Back to resultsGLPG2737 on Top of Orkambi in Subjects With Cystic Fibrosis (PELICAN)
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
GLPG2737
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis
Eligibility Criteria
Inclusion Criteria:
- Male or female subject ≥18 years of age on the day of signing the ICF.
- A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation.
- Stable intake of physician prescribed Orkambi (lumacaftor 400 mg/ivacaftor 250 mg b.i.d.) for at least 12 weeks prior to the first study drug administration, and planned continuation of Orkambi for the duration of the study.
- FEV1 ≥40% of predicted normal for age, gender and height at screening (pre- or postbronchodilator).
- Sweat chloride concentration ≥60 mmol/L at screening.
Exclusion Criteria:
- History of serious allergic reaction to any drug as determined by the investigator (e.g., anaphylaxis requiring hospitalization) and/or known sensitivity to any component of the study drug.
- 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 (including rhinosinusitis) requiring a change in therapy within 4 weeks prior to the first study drug administration.
- History of hepatic cirrhosis with portal hypertension (e.g.,signs/symptoms of splenomegaly, esophageal varices, etc.).
- Abnormal liver function test at screening, defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or alkaline phosphatase and/or gammaglutamyl transferase (GGT) ≥3 x the upper limit of normal (ULN), and/or total bilirubin ≥1.5 x the ULN at screening.
Sites / Locations
- Study Site II
- Study Site X
- Study Site III
- Study Site IV
- Study Site I
- Study Site V
- Study Site VI
- Study Site IX
- Study Site VIII
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
GLPG2737
Placebo
Arm Description
GLPG2737 will be provided as capsules for oral use.
Placebo will be provided as capsules for oral use.
Outcomes
Primary Outcome Measures
Change from baseline in sweat chloride concentration compared to placebo
To assess Change from baseline in sweat chloride concentration compared to placebo.
Secondary Outcome Measures
Change versus placebo in the proportion of subjects with adverse events.
To assess safety and tolerability by the number and percentage of subjects with adverse events.
Change from baseline in sweat chloride concentration.
To assess the change from baseline in sweat chloride concentration.
Change in percent predicted forced expiratory volume in 1 second (FEV1).
To assess the change from baseline in percent predicted forced expiratory volume in 1 second (FEV1).
Change in the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R).
To assess the change from baseline in the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R).
Maximum observed plasma concentration of GLPG2737 (Cmax)
To characterize the PK of GLPG2737 and its active metabolite, ivacaftor, and lumacaftor.
Area under the plasma concentration-time curve from time zero until 8 hours (AUC0-8h) post-dose calculated by the linear up - logarithmic down trapezoidal rule (on Day 14)
To characterize the PK of GLPG2737 and its active metabolite G1125498 (M4), ivacaftor, and lumacaftor.
Trough plasma concentration observed at the end of the dosing interval (Ctrough).
To characterize the PK of GLPG2737 and its active metabolite G1125498 (M4), ivacaftor, and lumacaftor.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03474042
Brief Title
GLPG2737 on Top of Orkambi in Subjects With Cystic Fibrosis
Acronym
PELICAN
Official Title
A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate GLPG2737 in Orkambi-treated Subjects With Cystic Fibrosis Homozygous for the F508del Mutation
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
November 29, 2017 (Actual)
Primary Completion Date
April 10, 2018 (Actual)
Study Completion Date
April 10, 2018 (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
No
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 GLPG2737 administered orally b.i.d. for 28 days to adult male and female subjects with a confirmed diagnosis of cystic fibrosis homozygous for the F508del CFTR mutation and on stable treatment with Orkambi.
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
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GLPG2737
Arm Type
Experimental
Arm Description
GLPG2737 will be provided as capsules for oral use.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will be provided as capsules for oral use.
Intervention Type
Drug
Intervention Name(s)
GLPG2737
Intervention Description
GLPG2737 oral capsules administered twice daily for 28 days on top of Orkambi.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo oral capsules administered twice daily for 28 days on top of Orkambi.
Primary Outcome Measure Information:
Title
Change from baseline in sweat chloride concentration compared to placebo
Description
To assess Change from baseline in sweat chloride concentration compared to placebo.
Time Frame
Between day 1 pre-morning dose and Day 28.
