Clinical trial NCT03711162: 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
Official title: A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled Multicenter 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: 2018-10-18
Enrollment: 525
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 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).


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 FVC up to Week 52
timeFrame: Baseline up to week 52
Secondary outcomes:
measure: Percentage of Participants With Disease Progression up to Week 52
timeFrame: Up to week 52
measure: Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS)
timeFrame: Up to EoS (week 121)
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 in FVC Until EoS
timeFrame: Baseline up to EoS (week 121)
measure: Percentage of Participants With Disease Progression Until EoS
timeFrame: Up to EoS (week 121)
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 121)
measure: Percentage of Participants With Respiratory Related Mortality Until EoS
timeFrame: Up to EoS (week 121)
measure: Percentage of Participants Hospitalized for Non-elective Lung Transplant Until EoS
timeFrame: Up to EoS (week 121)
measure: Percentage of Participants With Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation Until EoS
timeFrame: Up to EoS (week 121)
measure: Percentage of Participants With All Cause Mortality or Hospitalization for Non-elective Lung Transplant Until EoS
timeFrame: Up to EoS (week 121)
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 121)
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 121)
measure: Percentage of Participants With All-Cause Mortality or Respiratory-Related Hospitalizations Until EoS
timeFrame: Up to EoS (week 121)
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 112
timeFrame: Week 112
measure: Change From Baseline in FVC at Week 112
timeFrame: Baseline, week 112
measure: Percent Change From Baseline in FVC at Week 112
timeFrame: Baseline, week 112
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 112: FVC Change Within ≤5
timeFrame: Baseline, week 112
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 112: FVC Change Within ≤10
timeFrame: Baseline, week 112
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Baseline up to 30 days after the last dose (up to week 121)
measure: Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100
timeFrame: Baseline, week 52, week 100
measure: Change 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: Change From Baseline in European Quality Of Life (EQ) VAS at Week 52 and Week 100
timeFrame: Baseline, week 52, week 100
measure: Change 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 (AUC) 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 Total Distance Walked in Six-minute Walk Test (6MWT) 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, week 100
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona - PPDS
state: Arizona
city: Little Rock
country: United States
facility: Atria Clinical Research - BTC - PPDS
state: Arkansas
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Palm Springs
country: United States
facility: Respire Research
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Danbury
country: United States
facility: Western Connecticut Medical Group
state: Connecticut
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Brandon
country: United States
facility: PAB Clinical Research - ClinEdge - PPDS
state: Florida
city: Clearwater
country: United States
facility: St. Francis Medical Institute - BTC - PPDS
state: Florida
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System-NAVREF-PPDS
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Loxahatchee Groves
country: United States
facility: Advanced Pulmonary Research Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Council Bluffs
country: United States
facility: Pulmonary and Infections Disease Associates
state: Iowa
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital, Division of Pulmonary and Critical Care Medicine
state: Massachusetts
city: Boston
country: United States
facility: Caritas St. Elizabeth's Medical Center
state: Massachusetts
city: Dearborn
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Lung Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - PPDS
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Creighton University
state: Nebraska
city: Rochester
country: United States
facility: University of Rochester Medical Center - PPDS
state: New York
city: Greensboro
country: United States
facility: PulmonIx LLC
state: North Carolina
city: Cincinnati
country: United States
facility: UC Health Department of Internal Medicine, Pulmonary, Critical Care & Sleep Medicine
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: The Oregon Clinic
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: McKinney
country: United States
facility: Metroplex Pulmonary and Sleep Medicine Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Care
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Everett
country: United States
facility: Western Washington Medical Group
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Box Hill
country: Australia
facility: Box Hill Hospital
city: Camperdown
country: Australia
facility: Corte Royal Prince Alfred Hospital
city: Chermside
country: Australia
facility: Lung Research Queensland
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
city: Heidelberg
country: Australia
facility: Austin Health
city: Kent Town
country: Australia
facility: Respiratory Clinical Trials Pty Ltd
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Antwerp
country: Belgium
facility: ZNA Middelheim
city: Brussels
country: Belgium
facility: Hôpital Erasme
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: UZ Leuven
city: Yvoir
country: Belgium
facility: CHU UCL Namur asbl - Site Godinne
city: Porto Alegre
country: Brazil
facility: Irmandade Da Santa Casa de Misericordia de Porto Alegre
city: Santo André
country: Brazil
facility: Faculdade de Medicina Do ABC
city: Concepción
country: Chile
facility: Hospital Clínico Regional de Concepción Dr Guillermo Grant Benavente
city: Curicó
country: Chile
facility: Centro de Investigación Curico
city: Quillota
country: Chile
facility: Centro Respiratorio Integral LTDA. (CENRESIN)
city: Santiago
country: Chile
facility: Instituto Nacional Torax
city: Santiago
country: Chile
facility: Centro de Investigaciones Medicas Respiratorias CIMER
city: Santiago
country: Chile
facility: Hospital Dr Sotero Del Rio
city: Talca
country: Chile
facility: Centro de Investigacion del Maule
city: Valparaíso
country: Chile
facility: Hospital Carlos Van Buren
city: Viña Del Mar
country: Chile
facility: CINVEC- Estudos Clínicos Quinta Región Limitada
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha
country: Czechia
facility: Thomayerova nemocnice
city: Praha
country: Czechia
facility: Nemocnice Na Bulovce
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital
city: Hellerup
country: Denmark
facility: Gentofte Hospital
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Bad Berka
country: Germany
facility: Zentralklinik Bad Berka GmbH
city: Berlin
country: Germany
facility: Evangelische Lungenklinik
city: Coswig
country: Germany
facility: Fachkrankenhaus Coswig
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Thorax Klinik
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: Rosenheim
country: Germany
facility: Klinikum Rosenheim
city: Athens
country: Greece
facility: Sotiria Chest Hospital of Athens
city: Athens
country: Greece
facility: Attikon University General Hospital
city: Iraklio
country: Greece
facility: University General Hospital of Heraklion
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Thessaloníki
country: Greece
facility: Georgios Papanikolaou General Hospital of Thessaloniki
city: Hamamatsu
country: Japan
facility: Tenryu Hospital
city: Kumamoto
country: Japan
facility: Saiseikai Kumamoto Hospital
city: Sakai
country: Japan
facility: National Hospital Organization Kinki-Chuo Chest Medical Center
city: Seto
country: Japan
facility: Tosei General Hospital
city: Tokyo
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
city: Tokyo
country: Japan
facility: National Hospital Organization Kyushu Medical Center
city: Yokohama
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center
city: Chancay
country: Peru
facility: Hospital Chancay y Servicios Basicos de Salud
city: Lima Cercado
country: Peru
facility: Clinica Internacional - PPDS
city: Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen ESSALUD
city: San Isidro
country: Peru
facility: Clinica Ricardo Palma - PPDS
city: San Miguel
country: Peru
facility: Clinica Providencia (Inverconsult Sociedad Anonima)
city: Santiago De Surco
country: Peru
facility: Clinica San Pablo
city: Vigo
country: Spain
facility: CHUVI - H.U. Alvaro Cunquerio
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital Clinical de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge, Hospitalet De Llobregat
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Pamplona
country: Spain
facility: Clinica Universidad Navarra
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Valencia
country: Spain
facility: Consorcio Hospital General Universitario de Valencia
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University Shuang Ho Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Istanbul
country: Turkey
facility: Süreyyapaşa Göğüs Hastalıkları Ve Göğüs Cerrahisi Eğitim Ve Araştırma Hastanesi
city: İzmir
country: Turkey
facility: Ege Universitesi Tıp Fakultesi Hastanesi Gögus Hastalıkları Anabilim Dalı
city: İzmir
country: Turkey
facility: Uludag Universitesi Tıp Fakultesi Hastanesi Gögüs Hastalıkları Anabilim Dalı
city: Mersin
country: Turkey
facility: Mersin Üniversitesi Tıp Fakültesi Hastanesi Göğüs Hastalıkları Polikinliği
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital NHS Trust
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital - PPDS
city: Newcastle
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
Study officials:
affiliation: Galapagos NV
name: Galapagos Study Director, MD
role: STUDY_DIRECTOR
References:
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.