Roll Over Study From 1199.30 BIBF 1120 in Idiopathic Pulmonary Fibrosis (IPF)

A Phase II Open Label, Roll Over Study of the Long Term Tolerability, Safety and Efficacy of Oral BIBF 1120 in Patients With Idiopathic Pulmonary Fibrosis

The aim of this trial is to offer continuation of BIBF 1120 treatment for patients with Idiopathic Pulmonary Fibrosis (IPF) who have completed a prior clinical trial with that drug.

The primary objective will be to establish the long term tolerability and safety profile of BIBF 1120 in Idiopathic Pulmonary Fibrosis (IPF).

As a secondary objective the effects of long term treatment with BIBF 1120 on survival as well as safety and efficacy parameters will be investigated in an open-label, not randomized, un-controlled design.

Study Overview

• Status: Completed
• Conditions: Pulmonary Fibrosis
• Intervention / Treatment: Drug: BIBF 1120; Drug: BIBF 1120; Drug: BIBF 1120; Drug: BIBF 1120

• Study Type: Interventional
• Enrollment (Actual): 198
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Mendoza, Argentina, M5500CCG
    • INSARES
• Australia
  • South Australia
    • Glen Osmond, South Australia, Australia, 5064
      • Respiratory Clinical Trial Pty Ltd.
    • Woodville, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital-Lung Transplant Unit
• Belgium
  • Bruxelles, Belgium, 1070
    • ULB Hôpital Erasme
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Yvoir, Belgium, 5530
    • Yvoir - UNIV UCL de Mont-Godinne
• Brazil
  • Porto Alegre, Brazil, CEP90035-0
    • Irmandade Santa Casa de Misericordia de Porto Alegre
• Bulgaria
  • Sofia, Bulgaria, 1431
    • Special. Hospital for Active Treatment, Sv. Sofia 2nd Clinic
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • QEII Health Sciences Centre (Dalhousie University)
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
• Chile
  • Santiago, Chile, 7500000
    • Instituto Nacional del tórax
• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
  • Beijing, China, 100020
    • Beijing Chao-Yang Hospital
  • Nanjing, China, 210008
    • Nanjing Drum Tower hospital
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital
• Czechia
  • Prague 8, Czechia, 180 81
    • University Hospital Na Bulovce, Prague
  • Usti nad Labem, Czechia, 401 13
    • Masaryk Hospital, Usti nad Labem
• France
  • Bobigny, France, 93009
    • HOP Avicenne
  • DIJON Cedex, France, 21079
    • HOP Dijon, Pneumo, Dijon
  • Lille, France, 59037
    • HOP Calmette
  • Lille Cedex, France, 59037
    • HOP Calmette
  • Montpellier, France, 34295
    • HOP Arnaud de Villeneuve
  • Nice Cedex 1, France, 06002
    • HOP Pasteur
  • Paris Cedex 18, France, 75877
    • HOP Bichat
• Germany
  • Donaustauf, Germany, 93093
    • Klinik Donaustauf
  • Essen, Germany, 45239
    • Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
  • Freiburg/Breisgau, Germany, 79106
    • Universitatsklinikum Freiburg
  • Großhansdorf, Germany, 22927
    • Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • München, Germany, 81377
    • Klinikum der Universität München - Campus Großhadern
• Greece
  • Alexandroupolis, Greece, 68100
    • University General Hospital of Evros
  • Heraklion, Greece, 71100
    • University Hospital of Heraklion, University Pulmonology Cl
• Hungary
  • Deszk, Hungary, 6772
    • Csongrad County's Hosp.
  • Pecs, Hungary, 7623
    • University of Pecs, 1st internal Med. Dept., Pulmonology
• Ireland
  • Dublin, Ireland, 7
    • Mater Misericordiae University Hospital
• Italy
  • Ascoli Piceno, Italy, 63100
    • Ospedale C. G. Mazzoni
  • Milano, Italy, 20123
    • Osp. S. Giuseppe Fatebenefratelli
  • Modena, Italy, 41100
    • Università di Modena e Reggio Emilia
  • Napoli, Italy, 80131
    • Università Federico II
  • Roma, Italy, 00133
    • Pol. Universitario Tor Vergata
  • Siena, Italy, 53100
    • A.O.U. Senese Policlinico Santa Maria alle Scotte
  • Terni, Italy, 05100
    • Universita di Perugia
  • Trieste, Italy, 34100
    • Ospedale di Cattinara
• Mexico
  • Distrito Federal, Mexico, 14080
    • Instituto Nacional De Enfermedades Respiratorias Ismael Cosio Villegas
• Netherlands
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius ziekenhuis, locatie Nieuwegein
• Portugal
  • Coimbra, Portugal, 3041-801
    • CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
  • Lisboa, Portugal, 1064-035
    • CHLN, EPE - Hospital de Santa Maria
  • Lisboa, Portugal, 1750-001 L
    • Centro Hospitalar Lisboa Norte Hospital Pulido Valente
  • Porto, Portugal, 4202-451
    • Centro Hospitalar São João,EPE
• Russian Federation
  • Moscow, Russian Federation, 107564
    • Central Scientific Research Insitute of Tuberculosis
  • St. Petersburg, Russian Federation, 197089
    • Scientific Research Institute of Pulmonology
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Valencia, Spain, 46017
    • Hospital Dr. Peset
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Birmingham, United Kingdom, B15 2GW
    • Queen Elizabeth Hospital
  • Manchester, United Kingdom, M23 9QZ
    • The Medicines Evaluation Unit
  • Westbury On Trym, United Kingdom, BS10 5NB
    • Southmead Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Patient with a primary diagnosis of IPF (according to the 2000 American Thoracic Society/European Respiratory Society (ATS/ERS) criteria, who are willing to continue trial medication.
2. Written informed consent signed prior to entry into the study, in accordance with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) and local law
3. Completion of 1199.30 study and still under treatment (i.e. not discontinued in parent trial)

Exclusion criteria:

1. Any disease that may put the patient at risk when participating in this trial. Reconsider carefully all exclusion criteria of trial 1199.30. However, patients may qualify for participation even though exclusion criteria may have been met during the course of participation in 1199.30, if the investigator's benefit-risk assessment remains favourable.
2. Participation in another experimental clinical trial (except 1199.30) in the last 8 weeks.

3. Women who are breast feeding or of child bearing potential not using a highly effective method of birth control for at least one month prior to inclusion and at least 10 weeks after end of active therapy.

   Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1 % per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some Intra Uterine Devices (IUDs), sexual abstinence or vasectomized partner. Female patients will be considered of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.

4. Sexually active males not committing to using condoms during the course of the study and at least 10 weeks after the end of active therapy (except if their partner is not of childbearing potential).
5. Patients who require full-dose anticoagulation (e.g. vitamin K antagonists, heparin, hirudin etc).
6. Patients who require full-dose antiplatelet (e.g. acetyl salicylic acid, clopidogrel etc) therapy.
7. Known or suspected active alcohol or drug abuse.
8. Patient not compliant in previous trial, with trial medication or trial visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BIBF 1120 low qd; Low dose BIBF 1120 once daily	Drug: BIBF 1120; Intermediate dose BIBF 1120 twice daily; Drug: BIBF 1120; High dose BIBF 1120 twice daily; Drug: BIBF 1120; Low dose BIBF 1120 twice daily; Drug: BIBF 1120; Low dose BIBF 1120 once daily
EXPERIMENTAL: BIBF 1120 low bid; Low dose BIBF 1120 twice daily	Drug: BIBF 1120; Intermediate dose BIBF 1120 twice daily; Drug: BIBF 1120; High dose BIBF 1120 twice daily; Drug: BIBF 1120; Low dose BIBF 1120 twice daily; Drug: BIBF 1120; Low dose BIBF 1120 once daily
EXPERIMENTAL: BIBF 1120 medium bid; Intermediate dose BIBF 1120 twice daily	Drug: BIBF 1120; Intermediate dose BIBF 1120 twice daily; Drug: BIBF 1120; High dose BIBF 1120 twice daily; Drug: BIBF 1120; Low dose BIBF 1120 twice daily; Drug: BIBF 1120; Low dose BIBF 1120 once daily
EXPERIMENTAL: BIBF 1120 high bid; High dose BIBF 1120 twice daily	Drug: BIBF 1120; Intermediate dose BIBF 1120 twice daily; Drug: BIBF 1120; High dose BIBF 1120 twice daily; Drug: BIBF 1120; Low dose BIBF 1120 twice daily; Drug: BIBF 1120; Low dose BIBF 1120 once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual Rate of Decline in Forced Vital Capacity (FVC)	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.	From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival is defined as the time from the first intake of nintedanib in trial 1199.35 to death. For presentation of overall survival results, Kaplan-Meier estimates and confidence intervals (using Greenwood variance formula) for the overall on-treatment survival is calculated within each treatment arm.	From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months
Progression-Free Survival	Progression-free survival was defined as the time from the first nintedanib intake in trial 1199.35 to disease progression. For presentation of progression-free survival results, Kaplan-Meier estimates and confidence intervals (using Greenwood variance formula) for the overall on-treatment progression-free survival is calculated within each treatment arm.	From first trial drug intake in 1199.35 to disease progression; up to 61.8 months
Annual Rate of Decline in Haemoglobin Corrected Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Decrease	Haemoglobin corrected DLCO decrease was a secondary endpoint for the trial. It was considered important that all investigators used the same method of testing and recording data at each visit for each patient. Haemoglobin corrected DLCO was calculated for each patient using the following formulae: Males: Hb corrected DLCO = measured DLCO x (10.22 + Hb concentration) / (1.7 x Hb concentration) Females: Hb corrected DLCO = measured DLCO x (9.38 + Hb concentration) / (1.7 x Hb concentration). Annual rate of decline in haemoglobin corrected diffusing capacity of the lung for carbon monoxide (DLCO) decrease is presented.	From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months
Percentage of Patients With at Least One Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation	Percentage of patients with at least one acute idiopathic pulmonary fibrosis (IPF) exacerbation are presented. An exacerbation was defined as otherwise unexplained clinical features occurring within 1 month including all of the following: Progression of dyspnoea over several days to 4 weeks; New diffuse pulmonary infiltrates on chest X-ray and/or high-resolution computerised tomography (HRCT) Parenchymal abnormalities with no pneumothorax or pleural effusion (new ground-glass opacities) since the last visit; A decrease in arterial oxygen partial pressure (PaO2) of ≥10 mmHg or PaO2/fraction of inspired oxygen (FiO2) of <225 mmHg since the last visit; Exclusion of infection based on routine clinical practice and microbiological studies; Absence of other contributory causes such as congestive heart failure, pulmonary embolism, etc.	From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months
Incidence of Patients With at Least One Acute IPF Exacerbation Over Time	Incidence rate = (Patients with at least one acute IPF exacerbation / Total number of years at risk) x 100	From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months
Time to First Acute IPF Exacerbation	Due to rare events, the median of time to event is not calculable, thus Kaplan-Meier estimates (providing the percentage of patients without acute IPF exacerbation for a certain amount of time after treatment) and confidence intervals (using Greenwood variance formula) are reported and presented within each treatment arm as secondary endpoint.	From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months
Percentage of Patients With at Least One Adverse Events (AEs), With Investigator Defined Drug-Related AEs, AEs Leading to Discontinuation of Trial Drug, Serious AEs	Percentage of patients with at least one Adverse events (AEs), with investigator defined drug-related AEs, AEs leading to discontinuation of trial drug, serious AEs are presented	From the first nintedanib intake in trial 1199.35 to the last nintedanib intake + 28 days; up to 61.8 months + 28 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Richeldi L, Kreuter M, Selman M, Crestani B, Kirsten AM, Wuyts WA, Xu Z, Bernois K, Stowasser S, Quaresma M, Costabel U. Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension. Thorax. 2018 Jun;73(6):581-583. doi: 10.1136/thoraxjnl-2016-209701. Epub 2017 Oct 9.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 25, 2010
• Primary Completion (ACTUAL): September 26, 2016
• Study Completion (ACTUAL): September 26, 2016

Study Registration Dates

• First Submitted: July 6, 2010
• First Submitted That Met QC Criteria: July 26, 2010
• First Posted (ESTIMATE): July 27, 2010

Study Record Updates

• Last Update Posted (ACTUAL): June 6, 2019
• Last Update Submitted That Met QC Criteria: March 1, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Nintedanib
• Other Study ID Numbers: 1199.35; 2009-013788-21 (EUDRACT_NUMBER)