Secondary Outcome Measure Information:
Title
Change versus placebo in the proportion of subjects with adverse events.
Description
To assess safety and tolerability by the number and percentage of subjects with adverse events.
Time Frame
Between Day 1 and 3 weeks after the last dose.
Title
Change from baseline in sweat chloride concentration.
Description
To assess the change from baseline in sweat chloride concentration.
Time Frame
From baseline (pre-morning dose on Day 1) through 28 days.
Title
Change in percent predicted forced expiratory volume in 1 second (FEV1).
Description
To assess the change from baseline in percent predicted forced expiratory volume in 1 second (FEV1).
Time Frame
From baseline (pre-morning dose on Day 1) through 28 days.
Title
Change in the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R).
Description
To assess the change from baseline in the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R).
Time Frame
From baseline (pre-morning dose on Day 1) through 28 days.
Title
Maximum observed plasma concentration of GLPG2737 (Cmax)
Description
To characterize the PK of GLPG2737 and its active metabolite, ivacaftor, and lumacaftor.
Time Frame
Between day 1 pre-dose and day 14.
Title
Area under the plasma concentration-time curve from time zero until 8 hours (AUC0-8h) post-dose calculated by the linear up - logarithmic down trapezoidal rule (on Day 14)
Description
To characterize the PK of GLPG2737 and its active metabolite G1125498 (M4), ivacaftor, and lumacaftor.
Time Frame
Between day 1 pre-dose and day 14.
Title
Trough plasma concentration observed at the end of the dosing interval (Ctrough).
Description
To characterize the PK of GLPG2737 and its active metabolite G1125498 (M4), ivacaftor, and lumacaftor.
Time Frame
Between day 1 pre-dose and day 28.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female subject ≥18 years of age on the day of signing the ICF.
A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation.
Stable intake of physician prescribed Orkambi (lumacaftor 400 mg/ivacaftor 250 mg b.i.d.) for at least 12 weeks prior to the first study drug administration, and planned continuation of Orkambi for the duration of the study.
FEV1 ≥40% of predicted normal for age, gender and height at screening (pre- or postbronchodilator).
Sweat chloride concentration ≥60 mmol/L at screening.
Exclusion Criteria:
History of serious allergic reaction to any drug as determined by the investigator (e.g., anaphylaxis requiring hospitalization) and/or known sensitivity to any component of the study drug.
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 (including rhinosinusitis) requiring a change in therapy within 4 weeks prior to the first study drug administration.
History of hepatic cirrhosis with portal hypertension (e.g.,signs/symptoms of splenomegaly, esophageal varices, etc.).
Abnormal liver function test at screening, defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or alkaline phosphatase and/or gammaglutamyl transferase (GGT) ≥3 x the upper limit of normal (ULN), and/or total bilirubin ≥1.5 x the ULN at screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Van de Steen, MD MBA
Organizational Affiliation
Galapagos NV
Official's Role
Study Director
Facility Information:
Facility Name
Study Site II
City
Berlin
Country
Germany
Facility Name
Study Site X
City
Dresden
Country
Germany
Facility Name
Study Site III
City
Essen
Country
Germany
Facility Name
Study Site IV
City
Frankfurt
Country
Germany
Facility Name
Study Site I
City
Heidelberg
Country
Germany
Facility Name
Study Site V
City
Köln
Country
Germany
Facility Name
Study Site VI
City
München
Country
Germany
Facility Name
Study Site IX
City
Stuttgart
Country
Germany
Facility Name
Study Site VIII
City
Tübingen
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
31594690
Citation
van Koningsbruggen-Rietschel S, Conrath K, Fischer R, Sutharsan S, Kempa A, Gleiber W, Schwarz C, Hector A, Van Osselaer N, Pano A, Corveleyn S, Bwirire D, Santermans E, Muller K, Bellaire S, Van de Steen O. GLPG2737 in lumacaftor/ivacaftor-treated CF subjects homozygous for the F508del mutation: A randomized phase 2A trial (PELICAN). J Cyst Fibros. 2020 Mar;19(2):292-298. doi: 10.1016/j.jcf.2019.09.006. Epub 2019 Oct 5.
Results Reference
derived
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GLPG2737 on Top of Orkambi in Subjects With Cystic Fibrosis
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