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

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ClinicalTrials.gov Identifier: NCT03490331
Recruitment Status : Recruiting
First Posted : April 6, 2018
Last Update Posted : April 6, 2018
Sponsor:
Collaborator:
Paracelsus Medical University
Information provided by (Responsible Party):
Holostem Terapie Avanzate s.r.l.

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.

Condition or disease Intervention/treatment Phase
Junctional Epidermolysis Bullosa Other: Transplantation surgery of genetically corrected cultured epidermal autograft (ATMP) Phase 1 Phase 2

Detailed Description:

This is a 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 17) will be implanted into the selected area. The specialist surgeon will either use a local or general anaesthetic for the transplant 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 COL17A1 cDNA for Restoration of Epidermis in Patients With Junctional Epidermolysis Bullosa
Actual Study Start Date : March 19, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
Experimental: Genetically corrected cultured epidermal autograft

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)
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.
Other Name: Transplantation of Hologene17 study product (ATMP)




Primary Outcome Measures :
  1. Safety events (ADRs and SAEs) related to the study treatment (tolerability) [ Time Frame: 3 months after treatment ]
    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

  2. Safety events (ADRs and SAEs) related to the study treatment (tolerability) [ Time Frame: 12 months after treatment ]
    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


Secondary Outcome Measures :
  1. Skin stability in the short term (Treatment efficacy) [ Time Frame: 3 months after transplantation ]
    The skin stability will be evaluated by means of stripping test and visual inspection of the treated areas

  2. Skin functionality in the short term (Treatment efficacy) [ Time Frame: 3 months after transplantation ]
    The skin functionality will be evaluated by means of molecular testing on skin punch biopsies taken from the transplanted areas.

  3. Skin stability in the long term (Treatment efficacy) [ Time Frame: 12 months after transplantation ]
    The skin stability will be evaluated by means of stripping test and visual inspection of the treated areas

  4. Skin functionality in the long term (Treatment efficacy) [ Time Frame: 12 months after transplantation ]
    The skin functionality will be evaluated by means of molecular testing on skin punch biopsies taken from the transplanted areas.



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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Years to 54 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed and dated informed consent prior to any study-related procedures;
  2. Male and female patients between 6 years old to 54 years old;
  3. JEB molecular characterization by mutation analysis;
  4. 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;
  5. Presence of chronic (persistent or recurrent for more than 3 months) large wounds (>10 cm2) and/or persistent or recurrent erosions;
  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 metastasizing Squamous Cell Carcinomas (SCCs);
  4. Antibodies to type XVII 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 mellitus);
  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. Reliable contraception should be maintained throughout the study.
  8. 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
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03490331


Contacts
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Contact: Michele De Luca, MD +390592058064 clinicaltrial@pec.holostem.com
Contact: Giada Di Leo +390592058747 clinicaltrial@pec.holostem.com

Locations
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Austria
EB House Austria, Department of Dermatology, Paracelsus Medical University Recruiting
Salzburg, Austria, 5020
Contact: Johann W. Bauer, MD         
Sponsors and Collaborators
Holostem Terapie Avanzate s.r.l.
Paracelsus Medical University
Investigators
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Study Chair: Michele De Luca, MD Holostem Terapie Avanzate s.r.l.
Principal Investigator: Johann W. Bauer, MD Paracelsus Medical University - EB House

Additional Information:
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Responsible Party: Holostem Terapie Avanzate s.r.l.
ClinicalTrials.gov Identifier: NCT03490331    
Other Study ID Numbers: HTA-HG17-01
First Posted: April 6, 2018    Key Record Dates
Last Update Posted: April 6, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Holostem Terapie Avanzate s.r.l.:
JEB
Stem cells
Gene Therapy
Additional relevant MeSH terms:
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Epidermolysis Bullosa
Epidermolysis Bullosa, Junctional
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous