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

Cystic Fibrosis Clinical Trial

— SAPHIRA1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02707562
• Other study ID #: GLPG1837-CL-201
• Secondary ID: 2015-003291-77
• Status: Completed
• Phase: Phase 2
• First received: February 22, 2016
• Last updated: December 6, 2016
• Start date: February 2016
• Est. completion date: November 2016

Study information

• Verified date: March 2016
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Human Research Ethics CommitteeIreland: Health Products Regulatory AuthorityUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyCzech Republic: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• GLPG1837 dose 1
two GLPG1837 tablets in the morning and two GLPG1837 tablets in the evening, for one week
• GLPG1837 dose 2
two GLPG1837 tablets in the morning and two GLPG1837 tablets in the evening, for one week
• GLPG1837 dose 3
two GLPG1837 tablets in the morning and two GLPG1837 tablets in the evening, for two weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Countries where clinical trial is conducted

Australia,  Czech Republic,  Germany,  Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in adverse events	To evaluate the safety and tolerability of GLPG1837 in terms of adverse events at every visit	Up to 9 weeks	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	Changes in electrocardiogram	To evaluate the safety and tolerability of GLPG1837 in terms of abnormal electrocardiogram at every visit	Up to 7 weeks	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No