Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

NCT00514683 | Completed Phase 2 Results

• 1 other identifier: 1199.30
• Study Type: interventional
• Target: 432
• Locations: 25 countries
• Sites: 92

Brief Summary

The general purpose of this trial is to investigate the efficacy and safety of 4 dose strategies of BIBF 1120 treatment for 12 months, compared to placebo in patients with idiopathic pulmonary fibrosis. The primary objective of this study is to demonstrate whether at least one dose strategy is superior to placebo in patients with IPF, in modifying the rate of decline of Forced Vital Capacity (FVC). As a secondary objective, additional parameters will be assessed in order to differentiate between dose strategies on the basis of safety and efficacy

Conditions

Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (1)

• Rate of Decline in FVC

  Rate of decline in Forced Vital Capacity (FVC) evaluated from baseline until 52 weeks of treatment. The means presents actually the adjusted rate based on a MMRM with fixed terms for treatment\*time, gender\*height, gender\*age and random terms for patient effect, patient\*time.

  Baseline until 52 weeks

Secondary Outcomes (36)

• Absolute Change From Baseline in FVC%Pred

  Baseline and 52 weeks

• Absolute Change From Baseline in FVC

  Baseline and 52 weeks

• Relative Change From Baseline in FVC%Pred

  Baseline and 52 weeks

• Relative Change From Baseline in FVC

  Baseline and 52 weeks

• Number of Participants With Change From Baseline in FVC by Categories

  Baseline and 52 weeks

Study Arms (5)

dose 1

EXPERIMENTAL

low dose BIBF1120 once daily

Drug: low dose BIBF1120 once daily

dose 2

EXPERIMENTAL

low dose BIBF 1120 twice daily

Drug: low dose BIBF 1120 twice daily

dose 3

EXPERIMENTAL

intermediate dose BIBF 1120 twice daily

Drug: intermediate dose BIBF 1120 twice daily

dose 4

EXPERIMENTAL

high dose BIBF 1120 twice daily

Drug: high dose BIBF 1120 twice daily

placebo

PLACEBO COMPARATOR

placebo

Drug: placebo

Interventions

low dose BIBF1120 once daily DRUG

low dose BIBF1120 once daily

dose 1

low dose BIBF 1120 twice daily DRUG

low dose BIBF 1120 twice daily

dose 2

intermediate dose BIBF 1120 twice daily DRUG

intermediate dose BIBF 1120 twice daily

dose 3

high dose BIBF 1120 twice daily DRUG

high dose BIBF 1120 twice daily

dose 4

placebo DRUG

placebo

placebo

Eligibility Criteria

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

You may qualify if:

• Patient \>40 years
• Written informed consent signed prior to entry into the study
• IPF diagnosed (according to ATS / ERS criteria) less than 5 years prior to screening visit.
• HRCT within 12 months of randomisation and biopsy (the latter if needed to fulfil ATS/ERS criteria) centrally reviewed and consistent with diagnosis.
• FVC\>50 % of predicted value
• Predicted normal values will be calculated according to ESCS (R94-1408):
• Males :
• FVC predicted (L) = 5.76 x height (meters)- 0.026 x age (years) -4.34
• Females :
• FVC predicted (L) = 4.43 x height (meters)- 0.026 x age (years) -2.89
• Single breath DLCO (corrected for Hb) 30 - 79% inclusive of predicted .
• Different sites may use different prediction formulas, based on the method used to measure DLco. In any case, the method used must be in compliance with the ATS/ERS guideline on DLCO measurements (R06-2002), and the prediction formula appropriate for that method. Raw data (gas mixture, equation used for prediction of normal, further adjustments made if so) must be traced.
• Adjustment for haemoglobin (R06-2002):
• Males :
• DLCO predicted for Hb = DLCO predicted x (1.7Hb/\[10.22+Hb\])

You may not qualify if:

• AST, ALT \> 1.5 x ULN ;
• Bilirubin \> 1.5 x ULN
• Relevant airways obstruction
• Continuous oxygen supplementation at randomisation (defined as \> 15 hours supplemental oxygen per day).
• Active infection at screening or randomisation.
• Neutrophils \< 1500 / mm3
• International normalised ratio (INR) \> 1.5 and/or Partial thromboplastin time (PTT) \> 1.5 x ULN ;
• Platelets \< 100 000 /mL
• Haemoglobin \< 9.0 g/dL
• In the opinion of the Investigator, patient is likely to have lung transplantation during study
• Life expectancy for disease other than IPF \< 2.5 years (Investigator assessment).
• Other disease that may interfere with testing procedures or in judgement of Investigator may interfere with trial participation or may put the patient at risk when participating to this trial.
• Myocardial infarction during the previous 6 months
• Unstable angina during the previous month
• Other investigational therapy received within 8 weeks prior to screening visit.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (92)

1199.30.54002 Boehringer Ingelheim Investigational Site

Mendoza, Argentina

Location

1199.30.61005 Boehringer Ingelheim Investigational Site

South Brisbane, Queensland, Australia

Location

1199.30.61003 Boehringer Ingelheim Investigational Site

Toorak Gardens, South Australia, Australia

Location

1199.30.61004 Boehringer Ingelheim Investigational Site

Woodville, South Australia, Australia

Location

1199.30.61001 Royal Perth Hospital

Perth, Western Australia, Australia

Location

1199.30.32004 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1199.30.32001 Boehringer Ingelheim Investigational Site

Leuven, Belgium

Location

1199.30.32002 Boehringer Ingelheim Investigational Site

Yvoir, Belgium

Location

1199.30.55002 Boehringer Ingelheim Investigational Site

Porto Alegre, Brazil

Location

1199.30.55001 Boehringer Ingelheim Investigational Site

Vila Clementino, Brazil

Location

1199.30.06004 Boehringer Ingelheim Investigational Site

Sofia, Bulgaria

Location

1199.30.06005 Boehringer Ingelheim Investigational Site

Sofia, Bulgaria

Location

1199.30.01003 Division of Respirology

Halifax, Nova Scotia, Canada

Location

1199.30.01002 St. Joseph's Healthcare

Hamilton, Ontario, Canada

Location

1199.30.56001 Boehringer Ingelheim Investigational Site

Providencia, Chile

Location

1199.30.86001 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1199.30.86002 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1199.30.86005 Boehringer Ingelheim Investigational Site

Nanjing, China

Location

1199.30.86003 Boehringer Ingelheim Investigational Site

Shanghai, China

Location

1199.30.86004 Boehringer Ingelheim Investigational Site

Shenyang, China

Location

1199.30.42002 Boehringer Ingelheim Investigational Site

Prague, Czechia

Location

1199.30.42001 Boehringer Ingelheim Investigational Site

Ústí nad Labem, Czechia

Location

1199.30.3302A Boehringer Ingelheim Investigational Site

Bobigny, France

Location

1199.30.3306A Boehringer Ingelheim Investigational Site

Dijon, France

Location

1199.30.3303A Boehringer Ingelheim Investigational Site

Grenoble, France

Location

1199.30.3305A Boehringer Ingelheim Investigational Site

Lille, France

Location

1199.30.3305B Boehringer Ingelheim Investigational Site

Lille, France

Location

1199.30.3305C Boehringer Ingelheim Investigational Site

Lille, France

Location

1199.30.3304C Boehringer Ingelheim Investigational Site

Montpellier, France

Location

1199.30.3307A Boehringer Ingelheim Investigational Site

Nice, France

Location

1199.30.3301A Boehringer Ingelheim Investigational Site

Paris, France

Location

1199.30.49008 Boehringer Ingelheim Investigational Site

Bad Berka, Germany

Location

1199.30.49007 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1199.30.49006 Boehringer Ingelheim Investigational Site

Donaustauf, Germany

Location

1199.30.49001 Boehringer Ingelheim Investigational Site

Essen, Germany

Location

1199.30.49002 Boehringer Ingelheim Investigational Site

Freiburg/Breisgau, Germany

Location

1199.30.49003 Boehringer Ingelheim Investigational Site

Großhansdorf, Germany

Location

1199.30.49009 Boehringer Ingelheim Investigational Site

Leipzig, Germany

Location

1199.30.49004 Boehringer Ingelheim Investigational Site

Mainz, Germany

Location

1199.30.49005 Boehringer Ingelheim Investigational Site

München, Germany

Location

1199.30.30004 Boehringer Ingelheim Investigational Site

Alexandroupoli, Greece

Location

1199.30.30001 Boehringer Ingelheim Investigational Site

Heraklion, Greece

Location

1199.30.30002 Boehringer Ingelheim Investigational Site

Larissa, Greece

Location

1199.30.36002 Boehringer Ingelheim Investigational Site

Budapest, Hungary

Location

1199.30.36003 Boehringer Ingelheim Investigational Site

Budapest, Hungary

Location

1199.30.36004 Boehringer Ingelheim Investigational Site

Deszk, Hungary

Location

1199.30.36001 Boehringer Ingelheim Investigational Site

Pécs, Hungary

Location

1199.30.36005 Boehringer Ingelheim Investigational Site

Székesfehérvár, Hungary

Location

1199.30.35301 Mater Misericordiae Hospital

Dublin, Ireland

Location

1199.30.39008 Boehringer Ingelheim Investigational Site

Ascoli Piceno, Italy

Location

1199.30.39013 Boehringer Ingelheim Investigational Site

Busto Arsizio (va), Italy

Location

1199.30.39007 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1199.30.39001 Boehringer Ingelheim Investigational Site

Modena, Italy

Location

1199.30.39012 Boehringer Ingelheim Investigational Site

Napoli, Italy

Location

1199.30.39009 Boehringer Ingelheim Investigational Site

Pavia, Italy

Location

1199.30.39011 Boehringer Ingelheim Investigational Site

Roma, Italy

Location

1199.30.39010 Boehringer Ingelheim Investigational Site

Siena, Italy

Location

1199.30.39003 Boehringer Ingelheim Investigational Site

Terni, Italy

Location

1199.30.39004 Boehringer Ingelheim Investigational Site

Trieste, Italy

Location

1199.30.52001 Boehringer Ingelheim Investigational Site

Distrito Federal, Mexico

Location

1199.30.31002 Boehringer Ingelheim Investigational Site

Nieuwegein, Netherlands

Location

1199.30.35105 Boehringer Ingelheim Investigational Site

Coimbra, Portugal

Location

1199.30.35106 Boehringer Ingelheim Investigational Site

Coimbra, Portugal

Location

1199.30.35107 Boehringer Ingelheim Investigational Site

Lisbon, Portugal

Location

1199.30.35108 Boehringer Ingelheim Investigational Site

Lisbon, Portugal

Location

1199.30.35109 Boehringer Ingelheim Investigational Site

Lisbon, Portugal

Location

1199.30.35101 Boehringer Ingelheim Investigational Site

Porto, Portugal

Location

1199.30.07001 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

1199.30.07002 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

1199.30.07003 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

1199.30.27001 Boehringer Ingelheim Investigational Site

Bellville, South Africa

Location

1199.30.27003 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

1199.30.27002 Boehringer Ingelheim Investigational Site

Tygerberg, South Africa

Location

1199.30.82002 Boehringer Ingelheim Investigational Site

Gyunggido, South Korea

Location

1199.30.82004 Boehringer Ingelheim Investigational Site

Incheon, South Korea

Location

1199.30.82001 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1199.30.82003 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1199.30.82005 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1199.30.34001 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1199.30.34002 Boehringer Ingelheim Investigational Site

Valencia, Spain

Location

1199.30.88605 Boehringer Ingelheim Investigational Site

Taichung, Taiwan

Location

1199.30.88601 National Taiwan University

Taipei, Taiwan

Location

1199.30.88603 Tri-service General Hospital

Taipei, Taiwan

Location

1199.30.88606 Boehringer Ingelheim Investigational Site

Taipei, Taiwan

Location

1199.30.88604 Chang Gung Memorial Hosp-Linkou

Taoyuan District, Taiwan

Location

1199.30.90001 Boehringer Ingelheim Investigational Site

Ankara, Turkey (Türkiye)

Location

1199.30.90002 Boehringer Ingelheim Investigational Site

Istanbul, Turkey (Türkiye)

Location

1199.30.44006 Boehringer Ingelheim Investigational Site

Aberdeen, United Kingdom

Location

1199.30.44003 Boehringer Ingelheim Investigational Site

Birmingham, United Kingdom

Location

1199.30.44005 Boehringer Ingelheim Investigational Site

Birmingham, United Kingdom

Location

1199.30.44007 Boehringer Ingelheim Investigational Site

Manchester, United Kingdom

Location

1199.30.44001 Boehringer Ingelheim Investigational Site

Westbury on Trym, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 33902584 DERIVED

• 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.

  PMID: 28993537 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

• Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, Brown KK, Flaherty KR, Noble PW, Raghu G, Brun M, Gupta A, Juhel N, Kluglich M, du Bois RM. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011 Sep 22;365(12):1079-87. doi: 10.1056/NEJMoa1103690.

  PMID: 21992121 DERIVED

MeSH Terms

Conditions

Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

There were numerous additional pre-specified endpoints. Full results are available under the BI Transparency web page ( http://trials.boehringer-ingelheim.com/trial\_results.html )

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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 9, 2007
• First Posted: August 10, 2007
• Study Start: August 1, 2007
• Primary Completion: June 1, 2010
• Last Updated: January 6, 2015
• Results First Posted: January 6, 2015

Record last verified: 2015-01

Locations

FR (9); NL (1); RU (3); TU (2); AR (1); BE (3); BR (2); IE (1); ME (1); AU (4); CN (5); CZ (2); KR (5); ZA (3); TW (5); CA (2); DE (9); HU (5); BU (2); CL (1); GR (3); IT (10); PT (6); ES (2); GB (5)