A clinical study to test how effective and safe GLPG1690 is for subjects with idiopathic pulmonary fibrosis (IPF) when used together with standard medical treatment

• Register: EUCTR
• Last refreshed on: 26 April 2021
• Main ID: EUCTR2018-001405-87-CZ
• Date of registration: 06/12/2018
• Prospective Registration: Yes
• Primary sponsor: Galapagos NV
• Public title: A clinical study to test how effective and safe GLPG1690 is for subjects with idiopathic pulmonary fibrosis (IPF) when used together with standard medical treatment
• Scientific title: A Phase 3, randomized, double-blind, parallel-group, placebo-controlled, multi-center study to evaluate the efficacy and safety of two doses of GLPG1690 in addition to local standard of care for minimum 52 weeks in subjects with idiopathic pulmonary fibrosis.
• Date of first enrolment: 23/01/2019
• Target sample size: 750
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001405-87
• 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: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Chile, Czech Republic, Denmark, Finland, Germany, Greece, Peru, Spain, Taiwan, Turkey, United Kingdom, United States

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
- Male or female subject aged =40 years on the day of signing the ICF.
- A diagnosis of IPF within 5 years prior to the screening visit, as per applicable ATS/ERS/JRS/ALAT guideline at the time of diagnosis.
- Chest HRCT historically performed within 12 months prior to the screening visit and according to the minimum requirements for IPF diagnosis by central review based on subject’s HRCT only (if no LB available), or based on both HRCT and LB (with application of the different criteria in either situation). If an evaluable HRCT <12 months prior to screening is not available, an HRCT can be performed at screening to determine eligibility, according to the same requirements as the historical HRCT.
- Subjects receiving local standard of care for the treatment of IPF, defined as either pirfenidone or nintedanib at a stable dose for at least two months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason). A stable dose is defined as the highest dose tolerated by the subject during those two months.
- The extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan (investigator-determined).
- Meeting all of the following criteria during the screening period: FVC =45% predicted of normal, Forced expiratory volume in 1 second (FEV1)/FVC =0.7, DLCO corrected for Hb =30% predicted of normal.
- Estimated minimum life expectancy of at least 30 months for non IPF related disease in the opinion of the investigator.
- Male subjects and female subjects of childbearing potential agree to use highly effective contraception/preventive exposure measures from the time of first dose of IMP (for the male subject) or the signing of the ICF (for the female subject), during the study, and until 90 days (male) or 30 days (female) after the last dose of IMP.
- Able to walk at least 150 meters during the 6MWT at screening Visit 1; without having a contraindication to perform the 6MWT or without a condition putting the subject at risk of falling during the test (investigator’s discretion). The use of a cane is allowed, the use of a stroller is not allowed at all for any condition. At Visit 2, for the oxygen titration test, resting SpO2 should be =88% with maximum 6 L O2/minute; during the walk, SpO2 should be =83% with 6 L O2/minute or =88% with 0, 2 or 4 L O2/minute.
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 375
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 375

Exclusion criteria:
- 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, prostate cancer that has been medically managed through active surveillance or watchful waiting, squamous cell carcinoma of the skin if fully resected, and Ductal Carcinoma In Situ).
- Clinically significant abnormalities detected on ECG of either rhythm or conduction, a QTcF >450 ms, or a known long QT syndrome. Patients with implantable cardiovascular devices (e.g. pacemaker) affecting the QT interval time may be enrolled in the study based upon investigator judgment following cardiologist consultation if deemed necessary, and only after discussion with the medical monitor.
- Acute IPF exacerbation within 6 months prior to screening and/or during the screening period. The definition of an acute IPF exacerbation is as follows: Previous or concurrent diagnosis of IPF; Acute worsening or development of dyspnea typically < 1 month duration; Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern and deterioration not fully explained by cardiac failure or fluid overload
- Lower respiratory tract infection requiring treatment within 4 weeks prior to screening and/or during the screening period.
- Interstitial lung disease associated with known primary diseases (e.g. sarcoidosis and amyloidosis), exposures (e.g. radiation, silica, asbestos, and coal dust), or drugs (e.g. amiodarone).
- Diagnosis of severe pulmonary hypertension (investigator-determined).
- Unstable cardiovascular, pulmonary (other than IPF), or other disease within 6 months prior to screening or during the screening period (e.g. acute coronary disease, heart failure, and stroke).
- Had gastric perforation within 3 months prior to screening or during screening, and/or underwent major surgery within 3 months prior to screening, during screening or have major surgery planned during the study period.
- History of nintedanib-related increase in ALT and/or AST of >5xULN and increased susceptibility to elevated LFT; moderate to severe hepatic impairment (Child-Pugh B or C) and/or abnormal LFT at screening, defined as AST, and/or ALT, and/or total bilirubin =1.5xULN, and/or GGT =3xULN. Retesting is allowed once for abnormal LFT.
- Abnormal renal function defined as estimated creatinine clearance, calculated according to Cockcroft-Gault calculation (CCr) <30 mL/min. Retesting is allowed once.
- Use of any of the following therapies within 4 weeks prior to screening and during the screening period, or planned during the study: warfarin, imatinib, ambrisentan, azathioprine, cyclophosphamide, cyclosporine A, bosentan, methotrexate, sildenafil (except for occasional use), prednisone at steady dose >10 mg/day or equivalent.
- Clinical laboratory test suggestive of cholestasis with total serum bile acid levels >3xULN.


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

Health Condition(s) or Problem(s) studied

Idiopatic pulmonary fibrosis
MedDRA version: 20.0 Level: SOC Classification code 10038738 Term: Respiratory, thoracic and mediastinal disorders 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: Film-coated tablet
INN or Proposed INN: ziritaxestat
Current Sponsor code: G451990
Other descriptive name: GLPG1690
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: GLPG1690
Product Code: G451990
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ziritaxestat
Current Sponsor code: G451990
Other descriptive name: GLPG1690
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Rate of decline of FVC (in mL) over a period of 52 weeks

Secondary Objective: To evaluate the impact of two doses of GLPG1690 in addition to local standard of care compared to placebo in subjects with IPF on:
- Disease progression defined as deterioration of FVC or all-cause mortality at 52 weeks
- Respiratory-related hospitalization until the end of the study
- Changes in quality of life (measured by St. George’s Respiratory Questionnaire [SGRQ] total score) at 52 weeks

Main Objective: To evaluate the efficacy of two doses of GLPG1690 in addition to local standard of care compared to placebo in subjects with IPF as evaluated by the rate of decline of FVC over a period of 52 weeks

Timepoint(s) of evaluation of this end point: At week 52

Secondary Outcome(s)

Secondary end point(s): - Disease progression defined as the composite endpoint of first occurrence of =10% absolute decline in percent predicted forced vital capacity (%FVC) or all-cause mortality at 52 weeks
- Time to first respiratory-related hospitalization until the end of the study
- Change from baseline in the SGRQ total score at 52 weeks

Timepoint(s) of evaluation of this end point: Various timepoints during the trial as specified in the protocol

Secondary ID(s)

2018-001405-87-DK

NCT03711162

GLPG1690-CL-303

Source(s) of Monetary Support

Galapagos NV

Ethics review

Status: Approved
Approval date: 23/01/2019
Contact: