E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
|
E.1.1.1 | Medical condition in easily understood language |
RDEB is genetic skin disease characterized by generalized blistering. Local healing shall be achieved with transplants made from genetically corrected stem cells from the patients. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
|
E.2.2 | Secondary objectives of the trial |
•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.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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).
|
|
E.4 | Principal 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.
|
|
E.5 End points |
E.5.1 | 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). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
To evaluate the efficacy of one or more treatments with HOLOGENE 7 at three months and one year follow up. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Three months and one year. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the trial is defined as the last visit of the last patient after the last treatment if any. But at the end of the study, all consenting patients will be required to enter the safety and efficacy long-term follow-up period. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |