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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).

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ClinicalTrials.gov Identifier: NCT04093024
Recruitment Status : Recruiting
First Posted : September 17, 2019
Last Update Posted : September 13, 2021
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE September 16, 2019
First Posted Date  ICMJE September 17, 2019
Last Update Posted Date September 13, 2021
Actual Study Start Date  ICMJE December 3, 2019
Estimated Primary Completion Date January 28, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 16, 2019)
  • 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: Week 2 and Week 26 ]
  • N (%) of patients with treatment-emergent adverse events at week 24 [ Time Frame: Week 24 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2020)
  • N (%) of patients with treatment-emergent pathological findings of epiphyseal growth plate on imaging at week 24, and week 52 [ Time Frame: Week 24 and Week 52 ]
  • N (%) of patients with treatment-emergent pathological findings on dental examination or imaging at week 24, and week 52 [ Time Frame: Week 24 and Week 52 ]
  • N (%) of patients with treatment-emergent adverse events over the whole trial [ Time Frame: Up to 29 months ]
  • Change in height from baseline at week 24, week 52, week 76, and week 100 [ Time Frame: Baseline, Week 24, Week 52, weeky 76, and week 100 ]
  • Change in Forced Vital Capacity (FVC) % predicted from baseline at week 24, and week 52 [ Time Frame: Baseline, Week 24 and Week 52 ]
  • Absolute change from baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at week 24, and week 52 [ Time Frame: Baseline, Week 24 and Week 52 ]
  • Change in oxygen saturation (SpO2) on room air at rest from baseline at week 24, and week 52 [ Time Frame: Baseline, Week 24 and Week 52 ]
  • Change in 6-min walk distance from baseline at week 24, and week 52 [ Time Frame: Baseline, Week 24 and Week 52 ]
  • Patient acceptability based on the size of capsules at week 24 [ Time Frame: Week 24 ]
  • Patient acceptability based on the number of capsules at week 24 [ Time Frame: Week 24 ]
  • Time to first respiratory-related hospitalization over the whole trial [ Time Frame: Up to 29 months ]
  • Time to first acute Interstitial Lung Disease (ILD) exacerbation or death over the whole trial [ Time Frame: Up to 29 months ]
  • Time to death over the whole trial [ Time Frame: Up to 29 months ]
  • Change in sitting height from baseline at week 24, week 52, week 76, and week 100 [ Time Frame: Baseline, Week 24, Week 52, Week 76, and Week 100 ]
  • Change in leg length from baseline at week 24, week 52, week 76, and week 100 [ Time Frame: Baseline, Week 24, Week 52, Week 76, and Week 100 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 16, 2019)
  • N (%) of patients with treatment-emergent pathological findings of epiphyseal growth plate on imaging at week 24, and week 52 [ Time Frame: Week 24 and Week 52 ]
  • N (%) of patients with treatment-emergent pathological findings on dental examination or imaging at week 24, and week 52 [ Time Frame: Week 24 and Week 52 ]
  • N (%) of patients with treatment-emergent adverse events over the whole trial [ Time Frame: Up to 29 months ]
  • Change in height, sitting height, leg length from baseline at week 24 and week 52 [ Time Frame: Baseline, Week 24 and Week 52 ]
  • Change in Forced Vital Capacity (FVC) % predicted from baseline at week 24, and week 52 [ Time Frame: Baseline, Week 24 and Week 52 ]
  • Absolute change from baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at week 24, and week 52 [ Time Frame: Baseline, Week 24 and Week 52 ]
  • Change in oxygen saturation (SpO2) on room air at rest from baseline at week 24, and week 52 [ Time Frame: Baseline, Week 24 and Week 52 ]
  • Change in 6-min walk distance from baseline at week 24, and week 52 [ Time Frame: Baseline, Week 24 and Week 52 ]
  • Patient acceptability based on the size of capsules at week 24 [ Time Frame: Week 24 ]
  • Patient acceptability based on the number of capsules at week 24 [ Time Frame: Week 24 ]
  • Time to first respiratory-related hospitalization over the whole trial [ Time Frame: Up to 29 months ]
  • Time to first acute Interstitial Lung Disease (ILD) exacerbation or death over the whole trial [ Time Frame: Up to 29 months ]
  • Time to death over the whole trial [ Time Frame: Up to 29 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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).
Official Title  ICMJE 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.
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Lung Diseases, Interstitial
Intervention  ICMJE
  • Drug: Nintedanib (Ofev®)
    Capsule
  • Drug: Placebo
    Capsule
Study Arms  ICMJE
  • Experimental: Nintedanib (Ofev®)
    Intervention: Drug: Nintedanib (Ofev®)
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * 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). pii: 00805-2020. doi: 10.1183/23120541.00805-2020. eCollection 2021 Apr.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 16, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2022
Estimated Primary Completion Date January 28, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Boehringer Ingelheim 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Canada,   Czechia,   Denmark,   Finland,   France,   Germany,   Greece,   Hungary,   Italy,   Mexico,   Netherlands,   Norway,   Poland,   Portugal,   Russian Federation,   Spain,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04093024
Other Study ID Numbers  ICMJE 1199-0337
2018-004530-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
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:

  1. studies in products where Boehringer Ingelheim is not the license holder;
  2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
  3. 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

Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Boehringer Ingelheim
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP