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

NCT ID: NCT03733444

Last Updated: 2022-07-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 781 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-05
• Study Completion Date: 2021-03-30

Brief Summary

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).

Conditions

Idiopathic Pulmonary Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

GLPG1690

Intervention Type: DRUG

GLPG1690, film-coated tablets for oral use.

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).

Group Type: EXPERIMENTAL

GLPG1690

Intervention Type: DRUG

GLPG1690, film-coated tablets for oral use.

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).

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo, film-coated tablets for oral use.

Interventions

GLPG1690

GLPG1690, film-coated tablets for oral use.

Intervention Type: DRUG

Placebo

Matching placebo, film-coated tablets for oral use.

Intervention Type: DRUG

Other Intervention Names

ziritaxestat

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Galapagos NV

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Galapagos Study Director

Role: STUDY_DIRECTOR

Galapagos NV

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Arizona Pulmonary Specialists

Phoenix, Arizona, United States

University of Arizona College of Medicine

Tucson, Arizona, United States

Keck School of Medicine of USC

Los Angeles, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

UC Davis Medical Center

Sacramento, California, United States

University of California, San Francisco Medical Center

San Francisco, California, United States

St. Francis Medical Institute

Clearwater, Florida, United States

University of Miami

Miami, Florida, United States

Renstar Medical Research

Ocala, Florida, United States

Central Florida Pulmonary Group PA

Orlando, Florida, United States

Piedmont Healthcare

Atlanta, Georgia, United States

Emory University

Atlanta, Georgia, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Brigham and Womens Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Michigan Health System (UMHS)

Ann Arbor, Michigan, United States

Spectrum Health Medical Group

Grand Rapids, Michigan, United States

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Cardio Pulmonary Associates

Chesterfield, Missouri, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Atlantic Respiratory Institute

Summit, New Jersey, United States

Lovelace Scientific Resources Inc

Albuquerque, New Mexico, United States

Albany Medical Center

Albany, New York, United States

Columbia University Medical Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

Mercy Health - St. Vincent Medical Center

Toledo, Ohio, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Temple Lung Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina - PPDS

Charleston, South Carolina, United States

University of Vermont

Burlington, Vermont, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

Centro Médico Dra de Salvo

Buenos Aires, , Argentina

Hospital Privado Centro Médico de Córdoba

Córdoba, , Argentina

CEMER Centro Médico de Enfermedades Respiratorias

Florida, , Argentina

Hospital Zonal Especializado de Agudos y Crónicos Dr. Antonio A. Cetrangolo

Luján, , Argentina

Instituto de Investigaciones Clínicas Mar Del Plata

Mar del Plata, , Argentina

Fundacion Scherbovsky

Mendoza, , Argentina

South Health Campus

Calgary, , Canada

Hôtel Dieu Du Centre Hospitalier de L'université de Montréal

Montreal, , Canada

McGill University Health Centre Research Institute

Montreal, , Canada

Institut Universitaire de Cardiologie et de Pneumologie

Québec, , Canada

Toronto General Hospital

Toronto, , Canada

Vancouver General Hospital

Vancouver, , Canada

Pacific Lung Research Center

Vancouver, , Canada

Dr Anil Dhar Professional Medicine Corporation

Windsor, , Canada

Hôpital Nord AP-HM

Marseille, , France

Centre Hospitalier Regional Universitaire Montpellier

Montpellier, , France

Groupe Hospitalier Bichat Claude Bernard

Paris, , France

CHU de Reims

Reims, , France

Kliniken der Stadt Koln GmbH

Cologne, , Germany

Ruhrlandklinik

Essen, , Germany

Praxis Dr. med. Claus Keller

Frankfurt, , Germany

Universitätsmedizin Greifswald Klinik und Poliklinik für Innere Medizin B

Greifswald, , Germany

Pneumologisches Forschungsinstitut

Großhansdorf, , Germany

Lungenfachklinik Immenhausen

Immenhausen, , Germany

Krankenhaus Bethanien - Klinik für Pneumologie und Allergologie

Solingen, , Germany

Semmelweis Egyetem

Budapest, , Hungary

Veszprem Megyei Tudogyogyintezet

Farkasgyepű, , Hungary

Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktató Kórház

Miskolc, , Hungary

Tüdőgyógyintézet Törökbálint

Törökbálint, , Hungary

Barzilai Medical Center

Ashkelon, , Israel

Lady Davis Carmel Medical Center

Haifa, , Israel

Hadassah University Hospital Ein Kerem

Jerusalem, , Israel

Meir Medical Center

Kfar Saba, , Israel

Rabin Medical Center - PPDS

Petah Tikva, , Israel

Kaplan Medical Center

Rehovot, , Israel

Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele

Catania, Sicily, Italy

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi

Ancona, , Italy

Presidio Ospedaliero GB Morgagni L Pierantoni

Forlì, , Italy

Ospedale S. Giuseppe Multimedica

Milan, , Italy

Università Cattolica Del S Cuore

Roma, , Italy

Azienda Ospedaliera Universitaria Senese

Siena, , Italy

National Hospital Organization Ibarakihigashi National Hospital

Naka, Ibaraki, Japan

Tenryu Hospital

Hamamatsu, Shizuoka, Japan

Juntendo University Hospital

Bunkyō City, , Japan

National Hospital Organization Kyushu Medical Center

Fukuoka, , Japan

Fukuoka University Hospital

Fukuoka, , Japan

NHO Okinawa Hospital

Ginowan, , Japan

Hamamatsu University School of Medicine

Hamamatsu, , Japan

National Hospital Organization Himeji Medical Center

Himeji, , Japan

Hiroshima Prefectural Hospital

Hiroshima, , Japan

Kobe City Medical Center General Hospital

Hyōgo, , Japan

Saiseikai Kumamoto Hospital

Kumamoto, , Japan

Nagasaki University Hospital

Nagasaki, , Japan

Nagoya University Hospital

Nagoya, , Japan

Japanese Red Cross Okayama Hospital

Okayama, , Japan

National Hospital Organization Kinki-Chuo Chest Medical Center

Sakai, , Japan

Tohoku Medical and Pharmaceutical Hospital

Sendai, , Japan

Tosei General Hospital

Seto, , Japan

Tokyo Medical University Hospital

Shinjuku-Ku, , Japan

Tokushima University Hospital

Tokushima, , Japan

Center Hospital of the National Center for Global Health and Medicine

Tokyo, , Japan

Kanagawa Cardiovascular and Respiratory Center

Yokohama, , Japan

Centro de Investigación Medico Biologica y de Terapia Avanzada S.C.

Guadalajara, , Mexico

Instituto Nacional De Enfermedades (INER)

Mexico City, , Mexico

Hospital Universitatorio Dr. Jose Eleuterio González

Monterrey, , Mexico

Unidad de Investigación Clínica En Medicina SC

Monterrey, , Mexico

VU Medisch Centrum

Amsterdam, , Netherlands

OLVG locatie Oost

Amsterdam, , Netherlands

Martini Ziekenhuis

Groningen, , Netherlands

Zuyderland Medisch Centrum

Heerlen, , Netherlands

St. Antonius Ziekenhuis

Nieuwegein, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Greenlane Clinical Centre

Auckland, , New Zealand

NZ Respiratory & Sleep Institute

Auckland, , New Zealand

Christchurch Hospital

Christchurch, , New Zealand

Waikato Hospital

Hamilton, , New Zealand

Centrum Medycyny Oddechowej Mroz sp. j.

Bialystok, , Poland

Uniwersyteckie Centrum Kliniczne - PPDS

Gdansk, , Poland

PULMAG Arkadiusz Brodowski, Grzegorz Gasior S. C.

Katowice, , Poland

SP ZOZ Szpital Uniwersytecki w Krakowie

Krakow, , Poland

GRAŻYNA JASIENIAK-PINIS ATOPIA Niepubliczny Zakład Opieki Zdrowotnej Poradnie Specjalistyczne

Krakow, , Poland

SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im Norberta Barlickiego Uniwersytetu Medycznego w Lodzi

Lodz, , Poland

ETG Lublin

Lublin, , Poland

ETG Warszawa

Warsaw, , Poland

Tygerberg Hospital

Cape Town, , South Africa

University of Cape Town Lung Institute (UCTLI)

Cape Town, , South Africa

Dr Ismail Abdullah Private Practice

Cape Town, , South Africa

Ethekwini Hospital

Durban, , South Africa

Gateway Private Hospital

Durban, , South Africa

Milpark Hospital

Johannesburg, , South Africa

Soon Chun Hyang University Hospital Bucheon

Bucheon-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Gachon University Gil Medical Center

Incheon, , South Korea

Asan Medical Center - PPDS

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Soon Chun Hyang University Hospital Seoul

Seoul, , South Korea

Countries

United States; Argentina; Canada; France; Germany; Hungary; Israel; Italy; Japan; Mexico; Netherlands; New Zealand; Poland; South Africa; South Korea

References

Ford P, Kreuter M, Brown KK, Wuyts WA, Wijsenbeek M, Israel-Biet D, Hubbard R, Nathan SD, Nunes H, Penninckx B, Prasad N, Seghers I, Spagnolo P, Verbruggen N, Hirani N, Behr J, Kaner RJ, Maher TM. An adjudication algorithm for respiratory-related hospitalisation in idiopathic pulmonary fibrosis. ERJ Open Res. 2024 Jan 29;10(1):00636-2023. doi: 10.1183/23120541.00636-2023. eCollection 2024 Jan.

Reference Type: DERIVED

PMID: 38288082 (View on PubMed)

Maher TM, Ford P, Brown KK, Costabel U, Cottin V, Danoff SK, Groenveld I, Helmer E, Jenkins RG, Milner J, Molenberghs G, Penninckx B, Randall MJ, Van Den Blink B, Fieuw A, Vandenrijn C, Rocak S, Seghers I, Shao L, Taneja A, Jentsch G, Watkins TR, Wuyts WA, Kreuter M, Verbruggen N, Prasad N, Wijsenbeek MS; ISABELA 1 and 2 Investigators. Ziritaxestat, a Novel Autotaxin Inhibitor, and Lung Function in Idiopathic Pulmonary Fibrosis: The ISABELA 1 and 2 Randomized Clinical Trials. JAMA. 2023 May 9;329(18):1567-1578. doi: 10.1001/jama.2023.5355.

Reference Type: DERIVED

PMID: 37159034 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34662125 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31179008 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-001406-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GLPG1690-CL-304

Identifier Type: -

Identifier Source: org_study_id