Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
The main purpose of this study was to see how GLPG1690 works together with your current standard treatment on your lung function and IPF disease in general. The study also investigated how well GLPG1690 is tolerated (for example if you got any side effects while on study drug).
Interventions
DRUGGLPG1690
GLPG1690, film-coated tablets for oral use.
DRUGPlacebo
Matching placebo, film-coated tablets for oral use.
Sponsors
Galapagos NV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subject aged ≥40 years on the day of signing the Informed Consent Form (ICF). * A diagnosis of IPF within 5 years prior to the screening visit, as per applicable American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guidelines at the time of diagnosis. * Chest high-resolution computed tomography (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 lung biopsy (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, diffusing capacity of the lung for carbon monoxide (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 investigational medicinal product (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 6-Minute Walk Test (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 oxygen saturation (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.
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 QT interval corrected for heart rate using Fridericia's formula (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 \>5 x upper limit of the normal range (ULN) and increased susceptibility to elevated LFT; moderate to severe hepatic impairment (Child-Pugh B or C) and/or abnormal liver function test (LFT) at screening, defined as aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT), and/or total bilirubin ≥1.5 x upper limit of the normal range (ULN), and/or gamma glutamyl transferase (GGT) ≥3 x ULN. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Rate of Decline in FVC up to Week 52 | Baseline up to week 52 | FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS) | Up to EoS (week 121) | Percentage of participants with respiratory related hospitalization were reported in this measure. |
| Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 52 | Baseline, week 52 | SGRQ is a 50-item paper questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related quality of life (QOL) and well-being, split into 3 domains: symptoms score assessing the frequency and severity of respiratory symptoms (Items 1-8), activity score assessing the effects of breathlessness on mobility and physical activity (Items 11-17 and 36 to 44), and impacts score assessing the psychosocial impact of the disease (Items 9-10, 18-35 and 45-50). Each item has a specific weight. Domain scores = 100 \* summed weights from positive items in that component/sum of maximum weights for all non-missing items in that component Total score = 100 \* summed weights from positive items in the questionnaire/sum of maximum weights for all non-missing items in the questionnaire Scores were weighted such that each domain score ranged from 0 to 100 and the total score ranged from 0 to 100, with higher scores indicating the poorer health-related QOL. |
| Annual Rate of Decline in FVC Until EoS | Baseline up to EoS (week 121) | FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
| Percentage of Participants With Disease Progression Until EoS | Up to EoS (week 121) | Disease progression was defined as the composite occurrence of \>=10% absolute decline in percent predicted %FVC or all-cause mortality. FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
| Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 100 | Baseline, week 100 | SGRQ is a 50-item paper questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related quality of life (QOL) and well-being, split into 3 domains: symptoms score assessing the frequency and severity of respiratory symptoms (Items 1-8), activity score assessing the effects of breathlessness on mobility and physical activity (Items 11-17 and 36 to 44), and impacts score assessing the psychosocial impact of the disease (Items 9-10, 18-35 and 45-50). Each item has a specific weight. Domain scores = 100 \* summed weights from positive items in that component/sum of maximum weights for all non-missing items in that component Total score = 100 \* summed weights from positive items in the questionnaire/sum of maximum weights for all non-missing items in the questionnaire Scores were weighted such that each domain score ranged from 0 to 100 and the total score ranged from 0 to 100, with higher scores indicating the poorer health-related QOL. |
| Percentage of Participants With All Cause Hospitalization Until EoS | Up to EoS (week 121) | Percentage of participants with all cause hospitalization was reported for this measure. |
| Percentage of Participants With Respiratory Related Mortality Until EoS | Up to EoS (week 121) | Percentage of participants with respiratory related mortality until EoS were reported for this study. |
| Percentage of Participants Hospitalized for Non-elective Lung Transplant Until EoS | Up to EoS (week 121) | Percentage of Participants who were hospitalized for Non-elective lung transplant were reported for this measure. |
| Percentage of Participants With Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation Until EoS | Up to EoS (week 121) | Percentage of participants with acute IPF exacerbation until EoS were reported for this measure. |
| Percentage of Participants With All Cause Mortality or Hospitalization for Non-elective Lung Transplant Until EoS | Up to EoS (week 121) | Percentage of participants with all-cause mortality or hospitalization for non-elective lung transplant were reported for this measure. |
| Percentage of Participants With All Cause Mortality, Hospitalization for Non-elective Lung Transplant or Hospitalization for Qualifying for Lung Transplant Until EoS | Up to EoS (week 121) | Percentage of participants with all-cause mortality or hospitalization for non-elective lung transplant or hospitalization for qualifying for lung transplant were reported for this measure. |
| Percentage of Participants With All-Cause Mortality or Hospitalization That Meets >=10% Absolute Decline in %FVC or Respiratory-Related Hospitalization Until EoS | Up to EoS (week 121) | Percentage of participants with all-cause mortality or respiratory related hospitalization that meets \>=10% absolute decline in %FVC or respiratory-related hospitalization were reported for this measure. |
| Percentage of Participants With All-Cause Mortality or Respiratory-Related Hospitalizations Until EoS | Up to EoS (week 121) | Percentage of participants with all-cause mortality or respiratory related hospitalization were reported for this measure. |
| FVC at Week 52 | Week 52 | FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
| Change From Baseline in FVC at Week 52 | Baseline, week 52 | FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
| Percent Change From Baseline in FVC at Week 52 | Baseline, week 52 | FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
| Percentage of Participants With Disease Progression up to Week 52 | Up to week 52 | Disease progression was defined as the composite occurrence of more than or equal to (\>=)10 percent (%) absolute decline in percent predicted forced vital capacity (%FVC) or all-cause mortality. FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
| Change From Baseline in FVC at Week 112 | Baseline, week 112 | FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
| Percent Change From Baseline in FVC at Week 112 | Baseline, week 112 | FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
| Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤5 | Baseline, week 52 | FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
| Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 112: FVC Change Within ≤5 | Baseline, week 112 | FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
| Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤10 | Baseline, week 52 | FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
| Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 112: FVC Change Within ≤10 | Baseline, week 112 | FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Baseline up to 30 days after the last dose (up to week 121) | Safety was assessed by AEs, which included abnormalities identified during a medical test (example, laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study drug or was clinically significant. A Treatment emergent AE (TEAE) was defined as any AE that started or worsened after the first dose of study drug up to 30 days after the last dose of study drug. AEs were considered serious (SAEs) if the AE resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization. |
| Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Baseline, week 52, week 100 | Cough was evaluated using the LCQ. The LCQ was a 19-item questionnaire split into three domains: physical, psychological, and social. Scores were calculated by domain (range from 1 to 7, higher scores indicated a better health status) and then the total score was calculated by adding the individual domain score. Total score ranged from 3 to 21, with higher scores indicated a better health status. |
| Change From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100 | Baseline, week 52, week 100 | Cough was assessed using VAS score, ranged from 0 (no cough) to 100 millimeter (mm) (worst possible cough). |
| Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100 | Baseline, week 52, week 100 | Urge to Cough was assessed using VAS score, ranged from 0 (no urge to cough) to 100 mm (highest urge to cough). |
| Change From Baseline in European Quality Of Life (EQ) VAS at Week 52 and Week 100 | Baseline, week 52, week 100 | EuroQol outcome measurements is a printed 20 cm VAS that appears somewhat like a thermometer, on which a score from 0 (worst imaginable health state or death) to 100 (best imaginable health state) was marked by the participant (or, when necessary, their proxy) with the scale in view. |
| Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Baseline, week 52, week 100 | The K-BILD questionnaire was specifically developed to analyze the health status of participants with ILD. The questionnaire consists of 15 items (assessed by the participants on a scale ranging from 1 to 7, where 1 and 7 represent worst and best health status). Items are compiled into 3 domains: breathlessness and activities (range: 0-21), psychological (range: 0-34) , and chest symptoms (range: 0-8). To score the K-BILD, the Likert response scale weightings for individual items are combined and scores are transformed to a range of 0-100 by using logit values (higher scores indicate better health status). |
| Area Under The Concentration Time Curve (AUC) of Ziritaxtestat | Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose | Area under the concentration time curve of ziritaxtestat was reported. |
| Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat | Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose | Maximum Observed Plasma Concentration of Ziritaxtestat was reported. |
| Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 52 and Week 100 | Baseline, week 52, week 100 | The 6-MWT depicted the total distance covered by a participant during 6 minutes of walking. |
| Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100 | Baseline, week 52, week 100 | Change from baseline in DLCO (percent predicted hemoglobin level corrected) was reported for this measure.mmol/min/kPa: Millimole per minute per kilopascal |
| FVC at Week 112 | Week 112 | FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. |
Countries
Australia, Belgium, Brazil, Chile, Czechia, Denmark, Germany, Greece, Japan, Peru, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants with centrally confirmed diagnosis of idiopathic pulmonary fibrosis (IPF) were enrolled at 106 sites.
Pre-assignment details
A total of 1116 participants were screened for the study, and 525 were randomized and 523 were treated.
Participants by arm
| Arm | Count |
|---|---|
| GLPG1690 600 mg Participants received GLPG1690 (ziritaxestat) 600 mg, film-coated tablets orally once daily (mean GLPG1690 exposure was up to 325.3 days) in addition to local standard of care. Standard of care included either pirfenidone or nintedanib at a stable dose for at least 2 months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason). | 174 |
| GLPG1690 200 mg Participants received GLPG1690 (ziritaxestat) 200 mg as film-coated tablet for oral use once daily (mean GLPG1690 exposure was up to 356.0 days) in addition to local standard of care. Standard of care included either pirfenidone or nintedanib at a stable dose for at least 2 months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason). | 175 |
| Placebo Participants received GLPG1690 (ziritaxestat) matching placebo tablets for oral use once daily (mean GLPG1690 exposure was up to 353.4 days) in addition to local standard of care. Standard of care included either pirfenidone or nintedanib at a stable dose for at least 2 months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason). | 174 |
| Total | 523 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 | 4 |
| Overall Study | Death | 11 | 7 | 8 |
| Overall Study | Lack of Efficacy | 0 | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Miscellaneous | 1 | 2 | 2 |
| Overall Study | Not Treated | 1 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 2 | 0 |
| Overall Study | Protocol Specified Withdrawal Criteria Met | 0 | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 139 | 152 | 146 |
| Overall Study | Withdrawal by Subject | 17 | 10 | 10 |
Baseline characteristics
| Characteristic | GLPG1690 600 mg | GLPG1690 200 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 69.4 years STANDARD_DEVIATION 7.2 | 70.0 years STANDARD_DEVIATION 6.7 | 70.6 years STANDARD_DEVIATION 7.7 | 70.0 years STANDARD_DEVIATION 7.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants | 27 Participants | 26 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 129 Participants | 145 Participants | 148 Participants | 422 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 0 Participants | 4 Participants |
| Forced Vital Capacity (FVC) | 2947.0 mL STANDARD_DEVIATION 820.8 | 2873.2 mL STANDARD_DEVIATION 815.8 | 2943.3 mL STANDARD_DEVIATION 738.7 | 2921.1 mL STANDARD_DEVIATION 791.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 10 Participants | 6 Participants | 6 Participants | 22 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 9 Participants | 9 Participants | 29 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 152 Participants | 160 Participants | 159 Participants | 471 Participants |
| Sex: Female, Male Female | 32 Participants | 32 Participants | 28 Participants | 92 Participants |
| Sex: Female, Male Male | 142 Participants | 143 Participants | 146 Participants | 431 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 12 / 174 | 8 / 175 | 8 / 174 |
| other Total, other adverse events | 91 / 174 | 99 / 175 | 82 / 174 |
| serious Total, serious adverse events | 38 / 174 | 38 / 175 | 36 / 174 |
Outcome results
Primary
Annual Rate of Decline in FVC up to Week 52
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Baseline up to week 52
Population: Full Analysis Set - Efficacy (FAS-EF) included all randomized participants who received at least 1 dose of investigational product and excluded participants from the site found to have serious good clinical practice (GCP)-noncompliance issues.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | Annual Rate of Decline in FVC up to Week 52 | -124.6 mL/year | Standard Error 27.15 |
| GLPG1690 200 mg | Annual Rate of Decline in FVC up to Week 52 | -173.9 mL/year | Standard Error 26.31 |
| Placebo | Annual Rate of Decline in FVC up to Week 52 | -147.3 mL/year | Standard Error 26.72 |
p-value: 0.552595% CI: [-52.3, 97.6]Coefficient Regression Model
p-value: 0.477695% CI: [-100.5, 47.1]Coefficient Regression Model
Secondary
Annual Rate of Decline in FVC Until EoS
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Baseline up to EoS (week 121)
Population: Full Analysis Set - Efficacy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | Annual Rate of Decline in FVC Until EoS | -127.0 mL/year | Standard Error 24.01 |
| GLPG1690 200 mg | Annual Rate of Decline in FVC Until EoS | -175.5 mL/year | Standard Error 22.97 |
| Placebo | Annual Rate of Decline in FVC Until EoS | -146.4 mL/year | Standard Error 23.59 |
95% CI: [-46.9, 85.7]
95% CI: [-93.9, 35.8]
Secondary
Area Under The Concentration Time Curve (AUC) of Ziritaxtestat
Area under the concentration time curve of ziritaxtestat was reported.
Time frame: Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose
Population: Pharmacokinetic Analysis Set: All randomized participants who received at least one dose of IP and for whom evaluable PK data were available.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GLPG1690 600 mg | Area Under The Concentration Time Curve (AUC) of Ziritaxtestat | 10367 Nanogram * milliliter per hour (ng*mL/h) |
| GLPG1690 200 mg | Area Under The Concentration Time Curve (AUC) of Ziritaxtestat | 51136 Nanogram * milliliter per hour (ng*mL/h) |
| Placebo | Area Under The Concentration Time Curve (AUC) of Ziritaxtestat | 7095 Nanogram * milliliter per hour (ng*mL/h) |
| GLPG1690 600 mg/Nintedanib | Area Under The Concentration Time Curve (AUC) of Ziritaxtestat | 33796 Nanogram * milliliter per hour (ng*mL/h) |
| GLPG1690 200 mg/Pirfenidone | Area Under The Concentration Time Curve (AUC) of Ziritaxtestat | 6375 Nanogram * milliliter per hour (ng*mL/h) |
| GLPG1690 600 mg/Pirfenidone | Area Under The Concentration Time Curve (AUC) of Ziritaxtestat | 21188 Nanogram * milliliter per hour (ng*mL/h) |
Secondary
Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100
Change from baseline in DLCO (percent predicted hemoglobin level corrected) was reported for this measure.mmol/min/kPa: Millimole per minute per kilopascal
Time frame: Baseline, week 52, week 100
Population: FAS - EF with available data at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100 | Change at Week 52 | -0.640 mmol/min/kPa | Standard Error 0.1205 |
| GLPG1690 600 mg | Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100 | Change at Week 100 | -0.215 mmol/min/kPa | Standard Error 0.6737 |
| GLPG1690 200 mg | Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100 | Change at Week 52 | -0.137 mmol/min/kPa | Standard Error 0.1288 |
| GLPG1690 200 mg | Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100 | Change at Week 100 | -1.670 mmol/min/kPa | — |
| Placebo | Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100 | Change at Week 52 | -0.193 mmol/min/kPa | Standard Error 0.0907 |
| Placebo | Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100 | Change at Week 100 | -2.134 mmol/min/kPa | Standard Error 1.9836 |
Secondary
Change From Baseline in European Quality Of Life (EQ) VAS at Week 52 and Week 100
EuroQol outcome measurements is a printed 20 cm VAS that appears somewhat like a thermometer, on which a score from 0 (worst imaginable health state or death) to 100 (best imaginable health state) was marked by the participant (or, when necessary, their proxy) with the scale in view.
