A Study to Evaluate Long-term Safety of Nintedanib in Children and Adolescents With Interstitial Lung Disease (InPedILD®-ON)

Exclusion Criteria

• •For new patients:
• •1. Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT) \>1.5 x Upper limit of normal (ULN) at Visit 1.
• •2. Bilirubin \>1.5 x ULN at Visit 1.
• •3. Estimated Glomerular Filtration Rate (eGFR) \<30 mL/min/1.73 m² at Visit 1
• •4. Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment) at Visit 1.
• •5. Other investigational therapy received within 1 month or 5 half-lives (whichever is shorter but ≥1 week) prior to Visit 2 except investigational therapy received in InPedILD® trial.
• •6. 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 l/min/m²
• •* PAH requiring parenteral therapy with epoprostenol/treprostinil
• •7. In the opinion of the Investigator, other clinically significant pulmonary abnormalities.
• •8. Cardiovascular diseases, any of the following:
• •* Severe hypertension, uncontrolled under treatment, within 6 months of Visit 1. Uncontrolled hypertension is defined as
• •* In children 6 to ≤12 years old: ≥95th percentile + 12 mm Hg or ≥140/90 mm Hg (whichever is lower) (systolic or diastolic blood pressure equal to or greater than the calculated target value). Not applicable in France.
• •* In adolescents 13 to 17 years old: systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. Not applicable in France.
• •* Myocardial infarction within 6 months of Visit 1
• •* Unstable cardiac angina within 6 months of Visit 1
• •9. Bleeding risk, any of the following:
• •* Known genetic predisposition to bleeding
• •* Patients who require
• •* Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin)
• •* High dose antiplatelet therapy
• •* History of haemorrhagic central nervous system (CNS) event within 12 months of Visit 1
• •* Any of the following within 3 months of Visit 1:
• •* Haemoptysis or haematuria
• •* Active gastro-intestinal (GI) bleeding or GI - ulcers
• •* Major injury or surgery (investigator's judgment)
• •* Any of the following coagulation parameters at Visit 1:
• •* International normalized ratio (INR) \>2
• •* Prolongation of prothrombin time (PT) by \>1.5 x ULN
• •* Prolongation of activated partial thromboplastin time (aPTT) by \>1.5 x ULN
• •10. History of thrombotic event (including stroke and transient ischemic attack) within 12 months of Visit 1.
• •11. Known hypersensitivity to the trial medication or its components (i.e. soya lecithin).
• •12. Patients with documented allergy to peanut or soya.
• •13. 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.
• •14. Life expectancy for any concomitant disease other than ILD \<2.5 years (investigator assessment).
• •15. Female patients who are pregnant, nursing, or who plan to become pregnant while in the trial.
• •16. Patients not able or willing to adhere to trial procedures, including intake of study medication.
• •17. Patients who must or wish to take any drug considered likely to interfere with the safe conduct of the trial according to investigator's benefit-risk assessment for the individual patient
• •18. Patients with any diagnosed growth disorder such as growth hormone deficiency or any genetic disorder that is associated with short stature (e.g. Turner Syndrome, Noonan Syndrome, Russell-Silver Syndrome) and/or treatment with growth hormone therapy within 6 months before Visit 2. Patients with short stature considered by the investigator to be due to glucocorticoid therapy may be included.
• •19. Patients \<13.5 kg of weight at Visit 1 (same threshold to be used for male and female patients).
• •For roll-over patients from the InPedILD® study:
• •Only criteria 11, 12, 13, 15, 16, 17 and 19, listed for new patients are applicable with the following additional exclusion criterion:
• •For patients who prematurely discontinued treatment permanently in 1199-0337 but are potentially eligible and for completed patients from parent trial not able to roll over into the extension trial within 12 weeks following their End of Treatment Visit in the parent trial:
• •21. Patients who experienced drug-related adverse events during parent trial leading to permanent study treatment discontinuation.