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

NCT03711162 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: GLPG1690-CL-3032018-001405-87
• Study Type: interventional
• Target: 525
• Locations: 15 countries
• Sites: 132

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (34)

• Percentage of Participants With Disease Progression up to Week 52

  Up to week 52

• Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS)

  Up to EoS (week 121)

• Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 52

  Baseline, week 52

• Annual Rate of Decline in FVC Until EoS

  Baseline up to EoS (week 121)

• Percentage of Participants With Disease Progression Until EoS

  Up to EoS (week 121)

Study Arms (3)

GLPG1690 600 mg

EXPERIMENTAL

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 200 mg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

GLPG1690 DRUG

GLPG1690, film-coated tablets for oral use.

Also known as: ziritaxestat

GLPG1690 200 mg; GLPG1690 600 mg

Placebo DRUG

Matching placebo, film-coated tablets for oral use.

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Galapagos NV: lead

Study Sites (132)

Pulmonary Associates

Phoenix, Arizona, 85006, United States

Location

Mayo Clinic Arizona - PPDS

Scottsdale, Arizona, 85259, United States

Location

Atria Clinical Research - BTC - PPDS

Little Rock, Arkansas, 72209, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

Respire Research

Palm Springs, California, 92262, United States

Location

University of California San Diego

San Diego, California, 92037, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Western Connecticut Medical Group

Danbury, Connecticut, 06810, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

PAB Clinical Research - ClinEdge - PPDS

Brandon, Florida, 33511, United States

Location

St. Francis Medical Institute - BTC - PPDS

Clearwater, Florida, 33765, United States

Location

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

Gainesville, Florida, 32608, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Advanced Pulmonary Research Institute

Loxahatchee Groves, Florida, 33470, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Pulmonary and Infections Disease Associates

Council Bluffs, Iowa, 51503, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital, Division of Pulmonary and Critical Care Medicine

Boston, Massachusetts, 02114, United States

Location

Caritas St. Elizabeth's Medical Center

Boston, Massachusetts, 02135, United States

Location

Henry Ford Health System

Dearborn, Michigan, 48124, United States

Location

Minnesota Lung Center

Minneapolis, Minnesota, 55407, United States

Location

Mayo Clinic - PPDS

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Creighton University

Omaha, Nebraska, 68131, United States

Location

University of Rochester Medical Center - PPDS

Rochester, New York, 14642, United States

Location

PulmonIx LLC

Greensboro, North Carolina, 27403, United States

Location

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

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195-0001, United States

Location

The Oregon Clinic

Portland, Oregon, 97220, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Metroplex Pulmonary and Sleep Medicine Center

McKinney, Texas, 75069, United States

Location

University of Texas Health Science Center San Antonio

San Antonio, Texas, 78229, United States

Location

University of Utah Medical Care

Salt Lake City, Utah, 84108, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Western Washington Medical Group

Everett, Washington, 98208, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Royal Adelaide Hospital

Adelaide, 5000, Australia

Location

Flinders Medical Centre

Bedford Park, 5042, Australia

Location

Box Hill Hospital

Box Hill, VIC 3128, Australia

Location

Corte Royal Prince Alfred Hospital

Camperdown, NSW 2050, Australia

Location

Lung Research Queensland

Chermside, QLD 4060, Australia

Location

Concord Repatriation General Hospital

Concord, NSW 2139, Australia

Location

St Vincent's Hospital Sydney

Darlinghurst, NSW 2010, Australia

Location

Austin Health

Heidelberg, 3084, Australia

Location

Respiratory Clinical Trials Pty Ltd

Kent Town, SA 5067, Australia

Location

The Alfred Hospital

Melbourne, VIC 3004, Australia

Location

ZNA Middelheim

Antwerp, 2020, Belgium

Location

Hôpital Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHU UCL Namur asbl - Site Godinne

Yvoir, 5530, Belgium

Location

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, 90035-074, Brazil

Location

Faculdade de Medicina Do ABC

Santo André, 09060-870, Brazil

Location

Hospital Clínico Regional de Concepción Dr Guillermo Grant Benavente

Concepción, 4070038, Chile

Location

Centro de Investigación Curico

Curicó, 3341643, Chile

Location

Centro Respiratorio Integral LTDA. (CENRESIN)

Quillota, 2260000, Chile

Location

Instituto Nacional Torax

Santiago, 7500691, Chile

Location

Centro de Investigaciones Medicas Respiratorias CIMER

Santiago, 7500692, Chile

Location

Hospital Dr Sotero Del Rio

Santiago, 8207257, Chile

Location

Centro de Investigacion del Maule

Talca, 3465584, Chile

Location

Hospital Carlos Van Buren

Valparaíso, 2352499, Chile

Location

CINVEC- Estudos Clínicos Quinta Región Limitada

Viña del Mar, 2520024, Chile

Location

Fakultni nemocnice Brno

Brno, 62500, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava, 708 52, Czechia

