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

An Open-label Extension Trial of the Long Term Safety of Nintedanib in Patients With 'Systemic Sclerosis Associated Interstitial Lung Disease' (SSc-ILD)

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).

Study Overview

• Status: Completed
• Conditions: Lung Diseases, Interstitial
• Intervention / Treatment: Drug: Nintedanib

• Study Type: Interventional
• Enrollment (Actual): 444
• Phase: Phase 3

Expanded Access

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Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426BOR
    • Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich
  • Ciudad Autonoma Buenos Aires, Argentina, C1046AAQ
    • APRILLUS-Asistencia e Investigacion
  • Florida, Argentina, B1602DQD
    • CEMER-Centro Medico De Enfermedades Respiratorias
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Sydney, New South Wales, Australia, 2170
      • Liverpool Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
• Austria
  • Innsbruck, Austria, A-6020
    • Medical University of Innsbruck
• Belgium
  • Gent, Belgium, 9000
    • UNIV UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire de Liege
• Brazil
  • Curitiba, Brazil, 80440-080
    • Edumed - Educacao e Saude SA
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • HSCM
• Chile
  • Concepción, Chile, 4070038
    • Hospital Clínico Reg. de Concepción "Dr. G. Grant Benavente"
  • Talca, Chile, 3465586
    • Centro de Investigación del Maule
• China
  • Beijing, China, 100032
    • Peking Union Medical College Hospital
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Chengdu, China, 610041
    • West China Hospital
  • Hefei, China, 230022
    • The First Affiliated Hospital of Anhui Medical University
  • Shanghai, China, 200040
    • Huashan Hospital, Fudan University
  • Shenyang, China, 110001
    • The First Hospital of China Medical University
• Czechia
  • Prague, Czechia, 12850
    • Institute of Rheumathology Prague
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital
  • Odense, Denmark, 5000 C
    • Odense University Hospital
• Finland
  • Helsinki, Finland, 00290
    • HYKS Keuhkosairauksien tutkimusyksikkö
  • Turku, Finland, 20521
    • TYKS
• France
  • Bobigny, France, 93009
    • HOP Avicenne
  • Bron, France, 69677
    • HOP Louis Pradel
  • Lille, France, 59037
    • Hop Claude Huriez
  • Lille, France, 59037
    • CHRU LILLE
  • Montpellier, France, 34295
    • HOP Arnaud de Villeneuve
  • Nantes, France, 44093
    • HOP Hôtel-Dieu
  • Nice, France, 06001
    • HOP Pasteur
  • Paris, France, 75877
    • HOP Bichat
  • Rennes, France, 35033
    • HOP Pontchaillou
  • Rouen, France, 76000
    • HOP Charles Nicolle
  • Toulouse, France, 31059
    • HOP Larrey
  • Tours, France, 37044
    • HOP Bretonneau
• Germany
  • Donaustauf, Germany, 93093
    • Klinik Donaustauf
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus Dresden
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Greifswald, Germany, 17475
    • Universitätsmedizin Greifswald
  • Hamburg, Germany, 22763
    • Asklepios Klinik Altona
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69126
    • Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • Münster, Germany, 48149
    • Universitätsklinikum Münster
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen
• Greece
  • Athens, Greece, 11527
    • General Hospital of Athens "Laiko"
• India
  • Bangalore, India, 560054
    • Ramaiah Medical College and Hospitals
  • Chandigarh, India, 160012
    • Post Graduate Institute of Medical Education and Research
  • Delhi, India, 110060
    • Sir Gangaram Hospital
  • Hyderabad, India, 500082
    • Nizam's Institute of Medical Sciences
  • Hyderabad, India, 500034
    • Care hospital
  • Jaipur, India, 302039
    • Asthma Bhawan
  • Nagpur, India, 440012
    • Getwell Hospital & Research Institute
  • New Delhi, India, 110029
    • All India Institute of Medical Sciences
  • Pune, India, 411001
    • B.J. Medical College and Sasoon General Hospital
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Haifa, Israel, 31048
    • Bnei Zion Medical Center, Haifa
  • Petah Tiqwa, Israel, 49100
    • Rabin Medical Center Beilinson
  • Tel Aviv, Israel, 64239
    • Sourasky Medical Center
• Italy
  • Genova, Italy, 16132
    • Università degli Studi di Genova
  • Monza, Italy, 20900
    • A.O. San Gerardo di Monza
  • Napoli, Italy, 80138
    • A.O Universitaria - Università degli Studi della Campania Luigi Vanvitelli
  • Padova, Italy, 35128
    • Università degli Studi Padova
  • Roma, Italy, 00161
    • Azienda Universitaria-Universita' La Sapienza
• Japan
  • Aichi, Seto, Japan, 489-8642
    • Tosei General Hospital
  • Fukuoka, Kurume, Japan, 830-0011
    • Kurume University Hospital
  • Hokkaido, Sapporo, Japan, 060-8543
    • Sapporo Medical University Hospital
  • Hyogo, Himeji, Japan, 670-8520
    • National Hospital Organization Himeji Medical Center
  • Kanagawa, Kawasaki, Japan, 216-8511
    • St. Marianna University Hospital
  • Kanagawa, Sagamihara, Japan, 252-0375
    • Kitasato University Hospital
  • Kanagawa, Yokohama, Japan, 236-0051
    • Kanagawa Cardiovascular and Respiratory Center
  • Nagasaki, Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Osaka, Osakasayama, Japan, 589-8511
    • Kindai University Hospital
  • Osaka, Sakai, Japan, 591-8555
    • National Hospital Organization Kinki-Chuo Chest Medical Center
  • Osaka, Takatsuki, Japan, 569-8686
    • Osaka Medical College Hospital
  • Saitama, Iruma-gun, Japan, 350-0495
    • Saitama Medical University Hospital
  • Shizuoka, Hamamatsu, Japan, 431-3192
    • Hamamatsu University Hospital
  • Tokushima, Tokushima, Japan, 770-8503
    • Tokushima University Hospital
  • Tokyo, Bunkyo-Ku, Japan, 113-8431
    • Juntendo University Hospital
  • Tokyo, Bunkyo-Ku, Japan, 113-8603
    • Nippon Medical School Hospital
  • Tokyo, Ota-ku, Japan, 143-8541
    • Toho University Omori Medical Center
  • Tokyo, Shinjyuku-ku, Japan, 162-0054
    • Institute of Rheumatology Tokyo Women's Medical University
• Malaysia
  • Georgetown Pulau Pinang, Malaysia, 10990
    • Hospital Pulau Pinang
  • Kuala Lumpur, Malaysia, 59100
    • University of Malaya Medical Centre
• Mexico
  • Ciudad de México, Mexico, 14080
    • Instituto Nacional de Enfermedades Respiratorias Ismael Cosió Villegas
• Netherlands
  • Amsterdam, Netherlands, 1081HV
    • Amsterdam UMC Locatie VUMC
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum (LUMC)
  • Nijmegen, Netherlands, 6525 GA
    • Radboud Universitair Medisch Centrum
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medisch Centrum
• Norway
  • Oslo, Norway, N-0372
    • Oslo Universitetssykehus HF, Rikshospitalet
  • Tromsø, Norway, N-9038
    • Universitetssykehuset Nord-Norge, Tromsø
• Poland
  • Bydgoszcz, Poland, 85168
    • Dr.Biziel UnivHosp#2,Rheumat&Connec.Tissue Disease,Bydgoszcz
  • Krakow, Poland, 30033
    • Specialist Allergy-Internist Center ALL-MED
  • Rzeszow, Poland, 35205
    • EMED, Center of Medical Services,Private Prac,Rzeszow
  • Wroclaw, Poland, 50-368
    • Indep.Pblic Clin.Hosp#1,Dermatol,Venereol&Allerg.dep,Wroclaw
• Portugal
  • Almada, Portugal, 2801-951
    • Hospital Garcia de Orta, EPE
  • Amadora, Portugal, 2720-276
    • Hospital Fernando Fonseca, EPE
  • Coimbra, Portugal, 3000-075
    • CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
  • Ponte de Lima, Portugal, 4990-041
    • ULSAM, EPE - Hospital Conde de Bertiandos
  • Porto, Portugal, 4200-319
    • Centro Hospitalar Universitário São João,EPE
  • Vila Nova de Gaia, Portugal, 4434-502
    • Centro Hospitalar de Vila Nova de Gaia
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 08026
    • Hospital Santa Creu i Sant Pau
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Valencia, Spain, 46026
    • Hospital Politècnic La Fe
  • Valencia, Spain, 46017
    • Hospital Dr. Peset
  • Vigo, Spain, 36312
    • Hospital Álvaro Cunqueiro
• Sweden
  • Gothenburg, Sweden, 413 45
    • Clinical Rheumatology Research Center Sahlgrenska
• Switzerland
  • Zürich, Switzerland, 8091
    • University Hospital Zurich
• Thailand
  • Bangkok, Thailand, 10400
    • Ramathibodi hospital
  • Muang, Thailand, 40002
    • Srinagarind Hospital
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • Salford, United Kingdom, M6 8HD
    • Salford Royal Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Sacramento, California, United States, 95817
      • University of California Davis
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida College of Medicine
    • Miami, Florida, United States, 33125
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Hospital and Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University School of Medicine
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic, Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10021
      • Hospital For Special Surgery
    • New York, New York, United States, 10032
      • Columbia University Medical Center-New York Presbyterian Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Toledo, Ohio, United States, 43614
      • University of Toledo
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt University Medical Center - Vanderbilt Lung Institute at 100 Oaks
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health Sciences Center
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Medical Campus
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Nintedanib; Patients with Systemic Sclerosis associated Interstitial Lung Disease (SSc-ILD) who took part in the parent trials 1199.214 (Nintedanib or Placebo) or 1199-0340 (Nintedanib). Patients continued in this trial and received Nintedanib 150 mg (milligram) twice daily (bid) unless they had reduced their dose to 100 mg bid trial medication (Nintedanib or Placebo) in the parent trial. Patients receiving 100 mg bid trial medication at the end of the parent trial could receive either Nintedanib 100 mg bid or 150 mg bid at the discretion of the investigator.

Drug: Nintedanib; Administered twice daily; Other Names: OVEF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2017
• Primary Completion (Actual): January 25, 2023
• Study Completion (Actual): January 25, 2023

Study Registration Dates

• First Submitted: October 13, 2017
• First Submitted That Met QC Criteria: October 17, 2017
• First Posted (Actual): October 18, 2017

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Nintedanib
• Other Study ID Numbers: 1199-0225; 2016-003403-66 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No