Effect of Nintedanib on Biomarkers of Extracellular Matrix Turnover in Patients With Idiopathic Pulmonary Fibrosis and Limited Forced Vital Capacity Impairment
A 12-week, Double Blind, Randomised, Placebo Controlled, Parallel Group Trial Followed by a Single Active Arm Phase of 40 Weeks Evaluating the Effect of Oral Nintedanib 150 mg Twice Daily on Change in Biomarkers of Extracellular Matrix (ECM) Turnover in Patients With Idiopathic Pulmonary Fibrosis (IPF) and Limited Forced Vital Capacity (FVC) Impairment.
2 other identifiers
interventional
347
13 countries
86
Brief Summary
Identifying biomarkers to predict the clinical course and benefits of therapy early in the course of the disease remains one of the most urgent and relevant challenges to improve overall patient management, to prevent treatment delay or overtreatment. This study is conducted to examine the effect of nintedanib treatment on change in biomarkers indicative of extracellular matrix turnover which have been shown recently to correlate with disease progression. This study further aims to confirm the association of biomarker course during the first three months of treatment and disease progression.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Jun 2016
86 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 27, 2016
CompletedFirst Posted
Study publicly available on registry
June 2, 2016
CompletedStudy Start
First participant enrolled
June 9, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 4, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
June 8, 2018
CompletedResults Posted
Study results publicly available
August 6, 2019
CompletedDecember 21, 2023
December 1, 2023
1.2 years
May 27, 2016
May 29, 2019
December 18, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
The Rate of Change (Slope) in Blood C-reactive Protein Degraded by Matrix Metalloproteinase-1/8 (CRPM) From Baseline to Week 12.
The rate of change (slope) in blood C-reactive protein degraded by matrix metalloproteinase-1/8 (CRPM) from baseline to week 12 is presented. The mean presented is the adjusted rate based on a random coefficient regression (CRPM log 10 transformed) with fixed effects for gender, age, height and random effect of patient specific intercept and time.
baseline and 12 weeks
Secondary Outcomes (3)
Percentage of Patients With Disease Progression as Defined by Absolute Forced Vital Capacity (FVC) Decline >=10% or Death Until Week 52
52 weeks
The Rate of Change in Blood Collagen 1 Degraded by Matrix Metalloproteinase-2/9/13 (C1M) From Baseline to Week 12
baseline and 12 weeks
The Rate of Change in Blood Collagen 3 Degraded by Matrix Metalloproteinase-9 (C3M) From Baseline to Week 12
baseline and 12 weeks
Study Arms (2)
placebo
PLACEBO COMPARATORnintedanib
EXPERIMENTALInterventions
Eligibility Criteria
You may qualify if:
- Written informed consent consistent with International Conference on Harmonisation Good Clinical Practice and local laws, signed prior to participation in the trial including any study related procedures being performed;
- Male or female patients aged \>=40 years at Visit 1;
- A clinical diagnosis of Idiopathic pulmonary fibrosis (IPF) within the last 3 years from visit 0, based upon the American Thoracic Society/ European Respiratory Society /Japanese Respiratory Society/ Latin American Thoracic Association 2011 guideline;
- Chest high resolution computed tomography (HRCT) scan performed within 18 months of Visit 0;
- Combination of HRCT pattern, and surgical lung biopsy pattern (the latter if available) as assessed by central review are consistent with the diagnosis of Idiopathic pulmonary fibrosis;
- Forced vital capacity (FVC) \>=80% of predicted normal at Visit 1.
You may not qualify if:
- Alanine transaminase, Aspartate aminotransferase \> 1.5 fold upper limit of normal (ULN) at Visit 1;
- Total bilirubin \> 1.5 fold ULN at Visit 1;
- Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment);
- Relevant airways obstruction, i.e. pre-bronchodilator Forced expiratory volume in 1 second / Forced vital capacity \< 0.70;
- History of myocardial infarction within 6 months of visit 1 or unstable angina within 1 month of Visit 1;
- Bleeding Risk:
- Known genetic predisposition to bleeding;
- Patients who require fibrinolysis, full-dose therapeutic anticoagulation or high dose antiplatelet therapy;
- History of haemorrhagic central nervous system (CNS) event within 12 months prior to Visit 1;
- History of haemoptysis or haematuria, active gastro-intestinal bleeding or ulcers and/or major injury or surgery within 3 months prior to Visit 1;
- International normalised ratio (INR) \> 2 at Visit 1;
- Prothrombin time (PT) and partial thromboplastin time (PTT) \> 150% of ULN at Visit 1;
- Planned major surgery during the trial participation, including lung transplantation, major abdominal or major intestinal surgery;
- History of thrombotic event (including stroke and transient ischemic attack) within 12 months of Visit 1;
- Creatinine clearance \< 30 mL/min calculated by Cockcroft-Gault formula at Visit 1;
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (86)
Jasper Summit Research, LLC
Jasper, Alabama, 35501, United States
Western Connecticut Medical Group
Danbury, Connecticut, 06810, United States
St. Francis Medical Institute
Clearwater, Florida, 33765, United States
University of Florida College of Medicine
Jacksonville, Florida, 32209, United States
Minnesota Lung Center
Minneapolis, Minnesota, 55407, United States
The Lung Research Center, LLC
Chesterfield, Missouri, 63017, United States
Clinical Research Solutions
Dayton, Ohio, 45409, United States
Pulmonary Associates of Richmond, Inc.
Richmond, Virginia, 23225, United States
Royal Prince Alfred Hospital
Camperdown, Sydney, New South Wales, 2050, Australia
Concord General Repatriation Hospital -Ambulatory Care Unit
Concord, New South Wales, 2139, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
ULB Hopital Erasme
Brussels, 1070, Belgium
Edegem - UNIV UZ Antwerpen
Edegem, 2650, Belgium
UZ Leuven
Leuven, 3000, Belgium
Centre Hospitalier Universitaire de Liège
Liège, 4000, Belgium
Yvoir - UNIV UCL de Mont-Godinne
Yvoir, 5530, Belgium
University Hospital Olomouc
Olomouc, 779 00, Czechia
University Hospital Plzen, Plzen-Bory
Pilsen, 30599, Czechia
Thomayer Hospital
Prague, 14059, Czechia
University Hospital Na Bulovce, Prague
Prague, 180 81, Czechia
Masaryk Hospital, Usti nad Labem
Ústí nad Labem, 401 13, Czechia
HYKS Keuhkosairauksien
Helsinki, 00290, Finland
KYS, Keuhkosairauksien
Kuopio, 70210, Finland
OYS, sisätautien klinikka
Oulu, 90220, Finland
Tampere University Hospital
Tampere, FI-33520, Finland
TYKS, Keuhkosairauksien klinikka, Turku
Turku, 20520, Finland
HOP de la Cavale Blanche
Brest, 29609, France
HOP Louis Pradel
Bron, 69677, France
HOP Européen G. Pompidou
Paris, 75015, France
HOP Maison Blanche
Reims, 51092, France
HOP Pontchaillou
Rennes, 35033, France
HOP Civil
Strasbourg, 67091, France
HOP Bretonneau
Tours, 37044, France
CIMS Studienzentrum Bamberg GmbH
Bamberg, 96049, Germany
Helios Klinikum Emil von Behring
Berlin, 14165, Germany
Universitätsklinikum Gießen und Marburg GmbH
Giessen, 35392, Germany
Universitätsmedizin Greifswald
Greifswald, 17475, Germany
Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH
Großhansdorf, 22927, Germany
Medizinische Hochschule Hannover
Hanover, 30625, Germany
Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
Heidelberg, 69126, Germany
Lungenfachklinik Immenhausen
Immenhausen, 34376, Germany
Klinikum der Universität München - Campus Großhadern
München, 81377, Germany
Universitätsklinikum Münster
Münster, 48149, Germany
Semmelweis University
Budapest, 1125, Hungary
Csongrad County's Hosp.
Deszk, 6772, Hungary
Pulmonology Institute of Veszprem County, Farkasgyepu
Farkasgyepű, 8582, Hungary
BAZ County Central Hospital and University Teaching Hospital
Miskolc, 3526, Hungary
Tosei General Hospital
Aichi, Seto, 489-8642, Japan
Kurume University Hospital
Fukuoka, Kurume, 830-0011, Japan
Ibarakihigashi National Hospial
Ibaraki, Naka-gun, 319-1113, Japan
Kanagawa Cardiovascular and Respiratory Center
Kanagawa, Yokohama, 236-0051, Japan
Kindai University Hospital
Osaka, Osakasayama, 589-8511, Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
Osaka, Sakai, 591-8555, Japan
Tokushima University Hospital
Tokushima, Tokushima, 770-8503, Japan
Nippon Medical School Hospital
Tokyo, Bunkyo-ku, 113-8603, Japan
Toho University Omori Medical Center
Tokyo, Ota-ku, 143-8541, Japan
Global Health and Medicine Ctr
Tokyo, Shinjuku-ku, 162-8655, Japan
Our Doctor Clinical Trial Center, Department in Bydgoszcz
Bydgoszcz, 85065, Poland
Non-pub.Health Care NZOZ Profilaktyka W. Pierzchala,Katowice
Katowice, 40-752, Poland
Univ. Hospital in Krakow,Pulmonology Clinical Dept
Krakow, 31-066, Poland
John Paul II Cracovian Hosp
Krakow, 31-202, Poland
Norbert Barlicki University Clinical Hospital No.1, Lodz
Lodz, 90-153, Poland
Practice of Internists "Nasz Lekarz", Torun
Torun, 87-100, Poland
Seoul National University Bundang Hospital
Seongnam, 13620, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Hospital Clínic de Barcelona
Barcelona, 08036, Spain
Hospital Santa Creu i Sant Pau
Barcelona, 08041, Spain
Hospital de Galdakao
Galdakao, 48960, Spain
Hospital de Bellvitge
L'Hospitalet Llobregat (bcn), 08907, Spain
Hospital La Princesa
Madrid, 28006, Spain
Fundación Jiménez Díaz
Madrid, 28040, Spain
Hospital Clínico San Carlos
Madrid, 28040, Spain
Hospital Puerta de Hierro
Majadahonda (Madrid), 28220, Spain
Hospital Quirónsalud Madrid
Pozuelo de Alarcón, 28223, Spain
CS Parc Taulí
Sabadell, 08208, Spain
Hospital Virgen del Rocío
Seville, 41013, Spain
Hospital Clínico de Valencia
Valencia, 46010, Spain
Hospital Dr. Peset
Valencia, 46017, Spain
Southmead Hospital
Bristol, BS10 5NB, United Kingdom
Papworth Hospital
Cambridge, CB23 3RE, United Kingdom
Royal Devon and Exeter Hospital
Exeter, EX2 5DW, United Kingdom
Royal Brompton Hospital
London, SW3 6NP, United Kingdom
Wythenshawe Hospital
Manchester, M23 9LT, United Kingdom
Churchill Hospital
Oxford, OX3 7LE, United Kingdom
Related Publications (4)
Glaspole I, Bonella F, Bargagli E, Glassberg MK, Caro F, Stansen W, Quaresma M, Orsatti L, Bendstrup E. Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities. Respir Res. 2021 Apr 26;22(1):125. doi: 10.1186/s12931-021-01695-y.
PMID: 33902584DERIVEDNoth I, Cottin V, Chaudhuri N, Corte TJ, Johannson KA, Wijsenbeek M, Jouneau S, Michael A, Quaresma M, Rohr KB, Russell AM, Stowasser S, Maher TM; INMARK trial investigators. Home spirometry in patients with idiopathic pulmonary fibrosis: data from the INMARK trial. Eur Respir J. 2021 Jul 8;58(1):2001518. doi: 10.1183/13993003.01518-2020. Print 2021 Jul.
PMID: 33419890DERIVEDMaher TM, Stowasser S, Nishioka Y, White ES, Cottin V, Noth I, Selman M, Rohr KB, Michael A, Ittrich C, Diefenbach C, Jenkins RG; INMARK trial investigators. Biomarkers of extracellular matrix turnover in patients with idiopathic pulmonary fibrosis given nintedanib (INMARK study): a randomised, placebo-controlled study. Lancet Respir Med. 2019 Sep;7(9):771-779. doi: 10.1016/S2213-2600(19)30255-3. Epub 2019 Jul 17.
PMID: 31326319DERIVEDMaher TM, Stowasser S, Nishioka Y, White ES, Cottin V, Noth I, Selman M, Blahova Z, Wachtlin D, Diefenbach C, Jenkins RG. Investigating the effects of nintedanib on biomarkers of extracellular matrix turnover in patients with IPF: design of the randomised placebo-controlled INMARK(R)trial. BMJ Open Respir Res. 2018 Aug 20;5(1):e000325. doi: 10.1136/bmjresp-2018-000325. eCollection 2018.
PMID: 30167310DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Boehringer Ingelheim, Call Center
- Organization
- Boehringer Ingelheim
Study Officials
- STUDY CHAIR
Boehringer Ingelheim
Boehringer Ingelheim
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 27, 2016
First Posted
June 2, 2016
Study Start
June 9, 2016
Primary Completion
August 4, 2017
Study Completion
June 8, 2018
Last Updated
December 21, 2023
Results First Posted
August 6, 2019
Record last verified: 2023-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
- 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 the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
Once the criteria in section "Time Frame" are fulfilled, researchers can use the 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". Furthermore, researchers can 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.