568 - Helping Underdeveloped Lungs with Cells (HULC): Mesenchymal Stromal Cells in Extreme Preterm Infants at Risk of Developing Bronchopulmonary Dysplasia – A Phase 1 Study
Sunday, April 27, 2025
8:30am – 10:45am HST
Publication Number: 568.5401
Bernard Thébaud, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Brigitte Lemyre, University of Ottawa Faculty of Medicine, Ottawa, ON, Canada; Emanuela E. Ferretti, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada; Nadya M. Ben Fadel, University of Ottawa, Ottawa, ON, Canada; Laurent Renesme, children's hospital of eastern ontario, Ottawa, ON, Canada; Maher Shahroor, Sunnybrook Health Sciences Center, Toronto, ON, Canada; Michael S. Dunn, University of Toronto Temerty Faculty of Medicine, Toronto, ON, Canada; Elizabeth Asztalos, University of Toronto Temerty Faculty of Medicine, Toronto, ON, Canada; Saad Khan, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Samantha Hodgins, Ottawa Hospital Research Institute, Ottawa, ON, Canada; David Courtman, University of Ottawa Faculty of Medicine, Ottawa, ON, Canada; Marius A.. Möbius, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Sachsen, Germany; Daniel Freund, Center for Regenerative Therapies TU Dresden, Dresden, Sachsen, Germany; Mario Rüdiger, TU Dresden, Medical Faculty, Saxonian Center for feto/neonatal Health, SaxoCell, Dresden, Sachsen, Germany; Dean Fergusson, Ottawa Hospital Research Institute, Ottawa, ON, Canada
Neonatologist University of Ottawa Faculty of Medicine Ottawa, Ontario, Canada
Background: Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity. BPD accounts for life-long morbidity and lacks effective treatment. Preclinical data suggesting lung protective effects of human umbilical cord (UC)-derived mesenchymal stromal cell (MSC) provide the rationale for the clinical translation of UC-MSCs for BPD. Objective: This Phase I, open-label, multicenter, dose-escalation trial assessed the safety and feasibility of a single, intravenous (i.v.) injection of allogeneic human UC-MSCs in preterm infants at high risk of developing BPD. Design/Methods: Patients were included if they were born < 28 weeks gestation, still intubated and on mechanical ventilation with FiO2 30% or higher between postnatal day 7-28. The first three patients received low dose 1.0x106 UC-MSC/kg, the next three patients received intermediate dose (3.0x106 UC-MSCs/kg), and the final three patients received high dose (10x106 UC-MSCs/kg). Primary outcomes included the incidence of prespecified infusion-associated events and serious adverse events. The trial is registered with ClinicalTrials.gov (NCT04255147). Results: Nine preterm infants were enrolled between Oct 13, 2022 and Nov 6, 2023. The mean gestational age was 24.5±1.3 weeks and the mean birth weight 647±131g. UC-MSC were administered at a mean of 19.3±6.1 days after birth. No prespecified infusion-associated events or treatment-related adverse events were reported. There were no deaths. In the low dose group, all 3 patients had severe BPD (FiO2>30% or positive pressure at 36 weeks corrected) and were discharged home on oxygen. In the highest dosing group, no patient had severe BPD and only one was discharged home on oxygen. The following complications associated with prematurity were observed in the 9 patients: patent ductus arteriosus (n=3), necrotizing enterocolitis (n=1), severe retinopathy of prematurity (stage 3 or higher, n=2), intraventricular hemorrhage grade 1-2 (n=3), late-onset sepsis (n=5).
Conclusion(s): A single i.v. infusion of allogeneic UC-MSCs was well tolerated in nine extreme preterm infants at high risk of developing BPD. A phase 2 randomized trial is warranted to test the efficacy and safety of 10x106 UC-MSC/kg in a larger patient population.
