- - Children and adolescents 6 to 17 years old at Visit 2.
- - Signed and dated written informed consent and assent, where applicable, in accordance
with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) and
local legislation prior to admission to the trial.
- - Male or female patients.
Female of childbearing potential (WOCBP) must confirm that
sexual abstinence is standard practice and will be continued until 3 months after last
drug intake, or be ready and able to use a highly effective method of birth control
per International Conference on Harmonisation (ICH) M3 (R2) that results in a low
failure rate of less than 1% per year when used consistently and correctly, in
combination with one barrier method, from 28 days prior to initiation of study
treatment, during treatment and until 3 months after last drug intake. Sexual
abstinence is defined as abstinence from any sexual act that may result in pregnancy.
A list of contraception methods meeting these criteria is provided in the parental
- - Patients with evidence of fibrosing Interstitial Lung Disease (ILD) on High-Resolution
Computed Tomography (HRCT) within 12 months of Visit 1 as assessed by the investigator
and confirmed by central review.
- - Patients with Forced Vital Capacity (FVC)% predicted ≥25% at Visit 2.
normal values will be calculated according to GLI (Global Lung Initiative)]
- - Patients with clinically significant disease at Visit 2, as assessed by the
investigator based on any of the following:
- Fan score ≥3, or
- Documented evidence of clinical progression over time based on either
- a 5-10% relative decline in FVC% predicted accompanied by worsening
- a ≥10% relative decline in FVC % predicted, or
- increased fibrosis on HRCT, or
- other measures of clinical worsening attributed to progressive lung disease
(e.g. increased oxygen requirement, decreased diffusion capacity).
- - Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT)>1.5 x Upper
Level of Normal (ULN) at Visit 1.
- - Bilirubin >1.5 x ULN at Visit 1.
- - Creatinine clearance <30 mL/min calculated by Schwartz formula at Visit 1.
Laboratory parameters from Visit 1 have to satisfy the laboratory threshold values as
shown above. Visit 2 laboratory results will be available only after randomization. In
case at Visit 2 the results do no longer satisfy the entry criteria, the Investigator
has to decide whether it is justified that the patient remains on study drug. The
justification for decision needs to be documented. Laboratory parameters that are
found to be abnormal at Visit 1 are allowed to be re-tested (once) if it is thought to
be a measurement error (i.e. there was no abnormal result of this test in the recent
history of the patient and there is no related clinical sign) or the result of a
temporary and reversible medical condition, once that condition is resolved.]
- - Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic
impairment) at Visit 1.
- - Previous treatment with nintedanib.
- - Other investigational therapy received within 1 month or 5 half-lives (whichever is
shorter but ≥1 week) prior to Visit 2.
- - Significant pulmonary arterial hypertension (PAH) defined by any of the following:
- Previous clinical or echocardiographic evidence of significant right heart
- History of right heart catheterization showing a cardiac index ≤2 l/min/m²
- PAH requiring parenteral therapy with epoprostenol/treprostinil
- In the opinion of the Investigator, other clinically significant pulmonary
- - 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)
- In adolescents 13 to 17 years old: systolic blood pressure ≥140 mm Hg or
diastolic blood pressure ≥90 mm Hg
- Myocardial infarction within 6 months of Visit 1
- Unstable cardiac angina within 6 months of Visit 1
- 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 [Note: Prophylactic low dose heparin or
heparin flush as needed for maintenance of an indwelling intravenous device
(e.g. enoxaparin 4000 I.
U. s.c. per day), as well as prophylactic use of
antiplatelet therapy (e.g. acetyl salicylic acid up to 325 mg/day, or
clopidogrel at 75 mg/day, or equivalent doses of other antiplatelet therapy)
are not prohibited.]
- - History of haemorrhagic central nervous system (CNS) event within 12 months of
- 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
- 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 documented allergy to peanut or soya.
- - 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 any concomitant disease other than Interstitial Lung Disease
(ILD)<2.5 years (investigator assessment).
- - Female patients who are pregnant, nursing, or who plan to become pregnant while in the
- - Patients not able or willing to adhere to trial procedures, including intake of study
- - 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.
- - Patients <13.5 kg of weight at Visit 1 (same threshold to be used for male and female