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

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GLPG2222 50 mg
GLPG2222 100 mg
Placebo
GLPG2222 200 mg
GLPG2222 400 mg
Sponsored by
Galapagos NV
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Child Health Research Unit at UAB
  • University of Arkansas for medical Sciences
  • Central Florida Pulmonary Group
  • Cystic Fibrosis Center of Chicago
  • Maine Medical Center
  • John Hopkins University School of Medicine
  • Medical University of South Carolina
  • UZ Antwerpen
  • UZ Brussel
  • UZ Gent
  • UZ Leuven
  • AMC Amsterdam
  • Erasmus medisch centrum
  • Haga Ziekenhuis
  • UMC Utrecht
  • Mother and child health institute of Serbia
  • Hospital Universitari Vall d'Hebron
  • Hospital Universitario La Paz
  • Hospital Universitarii Plitecnic La Fe
  • Papworth Hospital
  • St James University Hospital
  • Liverpool Heart and Chest Hospital
  • Southampton general Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

Cohort A: GLPG2222 50 mg once daily (QD)

Cohort A: GLPG2222 100 mg QD

Cohort B: GLPG2222 200 mg QD

Cohort B: GLPG2222 400 mg QD

Cohort A Placebo

Cohort B Placebo

Arm Description

Participants received a single GLPG2222 50 mg tablet and two matching placebo tablets orally, QD for 29 days.

Participants received a single GLPG2222 100 mg tablet and two matching placebo tablets orally, QD for 29 days.

Participants received two GLPG2222 100 mg tablets and one matching placebo tablet orally, QD for 29 days.

Participants received two GLPG2222 150 mg tablets and one GLPG2222 100 mg tablet orally, QD for 29 days.

Participants received three matching placebo tablets, orally, QD for 29 days.

Participants received three matching placebo tablets, orally, QD for 29 days.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).
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.
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.
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.
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.
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.
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.

Full Information

First Posted
April 11, 2017
Last Updated
October 19, 2018
Sponsor
Galapagos NV
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1. Study Identification

Unique Protocol Identification Number
NCT03119649
Brief Title
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

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
March 18, 2017 (Actual)
Primary Completion Date
October 19, 2017 (Actual)
Study Completion Date
October 19, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Galapagos NV

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
59 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort A: GLPG2222 50 mg once daily (QD)
Arm Type
Experimental
Arm Description
Participants received a single GLPG2222 50 mg tablet and two matching placebo tablets orally, QD for 29 days.
Arm Title
Cohort A: GLPG2222 100 mg QD
Arm Type
Experimental
Arm Description
Participants received a single GLPG2222 100 mg tablet and two matching placebo tablets orally, QD for 29 days.
Arm Title
Cohort B: GLPG2222 200 mg QD
Arm Type
Experimental
Arm Description
Participants received two GLPG2222 100 mg tablets and one matching placebo tablet orally, QD for 29 days.
Arm Title
Cohort B: GLPG2222 400 mg QD
Arm Type
Experimental
Arm Description
Participants received two GLPG2222 150 mg tablets and one GLPG2222 100 mg tablet orally, QD for 29 days.
Arm Title
Cohort A Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received three matching placebo tablets, orally, QD for 29 days.
Arm Title
Cohort B Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received three matching placebo tablets, orally, QD for 29 days.
Intervention Type
Drug
Intervention Name(s)
GLPG2222 50 mg
Intervention Description
Oral tablet(s) containing GLPG2222
Intervention Type
Drug
Intervention Name(s)
GLPG2222 100 mg
Intervention Description
Oral tablet(s) containing GLPG2222
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching oral tablet(s) containing placebo
Intervention Type
Drug
Intervention Name(s)
GLPG2222 200 mg
Intervention Description
Oral tablet(s) containing GLPG2222
Intervention Type
Drug
Intervention Name(s)
GLPG2222 400 mg
Intervention Description
Oral tablet(s) containing GLPG2222
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events
Description
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).
Time Frame
First administration (Day 1) through Follow-up (Day 43)
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in Sweat Chloride Concentration at Day 29
Description
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).
Time Frame
Prior to dosing on Days 1 and 29, or at early discontinuation
Title
Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29
Description
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.
Time Frame
Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation
Title
Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29
Description
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.
Time Frame
Prior to dosing on Days 1 and 29, or at early discontinuation
Title
Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222
Description
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.
Time Frame
Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Title
Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL)
Description
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.
Time Frame
Days 15 and 29 (predose)
Title
Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h])
Description
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.
Time Frame
Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Title
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
Description
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.
Time Frame
Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subject ≥ 18 years of age, on the day of signing the Informed Consent Form (ICF). A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation Weight ≥ 40 kg. Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening Exclusion Criteria: 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. Unstable pulmonary status or respiratory tract infection requiring a change in therapy within 4 weeks of baseline. Need for supplemental oxygen during the day, and >2 liters per minute (LPM) while sleeping. Use of CFTR modulator therapy (e.g. lumacaftor or ivacaftor) within 4 weeks prior to the first study drug administration. History of hepatic cirrhosis with portal hypertension. 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) Estimated creatinine clearance < 60 mL/min using the Cockcroft-Gault formula at screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Van Steen, MD, MBA
Organizational Affiliation
Galapagos NV
Official's Role
Study Director
Facility Information:
Facility Name
Child Health Research Unit at UAB
City
Chatom
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of Arkansas for medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Central Florida Pulmonary Group
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Cystic Fibrosis Center of Chicago
City
Glenview
State/Province
Illinois
ZIP/Postal Code
60026
Country
United States
Facility Name
Maine Medical Center
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
John Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
UZ Antwerpen
City
Antwerp
Country
Belgium
Facility Name
UZ Brussel
City
Brussels
Country
Belgium
Facility Name
UZ Gent
City
Ghent
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
Country
Belgium
Facility Name
AMC Amsterdam
City
Amsterdam
Country
Netherlands
Facility Name
Erasmus medisch centrum
City
Rotterdam
Country
Netherlands
Facility Name
Haga Ziekenhuis
City
The Hague
Country
Netherlands
Facility Name
UMC Utrecht
City
Utrecht
Country
Netherlands
Facility Name
Mother and child health institute of Serbia
City
Novi Beograd
Country
Serbia
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
Country
Spain
Facility Name
Hospital Universitarii Plitecnic La Fe
City
Valencia
Country
Spain
Facility Name
Papworth Hospital
City
Cambridge
Country
United Kingdom
Facility Name
St James University Hospital
City
Leeds
Country
United Kingdom
Facility Name
Liverpool Heart and Chest Hospital
City
Liverpool
Country
United Kingdom
Facility Name
Southampton general Hospital
City
Southampton
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
31056441
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.
Results Reference
derived

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

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