A study looking at the safety of the drug GLPG1837 in patients with cystic fibrosis and the S1251N mutation

• Register: EUCTR
• Last refreshed on: 8 August 2016
• Main ID: EUCTR2015-003292-30-BE
• Date of registration: 26/11/2015
• Prospective Registration: Yes
• Primary sponsor: Galapagos NV
• Public title: A study looking at the safety of the drug GLPG1837 in patients with cystic fibrosis and the S1251N mutation
• Scientific title: A phase IIa, open-label study of two doses of GLPG1837 in subjects with cystic fibrosis and the S1251N mutation.
• Date of first enrolment: 18/01/2016
• Target sample size: 6
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003292-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Netherlands

Contacts

• Name: Clinical trial information desk
• Affiliation: Galapagos NV

• Name: Clinical trial information desk
• Affiliation: Galapagos NV

Key inclusion & exclusion criteria

Inclusion criteria:
1.Male or female subjects = 18 years of age, on the day of signing the
Informed Consent Form (ICF), with a confirmed diagnosis of cystic
fibrosis:
a. Clinical diagnosis of cystic fibrosis with signs/symptoms involving at
least two organ systems, and
b. Medical history of elevated sweat chloride =60 mmol/L by quantitative pilocarpine iontophoresis (documented in the subject's medical record) or 2 disease causing CFTR mutations (documented in the subject's medical record).
2.Gating S1251N CFTR mutation on at least one allele in the CFTR gene
(documented in the subject's medical record or CF registry); any known
or unknown mutation allowed on the 2nd allele. Subject inclusion can be performed, provided that genotype information is available in source
data.
3.Subject must meet one of the following:
a. Subjects currently receiving treatment with ivacaftor must be on a
stable regimen for at least 2 weeks prior to screening
Or
b. Subjects not on a treatment regimen with ivacaftor for at least 2 weeks prior to screening
4.Weight = 40.0 kg.
5.Subjects on stable concomitant treatment regimen for at least 4 weeks prior to baseline (excluding ivacaftor).
6.Pre- or post-bronchodilator FEV1 = 40% of predicted normal for age,
gender, height at screening.
7.Female subjects must have a negative blood pregnancy test.
Determination of serum follicle-stimulating hormone (FSH) will be done
for any suspected postmenopausal female with at least 12 months of
continuous spontaneous amenorrhea, with FSH levels > 40 IU/mL being
confirmative for menopause. For hysterectomy and tubal ligation,
documented confirmation will be requested.
8.Subjects will have to use highly effective contraceptive methods prior
to the first dose of the study drug, during the study, and for at least 12
weeks after the last dose of the study drug.
a. If the subject is a sexually active woman of childbearing potential, she and her male partner are required to simultaneously use 2 effective
contraceptive methods as listed in the protocol. Hormonal contraceptives will not be considered as an effective method; however, female subjects are not required to discontinue hormonal contraceptives. Female subjects who use contraception must have done so for at least 14 days prior to the first dose of the study drug.
b. Non-vasectomized sexually active male subjects with female partners
of childbearing potential must be willing to use a condom in addition to
having their female partner use another form of contraception as listed
in the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
1.History of sensitivity to any component of the study drug, or a history
of drug or other allergy that, in the investigator's opinion,
contraindicates the subject's participation in the study.
2.On an ivacaftor-containing treatment regimen and unable or unwilling to discontinue ivacaftor for the washout and treatment periods of the study.
3.Concomitant use of antifungal drugs (e.g. itraconazole, ketoconazole,
voriconazole, posaconazole) within 4 weeks of baseline.
4.A history of a clinically meaningful unstable or uncontrolled chronic
disease including underlying cystic fibrosis that makes the subject
unsuitable for inclusion in the study in the opinion of the investigator.
5.Liver cirrhosis and portal hypertension.
6.History of malignancy within the past 5 years (except for carcinoma in
situ of the uterine cervix and basal cell carcinoma of the skin that has
been treated with no evidence of recurrence).
7.Any significant change in the medical regimen (including dose and
frequency) for pulmonary health within 4 weeks of baseline, including:
antibiotics; corticosteroids (as defined in the protocol); inhaled
bronchodilators, hypertonic saline, mannitol or dornase alfa; ibuprofen
and airway clearance techniques. Individuals taking inhaled antibiotics
for suppression of chronic airways infection must be on a stable regimen
for at least 8 weeks prior to baseline and willing to continue the same
antibiotic through Day 29.
8.Unstable pulmonary status or respiratory tract infection (including
pulmonary exacerbation), based on the investigator's opinion, or
changes in therapy for pulmonary disease within 4 weeks of baseline as
defined in the protocol.
9.History of lung volume reduction surgery or lung transplant.
10.Use of continuous (24 hours per day) supplemental oxygen therapy.
11.Clinically significant abnormalities detected on electrocardiogram
(ECG) regarding either rhythm or conduction (e.g., QTcF = 450 ms, or a known long QT syndrome). A first degree heart block will not be
considered as a significant abnormality.
12.Use of medication known to prolong the QT interval (including herbal and naturopathic therapy).
13.History of solid organ or haematological transplantation or currently
on a transplantation waiting list.
14.Abnormal liver function defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), GGT > 3 x upper limit of the normal range or bilirubin > 2 x upper limit of the normal range.
15.Abnormal renal function defined as creatinine clearance < 50mL/min
using the Cockroft-Gault equation.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystic fibrosis with the S1251N mutation
MedDRA version: 18.1 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

Intervention(s)

Product Name: GLPG1837
Product Code: GLPG1837
Pharmaceutical Form: Tablet
INN or Proposed INN: Not Applicable
CAS Number: 1654725-02-6
Current Sponsor code: GLPG1837
Other descriptive name: GLPG1837
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 62.5-

Product Name: GLPG1837
Product Code: GLPG1837
Pharmaceutical Form: Tablet
INN or Proposed INN: Not Applicable
CAS Number: 1654725-02-6
Current Sponsor code: GLPG1837
Other descriptive name: GLPG1837
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-

Primary Outcome(s)

Main Objective: To evaluate the safety and tolerability of two oral doses of GLPG1837 in subjects with CF and at least one copy of the S1251N mutation.

Secondary Objective: To assess changes in sweat chloride from baseline (Day 1) as the biomarker of CFTR ion channel function
To explore the changes in pulmonary function (FEV1) from baseline.
To assess the pharmacokinetics of GLPG1837.

Timepoint(s) of evaluation of this end point: Various time points throughout the trial as specified in the protocol

Primary end point(s): Safety and tolerability will be assessed through:
•Adverse events (AEs)
•Physical examinations
•Vital signs
•12-lead ECG
•Oxygen saturation
•Safety laboratory assessments

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Various time points throughout the trial as specified in the protocol

Secondary end point(s): Efficacy will be assessed through:
•sweat chloride concentration testing
•measuring pulmonary function

Secondary ID(s)

GLPG1837-CL-202

Source(s) of Monetary Support

Galapagos NV