmonary Group; 🇺🇸 Orlando, Florida, United States

Erasmus medisch centrum; 🇳🇱 Rotterdam, Netherlands