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

NCT03733444 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: GLPG1690-CL-3042018-001406-29
• Study Type: interventional
• Target: 781
• Locations: 15 countries
• Sites: 132

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

Outcome Measures

Primary Outcomes (1)

• Annual Rate of Decline in Forced Vital Capacity (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 52 Weeks

  Up to week 52

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

  Up to EoS (week 125)

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

  Baseline, week 52

• Annual Rate of Decline of FVC Until EoS

  Baseline up to EoS (week 125)

• Percentage of Participants With Disease Progression Until EoS

  Up to EoS (week 125)

Study Arms (3)

GLPG1690, 600 milligrams (mg)

EXPERIMENTAL

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).

Drug: GLPG1690

GLPG1690, 200 mg

EXPERIMENTAL

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).

Drug: GLPG1690

Placebo

EXPERIMENTAL

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).

Drug: Placebo

Interventions

GLPG1690 DRUG

GLPG1690, film-coated tablets for oral use.

Also known as: ziritaxestat

GLPG1690, 200 mg; GLPG1690, 600 milligrams (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)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Arizona Pulmonary Specialists

Phoenix, Arizona, 85012, United States

Location

University of Arizona College of Medicine

Tucson, Arizona, 85724, United States

Location

Keck School of Medicine of USC

Los Angeles, California, 90033, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UC Davis Medical Center

Sacramento, California, 95816, United States

Location

University of California, San Francisco Medical Center

San Francisco, California, 94143, United States

Location

St. Francis Medical Institute

Clearwater, Florida, 33765, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Central Florida Pulmonary Group PA

Orlando, Florida, 32803, United States

Location

Piedmont Healthcare

Atlanta, Georgia, 30309, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Brigham and Womens Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System (UMHS)

Ann Arbor, Michigan, 48109, United States

Location

Spectrum Health Medical Group

Grand Rapids, Michigan, 49546, United States

Location

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Cardio Pulmonary Associates

Chesterfield, Missouri, 63017, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03765, United States

Location

Atlantic Respiratory Institute

Summit, New Jersey, 07901, United States

Location

Lovelace Scientific Resources Inc

Albuquerque, New Mexico, 87108, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University

Columbus, Ohio, 43203, United States

Location

Mercy Health - St. Vincent Medical Center

Toledo, Ohio, 43608, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Temple Lung Center

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina - PPDS

Charleston, South Carolina, 29425, United States

Location

University of Vermont

Burlington, Vermont, 05401, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Centro Médico Dra de Salvo

