|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Idiopatic pulmonary fibrosis
|Medical condition in easily understood language
|Idiopatic pulmonary fibrosis
|Diseases [C] - Respiratory Tract Diseases [C08]
|E.1.2 Medical condition or disease under investigation
|Respiratory, thoracic and mediastinal disorders
|System Organ Class
|10038738 - Respiratory, thoracic and mediastinal disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|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
|Secondary objectives of the trial
|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
|Trial contains a sub-study
|Principal 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.
|Principal 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 >450ms, 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 judgement following cardiologisch 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
- 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
- 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 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
|E.5 End points
|Primary end point(s)
|Rate of decline of FVC (in mL) over a period of 52 weeks
|Timepoint(s) of evaluation of this end point
|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
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days