Efficacy and Safety of Nintedanib in Patients With Progressive Fibrosing Interstitial Lung Disease (PF-ILD) (INBUILD®)

April 22, 2020 updated by: Boehringer Ingelheim

A Double Blind, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of Nintedanib Over 52 Weeks in Patients With Progressive Fibrosing Interstitial Lung Disease (PF-ILD)

The aim of the current study is to investigate the efficacy and safety of nintedanib over 52 weeks in patients with Progressive Fibrosing Interstitial Lung Disease (PF-ILD) defined as patients who present with features of diffuse fibrosing lung disease of >10% extent on high-resolution computed tomography (HRCT) and whose lung function and respiratory symptoms or chest imaging have worsened despite treatment with unapproved medications used in clinical practice to treat ILD. There is currently no efficacious treatment available for PF-ILD. Based on its efficacy and safety in Idiopathic Pulmonary Fibrosis (IPF), it is anticipated that Nintedanib will be a new treatment option for patients with PF-ILD.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
663

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Alberdi Sur, Argentina, X5003DCE
        • Centro Dr. Lazaro Langer S.R.L
      • C.a.b.a, Argentina, 1056
        • Centro de Investigaciones Metabólicas (CINME)
      • Ciudad Autónoma de Bs As, Argentina, C1180AAX
        • Sanatorio Guemes
      • Florida, Argentina, B1602DQD
        • CEMER-Centro Medico De Enfermedades Respiratorias
      • Mendoza, Argentina, M5500CCG
        • INSARES
      • Rosario, Argentina, S2000DEJ
        • Instituto Medico de la Fundacion Estudios Clinicos
  • Belgium
      • Angleur, Belgium, 4031
        • Centre Hospitalier Universitaire de Liege
      • Bruxelles, Belgium, 1070
        • ULB Hôpital Erasme
      • Leuven, Belgium, 3000
        • UZ Leuven
      • Yvoir, Belgium, 5530
        • Yvoir - UNIV UCL de Mont-Godinne
  • Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada, R2K 3S8
        • Concordia Hospital
    • Ontario
      • Hamilton, Ontario, Canada, L8N 4A6
        • St. Joseph's Healthcare Hamilton
      • Toronto, Ontario, Canada, M5G 2N2
        • Toronto General Hospital
    • Quebec
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • CHUS Fleurimont
  • Chile
      • Concepción, Chile, 4070038
        • Hospital Clínico Reg. de Concepción "Dr. G. Grant Benavente"
      • Providencia, Santiago De Chile, Chile, 7500000
        • Instituto Nacional del Tórax
      • Talca, Chile, 3465586
        • Centro de Investigación del Maule
  • China
      • Beijing, China, 100032
        • Peking Union Medical College Hospital
      • Guangzhou, China, 510120
        • First Affiliated Hospital of Guangzhou Medical University
      • Nanjing, China, 210008
        • Nanjing Drum Tower Hospital
      • Shenyang, China
        • The First Hospital of Chinese Medical University
  • France
      • Bobigny, France, 93009
        • HOP Avicenne
      • Bron, France, 69500
        • HOP Louis Pradel
      • Caen, France, 14033
        • HOP Côte de Nacre
      • Clamart, France, 92140
        • HOP d'Instruction des Armées Percy
      • Lille, France, 59037
        • HOP Calmette
      • Marseille, France, 13015
        • HOP Nord
      • Montpellier, France, 34295
        • HOP Arnaud de Villeneuve
      • Nice, France, 06001
        • HOP Pasteur
      • Paris, France, 75018
        • HOP Bichat
      • Reims, France, 51092
        • HOP Maison Blanche
      • Rennes, France, 35033
        • HOP Pontchaillou
      • Strasbourg, France, 67091
        • HOP Civil
      • Tours, France, 37000
        • HOP Bretonneau
  • Germany
      • Bonn, Germany, 53105
        • Universitätsklinikum Bonn AöR
      • Coswig, Germany, 01640
        • Fachkrankenhaus Coswig GmbH
      • Donaustauf, Germany, 93093
        • Klinik Donaustauf
      • Essen, Germany, 45239
        • Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
      • Hannover, Germany, 30625
        • Medizinische Hochschule Hannover
      • Heidelberg, Germany, 69126
        • Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
      • Solingen, Germany, 42699
        • Wissenschaftliches Institut Bethanien
      • Tübingen, Germany, 72076
        • Universitatsklinikum Tubingen
      • Wuppertal, Germany, 42283
        • Petrus-Krankenhaus
  • Italy
      • Catania, Italy, 95124
        • A.O.U. Policlinico Vittorio Emanuele
      • FORLì, Italy, 47121
        • Ospedale "G.B. Morgagni - L. Pierantoni" ausl forli
      • Modena, Italy, 41100
        • Azienda Ospedaliera Policlinico di Modena
      • Monza, Italy, 20900
        • A.O. San Gerardo di Monza
      • Roma, Italy, 00168
        • Policlinico Gemelli
      • Siena, Italy, 53100
        • A.O.U. Senese Policlinico Santa Maria alle Scotte
  • Japan
      • Aichi, Seto, Japan, 489-8642
        • Tosei General Hospital
      • Fukuoka, Kurume, Japan, 830-0011
        • Kurume University Hospital
      • Hokkaido, Sapporo, Japan, 060-8543
        • Sapporo Medical University Hospital
      • Hyogo, Himeji, Japan, 670-8520
        • National Hospital Organization Himeji Medical Center
      • Hyogo, Kobe, Japan, 650-0047
        • Kobe City Medical Center General Hospital
      • Ibaraki, Naka-gun, Japan, 319-1113
        • Ibarakihigashi National Hospial
      • Kanagawa, Yokohama, Japan, 236-0051
        • Kanagawa Cardiovascular and Respiratory Center
      • Kumamoto, Kumamoto, Japan, 861-4193
        • Saiseikai Kumamoto Hospital
      • Miyagi, Sendai, Japan, 980-8574
        • Tohoku University Hospital
      • Nagasaki, Nagasaki, Japan, 852-8501
        • Nagasaki University Hospital
      • Osaka, Sakai, Japan, 591-8555
        • National Hospital Organization Kinki-Chuo Chest Medical Center
      • Osaka, Takatsuki, Japan, 569-8686
        • Osaka Medical College Hospital
      • Shizuoka, Hamamatsu, Japan, 431-3192
        • Hamamatsu University Hospital
      • Tochigi, Shimotsuke, Japan, 329-0498
        • Jichi Medical University Hospital
      • Tokushima, Tokushima, Japan, 770-8503
        • Tokushima University Hospital
      • Tokyo, Bunkyo-ku, Japan, 113-8603
        • Nippon Medical School Hospital
      • Tokyo, Bunkyo-ku, Japan, 113-8519
        • Tokyo Medical and Dental University
      • Tokyo, Minato-ku, Japan, 105-8470
        • Toranomon Hospital
      • Tokyo, Shibuya-ku, Japan, 151-8528
        • JR Tokyo General Hospital
      • Tokyo, Shinjuku-ku, Japan, 162-8655
        • Global Health and Medicine Ctr
  • Korea, Republic of
      • Bucheon, Korea, Republic of, 14647
        • The Catholic University of Korea, Bucheon St.Mary's Hospital
      • Seongnam, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
  • Poland
      • Gdansk, Poland, 80-214
        • University Clinical Center, Gdansk
      • Katowice, Poland, 40-752
        • Leszek Giec Upper-Silesian Med.Cent.Silesian Med.Univ.
      • Lodz, Poland, 90-153
        • Norbert Barlicki University Clinical Hospital No.1, Lodz
      • Warszawa, Poland, 01-138
        • Nat.Instit.of Tuberculosis&LungDiseases,Outpat.Clin,warszawa
      • Zabrze, Poland, 41-803
        • Clinical Hospital No. 1, n.a. Prof. Szyszko from Silesian MA
  • Russian Federation
      • Kemerovo, Russian Federation, 650002
        • Res.Inst.-Compl.Iss.Cardi.Dis.
      • Moscow, Russian Federation, 119992
        • Moscow 1st State Med.Univ.n.a.I.M.Sechenov
      • Moscow, Russian Federation, 107564
        • Central Scientific Research Insitute of Tuberculosis
      • Moscow, Russian Federation, 105077
        • Pulmonology Scientific Research Institute
      • St. Petersburg, Russian Federation, 197101
        • Scientific Research Institute of Pulmonology
      • Yaroslavl, Russian Federation, 150003
        • Emergency Clinical Hospital n. a. N. V. Solovyev, Yaroslavl
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Vall d'Hebron
      • Barcelona, Spain, 08026
        • Hospital Santa Creu i Sant Pau
      • Cádiz, Spain, 11009
        • Hospital Puerta Del Mar
      • Galdakao, Spain, 48960
        • Hospital de Galdakao
      • L'Hospitalet de Llobregat, Spain, 08907
        • Hospital De Bellvitge
      • Madrid, Spain, 28046
        • Hospital La Paz
      • Madrid, Spain, 28006
        • Hospital La Princesa
      • Oviedo, Spain, 33011
        • Hospital Central de Asturias
      • Palma de Mallorca, Spain, 07120
        • Hospital Son Espases
      • San Cristóbal de La Laguna, Spain, 38320
        • Hospital de Canarias
      • Sevilla, Spain, 41013
        • Hospital Virgen del Rocío
      • Valencia, Spain, 46026
        • Hospital Politècnic La Fe
  • United Kingdom
      • Cardiff, United Kingdom, CF64 2XX
        • University Hospital Llandough
      • Edinburgh, United Kingdom, EH16 4SA
        • Royal Infirmary of Edinburgh
      • Leeds, United Kingdom, LS9 7TF
        • St James's University Hospital
      • London, United Kingdom, SW3 6NP
        • Royal Brompton Hospital
      • Manchester, United Kingdom, M23 9LT
        • Wythenshawe Hospital
      • Stoke-on-Trent, United Kingdom, ST4 6QG
        • Royal Stoke University Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • California
      • Los Angeles, California, United States, 90095
        • University of California Los Angeles
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • Sacramento, California, United States, 95817
        • University of California Davis
      • San Francisco, California, United States, 94143
        • University of California San Francisco
    • Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish Health
    • Connecticut
      • Danbury, Connecticut, United States, 06810
        • Pulmonary and Sleep Specialists
      • New Haven, Connecticut, United States, 06510
        • Yale University School of Medicine
    • Florida
      • Brandon, Florida, United States, 33511
        • Pulmonary and Sleep of Tampa Bay
      • Jacksonville, Florida, United States, 32209
        • University of Florida College of Medicine
      • Miami, Florida, United States, 33125
        • University of Miami
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland School of Medicine
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins Hospital
      • Towson, Maryland, United States, 21286
        • Pulmonary and Critical Care Associates of Baltimore
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Pulmonary and Critical Care Medicine
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
      • Grand Rapids, Michigan, United States, 49546
        • Spectrum Health
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Masonic Cancer Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic, Rochester
    • Missouri
      • Chesterfield, Missouri, United States, 63017
        • The Lung Research Center, LLC
    • Nebraska
      • Omaha, Nebraska, United States, 68124
        • Creighton University
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth-Hitchcock Medical Center
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, United States, 10032
        • Columbia University Medical Center-New York Presbyterian Hospital
      • New York, New York, United States, 10065
        • NewYork-Presbyterian/Weill Cornell Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27103
        • Southeastern Research Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Wexner Medical Center
    • Oregon
      • Portland, Oregon, United States, 97220
        • The Oregon Clinic
      • Portland, Oregon, United States, 97225
        • The Oregon Clinic
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Milton S. Hershey Medical Center
      • Oaks, Pennsylvania, United States, 19456
        • Temple University Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • University of South Carolina
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center
      • Fort Worth, Texas, United States, 76104
        • Texas Pul & Crit Care Conslt
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital
      • San Antonio, Texas, United States, 78229
        • Diagnostics Research Group
      • San Antonio, Texas, United States, 78229
        • Medical Arts and Research Center (MARC)
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • University of Utah Health Sciences Center
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Medical Campus
      • Richmond, Virginia, United States, 23225
        • Pulmonary Associates of Richmond, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Written Informed Consent consistent with International Conference on Harmonisation Harmonised Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local laws signed prior to entry into the study (and prior to any study procedure including shipment of High Resolution Computer Tomography (HRCT) to reviewer).
  • Male or female patients aged >= 18 years at Visit 1.

  • Patients with physician diagnosed Interstitial Lung Disease (ILD) who fulfil at least one of the following criteria for Progressive Fibrosing Interstitial Lung Disease (PF-ILD) within 24 months of screening visit (Visit 1) despite treatment with unapproved medications used in clinical practice to treat ILD, as assessed by the investigator (refer to Exclusion Criteria):

    • Clinically significant decline in Forced Vital Capacity (FVC) % pred based on a relative decline of >=10%
    • Marginal decline in FVC % pred based on a relative decline of .>=5-<10% combined with worsening of respiratory symptoms
    • Marginal decline in FVC % pred based on a relative decline of >=5-<10% combined with increasing extent of fibrotic changes on chest imaging
    • Worsening of respiratory symptoms as well as increasing extent of fibrotic changes on chest imaging [Note: Changes attributable to comorbidities e.g. infection, heart failure must be excluded. Unapproved medications used in the clinical practice to treat ILD include but are not limited to corticosteroid, azathioprine, mycophenolate mofetil (MMF), n-acetylcysteine (NAC), rituximab, cyclophosphamide, cyclosporine, tacrolimus].
  • Fibrosing lung disease on HRCT, defined as reticular abnormality with traction bronchiectasis with or without honeycombing, with disease extent of >10%, performed within 12 months of Visit 1 as confirmed by central readers.
  • For patients with underlying Connective Tissue Disease (CTD): stable CTD as defined by no initiation of new therapy or withdrawal of therapy for CTD within 6 weeks prior to Visit 1.
  • Carbon Monoxide Diffusion Capacity (DLCO) corrected for Haemoglobin (Hb) [visit 1] ≥ 30% and <80% predicted of normal at Visit 2
  • FVC >= 45% predicted at Visit 2

Exclusion criteria:

  • Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) > 1.5 x Upper Limit of Normal (ULN) at Visit 1
  • Bilirubin > 1.5 x ULN at Visit 1
  • Creatinine clearance <30 mL/min calculated by Cockcroft-Gault formula at Visit 1 [Note: Laboratory parameters from Visit 1 have to satisfy the laboratory threshold values as shown above. Visit 2 laboratory results will be available only after randomization. In case at Visit 2 the results do no longer satisfy the entry criteria, the Investigator has to decide whether it is justified that the patient remains on study drug. The justification for decision needs to be documented. Laboratory parameters that are found to be abnormal at Visit 1 are allowed to be re-tested (once) if it is thought to be a measurement error (i.e. there was no abnormal result of this test in the recent history of the patient and there is no related clinical sign) or the result of a temporary and reversible medical condition, once that condition is resolved].
  • Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment).
  • Previous treatment with nintedanib or pirfenidone.
  • Other investigational therapy received within 1 month or 6 half-lives (whichever was greater) prior to screening visit (Visit 1).
  • Use of any of the following medications for the treatment of Interstitial Lung Disease (ILD): azathioprine (AZA), cyclosporine, MMF, tacrolimus, oral corticosteroids (OCS) >20mg/day and the combination of OCS+AZA+NAC within 4 weeks of Visit 2, cyclophosphamide within 8 weeks of Visit 2, rituximab within 6 months of Visit 2.

Note: Patients whose Rheumatoid Arthritis (RA)/Connective Tissue Disease (CTD) is managed by these medications should not be considered for participation in the current study unless change in RA/CTD medication is medically indicated (see Inclusion Criteria)

  • Diagnosis of Idiopathic Pulmonary Fibrosis (IPF) based on American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) 2011 Guidelines.

  • Significant Pulmonary Arterial Hypertension (PAH) defined by any of the following:

    • Previous clinical or echocardiographic evidence of significant right heart failure
    • History of right heart catheterization showing a cardiac index <= 2 l/min/m²
    • PAH requiring parenteral therapy with epoprostenol/treprostinil
    • Primary obstructive airway physiology (pre-bronchodilator FEV1/FVC < 0.7 at Visit 1).
    • In the opinion of the Investigator, other clinically significant pulmonary abnormalities.
  • Major extrapulmonary physiological restriction (e.g. chest wall abnormality, large pleural effusion)

  • Cardiovascular diseases, any of the following:

    • Severe hypertension, uncontrolled under treatment (≥160/100 mmHg), within 6 month of Visit 1
    • Myocardial infarction within 6 months of Visit 1
    • Unstable cardiac angina within 6 months of Visit 1

  • Bleeding risk, any of the following:

    • Known genetic predisposition to bleeding.

    • Patients who require

      • Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin)
      • High dose antiplatelet therapy. [Note: Prophylactic low dose heparin or heparin flush as needed for maintenance of an indwelling intravenous device (e.g. enoxaparin 4000 I.U. s.c. per day), as well as prophylactic use of antiplatelet therapy (e.g. acetyl salicylic acid up to 325 mg/day, or clopidogrel at 75 mg/day, or equivalent doses of other antiplatelet therapy) are not prohibited].
    • History of haemorrhagic central nervous system (CNS) event within 12 months of Visit 1.

