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

NCT01335477 | Completed Phase 3 Results

• 2 other identifiers: 1199.342010-024252-29
• Study Type: interventional
• Target: 551
• Locations: 17 countries
• Sites: 108

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)

placebo

PLACEBO COMPARATOR

patient receives capsules identical to those containing active drug

Drug: placebo

BIBF 1120

EXPERIMENTAL

patient receives capsules containing BIBF 1120 twice a day

Drug: BIBF 1120

Interventions

placebo DRUG

placebo matching BIBF 1120 BID

placebo

BIBF 1120 DRUG

BIBF 1120 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; 5.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 (108)

1199.34.10078 Boehringer Ingelheim Investigational Site

Scottsdale, Arizona, United States

Location

1199.34.10086 Boehringer Ingelheim Investigational Site

San Francisco, California, United States

Location

1199.34.10093 Boehringer Ingelheim Investigational Site

Santa Barbara, California, United States

Location

1199.34.10077 Boehringer Ingelheim Investigational Site

Stanford, California, United States

Location

1199.34.10083 Boehringer Ingelheim Investigational Site

Torrance, California, United States

Location

1199.34.10080 Boehringer Ingelheim Investigational Site

Stamford, Connecticut, United States

Location

1199.34.10087 Boehringer Ingelheim Investigational Site

South Miami, Florida, United States

Location

1199.34.10100 Boehringer Ingelheim Investigational Site

Austell, Georgia, United States

Location

1199.34.10075 Boehringer Ingelheim Investigational Site

Chicago, Illinois, United States

Location

1199.34.10069 Boehringer Ingelheim Investigational Site

Olathe, Kansas, United States

Location

1199.34.10090 Boehringer Ingelheim Investigational Site

Lexington, Kentucky, United States

Location

1199.34.10079 Boehringer Ingelheim Investigational Site

Rochester, Minnesota, United States

Location

1199.34.10067 Boehringer Ingelheim Investigational Site

Chesterfield, Missouri, United States

Location

1199.34.10066 Boehringer Ingelheim Investigational Site

Lebanon, New Hampshire, United States

Location

1199.34.10085 Boehringer Ingelheim Investigational Site

Albany, New York, United States

Location

1199.34.10092 Boehringer Ingelheim Investigational Site

Jamaica, New York, United States

Location

1199.34.10074 Boehringer Ingelheim Investigational Site

Durham, North Carolina, United States

Location

1199.34.10088 Boehringer Ingelheim Investigational Site

Toledo, Ohio, United States

Location

1199.34.10070 Boehringer Ingelheim Investigational Site

Portland, Oregon, United States

Location

1199.34.10064 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

Location

1199.34.10089 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

Location

1199.34.10082 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

Location

1199.34.10095 Boehringer Ingelheim Investigational Site

Longview, Texas, United States

Location

1199.34.10060 Boehringer Ingelheim Investigational Site

San Antonio, Texas, United States

Location

1199.34.10084 Boehringer Ingelheim Investigational Site

Salt Lake City, Utah, United States

Location

1199.34.10101 Boehringer Ingelheim Investigational Site

Colchester, Vermont, United States

Location

1199.34.10073 Boehringer Ingelheim Investigational Site

Madison, Wisconsin, United States

Location

1199.34.02001 Boehringer Ingelheim Investigational Site

Calgary, Alberta, Canada

Location

1199.34.02003 Boehringer Ingelheim Investigational Site

Halifax, Nova Scotia, Canada

Location

1199.34.02002 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

Location

1199.34.56001 Boehringer Ingelheim Investigational Site

Santiago, Chile

Location

1199.34.86056 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1199.34.86052 Boehringer Ingelheim Investigational Site

Shanghai, China

Location

1199.34.86054 Boehringer Ingelheim Investigational Site

Shanghai, China

Location

1199.34.86055 Boehringer Ingelheim Investigational Site

Shanghai, China

Location

1199.34.86058 Boehringer Ingelheim Investigational Site

Shanghai, China

Location

1199.34.86051 Boehringer Ingelheim Investigational Site

Shenyang, China

Location

1199.34.86053 Boehringer Ingelheim Investigational Site

Shenyang, China

Location

1199.34.86057 Boehringer Ingelheim Investigational Site

Yinchuan, China

Location

1199.34.35801 Boehringer Ingelheim Investigational Site

Helsinki, Finland

Location

1199.34.33004 Boehringer Ingelheim Investigational Site

Dijon, France

Location

1199.34.33003 Boehringer Ingelheim Investigational Site

Lille, France

Location

1199.34.33005 Boehringer Ingelheim Investigational Site

Lyon, France

Location

1199.34.33007 Boehringer Ingelheim Investigational Site

Marseille, France

Location

1199.34.33002 Boehringer Ingelheim Investigational Site

Montpellier, France

Location

1199.34.33006 Boehringer Ingelheim Investigational Site

Toulouse, France

Location

1199.34.49003 Boehringer Ingelheim Investigational Site

Bad Berka, Germany

Location

1199.34.49002 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1199.34.49010 Boehringer Ingelheim Investigational Site

Buch, Germany

Location

1199.34.49011 Boehringer Ingelheim Investigational Site

Cologne, Germany

Location

1199.34.49005 Boehringer Ingelheim Investigational Site

Coswig, Germany

Location

1199.34.49001 Boehringer Ingelheim Investigational Site

Essen, Germany

Location

1199.34.49007 Boehringer Ingelheim Investigational Site

Greifswald, Germany

Location

1199.34.49009 Boehringer Ingelheim Investigational Site

Immenhausen, Germany

Location

1199.34.49006 Boehringer Ingelheim Investigational Site

München, Germany

Location

1199.34.49004 Boehringer Ingelheim Investigational Site

Münster, Germany

Location

1199.34.30005 Boehringer Ingelheim Investigational Site

Athens, Greece

Location

1199.34.30001 Boehringer Ingelheim Investigational Site

Heraklion, Greece

Location

1199.34.30004 Boehringer Ingelheim Investigational Site

Larissa, Greece

Location

1199.34.30002 Boehringer Ingelheim Investigational Site

Maroussi, Athens, Greece

Location

1199.34.30003 Boehringer Ingelheim Investigational Site

Nikaia, Greece

Location

1199.34.91051 Boehringer Ingelheim Investigational Site

Ahmedabad, India

Location

1199.34.91053 Boehringer Ingelheim Investigational Site

Banglore, India

Location

1199.34.91056 Boehringer Ingelheim Investigational Site

Jaipur, India

Location

1199.34.91054 Boehringer Ingelheim Investigational Site

Pune, India

Location

1199.34.91055 Boehringer Ingelheim Investigational Site

Pune, India

Location

1199.34.81059 Boehringer Ingelheim Investigational Site

Himeji, Hyogo, Japan

Location

1199.34.81063 Boehringer Ingelheim Investigational Site

Kawasaki, Kanagawa, Japan

Location

1199.34.81060 Boehringer Ingelheim Investigational Site

Kobe, Hyogo, Japan

Location

1199.34.81051 Boehringer Ingelheim Investigational Site

Minato-ku, Tokyo, Japan

Location

1199.34.81054 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, Japan

Location

1199.34.81055 Boehringer Ingelheim Investigational Site

Ogaki, Gifu, Japan

Location

1199.34.81058 Boehringer Ingelheim Investigational Site

Osaka-Sayama, Osaka, Japan

Location

1199.34.81057 Boehringer Ingelheim Investigational Site

Sakai, Osaka, Japan

Location

1199.34.81053 Boehringer Ingelheim Investigational Site

Seto, Aichi, Japan

Location

1199.34.81052 Boehringer Ingelheim Investigational Site

Shinjuku-ku, Tokyo, Japan

Location

1199.34.81056 Boehringer Ingelheim Investigational Site

Tenri, Nara, Japan

Location

1199.34.81062 Boehringer Ingelheim Investigational Site

Tokushima, Tokushima, Japan

Location

1199.34.81061 Boehringer Ingelheim Investigational Site

Yonago, Tottori, Japan

Location

1199.34.52001 Boehringer Ingelheim Investigational Site

Mexico City, Mexico

Location

1199.34.31002 Boehringer Ingelheim Investigational Site

Amsterdam, Netherlands

Location

1199.34.31001 Boehringer Ingelheim Investigational Site

Nieuwegein, Netherlands

Location

1199.34.31003 Boehringer Ingelheim Investigational Site

Rotterdam, Netherlands

Location

1199.34.35107 Boehringer Ingelheim Investigational Site

Amadora, Portugal

Location

1199.34.35105 Boehringer Ingelheim Investigational Site

Coimbra, Portugal

Location

1199.34.35102 Boehringer Ingelheim Investigational Site

Lisbon, Portugal

Location

1199.34.35103 Boehringer Ingelheim Investigational Site

Lisbon, Portugal

Location

1199.34.35101 Boehringer Ingelheim Investigational Site

Porto, Portugal

Location

1199.34.35106 Boehringer Ingelheim Investigational Site

Vila Nova de Gaia, Portugal

Location

1199.34.07001 Boehringer Ingelheim Investigational Site

Kazan', Russia

Location

1199.34.07003 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

1199.34.82002 Boehringer Ingelheim Investigational Site

Bucheon-si, South Korea

Location

1199.34.82004 Boehringer Ingelheim Investigational Site

Incheon, South Korea

Location

1199.34.82001 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1199.34.82003 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1199.34.82006 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1199.34.82007 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1199.34.34001 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1199.34.34003 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1199.34.34004 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1199.34.34005 Boehringer Ingelheim Investigational Site

L'Hospitalet de Llobregat, Spain

Location

1199.34.34009 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1199.34.34008 Boehringer Ingelheim Investigational Site

Seville, Spain

Location

1199.34.90003 Boehringer Ingelheim Investigational Site

Ankara, Turkey (Türkiye)

Location

1199.34.90001 Boehringer Ingelheim Investigational Site

Istanbul, Turkey (Türkiye)

Location

1199.34.90005 Boehringer Ingelheim Investigational Site

Istanbul, Turkey (Türkiye)

Location

1199.34.90002 Boehringer Ingelheim Investigational Site

Izmir, Turkey (Türkiye)

Location

1199.34.90004 Boehringer Ingelheim Investigational Site

Izmir, Turkey (Türkiye)

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.

  PMID: 30176872 DERIVED

• 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.

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• 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

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: May 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

ES (6); PT (6); CN (8); DE (10); JP (13); US (27); NL (3); TU (5); GR (5); RU (2); CL (1); KR (6); FI (1); ME (1); CA (3); FR (6); IN (5)