A Trial to Compare Nintedanib With Placebo for Patients With Scleroderma Related Lung Fibrosis
- Registration Number
- NCT02597933
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 580
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo patient receives capsules identical to those containing active drug Nintedanib Nintedanib patient receives capsules containing nintedanib twice a day
- Primary Outcome Measures
Name Time Method Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks up to week (wk) 52 after the start of administration Forced vital capacity (FVC) is the total amount of air exhaled during the lung function test.
For this endpoint reported means represent the adjusted rate.
- Secondary Outcome Measures
Name Time Method Annual Rate of Decline in FVC in Percentage (%) Predicted Over 52 Weeks up to 52 weeks after the start of administration Annual rate of decline in FVC in percentage (%) predicted over 52 weeks.
For this endpoint reported means represent the adjusted rate.Absolute Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52 Baseline and up to 52 weeks after the start of administration This is the first key secondary endpoint.
The modified Rodnan Skin Score (mRSS) is an evaluation of the patient's skin thickness rated by clinical palpation using a 0 to 3 scale. The scale differentiates between 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness with inability to pinch the skin into a fold.
The palpation is done for each of the 17 surface anatomic areas of the body: face, anterior chest, abdomen, fingers (right and left separately), forearms, upper arms, thighs, lower legs, dorsum of hands and feet. The sum of these individual values is defined as the total skin score. The mRSS has a range from 0 (no thickening) to 51 (severe thickening in all 17 areas). A high score corresponds to worse skin thickness.
Least square mean is actually the adjusted mean. Adjusted mean was based on all analysed patients in the model (not only patients with a baseline and measurement at Week 52).Absolute Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Week 52. Baseline and up to 52 weeks after the start of administration This is the second key secondary endpoint.
The Saint George's Respiratory Questionnaire measures the health status in patients with chronic airflow limitation. It consists of 2 parts that cover 3 domains: symptoms, activities, and impacts. The symptom domain relates to the effect, frequency and severity of respiratory symptoms. The activity domain relates to activities that cause or are limited by breathlessness. The impact domain evaluates a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. The scores of these domains range from 0 (no impairment) to 100 (worst possible). The calculated total score summarises the impact of the disease on overall health status. A high score corresponds to worse health.
Least square mean is actually the adjusted mean. Adjusted mean was based on all analysed patients in the model (not only patients with a baseline and measurement at Week 52).Absolute Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Dyspnoea Score at Week 52 Baseline and up to 52 weeks after the start of administration Absolute change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT) dyspnoea score at Week 52.
FACIT-Dyspnoea (Dyspnoea) 10 Item Short Form include a 4-point rating scale (no shortness of breath=0; mildly short of breath=1; moderately short of breath = 2; severely short of breath =3; or I did not do this in the past 7 days =4).
A raw score is calculated as: Sum individual item scores \* 10 / number of items answered. Raw scores are then converted to scale scores using the table included in the FACIT Dyspnoea Scale Short Form Scoring Guideline. FACIT dyspnea scale score ranges between 0 and 75.9.
The FACIT-Dyspnea short forms are scored such that a high score represents high levels of dyspnea.
Least square mean is actually the adjusted mean. Adjusted mean is based on all analysed patients in the model (not only patients with a baseline and measurement at week 52).Absolute Change From Baseline in FVC in mL at Week 52 Baseline and up to 52 weeks after the start of administration Absolute change from baseline in FVC in mL at Week 52. Least square mean is actually the adjusted mean. Adjusted mean was based on all analysed patients in the model (not only patients with a baseline and measurement at Week 52).
Relative Change From Baseline [%] of mRSS at Week 52 Baseline and up to 52 weeks after the start of administration Relative change from baseline \[%\] of mRSS at Week 52.
The modified Rodnan Skin Score (mRSS) is an evaluation of the patient's skin thickness rated by clinical palpation using a 0 to 3 scale. The scale differentiates between 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness with inability to pinch the skin into a fold.
The palpation is done for each of the 17 surface anatomic areas of the body: face, anterior chest, abdomen, fingers (right and left separately), forearms, upper arms, thighs, lower legs, dorsum of hands and feet. The sum of these individual values is defined as the total skin score. The mRSS has a range from 0 (no thickening) to 51 (severe thickening in all 17 areas). A high score corresponds to worse skin thickness.
Least square mean is actually the adjusted mean. Adjusted mean was based on all analysed patients in the model (not only patients with a baseline and measurement at Week 52).Time to Death From date of first trial drug intake up to date of death or last contact date (ie., up to 100 weeks) Time to event analysis of patients with death. The number of observed patients with death are reported.
The Percentage (%) of Responder Based on Combined Response Index in Systemic Sclerosis (CRISS) at Week 52 Week 52 The percentage (%) of responder based on Combined Response Index in Systemic Sclerosis (CRISS) at Week 52.
This is a composite endpoint, based on the mRSS, FVC percent predicted, HAQ-DI, patient's global impression of overall health Visual Analogue Scale (VAS) and physician's global impression of patient's overall health VAS, as well as the absence of significant worsening of interstitial lung disease, a new scleroderma renal crisis, left ventricular failure or pulmonary arterial hypertension.
The CRISS index score represents a probability of improvement and ranges between 0 and 1.
This is a 2 stage process to predict probability of improvement:
Step 1 - absence of major organ progression (SRC etc.) - score "0" Step 2 - predicted probability of improvement - (score "0 - 1")Absolute Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) in % Predicted at Week 52 Baseline and up to 52 weeks after the start of administration Absolute change from baseline in Carbon Monoxide Diffusion Capacity (DLco) in % predicted at Week 52.
Least square mean is actually the adjusted mean. Adjusted mean is based on all analysed patients in the model (not only patients with a baseline and measurement at week 52).Absolute Change From Baseline in Digital Ulcer Net Burden at Week 52 Baseline and up to 52 weeks after the start of administration 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) at Week 52.
It is calculated at a visit by counting the total number of fingertips with ulcers (i.e. number of fingers with presence of digital ulcer ticked "Yes") at the corresponding visit
Least square mean is actually the adjusted mean. Adjusted mean is based on all analysed patients in the model (not only patients with a baseline and measurement at week 52).Absolute Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52 Baseline and up to 52 weeks after the start of administration Absolute change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) score at Week 52.
The HAQ-DI score is calculated as follows:
Each question is scored 0-3 (where 0= "without difficulty" \& 3= "unable to do"). There are 8 categories (Dressing \& Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, Activities), each including 2 or 3 questions. The score for each category corresponds to maximum question score within each category.
Finally, HAQ-DI score corresponds to sum of the sub-scores of all 8 categories divided by number of categories completed. Please note that if there are fewer than 6 categories with responses, then a score cannot be calculated.
The HAQ-DI score scale has 25 possible values (i.e., 0, 0.125, 0.250, 0.375 ... 3). A high score corresponds to worse impairment.
Least square mean is actually the adjusted mean. Adjusted mean is based on all analysed patients in the model (not only patients with a baseline and measurement at week 52).
Trial Locations
- Locations (194)
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
ULB Hopital Erasme
🇧🇪Bruxelles, Belgium
Medical University of Innsbruck
🇦🇹Innsbruck, Austria
UZ Leuven
🇧🇪Leuven, Belgium
Sir Gangaram Hospital
🇮🇳New Delhi, India
EMED, Center of Medical Services,Private Prac,Rzeszow
🇵🇱Rzeszow, Poland
Ramathibodi Hospital
🇹🇭Ratchathewi, Thailand
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
University of Washington
🇺🇸Seattle, Washington, United States
University of Cincinnati Health
🇺🇸Cincinnati, Ohio, United States
Università degli Studi di Genova
🇮🇹Genova, Italy
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
University of Miami
🇺🇸Miami, Florida, United States
First Hospital of Jilin University
🇨🇳Changchun, China
Huashan Hospital, Fudan University
🇨🇳Shanghai, China
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
The Emory Clinic
🇺🇸Atlanta, Georgia, United States
Georgetown University
🇺🇸Washington, District of Columbia, United States
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, China
Columbia University Medical Center-New York Presbyterian Hospital
🇺🇸New York, New York, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
University of Florida College of Medicine
🇺🇸Jacksonville, Florida, United States
LKH-Univ. Hospital Graz
🇦🇹Graz, Austria
Brussels - UNIV Saint-Luc
🇧🇪Bruxelles, Belgium
Centre Hospitalier Universitaire de Liège
