Gene Therapy for patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB).

• Register: EUCTR
• Last refreshed on: 11 June 2018
• Main ID: EUCTR2015-004592-74-AT
• Date of registration: 19/01/2016
• Prospective Registration: Yes
• Primary sponsor: Holostem Terapie Avanzate s.r.l.
• Public title: Gene Therapy for patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB).
• Scientific 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. - HOLOGENE7
• Date of first enrolment: 01/06/2016
• Target sample size: 12
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004592-74
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria

Contacts

• Name: Clinical Trial Coordinator
• Affiliation: Holostem Terapie Avanzate s.r.l.

• Name: Clinical Trial Coordinator
• Affiliation: Holostem Terapie Avanzate s.r.l.

Key inclusion & exclusion 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.NC1 or NC2 antibody immunofluorescence or staining positive in Western Blot;
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).

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:
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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

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.

Intervention(s)

Product Name: HOLOGENE7
Product Code: HOLOGENE7
Pharmaceutical Form: Living tissue equivalent
INN or Proposed INN: Transduced keratinocytes suspension, containing epidermal stem cells genetically corrected with a COL7A1-encoding retroviral vector
Current Sponsor code: Hologene7 DS
Other descriptive name: Transduced keratinocytes suspension, containing epidermal stem cells genetically corrected with a COL7A1-encoding retroviral vector, obtained from secondary culture of ex vivo expanded autologous human keratinocytes.
Concentration unit: % percent
Concentration type: range
Concentration number: 50-100

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Three months

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).

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).

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.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Three months and one year.

Secondary end point(s): To evaluate the efficacy of one or more treatments with HOLOGENE 7 at three months and one year follow up.

Secondary ID(s)

NCT02984085

HOLOGENE7(HTA-HG7-01)

Source(s) of Monetary Support

Holostem Terapie Avanzate s.r.l.