GLPG2737 on Top of Orkambi in Subjects With Cystic Fibrosis

Phase 2

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: Placebo; Drug: GLPG2737

• Registration Number: NCT03474042
• Lead Sponsor: Galapagos NV

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-11-29
• Study First Submitted: 2018-03-15
• Study First Submitted QC: 2018-03-15
• Study First Posted: 2018-03-22
• Primary Completion: 2018-04-10
• Study Completion: 2018-04-10
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-08
• Last Update Posted: 2018-06-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo will be provided as capsules for oral use.
GLPG2737	GLPG2737	GLPG2737 will be provided as capsules for oral use.

Primary Outcome Measures

Name	Time	Method
Change from baseline in sweat chloride concentration compared to placebo	Between day 1 pre-morning dose and Day 28.	To assess Change from baseline in sweat chloride concentration compared to placebo.

Secondary Outcome Measures

Name	Time	Method
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)	Between day 1 pre-dose and day 14.	To characterize the PK of GLPG2737 and its active metabolite G1125498 (M4), ivacaftor, and lumacaftor.
Maximum observed plasma concentration of GLPG2737 (Cmax)	Between day 1 pre-dose and day 14.	To characterize the PK of GLPG2737 and its active metabolite, ivacaftor, and lumacaftor.
Change from baseline in sweat chloride concentration.	From baseline (pre-morning dose on Day 1) through 28 days.	To assess the change from baseline in sweat chloride concentration.
Change in the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R).	From baseline (pre-morning dose on Day 1) through 28 days.	To assess the change from baseline in the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R).
Trough plasma concentration observed at the end of the dosing interval (Ctrough).	Between day 1 pre-dose and day 28.	To characterize the PK of GLPG2737 and its active metabolite G1125498 (M4), ivacaftor, and lumacaftor.
Change versus placebo in the proportion of subjects with adverse events.	Between Day 1 and 3 weeks after the last dose.	To assess safety and tolerability by the number and percentage of subjects with adverse events.
Change in percent predicted forced expiratory volume in 1 second (FEV1).	From baseline (pre-morning dose on Day 1) through 28 days.	To assess the change from baseline in percent predicted forced expiratory volume in 1 second (FEV1).

Trial Locations

Locations (9)

Study Site II; 🇩🇪 Berlin, Germany

Study Site X; 🇩🇪 Dresden, Germany

Study Site III; 🇩🇪 Essen, Germany

Study Site IV; 🇩🇪 Frankfurt, Germany

Study Site I; 🇩🇪 Heidelberg, Germany

Study Site V; 🇩🇪 Köln, Germany

Study Site IX; 🇩🇪 Stuttgart, Germany

Study Site VIII; 🇩🇪 Tübingen, Germany

Study Site VI; 🇩🇪 München, Germany