Gene therapy for patients with Junctional Epidermolysis Bullosa (JEB)

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]; JEB is genetically and clinically heterogeneous characterized by mutations in COL17A1,encoding for Collagen17 protein.COLXVII is a collagenous transmembrane type II protein component of the hemidesmosomes and plays a key role in the adhesion of epidermis to the basement membrane. JEB is characterized by a wide range of severity: skin blistering, which can be generalized or localized, different degrees of mucosal involvement, enamel defects, dystrophy or loss of nails, and alopecia can occur.

• Registration Number: EUCTR2016-000095-17-AT
• Lead Sponsor: Holostem Terapie Avanzate s.r.l.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-06-07
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1)Signed and dated informed consent prior to any study-related procedures;
2)Male and female patients between 6 years old to 55 years old;
3)JEB molecular characterization by mutation analysis;
4)NC16A antibody immunofluorescence or positive staining in Western Blot analysis with polyclonal antibody produced against a synthetic peptide corresponding to amino acids 131-145 of human COL17A1;
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 metastasizing Squamous Cell Carcinomas (SCCs);
4. Antibodies to type XVII 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 required to undergo pregnancy test.
Parental control will be applied for the pediatric population when needed;
8. Allergy, sensitivity or intolerance to drugs, excipients or other material (as per Investigator’s brochure):
Transport medium (Dulbecco’s Modified Eagles Medium supplemented with L-glutamine); Fibrin support; Povidone iodine;
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