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

NCT02984085 | Terminated Phase 1

• 1 other identifier: HOLOGENE 7
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Recessive Dystrophic Epidermolysis Bullosa

Keywords

RDEB; Stem cells; Gene therapy

Outcome Measures

Primary Outcomes (1)

• Safety

  number and percentage of patients experiencing treatment-related adverse events (TRAEs), serious adverse events (SAEs) and serious adverse drug reactions (ADRs) up to 3 months after the first treatment.

  3-month

Secondary Outcomes (1)

• Efficacy

  3- and 12-months

Other Outcomes (2)

• Treatment success

  12-months

• Fibrin re-absorption

  1- and 4-weeks

Study Arms (1)

Genetically corrected cultured epidermal autograft

EXPERIMENTAL

The surgery will be carried out in 2 stages, the first aims at taking biopsy to isolate epidermal cells including stem cells. The biopsy will be processed in a laboratory of a regenerative medicine manufacturing site where they will be corrected, expanded and prepared as final sheets to be implanted. In the second surgery, genetically corrected cultured epidermal autograft (Hologene 7) will be implanted into the selected area. The specialist surgeon will either use a local or general anaesthetic for the implant operation. The treated area will be immobilized for some days after this operation. Antibiotics and anti-inflammatory drugs will be administered (if necessary) to prevent infections and to minimise swelling.

Drug: Genetically corrected cultured epidermal autograft (ATMP)

Interventions

Genetically corrected cultured epidermal autograft (ATMP) DRUG

Genetically corrected cultured epidermal autograft (Hologene 7) is intended for transplantation onto surgically prepared blistering skin areas of RDEB patients and permanent regeneration of a healthy, functional and renewing epidermis sustained by the engraftment of transduced epidermal stem cells. By taking some autologous epidermal cells, a new layer of transgenic tissue is grown in the laboratory. This layer of tissue is then implanted by a surgeon into the damaged area. The implantation can be done in one or more areas and repeated in case of failure of the first surgery.

Also known as: Hologene 7 Study product (ATMP)

Genetically corrected cultured epidermal autograft

Eligibility Criteria

• Age: 6 Years - 54 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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;
• Adult male and female patients (≥18 years old and \< 55); Paediatric patients aged 6 to 17 years will be also enrolled.
• RDEB molecular characterization by mutation analysis;
• Non-collagenous domain (NC1 or NC2) antibody immunofluorescence or staining positive in Western Blot;
• Presence of chronic (persistent for more than 3 months) large wounds (\>10 cm2) and/or erosion;
• A cooperative attitude to follow up the study procedures (Caregivers in case of minors).

You may not qualify if:

• Known or suspected intolerances against anaesthesia;
• Bad general condition (ECOG index \>1)
• Unresectable or metastasizing squamous cell carcinoma (SCCs);
• Antibodies to type VII collagen associated antigens demonstrated on indirect immunofluorescence;
• Clinical and/or laboratory signs of acute systemic infections at the time of screening. Patient can be re-screened after appropriate treatment;
• Severe systemic diseases (i.e. uncompensated diabetes);
• 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.
• 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
• Contraindications to the local or systemic antibiotics and/ or corticosteroids foreseen by the protocol;
• Contraindications to undergo extensive surgical procedures;
• 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;
• 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.

Sponsors & Collaborators

• Holostem s.r.l.: lead
• Paracelsus Medical University: collaborator

Study Sites (1)

EB House Austria, Department of Dermatology, Paracelsus Medical University

Salzburg, 5020, Austria

Location

Related Links

• Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells.
• Long-term stability and safety of transgenic cultured epidermal stem cells in gene therapy of junctional epidermolysis bullosa.
• Closure of a large chronic wound through transplantation of gene-corrected epidermal stem cells.

MeSH Terms

Conditions

Epidermolysis Bullosa Dystrophica

Interventions

cyclic adenosine-5'-trimetaphosphate

Condition Hierarchy (Ancestors)

Epidermolysis Bullosa; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Skin Diseases, Vesiculobullous

Study Officials

• Michele De Luca, MD/Professor

  Holostem s.r.l.

  STUDY DIRECTOR

• Johann W. Bauer, MD

  Paracelsus Medical University - EB House

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 6, 2016
• Study Start: January 30, 2017
• Primary Completion: August 6, 2018
• Study Completion: August 6, 2018
• Last Updated: February 16, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)