Study of GLPG1837 in Subjects With Cystic Fibrosis (S1251N Mutation) (SAPHIRA2)

• ClinicalTrials.gov Identifier: NCT02690519
• Recruitment Status: Completed
• First Posted: February 24, 2016
• Last Update Posted: October 11, 2016
• Sponsor: Galapagos NV
• Information provided by (Responsible Party): Galapagos NV

Study Description

Brief Summary:

At least 6 cystic fibrosis patients with the S1251N mutation will be treated for 4 weeks, consisting of two consecutive treatment periods of two weeks 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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: GLPG1837 dose 1; Drug: GLPG1837 dose 2	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IIa, Open-label Study of Two Doses of GLPG1837 in Subjects With Cystic Fibrosis and the S1251N Mutation
• Study Start Date: January 2016
• Actual Primary Completion Date: August 2016
• Actual Study Completion Date: September 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: GLPG1837 dose 1 and GLPG1837 dose 2; GLPG1837 twice daily oral dosing - morning and evening, for 4 weeks	Drug: GLPG1837 dose 1; one GLPG1837 tablet in the morning and one GLPG1837 tablet in the evening, for 2 weeks; Drug: GLPG1837 dose 2; one GLPG1837 tablet in the morning and one GLPG1837 tablet in the evening, for 2 weeks

Outcome Measures

Primary Outcome Measures :

1. Changes in adverse events [ Time Frame: Up to 9 weeks ]
   To evaluate the safety and tolerability of GLPG1837 in terms of adverse events at every visit
2. Changes in laboratory parameters [ Time Frame: Up to 7 weeks ]
   To evaluate the safety and tolerability of GLPG1837 in terms of abnormal laboratory parameters at every visit
3. Changes in vital signs [ Time Frame: Up to 9 weeks ]
   To evaluate the safety and tolerability of GLPG1837 in terms of abnormal vital signs at every visit
4. Changes in physical examination [ Time Frame: Up to 9 weeks ]
   To evaluate the safety and tolerability of GLPG1837 in terms of abnormal physical examination at every visit
5. Changes in electrocardiogram [ Time Frame: Up to 7 weeks ]
   To evaluate the safety and tolerability of GLPG1837 in terms of abnormal electrocardiogram at every visit

Secondary Outcome Measures :

1. Changes in sweat chloride concentration [ Time Frame: Up to 9 weeks ]
   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
2. Changes in pulmonary function (forced expiratory volume in 1 second, FEV1) assessed by spirometry [ Time Frame: Up to 9 weeks ]
   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
3. Plasma levels of GLPG1837 [ Time Frame: Up to 4 weeks ]
   To characterize the pharmacokinetics (PK) of GLPG1837 by measuring the amount in plasma between Day 1 and Day 29 at every visit

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Male or female subjects ≥ 18 years of age, with a confirmed diagnosis of cystic fibrosis
• Subjects with gating S1251N 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 half-life

Contacts and Locations

Locations

Belgium

University Hospital Antwerp

Antwerp, Belgium

University Hospital Ghent

Ghent, Belgium

University Hospitals Leuven

Leuven, Belgium

Netherlands

AMC

Amsterdam, Netherlands

UMC Utrecht

Utrecht, Netherlands

Sponsors and Collaborators

Galapagos NV

Investigators

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

More Information

• Responsible Party: Galapagos NV
• ClinicalTrials.gov Identifier: NCT02690519
• Other Study ID Numbers: GLPG1837-CL-202; 2015-003292-30 ( EudraCT Number )
• First Posted: February 24, 2016
• Last Update Posted: October 11, 2016
• Last Verified: March 2016

Keywords provided by Galapagos NV:

Cystic fibrosis S1251N mutation; GLPG1837

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases