MedPath

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

Phase 3
Completed
Conditions
Lung Diseases, Interstitial
Interventions
Registration Number
NCT03313180
Lead Sponsor
Boehringer Ingelheim
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
444
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
NintedanibNintedanibPatients 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.
Primary Outcome Measures
NameTimeMethod
Number of Patients With Any Adverse Event (AE) Over the Course of the TrialFirst trial medication intake up to last trial drug intake, plus 7 days residual effect period, up to approximate 60 months.

Number of patients with any adverse event (AE) over the course of the trial.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (159)

HOP Pasteur

🇫🇷

Nice, France

Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich

🇦🇷

Buenos Aires, Argentina

CEMER-Centro Medico De Enfermedades Respiratorias

🇦🇷

Florida, Argentina

UZ Leuven

🇧🇪

Leuven, Belgium

Inova Fairfax Medical Campus

🇺🇸

Falls Church, Virginia, United States

University of Toledo

🇺🇸

Toledo, Ohio, United States

Edumed - Educacao e Saude SA

🇧🇷

Curitiba, Brazil

Medical University of Innsbruck

🇦🇹

Innsbruck, Austria

UNIV UZ Gent

🇧🇪

Gent, Belgium

Hospital Clínico Reg. de Concepción "Dr. G. Grant Benavente"

🇨🇱

Concepción, Chile

Columbia University Medical Center-New York Presbyterian Hospital

🇺🇸

New York, New York, United States

Tulane University Hospital and Clinic

🇺🇸

New Orleans, Louisiana, United States

Hospital for Special Surgery

🇺🇸

New York, New York, United States

APRILLUS-Asistencia e Investigación

🇦🇷

Ciudad Autonoma Buenos Aires, Argentina

HYKS Keuhkosairauksien tutkimusyksikkö

🇫🇮

Helsinki, Finland

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

HOP Bretonneau

🇫🇷

Tours, France

HSCM

🇨🇦

Montreal, Quebec, Canada

West China Hospital

🇨🇳

Chengdu, China

The First Hospital of China Medical University

🇨🇳

Shenyang, China

HOP Avicenne

🇫🇷

Bobigny, France

Peking Union Medical College Hospital

🇨🇳

Beijing, China

The First Affiliated Hospital of Anhui Medical University

🇨🇳

Hefei, China

Huashan Hospital, Fudan University

🇨🇳

Shanghai, China

HOP Louis Pradel

🇫🇷

Bron, France

Institute of Rheumathology Prague

🇨🇿

Prague, Czechia

HOP Bichat

🇫🇷

Paris, France

Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

Northwestern University

🇺🇸

Chicago, Illinois, United States

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

St Vincent's Hospital Melbourne

🇦🇺

Fitzroy, Victoria, Australia

Johns Hopkins Hospital

🇺🇸

Baltimore, Maryland, United States

Liverpool Hospital

🇦🇺

Sydney, New South Wales, Australia

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Temple University Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

Royal Prince Alfred Hospital

🇦🇺

Camperdown, New South Wales, Australia

Royal Adelaide Hospital

🇦🇺

Adelaide, South Australia, Australia

Boston University School of Medicine

🇺🇸

Boston, Massachusetts, United States

The University of Texas Health Science Center at Houston

🇺🇸

Houston, Texas, United States

University of Washington

🇺🇸

Seattle, Washington, United States

Virginia Mason Medical Center

🇺🇸

Seattle, Washington, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

University of California Los Angeles

🇺🇸

Los Angeles, California, United States

University of California Davis

🇺🇸

Sacramento, California, United States

Stanford University Medical Center

🇺🇸

Stanford, California, United States

University of Colorado Denver

🇺🇸

Aurora, Colorado, United States

Georgetown University

🇺🇸

Washington, District of Columbia, United States

Yale University School of Medicine

🇺🇸

New Haven, Connecticut, United States

University of Florida College of Medicine

🇺🇸

Jacksonville, Florida, United States

University of Miami

🇺🇸

Miami, Florida, United States

The Emory Clinic

🇺🇸

Atlanta, Georgia, United States

University of Iowa Hospitals and Clinics

🇺🇸

Iowa City, Iowa, United States

Centre Hospitalier Universitaire de Liège

🇧🇪

Liège, Belgium

CHRU Lille

🇫🇷

Lille, France

HOP Claude Huriez

🇫🇷

Lille, France

HOP Arnaud de Villeneuve

🇫🇷

Montpellier, France

HOP Hôtel-Dieu

🇫🇷

Nantes, France

HOP Pontchaillou

🇫🇷

Rennes, France

HOP Charles Nicolle

🇫🇷

Rouen, France

HOP Larrey

🇫🇷

Toulouse, France

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

Universitätsklinikum Schleswig-Holstein, Campus Kiel

🇩🇪

Kiel, Germany

Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg

🇩🇪

Heidelberg, Germany

Universitätsklinikum Münster

🇩🇪

Münster, Germany

General Hospital of Athens "Laiko"

🇬🇷

Athens, Greece

Universitätsklinikum Tübingen

🇩🇪

Tübingen, Germany

Ramaiah Medical College and Hospitals

🇮🇳

Bangalore, India

Care Hospital

🇮🇳

Hyderabad, India

Sir Gangaram Hospital

🇮🇳

Delhi, India

Asthma Bhawan

🇮🇳

Jaipur, India

Post Graduate Institute of Medical Education and Research

🇮🇳

Chandigarh, India

Nizam's Institute of Medical Sciences

🇮🇳

Hyderabad, India

Getwell Hospital & Research Institute

🇮🇳

Nagpur, India

All India Institute of Medical Sciences

🇮🇳

New Delhi, India

Rambam Medical Center

🇮🇱

Haifa, Israel

B.J. Medical College and Sasoon General Hospital

🇮🇳

Pune, India

Bnei Zion Medical Center, Haifa

🇮🇱

Haifa, Israel

Rabin Medical Center Beilinson

🇮🇱

Petah Tiqwa, Israel

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, Italy

Tosei General Hospital

🇯🇵

Aichi, Seto, Japan

Kurume University Hospital

🇯🇵

Fukuoka, Kurume, Japan

National Hospital Organization Himeji Medical Center

🇯🇵

Hyogo, Himeji, Japan

Sapporo Medical University Hospital

🇯🇵

Hokkaido, Sapporo, 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

Tokushima University Hospital

🇯🇵

Tokushima, Tokushima, Japan

Hamamatsu University Hospital

🇯🇵

Shizuoka, Hamamatsu, Japan

Nippon Medical School Hospital

🇯🇵

Tokyo, Bunkyo-Ku, Japan

Juntendo University 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, Japan

University of Malaya Medical Centre

🇲🇾

Kuala Lumpur, Malaysia

Hospital Pulau Pinang

🇲🇾

Georgetown Pulau Pinang, Malaysia

Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas

🇲🇽

Ciudad de México, Mexico

Amsterdam UMC Locatie VUMC

🇳🇱

Amsterdam, Netherlands

Leids Universitair Medisch Centrum (LUMC)

🇳🇱

Leiden, Netherlands

Erasmus Medisch Centrum

🇳🇱

Rotterdam, Netherlands

Oslo Universitetssykehus HF, Rikshospitalet

🇳🇴

Oslo, Norway

Radboud Universitair Medisch Centrum

🇳🇱

Nijmegen, Netherlands

Universitetssykehuset Nord-Norge, Tromsø

🇳🇴

Tromsø, Norway

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, Poland

Hospital Garcia de Orta, EPE

🇵🇹

Almada, Portugal

Centro Hospitalar de Vila Nova de Gaia

🇵🇹

Vila Nova de Gaia, Portugal

CHUC - Centro Hospitalar e Universitário de Coimbra, EPE

🇵🇹

Coimbra, Portugal

Hospital Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital Fernando Fonseca, EPE

🇵🇹

Amadora, Portugal

Centro Hospitalar Universitário São João,EPE

🇵🇹

Porto, Portugal

ULSAM, EPE - Hospital Conde de Bertiandos

🇵🇹

Ponte de Lima, Portugal

Hospital Santa Creu i Sant Pau

🇪🇸

Barcelona, Spain

Hospital Dr. Peset

🇪🇸

Valencia, Spain

Hospital General Universitario Gregorio Marañón

🇪🇸

Madrid, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hospital Politècnic La Fe

🇪🇸

Valencia, Spain

Hospital Álvaro Cunqueiro

🇪🇸

Vigo, Spain

Clinical Rheumatology Research Center Sahlgrenska

🇸🇪

Gothenburg, Sweden

University Hospital Zurich

🇨🇭

Zürich, Switzerland

Ramathibodi Hospital

🇹🇭

Bangkok, Thailand

Srinagarind Hospital

🇹🇭

Muang, Thailand

Songklanagarind Hospital

🇹🇭

Songkhla, Thailand

Royal Free Hospital

🇬🇧

London, United Kingdom

Salford Royal Hospital

🇬🇧

Salford, United Kingdom

The First Hospital of Jilin University

🇨🇳

Changchun, China

University of California San Francisco

🇺🇸

San Francisco, California, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

University of Utah Health Sciences Center

🇺🇸

Salt Lake City, Utah, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

Aarhus University Hospital

🇩🇰

Aarhus N, Denmark

Odense University Hospital

🇩🇰

Odense, Denmark

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Mayo Clinic, Rochester

🇺🇸

Rochester, Minnesota, United States

Froedtert and The Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Vanderbilt University Medical Center - Vanderbilt Lung Institute at 100 Oaks

🇺🇸

Nashville, Tennessee, United States

TYKS

🇫🇮

Turku, Finland

Centro de Investigación del Maule

🇨🇱

Talca, Chile

Guy's Hospital

🇬🇧

London, United Kingdom

Royal Brompton Hospital

🇬🇧

London, United Kingdom

Thomas Jefferson University

🇺🇸

Philadelphia, Pennsylvania, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

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