Lung Diseases, InterstitialPhase 3InPedILD®NCT04093024
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)
A Phase 3 study testing Nintedanib in people with Lung Diseases, Interstitial, run by Boehringer Ingelheim at 43 sites in 21 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Lung Diseases, Interstitial
- What is being tested?
- Nintedanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 43 sitesin 21 countries
- Study dates
- 3 Dec 2019to 24 May 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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:
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- 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).
Who cannot join
- 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.
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- 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).
Trial locations and contacts
43 sites in 21 countries.
43 sites in 21 countries
United States9 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Children's Hospital Los Angeles
Los Angeles, California, 90027
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Weill Cornell Medicine
New York, New York, 10021
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15224
Seattle Children's Hospital
Seattle, Washington, 98105
Argentina3 sites
Hospital de Pediatría " Prof. Dr. Juan P. Garrahan"
CABA, C1245AAM
Hospital de Niños Dr. Ricardo Gutierrez
CABA, C1425EFD
INSARES
Mendoza, M5500CCG
Italy3 sites
Azienda Ospedaliera Meyer
Florence, 50139
Azienda Ospedaliera Universitaria di Padova
Padova, 35128
Osp. Pediatrico Bambin Gesù
Roma, 00165
Russia3 sites
Children's Hematology,Oncology&Immunology na Rogachev,Moscow
Moscow, 117198
State Novosibirsk Regional Clinical Hospital
Novosibirsk, 630087
St. Petersburg State Pediatric University
Saint Petersburg, 194100
Ukraine3 sites
Regional Children Clinical Hospital, Pulmonology, Kharkiv
Kharkiv, 61093
Institute of Phthisiology and Pulmonology n. a. F.G.Yanovsky
Kyiv, 03680
Regional clinical children hospital, Zaporizhya
Zaporizhya, 69063
Brazil2 sites
Serviços Medicos Respirar Sul Fluminense
Barra Mansa, 27323240
Centro de Pesquisa Clinica do Instituto da Crianca - HCFMUSP
São Paulo, 5403-900
Canada2 sites
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
BC Children's Hospital
Vancouver, British Columbia, V6H 3N1
France2 sites
HOP Intercommunal
Créteil, 94010
HOP Armand-Trousseau
Paris, 75571
Portugal2 sites
CHULC, EPE - Hospital Dona Estefânia
Lisbon, 1169-045
Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital Santa Maria
Lisbon, 1649-035
Spain2 sites
Hospital Vall d'Hebron
Barcelona, 08035
Hospital Virgen del Rocío
Seville, 41013
United Kingdom2 sites
Birmingham Children's Hospital
Birmingham, B4 6NH
King's College Hospital
London, SE5 9RS
Australia1 site
Women's and Children's Hospital
North Adelaide, South Australia, 5006
Greece1 site
General Hospital of Thessaloniki "Ippokrateio"
Thessaloniki, 54642
About this study
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
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).
- Conditions
- Lung Diseases, Interstitial
- Being tested
- Nintedanib, Placebo
- Medical subject headings
- Lung Diseases, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NintedanibDrug
Also called Ofev®
Capsule
PlaceboDrug
Capsule
| Study group | Role | What they receive |
|---|---|---|
| Double-blind period (DBP) + open-label Nintedanib period (OLNP): Randomised Nintedanib | Experimental | 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. Receives: Drug: Nintedanib |
| DBP+OLNP: Randomised placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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 outcomes (32)
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.
Measured: 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)
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.
Measured: Dental examination: at Week 12 and Week 24; Dental imaging: at Week 24
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 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.
Measured: Dental examination: at Week 12, 24, 34, and Week 52; Dental imaging: at Week 24 and at 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.
Measured: From first drug administration until the last drug intake, up to 92 weeks
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.
Measured: 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
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.
Measured: 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
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.
Measured: Measurements were assessed at Week 0 and at Week 76
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.
Measured: 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.
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.
Measured: Measurements were assessed at Week 0 and at Week 52
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.
Measured: Measurements were assessed at Week 0 and at Week 76
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below
Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - 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.
Measured: MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below
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.
Measured: MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below
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.
Measured: MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below
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.
Measured: 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
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.
Measured: 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
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.
Measured: MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below
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.
Measured: MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below
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.
Measured: Acceptability was assessed at Week 24
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.
Measured: Acceptability was assessed at Week 24
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.
Measured: Acceptability was assessed at Week 24
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.
Measured: From first drug administration until the last drug intake + 28 days residual effect period (REP), up to 92.6 weeks
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.
Measured: From first drug administration until the last drug intake + 28 days REP, up to 92.6 weeks
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.
Measured: From first drug administration until the last drug intake + 28 days REP, up to 92.6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2019
- Study start3 Dec 2019
- Primary completion24 May 2022
- Study completion24 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lung Diseases, InterstitialStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04093024
- Sponsor's protocol ID
- 1199-0337
- Other IDs
- 2018-004530-14, 2018
- Acronym
- InPedILD®
- Status last verified
- Jun 2024
- First submitted
- 16 Sep 2019
- Last updated
- 9 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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. Exceptions might apply, e.g. 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 (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency
Publications
Deterding R, Young LR, DeBoer EM, Warburton D, Cunningham S, Schwerk N, Flaherty KR, Brown KK, Dumistracel M, Erhardt E, Bertulis J, Gahlemann M, Stowasser S, Griese M; InPedILD trial investigators. Nintedanib in children and adolescents with fibrosing interstitial lung diseases. Eur Respir J. 2023 Feb 2;61(2):2201512. doi: 10.1183/13993003.01512-2022. Print 2023 Feb.
PubMed 36041751Deterding 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.
PubMed 34164554
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04093024
- Acronym / sponsor ID
- InPedILD® / 1199-0337
- Conditions
- Lung Diseases, Interstitial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 3 Dec 2019 (actual)
- Primary completion
- 24 May 2022 (actual)
- Study completion
- 24 May 2022 (actual)
- First posted
- 17 Sep 2019 (actual)
- Results
- Posted 31 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Double-blind period (DBP) + open-label Nintedanib period (OLNP): Randomised Nintedanib | Experimental | Drug: NintedanibThis 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. |
| DBP+OLNP: Randomised placebo | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- 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)]
Key exclusion criteria (40 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NintedanibAlso: Ofev®Capsule | Drug | Double-blind period (DBP) + open-label Nintedanib period (OLNP): Randomised Nintedanib |
| PlaceboCapsule | Drug | DBP+OLNP: Randomised placebo |
Primary outcome
Area Under the Plasma Concentration-time Curve at Steady State (AUCτ,ss) Based on Sampling at Steady State (at Week 2 and Week 26)
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
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
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
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.
32 secondary outcomes
Number of Participants With at Least One Treatment-emergent Pathological Finding of Epiphyseal Growth Plate on Imaging up to Week 24, and Week 52
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)
Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24
Time frame: Dental examination: at Week 12 and Week 24; Dental imaging: at Week 24
Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52
Time frame: Dental examination: at Week 12, 24, 34, and Week 52; Dental imaging: at Week 24 and at Week 52.
Number of Participants With Treatment-emergent Adverse Events Over the Whole Trial
Time frame: From first drug administration until the last drug intake, up to 92 weeks
Absolute Change From Baseline in Height at Week 24
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
Absolute Change From Baseline in Height at Week 52
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
Absolute Change From Baseline in Height at Week 76
Time frame: Measurements were assessed at Week 0 and at Week 76
Absolute Change From Baseline in Sitting Height at Week 24
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.
Absolute Change From Baseline in Sitting Height at Week 52
Time frame: Measurements were assessed at Week 0 and at Week 52
Absolute Change From Baseline in Sitting Height at Week 76
Time frame: Measurements were assessed at Week 0 and at Week 76
Absolute Change From Baseline in Leg Length at Week 24 - Left
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
Absolute Change From Baseline in Leg Length at Week 52 - Left
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
Absolute Change From Baseline in Leg Length at Week 76 - Left
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
Absolute Change From Baseline in Leg Length at Week 24 - Right
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
Absolute Change From Baseline in Leg Length at Week 52 - Right
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
Absolute Change From Baseline in Leg Length at Week 76 - Right
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
Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 24
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
Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 52
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
Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Parent Report
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
Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Parent Report
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
Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Participant Report
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
Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Participant Report
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
Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 24
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
Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 52
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
Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 24
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
Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 52
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
Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question
Time frame: Acceptability was assessed at Week 24
Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question
Time frame: Acceptability was assessed at Week 24
Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question
Time frame: Acceptability was assessed at Week 24
Number of Participants With Occurrence of First Respiratory-related Hospitalization Over the Whole Trial
Time frame: From first drug administration until the last drug intake + 28 days residual effect period (REP), up to 92.6 weeks
Number of Participants With Occurrence of First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over the Whole Trial
Time frame: From first drug administration until the last drug intake + 28 days REP, up to 92.6 weeks
Number of Participants With Occurrence of Death Over the Whole Trial
Time frame: From first drug administration until the last drug intake + 28 days REP, up to 92.6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36041751Deterding R, Young LR, DeBoer EM, Warburton D, Cunningham S, Schwerk N, Flaherty KR, Brown KK, Dumistracel M, Erhardt E, Bertulis J, Gahlemann M, Stowasser S, Griese M; InPedILD trial investigators. Nintedanib in children and adolescents with fibrosing interstitial lung diseases. Eur Respir J. 2023 Feb 2;61(2):2201512. doi: 10.1183/13993003.01512-2022. Print 2023 Feb.
- Derived from this study: PubMed 34164554Deterding 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No. 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. Exceptions might apply, e.g. 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 (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
43 sites in 21 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nintedanib in people with Lung Diseases, Interstitial, run by Boehringer Ingelheim at 43 sites in 21 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in United States, Argentina, Italy, Russia, Ukraine and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Plasma Concentration-time Curve at Steady State (AUCτ,ss) Based on Sampling at Steady State (at Week 2 and Week 26) (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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04093024, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2024.