MissionEB

Double blinded placebo control study of Mesenchymal Intravenous Stromal cell Infusions in children with recessive dystrophic Epidermolysis Bullosa. This trial is being carried out in collaboration with Dr Anna Martinez, Chief Investigator based at Great Ormond Street Hospital.

Background

Epidermolysis Bullosa (EB) is a heterogeneous group of inherited skin disorders which affects 1 in 17,000 live births and around half a million worldwide. Recessive dystrophic EB (RDEB), a severe subtype, is caused by mutations in the type VII collagen gene leading to reduced or absent type VII collagen. This results in skin blistering following minor mechanical trauma, leading to chronic erosions and extensive scars and contractures. There is no effective treatment for RDEB and management is supportive. It has a significant physical, emotional and socio-economic impact for patients and their families. Best practice treatment involves a multidisciplinary healthcare team, with daily dressings taking up to 4 hours. The average annual cost per child has been estimated at £40,000¹.

Mesenchymal stromal cells (MSCs) have been delivered intravenously to 10 children with RDEB in a clinical trial. Nine children went on to have two further infusions. The cells were 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 potentially be more effective.

¹ Angelis A, Kanavos P, López-Bastida J, Linertová R, Oliva-Moreno J, Serrano-Aguilar P, Posada-de-la-Paz M, Taruscio D, Schieppati A, Iskrov G, Brodszky V, von der Schulenburg JM, Chevreul K, Persson U, Fattore G; BURQOL-RD Research Network. Social/economic costs and health-related quality of life in patients with epidermolysis bullosa in Europe. Eur J Health Econ. 2016 Apr;17 Suppl 1(Suppl 1):31-42. doi: 10.1007/s10198-016-0783-4. Epub 2016 Apr 23. PMID: 27107597; PMCID: PMC4869727.

The MissionEB Trial

The MissionEB trial aims to assess if repeated infusions of UC-MSCs are safe and can benefit children with RDEB.

Objectives:

To assess the:

efficacy of repeated MSCs in improving disease severity, quality of life and symptoms (e.g. pain and itch reduction) in children with RDEB.
safety of repeated infusions of MSCs in this group.
costs and consequences of treatment with UC-MSCs versus usual care
To explore patients and parents views in relation to treatment effectiveness and acceptability.

Methods: 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 (DMEC). 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 (BCH), that both specialise in paediatric dermatology and are Nationally Commissioned centres for paediatric EB.

Timeline: 53m study; 8m set-up, 8m recruitment with 3m internal phase 1 de-escalation study; 15m follow-up, 12m open label study and 6m close-out, data analysis and write-up. (The length of the study will be 58 months in the event that the dose needs to be de-escalated, as the phase 1 study will be repeated at a lower dose).

Patient & Public Involvement

Patient support groups, DEBRA UK & Cure EB, patients/parents and the GOSH Young Person’s Advisory Group will input into the study materials and in sharing the results.

The MissionEB trial recently featured in the GOSH BRC Patient and Public Involvement Impact Case Studies 2020-21 which can be found here.

Funding

This study has been funded by The National Research Collaboration Programme (NIHR127963), an NHS England and NHS Improvement and National Institute for Health Research partnership. Additional funds were provided by the charity CureEB.

Sponsor

Great Ormond Street Hospital for Children NHS Foundation Trust.

Participating Sites

Site	Principal Investigator(s)	Contact Details
Great Ormond Street Hospital	Dr Anna Martinez Consultant Paediatric Dermatologist	anna.martinez@gosh.nhs.uk
Great Ormond Street Hospital	Dr Gabriela Petrof Consultant Paediatric Dermatologist	gabriela.petrof@gosh.nhs.uk
Birmingham Children’s Hospital	Dr Malobi Ogboli Consultant Dermatologist	malobi.ogboli@nhs.net
Birmingham Children’s Hospital	Dr Marie-Louise Lovgren Consultant Dermatologist	marie-louise.lovgren@nhs.net