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

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Brief Title

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

Official Title

Prospective, Open-label, Uncontrolled Clinical Trial to Assess the Safety and Efficacy of Autologous Cultured Epidermal Grafts Containing Epidermal Stem Cells Genetically Modified With a Gamma-retroviral (rv) Vector Carrying COL7A1 cDNA for Restoration of Epidermis in Patients With Recessive Dystrophic Epidermolysis Bullosa.

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.
    

Detailed Description

      This is a monocentric, prospective, open label, uncontrolled clinical trial, phase I/II.

      Patients will be screened according to the Study Inclusion and Exclusion criteria and will be
      candidate for the treatment if all inclusion and none of the exclusion criteria are met.

      After confirmation of eligibility, patients will undergo biopsy for the collection of the
      autologous epidermal cells to be used to produce the tissue for the treatment. In case all
      criteria are met, the transplantation of the new cultured transgenic epidermis will be
      planned according to the procedures and the need of the patient.

      The study treatment consists of a surgical intervention for new restored stem cells
      implantation.

      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. Therefore, the patient can have his second intervention. In
      this 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.

      Three months after the transplantation, primary endpoint will be evaluated by the
      Investigator. The study completion will be reached when 1 year (secondary endpoint) of
      follow-up after the last transplant in the last patient will be accomplished.

      The end of the trial is defined as the last visit of the last patient after the last
      treatment if any.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Safety

Secondary Outcome

 Efficacy

Condition

Recessive Dystrophic Epidermolysis Bullosa

Intervention

Genetically corrected cultured epidermal autograft (ATMP)

Study Arms / Comparison Groups

 Genetically corrected cultured epidermal autograft
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

3

Start Date

January 30, 2017

Completion Date

August 6, 2018

Primary Completion Date

August 6, 2018

Eligibility 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.
      

Gender

All

Ages

6 Years - 54 Years

Accepts Healthy Volunteers

No

Contacts

Michele De Luca, MD/Professor, , 

Location Countries

Austria

Location Countries

Austria

Administrative Informations


NCT ID

NCT02984085

Organization ID

HOLOGENE 7


Responsible Party

Sponsor

Study Sponsor

Holostem Terapie Avanzate s.r.l.

Collaborators

 Paracelsus Medical University

Study Sponsor

Michele De Luca, MD/Professor, Study Director, Holostem Terapie Avanzate s.r.l.


Verification Date

February 2022