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)
Idiopathic Pulmonary Fibrosis
About this trial
This is an interventional treatment trial for Idiopathic Pulmonary Fibrosis
Eligibility Criteria
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.
Sites / Locations
- Pulmonary Associates
- Mayo Clinic Arizona - PPDS
- Atria Clinical Research - BTC - PPDS
- David Geffen School of Medicine at UCLA
- Respire Research
- University of California San Diego
- Stanford University Medical Center
- University of Colorado
- National Jewish Health
- Western Connecticut Medical Group
- Yale University School of Medicine
- MedStar Georgetown University Hospital
- PAB Clinical Research - ClinEdge - PPDS
- St. Francis Medical Institute - BTC - PPDS
- North Florida/South Georgia Veterans Health System-NAVREF-PPDS
- University of Florida
- Advanced Pulmonary Research Institute
- Northwestern Memorial Hospital
- Pulmonary and Infections Disease Associates
- University of Louisville
- Tulane Medical Center
- University of Maryland Medical Center
- Massachusetts General Hospital, Division of Pulmonary and Critical Care Medicine
- Caritas St. Elizabeth's Medical Center
- Henry Ford Health System
- Minnesota Lung Center
- Mayo Clinic - PPDS
- Washington University School of Medicine
- Creighton University
- University of Rochester Medical Center - PPDS
- PulmonIx LLC
- UC Health Department of Internal Medicine, Pulmonary, Critical Care & Sleep Medicine
- Cleveland Clinic
- The Oregon Clinic
- Penn State Milton S Hershey Medical Center
- Hospital of the University of Pennsylvania
- Rhode Island Hospital
- Vanderbilt University Medical Center
- University of Texas Southwestern Medical Center
- Houston Methodist Hospital
- Metroplex Pulmonary and Sleep Medicine Center
- University of Texas Health Science Center San Antonio
- University of Utah Medical Care
- University of Virginia
- Western Washington Medical Group
- University of Washington Medical Center
- University of Wisconsin
- Royal Adelaide Hospital
- Flinders Medical Centre
- Box Hill Hospital
- Corte Royal Prince Alfred Hospital
- Lung Research Queensland
- Concord Repatriation General Hospital
- St Vincent's Hospital Sydney
- Austin Health
- Respiratory Clinical Trials Pty Ltd
- The Alfred Hospital
- ZNA Middelheim
- Hôpital Erasme
- Cliniques Universitaires Saint-Luc
- UZ Leuven
- CHU UCL Namur asbl - Site Godinne
- Irmandade Da Santa Casa de Misericordia de Porto Alegre
- Faculdade de Medicina Do ABC
- Hospital Clínico Regional de Concepción Dr Guillermo Grant Benavente
- Centro de Investigación Curico
- Centro Respiratorio Integral LTDA. (CENRESIN)
- Instituto Nacional Torax
- Centro de Investigaciones Medicas Respiratorias CIMER
- Hospital Dr Sotero Del Rio
- Centro de Investigacion del Maule
- Hospital Carlos Van Buren
- CINVEC- Estudos Clínicos Quinta Región Limitada
- Fakultni nemocnice Brno
- Fakultni nemocnice Ostrava
- Thomayerova nemocnice
- Nemocnice Na Bulovce
- Aarhus Universitetshospital
- Gentofte Hospital
- Odense Universitetshospital
- Zentralklinik Bad Berka GmbH
- Evangelische Lungenklinik
- Fachkrankenhaus Coswig
- Medizinische Hochschule Hannover
- Thorax Klinik
- Universitatsklinikum Leipzig
- Klinikum Rosenheim
- Sotiria Chest Hospital of Athens
- Attikon University General Hospital
- University General Hospital of Heraklion
- University General Hospital of Larissa
- Georgios Papanikolaou General Hospital of Thessaloniki
- Tenryu Hospital
- Saiseikai Kumamoto Hospital
- National Hospital Organization Kinki-Chuo Chest Medical Center
- Tosei General Hospital
- Center Hospital of the National Center for Global Health and Medicine
- National Hospital Organization Kyushu Medical Center
- Kanagawa Cardiovascular and Respiratory Center
- Hospital Chancay y Servicios Basicos de Salud
- Clinica Internacional - PPDS
- Hospital Nacional Guillermo Almenara Irigoyen ESSALUD
- Clinica Ricardo Palma - PPDS
- Clinica Providencia (Inverconsult Sociedad Anonima)
- Clinica San Pablo
- CHUVI - H.U. Alvaro Cunquerio
- Hospital Clinical de Barcelona
- Hospital Universitario de Bellvitge, Hospitalet De Llobregat
- Hospital Universitario de La Princesa
- Hospital Clinico San Carlos
- Clinica Universidad Navarra
- Hospital Universitario Marques de Valdecilla
- Consorcio Hospital General Universitario de Valencia
- Kaohsiung Medical University Hospital
- Far Eastern Memorial Hospital
- Taipei Medical University Shuang Ho Hospital
- National Taiwan University Hospital
- Süreyyapaşa Göğüs Hastalıkları Ve Göğüs Cerrahisi Eğitim Ve Araştırma Hastanesi
- Ege Universitesi Tıp Fakultesi Hastanesi Gögus Hastalıkları Anabilim Dalı
- Uludag Universitesi Tıp Fakultesi Hastanesi Gögüs Hastalıkları Anabilim Dalı
- Mersin Üniversitesi Tıp Fakültesi Hastanesi Göğüs Hastalıkları Polikinliği
- Birmingham Heartlands Hospital
- Southmead Hospital
- Papworth Hospital
- Castle Hill Hospital
- Royal Devon and Exeter Hospital NHS Trust
- Aintree University Hospital NHS Foundation Trust
- Royal Brompton Hospital
- Wythenshawe Hospital - PPDS
- The Newcastle Upon Tyne Hospitals NHS Foundation Trust
- Nottingham City Hospital
- Northern General Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Placebo Comparator
GLPG1690 600 mg
GLPG1690 200 mg
Placebo
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).
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).
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).