Congenital disorders of the skin, recessive dystrophic epidermolysis bullosa Skin and Connective Tissue Diseases Epidermolysis bullosa dystrophica
Conditions
Interventions
Current intervention as of 22/04/2022:
This is a prospective, randomised, placebo-controlled, double-blinded cross-over trial incorporating a phase 1 de-escalation study in the first 3 months and a 12
Sponsors
Great Ormond Street Hospital for Children NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
6 Months to 16 Years
Inclusion criteria
Inclusion criteria: 1. Diagnosis of RDEB characterised by partial or complete C7 deficiency including generalised severe and generalised intermediate subtypes 2. Aged >6 months and <16 years at time of enrolment 3. Responsible parent/guardian has voluntarily 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.
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 07/03/2023: 1. Other subtypes of EB such as EB simplex, EB junctional, dominant dystrophic EB, and Kindler EB 2. Received oral or topical corticosteroids for >7 consecutive days within 30 days or enrolment into this study, except for treatment with oral budesonide 3. Known allergy to any of the constituents of the investigational product 4. Signs of active infection that require treatment with oral or intravenous antibiotics within 7 days of screening 5. History or evidence of active malignancy, including cutaneous squamous cell carcinoma 6. Positive C7 ELISA and positive indirect immunofluorescence (IIF) with binding to the base of salt split skin at screening 7. 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 8. Received MSC infusions in the last 9 months 9. Simultaneous or previous participation in any interventional trial within 3 months before entering this trial. Participation in simultaneous registry and diagnostic trials during the trial is allowed. ____________ Previous participant exclusion criteria as of 22/04/2022 to 07/03/2023: 1. Other subtypes of EB such as EB simplex, EB junctional, dominant dystrophic EB, and Kindler EB 2. Received oral or topical corticosteroids for >7 consecutive days within 30 days or enrolment into this study, except for treatment with oral budesonide 3. Known allergy to any of the constituents of the investigational product 4. Signs of active infection that require treatment with oral or intravenous antibiotics within 7 days of screening 5. History or evidence of active malignancy, including cutaneous squamous cell carcinoma 6. Positive C7 ELISA and positive indirect immunofluorescence (IIF) with binding to the base of salt split skin 7. 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 8. Received MSC infusions in the last 9 months 9. Simultaneous or previous participation in any interventional trial within 3 months before entering this trial. Participation in simultaneous registry and diagnostic trials during the trial is allowed. ____________ Previous participant exclusion criteria: 1. Other subtypes of EB such as EB simplex, EB junctional, dominant dystrophic EB, and Kindler EB 2. Received oral or topical corticosteroids for >1 week within 30 days of enrolment into this study 3. Known allergy to any of the constituents of the investigational product 4. Signs of active infection that require treatment with oral or intravenous antibiotics within 7 days of screening 5. History or evidence of active malignancy, including cutaneous squamous cell carcinoma 6. Positive C7 ELISA and positive indirect immunofluorescence (IIF) with binding to the base of salt split skin 7. 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 8. Received MSC infusions in the last 9 months 9. Simultaneous or previous participation in any interventional trial within 3 months before entering this trial. Participation in simultaneous registry and diagnostic trials during the trial is allowed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 22/04/2022: Internal phase I dose de-escalation trial: Toxicity measured using the incidence of a Suspected Unexpected Serious Adverse Reaction (SUSAR) within 48 h of a patient receiving an infusion Main cross-over trial: Disease severity measured using the total score across all 5 domains of the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) at day 0 and 3 months post-infusion of UC-MSCs Open-label non-randomised study: Disease severity measured using the total score across all 5 domains of the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) at 4, 8, and 12 months of the open-label study NB: MissionEB is not an adequately powered study for feasibility reasons and as such, the judgement on efficacy of UC-MSCs will be based on totality of evidence from all clinical (primary and secondary) outcomes. ____________ Previous primary outcome measure: Internal phase I dose de-escalation trial: Toxicity measured using the incidence of a Suspected Unexpected Serious Adverse Reaction (SUSAR) within 48 h of a patient receiving an infusion Main cross-over trial: Disease severity measured using the total score across all 5 domains of the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) at day 0 and 3 months post-infusion of UC-MSCs Open-label non-randomised study: Disease severity measured using the total score across all 5 domains of the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) at 4, 8, and 12 months of the open-label study | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 22/04/2022: 1. Change in disease severity as measured by EBDASI at 6 months post infusion (from day 0, period baseline) for the cross-over study, and at 0, 4, 6, and 12 months for the open-label study. 2. Change in disease severity measured using instrument for scoring clinical outcomes of research for epidermolysis bullosa (iscorEB) at 3- and 6-months post infusion (from day 0, period baseline) for the cross-over study and at 0, 4, 6, and 12 months for the open-label study. 3. Change in general clinical appearance of skin disease measured using clinical photography at 3- and 6-months post infusion (from day 0, period baseline) for the cross-over study, and at 0 months, 0 months + 2 weeks, 4 months, 4 months + 2 weeks, 8 months, and 8 months + 2 weeks infusion visits and 12-month follow-up for the open-label study 4. Change to pain and itch as assessed by the Wong-Baker FACES Pain scale for children over 6 years old and Leuven itch scale scores at 3- and 6-months post infusion (from day 0, period baseline) for the cross-over study and 0 months, 0 months + 2 weeks, 4 months, 4 months + 2 weeks, 8 months, and 8 months + 2 weeks infusion visits and 12 month follow up for the open-label study. 5. Change to pain and itch as assessed by the amount of analgesia and itch medications required. Participants or their guardians will be asked to detail what pain and itch medication the participant has taken in the last 48 hours, including dose and frequency. At 3 months post infusion, clinicians blinded to treatment allocation will compare whether this is unchanged, increased or decreased since baseline (day 0, period baseline) for the cross-over study and at 0, 4, 8, and 12 months for the open-label study. 6. Change in quality of life according to validated Child Health Utility 9D (CHUD-9D) scoring system in children aged =7 years (an age appropriate by proxy version will be used for children aged 3 – 6) at 3- and 6-months post infusion | — |
Countries
England, United Kingdom
Outcome results
None listed