Randomized, Double-Blind, Parallel Group, Placebo-Controlled, Multicenter, Exploratory Phase IIa Study to Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of GLPG1690 Administered for 12 Weeks in Subjects with Idiopathic Pulmonary Fibrosis (IPF)

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2015-004157-41-GB
• Date of registration: 02/12/2015
• Prospective Registration: Yes
• Primary sponsor: Galapagos NV
• Public title: Randomized, Double-Blind, Parallel Group, Placebo-Controlled, Multicenter, Exploratory Phase IIa Study to Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of GLPG1690 Administered for 12 Weeks in Subjects with Idiopathic Pulmonary Fibrosis (IPF)
• Scientific title: Randomized, Double-Blind, Parallel Group, Placebo-Controlled, Multicenter, Exploratory Phase IIa Study to Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of GLPG1690 Administered for 12 Weeks in Subjects with Idiopathic Pulmonary Fibrosis (IPF)
• Date of first enrolment: 21/03/2016
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004157-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Ukraine, United Kingdom

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Galapagos NV

• Name: Clinical Trial Information Desk
• Affiliation: Galapagos NV

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subjects who are able and willing to sign the ICF as approved by the independent ethics committee (IEC).
2. Male or female subjects of non-child-bearing potential aged = 40 years on the day of signing the ICF.
Note: Female subjects will be considered of non-childbearing potential if they are either sterilized, ovariectomized, hysterectomized, or postmenopausal (i.e., at least 24 months of amenorrhea in the absence of other biological or physiological causes [in case of doubt, the subject’s follicle stimulating hormone [FSH] levels will be determined and the subject will be considered postmenopausal if the FSH level is = 35 mIU/mL).
3. Subjects with a chest HRCT performed within 12 months prior to Screening visit.
4. Subjects with IPF diagnosed by a multidisciplinary team and confirmed by central review of the subject’s HRCT pattern and SLB (if available)
5. Subjects meeting all of the following criteria:
a. FVC =50% predicted of normal
b. Diffusing capacity for the lungs for carbon monoxide (DLCO) = 30% predicted of normal (corrected for hemoglobin) (see Appendix 3 for additional details)
6. Subjects with a forced expiratory volume in 1 second (FEV1)/FVC (Tiffeneau-Pinelli index) ratio = 0.70 (based on pre-bronchodilator spirometry).
7. Subjects who are on stable supportive care (e.g., supplemental oxygen, pulmonary rehabilitation) for at least 3 weeks prior to screening and during screening period.
8. Subjects must be in a stable condition and acceptable for study participation based upon the results of a medical history, physical examination, vital signs, 12-lead ECG, and laboratory evaluation.
9. Subjects must have an estimated minimum life expectancy of 12 months in the opinion of the investigator.
10. Male subjects and their female partners must use a highly effective method of birth control.
11. Subjects who are able to understand the importance of adherence to study treatment, study procedures and requirements, including the concomitant medication restrictions.
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 19
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Subjects with a known hypersensitivity to any of the study drug ingredients or a history of a significant allergic reaction to any drug as determined by the investigator (e.g., anaphylaxis requiring hospitalization).
2. Subjects with a history of or a current immunosuppressive condition (e.g., human immunodeficiency virus [HIV] infection).
3. Subjects with a history of malignancy within the past 5 years (except for carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, and prostate cancer medically managed through active surveillance or watchful waiting).
4. Subjects with clinically significant abnormalities detected on ECG regarding either rhythm or conduction (e.g., QT interval corrected for heart rate using Fridericia’s formula [QTcF] =450 ms, or a known long QT syndrome).
Note: A first degree heart block will not be considered as a significant abnormality.
5. Subjects with acute IPF exacerbation within 6 weeks prior to screening and during the screening period.
6. Subject with a lower respiratory tract infection requiring antibiotics within 4 weeks prior to screening and during the screening period.
7. Subjects who have been smoking within 3 months prior to screening.
8. Interstitial lung disease (ILD) associated with known primary diseases (e.g., sarcoidosis, amyloidosis, etc.), exposures (e.g., radiation, silica, asbestos, coal dust, etc.), and drugs (e.g., amiodarone, etc.).
9. Subjects with a history of lung volume reduction surgery or lung transplant.
10. Subjects with an unstable cardiac or pulmonary disease (other than IPF) within 6 months prior to screening or during the screening period, including but not limited to:
a. unstable angina pectoris, myocardial infarction
b. congestive heart failure requiring hospitalization
11. Subjects with any clinical condition or circumstance that in the opinion of the investigator may make a subject unsuitable for inclusion or unable to complete the study or comply with study procedures and requirements.
12. Subjects with a contra-indication for bronchoscopy and bronchoalveolar lavage in the opinion of the investigator.
13. Subjects with an abnormal liver function defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin >3 x upper limit of the normal range (ULN).
14. Subjects with an abnormal renal function defined as creatinine clearance < 50 mL/min using the Cockroft-Gault equation.
15. Subjects participating in a drug/device or biologic investigational research study (concurrently with the current study or within 8 weeks prior to screening).
16. Subjects using of any of the following therapies within 4 weeks before screening:
a. Pirfenidone
b. Nintedanib
c. Warfarin
d. Imatinib
e. Ambrisentan
f. Azathioprine
g. Cyclophosphamide
h. Cyclosporine A
i. Prednisone at steady dose > 15 mg/day (for details, see Section 4.2.4)
j. Any experimental IPF therapy
17. Subjects with active alcoh

