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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03119649
• Other study ID #: GLPG2222-CL-202
• Status: Completed
• Phase: Phase 2
• Start date: March 18, 2017
• Est. completion date: October 19, 2017

Study information

• Verified date: October 2018
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: October 19, 2017
• Est. primary completion date: October 19, 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 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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• GLPG2222 50 mg
Oral tablet(s) containing GLPG2222
• GLPG2222 100 mg
Oral tablet(s) containing GLPG2222
• Placebo
Matching oral tablet(s) containing placebo
• GLPG2222 200 mg
Oral tablet(s) containing GLPG2222
• GLPG2222 400 mg
Oral tablet(s) containing GLPG2222

Locations

Country	Name	City	State
Belgium	UZ Antwerpen	Antwerp
Belgium	UZ Brussel	Brussels
Belgium	UZ Gent	Ghent
Belgium	UZ Leuven	Leuven
Netherlands	AMC Amsterdam	Amsterdam
Netherlands	Erasmus medisch centrum	Rotterdam
Netherlands	Haga Ziekenhuis	The Hague
Netherlands	UMC Utrecht	Utrecht
Serbia	Mother and child health institute of Serbia	Novi Beograd
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitarii Plitecnic La Fe	Valencia
United Kingdom	Papworth Hospital	Cambridge
United Kingdom	St James University Hospital	Leeds
United Kingdom	Liverpool Heart and Chest Hospital	Liverpool
United Kingdom	Southampton general Hospital	Southampton
United States	John Hopkins University School of Medicine	Baltimore	Maryland
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Child Health Research Unit at UAB	Chatom	Alabama
United States	Cystic Fibrosis Center of Chicago	Glenview	Illinois
United States	University of Arkansas for medical Sciences	Little Rock	Arkansas
United States	Central Florida Pulmonary Group	Orlando	Florida
United States	Maine Medical Center	Portland	Maine

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Countries where clinical trial is conducted

United States,  Belgium,  Netherlands,  Serbia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events	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).	First administration (Day 1) through Follow-up (Day 43)
Secondary	Mean Change From Baseline in Sweat Chloride Concentration at Day 29	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).	Prior to dosing on Days 1 and 29, or at early discontinuation
Secondary	Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29	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.	Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation
Secondary	Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29	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.	Prior to dosing on Days 1 and 29, or at early discontinuation
Secondary	Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222	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.	Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Secondary	Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL)	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.	Days 15 and 29 (predose)
Secondary	Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h])	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.	Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Secondary	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	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.	Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29