A study to evaluate long-term safety of nintedanib in children and adolescents with interstitial lung disease (InPedILD®-ON)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

4 Apr 2022 → 13 Aug 2025

Decision date (initial)

2024-09-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-515743-27-00

EudraCT number

2020-005554-23

WHO UTN

U1111-1305-7514

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety

The trial will assess the safety and tolerability of long-term treatment with nintedanib in pediatric patients with clinically significant fibrosing ILD. The primary objective is to estimate the incidence of treatment emergent adverse events over the whole trial.

Conditions and MedDRA coding

Childhood Interstitial Lung Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. For new patients: 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 (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 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 ILD on HRCT within 12 months of Visit 1 as assessed by the investigator and confirmed by central review.
5. Patients with 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
7. 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: Patients who completed the InPedILD™ trial as planned and who did not permanently prematurely discontinue study treatment.
8. For patients who 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: Criteria for new patients are applicable except criteria 4, and 6 and also except inclusion criterion 1 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.

Exclusion criteria 21

1. For new patients: AST and/or ALT >1.5 x ULN at Visit 1.
2. Bilirubin >1.5 x ULN at Visit 1.
3. eGFR <30 mL/min/1.73m² at Visit 1 (please refer to the study protocol). [Note: Laboratory parameters from Visit 1 have to satisfy the laboratory threshold values as shown above. Visit 2 laboratory results will be available only after the visit. 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.]
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: 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
7. In the opinion of the Investigator, other clinically significant pulmonary abnormalities.
8. Cardiovascular diseases, any of the following: a. Severe hypertension, uncontrolled under treatment, within 6 months of Visit 1. Uncontrolled hypertension is defined as i. 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) (please refer to Appendix 10.5). Not applicable in France. ii. In adolescents 13 to 17 years old: systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg (please refer to Appendix 10.5). In France, applicable for adolescents 12 to 17 years old. b. Myocardial infarction within 6 months of Visit 1 c. Unstable cardiac angina within 6 months of Visit 1
9. Bleeding risk, any of the following: a. Known genetic predisposition to bleeding b. Patients who require i. Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin) ii. High dose antiplatelet therapy c. History of haemorrhagic central nervous system (CNS) event within 12 months of Visit 1 d. Any of the following within 3 months of Visit 1: i. Haemoptysis or haematuria ii. Active gastro-intestinal (GI) bleeding or GI – ulcers iii. Major injury or surgery (investigator's judgment) e. Any of the following coagulation parameters at Visit 1: i. International normalized ratio (INR) >2 ii. Prolongation of prothrombin time (PT) by >1.5 x ULN iii. 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).
20. 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: Patient not compliant in parent trial (InPedILD™), with trial medication or trial visits, according to investigator's judgement. Rollover 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 favourable.
21. For patients who 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: 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: Patients who experienced drug-related adverse events during parent trial leading to permanent study treatment discontinuation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the incidence of treatment emergent adverse events over the whole trial.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Locations

8 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 85 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications