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

NCT ID: NCT03711162

Last Updated: 2022-07-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 525 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-28
• Study Completion Date: 2021-03-30

Brief Summary

The main purpose of this study was to see how GLPG1690 works together with your current standard treatment on your lung function and IPF disease in general. The study also investigated how well GLPG1690 is tolerated (for example if you got any side effects while on study drug).

Conditions

Idiopathic Pulmonary Fibrosis

Study Design

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

Study Groups

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).

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 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).

Group Type: EXPERIMENTAL

GLPG1690

Intervention Type: DRUG

GLPG1690, film-coated tablets for oral use.

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).

Group Type: PLACEBO_COMPARATOR

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, MD

Role: STUDY_DIRECTOR

Galapagos NV

Locations

Pulmonary Associates

Phoenix, Arizona, United States

Mayo Clinic Arizona - PPDS

Scottsdale, Arizona, United States

Atria Clinical Research - BTC - PPDS

Little Rock, Arkansas, United States

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Respire Research

Palm Springs, California, United States

University of California San Diego

San Diego, California, United States

Stanford University Medical Center

Stanford, California, United States

University of Colorado

Aurora, Colorado, United States

National Jewish Health

Denver, Colorado, United States

Western Connecticut Medical Group

Danbury, Connecticut, United States

Yale University School of Medicine

New Haven, Connecticut, United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

PAB Clinical Research - ClinEdge - PPDS

Brandon, Florida, United States

St. Francis Medical Institute - BTC - PPDS

Clearwater, Florida, United States

North Florida/South Georgia Veterans Health System-NAVREF-PPDS

Gainesville, Florida, United States

University of Florida

Gainesville, Florida, United States

Advanced Pulmonary Research Institute

Loxahatchee Groves, Florida, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Pulmonary and Infections Disease Associates

Council Bluffs, Iowa, United States

University of Louisville

Louisville, Kentucky, United States

Tulane Medical Center

New Orleans, Louisiana, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

Massachusetts General Hospital, Division of Pulmonary and Critical Care Medicine

Boston, Massachusetts, United States

Caritas St. Elizabeth's Medical Center

Boston, Massachusetts, United States

Henry Ford Health System

Dearborn, Michigan, United States

Minnesota Lung Center

Minneapolis, Minnesota, United States

Mayo Clinic - PPDS

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

Creighton University

Omaha, Nebraska, United States

University of Rochester Medical Center - PPDS

Rochester, New York, United States

PulmonIx LLC

Greensboro, North Carolina, United States

UC Health Department of Internal Medicine, Pulmonary, Critical Care & Sleep Medicine

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

The Oregon Clinic

Portland, Oregon, United States

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

Metroplex Pulmonary and Sleep Medicine Center

McKinney, Texas, United States

University of Texas Health Science Center San Antonio

San Antonio, Texas, United States

University of Utah Medical Care

Salt Lake City, Utah, United States

University of Virginia

Charlottesville, Virginia, United States

Western Washington Medical Group

Everett, Washington, United States

University of Washington Medical Center

Seattle, Washington, United States

University of Wisconsin

Madison, Wisconsin, United States

Royal Adelaide Hospital

Adelaide, , Australia

Flinders Medical Centre

Bedford Park, , Australia

Box Hill Hospital

Box Hill, , Australia

Corte Royal Prince Alfred Hospital

Camperdown, , Australia

Lung Research Queensland

Chermside, , Australia

Concord Repatriation General Hospital

Concord, , Australia

St Vincent's Hospital Sydney

Darlinghurst, , Australia

Austin Health

Heidelberg, , Australia

Respiratory Clinical Trials Pty Ltd

Kent Town, , Australia

The Alfred Hospital

Melbourne, , Australia

ZNA Middelheim

Antwerp, , Belgium

Hôpital Erasme

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

UZ Leuven

Leuven, , Belgium

CHU UCL Namur asbl - Site Godinne

Yvoir, , Belgium

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, , Brazil

Faculdade de Medicina Do ABC

Santo André, , Brazil

Hospital Clínico Regional de Concepción Dr Guillermo Grant Benavente

Concepción, , Chile

Centro de Investigación Curico

Curicó, , Chile

Centro Respiratorio Integral LTDA. (CENRESIN)

Quillota, , Chile

Instituto Nacional Torax

Santiago, , Chile

Centro de Investigaciones Medicas Respiratorias CIMER

Santiago, , Chile

Hospital Dr Sotero Del Rio

Santiago, , Chile

Centro de Investigacion del Maule

Talca, , Chile

Hospital Carlos Van Buren

Valparaíso, , Chile

CINVEC- Estudos Clínicos Quinta Región Limitada

Viña del Mar, , Chile

Fakultni nemocnice Brno

Brno, , Czechia

Fakultni nemocnice Ostrava

Ostrava, , Czechia

Thomayerova nemocnice

Prague, , Czechia

Nemocnice Na Bulovce

Prague, , Czechia

Aarhus Universitetshospital

Aarhus, , Denmark

Gentofte Hospital

Hellerup, , Denmark

Odense Universitetshospital

Odense, , Denmark

Zentralklinik Bad Berka GmbH

Bad Berka, , Germany

Evangelische Lungenklinik

Berlin, , Germany

Fachkrankenhaus Coswig

Coswig, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Thorax Klinik

Heidelberg, , Germany

Universitatsklinikum Leipzig

Leipzig, , Germany

Klinikum Rosenheim

Rosenheim, , Germany

Sotiria Chest Hospital of Athens

Athens, , Greece

Attikon University General Hospital

Athens, , Greece

University General Hospital of Heraklion

Heraklion, , Greece

University General Hospital of Larissa

Larissa, , Greece

Georgios Papanikolaou General Hospital of Thessaloniki

Thessaloniki, , Greece

Tenryu Hospital

Hamamatsu, , Japan

Saiseikai Kumamoto Hospital

Kumamoto, , Japan

National Hospital Organization Kinki-Chuo Chest Medical Center

Sakai, , Japan

Tosei General Hospital

Seto, , Japan

Center Hospital of the National Center for Global Health and Medicine

Tokyo, , Japan

National Hospital Organization Kyushu Medical Center

Tokyo, , Japan

Kanagawa Cardiovascular and Respiratory Center

Yokohama, , Japan

Hospital Chancay y Servicios Basicos de Salud

Chancay, , Peru

Hospital Nacional Guillermo Almenara Irigoyen ESSALUD

Lima, , Peru

Clinica Internacional - PPDS

Lima Cercado, , Peru

Clinica Ricardo Palma - PPDS

San Isidro, , Peru

Clinica Providencia (Inverconsult Sociedad Anonima)

San Miguel, , Peru

Clinica San Pablo

Santiago de Surco, , Peru

CHUVI - H.U. Alvaro Cunquerio

Vigo, Pontevedra, Spain

Hospital Clinical de Barcelona

Barcelona, , Spain

Hospital Universitario de Bellvitge, Hospitalet De Llobregat

Barcelona, , Spain

Hospital Universitario de La Princesa

Madrid, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Clinica Universidad Navarra

Pamplona, , Spain

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Consorcio Hospital General Universitario de Valencia

Valencia, , Spain

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

Far Eastern Memorial Hospital

New Taipei City, , Taiwan

Taipei Medical University Shuang Ho Hospital

New Taipei City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Süreyyapaşa Göğüs Hastalıkları Ve Göğüs Cerrahisi Eğitim Ve Araştırma Hastanesi

Istanbul, , Turkey (Türkiye)

Ege Universitesi Tıp Fakultesi Hastanesi Gögus Hastalıkları Anabilim Dalı

Izmir, , Turkey (Türkiye)

Uludag Universitesi Tıp Fakultesi Hastanesi Gögüs Hastalıkları Anabilim Dalı

Izmir, , Turkey (Türkiye)

Mersin Üniversitesi Tıp Fakültesi Hastanesi Göğüs Hastalıkları Polikinliği

Mersin, , Turkey (Türkiye)

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Southmead Hospital

Bristol, , United Kingdom

Papworth Hospital

Cambridge, , United Kingdom

Castle Hill Hospital

Cottingham, , United Kingdom

Royal Devon and Exeter Hospital NHS Trust

Exeter, , United Kingdom

Aintree University Hospital NHS Foundation Trust

Liverpool, , United Kingdom

Royal Brompton Hospital

London, , United Kingdom

Wythenshawe Hospital - PPDS

Manchester, , United Kingdom

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle, , United Kingdom

Nottingham City Hospital

Nottingham, , United Kingdom

Northern General Hospital

Sheffield, , United Kingdom

Countries

United States; Australia; Belgium; Brazil; Chile; Czechia; Denmark; Germany; Greece; Japan; Peru; Spain; Taiwan; Turkey (Türkiye); United Kingdom

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)

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

2018-001405-87

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GLPG1690-CL-303

Identifier Type: -

Identifier Source: org_study_id