Double blind placebo controlled study of mesenchymal intravenous stromal cell infusions in children with Recessive Dystrophic Epidermolysis Bullosa
Lay summary
Mesenchymal stromal cells (MSCs) are adult stem cells isolated from umbilical cord blood, bone marrow and other sources. MSCs can transform into other types of cells including skin and corneal cells.
In a previous study (EBSTEM), three doses of MSCs were delivered by a small plastic tube inserted into a vein (intravenous infusion) in ten children with RDEB. The MSCs were found to be safe and children reported reduced pain and itching. The beneficial effects lasted from 3-6 months.
The MSCs in EBSTEM were derived from bone marrow but there is evidence that MSCs derived from umbilical cord tissue (UC-MSCs) could be more effective.
Mission EB will give repeated intravenous infusions of UC-MSCs to see if they improve the skin disease and reduce pain and itching. Comparison will be made with children receiving infusions without the cells (placebo). If the cells are shown to be helpful, the aim is to introduce this cell therapy as part of routine clinical care for these children across England.
Scientific Summary
In a previous clinical trial, mesenchymal stromal cells (MSCs) were delivered intravenously to 10 children with RDEB in a clinical trial (EBSTEM) and found to improve wound quality, reduce skin itching and pain with no significant side effects. The beneficial effects lasted for 3-6 months. These cells were derived from bone marrow but there is evidence that MSCs derived from umbilical cord tissue (UC-MSCs) could be more effective.
Mission EB will assess if repeated infusions of UC-MSCs are safe and effective in children with severe RDEB.
This is a randomised, placebo controlled, double blinded, crossover trial with an internal phase 1 dose de-escalation trial in the first 3 months and a 12 month continued treatment follow-on open-label study following review of the data. The internal phase 1 dose de-escalation trial is for safety gatekeeping of the proposed dose, with the option of halving the dose if recommended by the data monitoring and ethics committee.
The open label non-randomised study will go ahead if the treatment is found to be effective during the randomised crossover trial. The trial will be conducted at two sites, Great Ormond Street Hospital (GOSH) and Birmingham Children’s Hospital.