🇧🇪Liège, Belgium
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Edumed - Educacao e Saude SA
🇧🇷Curitiba, Brazil
Hamamatsu University Hospital
🇯🇵Shizuoka, Hamamatsu, Japan
The Lung Research Center, LLC
🇺🇸Chesterfield, Missouri, United States
UNIV UZ Gent
🇧🇪Gent, Belgium
The First Hospital of Chinese Medical University
🇨🇳Shenyang, China
Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
National Hospital Organization Himeji Medical Center
🇯🇵Hyogo, Himeji, Japan
HOP Hôtel-Dieu
🇫🇷Nantes, France
Kindai University Hospital
🇯🇵Osaka, Osakasayama, Japan
Saint Joseph's Healthcare
🇨🇦Hamilton, Ontario, Canada
Beijing Chao-Yang Hospital
🇨🇳Beijing, China
Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich
🇦🇷Buenos Aires, Argentina
HOP Calmette
🇫🇷Lille, France
APRILLUS-Asistencia e Investigación
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Liverpool Hospital
🇦🇺Sydney, New South Wales, Australia
Centro de Investigación del Maule
🇨🇱Talca, Chile
Mount Sinai Hospital
🇨🇦Toronto, Ontario, Canada
HOP Larrey
🇫🇷Toulouse, France
West China Hospital
🇨🇳Chengdu, China
Thomayer Hospital
🇨🇿Praha 4, Czechia
Universitätsmedizin Greifswald
🇩🇪Greifswald, Germany
HOP Arnaud de Villeneuve
🇫🇷Montpellier, France
Institute of Rheumathology Prague
🇨🇿Prague, Czechia
CEMER-Centro Medico De Enfermedades Respiratorias
🇦🇷Florida, Argentina
HOP Avicenne
🇫🇷Bobigny, France
Peking Union Medical College Hospital
🇨🇳Beijing, China
Postgraduate Institute of Medical Education And Research
🇮🇳Chandigarh, India
Zhuzhou Central Hospital
🇨🇳Zhuzhou, China
Klinik Donaustauf
🇩🇪Donaustauf, Germany
Kanagawa Cardiovascular and Respiratory Center
🇯🇵Kanagawa, Yokohama, Japan
Kyoto University Hospital
🇯🇵Kyoto, Kyoto, Japan
Kurume University Hospital
🇯🇵Fukuoka, Kurume, Japan
HOP Charles Nicolle
🇫🇷Rouen, France
HOP Louis Pradel
🇫🇷Bron, France
HOP Claude Huriez
🇫🇷Lille, France
HOP Pontchaillou
🇫🇷Rennes, France
Asklepios Klinik Altona
🇩🇪Hamburg, Germany
Oslo Universitetssykehus HF, Rikshospitalet
🇳🇴Oslo, Norway
Indep.Pblic Clin.Hosp#1,Dermatol,Venereol&Allerg.dep,Wroclaw
🇵🇱Wroclaw, Poland
Hospital Garcia de Orta, EPE
🇵🇹Almada, Portugal
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
Iwate Medical University Hospital
🇯🇵Iwate, Morioka, Japan
St. Marianna University School of Medicine Hospital
🇯🇵Kanagawa, Kawasaki, Japan
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
HOP Bichat
🇫🇷Paris, France
Kitasato University Hospital
🇯🇵Kanagawa, Sagamihara, Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
🇯🇵Osaka, Sakai, Japan
A.O Universitaria - Università degli Studi della Campania Luigi Vanvitelli
🇮🇹Napoli, Italy
Università degli Studi Padova
🇮🇹Padova, Italy
Universitätsklinikum Schleswig-Holstein, Campus Kiel
🇩🇪Kiel, Germany
Hospital Tuanku Ja'afar
🇲🇾Seremban, Malaysia
A.O. San Gerardo di Monza
🇮🇹Monza, Italy
Tosei General Hospital
🇯🇵Aichi, Seto, Japan
Sapporo Medical University Hospital
🇯🇵Hokkaido, Sapporo, Japan
Centro Hospitalar São João,EPE
🇵🇹Porto, Portugal
Centro Hospitalar de Vila Nova de Gaia
🇵🇹Vila Nova de Gaia, Portugal
Salford Royal Hospital
🇬🇧Salford, United Kingdom
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Spain
Kantonspital St. Gallen, Rheumatologie Department
🇨🇭St. Gallen, Switzerland
Hospital Dr. Peset
🇪🇸Valencia, Spain
Universitätsspital Zürich
🇨🇭Zürich, Switzerland
Hospital Politècnic La Fe
🇪🇸Valencia, Spain
Clinical Rheumatology Research Center Sahlgrenska
🇸🇪Gothenburg, Sweden
Hospital Fernando Fonseca, EPE
🇵🇹Amadora, Portugal
Songklanagarind Hospital
🇹🇭Hat Yai, Thailand
Srinagarind Hospital
🇹🇭Muang, Thailand
Glasgow Royal Infirmary
🇬🇧Glasgow, United Kingdom
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Boston Medical Center
🇺🇸Boston, Massachusetts, 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
Odense Universitetshospital
🇩🇰Odense, Denmark
Aarhus Universitets Hospital
🇩🇰Århus, Denmark
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Vanderbilt Pulmonary Clinic
🇺🇸Nashville, Tennessee, United States
University of Utah Health Sciences Center
🇺🇸Salt Lake City, Utah, United States
Azienda Universitaria-Universita' La Sapienza
🇮🇹Roma, Italy
Nagasaki University Hospital
