Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01335464
First received: April 13, 2011
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

Idiopathic Pulmonary Fibrosis (IPF) is a chronic disease of unknown cause that results in scarring of the lung and there is a high unmet medical need for effective treatment to halt lung function decline, delay or avoid exacerbation (flare-ups), and ultimately to reduce the death rate.

In a large Phase 2 trial (1199.30) (NCT00514683), investigating the effects of 52 weeks of treatment with BIBF 1120 in patients with IPF, a positive effect was seen on lung function of patients treated with high dose of BIBF 1120 compared to placebo.

Hence it is the purpose of this trial to investigate and confirm the efficacy and safety of BIBF 1120 at a high dose in treating patients with IPF, compared with placebo. The trial will be conducted as a prospective, randomised design with the aim to collect safety and efficacy data.

Respiratory function is globally accepted for assessment of treatment effects in IPF patients. The chosen endpoint (Forced Vital Capacity (FVC) decline) is easy to obtain and is part of the usual examinations done in IPF patients.


Condition Intervention Phase
Pulmonary Fibrosis
Drug: placebo
Drug: BIBF 1120
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A 52 Weeks, Double Blind, Randomized, Placebo-controlled Trial Evaluating the Effect of Oral BIBF 1120, 150 mg Twice Daily, on Annual Forced Vital Capacity Decline, in Patients With Idiopathic Pulmonary Fibrosis (IPF)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • annual rate of decline in FVC (expressed in mL over 52 weeks). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in Saint-George Respiratory Questionnaire (SGRQ) total score at 52 weeks (expressed in points). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Time to first acute exacerbation (days). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Respiratory mortality (adjudicated; all data collected based on randomized set, including vital status follow-up, censored at 52 weeks). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Overall survival (all data collected based on randomized set, including vital status follow-up, censored at 52 weeks). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • On-treatment survival (on-treatment based on fatal adverse event + 28 days). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Absolute and relative change from baseline of FVC and FVC %pred up to 52 weeks [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • risk ratio of an acute IPF exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • changes from baseline in SGRQ domains : [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Time to death or lung transplant. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Absolute categorical change of FVC% up to 52 weeks: decrease by > 5, increase by > 5, and change within <= 5. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Absolute categorical change of FVC% up to 52 weeks: decrease by >10, increase by > 10, and change within <= 5. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • change from baseline in Shortness Of Breath Questionnaire (SOBQ) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • change from baseline in Cough And Sputum Assessment (CASAQ) score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • change from baseline in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ5D) score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • proportion of Patient's Global Impression of Change (PGIC) responders [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • proportion of SGRQ responders [ Time Frame: 52weeks ] [ Designated as safety issue: No ]
  • change from baseline in SGRQ-I total score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • change from baseline in SPO2 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • change from baaseline in DLCO [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Enrollment: 515
Study Start Date: April 2011
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBF 1120
patient receives capsules containing BIBF 1120 twice a day
Drug: BIBF 1120
BIBF1120 BID (twice daily)
Placebo Comparator: placebo
patient receives capsules identical to those containing active drug
Drug: placebo
placebo matching BIBF1120, BID

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Age >= 40 years;
  2. IPF diagnosed, according to most recent American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), Latin American Thoracic Association (ALAT) IPF guideline for diagnosis and management, within 5 years;
  3. Combination of High Resolution Computerized Tomography (HRCT) pattern, and if available surgical lung biopsy pattern, as assessed by central reviewers, are consistent with diagnosis of IPF
  4. Dlco (corrected for Hb): 30%-79% predicted of normal;
  5. FVC>= 50% predicted of normal

Exclusion criteria:

  1. Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) > 1.5 x Upper Limit of Normal (ULN)
  2. Bilirubin > 1.5 x ULN;
  3. Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC < 0.7);
  4. Patient likely to have lung transplantation during study (being on transplantation list is acceptable for participation);
  5. Myocardial infarction within 6 months;
  6. Unstable angina within 1 month;
  7. Bleeding risk (genetic predisposition; fibrinolysis or full-dose therapeutic anticoagulation or high dose antiplatelet therapy; history of hemorrhagic CNS event within 12 months; haemoptysis or haematuria or active gastro-intestinal bleeding or ulcers or major injury or surgery within 3 months);
  8. Thrombotic risk (inherited predisposition; history of thrombotic event (including stroke and transient ischemic attacks) within 12 months;
  9. International normalised ratio (INR) > 2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by > 50% of institutional ULN);
  10. N-ACetyl Cystein, prednisone > 15mg/day or equivalent received within 2 weeks of visit 1;
  11. Pirfenidone, azathioprine, cyclophosphamide, cyclosporine A received within 8 weeks of visit 1;
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01335464

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Locations
United States, Alabama
1199.32.10007 Boehringer Ingelheim Investigational Site
Birmingham, Alabama, United States
1199.32.10029 Boehringer Ingelheim Investigational Site
Jasper, Alabama, United States
United States, Arizona
1199.32.10013 Boehringer Ingelheim Investigational Site
Phoenix, Arizona, United States
United States, California
1199.32.10005 Boehringer Ingelheim Investigational Site
Los Angeles, California, United States
United States, Connecticut
1199.32.10022 Boehringer Ingelheim Investigational Site
Danbury, Connecticut, United States
United States, Delaware
1199.32.10025 Boehringer Ingelheim Investigational Site
Newark, Delaware, United States
United States, Florida
1199.32.10023 Boehringer Ingelheim Investigational Site
Weston, Florida, United States
United States, Iowa
1199.32.10001 Boehringer Ingelheim Investigational Site
Council Bluffs, Iowa, United States
United States, Kansas
1199.32.10028 Boehringer Ingelheim Investigational Site
Wichita, Kansas, United States
United States, Minnesota
1199.32.10016 Boehringer Ingelheim Investigational Site
Minneapolis, Minnesota, United States
United States, New Jersey
1199.32.10024 Boehringer Ingelheim Investigational Site
New Brunswich, New Jersey, United States
United States, New York
1199.32.10019 Boehringer Ingelheim Investigational Site
New York, New York, United States
United States, Ohio
1199.32.10004 Boehringer Ingelheim Investigational Site
Cincinnati, Ohio, United States
United States, Oregon
1199.32.10020 Boehringer Ingelheim Investigational Site
Portland, Oregon, United States
United States, Pennsylvania
1199.32.10002 Boehringer Ingelheim Investigational Site
Pittsburgh, Pennsylvania, United States
1199.32.10033 Boehringer Ingelheim Investigational Site
Pittsburgh, Pennsylvania, United States
United States, Rhode Island
1199.32.10008 Boehringer Ingelheim Investigational Site
Providence, Rhode Island, United States
United States, Tennessee
1199.32.10015 Boehringer Ingelheim Investigational Site
Nashville, Tennessee, United States
1199.32.10034 Boehringer Ingelheim Investigational Site
Shelbyville, Tennessee, United States
United States, Texas
1199.32.10009 Boehringer Ingelheim Investigational Site
Dallas, Texas, United States
1199.32.10018 Boehringer Ingelheim Investigational Site
McKinney, Texas, United States
United States, Virginia
1199.32.10021 Boehringer Ingelheim Investigational Site
Falls Church, Virginia, United States
1199.32.10003 Boehringer Ingelheim Investigational Site
Lynchburg, Virginia, United States
United States, Washington
1199.32.10038 Boehringer Ingelheim Investigational Site
Tacoma, Washington, United States
Australia, New South Wales
1199.32.61001 Boehringer Ingelheim Investigational Site
Camperdown, New South Wales, Australia
1199.32.61002 Boehringer Ingelheim Investigational Site
Concord, New South Wales, Australia
Australia, South Australia
1199.32.61003 Boehringer Ingelheim Investigational Site
Daw Park, South Australia, Australia
Australia, Victoria
1199.32.61005 Boehringer Ingelheim Investigational Site
Frankston, Victoria, Australia
1199.32.61004 Boehringer Ingelheim Investigational Site
Prahran, Victoria, Australia
Belgium
1199.32.32004 Boehringer Ingelheim Investigational Site
Bruxelles, Belgium
1199.32.32005 Boehringer Ingelheim Investigational Site
Jette, Belgium
1199.32.32001 Boehringer Ingelheim Investigational Site
Leuven, Belgium
1199.32.32002 Boehringer Ingelheim Investigational Site
Yvoir, Belgium
China
1199.32.86001 Boehringer Ingelheim Investigational Site
Beijing, China
1199.32.86002 Boehringer Ingelheim Investigational Site
Beijing, China
1199.32.86005 Boehringer Ingelheim Investigational Site
Changsha, China
1199.32.86004 Boehringer Ingelheim Investigational Site
Chengdu, China
1199.32.86003 Boehringer Ingelheim Investigational Site
Nanchang, China
1199.32.86006 Boehringer Ingelheim Investigational Site
Xi'An, China
Czech Republic
1199.32.42003 Boehringer Ingelheim Investigational Site
Prague 4, Czech Republic
1199.32.42002 Boehringer Ingelheim Investigational Site
Prague 8, Czech Republic
1199.32.42001 Boehringer Ingelheim Investigational Site
Usti nad Labem, Czech Republic
France
1199.32.33002 Boehringer Ingelheim Investigational Site
Bobigny, France
1199.32.33003 Boehringer Ingelheim Investigational Site
Nice Cedex 1, France
1199.32.33006 Boehringer Ingelheim Investigational Site
Paris Cedex 15, France
1199.32.33001 Boehringer Ingelheim Investigational Site
Paris Cedex 18, France
1199.32.33005 Boehringer Ingelheim Investigational Site
Paris cedex 20, France
1199.32.33007 Boehringer Ingelheim Investigational Site
Reims cedex, France
1199.32.33004 Boehringer Ingelheim Investigational Site
Rennes Cedex 9, France
Germany
1199.32.49008 Boehringer Ingelheim Investigational Site
Bamberg, Germany
1199.32.49005 Boehringer Ingelheim Investigational Site
Donaustauf, Germany
1199.32.49001 Boehringer Ingelheim Investigational Site
Essen, Germany
1199.32.49002 Boehringer Ingelheim Investigational Site
Freiburg/Breisgau, Germany
1199.32.49006 Boehringer Ingelheim Investigational Site
Gießen, Germany
1199.32.49003 Boehringer Ingelheim Investigational Site
Großhansdorf, Germany
1199.32.49007 Boehringer Ingelheim Investigational Site
Heidelberg, Germany
1199.32.49004 Boehringer Ingelheim Investigational Site
Mainz, Germany
India
1199.32.91003 Boehringer Ingelheim Investigational Site
Ahmedabad, India
1199.32.91002 Boehringer Ingelheim Investigational Site
Coimbatore, India
1199.32.91006 Boehringer Ingelheim Investigational Site
Jaipur, India
1199.32.91005 Boehringer Ingelheim Investigational Site
Kolkatta, India
1199.32.91001 Boehringer Ingelheim Investigational Site
Mumbai, India
Ireland
1199.32.35301 Boehringer Ingelheim Investigational Site
Dublin, Ireland
Israel
1199.32.97004 Boehringer Ingelheim Investigational Site
Haifa, Israel
1199.32.97001 Boehringer Ingelheim Investigational Site
Petah Tiqwa, Israel
1199.32.97002 Boehringer Ingelheim Investigational Site
Rehovot, Israel
Italy
1199.32.39012 Boehringer Ingelheim Investigational Site
Catania, Italy
1199.32.39004 Boehringer Ingelheim Investigational Site
Chieti Scalo, Italy
1199.32.39008 Boehringer Ingelheim Investigational Site
Forli', Italy
1199.32.39005 Boehringer Ingelheim Investigational Site
Milano, Italy
1199.32.39001 Boehringer Ingelheim Investigational Site
Modena, Italy
1199.32.39007 Boehringer Ingelheim Investigational Site
Monza, Italy
1199.32.39011 Boehringer Ingelheim Investigational Site
Napoli, Italy
1199.32.39002 Boehringer Ingelheim Investigational Site
Padova, Italy
1199.32.39006A Boehringer Ingelheim Investigational Site
Pisa, Italy
1199.32.39006B Boehringer Ingelheim Investigational Site
Pisa, Italy
1199.32.39010 Boehringer Ingelheim Investigational Site
Roma, Italy
1199.32.39009 Boehringer Ingelheim Investigational Site
Siena, Italy
Japan
1199.32.81006 Boehringer Ingelheim Investigational Site
Bunkyo-ku,Tokyo, Japan
1199.32.81005 Boehringer Ingelheim Investigational Site
Bunkyo-ku,Tokyo, Japan
1199.32.81007 Boehringer Ingelheim Investigational Site
Kiyose, Tokyo, Japan
1199.32.81004 Boehringer Ingelheim Investigational Site
Kumagaya, Saitama, Japan
1199.32.81009 Boehringer Ingelheim Investigational Site
Minato-ku, Tokyo, Japan
1199.32.81003 Boehringer Ingelheim Investigational Site
Naka-gun, Ibaraki, Japan
1199.32.81011 Boehringer Ingelheim Investigational Site
Ota-ku, Tokyo, Japan
1199.32.81001 Boehringer Ingelheim Investigational Site
Sendai, Miyagi, Japan
1199.32.81010 Boehringer Ingelheim Investigational Site
Shibuya-ku, Tokyo, Japan
1199.32.81002 Boehringer Ingelheim Investigational Site
Shimotsuke,Tochigi, Japan
1199.32.81008 Boehringer Ingelheim Investigational Site
Shinjuku-ku, Tokyo, Japan
1199.32.81012 Boehringer Ingelheim Investigational Site
Yokohama, Kanagawa, Japan
United Kingdom
1199.32.44006 Boehringer Ingelheim Investigational Site
Aberdeen, United Kingdom
1199.32.44003 Boehringer Ingelheim Investigational Site
Birmingham, United Kingdom
1199.32.44005 Boehringer Ingelheim Investigational Site
Birmingham, United Kingdom
1199.32.44009 Boehringer Ingelheim Investigational Site
Leeds, United Kingdom
1199.32.44004 Boehringer Ingelheim Investigational Site
Liverpool, United Kingdom
1199.32.44002 Boehringer Ingelheim Investigational Site
London, United Kingdom
1199.32.44008 Boehringer Ingelheim Investigational Site
Oxford, United Kingdom
1199.32.44001 Boehringer Ingelheim Investigational Site
Westbury on Trym, United Kingdom
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01335464     History of Changes
Other Study ID Numbers: 1199.32, 2010-024251-87
Study First Received: April 13, 2011
Last Updated: March 28, 2014
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Admin
Belgium: Federal Agency for Medicinal and Health Products
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
India: Drugs Controller General of India
Ireland: Medical Ethics Research Committee
Israel: Ministry of Health
Italy: Ethics Committee
Japan: Ministry of Health, Labor and Welfare
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial

ClinicalTrials.gov processed this record on July 24, 2014