Study of GLPG1837 in Subjects With Cystic Fibrosis (G551D Mutation) (SAPHIRA1)

A Phase IIa, Open-label Study of Multiple Doses of GLPG1837 in Subjects With Cystic Fibrosis and the G551D Mutation

32 cystic fibrosis patients with the G551D mutation will be treated for 4 weeks, consisting of three consecutive treatment periods: two 1-week periods followed by one 2-week period, evaluating one dose of GLPG1837 each. After the treatment period, there is a 7-10 days follow-up period.

During the course of the study, subjects will be examined for any side effects that may occur (safety and tolerability).

Changes in sweat chloride will be assessed as biomarker from baseline onwards, and changes in pulmonary function (efficacy) will be explored throughout the study. The amount of GLPG1837 present in the blood (pharmacokinetics) will also be determined.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: GLPG1837 dose 1; Drug: GLPG1837 dose 2; Drug: GLPG1837 dose 3

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Royal Adelaide Hospital
  • Chermside, Australia
    • The Prince Charles Hospital
  • Clayton, Australia
    • Monash Medical Centre
  • Nedlands, Australia
    • Sir Charles Gairdner Hospital
  • South Brisbane, Australia
    • Mater Adult Hospital
• Czech Republic
  • Praha 5, Czech Republic
    • Fakultni nemocnice v Motole
• Germany
  • Berlin, Germany
    • Charité Universitätsmedizin Berlin
  • Cologne, Germany
    • Universitätsklinkikum Koeln
  • Dresden, Germany
    • Uniklinik Carl-Gustav-Carus
  • München, Germany
    • Lungenheilkunde München-Pasing
• Ireland
  • Dublin, Ireland
    • St. Vincent'S University Hospital
  • Dublin, Ireland
    • Beamont Hospital
• United Kingdom
  • Glasgow, United Kingdom
    • Queen Elizabeth University Hospital
  • Liverpool, United Kingdom
    • Liverpool Heart and Chest Hospital
  • London, United Kingdom
    • Royal Brompton Hospital
  • Manchester, United Kingdom
    • The Medicines Evaluation Unit Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects ≥ 18 years of age, with a confirmed diagnosis of cystic fibrosis
• Subjects with gating G551D CFTR mutation on at least one allele in the CFTR gene
• Subjects currently receiving treatment with ivacaftor on a stable regimen or not on a treatment regimen with ivacaftor, for at least 2 weeks prior to screening
• Weight ≥ 40.0 kg
• Subjects on stable concomitant treatment regimen for at least 4 weeks prior to baseline (excluding ivacaftor)
• Pre- or post-bronchodilator FEV1 ≥ 40% of predicted normal
• Subject will have to use highly effective contraceptive methods

Exclusion Criteria:

• On an ivacaftor-containing treatment regimen and unable or unwilling to discontinue ivacaftor for the washout and treatment periods of the study
• Concomitant use of antifungal drugs within 4 weeks of baseline
• A history of a clinically meaningful unstable or uncontrolled chronic disease
• Liver cirrhosis and portal hypertension
• Any significant change in the medical regimen for pulmonary health within 4 weeks of baseline
• Unstable pulmonary status or respiratory tract infection or changes in therapy for pulmonary disease within 4 weeks of baseline
• Abnormal liver function
• Clinically significant abnormalities on ECG
• History of malignancy, solid organ/haematological transplantation
• Abnormal renal function
• Participation in another experimental therapy study within 30 days or 5 times halflife

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GLPG1837 dose 1, GLPG1837 dose 2, GLPG1837 dose 3; GLPG1837 twice daily oral dosing - morning and evening, for 4 weeks	Drug: GLPG1837 dose 1; two GLPG1837 tablets in the morning and two GLPG1837 tablets in the evening, for one week; Drug: GLPG1837 dose 2; two GLPG1837 tablets in the morning and two GLPG1837 tablets in the evening, for one week; Drug: GLPG1837 dose 3; two GLPG1837 tablets in the morning and two GLPG1837 tablets in the evening, for two weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in adverse events	To evaluate the safety and tolerability of GLPG1837 in terms of adverse events at every visit	Up to 9 weeks
Changes in laboratory parameters	To evaluate the safety and tolerability of GLPG1837 in terms of abnormal laboratory parameters at every visit	Up to 7 weeks
Changes in vital signs - composite outcome measure	To evaluate the safety and tolerability of GLPG1837 in terms of abnormal vital signs as measured by temperature, blood pressure, heart rate and respiratory rate, at every visit	Up to 9 weeks
Changes in physical examination - composite outcome measure	To evaluate the safety and tolerability of GLPG1837 in terms of abnormalities during physical examination at every visit	Up to 9 weeks
Changes in electrocardiogram	To evaluate the safety and tolerability of GLPG1837 in terms of abnormal electrocardiogram at every visit	Up to 7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in sweat chloride concentration	To evaluate the effect of GLPG1837 in terms of change in sweat chloride concentration, a biomarker to measure cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function at every visit	Up to 9 weeks
Changes in pulmonary function (forced expiratory volume in 1 second, FEV1) assessed by spirometry	To explore the effect of GLPG1837 in terms of change in pulmonary function (forced expiratory volume in 1 second, FEV1) assessed by spirometry at every visit	Up to 9 weeks
Plasma levels of GLPG1837: Cmax, the maximum observed plasma concentration	To characterize the pharmacokinetics (PK) of GLPG1837 by measuring the amount in plasma between Day 8 and Day 29 at every visit; On Day 29, an 8-hour profile will determine the Cmax, the maximum observed plasma concentration	Up to 3 weeks
Plasma levels of GLPG1837: tmax, the time of occurrence of Cmax	To characterize the pharmacokinetics (PK) of GLPG1837 by measuring the amount in plasma between Day 8 and Day 29 at every visit; On Day 29, an 8-hour profile will determine the tmax, the time of occurrence of Cmax	Up to 3 weeks
Plasma levels of GLPG1837: AUC, the area under the plasma concentration-time curve	To characterize the pharmacokinetics (PK) of GLPG1837 by measuring the amount in plasma between Day 8 and Day 29 at every visit; On Day 29, an 8-hour profile will determine the AUC, the area under the plasma concentration-time curve	Up to 3 weeks

Collaborators and Investigators

• Sponsor: Galapagos NV
• Investigators: Study Director: Olivier Van de Steen, MD, MBA, Galapagos NV

Publications and helpful links

General Publications

• Davies JC, Van de Steen O, van Koningsbruggen-Rietschel S, Drevinek P, Derichs N, McKone EF, Kanters D, Allamassey L, Namour F, de Kock H, Conrath K. GLPG1837, a CFTR potentiator, in p.Gly551Asp (G551D)-CF patients: An open-label, single-arm, phase 2a study (SAPHIRA1). J Cyst Fibros. 2019 Sep;18(5):693-699. doi: 10.1016/j.jcf.2019.05.006. Epub 2019 May 27.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: February 22, 2016
• First Submitted That Met QC Criteria: March 8, 2016
• First Posted (Estimate): March 14, 2016

Study Record Updates

• Last Update Posted (Estimate): December 7, 2016
• Last Update Submitted That Met QC Criteria: December 6, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Cystic fibrosis G551D mutation; GLPG1837
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: GLPG1837-CL-201; 2015-003291-77 (EudraCT Number)