Clinical trial NCT03474042: GLPG2737 on Top of Orkambi in Subjects With Cystic Fibrosis
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2018-03-22
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change from baseline in sweat chloride concentration compared to placebo
timeFrame: Between day 1 pre-morning dose and Day 28.
Secondary outcomes:
measure: Change versus placebo in the proportion of subjects with adverse events.
timeFrame: Between Day 1 and 3 weeks after the last dose.
measure: Change from baseline in sweat chloride concentration.
timeFrame: From baseline (pre-morning dose on Day 1) through 28 days.
measure: Change in percent predicted forced expiratory volume in 1 second (FEV1).
timeFrame: From baseline (pre-morning dose on Day 1) through 28 days.
measure: Change in the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R).
timeFrame: From baseline (pre-morning dose on Day 1) through 28 days.
measure: Maximum observed plasma concentration of GLPG2737 (Cmax)
timeFrame: Between day 1 pre-dose and day 14.
measure: 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)
timeFrame: Between day 1 pre-dose and day 14.
measure: Trough plasma concentration observed at the end of the dosing interval (Ctrough).
timeFrame: Between day 1 pre-dose and day 28.
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Study Site II
city: Dresden
country: Germany
facility: Study Site X
city: Essen
country: Germany
facility: Study Site III
city: Frankfurt
country: Germany
facility: Study Site IV
city: Heidelberg
country: Germany
facility: Study Site I
city: Köln
country: Germany
facility: Study Site V
city: München
country: Germany
facility: Study Site VI
city: Stuttgart
country: Germany
facility: Study Site IX
city: Tübingen
country: Germany
facility: Study Site VIII
Study officials:
affiliation: Galapagos NV
name: Olivier Van de Steen, MD MBA
role: STUDY_DIRECTOR
References:
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.