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Idiopathic Pulmonary FibrosisPhase 4NCT02788474

Effect of Nintedanib on Biomarkers of Extracellular Matrix Turnover in Patients With Idiopathic Pulmonary Fibrosis and Limited Forced Vital Capacity Impairment

A Phase 4 study testing nintedanib in people with Idiopathic Pulmonary Fibrosis, run by Boehringer Ingelheim at 86 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Idiopathic Pulmonary Fibrosis
What is being tested?
nintedanib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
347 participants
Where
86 sitesin 13 countries
Study dates
9 Jun 2016to 8 Jun 2018
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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:
Show all 26Show fewer
  • 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;
  • Treatment with nintedanib, pirfenidone, azathioprine, cyclophosphamide, cyclosporine, any other investigational drug, n-acetylcysteine, prednisone/prednisolone >15 mg daily or >30 mg every 2 days OR use of other systemic corticosteroids as well as any investigational drugs within 4 weeks of Visit 2;
  • Known hypersensitivity to nintedanib, peanut, soya or to any other components of the study medication;
  • Prior discontinuation of nintedanib treatment due to intolerability/ adverse events considered drug related;
  • A disease or condition which in the opinion of the investigator may interfere with testing procedures or put the patient at risk when participating in this trial;
  • Alcohol or drug abuse which in the opinion of the treating physician would interfere with the treatment and would affect patient's ability to participate in this trial;
  • Patients not able to understand and follow any study procedures such as but not limited to home spirometry, including completion of self-administered questionnaires without help;
  • Women who are pregnant, nursing, who plan to become pregnant while in the trial or female patients with positive pregnancy (ß-HCG) test at Visit 1 and/or Visit 2;
  • Women of childbearing potential4 not willing or able to use highly effective methods of birth control per International Conference on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly.
  • Patients with acute IPF exacerbation or any respiratory tract infection in the four weeks prior to Visit 1 or during the screening period;
  • Patients who are or have been participating in another trial with investigational drug/s within one month prior to Visit 1 and patients who have previously been enrolled in this trial;
  • Further exclusion criteria apply.

Trial locations and contacts

86 sites in 13 countries.

86 sites in 13 countries

Spain13 sites

  • Hospital Clínic de Barcelona

    Barcelona, 08036

  • Hospital Santa Creu i Sant Pau

    Barcelona, 08041

  • Hospital de Galdakao

    Galdakao, 48960

  • Hospital de Bellvitge

    L'Hospitalet Llobregat (bcn), 08907

  • Hospital La Princesa

    Madrid, 28006

  • Fundación Jiménez Díaz

    Madrid, 28040

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Puerta de Hierro

    Majadahonda (Madrid), 28220

  • Hospital Quirónsalud Madrid

    Pozuelo de Alarcón, 28223

  • CS Parc Taulí

    Sabadell, 08208

  • Hospital Virgen del Rocío

    Seville, 41013

  • Hospital Clínico de Valencia

    Valencia, 46010

  • Hospital Dr. Peset

    Valencia, 46017

Other trials in Spain

Germany10 sites

  • CIMS Studienzentrum Bamberg GmbH

    Bamberg, 96049

  • Helios Klinikum Emil von Behring

    Berlin, 14165

  • Universitätsklinikum Gießen und Marburg GmbH

    Giessen, 35392

  • Universitätsmedizin Greifswald

    Greifswald, 17475

  • Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH

    Großhansdorf, 22927

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg

    Heidelberg, 69126

  • Lungenfachklinik Immenhausen

    Immenhausen, 34376

  • Klinikum der Universität München - Campus Großhadern

    München, 81377

  • Universitätsklinikum Münster

    Münster, 48149

Other trials in Germany

Japan10 sites

  • Tosei General Hospital

    Aichi, Seto, 489-8642

  • Kurume University Hospital

    Fukuoka, Kurume, 830-0011

  • Ibarakihigashi National Hospial

    Ibaraki, Naka-gun, 319-1113

  • Kanagawa Cardiovascular and Respiratory Center

    Kanagawa, Yokohama, 236-0051

  • Kindai University Hospital

    Osaka, Osakasayama, 589-8511

  • National Hospital Organization Kinki-Chuo Chest Medical Center

    Osaka, Sakai, 591-8555

  • Tokushima University Hospital

    Tokushima, Tokushima, 770-8503

  • Nippon Medical School Hospital

    Tokyo, Bunkyo-ku, 113-8603

  • Toho University Omori Medical Center

    Tokyo, Ota-ku, 143-8541

  • Global Health and Medicine Ctr

    Tokyo, Shinjuku-ku, 162-8655

Other trials in Japan

United States8 sites

  • The Lung Research Center, LLC

    Chesterfield, Missouri, 63017

  • St. Francis Medical Institute

    Clearwater, Florida, 33765

  • Western Connecticut Medical Group

    Danbury, Connecticut, 06810

  • Clinical Research Solutions

    Dayton, Ohio, 45409

  • University of Florida College of Medicine

    Jacksonville, Florida, 32209

  • Jasper Summit Research, LLC

    Jasper, Alabama, 35501

  • Minnesota Lung Center

    Minneapolis, Minnesota, 55407

  • Pulmonary Associates of Richmond, Inc.

    Richmond, Virginia, 23225

Other trials in United States

France7 sites

  • HOP de la Cavale Blanche

    Brest, 29609

  • HOP Louis Pradel

    Bron, 69677

  • HOP Européen G. Pompidou

    Paris, 75015

  • HOP Maison Blanche

    Reims, 51092

  • HOP Pontchaillou

    Rennes, 35033

  • HOP Civil

    Strasbourg, 67091

  • HOP Bretonneau

    Tours, 37044

Other trials in France

Poland6 sites

  • Our Doctor Clinical Trial Center, Department in Bydgoszcz

    Bydgoszcz, 85065

  • Non-pub.Health Care NZOZ Profilaktyka W. Pierzchala,Katowice

    Katowice, 40-752

  • Univ. Hospital in Krakow,Pulmonology Clinical Dept

    Krakow, 31-066

  • John Paul II Cracovian Hosp

    Krakow, 31-202

  • Norbert Barlicki University Clinical Hospital No.1, Lodz

    Lodz, 90-153

  • Practice of Internists "Nasz Lekarz", Torun

    Torun, 87-100

Other trials in Poland

United Kingdom6 sites

  • Southmead Hospital

    Bristol, BS10 5NB

  • Papworth Hospital

    Cambridge, CB23 3RE

  • Royal Devon and Exeter Hospital

    Exeter, EX2 5DW

  • Royal Brompton Hospital

    London, SW3 6NP

  • Wythenshawe Hospital

    Manchester, M23 9LT

  • Churchill Hospital

    Oxford, OX3 7LE

Other trials in United Kingdom

Belgium5 sites

  • ULB Hopital Erasme

    Brussels, 1070

  • Edegem - UNIV UZ Antwerpen

    Edegem, 2650

  • UZ Leuven

    Leuven, 3000

  • Centre Hospitalier Universitaire de Liège

    Liège, 4000

  • Yvoir - UNIV UCL de Mont-Godinne

    Yvoir, 5530

Other trials in Belgium

Czechia5 sites

  • University Hospital Olomouc

    Olomouc, 779 00

  • University Hospital Plzen, Plzen-Bory

    Pilsen, 30599

  • Thomayer Hospital

    Prague, 14059

  • University Hospital Na Bulovce, Prague

    Prague, 180 81

  • Masaryk Hospital, Usti nad Labem

    Ústí nad Labem, 401 13

Other trials in Czechia

Finland5 sites

  • HYKS Keuhkosairauksien

    Helsinki, 00290

  • KYS, Keuhkosairauksien

    Kuopio, 70210

  • OYS, sisätautien klinikka

    Oulu, 90220

  • Tampere University Hospital

    Tampere, FI-33520

  • TYKS, Keuhkosairauksien klinikka, Turku

    Turku, 20520

Other trials in Finland

Australia4 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Royal Prince Alfred Hospital

    Camperdown, Sydney, New South Wales, 2050

  • Concord General Repatriation Hospital -Ambulatory Care Unit

    Concord, New South Wales, 2139

  • The Alfred Hospital

    Melbourne, Victoria, 3004

Other trials in Australia

Hungary4 sites

  • Semmelweis University

    Budapest, 1125

  • Csongrad County's Hosp.

    Deszk, 6772

  • Pulmonology Institute of Veszprem County, Farkasgyepu

    Farkasgyepű, 8582

  • BAZ County Central Hospital and University Teaching Hospital

    Miskolc, 3526

Other trials in Hungary

South Korea3 sites

  • Seoul National University Bundang Hospital

    Seongnam, 13620

  • Seoul National University Hospital

    Seoul, 03080

  • Asan Medical Center

    Seoul, 05505

Other trials in South Korea

About this study

Official title: 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.

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.

Being tested
nintedanib, placebo
Medical subject headings
Idiopathic Pulmonary Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • nintedanibDrug

  • placeboDrug

Study groups in NCT02788474
Study groupRoleWhat they receive
placeboPlacebo comparatorNot described
Receives: Drug: placebo
nintedanibExperimentalNot described
Receives: Drug: nintedanib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: baseline and 12 weeks

Secondary outcomes (3)

  1. Percentage of Patients With Disease Progression as Defined by Absolute Forced Vital Capacity (FVC) Decline >=10% or Death Until Week 52

    For this endpoint, disease progression was defined by absolute FVC (percentage of predicted) decline ≥10% or death up to Week 52 based on in-clinic supervised spirometry.

    This is a key secondary endpoint of the trial. This outcome measure is "percentage of patients with disease progression" and CRPM is included in the various models as a factor/covariate, and that this outcome measure, the percentage of progressors are displayed under "Measured values"

    Measured: 52 weeks

  2. The Rate of Change in Blood Collagen 1 Degraded by Matrix Metalloproteinase-2/9/13 (C1M) From Baseline to Week 12

    The rate of change in blood Collagen 1 degraded by matrix metalloproteinase-2/9/13 (C1M) from baseline to week 12 is presented.

    The mean presented is the adjusted rate based on a random coefficient regression (C1M (negative reciprocal root transformation)) with fixed effects for gender, age, height and random effect of patient specific intercept and time.

    Measured: baseline and 12 weeks

  3. The Rate of Change in Blood Collagen 3 Degraded by Matrix Metalloproteinase-9 (C3M) From Baseline to Week 12

    The rate of change in blood Collagen 3 degraded by matrix metalloproteinase-9 (C3M) from baseline to week 12 is presented.

    The mean presented is the adjusted rate based on a random coefficient regression (C3M- log 10 transformation) with fixed effects for gender, age, height and random effect of patient specific intercept and time.

    Measured: baseline and 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jun 2016 (estimated)
  2. Study start9 Jun 2016
  3. Primary completion4 Aug 2017
  4. Study completion8 Jun 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
347 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02788474
Sponsor's protocol ID
1199.227
Other IDs
2015-003148-38, 2015
Status last verified
Dec 2023
First submitted
27 May 2016
Last updated
21 Dec 2023
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 33902584

  • Noth 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.

    PubMed 33419890

  • Maher 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.

    PubMed 31326319

  • Maher 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.

    PubMed 30167310

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing nintedanib in people with Idiopathic Pulmonary Fibrosis, run by Boehringer Ingelheim at 86 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 86 sites in Spain, Germany, Japan, United States, France and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Rate of Change (Slope) in Blood C-reactive Protein Degraded by Matrix Metalloproteinase-1/8 (CRPM) From Baseline to Week 12. (time frame: baseline and 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02788474, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2023.

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