Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients
Condition: Pulmonary Fibrosis
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis
Intervention: placebo; BIBF 1120
Intervention description: placebo matching BIBF1120, BID; BIBF1120 BID (twice daily)
Intervention MeSH terms: Nintedanib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 515.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

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.
    

Eligibility 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;