Gene Therapy for patient with Junctional Epidermolysis Bullosa
- Conditions
- Inherited Epidermolysis Bullosa (EB) is a group of rare, devastating genetic disorders characterized by structural and mechanical fragility ofskin and mucosal membranes, impairing the patient's quality of life. Generalized JEB is a chronic, life-threatening condition caused bymutations in genes– encoding different chains of laminin 332. All of these mutations hamper hemidesmosome formation, causing blisters. The most frequent, and perhaps most severe, JEB is due to mutations in LAMB3.MedDRA version: 20.0Level: PTClassification code 10014989Term: Epidermolysis bullosaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2018-000261-36-IT
- Lead Sponsor
- HOLOSTEM TERAPIE AVANZATE S.R.L.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 6
Patients must meet all of the following inclusion criteria:
1.Signed and dated informed consent prior to any study-related procedures;
2.Male and female patients between 6-month-old and 55-year-old;
3.Diagnosis of generalized intermediate LAMB3-dependent JEB, confirmed by NGS or Sanger sequencing and immunofluorescence;
4.Detectable residual expression of laminin 332 (and its beta3 chain) by immunofluorescence and/or Western analysis;
5.Presence of blisters and/or = 10 cm2 erosions (persistent or recurrent for more than 3 months);
6.A cooperative attitude to follow the study procedures (caregivers in case of children);
7.Patients’ compliance with the study schedule and procedures, including complete immobilization of the transplanted areas for at least two weeks and hospitalization up to 1 month after transplantation.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Patients must not meet all of the following exclusion criteria:
1.Known or suspected intolerance to anaesthesia;
2.Bad general condition (ECOG index >1);
3.Presence of Squamous Cell Carcinomas (SCCs) in the area(s) qualified for treatment;
4.Clinical and/or laboratory signs of acute systemic infections at the time of screening. Patient can be re-screened after appropriate treatment;
5.Female subjects: pregnant or lactating women and all women with childbearing potential unless they are willing to use one or more reliable methods of contraception with a Pearl index =1. Reliable contraception should be maintained throughout the study.
A pregnancy test will be performed at screening in all women of childbearing potential and repeated before biopsy treatment and at all visits. A pregnancy test will not be required for post-menopausal women (physiologic menopause defined as 12 consecutive months of amenorrhea”) or women permanently sterilized (e.g. tubal occlusion, hysterectomy or bilateral salpingectomy).
Parental control will be applied for the pediatric population when needed;
6.Allergy, sensitivity or intolerance to study medication excipients or other material required by study protocol (as per Investigator’s brochure):
-Transport medium (Dulbecco’s Modified Eagles Medium supplemented with L-glutamine)
-Fibrin support
-Povidone iodine or Prontosan® (or equivalent selected for the treatment in consultation with the Sponsor Medical Expert)
7.Contraindications to the local or systemic antibiotics and/or corticosteroids foreseen by the protocol;
8.Contraindications to undergo extensive surgical procedures;
9.Presence of i) systemic diseases, ii) clinically significant or unstable concurrent disease, iii) other concomitant medical conditions, iv) other clinical contraindications to stem cell transplantation, which based on Investigator’s judgment, in consultation with the Sponsor Medical Expert may affect the participation in the study or the grafting procedure;
10.Patients (or parents in case of paediatric subject) unlikely to comply with the study protocol or unable to understand the nature and scope of the study or the possible benefits or unwanted effects of the study procedures and treatments.
11.Previous treatments or participation in clinical trials envisaging the use of cells (including bone marrow transplantation, BMT) and/or both in vivo or ex vivo gene therapy products.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method