Efficacy and Safety of Nintedanib in Patients With Progressive Fibrosing Interstitial Lung Disease (PF-ILD)

Inclusion criteria

• Written Informed Consent consistent with International Conference on Harmonisation Harmonised Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local laws signed prior to entry into the study (and prior to any study procedure including shipment of High Resolution Computer Tomography (HRCT) to reviewer).
• Male or female patients aged >= 18 years at Visit 1.
• Patients with physician diagnosed Interstitial Lung Disease (ILD) who fulfil at least one of the following criteria for Progressive Fibrosing Interstitial Lung Disease (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):
• Clinically significant decline in Forced Vital Capacity (FVC) % pred based on a relative decline of >=10%
• Marginal decline in FVC % pred based on a relative decline of .>=5- =5- 10%, performed within 12 months of Visit 1 as confirmed by central readers.
• For patients with underlying Connective Tissue Disease (CTD): stable CTD as defined by no initiation of new therapy or withdrawal of therapy for CTD within 6 weeks prior to Visit 1.
• Carbon Monoxide Diffusion Capacity (DLCO) corrected for Haemoglobin (Hb) [visit 1] ≥ 30% and = 45% predicted at Visit 2

Exclusion criteria

• Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) > 1.5 x Upper Limit of Normal (ULN) at Visit 1
• Bilirubin > 1.5 x ULN at Visit 1
• 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.

Note: Patients whose Rheumatoid Arthritis (RA)/Connective Tissue Disease (CTD) is managed by these medications should not be considered for participation in the current study unless change in RA/CTD medication is medically indicated (see Inclusion Criteria)

• Diagnosis of Idiopathic Pulmonary Fibrosis (IPF) based on American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) 2011 Guidelines.
• Significant Pulmonary Arterial Hypertension (PAH) defined by any of the following:
• Previous clinical or echocardiographic evidence of significant right heart failure
• History of right heart catheterization showing a cardiac index 2, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) by >1.5 x ULN at Visit 1.
• History of thrombotic event (including stroke and transient ischemic attack) within 12 months of Visit 1.
• Known hypersensitivity to the trial medication or its components (i.e. soya lecithin)
• Patients with peanut allergy.
• 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.
• Life expectancy for disease other than ILD < 2.5 years (Investigator assessment).
• Planned major surgical procedures.
• Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
• 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.
• In the opinion of the Investigator, active alcohol or drug abuse.
• Patients not able to understand or follow trial procedures including completion of self-administered questionnaires without help. *A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral o