Open-label, Pivotal Clinical Trial to Confirm Efficacy and Safety of Autologous Grafts Containing Stem Cells Genetically Modified for Epidermis Restoration in Patients With Junctional Epidermolysis Bullosa

NCT05111600 | Terminated Phase 2

• 1 other identifier: HTA-HG5-02
• Study Type: interventional
• Target: 2
• Locations: 2 countries
• Sites: 2

Brief Summary

Prospective, multicenter and multinational, open-label, uncontrolled clinical study to assess the safety and efficacy of autologous cultured epidermal grafts containing epidermal stem cells genetically modified transduced with a LAMB3-gamma retroviral vector. The purpose of this study is to demonstrate the safety and efficacy after one or more treatments with genetically corrected cultured epidermal autograft (Hologene 5) for restoration of the epidermis in patients with generalized intermediate LAMB3-dependent Junctional Epidermolysis Bullosa.

Conditions

Junctional Epidermolysis Bullosa Non-Herlitz Type

Outcome Measures

Primary Outcomes (6)

• Re-epithelialization

  Re-epithelialization in absence of blisters in at least 50% of the transplanted area measured by the Investigator

  12 months

• Protein residual expression

  Protein residual expression resulting in 'Yes' or 'Partial' measured by Immunofluorescence

  12 months

• Expression of transgenic mRNA

  Expression of transgenic mRNA resulting in 'Yes' or 'Partial' measured by In situ hybridization

  12 months

• Hemidesmosomes presence

  Presence of hemidesmosomes measured by electron microscopy

  12 months

• Skin stability

  Negativity or positivity at the stripping test

  12 months

• Patient Reported Outcome

  Chnage in Patient Reported Outcome score measured by 5-points Likert scale, where: 1=Definitely Worsened, 2=Slightly Worsened, 3=Unchanged, 4=Slightly Improved, 5=Definitely Improved

  12 months

Secondary Outcomes (6)

• Re-epithelialization by Independent Assessor

  12 months

• Quality of Life improvement

  12 months

• Treatment-emergent adverse events

  12 months

• Serious adverse events

  12 months

• Adverse events of special interest

  12 months

Study Arms (1)

Treatment

EXPERIMENTAL

After confirmation of eligibility criteria and ICF signature, subject undergoes to skin biopsy for collection of autologous epidermal cells to be used to produce IMP under GMP process. Approximately 2 months later, IMP is transplanted on selected area.

Drug: Transplantation

Interventions

Transplantation DRUG

Implantation of autologous cultured grafts containing genetically modified stem cells for restoration of functional skin on pre-selected areas

Also known as: Engraftment

Treatment

Eligibility Criteria

• Age: 6 Months - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent prior to any study-related procedures.
• Male and female patients between 6 months and 65 years old;
• Diagnosis of generalized intermediate LAMB3-dependent JEB, confirmed by NGS or Sanger sequencing and/or immunofluorescence;
• Detectable residual expression of laminin 332 (and its beta-3 chain) by immunofluorescence and/or Western Blot analysis;
• Presence of blisters and/or ≥ 6 cm2 erosions (persistent or recurrent for more than 3 months); the area of the erosion can be considered as the sum of smaller areas in the same body part (i.e. leg, thigh, arm, …)
• A cooperative attitude to follow the study procedures (caregivers in case of children);
• Patients' compliance with the study schedule and procedures, including complete immobilization of the transplanted areas for at least two weeks and hospitalization up to 1 month after transplantation.

You may not qualify if:

• Known or suspected intolerance to anaesthesia;
• Bad general condition (ECOG index \>1);
• Presence of any skin cancers in the area(s) qualified for treatment;
• Clinical and/or laboratory signs of acute systemic infections at the time of screening. Patient can be re-screened after appropriate treatment;
• Female subjects: Pregnant (as evident by a positive urine hCG or serum-hCG test) or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential \[WOCBP\]) UNLESS they are willing to use highly effective birth control methods;
• Allergy, sensitivity or intolerance to study medication excipients or other material required by study protocol (as per Investigator's brochure)
• Contraindications to the local or systemic antibiotics and/or corticosteroids foreseen by the protocol;
• Contraindications to undergo extensive surgical procedures;
• Presence of i) systemic diseases, ii) clinically significant or unstable concurrent disease, iii) other concomitant medical conditions, iv) other clinical contraindications to stem cell transplantation, which based on Investigator's judgment, in consultation with the Sponsor Medical Expert may affect the participation in the study or the 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.
• Previous treatments or clinical trials envisaging the use of cells (including bone marrow transplantation, BMT) and/or both in vivo or ex vivo gene therapy products.

Sponsors & Collaborators

• Holostem s.r.l.: lead
• IRCCS San Raffaele: collaborator
• University of Modena and Reggio Emilia: collaborator

Study Sites (2)

Hopital Necker-Enfants Malades

Paris, France

Location

Struttura Complessa di Dermatologia Azienda Ospedaliero Universitaria Policlinico di Modena

Modena, Italy

Location

Related Links

• Hologene 5: A Phase II/III Clinical Trial of Combined Cell and Gene Therapy of Junctional Epidermolysis Bullosa

MeSH Terms

Conditions

Epidermolysis Bullosa, Junctional, Non-Herlitz Type

Interventions

Transplantation

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Study Officials

• Cristina Magnoni, MD, Surgeon

  Struttura Complessa di Dermatologia Azienda Ospedaliero Universitaria Policlinico di Modena

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: November 8, 2021
• Study Start: July 15, 2022
• Primary Completion: March 12, 2024
• Study Completion: November 22, 2024
• Last Updated: February 19, 2025

Record last verified: 2025-02

Locations

FR (1); IT (1)