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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

Tracking Information
First Submitted Date  ICMJE April 11, 2017
First Posted Date  ICMJE April 18, 2017
Results First Submitted Date  ICMJE October 19, 2018
Results First Posted Date  ICMJE November 16, 2018
Last Update Posted Date November 16, 2018
Actual Study Start Date  ICMJE March 18, 2017
Actual Primary Completion Date October 19, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2018)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: April 17, 2017)
Safety and tolerability assessments determined by number of subjects with adverse events [ Time Frame: from baseline up to day 43 (final FU visit) ]
To evaluate the safety and tolerability of GLPG2222 as compared to placebo in terms of adverse events
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2018)
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2017)
  • Change from baseline in Sweat chloride concentration [ Time Frame: from baseline up to day 29 ]
    To evaluate the effect of GLPG2222 on CFTR activity as compared to placebo
  • Absolute change from baseline of FEV1 (L) for age, gender and height as assessed by spirometry [ Time Frame: from baseline up to day 29 ]
    To evaluate the effect of GLPG2222 on respiratory symptoms as compared to placebo
  • Percent predicted FEV1 for age, gender and height as assessed by spirometry [ Time Frame: from baseline up to day 29 ]
    To evaluate the effect of GLPG2222 on respiratory symptoms as compared to placebo
  • Change from baseline on the respiratory domain of Revised Cystic Fibrosis Questionnaire (CFQ-R) [ Time Frame: from baseline up to day 29 ]
    To evaluate the effect of GLPG2222 on respiratory symptoms as compared to placebo
  • Cmax (maximum observed plasma concentration) of GLPG2222 [ Time Frame: pre-dose on day 15 and on day 29 ]
    To evaluate the PK of GLPG2222
  • Cthrough (plasma concentration observed at pre-dose) [ Time Frame: pre-dose on day 15 and on day 29 ]
    To evaluate PK of GLPG2222
  • tmax (time to the occurrence of Cmax) [ Time Frame: pre-dose on day 15 and on day 29 ]
    To evaluate PK of GLPG2222
  • AUC(t) (area under the plasma concentration-time curve over the dosing interval) [ Time Frame: pre-dose on day 15 and on day 29 ]
    To evaluate PK of GLPG2222
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Multiple Doses of GLPG2222 in Adult Subjects With Cystic Fibrosis
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • Drug: GLPG2222 50 mg
    Oral tablet(s) containing GLPG2222
  • Drug: GLPG2222 100 mg
    Oral tablet(s) containing GLPG2222
  • Drug: Placebo
    Matching oral tablet(s) containing placebo
  • Drug: GLPG2222 200 mg
    Oral tablet(s) containing GLPG2222
  • Drug: GLPG2222 400 mg
    Oral tablet(s) containing GLPG2222
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: GLPG2222 50 mg
    • Drug: 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.
    Interventions:
    • Drug: GLPG2222 100 mg
    • Drug: 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.
    Interventions:
    • Drug: Placebo
    • Drug: GLPG2222 200 mg
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: GLPG2222 400 mg
  • Placebo Comparator: Cohort A Placebo
    Participants received three matching placebo tablets, orally, QD for 29 days.
    Intervention: Drug: Placebo
  • Placebo Comparator: Cohort B Placebo
    Participants received three matching placebo tablets, orally, QD for 29 days.
    Intervention: Drug: Placebo
Publications * Bell SC, Barry PJ, De Boeck K, Drevinek P, Elborn JS, Plant BJ, Minić 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 17, 2017)
59
Original Estimated Enrollment  ICMJE
 (submitted: April 17, 2017)
50
Actual Study Completion Date  ICMJE October 19, 2017
Actual Primary Completion Date October 19, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Netherlands,   Serbia,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03119649
Other Study ID Numbers  ICMJE GLPG2222-CL-202
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Galapagos NV
Study Sponsor  ICMJE Galapagos NV
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Olivier Van Steen, MD, MBA Galapagos NV
PRS Account Galapagos NV
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP