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InPedILD®: A Study to Find Out How Nintedanib is Taken up in the Body and How Well it is Tolerated in Children and Adolescents With Interstitial Lung Disease (ILD)

Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT04093024
Collaborator
(none)
39
Enrollment
43
Locations
2
Arms
29.7
Actual Duration (Months)
0.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main objective of the study is to evaluate dose-exposure and safety of nintedanib in children and adolescents with fibrosing Interstitial Lung Disease (ILD).

Condition or Disease Intervention/Treatment Phase
  • Drug: Nintedanib (Ofev®)
  • Drug: Placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
39 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Double Blind, Randomised, Placebo-controlled Trial to Evaluate the Dose-exposure and Safety of Nintedanib Per os on Top of Standard of Care for 24 Weeks, Followed by Open Label Treatment With Nintedanib of Variable Duration, in Children and Adolescents (6 to 17 Year-old) With Clinically Significant Fibrosing Interstitial Lung Disease
Actual Study Start Date :
Dec 3, 2019
Actual Primary Completion Date :
May 24, 2022
Actual Study Completion Date :
May 24, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Nintedanib (Ofev®)

Drug: Nintedanib (Ofev®)
Capsule
Placebo Comparator: Placebo

Drug: Placebo
Capsule

Outcome Measures

Primary Outcome Measures

  1. Area under the Plasma Concentration-Time Curve at Steady State (AUCτ,ss) based on sampling at steady state (at week 2 and week 26); [Week 2 and Week 26]

  2. N (%) of patients with treatment-emergent adverse events at week 24 [Week 24]

Secondary Outcome Measures

  1. N (%) of patients with treatment-emergent pathological findings of epiphyseal growth plate on imaging at week 24, and week 52 [Week 24 and Week 52]

  2. N (%) of patients with treatment-emergent pathological findings on dental examination or imaging at week 24, and week 52 [Week 24 and Week 52]

  3. N (%) of patients with treatment-emergent adverse events over the whole trial [Up to 29 months]

  4. Change in height from baseline at week 24, week 52, week 76, and week 100 [Baseline, Week 24, Week 52, weeky 76, and week 100]

  5. Change in Forced Vital Capacity (FVC) % predicted from baseline at week 24, and week 52 [Baseline, Week 24 and Week 52]

  6. Absolute change from baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at week 24, and week 52 [Baseline, Week 24 and Week 52]

  7. Change in oxygen saturation (SpO2) on room air at rest from baseline at week 24, and week 52 [Baseline, Week 24 and Week 52]

  8. Change in 6-min walk distance from baseline at week 24, and week 52 [Baseline, Week 24 and Week 52]

  9. Patient acceptability based on the size of capsules at week 24 [Week 24]

  10. Patient acceptability based on the number of capsules at week 24 [Week 24]

  11. Time to first respiratory-related hospitalization over the whole trial [Up to 29 months]

  12. Time to first acute Interstitial Lung Disease (ILD) exacerbation or death over the whole trial [Up to 29 months]

  13. Time to death over the whole trial [Up to 29 months]

  14. Change in sitting height from baseline at week 24, week 52, week 76, and week 100 [Baseline, Week 24, Week 52, Week 76, and Week 100]

  15. Change in leg length from baseline at week 24, week 52, week 76, and week 100 [Baseline, Week 24, Week 52, Week 76, and Week 100]

Eligibility Criteria

Criteria

Ages Eligible for Study:
6 Years to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • 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 information.

  • 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. [Note: Predicted 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 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).

Exclusion Criteria:

  • 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. [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 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 failure

  • 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 abnormalities.

  • 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 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

  • 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 trial.

  • Patients not able or willing to adhere to trial procedures, including intake of study medication.

  • 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 patients).

Contacts and Locations

Locations

Site City State Country Postal Code
1 Children's Hospital Los Angeles Los Angeles California United States 90027
2 Children's Hospital Colorado Aurora Colorado United States 80045
3 Riley Hospital for Children at Indiana University Health Indianapolis Indiana United States 46202
4 Children's Mercy Hospitals and Clinics Kansas City Missouri United States 64108
5 Weill Cornell Medicine New York New York United States 10021
6 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
7 Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15224
8 Vanderbilt University Medical Center Nashville Tennessee United States 37232
9 Seattle Children's Hospital Seattle Washington United States 98105
10 Hospital de Pediatría " Prof. Dr. Juan P. Garrahan" Caba Argentina C1245AAM
11 Hospital de Niños Dr. Ricardo Gutierrez Caba Argentina C1425EFD
12 INSARES Mendoza Argentina M5500CCG
13 Women's and Children's Hospital North Adelaide South Australia Australia 5006
14 Brussels - UNIV HUDERF Bruxelles Belgium 1020
15 Serviços Medicos Respirar Sul Fluminense Barra Mansa Brazil 27323240
16 Centro de Pesquisa Clinica do Instituto da Crianca - HCFMUSP Sao Paulo Brazil 5403-900
17 BC Children's Hospital Vancouver British Columbia Canada V6H 3N1
18 The Hospital for Sick Children Toronto Ontario Canada M5G 1X8
19 Teaching Hospital Motol, Oncology Clinic Praha 5 Czechia 150 06
20 Aarhus University Hospital Aarhus N Denmark 8200
21 Tampere University Hospital Tampere Finland 33520
22 HOP Intercommunal Créteil France 94010
23 HOP Armand-Trousseau Paris France 75571
24 General Hospital of Thessaloniki "Ippokrateio" Thessaloniki Greece 54642
25 Semmelweis University Budapest Hungary 1122
26 Azienda Ospedaliera Meyer Firenze Italy 50139
27 Azienda Ospedaliera Universitaria di Padova Padova Italy 35128
28 Osp. Pediatrico Bambin Gesù Roma Italy 00165
29 Clinical Research Institute S.C. Tlalnepantla Mexico 54055
30 Oslo Universitetssykehus HF, Rikshospitalet Oslo Norway N-0372
31 Independent Public Teaching Children's Hospital Warsaw Poland 02091
32 CHULC, EPE - Hospital Dona Estefânia Lisboa Portugal 1169-045
33 Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital Santa Maria Lisboa Portugal 1649-035
34 Children's Hematology,Oncology&Immunology na Rogachev,Moscow Moscow Russian Federation 117198
35 State Novosibirsk Regional Clinical Hospital Novosibirsk Russian Federation 630087
36 St. Petersburg State Pediatric University St. Petersburg Russian Federation 194100
37 Hospital Vall d'Hebron Barcelona Spain 08035
38 Hospital Virgen del Rocío Sevilla Spain 41013
39 Regional Children Clinical Hospital, Pulmonology, Kharkiv Kharkiv Ukraine 61093
40 Institute of Phthisiology and Pulmonology n. a. F.G.Yanovsky Kyiv Ukraine 03680
41 Regional clinical children hospital, Zaporizhya Zaporizhya Ukraine 69063
42 Birmingham Children's Hospital Birmingham United Kingdom B4 6NH
43 King's College Hospital London United Kingdom SE5 9RS

Sponsors and Collaborators

  • Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT04093024
Other Study ID Numbers:
  • 1199-0337
  • 2018-004530-14
First Posted:
Sep 17, 2019
Last Update Posted:
Jun 22, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Interstitial
Nintedanib

Study Results

No Results Posted as of Jun 22, 2022