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

Pulmonary Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01170065
• Other study ID #: 1199.35
• Secondary ID: 2009-013788-21
• Status: Completed
• Phase: Phase 2
• Start date: June 25, 2010
• Est. completion date: September 26, 2016

Study information

• Verified date: February 2019
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 198
• Est. completion date: September 26, 2016
• Est. primary completion date: September 26, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• BIBF 1120
Intermediate dose BIBF 1120 twice daily
• BIBF 1120
High dose BIBF 1120 twice daily
• BIBF 1120
Low dose BIBF 1120 twice daily
• BIBF 1120
Low dose BIBF 1120 once daily

Locations

Country	Name	City	State
Argentina	INSARES	Mendoza
Australia	Respiratory Clinical Trial Pty Ltd.	Glen Osmond	South Australia
Australia	Royal Perth Hospital-Lung Transplant Unit	Perth	Western Australia
Australia	The Queen Elizabeth Hospital	Woodville	South Australia
Belgium	ULB Hopital Erasme	Bruxelles
Belgium	UZ Leuven	Leuven
Belgium	Yvoir - UNIV UCL de Mont-Godinne	Yvoir
Brazil	Irmandade Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Bulgaria	Special. Hospital for Active Treatment, Sv. Sofia 2nd Clinic	Sofia
Canada	QEII Health Sciences Centre (Dalhousie University)	Halifax	Nova Scotia
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Chile	Instituto Nacional del Tórax	Santiago
China	Beijing Chao-Yang Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Nanjing Drum Tower Hospital	Nanjing
China	Shanghai Pulmonary Hospital	Shanghai
Czechia	University Hospital Na Bulovce, Prague	Prague 8
Czechia	Masaryk Hospital, Usti nad Labem	Usti nad Labem
France	HOP Avicenne	Bobigny
France	HOP Dijon, Pneumo, Dijon	DIJON Cedex
France	HOP Calmette	Lille
France	HOP Calmette	Lille Cedex
France	HOP Arnaud de Villeneuve	Montpellier
France	HOP Pasteur	Nice Cedex 1
France	HOP Bichat	Paris Cedex 18
Germany	Klinik Donaustauf	Donaustauf
Germany	Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH	Essen
Germany	Universitätsklinikum Freiburg	Freiburg/Breisgau
Germany	Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH	Großhansdorf
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Klinikum der Universität München - Campus Großhadern	München
Greece	University General Hospital of Evros	Alexandroupolis
Greece	University Hospital of Heraklion, University Pulmonology Cl	Heraklion
Hungary	Csongrad County's Hosp.	Deszk
Hungary	University of Pecs, 1st internal Med. Dept., Pulmonology	Pecs
Ireland	Mater Misericordiae University Hospital	Dublin
Italy	Ospedale C. G. Mazzoni	Ascoli Piceno
Italy	Osp. S. Giuseppe Fatebenefratelli	Milano
Italy	Università di Modena e Reggio Emilia	Modena
Italy	Università Federico II	Napoli
Italy	Pol. Universitario Tor Vergata	Roma
Italy	A.O.U. Senese Policlinico Santa Maria alle Scotte	Siena
Italy	Università di Perugia	Terni
Italy	Ospedale di Cattinara	Trieste
Mexico	Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas	Distrito Federal
Netherlands	St. Antonius ziekenhuis, locatie Nieuwegein	Nieuwegein
Portugal	CHUC - Centro Hospitalar e Universitário de Coimbra, EPE	Coimbra
Portugal	Centro Hospitalar Lisboa Norte Hospital Pulido Valente	Lisboa
Portugal	CHLN, EPE - Hospital de Santa Maria	Lisboa
Portugal	Centro Hospitalar São João,EPE	Porto
Russian Federation	Central Scientific Research Insitute of Tuberculosis	Moscow
Russian Federation	Scientific Research Institute of Pulmonology	St. Petersburg
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Dr. Peset	Valencia
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	The Medicines Evaluation Unit	Manchester
United Kingdom	Southmead Hospital	Westbury On Trym

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Czechia,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Mexico,  Netherlands,  Portugal,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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