MSC EVs in Dystrophic Epidermolysis Bullosa

STUDY DESIGN: This is a prospective, open label, randomized, multi-center study, with intra-subject paired wound standard of care control, intended to assess the safety and preliminary efficacy of administering EVs derived from allogeneic MSCs to 10-50 cm2 wounds in RDEB subjects with wounds persisting for at least four weeks.

After providing written informed consent (assent with parental written consent for pediatric subjects) and undergoing screening evaluations, eligible subjects have a single set of paired wounds identified that are determined by either subject/caregiver reporting, medical history or other reliable sources to have been present for a minimum of four weeks. One of each pair is randomized to treatment with EVs in conjunction with standard of care. The other wound of each pair receives standard of care alone, without EV treatment. All wounds on study continue to receive standard of care throughout the study. For the EV treated wounds, up to six administrations of EVs occur approximately two weeks apart over a period of 10 weeks. If the treated wound closes prior to six administrations, no additional doses are given unless the wound reopens during the treatment period, in which case the original retreatment schedule resumes but is not extended. Subjects with wound closure identified at one of the treatment visits should return for all subsequent visits to verify wound closure and assess the scar quality of the wound, unless the closure is identified at the final study visit, in which case no additional visits are required.

Wound closure is determined by complete re-epithelialization that is not subject to re-injury during dressing changes or as a result of normal daily activities (e.g., wearing clothing, eating, sleeping). This is confirmed by the investigator at least two weeks after initial closure (unless closure is identified at the final study visit). At the conclusion of the 10-weektreatment period, the wounds are followed every 4 weeks for a period of 12 weeks. At no time during the study does closure status of the control wound influence the EV treatment or visit schedule.

STUDY OBJECTIVES:

Primary Objectives:

Determine the safety of applying multiple administrations of EVs derived from allogeneic MSCs to 10-50 cm2 RDEB wounds that have persisted for at least four weeks

Determine if EVs plus standard of care can promote wound healing in RDEB subjects compared to standard of care alone control