Mesenchymal stromal cells infusions in children with recessive dystrophic epidermolysis bullosa (MissionEB): a randomized controlled trial

Abstract Recessive dystrophic epidermolysis bullosa (RDEB) is one of the most severe forms of epidermolysis bullosa caused by loss-of-function mutations in the type VII collagen gene (COL7A1) leading to extensive skin and mucosal fragility and systemic complications. No active treatment is currently available. This study assesses whether repeated infusions of allogeneic umbilical cord-derived mesenchymal stromal cells are safe and can benefit children with RDEB. This is a double-blinded, randomized (1 : 1), placebo-controlled crossover trial with an internal dose de-escalation trial for safety and a further 12-month open-label study following review of the data. Around 36 participants with RDEB who are older than 6 months and younger than 16 years are being recruited at Great Ormond Street Hospital and Birmingham Children's Hospital. Participants will receive two intravenous infusions (days 0 and 14), at a dose of 2–3 × 106 cells kg–1 that could be adjusted to 1–1.5 × 106 cells kg–1 based on observed toxicities. Outcomes assessed at 3 and 6 months from day 0 in each crossover period include changes in EBDASI, iscorEB, pain, itch and quality of life scores. This is the largest cell-therapy study in children with RDEB. Previous nonrandomized trials have suggested that intravenous mesenchymal stromal cells are safe in children with RDEB and indicated early evidence of benefit. There was a need for a robust controlled study to validate these findings. The study is funded by the National Research Collaboration Programme (NIHR127963), an NHS England and NHS Improvement and National Institute for Health Research partnership, and Cure EB. ISRCTN registry (ISRCTN14409785).