Location

Thomayerova nemocnice

Prague, 14059, Czechia

Location

Nemocnice Na Bulovce

Prague, 180 81, Czechia

Location

Aarhus Universitetshospital

Aarhus, 8200, Denmark

Location

Gentofte Hospital

Hellerup, 2900, Denmark

Location

Odense Universitetshospital

Odense, 5000, Denmark

Location

Zentralklinik Bad Berka GmbH

Bad Berka, 99437, Germany

Location

Evangelische Lungenklinik

Berlin, 13125, Germany

Location

Fachkrankenhaus Coswig

Coswig, 01640, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Thorax Klinik

Heidelberg, 69126, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

Klinikum Rosenheim

Rosenheim, 83022, Germany

Location

Sotiria Chest Hospital of Athens

Athens, 11527, Greece

Location

Attikon University General Hospital

Athens, 12464, Greece

Location

University General Hospital of Heraklion

Heraklion, 71110, Greece

Location

University General Hospital of Larissa

Larissa, 41110, Greece

Location

Georgios Papanikolaou General Hospital of Thessaloniki

Thessaloniki, 57010, Greece

Location

Tenryu Hospital

Hamamatsu, 434-8511, Japan

Location

Saiseikai Kumamoto Hospital

Kumamoto, 861-4193, Japan

Location

National Hospital Organization Kinki-Chuo Chest Medical Center

Sakai, 591-8555, Japan

Location

Tosei General Hospital

Seto, 489-0065, Japan

Location

Center Hospital of the National Center for Global Health and Medicine

Tokyo, 162-0052, Japan

Location

National Hospital Organization Kyushu Medical Center

Tokyo, 810-8563, Japan

Location

Kanagawa Cardiovascular and Respiratory Center

Yokohama, 236-0051, Japan

Location

Hospital Chancay y Servicios Basicos de Salud

Chancay, 15131, Peru

Location

Hospital Nacional Guillermo Almenara Irigoyen ESSALUD

Lima, Peru

Location

Clinica Internacional - PPDS

Lima Cercado, Peru

Location

Clinica Ricardo Palma - PPDS

San Isidro, Peru

Location

Clinica Providencia (Inverconsult Sociedad Anonima)

San Miguel, Peru

Location

Clinica San Pablo

Santiago de Surco, Peru

Location

CHUVI - H.U. Alvaro Cunquerio

Vigo, Pontevedra, 36312, Spain

Location

Hospital Clinical de Barcelona

Barcelona, 03036, Spain

Location

Hospital Universitario de Bellvitge, Hospitalet De Llobregat

Barcelona, 08097, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Clinica Universidad Navarra

Pamplona, 31008, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Consorcio Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Kaohsiung Medical University Hospital

Kaohsiung City, 807, Taiwan

Location

Far Eastern Memorial Hospital

New Taipei City, 220, Taiwan

Location

Taipei Medical University Shuang Ho Hospital

New Taipei City, 23561, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Süreyyapaşa Göğüs Hastalıkları Ve Göğüs Cerrahisi Eğitim Ve Araştırma Hastanesi

Istanbul, 34854, Turkey (Türkiye)

Location

Ege Universitesi Tıp Fakultesi Hastanesi Gögus Hastalıkları Anabilim Dalı

Izmir, 35100, Turkey (Türkiye)

Location

Uludag Universitesi Tıp Fakultesi Hastanesi Gögüs Hastalıkları Anabilim Dalı

Izmir, 35100, Turkey (Türkiye)

Location

Mersin Üniversitesi Tıp Fakültesi Hastanesi Göğüs Hastalıkları Polikinliği

Mersin, 33169, Turkey (Türkiye)

Location

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

Southmead Hospital

Bristol, BS10 5NB, United Kingdom

Location

Papworth Hospital

Cambridge, CB233RE, United Kingdom

Location

Castle Hill Hospital

Cottingham, HU16 5JQ, United Kingdom

Location

Royal Devon and Exeter Hospital NHS Trust

Exeter, EX2 5DW, United Kingdom

Location

Aintree University Hospital NHS Foundation Trust

Liverpool, L9 7AL, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Wythenshawe Hospital - PPDS

Manchester, M23 9LT, United Kingdom

Location

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle, NE14LP, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Northern General Hospital

Sheffield, S5 7AU, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 38288082 DERIVED

• 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.

  PMID: 37159034 DERIVED

• 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.

  PMID: 31179008 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

GLPG1690

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

This Study was prematurely terminated based on recommendations of the Independent Data Monitoring Committee.

Results Point of Contact

• Title: Galapagos Medical Information
• Organization: Galapagos NV

medicalinfo@glpg.com

+32 15 342900

Study Officials

• Galapagos Study Director, MD

  Galapagos NV

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 18, 2018
• Study Start: November 28, 2018
• Primary Completion: March 30, 2021
• Study Completion: March 30, 2021
• Last Updated: July 29, 2022
• Results First Posted: July 29, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

GR (5); CZ (4); PE (6); GB (11); TU (4); BR (2); AU (10); DK (3); BE (5); CL (9); ES (8); TW (4); US (47); JP (7); DE (7)