A Clinical Study to Test How Effective and Safe GLPG1690 is for Participants With Idiopathic Pulmonary Fibrosis (IPF) When Used Together With Standard of Care (ISABELA2)

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

The main purpose of this study was to see how GLPG1690 works together with the 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 get any side effects while on study drug).

Study Overview

• Status: Terminated
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: GLPG1690; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 781
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ABP
    • Centro Médico Dra de Salvo
  • Córdoba, Argentina, X5016KEH
    • Hospital Privado Centro Medico de Cordoba
  • Florida, Argentina, B1602DQD
    • CEMER Centro Medico de Enfermedades Respiratorias
  • Luján, Argentina, B6700CNR
    • Hospital Zonal Especializado de Agudos y Crónicos Dr. Antonio A. Cetrangolo
  • Mar Del Plata, Argentina, B7600FZN
    • Instituto de Investigaciones Clínicas Mar del Plata
  • Mendoza, Argentina, 5500
    • Fundacion Scherbovsky
• Canada
  • Calgary, Canada, T3M 1M4
    • South Health Campus
  • Montréal, Canada, H2L 4M1
    • Hôtel Dieu Du Centre Hospitalier de L'université de Montréal
  • Montréal, Canada, QC H3S 1Y9
    • McGill University Health Centre Research Institute
  • Québec, Canada, G1V 4G5
    • Institut Universitaire de Cardiologie et de Pneumologie
  • Toronto, Canada, M5G 2N2
    • Toronto General Hospital
  • Vancouver, Canada, V5Z 1M9
    • Vancouver General Hospital
  • Vancouver, Canada, V6Z 1Y6
    • Pacific Lung Research Center
  • Windsor, Canada, N8W1L9
    • Dr Anil Dhar Professional Medicine Corporation
• France
  • Marseille, France, 13915
    • Hopital Nord AP-HM
  • Montpellier, France, 34295
    • Centre Hospitalier Régional Universitaire Montpellier
  • Paris, France, 75018
    • Groupe Hospitalier Bichat Claude Bernard
  • Reims, France, 51092
    • CHU de Reims
• Germany
  • Essen, Germany, 45239
    • Ruhrlandklinik
  • Frankfurt, Germany, 60389
    • Praxis Dr. med. Claus Keller
  • Greifswald, Germany, 17475
    • Universitätsmedizin Greifswald Klinik und Poliklinik für Innere Medizin B
  • Großhansdorf, Germany, 22927
    • Pneumologisches Forschungsinstitut
  • Immenhausen, Germany, 34376
    • Lungenfachklinik Immenhausen
  • Köln, Germany, 51109
    • Kliniken der Stadt Köln GmbH
  • Solingen, Germany, 42699
    • Krankenhaus Bethanien - Klinik für Pneumologie und Allergologie
• Hungary
  • Budapest, Hungary, 1125
    • Semmelweis Egyetem
  • Farkasgyepű, Hungary, 8582
    • Veszprem Megyei Tudogyogyintezet
  • Miskolc, Hungary, 3529
    • Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktato Korhaz
  • Törökbálint, Hungary, 2045
    • Tudogyogyintezet Torokbalint
• Israel
  • Ashkelon, Israel, 78278
    • Barzilai Medical Center
  • Haifa, Israel, 34362
    • Lady Davis Carmel Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah University Hospital Ein Kerem
  • Kfar Saba, Israel, 44281
    • Meir Medical Center
  • Petah tikva, Israel, 49100
    • Rabin Medical Center - PPDS
  • Reẖovot, Israel, 7661041
    • Kaplan Medical Center
• Italy
  • Ancona, Italy, 60020
    • Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
  • Forlì, Italy, 47121
    • Presidio Ospedaliero GB Morgagni L Pierantoni
  • Milano, Italy, 20123
    • Ospedale S. Giuseppe Multimedica
  • Roma, Italy, 00168
    • Università Cattolica Del S Cuore
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese
  • Sicilia
    • Catania, Sicilia, Italy, 95123
      • Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
• Japan
  • Bunkyo, Japan, 113-8431
    • Juntendo University Hospital
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Ginowan, Japan, 901-2214
    • NHO Okinawa Hospital
  • Hamamatsu, Japan, 431-3192
    • Hamamatsu University School of Medicine
  • Himeji, Japan, 670-8520
    • National Hospital Organization Himeji Medical Center
  • Hiroshima, Japan, 734-8530
    • Hiroshima Prefectural Hospital
  • Hyōgo, Japan, 650-0047
    • Kobe City Medical Center General Hospital
  • Kumamoto, Japan, 861-4101
    • Saiseikai Kumamoto Hospital
  • Nagasaki, Japan, 852-8102
    • Nagasaki University Hospital
  • Nagoya, Japan, 466-8560
    • Nagoya University Hospital
  • Okayama, Japan, 700-8607
    • Japanese Red Cross Okayama Hospital
  • Sakai, Japan, 591-8555
    • National Hospital Organization Kinki-chuo Chest Medical Center
  • Sendai, Japan, 983-8512
    • Tohoku Medical and Pharmaceutical Hospital
  • Seto, Japan, 489-8642
    • Tosei General Hospital
  • Shinjuku-Ku, Japan, 160-0023
    • Tokyo Medical University Hospital
  • Tokushima, Japan, 770-8503
    • Tokushima University Hospital
  • Tokyo, Japan, 162-8655
    • Center Hospital of the National Center for Global Health and Medicine
  • Yokohama, Japan, 236-0051
    • Kanagawa Cardiovascular and Respiratory Center
  • Ibaraki
    • Naka, Ibaraki, Japan, 319-1113
      • National Hospital Organization Ibarakihigashi National Hospital
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 434-8511
      • Tenryu Hospital
• Korea, Republic of
  • Incheon, Korea, Republic of, 405760
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center - PPDS
  • Seoul, Korea, Republic of, 135-170
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 140-743
    • Soon Chun Hyang University Hospital Seoul
  • Gyeonggi-do
    • Bucheon, Gyeonggi-do, Korea, Republic of, 420-767
      • Soon Chun Hyang University Hospital Bucheon
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
      • Seoul National University Bundang Hospital
• Mexico
  • Ciudad de mexico, Mexico, 14080
    • Instituto Nacional De Enfermedades (INER)
  • Guadalajara, Mexico, 44130
    • Centro de Investigacion Medico Biologica y de Terapia Avanzada S.C.
  • Monterrey, Mexico, 64460
    • Hospital Universitatorio Dr. Jose Eleuterio González
  • Monterrey, Mexico, 64718
    • Unidad de Investigación Clínica En Medicina SC
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU Medisch Centrum
  • Amsterdam, Netherlands, 1091 AC
    • OLVG locatie Oost
  • Groningen, Netherlands, 9700 RM
    • Martini Ziekenhuis
  • Heerlen, Netherlands, 6419 PC
    • Zuyderland Medisch Centrum
  • Nieuwegein, Netherlands, 3425 CM
    • St. Antonius Ziekenhuis
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC
• New Zealand
  • Auckland, New Zealand, 1051
    • Greenlane Clinical Centre
  • Auckland, New Zealand, 1149
    • NZ Respiratory & Sleep Institute
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
  • Hamilton, New Zealand, 3204
    • Waikato Hospital
• Poland
  • Białystok, Poland, 15-044
    • Centrum Medycyny Oddechowej Mroz sp. j.
  • Gdańsk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne - PPDS
  • Katowice, Poland, 40-753
    • PULMAG Arkadiusz Brodowski, Grzegorz Gasior S. C.
  • Kraków, Poland, 31-153
    • Sp Zoz Szpital Uniwersytecki W Krakowie
  • Kraków, Poland, 31-159
    • Grażyna Jasieniak-Pinis ATOPIA Niepubliczny Zakład Opieki Zdrowotnej Poradnie Specjalistyczne
  • Lublin, Poland, 20-314
    • Etg Lublin
  • Warszawa, Poland, 02-777
    • Etg Warszawa
  • Łódź, Poland, 90-153
    • SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
• South Africa
  • Cape Town, South Africa, 7505
    • Tygerberg Hospital
  • Cape Town, South Africa, 7700
    • University of Cape Town Lung Institute (UCTLI)
  • Cape Town, South Africa, 7764
    • Dr Ismail Abdullah Private Practice
  • Durban, South Africa, 4017
    • Ethekwini Hospital
  • Durban, South Africa, 4091
    • Gateway Private Hospital
  • Johannesburg, South Africa, 2193
    • Milpark Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Pulmonary Specialists
    • Tucson, Arizona, United States, 85724
      • University of Arizona College of Medicine
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Los Angeles, California, United States, 90033
      • Keck School of Medicine of USC
    • Sacramento, California, United States, 95816
      • UC Davis Medical Center
    • San Francisco, California, United States, 94143
      • University of California, San Francisco Medical Center
  • Florida
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical Institute
    • Miami, Florida, United States, 33136
      • University of Miami
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group PA
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30309
      • Piedmont Healthcare
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System (UMHS)
    • Grand Rapids, Michigan, United States, 49546
      • Spectrum Health Medical Group
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Cardio Pulmonary Associates
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03765
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Atlantic Respiratory Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • Lovelace Scientific Resources Inc
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43203
      • Ohio State University
    • Toledo, Ohio, United States, 43608
      • Mercy Health - St. Vincent Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple Lung Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina - PPDS
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: GLPG1690, 600 milligrams (mg); Participants received GLPG1690 (ziritaxestat) 600 mg as film-coated tablet orally, once daily (mean treatment duration was 332.9 days). 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).	Drug: GLPG1690; GLPG1690, film-coated tablets for oral use.; Other Names: ziritaxestat
EXPERIMENTAL: GLPG1690, 200 mg; Participants received GLPG1690 (ziritaxestat) 200 mg as film-coated tablet orally, once daily (mean treatment duration was 336.9 days). 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).	Drug: GLPG1690; GLPG1690, film-coated tablets for oral use.; Other Names: ziritaxestat
EXPERIMENTAL: Placebo; Participants received GLPG1690 (ziritaxestat) matching placebo tablets orally, once daily (mean treatment duration was 346.2 days). 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).	Drug: Placebo; Matching placebo, film-coated tablets for oral use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual Rate of Decline in Forced Vital Capacity (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.	Baseline up to week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, week 52
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.	Week 52
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.	Baseline, week 52
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.	Baseline, week 52
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.	Baseline, week 52
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.	Baseline, week 52
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).	Baseline, week 52, week 100
Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat	Maximum Observed Plasma Concentration of Ziritaxtestat was reported.	Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose
Percentage of Participants With Disease Progression Up to 52 Weeks	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.	Up to week 52
Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS)	Percentage of participants with respiratory related to hospitalization were reported in this measure.	Up to EoS (week 125)
Annual Rate of Decline of 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.	Baseline up to EoS (week 125)
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.	Up to EoS (week 125)
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.	Baseline, week 100
Percentage of Participants With All Cause Hospitalization Until EoS	Percentage of participants with all cause hospitalization was reported for this measure.	Up to EoS (week 125)
Percentage of Participants With Respiratory Related Mortality Until EoS	Percentage of participants with respiratory related mortality until end of study were reported for this study.	Up to EoS (week 125)
Percentage of Participants Hospitalized for Non-Elective Lung Transplant Until EoS	Percentage of Participants who were hospitalized for lung transplant were reported for this measure.	Up to EoS (week 125)
Percentage of Participants With Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation Until EoS	Percentage of participants with acute IPF exacerbation until end of study were reported for this measure.	Up to EoS (week 125)
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.	Up to EoS (week 125)
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 qualifying for lung transplant were reported for this measure.	Up to EoS (week 125)
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.	Up to EoS (week 125)
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.	Up to EoS (week 125)
FVC at Week 100	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.	Week 100
Change From Baseline in FVC at Week 100	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.	Baseline, week 100
Percent Change From Baseline in FVC at Week 100	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.	Baseline, week 100
Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 100: 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.	Baseline, week 100
Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 100: 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.	Baseline, week 100
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	Safety was assessed by adverse events (AEs), which included abnormalities identified during a medical test (e.g. 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.	Baseline up to EoS (up to Week 125)
Changes From Baseline in Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100	Cough was evaluated using the LCQ. The LCQ is a 19-item questionnaire split into three domains: physical, psychological, and social. Scores were calculated by domain (range from 1 to 7) 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.	Baseline, week 52, week 100
Changes 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).	Baseline, week 52, week 100
Changes From Baseline in EuroQOL 5-Dimensions Questionnaire at Week 52 and Week 100	EuroQol outcome measurements was a printed 20 centimeter (cm) EQ visual analogue scale (EQ 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.	Baseline, week 52, week 100
Changes From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100	The King's Brief Interstitial Lung Disease questionnaire (K-BILD) was specifically developed to analyze the health status of participants with OLD, the questionnaire consists of of 15 items (assessed by participants on scale ranging from 1 to 7, where 1 and 7 represents 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).	Baseline, week 52, week 100
Area Under The Concentration Time Curve of Ziritaxtestat	Area under the concentration time curve of ziritaxtestat was reported	Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose
Change From Baseline in Functional Exercise Capacity, Assessed by The 6-Minute Walk Test (6MWT) Distance, at Week 52 and Week 100	The 6MWT depicts the total distance covered by a participant during 6 minutes walking.	Baseline, week 52, week 100
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 diffusing capacity of the lung for carbon monoxide (percent predicted hemoglobin level corrected) was reported for this measure. mmol/min/kPa: Millimole per minute per kilopascal	Baseline, week 52 and week 100

Collaborators and Investigators

• Sponsor: Galapagos NV

Publications and helpful links

General Publications

• Deng X, Salgado-Polo F, Shao T, Xiao Z, Van R, Chen J, Rong J, Haider A, Shao Y, Josephson L, Perrakis A, Liang SH. Imaging Autotaxin In Vivo with 18F-Labeled Positron Emission Tomography Ligands. J Med Chem. 2021 Oct 28;64(20):15053-15068. doi: 10.1021/acs.jmedchem.1c00913. Epub 2021 Oct 18.
• Maher TM, Kreuter M, Lederer DJ, Brown KK, Wuyts W, Verbruggen N, Stutvoet S, Fieuw A, Ford P, Abi-Saab W, Wijsenbeek M. Rationale, design and objectives of two phase III, randomised, placebo-controlled studies of GLPG1690, a novel autotaxin inhibitor, in idiopathic pulmonary fibrosis (ISABELA 1 and 2). BMJ Open Respir Res. 2019 May 21;6(1):e000422. doi: 10.1136/bmjresp-2019-000422. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 5, 2018
• Primary Completion (ACTUAL): March 30, 2021
• Study Completion (ACTUAL): March 30, 2021

Study Registration Dates

• First Submitted: November 5, 2018
• First Submitted That Met QC Criteria: November 5, 2018
• First Posted (ACTUAL): November 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 29, 2022
• Last Update Submitted That Met QC Criteria: July 6, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: GLPG1690-CL-304; 2018-001406-29 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No