🇯🇵Nagasaki, Nagasaki, Japan
Juntendo University Hospital
🇯🇵Tokyo, Bunkyo-Ku, Japan
Nippon Medical School Hospital
🇯🇵Tokyo, Bunkyo-Ku, Japan
Tokushima University Hospital
🇯🇵Tokushima, Tokushima, Japan
Institute of Rheumatology Tokyo Women's Medical University
🇯🇵Tokyo, Shinjyuku-ku, Japan
Klinikum der Universität München - Campus Großhadern
🇩🇪München, Germany
Froedtert and The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Mayo Clinic-Rochester
🇺🇸Rochester, Minnesota, United States
Beijing Hospital
🇨🇳Beijing, China
Stanford University Medical Center
🇺🇸Stanford, California, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Tulane University Hospital and Clinic
🇺🇸New Orleans, Louisiana, United States
University of Minnesota Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
University of Toledo
🇺🇸Toledo, Ohio, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
The University Of Texas at Houston
🇺🇸Houston, Texas, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Hospital Clínico Reg. de Concepción "Dr. G. Grant Benavente"
🇨🇱Concepción, Chile
HSCM
🇨🇦Montreal, Quebec, Canada
HYKS Keuhkosairauksien
🇫🇮Helsinki, Finland
TYKS, Keuhkosairauksien klinikka, Turku
🇫🇮Turku, Finland
HOP Pasteur
🇫🇷Nice, France
HOP Cochin
🇫🇷Paris, France
HOP Bretonneau
🇫🇷Tours, France
Kerckhoff-Klinik, Bad Nauheim
🇩🇪Bad Nauheim, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Semmelweis University, Dept. Pulmonology
🇭🇺Budapest, Hungary
General Hospital of Athens "Laiko"
🇬🇷Athens, Greece
St John's Medical College
🇮🇳Bangalore, India
Mazumdar Shaw Medical centre
🇮🇳Bangalore, India
Ramaiah Medical College and Hospitals
🇮🇳Bangalore, India
Nizam's Institute of Medical Sciences
🇮🇳Hyderabad, India
Care Hospital
🇮🇳Hyderabad, India
Asthma Bhawan
🇮🇳Jaipur, India
P.D. Hinduja National Hospital
🇮🇳Mumbai, India
All India Institute of Medical Science
🇮🇳New Delhi, India
Getwell Hospital & Research Institute
🇮🇳Nagpur, India
Jehangir Clinical Development Centre Pvt. Ltd.
🇮🇳Pune, India
B.J. Medical College and Sasoon General Hospital
🇮🇳Pune, India
Inamdar Multispeciality Hospital
🇮🇳Pune, India
Christian Medical College
🇮🇳Vellore, India
Cork University Hospital
🇮🇪Cork, Ireland
Rambam Medical Center
🇮🇱Haifa, Israel
Mater Misericordiae University Hospital
🇮🇪Dublin 7, Ireland
Bnei Zion Medical Center, Haifa
🇮🇱Haifa, Israel
Rabin Medical Center Beilinson
🇮🇱Petah Tiqwa, Israel
Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Az. Ospedaliere Umberto I di Ancona
🇮🇹Ancona, Italy
Osaka Medical College Hospital
🇯🇵Osaka, Takatsuki, Japan
Saitama Medical University Hospital
🇯🇵Saitama, Iruma-gun, Japan
Toho University Omori Medical Center
🇯🇵Tokyo, Ota-ku, Japan
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Hospital Pulau Pinang
🇲🇾Pulau Pinang, Malaysia
Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas
🇲🇽Ciudad de México, Mexico
Hospital Selayang
🇲🇾Selangor, Malaysia
Leids Universitair Medisch Centrum (LUMC)
🇳🇱Leiden, Netherlands
VU Medisch Centrum
🇳🇱Amsterdam, Netherlands
Radboud Universitair Medisch Centrum
🇳🇱Nijmegen, Netherlands
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Dr.Biziel UnivHosp#2,Rheumat&Connec.Tissue Disease,Bydgoszcz
🇵🇱Bydgoszcz, Poland
Dobry Lekarz,Spec.Med.Clinics,Private Prac,Krakow
🇵🇱Krakow, Poland
Universitetssykehuset Nord-Norge, Tromsø
🇳🇴Tromsø, Norway
ULSAM, EPE - Hospital Conde de Bertiandos
🇵🇹Ponte de Lima, Portugal
CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
🇵🇹Coimbra, Portugal
Hospital Álvaro Cunqueiro
🇪🇸Vigo, Spain
Royal Free Hospital
🇬🇧London, United Kingdom
University of South Carolina
🇺🇸Columbia, South Carolina, United States
Universitätsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Inova Fairfax Medical Campus
🇺🇸Falls Church, Virginia, United States
Universitätsklinikum Köln (AöR)
🇩🇪Köln, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
University of Louisville
🇺🇸Louisville, Kentucky, United States
University of California Davis
🇺🇸Sacramento, California, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Royal Brompton Hospital
🇬🇧London, United Kingdom
Guy's Hospital
🇬🇧London, United Kingdom
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States