TY - JOUR T1 - Study design of a randomised, placebo-controlled trial of nintedanib in children and adolescents with fibrosing interstitial lung disease JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00805-2020 SP - 00805-2020 AU - Robin Deterding AU - Matthias Griese AU - Gail Deutsch AU - David Warburton AU - Emily M. DeBoer AU - Steven Cunningham AU - Annick Clement AU - Nicolaus Schwerk AU - Kevin R. Flaherty AU - Kevin K. Brown AU - Florian Voss AU - Ulrike Schmid AU - Rozsa Schlenker-Herceg AU - Daniela Verri AU - Mihaela Dumistracel AU - Marilisa Schiwek AU - Susanne Stowasser AU - Kay Tetzlaff AU - Emmanuelle Clerisme-Beaty AU - Lisa R. Young Y1 - 2021/01/01 UR - http://openres.ersjournals.com/content/early/2021/02/04/23120541.00805-2020.abstract N2 - Introduction Childhood interstitial lung disease (chILD) comprises >200 rare respiratory disorders, with no currently approved therapies and variable prognosis. Nintedanib reduces the rate of forced vital capacity (FVC) decline in adults with progressive fibrosing ILDs. We present the design of a multicentre, prospective, double-blind, randomised, placebo-controlled clinical trial of nintedanib in patients with fibrosing chILD (1199-0337 or InPedILD™; ClinicalTrials.gov: NCT04093024).Methods and analysis Male or female children and adolescents aged 6–17 years (≥30; including ≥20 adolescents aged 12–17 years) with clinically significant fibrosing ILD will be randomised 2:1 to receive oral nintedanib or placebo on top of standard of care for 24 weeks (double-blind), followed by variable duration nintedanib (open-label). Nintedanib dosing will be based on body weight-dependent allometric scaling, with single-step dose reductions permitted to manage adverse events. Eligible patients will have evidence of fibrosis on high-resolution computed tomography (within 12 months of their first screening visit), FVC ≥25% predicted, and clinically significant disease (Fan score of ≥3 or evidence of clinical progression over time). Patients with underlying chronic liver disease, significant pulmonary arterial hypertension, cardiovascular disease, or increased bleeding risk are ineligible. The primary endpoints are pharmacokinetics and the proportion of patients with treatment-emergent adverse events at Week 24. Secondary endpoints include change in FVC% predicted from baseline, Pediatric Quality of Life Questionnaire™, oxygen saturation, and 6-minute walk distance at Weeks 24 and 52. Additional efficacy and safety endpoints will be collected to explore long-term effects. #PedILD. #InPedILD.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of Interest: R. Deterding reports scientific advisory and consulting fees paid to the University of Colorado, and manuscript preparation assistance from Boehringer Ingelheim Pharmaceuticals Inc., during the conduct of the study.Conflict of Interest: Dr. Griese reports personal fees from Böhringer-Ingelheim, during the conduct of the study; grants from Böhringer-Ingelheim, outside the submitted work.Conflict of Interest: G. Deutsch reports consulting fees paid to Seattle Children's Hospital by Boehringer Ingelheim during the conduct of the study.Conflict of Interest: I serve in an advisory role for Boehringer Ingelheim on the evaluation of Nintedanib as a potential treatment for chILD and have received reimbursement for travel and consultation in this role.Conflict of Interest: E.M. DeBoer reports consulting fees from Boehringer Ingelheim and Parexel, and consulting fees from and stock in EvoEndoscopy, outside the submitted work.Conflict of Interest: S. Cunningham reports consultancy fees paid to the University of Edinburgh by Boehringer Ingelheim during the conduct of the study.Conflict of Interest: Dr. clement has nothing to disclose.Conflict of Interest: N. Schwerk reports consulting fees from Boehringer Ingelheim outside the submitted work.Conflict of Interest: Dr. Flaherty reports grants and personal fees from Boehringer Ingelheim, personal fees from Roche/Genentedch, personal fees from Bellerophan, personal fees from Respivant, personal fees from Blade Therapeutics, outside the submitted work.Conflict of Interest: Dr. Brown reports the following outside the submitted work: grants from NIH, and advisory board participation for the following Biogen, Blade, Boehringer Ingelheim, Galapagos, Galecto, Genoa, Lifemax, MedImmune, OSIC (Open Source Imaging Consortium), Pliant, ProMetic, Third Pole, Theravance, Three Lakes Partners, Veracyte.Conflict of Interest: F. Voß is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG.Conflict of Interest: Dr. Schmid is an employee of Boehringer IngelheimConflict of Interest: R. Schlenker-Herceg is an employee of Boehringer Ingelheim.Conflict of Interest: D. Verri is an employee of Boehringer Ingelheim Italia SpA.Conflict of Interest: M. Dumistracel is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG.Conflict of Interest: M. Schiwek is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG.Conflict of Interest: Dr. Stowasser reports being an employee of Boehringer Ingelheim International GmbH, the manufacturer of nintedanib.Conflict of Interest: K. Tetzlaff is an employee of Boehringer Ingelheim International GmbH.Conflict of Interest: Dr. Clerisme-Beaty reports being a paid employee of Boehringer Ingelheim, during the conduct of the study.Conflict of Interest: Dr. Young reports other from Boehringer Ingelheim, personal fees from Boehringer Ingelheim, grants from NIH, during the conduct of the study. ER -