Time frame: Baseline, week 52, week 100
Population: FAS-EF with available data at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in European Quality Of Life (EQ) VAS at Week 52 and Week 100 | Change at Week 52 | -1.4 Score on a scale | Standard Deviation 16.2 |
| GLPG1690 600 mg | Change From Baseline in European Quality Of Life (EQ) VAS at Week 52 and Week 100 | Change at Week 100 | 7.2 Score on a scale | Standard Deviation 12.3 |
| GLPG1690 200 mg | Change From Baseline in European Quality Of Life (EQ) VAS at Week 52 and Week 100 | Change at Week 52 | -6.1 Score on a scale | Standard Deviation 17.3 |
| GLPG1690 200 mg | Change From Baseline in European Quality Of Life (EQ) VAS at Week 52 and Week 100 | Change at Week 100 | -9.3 Score on a scale | Standard Deviation 25.2 |
| Placebo | Change From Baseline in European Quality Of Life (EQ) VAS at Week 52 and Week 100 | Change at Week 52 | -3.7 Score on a scale | Standard Deviation 16.5 |
| Placebo | Change From Baseline in European Quality Of Life (EQ) VAS at Week 52 and Week 100 | Change at Week 100 | -2.1 Score on a scale | Standard Deviation 23.8 |
Secondary
Change From Baseline in FVC at Week 112
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Baseline, week 112
Population: FAS - EF with available data at specified time point. No participant was available for analysis at Week 112 for arms GLPG1690 200 mg and Placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in FVC at Week 112 | -55.75 mL | Standard Error 277.75 |
Secondary
Change From Baseline in FVC at Week 52
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Baseline, week 52
Population: FAS-EF with available data at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in FVC at Week 52 | -145.94 mL | Standard Error 31.799 |
| GLPG1690 200 mg | Change From Baseline in FVC at Week 52 | -182.29 mL | Standard Error 30.286 |
| Placebo | Change From Baseline in FVC at Week 52 | -133.24 mL | Standard Error 31.819 |
Secondary
Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100
The K-BILD questionnaire was specifically developed to analyze the health status of participants with ILD. The questionnaire consists of 15 items (assessed by the participants on a scale ranging from 1 to 7, where 1 and 7 represent worst and best health status). Items are compiled into 3 domains: breathlessness and activities (range: 0-21), psychological (range: 0-34) , and chest symptoms (range: 0-8). To score the K-BILD, the Likert response scale weightings for individual items are combined and scores are transformed to a range of 0-100 by using logit values (higher scores indicate better health status).
Time frame: Baseline, week 52, week 100
Population: FAS-EF with available data at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Breathlessness and Activities Score: Change at Week 52 | -0.256 Score on a scale | Standard Deviation 20.896 |
| GLPG1690 600 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Breathlessness and Activities Score: Change at Week 100 | 1.417 Score on a scale | Standard Deviation 19.427 |
| GLPG1690 600 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Psychological Score: Change at Week 52 | 0.429 Score on a scale | Standard Deviation 18.24 |
| GLPG1690 600 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Psychological Score: Change at Week 100 | -4.417 Score on a scale | Standard Deviation 30.117 |
| GLPG1690 600 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Chest Symptoms Score: Change at Week 52 | -1.624 Score on a scale | Standard Deviation 20.367 |
| GLPG1690 600 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Chest Symptoms Score: Change at Week 100 | 0.850 Score on a scale | Standard Deviation 13.686 |
| GLPG1690 600 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Total Score: Change at Week 52 | -0.276 Score on a scale | Standard Deviation 13.69 |
| GLPG1690 600 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Total Score: Change at Week 100 | -0.383 Score on a scale | Standard Deviation 15.09 |
| GLPG1690 200 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Psychological Score: Change at Week 52 | -2.583 Score on a scale | Standard Deviation 15.555 |
| GLPG1690 200 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Total Score: Change at Week 52 | -2.306 Score on a scale | Standard Deviation 10.398 |
| GLPG1690 200 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Psychological Score: Change at Week 100 | -6.478 Score on a scale | Standard Deviation 9.193 |
| GLPG1690 200 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Chest Symptoms Score: Change at Week 52 | -2.095 Score on a scale | Standard Deviation 20.002 |
| GLPG1690 200 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Chest Symptoms Score: Change at Week 100 | -2.667 Score on a scale | Standard Deviation 19.951 |
| GLPG1690 200 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Breathlessness and Activities Score: Change at Week 52 | -5.031 Score on a scale | Standard Deviation 13.512 |
| GLPG1690 200 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Breathlessness and Activities Score: Change at Week 100 | -9.733 Score on a scale | Standard Deviation 15.973 |
| GLPG1690 200 mg | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Total Score: Change at Week 100 | -5.444 Score on a scale | Standard Deviation 7.726 |
| Placebo | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Psychological Score: Change at Week 52 | -2.421 Score on a scale | Standard Deviation 17.049 |
| Placebo | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Breathlessness and Activities Score: Change at Week 100 | -3.843 Score on a scale | Standard Deviation 19.788 |
| Placebo | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Breathlessness and Activities Score: Change at Week 52 | -4.545 Score on a scale | Standard Deviation 15.25 |
| Placebo | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Psychological Score: Change at Week 100 | -2.743 Score on a scale | Standard Deviation 10.93 |
| Placebo | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Total Score: Change at Week 52 | -2.484 Score on a scale | Standard Deviation 10.863 |
| Placebo | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Chest Symptoms Score: Change at Week 100 | -3.371 Score on a scale | Standard Deviation 16.023 |
| Placebo | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Chest Symptoms Score: Change at Week 52 | -2.790 Score on a scale | Standard Deviation 20.052 |
| Placebo | Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 | Total Score: Change at Week 100 | -2.371 Score on a scale | Standard Deviation 10.52 |
Secondary
Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 100
SGRQ is a 50-item paper questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related quality of life (QOL) and well-being, split into 3 domains: symptoms score assessing the frequency and severity of respiratory symptoms (Items 1-8), activity score assessing the effects of breathlessness on mobility and physical activity (Items 11-17 and 36 to 44), and impacts score assessing the psychosocial impact of the disease (Items 9-10, 18-35 and 45-50). Each item has a specific weight. Domain scores = 100 \* summed weights from positive items in that component/sum of maximum weights for all non-missing items in that component Total score = 100 \* summed weights from positive items in the questionnaire/sum of maximum weights for all non-missing items in the questionnaire Scores were weighted such that each domain score ranged from 0 to 100 and the total score ranged from 0 to 100, with higher scores indicating the poorer health-related QOL.
Time frame: Baseline, week 100
Population: Full Analysis Set - Efficacy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GLPG1690 600 mg | Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 100 | 11.4 Score on a scale |
| GLPG1690 200 mg | Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 100 | 10.5 Score on a scale |
| Placebo | Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 100 | 7.7 Score on a scale |
95% CI: [-11.5, 19]
95% CI: [-11.1, 16.8]
Secondary
Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 52
SGRQ is a 50-item paper questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related quality of life (QOL) and well-being, split into 3 domains: symptoms score assessing the frequency and severity of respiratory symptoms (Items 1-8), activity score assessing the effects of breathlessness on mobility and physical activity (Items 11-17 and 36 to 44), and impacts score assessing the psychosocial impact of the disease (Items 9-10, 18-35 and 45-50). Each item has a specific weight. Domain scores = 100 \* summed weights from positive items in that component/sum of maximum weights for all non-missing items in that component Total score = 100 \* summed weights from positive items in the questionnaire/sum of maximum weights for all non-missing items in the questionnaire Scores were weighted such that each domain score ranged from 0 to 100 and the total score ranged from 0 to 100, with higher scores indicating the poorer health-related QOL.
Time frame: Baseline, week 52
Population: Full Analysis Set- Efficacy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 52 | 3.3 Score on a scale | Standard Error 1.41 |
| GLPG1690 200 mg | Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 52 | 4.1 Score on a scale | Standard Error 1.32 |
| Placebo | Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 52 | 3.8 Score on a scale | Standard Error 1.36 |
p-value: 0.78595% CI: [-4.4, 3.3]Mixed Models Analysis
p-value: 0.861795% CI: [-3.4, 4.1]Mixed Models Analysis
Secondary
Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 52 and Week 100
The 6-MWT depicted the total distance covered by a participant during 6 minutes of walking.
Time frame: Baseline, week 52, week 100
Population: FAS - EF with available data at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 52 and Week 100 | Change at Week 52 | -36.34 Meter | Standard Error 7.805 |
| GLPG1690 600 mg | Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 52 and Week 100 | Change at Week 100 | -83.00 Meter | Standard Error 17.521 |
| GLPG1690 200 mg | Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 52 and Week 100 | Change at Week 52 | -15.65 Meter | Standard Error 9.865 |
| GLPG1690 200 mg | Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 52 and Week 100 | Change at Week 100 | -79.00 Meter | Standard Error 13 |
| Placebo | Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 52 and Week 100 | Change at Week 52 | -34.75 Meter | Standard Error 11.546 |
| Placebo | Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 52 and Week 100 | Change at Week 100 | -137.87 Meter | Standard Error 93.135 |
Secondary
Change From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100
Cough was assessed using VAS score, ranged from 0 (no cough) to 100 millimeter (mm) (worst possible cough).
Time frame: Baseline, week 52, week 100
Population: FAS-EF with available data at specified time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100 | Change at Week 100 | 8.0 mm | Standard Deviation 23.1 |
| GLPG1690 600 mg | Change From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100 | Change at Week 52 | 2.9 mm | Standard Deviation 27.9 |
| GLPG1690 200 mg | Change From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100 | Change at Week 100 | 0.3 mm | Standard Deviation 24 |
| GLPG1690 200 mg | Change From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100 | Change at Week 52 | 3.2 mm | Standard Deviation 25.1 |
| Placebo | Change From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100 | Change at Week 52 | 2.3 mm | Standard Deviation 27.3 |
| Placebo | Change From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100 | Change at Week 100 | 25.4 mm | Standard Deviation 39.1 |
Secondary
Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100
Urge to Cough was assessed using VAS score, ranged from 0 (no urge to cough) to 100 mm (highest urge to cough).
Time frame: Baseline, week 52, week 100
Population: FAS-EF with available data at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100 | Change at Week 100 | 5.7 mm | Standard Deviation 22 |
| GLPG1690 600 mg | Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100 | Change at Week 52 | 1.8 mm | Standard Deviation 26.8 |
| GLPG1690 200 mg | Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100 | Change at Week 52 | 1.5 mm | Standard Deviation 23.2 |
| GLPG1690 200 mg | Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100 | Change at Week 100 | -1.9 mm | Standard Deviation 24.8 |
| Placebo | Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100 | Change at Week 52 | 1.1 mm | Standard Deviation 24.9 |
| Placebo | Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100 | Change at Week 100 | 24.3 mm | Standard Deviation 40.6 |
Secondary
Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100
Cough was evaluated using the LCQ. The LCQ was a 19-item questionnaire split into three domains: physical, psychological, and social. Scores were calculated by domain (range from 1 to 7, higher scores indicated a better health status) and then the total score was calculated by adding the individual domain score. Total score ranged from 3 to 21, with higher scores indicated a better health status.
Time frame: Baseline, week 52, week 100
Population: FAS - EF with available data at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1690 600 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Psychological Score: Change at Week 100 | -0.595 Score on a scale | Standard Deviation 0.941 |
| GLPG1690 600 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Physical Score: Change at Week 52 | 0.024 Score on a scale | Standard Deviation 1.218 |
| GLPG1690 600 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Physical Score: Change at Week 100 | -0.208 Score on a scale | Standard Deviation 0.452 |
| GLPG1690 600 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Psychological Score: Change at Week 52 | -0.122 Score on a scale | Standard Deviation 1.397 |
| GLPG1690 600 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Social Score: Change at Week 52 | -0.065 Score on a scale | Standard Deviation 1.344 |
| GLPG1690 600 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Social Score: Change at Week 100 | -0.458 Score on a scale | Standard Deviation 1.269 |
| GLPG1690 600 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Total Score: Change at Week 52 | -0.163 Score on a scale | Standard Deviation 3.778 |
| GLPG1690 600 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Total Score: Change at Week 100 | -1.262 Score on a scale | Standard Deviation 2.295 |
| GLPG1690 200 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Total Score: Change at Week 52 | -0.791 Score on a scale | Standard Deviation 3.028 |
| GLPG1690 200 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Psychological Score: Change at Week 100 | -0.254 Score on a scale | Standard Deviation 0.892 |
| GLPG1690 200 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Social Score: Change at Week 52 | -0.351 Score on a scale | Standard Deviation 1.147 |
| GLPG1690 200 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Social Score: Change at Week 100 | -0.333 Score on a scale | Standard Deviation 1.237 |
| GLPG1690 200 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Physical Score: Change at Week 52 | -0.215 Score on a scale | Standard Deviation 0.966 |
| GLPG1690 200 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Total Score: Change at Week 100 | -0.810 Score on a scale | Standard Deviation 0.9249 |
| GLPG1690 200 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Physical Score: Change at Week 100 | -0.222 Score on a scale | Standard Deviation 1.2 |
| GLPG1690 200 mg | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Psychological Score: Change at Week 52 | -0.225 Score on a scale | Standard Deviation 1.204 |
| Placebo | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Physical Score: Change at Week 52 | -0.151 Score on a scale | Standard Deviation 0.835 |
| Placebo | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Psychological Score: Change at Week 52 | -0.044 Score on a scale | Standard Deviation 1.02 |
| Placebo | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Social Score: Change at Week 100 | 0.321 Score on a scale | Standard Deviation 0.997 |
| Placebo | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Psychological Score: Change at Week 100 | 0.367 Score on a scale | Standard Deviation 0.899 |
| Placebo | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Total Score: Change at Week 52 | -0.247 Score on a scale | Standard Deviation 2.68 |
| Placebo | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Physical Score: Change at Week 100 | -0.286 Score on a scale | Standard Deviation 0.847 |
| Placebo | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Social Score: Change at Week 52 | -0.052 Score on a scale | Standard Deviation 1.08 |
| Placebo | Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 | Total Score: Change at Week 100 | 0.403 Score on a scale | Standard Deviation 2.497 |
Secondary
FVC at Week 112
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Week 112
Population: FAS-EF with available data at specified time point. No participant was available for analysis at Week 112 for arm GLPG1690 200 mg and Placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | FVC at Week 112 | 3262.00 mL | Standard Error 15 |
Secondary
FVC at Week 52
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Week 52
Population: FAS-EF with available data at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | FVC at Week 52 | 2886.20 mL | Standard Error 83.969 |
| GLPG1690 200 mg | FVC at Week 52 | 2662.90 mL | Standard Error 79.056 |
| Placebo | FVC at Week 52 | 3021.99 mL | Standard Error 78.415 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat
Maximum Observed Plasma Concentration of Ziritaxtestat was reported.
Time frame: Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GLPG1690 600 mg | Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat | 864 Nanogram per milliliter (ng/mL) |
| GLPG1690 200 mg | Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat | 3962 Nanogram per milliliter (ng/mL) |
| Placebo | Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat | 583 Nanogram per milliliter (ng/mL) |
| GLPG1690 600 mg/Nintedanib | Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat | 2686 Nanogram per milliliter (ng/mL) |
| GLPG1690 200 mg/Pirfenidone | Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat | 591 Nanogram per milliliter (ng/mL) |
| GLPG1690 600 mg/Pirfenidone | Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat | 2009 Nanogram per milliliter (ng/mL) |
Secondary
Percentage of Participants Hospitalized for Non-elective Lung Transplant Until EoS
Percentage of Participants who were hospitalized for Non-elective lung transplant were reported for this measure.
Time frame: Up to EoS (week 121)
Population: Full Analysis Set - Efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants Hospitalized for Non-elective Lung Transplant Until EoS | 0.0 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants Hospitalized for Non-elective Lung Transplant Until EoS | 0.0 Percentage of participants |
| Placebo | Percentage of Participants Hospitalized for Non-elective Lung Transplant Until EoS | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 112: FVC Change Within ≤10
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Baseline, week 112
Population: FAS - EF with available data at specified time point. No participant was available for analysis at Week 112 for arms GLPG1690 200 mg and Placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 112: FVC Change Within ≤10 | 100 Percentage of participants |
Secondary
Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 112: FVC Change Within ≤5
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Baseline, week 112
Population: FAS - EF with available data at specified time point. No participant was available for analysis at Week 112 for arms GLPG1690 200 mg and Placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 112: FVC Change Within ≤5 | 50.0 Percentage of participants |
Secondary
Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤10
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Baseline, week 52
Population: FAS - EF with available data at specified time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤10 | 97.6 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤10 | 97.9 Percentage of participants |
| Placebo | Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤10 | 96.8 Percentage of participants |
Secondary
Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤5
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Baseline, week 52
Population: FAS - EF with available data at specified time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤5 | 90.2 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤5 | 92.8 Percentage of participants |
| Placebo | Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤5 | 89.4 Percentage of participants |
Secondary
Percentage of Participants With Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation Until EoS
Percentage of participants with acute IPF exacerbation until EoS were reported for this measure.
Time frame: Up to EoS (week 121)
Population: Full Analysis Set - Efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation Until EoS | 4.7 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation Until EoS | 4.7 Percentage of participants |
| Placebo | Percentage of Participants With Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation Until EoS | 3.7 Percentage of participants |
95% CI: [0.44, 3.81]
95% CI: [0.42, 3.5]
Secondary
Percentage of Participants With All Cause Hospitalization Until EoS
Percentage of participants with all cause hospitalization was reported for this measure.
Time frame: Up to EoS (week 121)
Population: Full Analysis Set - Efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With All Cause Hospitalization Until EoS | 18.3 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With All Cause Hospitalization Until EoS | 21.6 Percentage of participants |
| Placebo | Percentage of Participants With All Cause Hospitalization Until EoS | 18.9 Percentage of participants |
95% CI: [0.65, 1.78]
95% CI: [0.76, 1.98]
Secondary
Percentage of Participants With All Cause Mortality, Hospitalization for Non-elective Lung Transplant or Hospitalization for Qualifying for Lung Transplant Until EoS
Percentage of participants with all-cause mortality or hospitalization for non-elective lung transplant or hospitalization for qualifying for lung transplant were reported for this measure.
Time frame: Up to EoS (week 121)
Population: Full Analysis Set - Efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With All Cause Mortality, Hospitalization for Non-elective Lung Transplant or Hospitalization for Qualifying for Lung Transplant Until EoS | 7.1 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With All Cause Mortality, Hospitalization for Non-elective Lung Transplant or Hospitalization for Qualifying for Lung Transplant Until EoS | 4.7 Percentage of participants |
| Placebo | Percentage of Participants With All Cause Mortality, Hospitalization for Non-elective Lung Transplant or Hospitalization for Qualifying for Lung Transplant Until EoS | 4.9 Percentage of participants |
95% CI: [0.66, 4.08]
95% CI: [0.36, 2.61]
Secondary
Percentage of Participants With All Cause Mortality or Hospitalization for Non-elective Lung Transplant Until EoS
Percentage of participants with all-cause mortality or hospitalization for non-elective lung transplant were reported for this measure.
Time frame: Up to EoS (week 121)
Population: FAS - EF with available data at specified time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With All Cause Mortality or Hospitalization for Non-elective Lung Transplant Until EoS | 7.1 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With All Cause Mortality or Hospitalization for Non-elective Lung Transplant Until EoS | 4.7 Percentage of participants |
| Placebo | Percentage of Participants With All Cause Mortality or Hospitalization for Non-elective Lung Transplant Until EoS | 4.9 Percentage of participants |
95% CI: [0.66, 4.08]
95% CI: [0.36, 2.61]
Secondary
Percentage of Participants With All-Cause Mortality or Hospitalization That Meets >=10% Absolute Decline in %FVC or Respiratory-Related Hospitalization Until EoS
Percentage of participants with all-cause mortality or respiratory related hospitalization that meets \>=10% absolute decline in %FVC or respiratory-related hospitalization were reported for this measure.
Time frame: Up to EoS (week 121)
Population: Full Analysis Set - Efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With All-Cause Mortality or Hospitalization That Meets >=10% Absolute Decline in %FVC or Respiratory-Related Hospitalization Until EoS | 13.6 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With All-Cause Mortality or Hospitalization That Meets >=10% Absolute Decline in %FVC or Respiratory-Related Hospitalization Until EoS | 11.1 Percentage of participants |
| Placebo | Percentage of Participants With All-Cause Mortality or Hospitalization That Meets >=10% Absolute Decline in %FVC or Respiratory-Related Hospitalization Until EoS | 14.0 Percentage of participants |
95% CI: [0.59, 1.91]
95% CI: [0.43, 1.46]
Secondary
Percentage of Participants With All-Cause Mortality or Respiratory-Related Hospitalizations Until EoS
Percentage of participants with all-cause mortality or respiratory related hospitalization were reported for this measure.
Time frame: Up to EoS (week 121)
Population: Full Analysis Set - Efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With All-Cause Mortality or Respiratory-Related Hospitalizations Until EoS | 13.6 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With All-Cause Mortality or Respiratory-Related Hospitalizations Until EoS | 11.1 Percentage of participants |
| Placebo | Percentage of Participants With All-Cause Mortality or Respiratory-Related Hospitalizations Until EoS | 14.0 Percentage of participants |
95% CI: [0.59, 1.91]
95% CI: [0.43, 1.46]
Secondary
Percentage of Participants With Disease Progression Until EoS
Disease progression was defined as the composite occurrence of \>=10% absolute decline in percent predicted %FVC or all-cause mortality. FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Up to EoS (week 121)
Population: Full Analysis Set - Efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With Disease Progression Until EoS | 23.1 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With Disease Progression Until EoS | 24.6 Percentage of participants |
| Placebo | Percentage of Participants With Disease Progression Until EoS | 21.3 Percentage of participants |
95% CI: [0.68, 1.95]
95% CI: [0.74, 2.09]
Secondary
Percentage of Participants With Disease Progression up to Week 52
Disease progression was defined as the composite occurrence of more than or equal to (\>=)10 percent (%) absolute decline in percent predicted forced vital capacity (%FVC) or all-cause mortality. FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Up to week 52
Population: Full Analysis Set- Efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With Disease Progression up to Week 52 | 17.8 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With Disease Progression up to Week 52 | 18.7 Percentage of participants |
| Placebo | Percentage of Participants With Disease Progression up to Week 52 | 18.3 Percentage of participants |
p-value: 0.964895% CI: [0.56, 1.74]Regression, Logistic
p-value: 0.85395% CI: [0.6, 1.84]Regression, Logistic
Secondary
Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS)
Percentage of participants with respiratory related hospitalization were reported in this measure.
Time frame: Up to EoS (week 121)
Population: Full Analysis Set- Efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS) | 9.5 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS) | 9.4 Percentage of participants |
| Placebo | Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS) | 9.8 Percentage of participants |
95% CI: [0.5, 2.05]
95% CI: [0.47, 1.88]
Secondary
Percentage of Participants With Respiratory Related Mortality Until EoS
Percentage of participants with respiratory related mortality until EoS were reported for this study.
Time frame: Up to EoS (week 121)
Population: Full Analysis Set - Efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With Respiratory Related Mortality Until EoS | 3.6 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With Respiratory Related Mortality Until EoS | 4.1 Percentage of participants |
| Placebo | Percentage of Participants With Respiratory Related Mortality Until EoS | 1.8 Percentage of participants |
Secondary
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Safety was assessed by AEs, which included abnormalities identified during a medical test (example, laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study drug or was clinically significant. A Treatment emergent AE (TEAE) was defined as any AE that started or worsened after the first dose of study drug up to 30 days after the last dose of study drug. AEs were considered serious (SAEs) if the AE resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization.
Time frame: Baseline up to 30 days after the last dose (up to week 121)
Population: FAS consisted of all randomized participants who received at least 1 dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GLPG1690 600 mg | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 78.7 Percentage of participants |
| GLPG1690 600 mg | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 21.8 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 84.6 Percentage of participants |
| GLPG1690 200 mg | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 21.7 Percentage of participants |
| Placebo | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 84.5 Percentage of participants |
| Placebo | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 20.7 Percentage of participants |
Secondary
Percent Change From Baseline in FVC at Week 112
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Baseline, week 112
Population: FAS - EF with available data at specified time point. No participant was available for analysis at Week 112 for arms GLPG1690 200 mg and Placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | Percent Change From Baseline in FVC at Week 112 | -0.95 Percent change | Standard Error 8.288 |
Secondary
Percent Change From Baseline in FVC at Week 52
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
Time frame: Baseline, week 52
Population: FAS-EF with available data at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | Percent Change From Baseline in FVC at Week 52 | -4.57 Percent change | Standard Error 0.992 |
| GLPG1690 200 mg | Percent Change From Baseline in FVC at Week 52 | -6.46 Percent change | Standard Error 1.115 |
| Placebo | Percent Change From Baseline in FVC at Week 52 | -4.48 Percent change | Standard Error 0.978 |