Clinical trial NCT03733444: 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
Official title: A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of Two Doses of GLPG1690 in Addition to Local Standard of Care for Minimum 52 Weeks in Subjects With Idiopathic Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2018-11-07
Enrollment: 781
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Annual Rate of Decline in Forced Vital Capacity (FVC) up to Week 52
timeFrame: Baseline up to week 52
Secondary outcomes:
measure: Percentage of Participants With Disease Progression Up to 52 Weeks
timeFrame: Up to week 52
measure: Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS)
timeFrame: Up to EoS (week 125)
measure: Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 52
timeFrame: Baseline, week 52
measure: Annual Rate of Decline of FVC Until EoS
timeFrame: Baseline up to EoS (week 125)
measure: Percentage of Participants With Disease Progression Until EoS
timeFrame: Up to EoS (week 125)
measure: Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 100
timeFrame: Baseline, week 100
measure: Percentage of Participants With All Cause Hospitalization Until EoS
timeFrame: Up to EoS (week 125)
measure: Percentage of Participants With Respiratory Related Mortality Until EoS
timeFrame: Up to EoS (week 125)
measure: Percentage of Participants Hospitalized for Non-Elective Lung Transplant Until EoS
timeFrame: Up to EoS (week 125)
measure: Percentage of Participants With Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation Until EoS
timeFrame: Up to EoS (week 125)
measure: Percentage of Participants With All Cause Mortality or Hospitalization for Non-elective Lung Transplant Until EoS
timeFrame: Up to EoS (week 125)
measure: Percentage of Participants With All Cause Mortality, Hospitalization for Non-elective Lung Transplant or Hospitalization for Qualifying for Lung Transplant Until EoS
timeFrame: Up to EoS (week 125)
measure: Percentage of Participants With All-Cause Mortality or Hospitalization That Meets >=10% Absolute Decline in %FVC or Respiratory-Related Hospitalization Until EoS
timeFrame: Up to EoS (week 125)
measure: Percentage of Participants With All-Cause Mortality or Respiratory-Related Hospitalizations Until EoS
timeFrame: Up to EoS (week 125)
measure: FVC at Week 52
timeFrame: Week 52
measure: Change From Baseline in FVC at Week 52
timeFrame: Baseline, week 52
measure: Percent Change From Baseline in FVC at Week 52
timeFrame: Baseline, week 52
measure: FVC at Week 100
timeFrame: Week 100
measure: Change From Baseline in FVC at Week 100
timeFrame: Baseline, week 100
measure: Percent Change From Baseline in FVC at Week 100
timeFrame: Baseline, week 100
measure: Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤5
timeFrame: Baseline, week 52
measure: Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 100: FVC Change Within ≤5
timeFrame: Baseline, week 100
measure: Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤10
timeFrame: Baseline, week 52
measure: Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 100: FVC Change Within ≤10
timeFrame: Baseline, week 100
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Baseline up to EoS (up to Week 125)
measure: Changes From Baseline in Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100
timeFrame: Baseline, week 52, week 100
measure: Changes From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100
timeFrame: Baseline, week 52, week 100
measure: Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100
timeFrame: Baseline, week 52, week 100
measure: Changes From Baseline in EuroQOL 5-Dimensions Questionnaire at Week 52 and Week 100
timeFrame: Baseline, week 52, week 100
measure: Changes From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100
timeFrame: Baseline, week 52, week 100
measure: Area Under The Concentration Time Curve of Ziritaxtestat
timeFrame: Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose
measure: Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat
timeFrame: Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose
measure: Change From Baseline in Functional Exercise Capacity, Assessed by The 6-Minute Walk Test (6MWT) Distance, at Week 52 and Week 100
timeFrame: Baseline, week 52, week 100
measure: Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100
timeFrame: Baseline, week 52 and week 100
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialists
state: Arizona
city: Tucson
country: United States
facility: University of Arizona College of Medicine
state: Arizona
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Medical Center
state: California
city: Clearwater
country: United States
facility: St. Francis Medical Institute
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group PA
state: Florida
city: Atlanta
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System (UMHS)
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Medical Group
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Chesterfield
country: United States
facility: Cardio Pulmonary Associates
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Summit
country: United States
facility: Atlantic Respiratory Institute
state: New Jersey
city: Albuquerque
country: United States
facility: Lovelace Scientific Resources Inc
state: New Mexico
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Toledo
country: United States
facility: Mercy Health - St. Vincent Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple Lung Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina - PPDS
state: South Carolina
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Buenos Aires
country: Argentina
facility: Centro Médico Dra de Salvo
city: Córdoba
country: Argentina
facility: Hospital Privado Centro Médico de Córdoba
city: Florida
country: Argentina
facility: CEMER Centro Médico de Enfermedades Respiratorias
city: Luján
country: Argentina
facility: Hospital Zonal Especializado de Agudos y Crónicos Dr. Antonio A. Cetrangolo
city: Mar Del Plata
country: Argentina
