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

NCT01335464 | Completed Phase 3 Results

• 2 other identifiers: 1199.322010-024251-87
• Study Type: interventional
• Target: 515
• Locations: 13 countries
• Sites: 98

Brief Summary

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.

Conditions

Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (1)

• Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks

  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

  52 weeks

Secondary Outcomes (28)

• Change From Baseline in Saint-George's Respiratory Questionnaire (SGRQ) Total Score at 52 Weeks

  baseline and 52 weeks

• Time to First Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation

  52 weeks

• Absolute Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks

  Baseline and 52 weeks

• Relative Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks

  Baseline and 52 weeks

• Absolute Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks

  Baseline and 52 weeks

Study Arms (2)

BIBF 1120

EXPERIMENTAL

patient receives capsules containing BIBF 1120 twice a day

Drug: BIBF 1120

placebo

PLACEBO COMPARATOR

patient receives capsules identical to those containing active drug

Drug: placebo

Interventions

placebo DRUG

placebo matching BIBF1120, BID

placebo

BIBF 1120 DRUG

BIBF1120 BID (twice daily)

BIBF 1120

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 40 years;
• 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;
• 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
• Dlco (corrected for Hb): 30%-79% predicted of normal;
• FVC\>= 50% predicted of normal

You may not qualify if:

• Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) \> 1.5 x Upper Limit of Normal (ULN)
• Bilirubin \> 1.5 x ULN;
• Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC \< 0.7);
• Patient likely to have lung transplantation during study (being on transplantation list is acceptable for participation);
• Myocardial infarction within 6 months;
• Unstable angina within 1 month;
• 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);
• Thrombotic risk (inherited predisposition; history of thrombotic event (including stroke and transient ischemic attacks) within 12 months;
• International normalised ratio (INR) \> 2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by \> 50% of institutional ULN);
• N-ACetyl Cystein, prednisone \> 15mg/day or equivalent received within 2 weeks of visit 1;
• Pirfenidone, azathioprine, cyclophosphamide, cyclosporine A received within 8 weeks of visit 1;

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (98)

