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

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GLPG1837 dose 1
GLPG1837 dose 2
GLPG1837 dose 3
Sponsored by
Galapagos NV
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic fibrosis G551D mutation, GLPG1837

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Royal Adelaide Hospital
  • The Prince Charles Hospital
  • Monash Medical Centre
  • Sir Charles Gairdner Hospital
  • Mater Adult Hospital
  • Fakultni nemocnice v Motole
  • Charité Universitätsmedizin Berlin
  • Universitätsklinkikum Koeln
  • Uniklinik Carl-Gustav-Carus
  • Lungenheilkunde München-Pasing
  • Beamont Hospital
  • St. Vincent's University Hospital
  • Queen Elizabeth University Hospital
  • Liverpool Heart and Chest Hospital
  • Royal Brompton Hospital
  • The Medicines Evaluation Unit Ltd

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GLPG1837 dose 1, GLPG1837 dose 2, GLPG1837 dose 3

Arm Description

GLPG1837 twice daily oral dosing - morning and evening, for 4 weeks

Outcomes

Primary Outcome Measures

Changes in adverse events
To evaluate the safety and tolerability of GLPG1837 in terms of adverse events at every visit
Changes in laboratory parameters
To evaluate the safety and tolerability of GLPG1837 in terms of abnormal laboratory parameters at every visit
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
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
Changes in electrocardiogram
To evaluate the safety and tolerability of GLPG1837 in terms of abnormal electrocardiogram at every visit

Secondary Outcome Measures

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
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
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
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
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

Full Information

First Posted
February 22, 2016
Last Updated
December 6, 2016
Sponsor
Galapagos NV
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1. Study Identification

Unique Protocol Identification Number
NCT02707562
Brief Title
Study of GLPG1837 in Subjects With Cystic Fibrosis (G551D Mutation)
Acronym
SAPHIRA1
Official Title
A Phase IIa, Open-label Study of Multiple Doses of GLPG1837 in Subjects With Cystic Fibrosis and the G551D Mutation
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
February 2016 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Galapagos NV

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Cystic fibrosis G551D mutation, GLPG1837

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GLPG1837 dose 1, GLPG1837 dose 2, GLPG1837 dose 3
Arm Type
Experimental
Arm Description
GLPG1837 twice daily oral dosing - morning and evening, for 4 weeks
Intervention Type
Drug
Intervention Name(s)
GLPG1837 dose 1
Intervention Description
two GLPG1837 tablets in the morning and two GLPG1837 tablets in the evening, for one week
Intervention Type
Drug
Intervention Name(s)
GLPG1837 dose 2
Intervention Description
two GLPG1837 tablets in the morning and two GLPG1837 tablets in the evening, for one week
Intervention Type
Drug
Intervention Name(s)
GLPG1837 dose 3
Intervention Description
two GLPG1837 tablets in the morning and two GLPG1837 tablets in the evening, for two weeks
Primary Outcome Measure Information:
Title
Changes in adverse events
Description
To evaluate the safety and tolerability of GLPG1837 in terms of adverse events at every visit
Time Frame
Up to 9 weeks
Title
Changes in laboratory parameters
Description
To evaluate the safety and tolerability of GLPG1837 in terms of abnormal laboratory parameters at every visit
Time Frame
Up to 7 weeks
Title
Changes in vital signs - composite outcome measure
Description
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
Time Frame
Up to 9 weeks
Title
Changes in physical examination - composite outcome measure
Description
To evaluate the safety and tolerability of GLPG1837 in terms of abnormalities during physical examination at every visit
Time Frame
Up to 9 weeks
Title
Changes in electrocardiogram
Description
To evaluate the safety and tolerability of GLPG1837 in terms of abnormal electrocardiogram at every visit
Time Frame
Up to 7 weeks
Secondary Outcome Measure Information:
Title
Changes in sweat chloride concentration
Description
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
Time Frame
Up to 9 weeks
Title
Changes in pulmonary function (forced expiratory volume in 1 second, FEV1) assessed by spirometry
Description
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
Time Frame
Up to 9 weeks
Title
Plasma levels of GLPG1837: Cmax, the maximum observed plasma concentration
Description
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
Time Frame
Up to 3 weeks
Title
Plasma levels of GLPG1837: tmax, the time of occurrence of Cmax
Description
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
Time Frame
Up to 3 weeks
Title
Plasma levels of GLPG1837: AUC, the area under the plasma concentration-time curve
Description
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
Time Frame
Up to 3 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Van de Steen, MD, MBA
Organizational Affiliation
Galapagos NV
Official's Role
Study Director
Facility Information:
Facility Name
Royal Adelaide Hospital
City
Adelaide
Country
Australia
Facility Name
The Prince Charles Hospital
City
Chermside
Country
Australia
Facility Name
Monash Medical Centre
City
Clayton
Country
Australia
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
Country
Australia
Facility Name
Mater Adult Hospital
City
South Brisbane
Country
Australia
Facility Name
Fakultni nemocnice v Motole
City
Praha 5
Country
Czech Republic
Facility Name
Charité Universitätsmedizin Berlin
City
Berlin
Country
Germany
Facility Name
Universitätsklinkikum Koeln
City
Cologne
Country
Germany
Facility Name
Uniklinik Carl-Gustav-Carus
City
Dresden
Country
Germany
Facility Name
Lungenheilkunde München-Pasing
City
München
Country
Germany
Facility Name
Beamont Hospital
City
Dublin
Country
Ireland
Facility Name
St. Vincent's University Hospital
City
Dublin
Country
Ireland
Facility Name
Queen Elizabeth University Hospital
City
Glasgow
Country
United Kingdom
Facility Name
Liverpool Heart and Chest Hospital
City
Liverpool
Country
United Kingdom
Facility Name
Royal Brompton Hospital
City
London
Country
United Kingdom
Facility Name
The Medicines Evaluation Unit Ltd
City
Manchester
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
31147302
Citation
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.
Results Reference
derived

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

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