facility: Instituto de Investigaciones Clínicas Mar Del Plata
city: Mendoza
country: Argentina
facility: Fundacion Scherbovsky
city: Calgary
country: Canada
facility: South Health Campus
city: Montréal
country: Canada
facility: Hôtel Dieu Du Centre Hospitalier de L'université de Montréal
city: Montréal
country: Canada
facility: McGill University Health Centre Research Institute
city: Québec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie
city: Toronto
country: Canada
facility: Toronto General Hospital
city: Vancouver
country: Canada
facility: Vancouver General Hospital
city: Vancouver
country: Canada
facility: Pacific Lung Research Center
city: Windsor
country: Canada
facility: Dr Anil Dhar Professional Medicine Corporation
city: Marseille
country: France
facility: Hôpital Nord AP-HM
city: Montpellier
country: France
facility: Centre Hospitalier Regional Universitaire Montpellier
city: Paris
country: France
facility: Groupe Hospitalier Bichat Claude Bernard
city: Reims
country: France
facility: CHU de Reims
city: Essen
country: Germany
facility: Ruhrlandklinik
city: Frankfurt
country: Germany
facility: Praxis Dr. med. Claus Keller
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald Klinik und Poliklinik für Innere Medizin B
city: Großhansdorf
country: Germany
facility: Pneumologisches Forschungsinstitut
city: Immenhausen
country: Germany
facility: Lungenfachklinik Immenhausen
city: Köln
country: Germany
facility: Kliniken der Stadt Koln GmbH
city: Solingen
country: Germany
facility: Krankenhaus Bethanien - Klinik für Pneumologie und Allergologie
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Farkasgyepű
country: Hungary
facility: Veszprem Megyei Tudogyogyintezet
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktató Kórház
city: Törökbálint
country: Hungary
facility: Tüdőgyógyintézet Törökbálint
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petah tikva
country: Israel
facility: Rabin Medical Center - PPDS
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
state: Sicilia
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
city: Forlì
country: Italy
facility: Presidio Ospedaliero GB Morgagni L Pierantoni
city: Milano
country: Italy
facility: Ospedale S. Giuseppe Multimedica
city: Roma
country: Italy
facility: Università Cattolica Del S Cuore
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese
city: Naka
country: Japan
facility: National Hospital Organization Ibarakihigashi National Hospital
state: Ibaraki
city: Hamamatsu
country: Japan
facility: Tenryu Hospital
state: Shizuoka
city: Bunkyo
country: Japan
facility: Juntendo University Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Ginowan
country: Japan
facility: NHO Okinawa Hospital
city: Hamamatsu
country: Japan
facility: Hamamatsu University School of Medicine
city: Himeji
country: Japan
facility: National Hospital Organization Himeji Medical Center
city: Hiroshima
country: Japan
facility: Hiroshima Prefectural Hospital
city: Hyōgo
country: Japan
facility: Kobe City Medical Center General Hospital
city: Kumamoto
country: Japan
facility: Saiseikai Kumamoto Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Nagoya
country: Japan
facility: Nagoya University Hospital
city: Okayama
country: Japan
facility: Japanese Red Cross Okayama Hospital
city: Sakai
country: Japan
facility: National Hospital Organization Kinki-Chuo Chest Medical Center
city: Sendai
country: Japan
facility: Tohoku Medical and Pharmaceutical Hospital
city: Seto
country: Japan
facility: Tosei General Hospital
city: Shinjuku-Ku
country: Japan
facility: Tokyo Medical University Hospital
city: Tokushima
country: Japan
facility: Tokushima University Hospital
city: Tokyo
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
city: Yokohama
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center
city: Bucheon
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - PPDS
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Seoul
city: Ciudad de mexico
country: Mexico
facility: Instituto Nacional De Enfermedades (INER)
city: Guadalajara
country: Mexico
facility: Centro de Investigación Medico Biologica y de Terapia Avanzada S.C.
city: Monterrey
country: Mexico
facility: Hospital Universitatorio Dr. Jose Eleuterio González
city: Monterrey
country: Mexico
facility: Unidad de Investigación Clínica En Medicina SC
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Amsterdam
country: Netherlands
facility: OLVG locatie Oost
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Heerlen
country: Netherlands
facility: Zuyderland Medisch Centrum
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Auckland
country: New Zealand
facility: Greenlane Clinical Centre
city: Auckland
country: New Zealand
facility: NZ Respiratory & Sleep Institute
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Białystok
country: Poland
facility: Centrum Medycyny Oddechowej Mroz sp. j.
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne - PPDS
city: Katowice
country: Poland
facility: PULMAG Arkadiusz Brodowski, Grzegorz Gasior S. C.
city: Kraków
country: Poland
facility: SP ZOZ Szpital Uniwersytecki w Krakowie
city: Kraków
country: Poland
facility: GRAŻYNA JASIENIAK-PINIS ATOPIA Niepubliczny Zakład Opieki Zdrowotnej Poradnie Specjalistyczne
city: Lublin
country: Poland
facility: ETG Lublin
city: Warszawa
country: Poland
facility: ETG Warszawa
city: Łódź
country: Poland
facility: SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
city: Cape Town
country: South Africa
facility: Tygerberg Hospital
city: Cape Town
country: South Africa
facility: University of Cape Town Lung Institute (UCTLI)
city: Cape Town
country: South Africa
facility: Dr Ismail Abdullah Private Practice
city: Durban
country: South Africa
facility: Ethekwini Hospital
city: Durban
country: South Africa
facility: Gateway Private Hospital
city: Johannesburg
country: South Africa
facility: Milpark Hospital
Study officials:
affiliation: Galapagos NV
name: Galapagos Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.