Double-blinded placebo-controlled crossover study of Mesenchymal Intravenous Stromal cell Infusions in children with recessive dystrophic Epidermolysis Bullosa
Congenital disorders of the skin, recessive dystrophic epidermolysis bullosa
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 month continued treatment follow-on open-label study following review of the data by NIHR. The trial will be conducted at 2 sites that both specialise in paediatric dermatology: Great Ormond Street Hospital and Birmingham Children's Hospital. Screening visit (Visit 1): Each child will undergo an initial screening consisting of confirmation of consent from parent/guardian, physical examination, assessment of vital signs, disease severity assessment, concomitant medication review, routine safety bloods. Blood will be taken for DNA analysis and a skin biopsy performed for immunofluorescence testing if this information is not already available. Menstruating and sexually active participants will be asked to take a pregnancy test. Patients will be also asked if they would like to consent to the storage of blood samples for future research. Randomisation: All study participants will be randomised to receive two consecutive intravenous MSCs or placebo infusions at 0 and 14 days. After the outcome assessment at 9 months, all children will be crossed over and receive either MSCs or placebo at 9 months and 14 days later. The placebo effect is expected to tail off by 3 months. Follow up visits (Randomised crossover study, including phase I): All children will be followed up every 3 months for the first year following the first infusion. Outcome measures will be taken at 3, 6, 12, and 15 months. Infusion visits will be at day 0 and 14 days, 9 months and 2 weeks later. 1. On day 0 (Visit 2), participants will receive the first infusion and be assessed for pregnancy test (menstruating and sexually active participants only), physical examination, vital signs, disease severity assessment, pain and itch assessment, quality of life questionnaire, pain and itch medication review, con
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.
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 contracep