The aim of the current study is to investigate the efficacy and safety of 150 mg bid nintedanib over 52 weeks in patients with Progressive Fibrosing Interstitial Lung Disease (PF-ILD) defined as patients who present with features of diffuse fibrosing lung disease of >10% extent on high-resolution computed tomography (HRCT) and whose lung function and respiratory symptoms or chest imaging have worsened despite treatment with unapproved medications used in clinical practice to treat ILD.
Conditions
Interventions
Trade Name: Ofev
Product Name: Nintedanib 100 mg capsules
Product Code: Nintedanib
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Nintedanib
CAS Number: 656247-17-5
Other descriptive name: N
Sponsors
Boehringer Ingelheim
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written Informed Consent consistent with ICH-GCP and local laws signed prior to entry into the study (and prior to any study procedure including shipment of HRCT to reviewer). 2. Male or female patients aged = 18 years at Visit 1. 3. Patients with physician diagnosed ILD who fulfil at least one of the following criteria for PF-ILD within 24 months of screening visit (Visit 1) despite treatment with unapproved medications used in clinical practice to treat ILD, as assessed by the investigator (refer to Exclusion Criteria): a. Clinically significant decline in FVC % pred based on a relative decline of =10% b. Marginal decline in FVC % pred based on a relative decline of =5-10%, performed within 12 months of Visit 1 as confirmed by central readers. 5. For patients with underlying CTD: stable CTD as defined by no initiation of new therapy or withdrawal of therapy for CTD within 6 weeks prior to Visit 1. 6. DLCO corrected for Haemoglobin (Hb) [visit 1] = 30% and =65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: 1. AST, ALT > 1.5 x ULN at Visit 1 2. Bilirubin > 1.5 x ULN at Visit 1 3. Creatinine clearance 20mg/day and the combination of OCS+AZA+NAC within 4 weeks of Visit 2, cyclophosphamide within 8 weeks of Visit 2, rituximab within 6 months of Visit 2. 8. Diagnosis of IPF based on ATS/ERS/JRS/ALAT 2011 Guidelines. 9. Significant Pulmonary Arterial Hypertension (PAH) defined by any of the following: a. Previous clinical or echocardiographic evidence of significant right heart failure b. History of right heart catheterization showing a cardiac index = 2 l/min/m² c. PAH requiring parenteral therapy with epoprostenol/treprostinil 10. Primary obstructive airway physiology (pre-bronchodilator FEV1/FVC 2, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) by >1.5 x ULN at Visit 1. 15. History of thrombotic event (including stroke and transient ischemic attack) within 12 months of Visit 1. 16. Known hypersensitivity to the trial medication or its components (i.e. soya lecithin) 17. Patients with peanut allergy. 18. Other disease that may interfere with testing procedures or in the judgment of the Investigator may interfere with trial participation or may put the patient at risk when participating in this trial. 19. Life expectancy for disease other than ILD < 2.5 years (Investigator assessment). 20. Planned major surgical procedures. 21. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. 22. Women of childbearing potential not willing or able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly as well as one barrier method for 28 days prior to and 3 months after nintedanib administration. A list of contraception methods meeting these criteria is provided in the patient information
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate a reduction of lung function decline, as measured by the annual rate of decline in FVC for nintedanib compared to placebo.;Secondary Objective: The main secondary objectives of the trial are to investigate the effect of treatment on quality of life using the King's Brief Interstitial Lung Disease Questionnaire (K-BILD), and to assess the effect of nintedanib on time to first acute ILD exacerbation and overall survival over 52 weeks.;Primary end point(s): 1: Annual rate of decline in Forced Vital Capacity ;Timepoint(s) of evaluation of this end point: 1: 52 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1: Absolute change from baseline in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) total score at week 52 2: Time to first acute ILD exacerbation or death over 52 weeks 3: Time to death over 52 weeks 4: Time to death due to respiratory cause over 52 weeks 5: Time to progression (defined as a equal or more than 10 percent absolute decline in FVC percent pred) or death over 52 weeks 6: Proportion of patients with a relative decline from baseline in FVC percent pred of more than 10 percent at week 52 7: Proportion of patients with a relative decline from baseline in FVC percent pred of more than 5 percent at week 52 8: Absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms dyspnea domain score at week 52 9: Absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms cough domain score at week 52 ;Timepoint(s) of evaluation of this end point: 1: 52 weeks 2: 52 weeks 3: 52 weeks 4: 52 weeks 5: 52 weeks 6: 52 weeks 7: 52 weeks 8: 52 weeks 9: 52 weeks | — |
Countries
Argentina, Australia, Belgium, Canada, Chile, China, France, Germany, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim
Outcome results
None listed