Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02984085
Other study ID # HOLOGENE 7
Secondary ID
Status Terminated
Phase Phase 1/Phase 2
First received
Last updated
Start date January 30, 2017
Est. completion date August 6, 2018

Study information

Verified date February 2022
Source Holostem Terapie Avanzate s.r.l.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 3
Est. completion date August 6, 2018
Est. primary completion date August 6, 2018
Accepts healthy volunteers No
Gender All
Age group 6 Years to 54 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Genetically corrected cultured epidermal autograft (ATMP)
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.

Locations

Country Name City State
Austria EB House Austria, Department of Dermatology, Paracelsus Medical University Salzburg

Sponsors (2)

Lead Sponsor Collaborator
Holostem Terapie Avanzate s.r.l. Paracelsus Medical University

Country where clinical trial is conducted

Austria, 

Outcome

Type Measure Description Time frame Safety issue
Other Treatment success Percentage of patients defined as "success" by Investigator site according to the same parameters as for the primary and key secondary efficacy assessments 12 months after last treatment; 12-months
Other Fibrin re-absorption • Complete matrix re-absorption (by visual inspection) one week after the transplantation and clinical success (defined as the primary efficacy assessment) at early assessment time points (1 and 4 weeks after transplantation). 1- and 4-weeks
Primary 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 Efficacy Percentage of patients with clinical success after one or more treatments with study product at 3 and 12 months follow up.
Clinically success is reached when both the following conditions are met:
o Regeneration of a clinically normal appearing skin with absence of detectable blister.
AND
o Restoration of type VII collagen expression and restoration of anchoring fibrils in the treated area.
3- and 12-months
See also
  Status Clinical Trial Phase
Completed NCT02493816 - Safety Study of Gene-modified Autologous Fibroblasts in Recessive Dystrophic Epidermolysis Bullosa Phase 1
Completed NCT04599881 - A Study of PTR-01 in Recessive Dystrophic Epidermolysis Bullosa Phase 2
Completed NCT04520022 - Safety and Effectiveness Study of Allogeneic Umbilical Cord Blood-derived Mesenchymal Stem Cell in Patients With RDEB Phase 1/Phase 2
Not yet recruiting NCT03632265 - Study of EB-101 for the Treatment of Recessive Dystrophic Epidermolysis Bullosa Phase 3
Recruiting NCT05944250 - A Pilot Study to Evaluate a Temporary Skin Substitute (Spincare® Matrix) for Wound Healing in RDEB Patients N/A
Recruiting NCT04917887 - Long-Term Follow-up Protocol
Completed NCT04917874 - A Long-term Treatment With B-VEC for Dystrophic Epidermolysis Bullosa Phase 3
Not yet recruiting NCT04285294 - Molecular Signatures of Cutaneous Squamous Cell Carcinoma During Recessive Dystrophic Epidermolysis Bullosa
Active, not recruiting NCT04213261 - A Study of FCX-007 for Recessive Dystrophic Epidermolysis Bullosa Phase 3
Active, not recruiting NCT02323789 - Mesenchymal Stromal Cells in Adults With Recessive Dystrophic Epidermolysis Bullosa Phase 1/Phase 2
Recruiting NCT01874769 - Study of Immune Tolerance and Capacity for Wound Healing of Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB) N/A
Recruiting NCT03392909 - Intravenous Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Phase 1/Phase 2
Completed NCT03752905 - A Phase 1/2 Trial of PTR-01 in Adult Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB) Phase 1/Phase 2
Completed NCT04227106 - Phase 3, Open-label Clinical Trial of EB-101 for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB) Phase 3
Completed NCT02698735 - Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Nonsense Mutation Patients Phase 1/Phase 2
Completed NCT03012191 - Gentamicin for RDEB Phase 1/Phase 2
Completed NCT03529877 - Allogeneic ABCB5-positive Stem Cells for Treatment of Epidermolysis Bullosa Phase 1/Phase 2
Completed NCT05143190 - Extension Study to PTR-01-002 (A Study in Recessive Dystrophic Epidermolysis Bullosa (RDEB) Patients Previously Treated With PTR-01) Phase 2
Recruiting NCT04177498 - Rigosertib in Patients With Recessive Dystrophic Epidermolysis Bullosa Associated SCC Early Phase 1
Completed NCT04491604 - Ph 3 Efficacy and Safety of B-VEC for the Treatment of DEB Phase 3