Inherited Epidermolysis Bullosa (EB) is a group of rare, devastating genetic disorders characterized by structural and mechanical fragility of skin and mucosal membranes, impairing the patient’s quality of life. Generalized JEB is a chronic, life-threatening condition caused by mutations 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
Conditions
Interventions
Product Name: Hologene 5
Pharmaceutical Form: Living tissue equivalent
INN or Proposed INN: Not Yet Assigned
CAS Number: Not Assigned
Current Sponsor code: Hologene 5 DS
Other descriptive name: Ex-viv
Sponsors
Holostem Terapie Avanzate s.r.l.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated informed consent prior to any study-related procedures. For pediatric patients parental consent must be obtained; 2. Male and female patients from 1 y.o.; 3. Clinical and molecular diagnosis of LAMB3-dependent Junctional Epidermolysis Bullosa (by NGS or Sanger sequencing and/or immunofluorescence); 4. Detectable residual expression of laminin 332 (and its beta3 chain) by immunofluorescence and/or Western Blot analysis; 5. Presence of blisters or wounds (persistent or recurrent for more than 3 months). Persistence for more than 1 month should be considered for minors of 1 year of age; 6. Patients’ compliance with the study schedule and procedures and willingness to accomplish all the required follow up visits. Are the trial subjects under 18? yes Number of subjects for this age range: 4 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. Contraindications to undergo surgical procedures (i.e. known or suspected hypersensitivity to local or general anaesthesia); 2. Bad general condition (ECOG index >1); 3. Presence of any skin cancers in the area(s) qualified for Hologene-5 treatment; 4. Evidence of systemic infections. Patient can be -rescreened after appropriate treatment and recovering; 5. Female subjects: Pregnant or lactating women and all women with physiologically capable of becoming pregnant (i.e. women of childbearing potential [WOCBP]) unless they are willing to use highly effective birth control reliable methods such as: a. Placement of an intrauterine device (IUD) or intrauterine releasing system (IUS); b. Oral, intravaginal, transdermal combined estrogen and progestogen containing hormonal contraception or oral, injectable, implantable progestogen only hormonal contraception; c. Bilateral tubal occlusion; d. Partner vasectomy (provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success); e. Sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. Women of non-childbearing potential defined as physiologically incapable of becoming pregnant: premenarchal, post-menopausal (defined as no menses for 12 months without an alternative medical cause) or permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) are eligible. If indicated, as per Investigator’s request, postmenopausal status may be confirmed by follicle-stimulating hormone levels (according to local laboratory ranges) in women not using hormonal contraception or hormonal replacement therapy; 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 postmenopausal women (physiologic menopause defined as “12 consecutive months of amenorrhea”) or women permanently sterilized (e.g. tubal occlusion, hysterectomy or bilateral salpingectomy). Contraception has to be maintained until the end of study visit (6 months after the last graft). Parental control will be applied for the pediatric population when needed; 6. Known allergy to any of the constituents of the product or study medication excipients or other material required by study protocol (as per Investigator’s Brochure) 7. 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; 8. Inability to understand the study and to cooperate with the scope of the study (in case of children this is required for caregivers); 9. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective is to evaluate the safety of Hologene-5 and the procedures associated with the administration of the IMP (infections, lack of engraftment, transplant rejection, immunoreactions etc.) and the patient’s safety measured by occurrence of AEs, TEAEs, AESIs, SAEs at any time during the study.;Secondary Objective: To evaluate Hologene-5 efficacy as clinical and functional restoration of skin integrity.;Primary end point(s): Primary Endpoints • Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Adverse Events of Special Interest (AESI), and Adverse Drug Reaction (ADRs); • Vital signs and laboratory results.;Timepoint(s) of evaluation of this end point: 1, 3, and 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints • Transplantation efficacy at 1-, 3- and 6-months follow-up measured as change in % of reepithelization through imitoWound imaging application by the Investigator; • Transplantation efficacy at 3, 6 months follow-up measured as evidence of molecular correction (LAMB3 expression) based on immunofluorescence and/or in situ hybridization and/or PCR; • Transplantation efficacy at 6 months follow-up measured by mechanical stress test (strip test); • Transplantation efficacy at 1, 3 and 6 months follow-up measured as change versus baseline by Investigator judgment based on clinical inspection.;Timepoint(s) of evaluation of this end point: 1, 3, and 6 months | — |
Countries
Germany
Contacts
Public ContactPatrick Santoro
CROSS Research SA
Outcome results
None listed