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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) (InPedILD®)

Primary Purpose

Lung Diseases, Interstitial

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Nintedanib

Placebo

About this trial

This is an interventional treatment trial for Lung Diseases, Interstitial

Eligibility Criteria

6 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

Children's Hospital Los Angeles
Children's Hospital Colorado
Riley Hospital for Children at Indiana University Health
Children's Mercy Hospitals and Clinics
Weill Cornell Medicine
Children's Hospital of Philadelphia
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
Vanderbilt University Medical Center
Seattle Children's Hospital
Hospital de Pediatría " Prof. Dr. Juan P. Garrahan"
Hospital de Niños Dr. Ricardo Gutierrez
INSARES
Women's and Children's Hospital
Brussels - UNIV HUDERF
Serviços Medicos Respirar Sul Fluminense
Centro de Pesquisa Clinica do Instituto da Crianca - HCFMUSP
BC Children's Hospital
The Hospital for Sick Children
Teaching Hospital Motol, Oncology Clinic
Aarhus University Hospital
Tampere University Hospital
HOP Intercommunal
HOP Armand-Trousseau
General Hospital of Thessaloniki "Ippokrateio"
Semmelweis University
Azienda Ospedaliera Meyer
Azienda Ospedaliera Universitaria di Padova
Osp. Pediatrico Bambin Gesù
Clinical Research Institute S.C.
Oslo Universitetssykehus HF, Rikshospitalet
Independent Public Teaching Children's Hospital
CHULC, EPE - Hospital Dona Estefânia
Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital Santa Maria
Children's Hematology,Oncology&Immunology na Rogachev,Moscow
State Novosibirsk Regional Clinical Hospital
St. Petersburg State Pediatric University
Hospital Vall d'Hebron
Hospital Virgen del Rocío
Regional Children Clinical Hospital, Pulmonology, Kharkiv
Institute of Phthisiology and Pulmonology n. a. F.G.Yanovsky
Regional clinical children hospital, Zaporizhya
Birmingham Children's Hospital
King's College Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Double-blind period (DBP) + open-label Nintedanib period (OLNP): Randomised Nintedanib

DBP+OLNP: Randomised placebo

Arm Description

This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose. Medication dosage was per administration 50 milligram (mg) [2 capsules with strength 25 mg],75 mg [3 capsules with strength 25 mg], 100 mg [1 capsule with strength 100 mg or 4 capsules with strength 25 mg] or 150 mg [1 capsule with strength 150 mg or 6 capsules with strength 25 mg] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arms. DBP: Planned was from first randomised trial drug intake to last blinded drug intake. OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake.

Placebo randomised participants were treated orally with a Nintedanib matching placebo soft capsule twice daily in the double-blind period (DBP). Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily. Medication dosage was per administration 50 milligram (mg) [2 25 mg capsules (cap)],75 mg [3 25 mg cap], 100 mg [1 100 mg or 4 25 mg cap] or 150 mg [1 150 mg or 6 25 mg cap] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed. The dose interval was approximately 12 hours between one and the next dose. Here participants received placebo first (DBP) and then Nintedanib (OLNP). DBP: Planned was from first to last randomised blinded drug intake. OLNP: Planned was from first to last open-label Nintedanib intake.

Outcomes

Primary Outcome Measures

Area Under the Plasma Concentration-time Curve at Steady State (AUCτ,ss) Based on Sampling at Steady State (at Week 2 and Week 26)

Area under the plasma concentration-time curve at steady state (AUCt,ss) based on sampling at steady state (at Week 2 and Week 26) after multiple oral administration of Nintedanib by age group over all treatments. Values of samples taken at Week 2 (for randomised Nintedanib participants) and at Week 26 (for randomised placebo participants) were used. Missing values at Week 2 of randomised Nintedanib participants were replaced with values taken at Week 26.

Number of Participants With Treatment-emergent Adverse Events During the Double-blind Period

Treatment-emergent was defined as: Adverse events with onset or worsening on or after date of treatment start until end of double-blind period (defined as the day before first intake of open-label nintedanib or last double-blind drug intake + residual effect period, whichever is earlier) were considered as treatment-emergent and were included in the analysis. Adverse events were counted under the treatment as randomized for the double-blind period.

Secondary Outcome Measures

Number of Participants With at Least One Treatment-emergent Pathological Finding of Epiphyseal Growth Plate on Imaging up to Week 24, and Week 52

Number of participants with at least one treatment-emergent pathological finding of the epiphyseal growth plate imaging (Magnetic Resonance Imaging (MRI)s/x-rays) were analyzed cumulatively and based on central review.

Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24

Number of participants with treatment-emergent pathological findings on dental examination (clinical examination) based on dentist assessment or imaging (panoramic x-ray) based on central review were analyzed. Number of participants with treatment-emergent pathological findings on dental imaging were analyzed cumulatively.

Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52

Number of Participants With Treatment-emergent Adverse Events Over the Whole Trial

Treatment-emergent was defined as: Adverse events with onset or worsening on or after date of treatment start until last drug intake + residual effect period was considered as treatment-emergent and was included in the analysis. Adverse events were counted under the treatment as randomized for the double-blind period.

Absolute Change From Baseline in Height at Week 24

Absolute change from baseline in height at Week 24 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in height at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Height at Week 52

Absolute change from baseline in height at Week 52 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in height at Week 52 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Height at Week 76

Absolute change from baseline in height at Week 76 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. MMRM has been calculated but did not provide estimates for this time point due to low sample size. Thus, change in height from baseline to Week 76 was analyzed descriptively only.

Absolute Change From Baseline in Sitting Height at Week 24

Absolute change from baseline in sitting height at Week 24 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in sitting height at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Sitting Height at Week 52

Absolute change from baseline in sitting height at Week 52 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. MMRM has been calculated but did not provide estimates for this time point due to low sample size. Thus, change in sitting height from baseline to Week 52 was analyzed descriptively only.

Absolute Change From Baseline in Sitting Height at Week 76

Absolute change from baseline in sitting height at Week 76 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was take per time point. MMRM has been calculated but did not provide estimates for this time point due to low sample size. Thus, change in sitting height from baseline to Week 76 was analyzed descriptively only.

Absolute Change From Baseline in Leg Length at Week 24 - Left

Absolute change from baseline in left leg length at Week 24 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in left leg length at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Leg Length at Week 52 - Left

Absolute change from baseline in left leg length at Week 52 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in left leg length at Week 52 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Leg Length at Week 76 - Left

Absolute change from baseline in left leg length at Week 76 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in left leg length at Week 76 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Leg Length at Week 24 - Right

Absolute change from baseline in right leg length at Week 24 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in right leg length at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Leg Length at Week 52 - Right

Absolute change from baseline in right leg length at Week 52 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in right leg length at Week 52 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Leg Length at Week 76 - Right

Absolute change from baseline in right leg length at Week 76 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in right leg length at Week 76 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 24

Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. The predicted values were calculated according to the Global Lungs Initiative (GLI) 2012 equations. Absolute change from baseline in Forced Vital Capacity (FVC) % predicted at Week 24 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 52

Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. The predicted values were calculated according to the Global Lungs Initiative (GLI) 2012 equations. Absolute change from baseline in Forced Vital Capacity (FVC) % predicted at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Parent Report

The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ reported by parents was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Parent Report

Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Participant Report

The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Participant Report

The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 24

Oxygen saturation (SpO₂) was measured after minimum 5 minutes on room air by standard pulse oximetry at rest. Absolute change from baseline in SpO₂ at Week 24 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 52

Oxygen saturation (SpO₂) was measured after minimum 5 minutes on room air by standard pulse oximetry at rest. Absolute change from baseline in SpO₂ at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 24

Absolute change from baseline in 6 minutes (min) walk distance at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 52

Absolute change from baseline in 6 minutes (min) walk distance at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question

Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the capsule size was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for participants. In case the participant was considered not old enough as per investigator judgment the caregiver could assist with the completion. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules.

Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question

Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the capsule size was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for investigators. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules.

Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question

Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the number of capsule was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for participants. In case the participant was considered not old enough as per investigator judgment the caregiver could assist with the completion. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules. Medication dosage was based on the participant's body weight and number of capsules per administration ranged from 2 to >6 capsules.

Number of Participants With Occurrence of First Respiratory-related Hospitalization Over the Whole Trial

Number of participants with occurrence of first respiratory-related hospitalization over the whole trial. The number of participants with first respiratory-related hospitalization is reported instead of a metric summarizing the time-to-event data with unit of time, as the numbers resulting from the Kaplan-Meier-analysis were even below the first quartile.

Number of Participants With Occurrence of First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over the Whole Trial

Number of participants with occurrence of first acute Interstitial Lung Disease (ILD) exacerbation or death over the whole trial. The number of participants with first acute ILD exacerbation is reported instead of a metric summarizing the time-to-event data with unit of time, as the numbers resulting from the Kaplan-Meier-analysis were even below the first quartile.

Number of Participants With Occurrence of Death Over the Whole Trial

Number of participants with occurrence of death over the whole trial over the whole trial was computed. The number of participants with occurrence of death is reported instead of a metric summarizing the time-to-event data with unit of time, as the numbers resulting from the Kaplan-Meier-analysis were even below the first quartile.

Full Information

NCT ID

NCT04093024

First Posted

September 16, 2019

Last Updated

March 31, 2023

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT04093024

Brief 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)

Acronym

InPedILD®

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

December 3, 2019 (Actual)

Primary Completion Date

May 24, 2022 (Actual)

Study Completion Date

May 24, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Diseases, Interstitial

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Double-blind period (DBP) + open-label Nintedanib period (OLNP): Randomised Nintedanib

Arm Type

Experimental

Arm Description

Arm Title

DBP+OLNP: Randomised placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Nintedanib

Other Intervention Name(s)

Ofev®

Intervention Description

Capsule

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Capsule

Primary Outcome Measure Information:

Title

Area Under the Plasma Concentration-time Curve at Steady State (AUCτ,ss) Based on Sampling at Steady State (at Week 2 and Week 26)

Description

Time Frame

At Week 2 and at Week 26: at 5 minutes before and at 0, 1, 2, 3, 4, 6, and 8 hours post administration of the morning dose

Title

Number of Participants With Treatment-emergent Adverse Events During the Double-blind Period

Description

Time Frame

From first drug administration until the earlier of (i) first intake of open-label nintedanib (exclusive) and (ii) last drug intake, up to 28 weeks

Secondary Outcome Measure Information:

Title

Number of Participants With at Least One Treatment-emergent Pathological Finding of Epiphyseal Growth Plate on Imaging up to Week 24, and Week 52

Description

Time Frame

Up to Week 24 (included values at Week 12 and Week 24); Up to Week 52 (included values at Week 12, 24, 36 and 52)

Title

Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24

Description

Time Frame

Dental examination: at Week 12 and Week 24; Dental imaging: at Week 24

Title

Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52

Description

Time Frame

Dental examination: at Week 12, 24, 34, and Week 52; Dental imaging: at Week 24 and at Week 52.

Title

Number of Participants With Treatment-emergent Adverse Events Over the Whole Trial

Description

Time Frame

From first drug administration until the last drug intake, up to 92 weeks

Title

Absolute Change From Baseline in Height at Week 24

Description

Time Frame

MMRM included measurements pre-administration at -4 weeks and at 0, 12, 24, 36, 52, 64, 76, and 88 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Title

Absolute Change From Baseline in Height at Week 52

Description

Time Frame

MMRM included measurements pre-administration at -4 weeks and at 0, 12, 24, 36, 52, 64, 76, and 88 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Title

Absolute Change From Baseline in Height at Week 76

Description

Time Frame

Measurements were assessed at Week 0 and at Week 76

Title

Absolute Change From Baseline in Sitting Height at Week 24

Description

Time Frame

MMRM included measurements pre-administration at -4 weeks and at 0, 12, 24, 36, 52, 64, 76, and 88 weeks after first drug administration. MMRM values at Week 24 are reported in the table below.

Title

Absolute Change From Baseline in Sitting Height at Week 52

Description

Time Frame

Measurements were assessed at Week 0 and at Week 52

Title

Absolute Change From Baseline in Sitting Height at Week 76

Description

Time Frame

Measurements were assessed at Week 0 and at Week 76

Title

Absolute Change From Baseline in Leg Length at Week 24 - Left

Description

Time Frame

MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Title

Absolute Change From Baseline in Leg Length at Week 52 - Left

Description

Time Frame

MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Title

Absolute Change From Baseline in Leg Length at Week 76 - Left

Description

Time Frame

MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 76 are reported in the table below

Title

Absolute Change From Baseline in Leg Length at Week 24 - Right

Description

Time Frame

MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Title

Absolute Change From Baseline in Leg Length at Week 52 - Right

Description

Time Frame

MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Title

Absolute Change From Baseline in Leg Length at Week 76 - Right

Description

Time Frame

MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 76 are reported in the table below

Title

Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 24

Description

Time Frame

MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Title

Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 52

Description

Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. The predicted values were calculated according to the Global Lungs Initiative (GLI) 2012 equations. Absolute change from baseline in Forced Vital Capacity (FVC) % predicted at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Time Frame

MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Title

Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Parent Report

Description

Time Frame

MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Title

Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Parent Report

Description

Time Frame

MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Title

Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Participant Report

Description

The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Time Frame

MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Title

Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Participant Report

Description

The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.

Time Frame

MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Title

Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 24

Description

Time Frame

MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Title

Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 52

Description

Time Frame

MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Title

Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 24

Description

Time Frame

MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below

Title

Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 52

Description

Time Frame

MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below

Title

Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question

Description

Time Frame

Acceptability was assessed at Week 24

Title

Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question

Description

Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the capsule size was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for investigators. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules.

Time Frame

Acceptability was assessed at Week 24

Title

Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question

Description

Time Frame

Acceptability was assessed at Week 24

Title

Number of Participants With Occurrence of First Respiratory-related Hospitalization Over the Whole Trial

Description

Time Frame

From first drug administration until the last drug intake + 28 days residual effect period (REP), up to 92.6 weeks

Title

Number of Participants With Occurrence of First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over the Whole Trial

Description

Time Frame

From first drug administration until the last drug intake + 28 days REP, up to 92.6 weeks

Title

Number of Participants With Occurrence of Death Over the Whole Trial

Description

Time Frame

From first drug administration until the last drug intake + 28 days REP, up to 92.6 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

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).

Facility Information:

Facility Name

Children's Hospital Los Angeles

City

Los Angeles

State/Province

California

ZIP/Postal Code

90027

Country

United States

Facility Name

Children's Hospital Colorado

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Riley Hospital for Children at Indiana University Health

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Children's Mercy Hospitals and Clinics

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64108

Country

United States

Facility Name

Weill Cornell Medicine

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

Facility Name

Children's Hospital of Philadelphia

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15224

Country

United States

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

Seattle Children's Hospital

City

Seattle

State/Province

Washington

ZIP/Postal Code

98105

Country

United States

Facility Name

Hospital de Pediatría " Prof. Dr. Juan P. Garrahan"

City

Caba

ZIP/Postal Code

C1245AAM

Country

Argentina

Facility Name

Hospital de Niños Dr. Ricardo Gutierrez

City

Caba

ZIP/Postal Code

C1425EFD

Country

Argentina

Facility Name

INSARES

City

Mendoza

ZIP/Postal Code

M5500CCG

Country

Argentina

Facility Name

Women's and Children's Hospital

City

North Adelaide

State/Province

South Australia

ZIP/Postal Code

5006

Country

Australia

Facility Name

Brussels - UNIV HUDERF

City

Bruxelles

ZIP/Postal Code

1020

Country

Belgium

Facility Name

Serviços Medicos Respirar Sul Fluminense

City

Barra Mansa

ZIP/Postal Code

27323240

Country

Brazil

Facility Name

Centro de Pesquisa Clinica do Instituto da Crianca - HCFMUSP

City

Sao Paulo

ZIP/Postal Code

5403-900

Country

Brazil

Facility Name

BC Children's Hospital

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V6H 3N1

Country

Canada

Facility Name

The Hospital for Sick Children

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1X8

Country

Canada

Facility Name

Teaching Hospital Motol, Oncology Clinic

City

Praha 5

ZIP/Postal Code

150 06

Country

Czechia

Facility Name

Aarhus University Hospital

City

Aarhus N

ZIP/Postal Code

8200

Country

Denmark

Facility Name

Tampere University Hospital

City

Tampere

ZIP/Postal Code

33520

Country

Finland

Facility Name

HOP Intercommunal

City

Créteil

ZIP/Postal Code

94010

Country

France

Facility Name

HOP Armand-Trousseau

City

Paris

ZIP/Postal Code

75571

Country

France

Facility Name

General Hospital of Thessaloniki "Ippokrateio"

City

Thessaloniki

ZIP/Postal Code

54642

Country

Greece

Facility Name

Semmelweis University

City

Budapest

ZIP/Postal Code

1122

Country

Hungary

Facility Name

Azienda Ospedaliera Meyer

City

Firenze

ZIP/Postal Code

50139

Country

Italy

Facility Name

Azienda Ospedaliera Universitaria di Padova

City

Padova

ZIP/Postal Code

35128

Country

Italy

Facility Name

Osp. Pediatrico Bambin Gesù

City

Roma

ZIP/Postal Code

00165

Country

Italy

Facility Name

Clinical Research Institute S.C.

City

Tlalnepantla

ZIP/Postal Code

54055

Country

Mexico

Facility Name

Oslo Universitetssykehus HF, Rikshospitalet

City

Oslo

ZIP/Postal Code

N-0372

Country

Norway

Facility Name

Independent Public Teaching Children's Hospital

City

Warsaw

ZIP/Postal Code

02091

Country

Poland

Facility Name

CHULC, EPE - Hospital Dona Estefânia

City

Lisboa

ZIP/Postal Code

1169-045

Country

Portugal

Facility Name

Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital Santa Maria

City

Lisboa

ZIP/Postal Code

1649-035

Country

Portugal

Facility Name

Children's Hematology,Oncology&Immunology na Rogachev,Moscow

City

Moscow

ZIP/Postal Code

117198

Country

Russian Federation

Facility Name

State Novosibirsk Regional Clinical Hospital

City

Novosibirsk

ZIP/Postal Code

630087

Country

Russian Federation

Facility Name

St. Petersburg State Pediatric University

City

St. Petersburg

ZIP/Postal Code

194100

Country

Russian Federation

Facility Name

Hospital Vall d'Hebron

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Hospital Virgen del Rocío

City

Sevilla

ZIP/Postal Code

41013

Country

Spain

Facility Name

Regional Children Clinical Hospital, Pulmonology, Kharkiv

City

Kharkiv

ZIP/Postal Code

61093

Country

Ukraine

Facility Name

Institute of Phthisiology and Pulmonology n. a. F.G.Yanovsky

City

Kyiv

ZIP/Postal Code

03680

Country

Ukraine

Facility Name

Regional clinical children hospital, Zaporizhya

City

Zaporizhya

ZIP/Postal Code

69063

Country

Ukraine

Facility Name

Birmingham Children's Hospital

City

Birmingham

ZIP/Postal Code

B4 6NH

Country

United Kingdom

Facility Name

King's College Hospital

City

London

ZIP/Postal Code

SE5 9RS

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing

Citations:

PubMed Identifier

34164554

Citation

Deterding R, Griese M, Deutsch G, Warburton D, DeBoer EM, Cunningham S, Clement A, Schwerk N, Flaherty KR, Brown KK, Voss F, Schmid U, Schlenker-Herceg R, Verri D, Dumistracel M, Schiwek M, Stowasser S, Tetzlaff K, Clerisme-Beaty E, Young LR. Study design of a randomised, placebo-controlled trial of nintedanib in children and adolescents with fibrosing interstitial lung disease. ERJ Open Res. 2021 Jun 21;7(2):00805-2020. doi: 10.1183/23120541.00805-2020. eCollection 2021 Apr.

Results Reference

derived

Links:

URL

https://www.mystudywindow.com

Description

Related Info

Learn more about this trial

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)

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