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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04093024




Registration number
NCT04093024
Ethics application status
Date submitted
16/09/2019
Date registered
17/09/2019
Date last updated
1/12/2020

Titles & IDs
Public title
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).
Scientific 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.
Secondary ID [1] 0 0
2018-004530-14
Secondary ID [2] 0 0
1199-0337
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung Diseases, Interstitial 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nintedanib (Ofev®)
Treatment: Drugs - Placebo

Experimental: Nintedanib (Ofev®) -

Placebo Comparator: Placebo -


Treatment: Drugs: Nintedanib (Ofev®)
Capsule

Treatment: Drugs: Placebo
Capsule

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area under the Plasma Concentration-Time Curve at Steady State (AUCt,ss) based on sampling at steady state (at week 2 and week 26);
Timepoint [1] 0 0
Week 2 and Week 26
Primary outcome [2] 0 0
N (%) of patients with treatment-emergent adverse events at week 24
Timepoint [2] 0 0
Week 24
Secondary outcome [1] 0 0
N (%) of patients with treatment-emergent pathological findings of epiphyseal growth plate on imaging at week 24, and week 52
Timepoint [1] 0 0
Week 24 and Week 52
Secondary outcome [2] 0 0
N (%) of patients with treatment-emergent pathological findings on dental examination or imaging at week 24, and week 52
Timepoint [2] 0 0
Week 24 and Week 52
Secondary outcome [3] 0 0
N (%) of patients with treatment-emergent adverse events over the whole trial
Timepoint [3] 0 0
Up to 29 months
Secondary outcome [4] 0 0
Change in height from baseline at week 24, week 52, week 76, and week 100
Timepoint [4] 0 0
Baseline, Week 24, Week 52, weeky 76, and week 100
Secondary outcome [5] 0 0
Change in Forced Vital Capacity (FVC) % predicted from baseline at week 24, and week 52
Timepoint [5] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [6] 0 0
Absolute change from baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at week 24, and week 52
Timepoint [6] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [7] 0 0
Change in oxygen saturation (SpO2) on room air at rest from baseline at week 24, and week 52
Timepoint [7] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [8] 0 0
Change in 6-min walk distance from baseline at week 24, and week 52
Timepoint [8] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [9] 0 0
Patient acceptability based on the size of capsules at week 24
Timepoint [9] 0 0
Week 24
Secondary outcome [10] 0 0
Patient acceptability based on the number of capsules at week 24
Timepoint [10] 0 0
Week 24
Secondary outcome [11] 0 0
Time to first respiratory-related hospitalization over the whole trial
Timepoint [11] 0 0
Up to 29 months
Secondary outcome [12] 0 0
Time to first acute Interstitial Lung Disease (ILD) exacerbation or death over the whole trial
Timepoint [12] 0 0
Up to 29 months
Secondary outcome [13] 0 0
Time to death over the whole trial
Timepoint [13] 0 0
Up to 29 months
Secondary outcome [14] 0 0
Change in sitting height from baseline at week 24, week 52, week 76, and week 100
Timepoint [14] 0 0
Baseline, Week 24, Week 52, Week 76, and Week 100
Secondary outcome [15] 0 0
Change in leg length from baseline at week 24, week 52, week 76, and week 100
Timepoint [15] 0 0
Baseline, Week 24, Week 52, Week 76, and Week 100

Eligibility
Key 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).
Minimum age
6 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
Argentina
State/province [9] 0 0
Caba
Country [10] 0 0
Brazil
State/province [10] 0 0
Barra Mansa
Country [11] 0 0
Brazil
State/province [11] 0 0
São Bernardo do Campo
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Czechia
State/province [13] 0 0
Praha 5
Country [14] 0 0
Denmark
State/province [14] 0 0
Aarhus N
Country [15] 0 0
Denmark
State/province [15] 0 0
København Ø
Country [16] 0 0
Finland
State/province [16] 0 0
Helsinki
Country [17] 0 0
Finland
State/province [17] 0 0
Tampere
Country [18] 0 0
France
State/province [18] 0 0
Créteil
Country [19] 0 0
France
State/province [19] 0 0
Paris
Country [20] 0 0
Greece
State/province [20] 0 0
Thessaloniki
Country [21] 0 0
Hungary
State/province [21] 0 0
Budapest
Country [22] 0 0
Italy
State/province [22] 0 0
Roma
Country [23] 0 0
Mexico
State/province [23] 0 0
Tlalnepantla
Country [24] 0 0
Netherlands
State/province [24] 0 0
Amsterdam
Country [25] 0 0
Norway
State/province [25] 0 0
Oslo
Country [26] 0 0
Poland
State/province [26] 0 0
Warsaw
Country [27] 0 0
Portugal
State/province [27] 0 0
Lisboa
Country [28] 0 0
Portugal
State/province [28] 0 0
Porto
Country [29] 0 0
Russian Federation
State/province [29] 0 0
Moscow
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Novosibirsk
Country [31] 0 0
Russian Federation
State/province [31] 0 0
St. Petersburg
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Yaroslavl
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
Spain
State/province [35] 0 0
Sevilla
Country [36] 0 0
Ukraine
State/province [36] 0 0
Kharkiv
Country [37] 0 0
Ukraine
State/province [37] 0 0
Kyiv
Country [38] 0 0
Ukraine
State/province [38] 0 0
Zaporizhya

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT04093024
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Boehringer Ingelheim
Address 0 0
Country 0 0
Phone 0 0
1-800-243-0127
Fax 0 0
Email 0 0
clintriage.rdg@boehringer-ingelheim.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04093024