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

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ClinicalTrials.gov Identifier: NCT03119649
Recruitment Status : Completed
First Posted : April 18, 2017
Results First Posted : November 16, 2018
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: GLPG2222 50 mg Drug: GLPG2222 100 mg Drug: Placebo Drug: GLPG2222 200 mg Drug: GLPG2222 400 mg Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 18, 2017
Actual Primary Completion Date : October 19, 2017
Actual Study Completion Date : October 19, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: Cohort A: GLPG2222 50 mg once daily (QD)
Participants received a single GLPG2222 50 mg tablet and two matching placebo tablets orally, QD for 29 days.
Drug: GLPG2222 50 mg
Oral tablet(s) containing GLPG2222

Drug: Placebo
Matching oral tablet(s) containing placebo

Experimental: Cohort A: GLPG2222 100 mg QD
Participants received a single GLPG2222 100 mg tablet and two matching placebo tablets orally, QD for 29 days.
Drug: GLPG2222 100 mg
Oral tablet(s) containing GLPG2222

Drug: Placebo
Matching oral tablet(s) containing placebo

Experimental: Cohort B: GLPG2222 200 mg QD
Participants received two GLPG2222 100 mg tablets and one matching placebo tablet orally, QD for 29 days.
Drug: Placebo
Matching oral tablet(s) containing placebo

Drug: GLPG2222 200 mg
Oral tablet(s) containing GLPG2222

Experimental: Cohort B: GLPG2222 400 mg QD
Participants received two GLPG2222 150 mg tablets and one GLPG2222 100 mg tablet orally, QD for 29 days.
Drug: Placebo
Matching oral tablet(s) containing placebo

Drug: GLPG2222 400 mg
Oral tablet(s) containing GLPG2222

Placebo Comparator: Cohort A Placebo
Participants received three matching placebo tablets, orally, QD for 29 days.
Drug: Placebo
Matching oral tablet(s) containing placebo

Placebo Comparator: Cohort B Placebo
Participants received three matching placebo tablets, orally, QD for 29 days.
Drug: Placebo
Matching oral tablet(s) containing placebo




Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events [ Time Frame: 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 :
  1. Mean Change From Baseline in Sweat Chloride Concentration at Day 29 [ Time Frame: 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).

  2. Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29 [ Time Frame: 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.

  3. Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29 [ Time Frame: 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.

  4. Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222 [ Time Frame: 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.

  5. Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL) [ Time Frame: 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.

  6. Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h]) [ Time Frame: 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.

  7. 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 [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03119649


Locations
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United States, Alabama
Child Health Research Unit at UAB
Chatom, Alabama, United States, 35233
United States, Arkansas
University of Arkansas for medical Sciences
Little Rock, Arkansas, United States, 72205
United States, Florida
Central Florida Pulmonary Group
Orlando, Florida, United States, 32803
United States, Illinois
Cystic Fibrosis Center of Chicago
Glenview, Illinois, United States, 60026
United States, Maine
Maine Medical Center
Portland, Maine, United States, 04102
United States, Maryland
John Hopkins University School of Medicine
Baltimore, Maryland, United States, 21205
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Belgium
UZ Antwerpen
Antwerp, Belgium
UZ Brussel
Brussels, Belgium
UZ Gent
Ghent, Belgium
UZ Leuven
Leuven, Belgium
Netherlands
AMC Amsterdam
Amsterdam, Netherlands
Erasmus medisch centrum
Rotterdam, Netherlands
Haga Ziekenhuis
The Hague, Netherlands
UMC Utrecht
Utrecht, Netherlands
Serbia
Mother and child health institute of Serbia
Novi Beograd, Serbia
Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain
Hospital Universitario La Paz
Madrid, Spain
Hospital Universitarii Plitecnic La Fe
Valencia, Spain
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 Kingdom
Sponsors and Collaborators
Galapagos NV
Investigators
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Study Director: Olivier Van Steen, MD, MBA Galapagos NV
  Study Documents (Full-Text)

Documents provided by Galapagos NV:
Study Protocol  [PDF] December 6, 2016
Statistical Analysis Plan  [PDF] November 10, 2017


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Responsible Party: Galapagos NV
ClinicalTrials.gov Identifier: NCT03119649     History of Changes
Other Study ID Numbers: GLPG2222-CL-202
First Posted: April 18, 2017    Key Record Dates
Results First Posted: November 16, 2018
Last Update Posted: November 16, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases