Condition category
Skin and Connective Tissue Diseases
Date applied
11/06/2012
Date assigned
08/08/2012
Last edited
20/01/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims:
Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a severe inherited skin disease caused by lack of collagen VII - the protein that 'sticks' the top and bottom layer of the skin together. It is a severe condition leading to skin fragility, blisters and wounds which are slow to heal or leave non-healing open wounds. There is desperate need to develop new treatments for RDEB and attempts are being made to develop clinical trials using different types of therapies. This current research project aims to find out if using a particular type of cell is safe to use and can improve the skin disease in this genetic disease.

Who can participate?
Children with a diagnosis of RDEB, aged 1 to 17 years.

What does the study involve?
The study will consist of a total of 7 visits. The first visit will consist of a screening consultation with a study doctors, during the one the study will be thoroughly explained and questions answered. If the parent and child decide to participate, an informed consent form will be signed. Six further visits will be scheduled after this, during which different procedures will be carried out: cell infusions, blood tests and skin biopsies. Also, various assessments of the wounds, pain and quality of life will be done using different scoring systems.

What are the possible benefits and risks of participating?
If the treatment works, the skin disease may become milder with fewer blisters and wounds that hopefully heal faster. However, we don't know how long the effects will last. We will follow the child in the context of the clinical trial for 6 months and then continue to collect information about the skin disease during the routine clinical appointments for up to 1 year. If the cell treatment proves safe and study participants benefit from it, there will be the possibility to administer further cell treatments. We also hope that the information we gather from this clinical trial will contribute to future studies for therapies of individuals with RDEB. Mesenchymal Stem Cells (MSCs) have been used in clinical trials for other medical conditions with no severe side effects recorded and recent studies in using MSCs for children with RDEB in other countries have reported no serious adverse reactions. Although not expected, the infusion of any blood product carries a small risk of complications such as allergic reaction, infection or other unpredicted reactions that could potentially require medical care and hospitalisation. Blood taking and skin biopsies could result in pain, bruising and/or infection at the injection site. Infection can be treated with a short course of oral antibiotics.

Where is the study run from?
The study will take place at Great Ormond Street Hospital for Children in London, UK.

When is the study starting and how long is it expected to last for?
We are aiming to start the study on the 14/10/2012 . Study participants will be followed up in the context of the clinical trial for 6 months and then continue to collect information about the skin disease during the routine clinical appointments for up to 1 year.

Who is funding the study?
Dystrophic Epidermolysis Bullosa Research Association (DebRA) and sponsored by King's College London.

Who is the main contact?
Professor John McGrath
john.mcgrath@kcl.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof John Alexander McGrath

ORCID ID

Contact details

King's College London
St John's Institute of Dermatology
9th Floor
Tower Wing
Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
+44 (0)20 7188 6353
john.mcgrath@kcl.ac.uk

Additional identifiers

EudraCT number

2012-001394-87

ClinicalTrials.gov number

Protocol/serial number

19312-1

Study information

Scientific title

A prospective phase I/II study to evaluate the use of allogeneic mesenchymal stromal cells for the treatment of skin disease in children with recessive dystrophic epidermolysis bullosa

Acronym

EBSTEM

Study hypothesis

Mesenchymal stromal cells (also known as mesenchymal stem cells, MSC) have been identified as bone marrow derived multipotent stem cells of non-haematopoetic lineage that are present in tiny quantities in the circulation (1 in 104 nucleated cells). MSCs can be isolated from bone marrow but also from subcutaneous fat, umbilical cord blood, placenta and definitive teeth. MSCs have been shown to differentiate into a number of different cell types of stromal lineage including osteoblasts, adipocytes and chondrocytes. There is an intense amount of research interest in the clinical application of MSCs in the treatment of degenerative or inflammatory diseases. Mesenchymal stem cells (MSC) have been shown to home to wounded tissue and mediate wound healing. It is, therefore, anticipated that bone marrow derived tissue cultured MSCs, if injected systemically, will lead to increased amounts of type VII collagen production as well as the production of a variety of growth factors and cytokines both to stimulate wound healing as well as inducing type VII collagen synthesis in the patient's own keratinocytes and fibroblasts. Recent studies in animal models and humans have demonstrated that MSCs have the potential to improve skin function. This project aims to translate those initial findings into a clinical trial of MSCs given intravenously into children with RDEB. The goal is to see whether this is safe, feasible and of potential value to those living with this condition.

On 20/01/2015 the following changes were made to the trial record:
1. The overall trial start date was changed from 01/10/2012 to 14/06/2013.
2. The overall trial end date was changed from 01/10/2014 to 11/12/2014.

Ethics approval

NRES Committee London-Bloomsbury, 23/11/2012, ref: 12/LO/1258

Study design

Phase I/II non-randomised open-label single-centre proof of concept

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Recessive dystrophic epidermolysis bullosa

Intervention

Children with RDEB from Great Ormond Street NHS Trust will be invited to take part in the study. Each subject will undergo an initial screening including physical examination, vital signs and disease severity assessment. This will also include a skin biopsy and blood test investigations. All study participants will receive three intravenous MSC infusions at baseline Day 0, Day 7 and Day 28. The patients will then be additionally reviewed at Day 60, Day 100 and Day 180 after the first infusion (total 7 visits, including screening visit). During the study visits, the participant will be reviewed by a doctor who will assess the disease severity, blister counts, pain and quality of life issues. Blood tests will be performed on six occasions. A skin biopsy will be repeated at screening and Day 60. At Day 0 and Day 100 the time taken to form a small suction blister will be assessed. The parents of each child will be invited to have their skin fragility tested as well, by measuring the time to forming a suction blister and this will be correlated with their child's time. Suction blisters times provide a functional measurement of skin integrity and resistance to blistering. Photographs of body areas will be taken by the participants' parents/guardians at different timepoints during dressing changes. Investigators will also take clinical photographs during the study visits to assess the appearance of affected body areas. After the first 6 months the children will be followed up clinically every 3 to 6 months by the GOSH clinical team and no scheduled interventions are planned unless they are clinically indicated

Intervention type

Drug

Phase

Phase I/II

Drug names

Primary outcome measures

Current primary outcome measures as of 15/01/2015:
To evaluate the safety of allogeneic intravenously administered MSCs in children with RDEB over a 12-month period

Previous primary outcome measures:
To evaluate the safety of allogeneic intravenously administered MSCs in children with RDEB over a 24-month period

Secondary outcome measures

1. Increase in collagen VII deposition at the DEJ post treatment
2. Quantitative analysis of the donor cells dermal chimerism
3. Improvement of haematological and serological markers of generalised inflammation
4. General clinical appearance of the skin based on medical photographs, generalised severity score and BEBSS score
5. Improved quality of life
6. Pain scoring
7. Reduction in blister numbers
8. Increase in skin strength measured by increased time to blister formation after skin suction at screening and D120

Overall trial start date

14/06/2013

Overall trial end date

11/12/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Subjects who have a diagnosis of recessive dystrophic epidermolysis bullosa (RDEB) characterised by partial or complete collagen VII deficiency
2. Subjects who are ≥ 12 months and ≤ 17 years of age at the time of enrolment
3. Subjects whose responsible relative/guardian has voluntary signed and dated an Informed Consent Form (ICF) prior to the first study intervention. Whenever the minor child is able to give consent, the minor's assent will be obtained in addition to the signed consent of the minor's legal guardian.

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

6 to 10 participants

Participant exclusion criteria

Current exclusion criteria as of 10/09/2013:
1. Subjects who have had other investigational medicinal products within 90 days prior to screening or during the treatment phase
2. Subjects who have received immunotherapy including oral corticosteroids for more than 1 week (intranasal and topical preparations are permitted) or chemotherapy within 60 days of enrolment into this study
3. Subjects with a known allergy to any of the constituents of the investigational product
4. Subjects with signs of active infection
5. Subjects with a medical history or evidence of malignancy, including cutaneous squamous cell carcinoma
6. Subjects with both positive C7 ELISA and a positive indirect immunofluorescence (IIF) with binding to the base of salt split skin
7. Subjects who are pregnant or of child-bearing potential who are not abstinent or practicing an acceptable means of contraception, as determined by the Investigator, for the duration of the treatment phase

Previous exclusion criteria:
1. Subjects who have had other investigational medicinal products within 90 days prior to screening or during the treatment phase
2. Subjects who have received immunotherapy including oral corticosteroids for more than 1 week (intranasal and topical preparations are permitted) or chemotherapy within 60 days of enrolment into this study
3. Subjects with a known allergy to any of the constituents of the investigational product
4. Subjects with signs of active infection
5. Subjects with a medical history or evidence of malignancy, including cutaneous squamous cell carcinoma
6. Subjects with positive serum antibodies to C7 confirmed by ELISA
7. Subjects who are pregnant or of child-bearing potential who are not abstinent or practicing an acceptable means of contraception, as determined by the Investigator, for the duration of the treatment phase

Recruitment start date

14/06/2013

Recruitment end date

03/10/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Great Ormond Street Hospital for Children NHS Foundation Trust
Great Ormond Street
London
WC1N 3JH
United Kingdom

Sponsor information

Organisation

King's College London (UK)

Sponsor details

Great Maze Pond
London
SE1 9RT
United Kingdom
+44 (0)20 7188 6409
john.mcgrath@kcl.ac.uk

Sponsor type

University/education

Website

http://www.kcl.ac.uk/medicine/research/divisions/gmm/sections/dermatology/index.aspx

Funders

Funder type

Charity

Funder name

Dystrophic Epidermolysis Bullosa Research Association [DebRA] (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

It is intended that the results of the study will be reported and disseminated through posters and oral presentations at international conferences, scientific meetings and in high-impact peer-reviewed journals. Publicity will be performed through press releases at the local, national and international level. Press releases will be co-ordinated through King’s College London and Great Ormond Street Hospital. DebRA, the patient advocacy group, will also inform patients and potential participants through their website and newsletters.

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes