A Trial to Evaluate the Safety of Long Term Treatment With Nintedanib in Patients With Scleroderma Related Lung Fibrosis

Lung Diseases, Interstitial Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03313180
• Other study ID #: 1199-0225
• Secondary ID: 2016-003403-66
• Status: Completed
• Phase: Phase 3
• Start date: November 27, 2017
• Est. completion date: January 25, 2023

Study information

• Verified date: January 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 444
• Est. completion date: January 25, 2023
• Est. primary completion date: January 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Diseases
• Lung Diseases, Interstitial

Intervention

Drug:
• Nintedanib
Administered twice daily

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  India,  Israel,  Italy,  Japan,  Malaysia,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Spain,  Sweden,  Switzerland,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Any Adverse Event (AE) Over the Course of the Trial	Number of patients with any adverse event (AE) over the course of the trial.	First trial medication intake up to last trial drug intake, plus 7 days residual effect period, up to approximate 60 months.

External Links

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