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A Trial to Compare Nintedanib With Placebo for Patients With Scleroderma Related Lung Fibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02597933
Recruitment Status : Completed
First Posted : November 5, 2015
Last Update Posted : December 7, 2018
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
Systemic Sclerosis (SSc) is a devastating disease of unknown etiology. Patients suffer from multiple organ fibrosis whereas lung fibrosis (interstitial lung disease, ILD) is one of the main driver for mortality. There is preclinical evidence for efficacy of nintedanib in SSc and associated ILD (SSc-ILD) and the anti-fibrotic efficacy of nintedanib was proven in idiopathic pulmonary fibrosis patients, who are presenting a similar pattern regarding lung fibrosis. Hence it is the purpose of the trial to confirm the efficacy and safety of nintedanib 150 mg bid in treating patients with SSc-ILD, compared with placebo. The trial will be conducted as a double blind, randomised, placebo-controlled trial with primary efficacy evaluation at week 52 and placebo-controlled treatment until last patient out (up to a maximum of 100 weeks). Respiratory function is globally accepted for assessment of treatment effects in patients with lung fibrosis. The chosen endpoint (Forced Vital Capacity (FVC) decline) is easy to obtain and is part of the usual examinations done in patients with SSc-ILD.

Condition or disease Intervention/treatment Phase
Scleroderma, Systemic Drug: Nintedanib Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 580 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Double Blind, Randomised, Placebo-controlled Trial Evaluating Efficacy and Safety of Oral Nintedanib Treatment for at Least 52 Weeks in Patients With Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD)
Actual Study Start Date : November 12, 2015
Actual Primary Completion Date : October 31, 2018
Actual Study Completion Date : November 28, 2018

Arm Intervention/treatment
Experimental: Nintedanib
patient receives capsules containing nintedanib twice a day
Drug: Nintedanib
Placebo Comparator: Placebo
patient receives capsules identical to those containing active drug
Drug: Placebo

Primary Outcome Measures :
  1. Annual rate of decline in FVC in mL [ Time Frame: 52 weeks ]

Secondary Outcome Measures :
  1. Time to all-cause mortality [ Time Frame: 52 weeks ]
  2. Absolute change from baseline in FACIT dyspnoea score [ Time Frame: 52 weeks ]
  3. Absolute change from baseline in the mRSS [ Time Frame: 52 weeks ]
  4. Absolute change from baseline in SGRQ total score [ Time Frame: 52 weeks ]
  5. Annual rate of decline in FVC in percent predicted [ Time Frame: 52 weeks ]
  6. Absolute change from baseline in FVC in mL [ Time Frame: 52 weeks ]
  7. Relative change from baseline (%) of mRSS [ Time Frame: 52 weeks ]
  8. Absolute change from baseline in DLCO in percent predicted [ Time Frame: 52 weeks ]
  9. Absolute change from baseline in digital ulcer net burden (defined as the number of new digital ulcers (DUs) plus the number of DUs that have been verified at any earlier assessment during the trial) [ Time Frame: 52 weeks ]
  10. Absolute change from baseline in SHAQ total score [ Time Frame: 52 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  • Age >= 18 years
  • 2013 ACR / EULAR classification criteria for SSc fulfilled
  • SSc disease onset (defined by first non-Raynaud symptom) within 7 years
  • SSc related Interstitial Lung Disease confirmed by HRCT; Extent of fibrotic disease in the lung >= 10%
  • FVC >= 40% of predicted normal
  • DLCO 30% to 89% of predicted normal

Exclusion criteria:

  • AST, ALT >1.5 x ULN
  • Bilirubin >1.5 x ULN
  • Creatinine clearance <30 mL/min
  • Airway obstruction (pre-bronchodilator FEV1/FVC <0.7)
  • Other clinically significant pulmonary abnormalities
  • Significant PH
  • Cardiovascular diseases
  • More than 3 digital fingertip ulcers or a history of severe digital necrosis requiring hospitalization or severe other ulcers
  • Bleeding risk (such as predisposition to bleeding, fibrinolysis, full-dose anticoagulation, high dose antiplatelet therapy, history of hemorrhagic central nervous system (CNS) event within last year
  • international normalised ratio (INR) >2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by >1.5 x ULN)
  • History of thrombotic event within last year
  • Clinical signs of malabsorption or needing parenteral nutrition
  • Previous treatment with nintedanib or pirfenidone
  • Treatment with prednisone >10 mg/day, azathioprine, hydroxychloroquine, colchizine, D-penicillamine, sulfasalazine, cyclophosphamide, rituximab, tocilizumab, abatacept, leflunomide, tacrolimus, newer anti-arthritic treatments like tofacitinib and ciclosporine A, potassium para-aminobenzoate
  • Unstable background therapy with either mycophenolate mofetil or methotrexate
  • Previous or planned hematopoietic stem cell transplantation
  • Patients with underlying chronic liver disease (Child Pugh A, B, C hepatic impairment)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02597933

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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
University of California Los Angeles
Los Angeles, California, United States, 90095
University of California Davis
Sacramento, California, United States, 95817
University of California San Francisco
San Francisco, California, United States, 94143
Stanford University Medical Center
Stanford, California, United States, 94305-5236
United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20007
United States, Florida
University of Florida College of Medicine
Jacksonville, Florida, United States, 32209
University of Miami
Miami, Florida, United States, 33125
United States, Georgia
The Emory Clinic
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Louisiana
Tulane University Hospital and Clinic
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21224
United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
University of Minnesota Masonic Cancer Center
Minneapolis, Minnesota, United States, 55455
Mayo Clinic-Rochester
Rochester, Minnesota, United States, 55905
United States, Missouri
The Lung Research Center, LLC
Chesterfield, Missouri, United States, 63017
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Hospital for Special Surgery
New York, New York, United States, 10021
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Columbia University Medical Center-New York Presbyterian Hospital
New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
University of Cincinnati Health
Cincinnati, Ohio, United States, 45219
Cleveland Clinic
Cleveland, Ohio, United States, 44195
University of Toledo
Toledo, Ohio, United States, 43614
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Temple University Hospital
Philadelphia, Pennsylvania, United States, 19140
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
University of South Carolina
Columbia, South Carolina, United States, 29203
United States, Tennessee
Vanderbilt Pulmonary Clinic
Nashville, Tennessee, United States, 37232-5735
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
The University Of Texas at Houston
Houston, Texas, United States, 77030
United States, Utah
University of Utah Health Sciences Center
Salt Lake City, Utah, United States, 84108
United States, Virginia
Inova Fairfax Medical Campus
Falls Church, Virginia, United States, 22042
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
University of Washington
Seattle, Washington, United States, 98195
United States, Wisconsin
Froedtert and The Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich
Buenos Aires, Argentina, C1426BOR
APRILLUS-Asistencia e Investigación
Ciudad Autonoma Buenos Aires, Argentina, C1046AAQ
CEMER-Centro Medico De Enfermedades Respiratorias
Florida, Argentina, B1602DQD
Australia, New South Wales
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
Liverpool Hospital
Sydney, New South Wales, Australia, 2170
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
St Vincent's Hospital Melbourne
Fitzroy, Victoria, Australia, 3065
LKH-Univ. Hospital Graz
Graz, Austria, 8036
Medical University of Innsbruck
Innsbruck, Austria, 6020
ULB Hopital Erasme
Bruxelles, Belgium, 1070
Brussels - UNIV Saint-Luc
Bruxelles, Belgium, 1200
Gent, Belgium, 9000
UZ Leuven
Leuven, Belgium, 3000
Centre Hospitalier Universitaire de Liège
Liège, Belgium, 4000
Edumed - Educacao e Saude SA
Curitiba, Brazil, 80440-080
Canada, Ontario
Saint Joseph's Healthcare
Hamilton, Ontario, Canada, L8N 4A6
Mount Sinai Hospital
Toronto, Ontario, Canada, M5T 3L9
Canada, Quebec
Montreal, Quebec, Canada, H4J 1C5
Hospital Clínico Reg. de Concepción "Dr. G. Grant Benavente"
Concepción, Chile, 4070038
Centro de Investigación del Maule
Talca, Chile, 3465586
Peking Union Medical College Hospital
Beijing, China, 100032
Beijing Chao-Yang Hospital
Beijing, China
Beijing Hospital
Beijing, China
First Hospital of Jilin University
Changchun, China
West China Hospital
Chengdu, China, 610041
The First Affiliated Hospital of Anhui Medical University
Hefei, China, 230022
Huashan Hospital, Fudan University
Shanghai, China, 200040
The First Hospital of Chinese Medical University
Shenyang, China
Zhuzhou Central Hospital
Zhuzhou, China, 412007
Institute of Rheumathology Prague
Prague, Czechia, 12850
Thomayer Hospital
Praha 4, Czechia, 14059
Odense Universitetshospital
Odense, Denmark, 5000 C
Aarhus Universitets Hospital
Århus, Denmark, 8000
HYKS Keuhkosairauksien
Helsinki, Finland, 00290
TYKS, Keuhkosairauksien klinikka, Turku
Turku, Finland, 20520
HOP Avicenne
Bobigny, France, 93009
HOP Louis Pradel
Bron, France, 69677
HOP Calmette
Lille, France, 59037
HOP Claude Huriez
Lille, France, 59037
HOP Arnaud de Villeneuve
Montpellier, France, 34295
HOP Hôtel-Dieu
Nantes, France, 44000
HOP Pasteur
Nice, France, 06001
HOP Cochin
Paris, France, 75014
HOP Bichat
Paris, France, 75018
HOP Pontchaillou
Rennes, France, 35033
HOP Charles Nicolle
Rouen, France, 76000
HOP Larrey
Toulouse, France, 31059
HOP Bretonneau
Tours, France, 37044
Kerckhoff-Klinik, Bad Nauheim
Bad Nauheim, Germany, 61231
Klinik Donaustauf
Donaustauf, Germany, 93093
Universitätsklinikum Carl Gustav Carus Dresden
Dresden, Germany, 01307
Universitätsklinikum Erlangen
Erlangen, Germany, 91054
Universitätsmedizin Greifswald
Greifswald, Germany, 17475
Asklepios Klinik Altona
Hamburg, Germany, 22763
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
Heidelberg, Germany, 69126
Universitätsklinikum Schleswig-Holstein, Campus Kiel
Kiel, Germany, 24105
Universitätsklinikum Köln (AöR)
Köln, Germany, 50937
Klinikum der Universität München - Campus Großhadern
München, Germany, 80336
Universitätsklinikum Münster
Münster, Germany, 48149
Universitätsklinikum Tübingen
Tübingen, Germany, 72076
General Hospital of Athens "Laiko"
Athens, Greece, 115 27
General Hospital of Athens "Laiko"
Athens, Greece, 11527
Semmelweis University, Dept. Pulmonology
Budapest, Hungary, 1125
St John's Medical College
Bangalore, India, 560 034
Ramaiah Medical College and Hospitals
Bangalore, India, 560054
Mazumdar Shaw Medical centre
Bangalore, India, 560099
Postgraduate Institute of Medical Education And Research
Chandigarh, India, 160012
Care Hospital
Hyderabad, India, 500034
Nizam's Institute of Medical Sciences
Hyderabad, India, 500082
Asthma Bhawan
Jaipur, India, 302039
P.D. Hinduja National Hospital
Mumbai, India, 400016
Getwell Hospital & Research Institute
Nagpur, India, 440012
All India Institute of Medical Science
New Delhi, India, 110029
Sir Gangaram Hospital
New Delhi, India, 110060
Jehangir Clinical Development Centre Pvt. Ltd.
Pune, India, 411 001
B.J. Medical College and Sasoon General Hospital
Pune, India, 411001
Inamdar Multispeciality Hospital
Pune, India, 411040
Christian Medical College
Vellore, India, 632 004
Cork University Hospital
Cork, Ireland
Mater Misericordiae University Hospital
Dublin 7, Ireland
Bnei Zion Medical Center, Haifa
Haifa, Israel, 31048
Rambam Medical Center
Haifa, Israel, 3109601
Rabin Medical Center Beilinson
Petah Tiqwa, Israel, 49100
Sourasky Medical Center
Tel Aviv, Israel, 64239
Az. Ospedaliere Umberto I di Ancona
Ancona, Italy, 60126
Università degli Studi di Genova
Genova, Italy, 16132
A.O. San Gerardo di Monza
Monza, Italy, 20900
A.O Universitaria - Università degli Studi della Campania Luigi Vanvitelli
Napoli, Italy, 80138
Università degli Studi Padova
Padova, Italy, 35128
Azienda Universitaria-Universita' La Sapienza
Roma, Italy, 00161
Tosei General Hospital
Aichi, Seto, Japan, 489-8642
Kurume University Hospital
Fukuoka, Kurume, Japan, 830-0011
Sapporo Medical University Hospital
Hokkaido, Sapporo, Japan, 060-8543
National Hospital Organization Himeji Medical Center
Hyogo, Himeji, Japan, 670-8520
Iwate Medical University Hospital
Iwate, Morioka, Japan, 020-8505
St. Marianna University School of Medicine Hospital
Kanagawa, Kawasaki, Japan, 216-8511