Buenos Aires, C1426ABP, Argentina

Location

Hospital Privado Centro Médico de Córdoba

Córdoba, X5016KEH, Argentina

Location

CEMER Centro Médico de Enfermedades Respiratorias

Florida, B1602DQD, Argentina

Location

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

Luján, B6700CNR, Argentina

Location

Instituto de Investigaciones Clínicas Mar Del Plata

Mar del Plata, B7600FZN, Argentina

Location

Fundacion Scherbovsky

Mendoza, 5500, Argentina

Location

South Health Campus

Calgary, T3M 1M4, Canada

Location

Hôtel Dieu Du Centre Hospitalier de L'université de Montréal

Montreal, H2L 4M1, Canada

Location

McGill University Health Centre Research Institute

Montreal, QC H3S 1Y9, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie

Québec, G1V 4G5, Canada

Location

Toronto General Hospital

Toronto, M5G 2N2, Canada

Location

Vancouver General Hospital

Vancouver, V5Z 1M9, Canada

Location

Pacific Lung Research Center

Vancouver, V6Z 1Y6, Canada

Location

Dr Anil Dhar Professional Medicine Corporation

Windsor, N8W1L9, Canada

Location

Hôpital Nord AP-HM

Marseille, 13915, France

Location

Centre Hospitalier Regional Universitaire Montpellier

Montpellier, 34295, France

Location

Groupe Hospitalier Bichat Claude Bernard

Paris, 75018, France

Location

CHU de Reims

Reims, 51092, France

Location

Kliniken der Stadt Koln GmbH

Cologne, 51109, Germany

Location

Ruhrlandklinik

Essen, 45239, Germany

Location

Praxis Dr. med. Claus Keller

Frankfurt, 60389, Germany

Location

Universitätsmedizin Greifswald Klinik und Poliklinik für Innere Medizin B

Greifswald, 17475, Germany

Location

Pneumologisches Forschungsinstitut

Großhansdorf, 22927, Germany

Location

Lungenfachklinik Immenhausen

Immenhausen, 34376, Germany

Location

Krankenhaus Bethanien - Klinik für Pneumologie und Allergologie

Solingen, 42699, Germany

Location

Semmelweis Egyetem

Budapest, 1125, Hungary

Location

Veszprem Megyei Tudogyogyintezet

Farkasgyepű, 8582, Hungary

Location

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

Miskolc, 3529, Hungary

Location

Tüdőgyógyintézet Törökbálint

Törökbálint, 2045, Hungary

Location

Barzilai Medical Center

Ashkelon, 78278, Israel

Location

Lady Davis Carmel Medical Center

Haifa, 34362, Israel

Location

Hadassah University Hospital Ein Kerem

Jerusalem, 91120, Israel

Location

Meir Medical Center

Kfar Saba, 44281, Israel

Location

Rabin Medical Center - PPDS

Petah Tikva, 49100, Israel

Location

Kaplan Medical Center

Rehovot, 7661041, Israel

Location

Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele

Catania, Sicily, 95123, Italy

Location

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

Ancona, 60020, Italy

Location

Presidio Ospedaliero GB Morgagni L Pierantoni

Forlì, 47121, Italy

Location

Ospedale S. Giuseppe Multimedica

Milan, 20123, Italy

Location

Università Cattolica Del S Cuore

Roma, 00168, Italy

Location

Azienda Ospedaliera Universitaria Senese

Siena, 53100, Italy

Location

National Hospital Organization Ibarakihigashi National Hospital

Naka, Ibaraki, 319-1113, Japan

Location

Tenryu Hospital

Hamamatsu, Shizuoka, 434-8511, Japan

Location

Juntendo University Hospital

Bunkyō City, 113-8431, Japan

Location

National Hospital Organization Kyushu Medical Center

Fukuoka, 810-8563, Japan

Location

Fukuoka University Hospital

Fukuoka, 814-0180, Japan

Location

NHO Okinawa Hospital

Ginowan, 901-2214, Japan

Location

Hamamatsu University School of Medicine

Hamamatsu, 431-3192, Japan

Location

National Hospital Organization Himeji Medical Center

Himeji, 670-8520, Japan

Location

Hiroshima Prefectural Hospital

Hiroshima, 734-8530, Japan

Location

Kobe City Medical Center General Hospital

Hyōgo, 650-0047, Japan

Location

Saiseikai Kumamoto Hospital

Kumamoto, 861-4101, Japan

Location

Nagasaki University Hospital

Nagasaki, 852-8102, Japan

Location

Nagoya University Hospital

Nagoya, 466-8560, Japan

Location

Japanese Red Cross Okayama Hospital

Okayama, 700-8607, Japan

Location

National Hospital Organization Kinki-Chuo Chest Medical Center

Sakai, 591-8555, Japan

Location

Tohoku Medical and Pharmaceutical Hospital

Sendai, 983-8512, Japan

Location

Tosei General Hospital

Seto, 489-8642, Japan

Location

Tokyo Medical University Hospital

Shinjuku-Ku, 160-0023, Japan

Location

Tokushima University Hospital

Tokushima, 770-8503, Japan

Location

Center Hospital of the National Center for Global Health and Medicine

Tokyo, 162-8655, Japan

Location

Kanagawa Cardiovascular and Respiratory Center

Yokohama, 236-0051, Japan

Location

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

Guadalajara, 44130, Mexico

Location

Instituto Nacional De Enfermedades (INER)

Mexico City, 14080, Mexico

Location

Hospital Universitatorio Dr. Jose Eleuterio González

Monterrey, 64460, Mexico

Location

Unidad de Investigación Clínica En Medicina SC

Monterrey, 64718, Mexico

Location

VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

OLVG locatie Oost

Amsterdam, 1091 AC, Netherlands

Location

Martini Ziekenhuis

Groningen, 9700 RM, Netherlands

Location

Zuyderland Medisch Centrum

Heerlen, 6419 PC, Netherlands

Location

St. Antonius Ziekenhuis

Nieuwegein, 3425 CM, Netherlands

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Greenlane Clinical Centre

Auckland, 1051, New Zealand

Location

NZ Respiratory & Sleep Institute

Auckland, 1149, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Waikato Hospital

Hamilton, 3204, New Zealand

Location

Centrum Medycyny Oddechowej Mroz sp. j.

Bialystok, 15-044, Poland

Location

Uniwersyteckie Centrum Kliniczne - PPDS

Gdansk, 80-952, Poland

Location

PULMAG Arkadiusz Brodowski, Grzegorz Gasior S. C.

Katowice, 40-753, Poland

Location

SP ZOZ Szpital Uniwersytecki w Krakowie

Krakow, 31-153, Poland

Location

GRAŻYNA JASIENIAK-PINIS ATOPIA Niepubliczny Zakład Opieki Zdrowotnej Poradnie Specjalistyczne

Krakow, 31-159, Poland

Location

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

Lodz, 90-153, Poland

Location

ETG Lublin

Lublin, 20-314, Poland

Location

ETG Warszawa

Warsaw, 02-777, Poland

Location

Tygerberg Hospital

Cape Town, 7505, South Africa

Location

University of Cape Town Lung Institute (UCTLI)

Cape Town, 7700, South Africa

Location

Dr Ismail Abdullah Private Practice

Cape Town, 7764, South Africa

Location

Ethekwini Hospital

Durban, 4017, South Africa

Location

Gateway Private Hospital

Durban, 4091, South Africa

Location

Milpark Hospital

Johannesburg, 2193, South Africa

Location

Soon Chun Hyang University Hospital Bucheon

Bucheon-si, Gyeonggi-do, 420-767, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 463-707, South Korea

Location

Gachon University Gil Medical Center

Incheon, 405760, South Korea

Location

Asan Medical Center - PPDS

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 135-170, South Korea

Location

Soon Chun Hyang University Hospital Seoul

Seoul, 140-743, South Korea

Location

Related Publications (4)

• 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

• 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.

  PMID: 34662125 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

Results Point of Contact

• Title: Galapagos Medical Information
• Organization: Galapagos NV

medicalinfo@glpg.com

+32 15 342900

Study Officials

• Galapagos Study Director

  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: November 5, 2018
• First Posted: November 7, 2018
• Study Start: November 5, 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

PL (8); ME (4); CA (8); IT (6); AR (6); FR (4); IL (6); JP (21); NL (6); KR (6); HU (4); ZA (6); NZ (4); US (36); DE (7)