A Clinical Study to Test How Effective and Safe GLPG1690 is for Subjects With Idiopathic Pulmonary Fibrosis (IPF) When Used Together With Standard of Care (ISABELA1)

A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled Multicenter 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 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).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 525
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
  • Bedford Park, Australia, 5042
    • Flinders Medical Centre
  • Box Hill, Australia, VIC 3128
    • Box Hill Hospital
  • Camperdown, Australia, NSW 2050
    • Corte Royal Prince Alfred Hospital
  • Chermside, Australia, QLD 4060
    • Lung Research Queensland
  • Concord, Australia, NSW 2139
    • Concord Repatriation General Hospital
  • Darlinghurst, Australia, NSW 2010
    • St Vincent'S Hospital Sydney
  • Heidelberg, Australia, 3084
    • Austin Health
  • Kent Town, Australia, SA 5067
    • Respiratory Clinical Trials Pty Ltd
  • Melbourne, Australia, VIC 3004
    • The Alfred Hospital
• Belgium
  • Antwerp, Belgium, 2020
    • ZNA Middelheim
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Brussels, Belgium, 1070
    • Hopital Erasme
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Yvoir, Belgium, 5530
    • CHU UCL Namur asbl - Site Godinne
• Brazil
  • Porto Alegre, Brazil, 90035-074
    • Irmandade da Santa Casa de Misericórdia de Porto Alegre
  • Santo André, Brazil, 09060-870
    • Faculdade de Medicina do ABC
• Chile
  • Concepción, Chile, 4070038
    • Hospital Clínico Regional de Concepción Dr Guillermo Grant Benavente
  • Curicó, Chile, 3341643
    • Centro de Investigación Curico
  • Quillota, Chile, 2260000
    • Centro Respiratorio Integral LTDA. (CENRESIN)
  • Santiago, Chile, 7500691
    • Instituto Nacional Torax
  • Santiago, Chile, 7500692
    • Centro de Investigaciones Medicas Respiratorias CIMER
  • Santiago, Chile, 8207257
    • Hospital Dr Sotero del Rio
  • Talca, Chile, 3465584
    • Centro de Investigación del Maule
  • Valparaíso, Chile, 2352499
    • Hospital Carlos Van Buren
  • Viña Del Mar, Chile, 2520024
    • CINVEC- Estudos Clínicos Quinta Región Limitada
• Czechia
  • Brno, Czechia, 62500
    • Fakultni nemocnice Brno
  • Ostrava, Czechia, 708 52
    • Fakultni nemocnice Ostrava
  • Praha, Czechia, 180 81
    • Nemocnice Na Bulovce
  • Praha, Czechia, 14059
    • Thomayerova nemocnice
• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus Universitetshospital
  • Hellerup, Denmark, 2900
    • Gentofte Hospital
  • Odense, Denmark, 5000
    • Odense Universitetshospital
• Germany
  • Bad Berka, Germany, 99437
    • Zentralklinik Bad Berka GmbH
  • Berlin, Germany, 13125
    • Evangelische Lungenklinik
  • Coswig, Germany, 01640
    • Fachkrankenhaus Coswig
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69126
    • Thorax Klinik
  • Leipzig, Germany, 04103
    • Universitatsklinikum Leipzig
  • Rosenheim, Germany, 83022
    • Klinikum Rosenheim
• Greece
  • Athens, Greece, 11527
    • Sotiria Chest Hospital of Athens
  • Athens, Greece, 12464
    • Attikon University General Hospital
  • Iraklio, Greece, 71110
    • University General Hospital of Heraklion
  • Larissa, Greece, 41110
    • University General Hospital of Larissa
  • Thessaloníki, Greece, 57010
    • Georgios Papanikolaou General Hospital of Thessaloniki
• Japan
  • Hamamatsu, Japan, 434-8511
    • Tenryu Hospital
  • Kumamoto, Japan, 861-4193
    • Saiseikai Kumamoto Hospital
  • Sakai, Japan, 591-8555
    • National Hospital Organization Kinki-chuo Chest Medical Center
  • Seto, Japan, 489-0065
    • Tosei General Hospital
  • Tokyo, Japan, 162-0052
    • Center Hospital of the National Center for Global Health and Medicine
  • Tokyo, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center
  • Yokohama, Japan, 236-0051
    • Kanagawa Cardiovascular and Respiratory Center
• Peru
  • Chancay, Peru, 15131
    • Hospital Chancay y Servicios Basicos de Salud
  • Lima, Peru
    • Hospital Nacional Guillermo Almenara Irigoyen ESSALUD
  • Lima Cercado, Peru
    • Clinica Internacional - PPDS
  • San Isidro, Peru
    • Clinica Ricardo Palma - PPDS
  • San Miguel, Peru
    • Clinica Providencia (Inverconsult Sociedad Anonima)
  • Santiago De Surco, Peru
    • Clinica San Pablo
• Spain
  • Barcelona, Spain, 03036
    • Hospital Clinical de Barcelona
  • Barcelona, Spain, 08097
    • Hospital Universitario de Bellvitge, Hospitalet De Llobregat
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28006
    • Hospital Universitario de la Princesa
  • Pamplona, Spain, 31008
    • Clinica Universidad Navarra
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Valencia, Spain, 46014
    • Consorcio Hospital General Universitario de Valencia
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36312
      • CHUVI - H.U. Alvaro Cunquerio
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Hospital
  • New Taipei City, Taiwan, 220
    • Far Eastern Memorial Hospital
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University Shuang Ho Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• Turkey
  • Istanbul, Turkey, 34854
    • Süreyyapaşa Göğüs Hastalıkları Ve Göğüs Cerrahisi Eğitim Ve Araştırma Hastanesi
  • Mersin, Turkey, 33169
    • Mersin Üniversitesi Tıp Fakültesi Hastanesi Göğüs Hastalıkları Polikinliği
  • İzmir, Turkey, 35100
    • Ege Universitesi Tıp Fakultesi Hastanesi Gögus Hastalıkları Anabilim Dalı
  • İzmir, Turkey, 35100
    • Uludag Universitesi Tıp Fakultesi Hastanesi Gögüs Hastalıkları Anabilim Dalı
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Bristol, United Kingdom, BS10 5NB
    • Southmead Hospital
  • Cambridge, United Kingdom, CB233RE
    • Papworth Hospital
  • Cottingham, United Kingdom, HU16 5JQ
    • Castle Hill Hospital
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter Hospital NHS Trust
  • Liverpool, United Kingdom, L9 7AL
    • Aintree University Hospital NHS Foundation Trust
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • Manchester, United Kingdom, M23 9LT
    • Wythenshawe Hospital - PPDS
  • Newcastle, United Kingdom, NE14LP