Kitasato University Hospital
Kanagawa, Sagamihara, Japan, 252-0375
Kanagawa Cardiovascular and Respiratory Center
Kanagawa, Yokohama, Japan, 236-0051
Kyoto University Hospital
Kyoto, Kyoto, Japan, 606-8507
Nagasaki University Hospital
Nagasaki, Nagasaki, Japan, 852-8501
Kindai University Hospital
Osaka, Osakasayama, Japan, 589-8511
National Hospital Organization Kinki-Chuo Chest Medical Center
Osaka, Sakai, Japan, 591-8555
Osaka Medical College Hospital
Osaka, Takatsuki, Japan, 569-8686
Saitama Medical University Hospital
Saitama, Iruma-gun, Japan, 350-0495
Hamamatsu University Hospital
Shizuoka, Hamamatsu, Japan, 431-3192
Tokushima University Hospital
Tokushima, Tokushima, Japan, 770-8503
Juntendo University Hospital
Tokyo, Bunkyo-Ku, Japan, 113-8431
Nippon Medical School Hospital
Tokyo, Bunkyo-Ku, Japan, 113-8603
Toho University Omori Medical Center
Tokyo, Ota-ku, Japan, 143-8541
Institute of Rheumatology Tokyo Women's Medical University
Tokyo, Shinjyuku-ku, Japan, 162-0054
University Malaya Medical Centre
Kuala Lumpur, Malaysia, 59100
Hospital Pulau Pinang
Pulau Pinang, Malaysia, 10990
Hospital Selayang
Selangor, Malaysia, 68100
Hospital Tuanku Ja'afar
Seremban, Malaysia, 70300
Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas
Ciudad de México, Mexico, 14080
VU Medisch Centrum
Amsterdam, Netherlands, 1081HV
Leids Universitair Medisch Centrum (LUMC)
Leiden, Netherlands, 2333 ZA
Radboud Universitair Medisch Centrum
Nijmegen, Netherlands, 6525 GA
Erasmus Medisch Centrum
Rotterdam, Netherlands, 3015 CE
Oslo Universitetssykehus HF, Rikshospitalet
Oslo, Norway, N-0372
Universitetssykehuset Nord-Norge, Tromsø
Tromsø, Norway, N-9038
Dr.Biziel UnivHosp#2,Rheumat&Connec.Tissue Disease,Bydgoszcz
Bydgoszcz, Poland, 85168
Dobry Lekarz,Spec.Med.Clinics,Private Prac,Krakow
Krakow, Poland, 31011
EMED, Center of Medical Services,Private Prac,Rzeszow
Rzeszow, Poland, 35205
Indep.Pblic Clin.Hosp#1,Dermatol,Venereol&Allerg.dep,Wroclaw
Wroclaw, Poland, 50 368
Hospital Garcia de Orta, EPE
Almada, Portugal, 2801-951
Hospital Fernando Fonseca, EPE
Amadora, Portugal, 2720-276
CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
Coimbra, Portugal, 3000-075
ULSAM, EPE - Hospital Conde de Bertiandos
Ponte de Lima, Portugal, 4990-041
Centro Hospitalar São João,EPE
Porto, Portugal, 4200-319
Centro Hospitalar de Vila Nova de Gaia
Vila Nova de Gaia, Portugal, 4434-502
Hospital Vall d'Hebron
Barcelona, Spain, 08035
Hospital Santa Creu i Sant Pau
Barcelona, Spain, 08041
Hospital General Universitario Gregorio Marañón
Madrid, Spain, 28007
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital Universitario Marqués de Valdecilla
Santander, Spain, 39008
Hospital Dr. Peset
Valencia, Spain, 46017
Hospital Politècnic La Fe
Valencia, Spain, 46026
Hospital Álvaro Cunqueiro
Vigo, Spain, 36312
Clinical Rheumatology Research Center Sahlgrenska
Gothenburg, Sweden, 413 45
Kantonspital St. Gallen, Rheumatologie Department
St. Gallen, Switzerland, 9007
Universitätsspital Zürich
Zürich, Switzerland, 8091
Songklanagarind Hospital
Hat Yai, Thailand, 90110
Srinagarind Hospital
Muang, Thailand, 40002
Ramathibodi Hospital
Ratchathewi, Thailand, 10400
United Kingdom
Glasgow Royal Infirmary
Glasgow, United Kingdom, G4 0SF
Royal Free Hospital
London, United Kingdom, NW3 2QG
Guy's Hospital
London, United Kingdom, SE1 9RT
Royal Brompton Hospital
London, United Kingdom, SW3 6NP
Salford Royal Hospital
Salford, United Kingdom, M6 8HD
Sponsors and Collaborators
Boehringer Ingelheim
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Boehringer Ingelheim Identifier: NCT02597933     History of Changes
Other Study ID Numbers: 1199.214
2015-000392-28 ( EudraCT Number )
First Posted: November 5, 2015    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018
Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Connective Tissue Diseases
Skin Diseases
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action