1199.32.10007 Boehringer Ingelheim Investigational Site

Birmingham, Alabama, United States

Location

1199.32.10029 Boehringer Ingelheim Investigational Site

Jasper, Alabama, United States

Location

1199.32.10013 Boehringer Ingelheim Investigational Site

Phoenix, Arizona, United States

Location

1199.32.10005 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

Location

1199.32.10022 Boehringer Ingelheim Investigational Site

Danbury, Connecticut, United States

Location

1199.32.10025 Boehringer Ingelheim Investigational Site

Newark, Delaware, United States

Location

1199.32.10023 Boehringer Ingelheim Investigational Site

Weston, Florida, United States

Location

1199.32.10001 Boehringer Ingelheim Investigational Site

Council Bluffs, Iowa, United States

Location

1199.32.10028 Boehringer Ingelheim Investigational Site

Wichita, Kansas, United States

Location

1199.32.10016 Boehringer Ingelheim Investigational Site

Minneapolis, Minnesota, United States

Location

1199.32.10024 Boehringer Ingelheim Investigational Site

New Brunswich, New Jersey, United States

Location

1199.32.10019 Boehringer Ingelheim Investigational Site

New York, New York, United States

Location

1199.32.10004 Boehringer Ingelheim Investigational Site

Cincinnati, Ohio, United States

Location

1199.32.10020 Boehringer Ingelheim Investigational Site

Portland, Oregon, United States

Location

1199.32.10002 Boehringer Ingelheim Investigational Site

Pittsburgh, Pennsylvania, United States

Location

1199.32.10033 Boehringer Ingelheim Investigational Site

Pittsburgh, Pennsylvania, United States

Location

1199.32.10008 Boehringer Ingelheim Investigational Site

Providence, Rhode Island, United States

Location

1199.32.10015 Boehringer Ingelheim Investigational Site

Nashville, Tennessee, United States

Location

1199.32.10034 Boehringer Ingelheim Investigational Site

Shelbyville, Tennessee, United States

Location

1199.32.10009 Boehringer Ingelheim Investigational Site

Dallas, Texas, United States

Location

1199.32.10018 Boehringer Ingelheim Investigational Site

McKinney, Texas, United States

Location

1199.32.10021 Boehringer Ingelheim Investigational Site

Falls Church, Virginia, United States

Location

1199.32.10003 Boehringer Ingelheim Investigational Site

Lynchburg, Virginia, United States

Location

1199.32.10038 Boehringer Ingelheim Investigational Site

Tacoma, Washington, United States

Location

1199.32.61001 Boehringer Ingelheim Investigational Site

Camperdown, New South Wales, Australia

Location

1199.32.61002 Boehringer Ingelheim Investigational Site

Concord, New South Wales, Australia

Location

1199.32.61003 Boehringer Ingelheim Investigational Site

Daw Park, South Australia, Australia

Location

1199.32.61005 Boehringer Ingelheim Investigational Site

Frankston, Victoria, Australia

Location

1199.32.61004 Boehringer Ingelheim Investigational Site

Prahran, Victoria, Australia

Location

1199.32.32004 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1199.32.32005 Boehringer Ingelheim Investigational Site

Jette, Belgium

Location

1199.32.32001 Boehringer Ingelheim Investigational Site

Leuven, Belgium

Location

1199.32.32002 Boehringer Ingelheim Investigational Site

Yvoir, Belgium

Location

1199.32.86001 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1199.32.86002 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1199.32.86005 Boehringer Ingelheim Investigational Site

Changsha, China

Location

1199.32.86004 Boehringer Ingelheim Investigational Site

Chengdu, China

Location

1199.32.86003 Boehringer Ingelheim Investigational Site

Nanchang, China

Location

1199.32.86006 Boehringer Ingelheim Investigational Site

Xi'an, China

Location

1199.32.42002 Boehringer Ingelheim Investigational Site

Prague, Czechia

Location

1199.32.42003 Boehringer Ingelheim Investigational Site

Prague, Czechia

Location

1199.32.42001 Boehringer Ingelheim Investigational Site

Ústí nad Labem, Czechia

Location

1199.32.33002 Boehringer Ingelheim Investigational Site

Bobigny, France

Location

1199.32.33003 Boehringer Ingelheim Investigational Site

Nice, France

Location

1199.32.33001 Boehringer Ingelheim Investigational Site

Paris, France

Location

1199.32.33005 Boehringer Ingelheim Investigational Site

Paris, France

Location

1199.32.33006 Boehringer Ingelheim Investigational Site

Paris, France

Location

1199.32.33007 Boehringer Ingelheim Investigational Site

Reims, France

Location

1199.32.33004 Boehringer Ingelheim Investigational Site

Rennes, France

Location

1199.32.49008 Boehringer Ingelheim Investigational Site

Bamberg, Germany

Location

1199.32.49005 Boehringer Ingelheim Investigational Site

Donaustauf, Germany

Location

1199.32.49001 Boehringer Ingelheim Investigational Site

Essen, Germany

Location

1199.32.49002 Boehringer Ingelheim Investigational Site

Freiburg/Breisgau, Germany

Location

1199.32.49006 Boehringer Ingelheim Investigational Site

Giessen, Germany

Location

1199.32.49003 Boehringer Ingelheim Investigational Site

Großhansdorf, Germany

Location

1199.32.49007 Boehringer Ingelheim Investigational Site

Heidelberg, Germany

Location

1199.32.49004 Boehringer Ingelheim Investigational Site

Mainz, Germany

Location

1199.32.91003 Boehringer Ingelheim Investigational Site

Ahmedabad, India

Location

1199.32.91002 Boehringer Ingelheim Investigational Site

Coimbatore, India

Location

1199.32.91006 Boehringer Ingelheim Investigational Site

Jaipur, India

Location

1199.32.91005 Boehringer Ingelheim Investigational Site

Kolkata, India

Location

1199.32.91001 Boehringer Ingelheim Investigational Site

Mumbai, India

Location

1199.32.35301 Boehringer Ingelheim Investigational Site

Dublin, Ireland

Location

1199.32.97004 Boehringer Ingelheim Investigational Site

Haifa, Israel

Location

1199.32.97001 Boehringer Ingelheim Investigational Site

Petah Tikva, Israel

Location

1199.32.97002 Boehringer Ingelheim Investigational Site

Rehovot, Israel

Location

1199.32.39012 Boehringer Ingelheim Investigational Site

Catania, Italy

Location

1199.32.39004 Boehringer Ingelheim Investigational Site

Chieti Scalo, Italy

Location

1199.32.39008 Boehringer Ingelheim Investigational Site

Forlì, Italy

Location

1199.32.39005 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1199.32.39001 Boehringer Ingelheim Investigational Site

Modena, Italy

Location

1199.32.39007 Boehringer Ingelheim Investigational Site

Monza, Italy

Location

1199.32.39011 Boehringer Ingelheim Investigational Site

Napoli, Italy

Location

1199.32.39002 Boehringer Ingelheim Investigational Site

Padua, Italy

Location

1199.32.39006A Boehringer Ingelheim Investigational Site

Pisa, Italy

Location

1199.32.39006B Boehringer Ingelheim Investigational Site

Pisa, Italy

Location

1199.32.39010 Boehringer Ingelheim Investigational Site

Roma, Italy

Location

1199.32.39009 Boehringer Ingelheim Investigational Site

Siena, Italy

Location

1199.32.81005 Boehringer Ingelheim Investigational Site

Bunkyo-ku,Tokyo, Japan

Location

1199.32.81006 Boehringer Ingelheim Investigational Site

Bunkyo-ku,Tokyo, Japan

Location

1199.32.81007 Boehringer Ingelheim Investigational Site

Kiyose, Tokyo, Japan

Location

1199.32.81004 Boehringer Ingelheim Investigational Site

Kumagaya, Saitama, Japan

Location

1199.32.81009 Boehringer Ingelheim Investigational Site

Minato-ku, Tokyo, Japan

Location

1199.32.81003 Boehringer Ingelheim Investigational Site

Naka-gun, Ibaraki, Japan

Location

1199.32.81011 Boehringer Ingelheim Investigational Site

Ota-ku, Tokyo, Japan

Location

1199.32.81001 Boehringer Ingelheim Investigational Site

Sendai, Miyagi, Japan

Location

1199.32.81010 Boehringer Ingelheim Investigational Site

Shibuya-ku, Tokyo, Japan

Location

1199.32.81002 Boehringer Ingelheim Investigational Site

Shimotsuke,Tochigi, Japan

Location

1199.32.81008 Boehringer Ingelheim Investigational Site

Shinjuku-ku, Tokyo, Japan

Location

1199.32.81012 Boehringer Ingelheim Investigational Site

Yokohama, Kanagawa, Japan

Location

1199.32.44006 Boehringer Ingelheim Investigational Site

Aberdeen, United Kingdom

Location

1199.32.44003 Boehringer Ingelheim Investigational Site

Birmingham, United Kingdom

Location

1199.32.44005 Boehringer Ingelheim Investigational Site

Birmingham, United Kingdom

Location

1199.32.44009 Boehringer Ingelheim Investigational Site

Leeds, United Kingdom

Location

1199.32.44004 Boehringer Ingelheim Investigational Site

Liverpool, United Kingdom

Location

1199.32.44002 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1199.32.44008 Boehringer Ingelheim Investigational Site

Oxford, United Kingdom

Location

1199.32.44001 Boehringer Ingelheim Investigational Site

Westbury on Trym, United Kingdom

Location

Related Publications (14)

• Glaspole I, Bonella F, Bargagli E, Glassberg MK, Caro F, Stansen W, Quaresma M, Orsatti L, Bendstrup E. Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities. Respir Res. 2021 Apr 26;22(1):125. doi: 10.1186/s12931-021-01695-y.

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• Jouneau S, Crestani B, Thibault R, Lederlin M, Vernhet L, Valenzuela C, Wijsenbeek M, Kreuter M, Stansen W, Quaresma M, Cottin V. Analysis of body mass index, weight loss and progression of idiopathic pulmonary fibrosis. Respir Res. 2020 Nov 25;21(1):312. doi: 10.1186/s12931-020-01528-4.

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• Brown KK, Martinez FJ, Walsh SLF, Thannickal VJ, Prasse A, Schlenker-Herceg R, Goeldner RG, Clerisme-Beaty E, Tetzlaff K, Cottin V, Wells AU. The natural history of progressive fibrosing interstitial lung diseases. Eur Respir J. 2020 Jun 25;55(6):2000085. doi: 10.1183/13993003.00085-2020. Print 2020 Jun.

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• Richeldi L, Kolb M, Jouneau S, Wuyts WA, Schinzel B, Stowasser S, Quaresma M, Raghu G. Efficacy and safety of nintedanib in patients with advanced idiopathic pulmonary fibrosis. BMC Pulm Med. 2020 Jan 8;20(1):3. doi: 10.1186/s12890-019-1030-4.

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• Kreuter M, Koegler H, Trampisch M, Geier S, Richeldi L. Differing severities of acute exacerbations of idiopathic pulmonary fibrosis (IPF): insights from the INPULSIS(R) trials. Respir Res. 2019 Apr 11;20(1):71. doi: 10.1186/s12931-019-1037-7.

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• Xu Z, Li H, Wen F, Bai C, Chen P, Fan F, Hu N, Stowasser S, Kang J. Subgroup Analysis for Chinese Patients Included in the INPULSIS(R) Trials on Nintedanib in Idiopathic Pulmonary Fibrosis. Adv Ther. 2019 Mar;36(3):621-631. doi: 10.1007/s12325-019-0887-1. Epub 2019 Feb 7.

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• Costabel U, Behr J, Crestani B, Stansen W, Schlenker-Herceg R, Stowasser S, Raghu G. Anti-acid therapy in idiopathic pulmonary fibrosis: insights from the INPULSIS(R) trials. Respir Res. 2018 Sep 3;19(1):167. doi: 10.1186/s12931-018-0866-0.

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• Collard HR, Richeldi L, Kim DS, Taniguchi H, Tschoepe I, Luisetti M, Roman J, Tino G, Schlenker-Herceg R, Hallmann C, du Bois RM. Acute exacerbations in the INPULSIS trials of nintedanib in idiopathic pulmonary fibrosis. Eur Respir J. 2017 May 19;49(5):1601339. doi: 10.1183/13993003.01339-2016. Print 2017 May.

  PMID: 28526798 DERIVED

• Paterniti MO, Bi Y, Rekic D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2017 Sep;14(9):1395-1402. doi: 10.1513/AnnalsATS.201606-458OC.

  PMID: 28388260 DERIVED

• Rinciog C, Watkins M, Chang S, Maher TM, LeReun C, Esser D, Diamantopoulos A. A Cost-Effectiveness Analysis of Nintedanib in Idiopathic Pulmonary Fibrosis in the UK. Pharmacoeconomics. 2017 Apr;35(4):479-491. doi: 10.1007/s40273-016-0480-2.

  PMID: 28039616 DERIVED

• Kolb M, Richeldi L, Behr J, Maher TM, Tang W, Stowasser S, Hallmann C, du Bois RM. Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung volume. Thorax. 2017 Apr;72(4):340-346. doi: 10.1136/thoraxjnl-2016-208710. Epub 2016 Sep 26.

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• Corte T, Bonella F, Crestani B, Demedts MG, Richeldi L, Coeck C, Pelling K, Quaresma M, Lasky JA. Safety, tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis. Respir Res. 2015 Sep 24;16:116. doi: 10.1186/s12931-015-0276-5.

  PMID: 26400368 DERIVED

• Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y, Kim DS, Kolb M, Nicholson AG, Noble PW, Selman M, Taniguchi H, Brun M, Le Maulf F, Girard M, Stowasser S, Schlenker-Herceg R, Disse B, Collard HR; INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2071-82. doi: 10.1056/NEJMoa1402584. Epub 2014 May 18.

  PMID: 24836310 DERIVED

• Richeldi L, Cottin V, Flaherty KR, Kolb M, Inoue Y, Raghu G, Taniguchi H, Hansell DM, Nicholson AG, Le Maulf F, Stowasser S, Collard HR. Design of the INPULSIS trials: two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis. Respir Med. 2014 Jul;108(7):1023-30. doi: 10.1016/j.rmed.2014.04.011. Epub 2014 Apr 29.

  PMID: 24834811 DERIVED

MeSH Terms

Conditions

Pulmonary Fibrosis

Interventions

nintedanib

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2011
• First Posted: April 14, 2011
• Study Start: April 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: July 25, 2016
• Results First Posted: February 13, 2015

Record last verified: 2016-06

Locations

IE (1); DE (8); FR (7); US (24); AU (5); IN (5); GB (8); JP (12); IL (3); BE (4); CN (6); CZ (3); IT (12)