    • The Newcastle Upon Tyne Hospitals NHS Foundation Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
  • Sheffield, United Kingdom, S5 7AU
    • Northern General Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona - PPDS
  • Arkansas
    • Little Rock, Arkansas, United States, 72209
      • Atria Clinical Research - BTC - PPDS
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA
    • Palm Springs, California, United States, 92262
      • RESPIRE Research
    • San Diego, California, United States, 92037
      • University of California San Diego
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Western Connecticut Medical Group
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Brandon, Florida, United States, 33511
      • PAB Clinical Research - ClinEdge - PPDS
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical Institute - BTC - PPDS
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Gainesville, Florida, United States, 32608
      • North Florida/South Georgia Veterans Health System-NAVREF-PPDS
    • Loxahatchee Groves, Florida, United States, 33470
      • Advanced Pulmonary Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Iowa
    • Council Bluffs, Iowa, United States, 51503
      • Pulmonary and Infections Disease Associates
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • Caritas St. Elizabeth's Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital, Division of Pulmonary and Critical Care Medicine
  • Michigan
    • Dearborn, Michigan, United States, 48124
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minnesota Lung Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - PPDS
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton University
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center - PPDS
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • PulmonIx LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • UC Health Department of Internal Medicine, Pulmonary, Critical Care & Sleep Medicine
    • Cleveland, Ohio, United States, 44195-0001
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97220
      • The Oregon Clinic
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • McKinney, Texas, United States, 75069
      • Metroplex Pulmonary and Sleep Medicine Center
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Medical Care
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Washington
    • Everett, Washington, United States, 98208
      • Western Washington Medical Group
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 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 Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	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 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).	Drug: GLPG1690; GLPG1690, film-coated tablets for oral use.; Other Names: ziritaxestat
Placebo Comparator: 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).	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 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
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.	Up to week 52
Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS)	Percentage of participants with respiratory related hospitalization were reported in this measure.	Up to EoS (week 121)
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
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.	Baseline up to EoS (week 121)
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 121)
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 121)
Percentage of Participants With Respiratory Related Mortality Until EoS	Percentage of participants with respiratory related mortality until EoS were reported for this study.	Up to EoS (week 121)
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.	Up to EoS (week 121)
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.	Up to EoS (week 121)
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 121)
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.	Up to EoS (week 121)
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 121)
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 121)
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
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.	Week 112
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.	Baseline, week 112
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.	Baseline, week 112
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 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.	Baseline, week 112
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
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.	Baseline, week 112
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.	Baseline up to 30 days after the last dose (up to week 121)
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.	Baseline, week 52, week 100
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).	Baseline, week 52, week 100
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
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.	Baseline, week 52, week 100
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).	Baseline, week 52, week 100
Area Under The Concentration Time Curve (AUC) 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
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
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.	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 DLCO (percent predicted hemoglobin level corrected) was reported for this measure.mmol/min/kPa: Millimole per minute per kilopascal	Baseline, week 52, week 100

Collaborators and Investigators

• Sponsor: Galapagos NV
• Investigators: Study Director: Galapagos Study Director, MD, Galapagos NV

Publications and helpful links

General Publications

• 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 28, 2018
• Primary Completion (Actual): March 30, 2021
• Study Completion (Actual): March 30, 2021

Study Registration Dates

• First Submitted: October 15, 2018
• First Submitted That Met QC Criteria: October 17, 2018
• First Posted (Actual): October 18, 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-303; 2018-001405-87 (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