Clinical trial NCT03313180: A Trial to Evaluate the Safety of Long Term Treatment With Nintedanib in Patients With Scleroderma Related Lung Fibrosis
Official title: An Open-label Extension Trial of the Long Term Safety of Nintedanib in Patients With 'Systemic Sclerosis Associated Interstitial Lung Disease' (SSc-ILD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Diseases, Interstitial
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2017-10-18
Enrollment: 444
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main objective is to assess long term safety of treatment with oral nintedanib in patients with Systemic Sclerosis associated Interstitial Lung Disease (SSc-ILD).


Eligibility criteria: Inclusion Criteria:

* Patients who completed the parent trial 1199.214/1199-0340 per protocol and did not permanently discontinue study treatment
* Signed and dated written informed consent in accordance with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
* Women of childbearing potential must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly as well as one barrier method for 28 days prior to nintedanib treatment initiation, during the trial and for 3 months after last intake of nintedanib.
* Further inclusion criteria apply

Exclusion Criteria:

* Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) \> 3 x Upper Limit of Normal (ULN)
* Bilirubin \> 2 x ULN
* Creatinine clearance \<30 mL/min calculated by Cockcroft-Gault formula.
* Clinically relevant anaemia at investigators discretion.
* Bleeding risk, any of the following

  * Known genetic predisposition to bleeding according to the judgement of the investigator
  * Patients who require

    * Fibrinolysis, full-dose therapeutic anticoagulation
    * High dose antiplatelet therapy.
  * Hemorrhagic central nervous system (CNS) event after completion of the parent trial 1199.214/1199-0340
  * Any of the following after last treatment of 1199.214/1199-0340:

    * Haemoptysis or haematuria
    * Active gastro-intestinal bleeding or Gastrointestinal (GI) - ulcers
    * Gastric antral vascular ectasia (GAVE)
    * Major injury or surgery
  * Coagulation parameters: International normalised ratio (INR) \>2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by \>1.5 x ULN at Visit 1.
* New major thrombo-embolic events developed after completion of the parent trial 1199.214/1199-0340:

  * Stroke;
  * Deep vein thrombosis;
  * Pulmonary embolism;
  * Myocardial infarction.
* Major surgery performed within the next 3 months
* Time period \> 12 weeks between last drug intake in 1199.214 or \> 1 week between last nintedanib intake in trial 1199-0340 and Visit 2 of this trial
* Usage of any investigational drug after completion of 1199.214/1199-0340 or planned usage of an investigational drug during the course of this trial.
* A disease or condition which may put the patient at risk because of participation in this trial (e.g. clinically relevant intestinal pseudoobstruction) or limit the patient's ability to participate in this trial
* Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial subject or unlikely to complete the trial
* Known hypersensitivity to the trial medication or its components (i.e. soya lecithin).
* Women who are pregnant, nursing, or who plan to become pregnant while in the trial
* Previous enrolment in this trial
* Further exclusion criteria apply

Primary outcomes:
measure: Number of Patients With Any Adverse Event (AE) Over the Course of the Trial
timeFrame: First trial medication intake up to last trial drug intake, plus 7 days residual effect period, up to approximate 60 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Tulane University Hospital and Clinic
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic, Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center-New York Presbyterian Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center - Vanderbilt Lung Institute at 100 Oaks
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Falls Church
country: United States
facility: Inova Fairfax Medical Campus
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Froedtert and The Medical College of Wisconsin
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: APRILLUS-Asistencia e Investigación
city: Florida
country: Argentina
facility: CEMER-Centro Medico De Enfermedades Respiratorias
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
city: Gent
country: Belgium
facility: UNIV UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Curitiba
country: Brazil
facility: Edumed - Educacao e Saude SA
city: Montreal
country: Canada
facility: HSCM
state: Quebec
city: Concepción
country: Chile
facility: Hospital Clínico Reg. de Concepción "Dr. G. Grant Benavente"
city: Talca
country: Chile
facility: Centro de Investigación del Maule
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Chengdu
country: China
facility: West China Hospital
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Prague
country: Czechia
facility: Institute of Rheumathology Prague
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Helsinki
country: Finland
facility: HYKS Keuhkosairauksien tutkimusyksikkö
city: Turku
country: Finland
facility: TYKS
city: Bobigny
country: France
facility: HOP Avicenne
city: Bron
country: France
facility: HOP Louis Pradel
city: Lille
country: France
facility: CHRU Lille
city: Lille
country: France
facility: HOP Claude Huriez
city: Montpellier
country: France
facility: HOP Arnaud de Villeneuve
city: Nantes
country: France
facility: HOP Hôtel-Dieu
city: Nice
country: France
facility: HOP Pasteur
city: Paris
country: France
facility: HOP Bichat
city: Rennes
country: France
facility: HOP Pontchaillou
city: Rouen
country: France
facility: HOP Charles Nicolle
city: Toulouse
country: France
facility: HOP Larrey
city: Tours
country: France
facility: HOP Bretonneau
city: Donaustauf
country: Germany
facility: Klinik Donaustauf
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Kiel
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Athens
country: Greece
facility: General Hospital of Athens "Laiko"
city: Bangalore
country: India
facility: Ramaiah Medical College and Hospitals
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education and Research
city: Delhi
country: India
facility: Sir Gangaram Hospital
city: Hyderabad
country: India
facility: Care Hospital
city: Hyderabad
country: India
facility: Nizam's Institute of Medical Sciences
city: Jaipur
country: India
facility: Asthma Bhawan
city: Nagpur
country: India
facility: Getwell Hospital & Research Institute
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
city: Pune
country: India
facility: B.J. Medical College and Sasoon General Hospital
city: Haifa
country: Israel
facility: Bnei Zion Medical Center, Haifa
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Petah Tiqwa
country: Israel
facility: Rabin Medical Center Beilinson
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Genova
country: Italy
facility: Università degli Studi di Genova
city: Monza
country: Italy
facility: A.O. San Gerardo di Monza
city: Napoli
country: Italy
facility: A.O Universitaria - Università degli Studi della Campania Luigi Vanvitelli
city: Padova
country: Italy
facility: Università degli Studi Padova
city: Roma
country: Italy
facility: Azienda Universitaria-Universita' La Sapienza
city: Aichi, Seto
country: Japan
facility: Tosei General Hospital
city: Fukuoka, Kurume
country: Japan
facility: Kurume University Hospital
city: Hokkaido, Sapporo
country: Japan
facility: Sapporo Medical University Hospital
city: Hyogo, Himeji
country: Japan
facility: National Hospital Organization Himeji Medical Center
city: Kanagawa, Kawasaki
country: Japan
facility: St. Marianna University Hospital
city: Kanagawa, Sagamihara
country: Japan
facility: Kitasato University Hospital
city: Kanagawa, Yokohama
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center
city: Nagasaki, Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Osaka, Osakasayama
country: Japan
facility: Kindai University Hospital
city: Osaka, Sakai
country: Japan
facility: National Hospital Organization Kinki-Chuo Chest Medical Center
city: Osaka, Takatsuki
country: Japan
facility: Osaka Medical College Hospital
city: Saitama, Iruma-gun
country: Japan
facility: Saitama Medical University Hospital
city: Shizuoka, Hamamatsu
country: Japan
facility: Hamamatsu University Hospital
city: Tokushima, Tokushima
country: Japan
facility: Tokushima University Hospital
city: Tokyo, Bunkyo-Ku
country: Japan
facility: Juntendo University Hospital
city: Tokyo, Bunkyo-Ku
country: Japan
facility: Nippon Medical School Hospital
city: Tokyo, Ota-ku
country: Japan
facility: Toho University Omori Medical Center
city: Tokyo, Shinjyuku-ku
country: Japan
facility: Institute of Rheumatology Tokyo Women's Medical University
city: Georgetown Pulau Pinang
country: Malaysia
facility: Hospital Pulau Pinang
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
city: Ciudad de México
country: Mexico
facility: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC Locatie VUMC
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum (LUMC)
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Rikshospitalet
city: Tromsø
country: Norway
facility: Universitetssykehuset Nord-Norge, Tromsø
city: Bydgoszcz
country: Poland
facility: Dr.Biziel UnivHosp#2,Rheumat&Connec.Tissue Disease,Bydgoszcz
city: Krakow
country: Poland
facility: Specialist Allergy-Internist Center ALL-MED
city: Rzeszow
country: Poland
facility: EMED, Center of Medical Services,Private Prac,Rzeszow
city: Wroclaw
country: Poland
facility: Indep.Pblic Clin.Hosp#1,Dermatol,Venereol&Allerg.dep,Wroclaw
city: Almada
country: Portugal
facility: Hospital Garcia de Orta, EPE
city: Amadora
country: Portugal
facility: Hospital Fernando Fonseca, EPE
city: Coimbra
country: Portugal
facility: CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
city: Ponte de Lima
country: Portugal
facility: ULSAM, EPE - Hospital Conde de Bertiandos
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário São João,EPE
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Dr. Peset
city: Valencia
country: Spain
facility: Hospital Politècnic La Fe
city: Vigo
country: Spain
facility: Hospital Álvaro Cunqueiro
city: Gothenburg
country: Sweden
facility: Clinical Rheumatology Research Center Sahlgrenska
city: Zürich
country: Switzerland
facility: University Hospital Zurich
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Muang
country: Thailand
facility: Srinagarind Hospital
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
Study officials:
References: