E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
JEB is genetically and clinically heterogeneous characterized by mutations in COL17A1,encoding for Collagen17 protein. COLXVII is a collagenous transmembrane type II protein component of the hemidesmosomes and plays a key role in the adhesion of epidermis to the basement membrane. JEB is characterized by a wide range of severity: skin blistering, which can be generalized or localized, different degrees of mucosal involvement, enamel defects, dystrophy or loss of nails, and alopecia can occur. |
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E.1.1.1 | Medical condition in easily understood language |
JEB is genetic skin disease characterized by generalized blistering. Local healing shall be achieved with transplants made from genetically corrected stem cells from the patients. |
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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 the study product up to three months after the first treatment in patients with Epidermolysis Bullosa due to autosomal recessive mutations in the gene encoding for collagen XVII (COL17A1).
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of one or more treatments with the study product at three months and one year follow up.
To evaluate: - the efficacy of one or more treatments with the study product at 1 week (Visit 5), 1 month (Visit 6), 6 months (Visit 8) and 9 months (Visit 9) after transplantation - the long term safety at one year after one or more treatments - the potential immune reactions against the transgene - the increase of Quality of life score, evaluated by QOLEB, EBDASI, PGA from baseline |
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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; 2)Male and female patients between 6 years old to 55 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).
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E.4 | Principal 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); 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 required to undergo pregnancy test. Parental control will be applied for the pediatric population when needed; 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To investigate the safety of the study product up to three months after the first treatment in patients with Epidermolysis Bullosa due to autosomal recessive mutations in the gene encoding for collagen XVII (COL17A1).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To evaluate the efficacy of one or more treatments with the study product at three months and one year follow up.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Three months and one year. |
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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 | No |
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
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |