| Eligibility |
Inclusion Criteria:
For new patients:
1. Children and adolescents 6 to 17 years old at Visit 2. In France, only adolescents 12
to 17 years old at Visit 2.
2. Signed and dated written informed consent and assent, where applicable, in accordance
with ICH-GCP and local legislation prior to admission to the trial.
3. Male or female patients. Female of childbearing potential (WOCBP1) 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 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.
4. 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.
5. Patients with Forced Vital Capacity (FVC) % predicted =25% at Visit 2.
6. 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
symptoms, or
- 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).
For roll-over patients from the InPedILD® study:
Only criteria 2 and 3 listed for new patients are applicable with the following
additional inclusion criterion:
7. Patients who completed the InPedILD® trial as planned and who did not permanently
prematurely discontinue study treatment.
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:
Inclusion criteria for new patients are applicable except criteria 4, and 6 (as eligibility
for these criteria has been confirmed already in 1199-0337 and does not need to be
repeated) and also except inclusion criterion 1 for completed patients from parent trial
not able to roll over within 12 weeks following their End of Treatment Visit in the parent
trial.
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:
20. Patient not compliant in parent trial (InPedILD®), with trial medication or trial
visits, according to investigator's judgement. Roll-over patients may qualify for
participation even though other exclusion criteria may have been met during the
participation in InPedILD®, if the investigator's benefit-risk assessment for the
individual patient remains favorable.
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:
All exclusion criteria for new patients are applicable. In addition, the following
additional exclusion criterion is applicable for patients who prematurely discontinued
treatment permanently in 1199-0337:
21. Patients who experienced drug-related adverse events during parent trial leading to
permanent study treatment discontinuation.
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