    • Any of the following within 3 months of Visit 1:

      • Haemoptysis or haematuria
      • Active gastro-intestinal (GI) bleeding or GI - ulcers
      • Major injury or surgery (Investigators judgment).
    • Coagulation parameters: International normalized ratio (INR) >2, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) by >1.5 x ULN at Visit 1.
  • History of thrombotic event (including stroke and transient ischemic attack) within 12 months of Visit 1.
  • Known hypersensitivity to the trial medication or its components (i.e. soya lecithin)
  • Patients with peanut allergy.
  • Other disease that may interfere with testing procedures or in the judgment of the Investigator may interfere with trial participation or may put the patient at risk when participating in this trial.
  • Life expectancy for disease other than ILD < 2.5 years (Investigator assessment).
  • Planned major surgical procedures.
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
  • Women of childbearing potential* not willing or 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 and 3 months after nintedanib administration. A list of contraception methods meeting these criteria is provided in the patient information.
  • In the opinion of the Investigator, active alcohol or drug abuse.
  • Patients not able to understand or follow trial procedures including completion of self-administered questionnaires without help. *A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
PLACEBO_COMPARATOR: Placebo
Drug: Placebo
EXPERIMENTAL: Nintedanib
Drug: Nintedanib
Other Names:
  • OVEF

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Annual Rate of Decline in Forced Vital Capacity - Overall Population
Time Frame: Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Overall population consists of all randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only or HRCT fibrotic pattern= Other fibrotic patterns. Annual rate of decline in Forced Vital Capacity in milliliter (mL) per year in the overall population is based on a random coefficient regression with fixed effects for treatment, HRCT fibrotic pattern, and baseline FVC [mL], and including treatment-by-time and baseline-by-time interactions. Within-participant errors are modelled by an unstructured variance-covariance matrix.
Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Annual Rate of Decline in Forced Vital Capacity - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time Frame: Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Annual rate of decline in Forced Vital Capacity in milliliter (mL) per year in participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only is based on a random coefficient regression with fixed effects for treatment, baseline FVC [mL], and including treatment-by-time and baseline-by-time interactions. Within-participant errors are modelled by an unstructured variance-covariance matrix.
Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Absolute Change From Baseline in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) Total Score at Week 52 - Overall Population
Time Frame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
King's Brief Interstitial Lung Disease questionnaire (K-BILD) consists of 15 items and 3 domains: breathlessness and activities, psychological, and chest symptoms. Possible score ranges from 0-100, score of 100 representing the best health status. If missing items were >50% per domain, the domain score was set to missing. If any of the domain scores were missing, the total score was set to missing. Absolute change from baseline in K-BILD Total score at week 52 in the overall population was based on a Mixed Model Repeated Measures (MMRM), with fixed effects for baseline K-BILD Total score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interactions and random effect for participant. Visit was the repeated measure. Within-participant errors were modelled by unstructured variance-covariance matrix.
Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Absolute Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Total Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time Frame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
King's Brief Interstitial Lung Disease questionnaire (K-BILD) consists of 15 items and 3 domains: breathlessness and activities, psychological, and chest symptoms. Possible score ranges from 0-100, score of 100 representing the best health status. If missing items were >50% per domain, the domain score was set to missing. If any of the domain scores were missing, the total score was set to missing. Absolute change from baseline in K-BILD Total score at week 52 in participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only was based on a Mixed Model Repeated Measures (MMRM), with fixed effects for baseline K-BILD Total score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interactions and random effect for participant. Visit was the repeated measure. Within-participant errors were modelled by unstructured variance-covariance matrix.
Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Overall Population
Time Frame: From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days
Time to first acute ILD exacerbation or death over 52 weeks was defined as time to first acute ILD exacerbation or death due to any cause within the first 52 weeks and was computed as earliest of date of first documented acute ILD exacerbation or death - date of first drug intake + 1. Participants alive who did not experience any ILD exacerbation event or with unknown status within the first 52 weeks were censored.
From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days
Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time Frame: From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days
Time to first acute ILD exacerbation or death over 52 weeks was defined as time to first acute ILD exacerbation or death due to any cause within the first 52 weeks and was computed as earliest of date of first documented acute ILD exacerbation or death - date of first drug intake + 1. Participants alive who did not experience any ILD exacerbation event or with unknown status within the first 52 weeks were censored.
From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days
Time to Death Over 52 Weeks - Overall Population
Time Frame: From first drug intake until date of death or last contact date, up to 372 days
Time to death over 52 weeks defined as the time from date of first drug intake until date of death from any cause for participants with known date of death (from any cause) within the first 52 weeks. Participants with no event (death from any cause) or unknown status within the first 52 weeks were censored.
From first drug intake until date of death or last contact date, up to 372 days
Time to Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time Frame: From first drug intake until date of death or last contact date, up to 372 days
Time to death over 52 weeks defined as the time from date of first drug intake until date of death from any cause for participants with known date of death (from any cause) within the first 52 weeks. Participants with no event (death from any cause) or unknown status within the first 52 weeks were censored.
From first drug intake until date of death or last contact date, up to 372 days
Time to Death Due to Respiratory Cause Over 52 Weeks - Overall Population
Time Frame: From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days
Time to death due to respiratory cause over 52 weeks is defined as the time from date of first drug intake until date of death attributed to respiratory causes (determined by an independent Adjudication Committee) for participants with known date of death (from respiratory causes) within the first 52 weeks. Participants with no event (death from respiratory causes) or unknown status within the first 52 weeks were censored. As less than 4.95% of the total of participants in the analysis population experienced an event, only descriptive statistics were performed, as pre-specified.
From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days
Time to Death Due to Respiratory Cause Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time Frame: From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days
Time to death due to respiratory cause over 52 weeks is defined as the time from date of first drug intake until date of death attributed to respiratory causes (determined by an independent Adjudication Committee) for participants with known date of death (from respiratory causes) within the first 52 weeks. Participants with no event (death from respiratory causes) or unknown status within the first 52 weeks were censored. As less than 4.95% of the total of participants in the analysis population experienced an event, only descriptive statistics were performed, as pre-specified.
From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days
Time to Progression or Death Over 52 Weeks - Overall Population
Time Frame: From first drug intake until date of progression or date of death or last contact date, up to 372 days
Time to progression or death over 52 weeks is defined as the time from date of first drug intake to date of progression, or date of death (from any cause) if a participant died earlier. Participants with no event (progression or death from any cause) or unknown status were censored. Date of progression is defined as the date when ≥ 10% of absolute decline in FVC percent predicted compared to baseline occured for the first time. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent.
From first drug intake until date of progression or date of death or last contact date, up to 372 days
Time to Progression or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time Frame: From first drug intake until date of progression or date of death or last contact date, up to 372 days
Time to progression or death over 52 weeks is defined as the time from date of first drug intake to date of progression, or date of death (from any cause) if a participant died earlier. Participants with no event (progression or death from any cause) or unknown status were censored. Date of progression is defined as the date when ≥ 10% of absolute decline in FVC percent predicted compared to baseline occured for the first time. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent.
From first drug intake until date of progression or date of death or last contact date, up to 372 days
Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Overall Population
Time Frame: Baseline and up to 52 weeks after first drug intake
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 10% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 10% and those participants with missing data (worst case analysis).
Baseline and up to 52 weeks after first drug intake
Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time Frame: Baseline and up to 52 weeks after first drug intake
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 10% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 10% and those participants with missing data (worst case analysis).
Baseline and up to 52 weeks after first drug intake
Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Overall Population
Time Frame: Baseline and up to 52 weeks after first drug intake
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 5% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 5% and those participants with missing data (worst case analysis).
Baseline and up to 52 weeks after first drug intake
Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time Frame: Baseline and up to 52 weeks after first drug intake
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 5% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 5% and those participants with missing data (worst case analysis).
Baseline and up to 52 weeks after first drug intake
Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 - Overall Population
Time Frame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms dyspnea domain score (dyspnea score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in dyspnea score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline dyspnea score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline dyspnea score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Absolute Change From Baseline in L-PF Symptoms Dyspnea Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time Frame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms dyspnea domain score (dyspnea score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in dyspnea score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline dyspnea score, visit, treatment-by-visit interaction, baseline dyspnea score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Absolute Change From Baseline in L-PF Symptoms Cough Domain Score at Week 52 - Overall Population
Time Frame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms cough domain score (cough score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in cough score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline cough score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline cough score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time Frame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms cough domain score (cough score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in cough score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline cough score, visit, treatment-by-visit interaction, baseline cough score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)

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Sponsor

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Boehringer Ingelheim

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General Publications

Helpful Links

Study record dates

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Study Major Dates

Study Start (ACTUAL)

Study Start

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January 17, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 23, 2019

Study Completion (ACTUAL)

Study Completion

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August 12, 2019

Study Registration Dates

First Submitted

First Submitted

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December 19, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

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December 19, 2016

First Posted (ESTIMATE)

First Posted

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December 21, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

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May 5, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

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April 22, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2020

More Information

Terms related to this study

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Other Study ID Numbers

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  • 1199.247
  • 2015-003360-37 (EUDRACT_NUMBER)

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