Clinical Trial to Assess Safety and Efficacy of Autologous Cultured Epidermal Grafts Containing Epidermal Stem Cells Genetically Modified in Patients With RDEB.

• Status: Active, not recruiting
• Trial end date: 2021-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Prospective open-label, uncontrolled clinical study to assess the safety and efficacy of autologous cultured epidermal grafts containing epidermal stem cells genetically modified with the aid of a gamma-retroviral vector carrying COL7A1 complementary DNA (cDNA) for restoration of the epidermis in patients with recessive dystrophic epidermolysis bullosa. The purpose of this study is to demonstrate the safety and efficacy after one or more treatments with genetically corrected cultured epidermal autograft (Hologene 7) in patients suffering of recessive dystrophic epidermolysis bullosa (RDEB) with COL7A1 mutation.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Holostem Terapie Avanzate s.r.l.
• Collaborator: Paracelsus Medical University

Criteria

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. Non-collagenous domain (NC1 or NC2) antibody immunofluorescence or staining positive in Western Blot;

5. Presence of chronic (persistent for more than 3 months) large wounds (>10 cm2) and/or erosion;

6. A cooperative attitude to follow up the study procedures (Caregivers in case of minors).

Exclusion Criteria:

1. Known or suspected intolerances against anaesthesia;

2. Bad general condition (ECOG index >1)

3. Unresectable or metastasizing squamous cell carcinoma (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.

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.