Clinical Trial to Assess Safety and Efficacy of Autologous Cultured Epidermal Grafts Containing Epidermal Stem Cells Genetically Modified in Patients With JEB (HOLOGENE17)

NCT03490331 | Terminated Phase 1

• 1 other identifier: HTA-HG17-01
• Study Type: interventional
• Target: 1
• 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 COL17A1 complementary DNA (cDNA) for restoration of the epidermis in patients with junctional 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 17) in patients suffering of junctional epidermolysis bullosa (JEB) with COL17A1 mutation.

Conditions

Junctional Epidermolysis Bullosa

Keywords

JEB; Stem cells; Gene Therapy

Outcome Measures

Primary Outcomes (2)

• Safety events (ADRs and SAEs) related to the study treatment (tolerability)

  Number of patients experiencing treatment-related adverse events (TRAEs) - either to the epidermal graft and to the surgical procedures. Adverse events (serious and not serious) and adverse drug reactions (ADRs) will be collected and described

  3 months after treatment

• Safety events (ADRs and SAEs) related to the study treatment (tolerability)

  Percentage of patients experiencing treatment-related adverse events (TRAEs) - either to the epidermal graft and to the surgical procedures. Adverse events (serious and not serious) and adverse drug reactions (ADRs) will be collected and described

  12 months after treatment

Secondary Outcomes (4)

• Skin stability in the short term (Treatment efficacy)

  3 months after transplantation

• Skin functionality in the short term (Treatment efficacy)

  3 months after transplantation

• Skin stability in the long term (Treatment efficacy)

  12 months after transplantation

• Skin functionality in the long term (Treatment efficacy)

  12 months after transplantation

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 (Hologene17) 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.

Other: Transplantation surgery of genetically corrected cultured epidermal autograft (ATMP)

Interventions

Transplantation surgery of genetically corrected cultured epidermal autograft (ATMP) OTHER

Surgergical procedure for transplantation under anaesthesia of genetically corrected cultured epidermal autograft (Hologene17) on blistering skin areas of JEB patients. By taking some autologous epidermal cells, a new layer of transgenic tissue is grown in the laboratory. This layer of tissue - containing genetically modified stem cells - 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: Transplantation of Hologene17 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;
• Male and female patients between 6 years old to 54 years old;
• JEB molecular characterization by mutation analysis;
• 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;
• Presence of chronic (persistent or recurrent for more than 3 months) large wounds (\>10 cm2) and/or persistent or recurrent erosions;
• 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 metastasizing Squamous Cell Carcinomas (SCCs);
• Antibodies to type XVII 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 mellitus);
• 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.
• 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
• 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

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

MeSH Terms

Conditions

Epidermolysis Bullosa, Junctional

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; Skin Diseases; Skin and Connective Tissue 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: March 18, 2018
• First Posted: April 6, 2018
• Study Start: March 19, 2018
• Primary Completion: September 11, 2018
• Study Completion: September 11, 2018
• Last Updated: March 7, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)