RDEB is characterized by generalized skin blistering, erosions, crusts, atrophic scarring, onychodystrophy and loss of nails, mutilating pseudosyndactyly of hands and feet, as well as oral cavity lesions, esophageal strictures and eye and genitourinary tract lesions, all of which can also lead to anemia, iron deficiency and growth delay. Aggressive metastasizing squamous cell carcinomas are a common complication of RDEB, which reduce patients’ average life expectancy to less than 40 years.
Conditions
Interventions
Product Name: HOLOGENE7
Product Code: HOLOGENE7
Pharmaceutical Form: Living tissue equivalent
INN or Proposed INN: Transduced keratinocytes suspension, containing epidermal stem cells genetically corr
Sponsors
Holostem Terapie Avanzate s.r.l.
Eligibility
Sex/Gender
All
Inclusion 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 10 cm2) and/or persistent or recurrent erosions; 6.A cooperative attitude to follow up the study procedures (Caregivers in case of minors). Are the trial subjects under 18? yes Number of subjects for this age range: 6 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 6 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Known or suspected intolerances against anaesthesia; 2.Bad general condition (ECOG index >1) 3.Unresectable or metastasizing 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. Reliable contraception should be maintained throughout the study. A pregnancy test in urine will be performed at screening in all women of childbearing potential, and repeated before biopsy treatment and at all visits. Any postmenopausal women (physiologic menopause defined as “12 consecutive months of amenorrhea”) or women permanently sterilized (e.g. tubal occlusion, hysterectomy or bilateral salpingectomy) will not be require to undergo pregnancy test. Parental control will be applied for the pediatric population when needed. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety of HOLOGENE 7 up to three months after the first treatment in patients with Epidermolysis Bullosa due to autosomal recessive mutations in the gene encoding for collagen VII (COL7A1).;Secondary Objective: •To evaluate the efficacy of one or more treatments with HOLOGENE 7 at three months and one year follow up •Percentage of re-epithelialization during follow up; •Clinical and mechanical skin stability on the transplanted areas follow up •Restoration of type VII collagen expression in regenerated epidermis; •Restoration of anchoring fibrils in grafted skin; •Potential immune reactions against the transgene; •Quality of life evaluated by QOLEB, EBDASI, PGA; •Long-term safety. •Safety after one or more treatments with HOLOGENE 7. •To evaluate the clinical safety profile of treatment with HOLOGENE 7, including biopsy, HOLOGENE 7 transplantation procedure and post-transplantation treatment. ;Primary end point(s): To investigate the safety of HOLOGENE 7 up to three months after the first treatment in patients with Epidermolysis Bullosa due to autosomal recessive mutations in the gene encoding for collagen VII (COL7A1).;Timepoint(s) of evaluation of this end point: Three months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate the efficacy of one or more treatments with HOLOGENE 7 at three months and one year follow up.;Timepoint(s) of evaluation of this end point: Three months and one year. | — |
Countries
Austria
Contacts
Public ContactClinical Trial Coordinator
Holostem Terapie Avanzate s.r.l.
Outcome results
None listed