Gene Therapy for patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB).

Phase 1

• Conditions: RDEB is characterized by generalized skin blistering, erosions, crusts, atrophic scarring, onychodystrophy and loss of nails, mutilating pseudosyndactyly of hands and feet, as well as oral cavity lesions, esophageal strictures and eye and genitourinary tract lesions, all of which can also lead to anemia, iron deficiency and growth delay. Aggressive metastasizing squamous cell carcinomas are a common complication of RDEB, which reduce patients’ average life expectancy to less than 40 years.; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2015-004592-74-AT
• Lead Sponsor: Holostem Terapie Avanzate s.r.l.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-01-19
• Last Update Posted: 11 June 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1.Signed and dated informed consent prior to any study-related procedures. Informed consent will also include the possibility of additional transplantations and of the rolling over to the long-term extension period;
2.Adult male and female patients (=18 years old and < 55);
Paediatric patients aged 6 to 17 years will be also enrolled.
3.RDEB molecular characterization by mutation analysis;
4.NC1 or NC2 antibody immunofluorescence or staining positive in Western Blot;
5.Presence of chronic (persistent or recurrent for more than 3 months) large wounds (>10 cm2) and/or persistent or recurrent erosions;
6.A cooperative attitude to follow up the study procedures (Caregivers in case of minors).

Are the trial subjects under 18? yes
Number of subjects for this age range: 6
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 6
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Known or suspected intolerances against anaesthesia;
2.Bad general condition (ECOG index >1)
3.Unresectable or metastasizing SCCs;
4.Antibodies to type VII collagen associated antigens demonstrated on indirect immunofluorescence;
5.Clinical and/or laboratory signs of acute systemic infections at the time of screening. Patient can be re-screened after appropriate treatment;
6.Severe systemic diseases (i.e. uncompensated diabetes);
7.Female subjects: pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of 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 in urine will be performed at screening in all women of childbearing potential, and repeated before biopsy treatment and at all visits. Any postmenopausal women (physiologic menopause defined as 12 consecutive months of amenorrhea”) or women permanently sterilized (e.g. tubal occlusion, hysterectomy or bilateral salpingectomy) will not be require to undergo pregnancy test.
Parental control will be applied for the pediatric population when needed.
8.Allergy, sensitivity or intolerance to drugs or excipients (hypersensitivity to any of the excipients listed in Investigator’s brochure or in this protocol):
-Transport medium (Dulbecco’s Modified Eagles Medium supplemented with L-glutamine)
-Fibrin support
-Betaisodona
9.Contraindications to the local or systemic antibiotics and/ or corticosteroids foreseen by the protocol;
10.Contraindications to undergo extensive surgical procedures;
11.Clinically significant or unstable concurrent disease or other clinical contraindications to stem cell transplantation based upon investigator’s judgment or other concomitant medical conditions affecting grafting procedure;
12.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.
13.Participation in another clinical trial where investigational drug was received less than 6 months prior to screening visit.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified