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.

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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.

Funding

This study has been funded by The Efficacy and Mechanism Evaluation (EME) Programme (an MRC and NIHR partnership), NHS England and Cure EB.

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

Study Team

Please contact us on our central team email address: missioneb@sheffield.ac.uk

Name

Role

Organisation

Contact

Dr Anna Martinez

Chief Investigator 

Great Ormond Street Hospital

anna.martinez@gosh.nhs.uk

Dr Gabriela Petrof

Co- Investigator and Co-applicant 

Great Ormond Street Hospital

gabriela.petrof@gosh.nhs.uk

Professor John A McGrath

Co-applicant 

King’s College London

john.mcgrath@kcl.ac.uk

Professor Francesco Dazzi

Co-applicant

King’s College London

francesco.dazzi@kcl.ac.uk

Malobi Ogboli

Principal Investigator and Co-applicant

Birmingham Children’s Hospital

malobi.ogboli@nhs.net

Marie-Louise Lovgren

Principal Investigator and Co-applicant

Birmingham Children’s Hospital

marie-louise.lovgren@nhs.net

Professor Cindy Cooper

Director, Clinical Trials Research Unit and Co-applicant 

Clinical Trials Research Unit,
The University of Sheffield

c.cooper@sheffield.ac.uk

Diana Papaioannou

CTRU Assistant Director and Co-applicant 

Clinical Trials Research Unit,
The University of Sheffield

d.papaioannou@sheffield.ac.uk

Professor Steven Julious

Professor of Medical Statistics and Co-applicant 

Clinical Trials Research Unit,
The University of Sheffield

s.a.julious@sheffield.ac.uk

Katie Biggs

Co-applicant 

Clinical Trials Research Unit,
The University of Sheffield

c.e.biggs@sheffield.ac.uk

Dr Munya Dimairo

Statistician and Co-applicant 

Clinical Trials Research Unit,
The University of Sheffield

m.dimairo@sheffield.ac.uk

Professor Paul Tappenden

Professor of Health Economic Modelling and Co-applicant 

Health Economics and Decision Science,
The University of Sheffield

p.tappenden@sheffield.ac.uk

Rachel Glover

Trial Manager 

Clinical Trials Research Unit,
The University of Sheffield

r.e.glover@sheffield.ac.uk

Louise Turner

Trial Support Officer

Clinical Trials Research Unit,
The University of Sheffield

louise.turner@sheffield.ac.uk

Simon Waterhouse

Lead Data Specialist

Clinical Trials Research Unit,
The University of Sheffield

s.waterhouse@sheffield.ac.uk

Emily Turton

Data Specialist

Clinical Trials Research Unit,
The University of Sheffield

e.j.turton@sheffield.ac.uk

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