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

Health Condition(s) or Problem(s) studied

Idiopathic pulmonary fibrosis (IPF)
MedDRA version: 18.1 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: GLPG1690
Product Code: G451990
Pharmaceutical Form: Capsule
Current Sponsor code: G451990
Other descriptive name: GLPG1690
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): 1. Evaluation of Safety and tolerability
- AE monitoring
- Clinical laboratory examinations
- Vital signs
- Physical examination
- 12-lead ECG
2. Characterisation of PK and PD properties of the IMP
- Blood sampling (PK)
- Blood sampling (PD)

Timepoint(s) of evaluation of this end point: - AE monitoring: From signing informed consent until follow-up visit at multiple timepoints
- Clinical laboratory examinations, vital signs, physical examination: Screening, Baseline, W1 D7, W2 D14, W4 D28, W8 D56, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)
- 12-lead ECG: Screening, W1 D7, W2 D14, W4 D28, W8 D56, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)
- Blood sampling (PK): Baseline, W1 D7, W2 D14, W4 D28, W8 D56, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)
- Blood sampling (PD): Baseline, W4 D28, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)

Main Objective: - to evaluate the safety and tolerability of GLPG1690
- to characterize the PK and PD properties of GLPG1690

Secondary Objective: - to evaluate the change from baseline in FVC
- to explore the change in biomarkers in blood and BALF
- to evaluate the change in quality of life measures
- to evaluate the change in FRI parameters

Secondary Outcome(s)

Secondary end point(s): - change from baseline in FVC, through spirometry
- change in biomarkers in blood and BALF
- change in FRI Parameters through HRCT
- change in quality of life (QOL) measures through SGRQ

Timepoint(s) of evaluation of this end point: - Spirometry: Screening, Baseline, W1 D7, W2 D14, W4 D28, W8 D56, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)
- Biomarker blood samples: Baseline, W4 D28, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)
- BALF sample: Baseline, W12 D84, Early Discontinuation Visit
- HRCT: Baseline, W12 D84, Early Discontinuation Visit
- SGRQ (QOL assessment): Baseline, W4 D28, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)

Secondary ID(s)

GLPG1690­CL­202

Source(s) of Monetary Support

Galapagos NV

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 13/05/2018
• Date Completed: 02/05/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-004157-41/results