E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of corneal lesions with associated moderate (at least two corneal quadrants, central corneal involvement resulting in severe visual impairment) to severe limbal stem cell deficiency due to ocular burns |
Trattamento di lesioni corneali con relativo deficit di cellule staminali limbari da moderato (almeno due quadranti della cornea, coinvolgimento centrale della cornea con conseguente grave compromissione dell’acutezza visiva) a grave dovuto a ustioni oculari |
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E.1.1.1 | Medical condition in easily understood language |
corneal lesions with associated moderate to severe limbal stem cell deficiency due to ocular burns |
Lesioni corneali associate a riduzione da moderata a severa di cellule staminali limbari dovuta a bruciature uculari |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011012 |
E.1.2 | Term | Corneal epithelium opacity |
E.1.2 | System Organ Class | 100000004853 |
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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 demonstrate the efficacy of Holoclar® at one year after the first treatment in patients suffering from moderate (vascularization in two-three corneal quadrants with central corneal involvement) to severe (vascularization in four corneal quadrants with central corneal involvement) LSCD with severe visual impairment and secondary to ocular burns, in terms of percentage of patients with a success of transplantation at approximately 12 months from the first Holoclar® treatment. |
Dimostrare l’efficacia di Holoclar dopo un anno dal primo trattamento in pazienti con deficit di cellule staminali limbari (LSCD) da moderato (vascolarizzazione in 2-3 quadranti con coinvolgimento della cornea centrale) a grave (vascolarizzazione in quattro quadranti corneali con coinvolgimento della cornea centrale) a causa di ustioni oculari. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of one or two treatments with Holoclar at one year after the last treatment. |
Valutare l’efficacia di uno o due trattamenti con Holoclar dopo un anno dall’ultimo trattamento. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent prior to any study-related procedures. Informed consent will also include the possibility of a second transplantation and of the rolling over to the long-term extension study HOLOCORE-FU. In case the patient will be judged by the investigator as eligible to a second transplantation, an additional written addendum to the first informed consent form will have to be obtained to proceed with the second ACLSCT; 2. Adult male and female patients (=18 years old); Five Paediatric patients aged 2 to 17 years will be also enrolled for safety purposes only. 3. LSCD secondary to unilateral or bilateral physical or chemical ocular burns, with at least 1-2 mm2 of undamaged limbus to harvest stem cells for expansion in culture. LSCD will be considered for inclusion in presence of superficial neo-vascularization invading at least two corneal quadrants with central corneal involvement (including corneal neo-vascularization or corneal opacity) according to the independent assessors; 4. Stability of LSCD, defined by a duration of disease of at least 24 months (12 months for minors) at the time of the Screening Visit and presence of continuum epithelium as per fluorescein staining scored as none or trace. 5. Presence of severe impairment in visual acuity defined by a score after best correction (i.e. Best Corrected Visual Acuity) equal or below 1/10th (or 20/200) at the Snellen chart (legal blindness) ; 6. Absence of other clinical contraindications to ACLSC transplantation based upon investigator’s judgment; 7. A cooperative attitude to follow up the study procedures (Caregivers in case of minors).
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1. Consenso informato scritto prima di qualsiasi procedura correlata allo studio. Il consenso informato prevede inoltre la possibilità di un secondo trapianto e dell‘arruolamento per lo studio di estensione a lungo termine HOLOCORE-FU. Nel caso in cui il ricercatore giudicherà il paziente idoneo ad un secondo trapianto, sarà necessario allegare un ulteriore documento scritto al primo consenso informato che permetta di procedere al secondo ACLSCT; 2. Pazienti adulti maschi e femmine (=18 anni); Verranno arruolati anche cinque pazienti pediatrici di età compresa tra i 2 e i 17 anni a solo scopo precauzionale. 3. LSCD secondario a ustioni oculari unilaterali o bilaterali di natura chimica o fisica, con almeno 1 - 2 mm2 di limbo non danneggiato che consenta di raccogliere cellule per l’espansione in coltura. L’LSCD verrà preso in considerazione per l’inclusione in presenza di neovascolarizzazione superficiale in almeno due quadranti della cornea con coinvolgimento centrale della cornea (tra cui neovascolarizzazione corneale o opacità corneale) secondo il giudizio di valutatori indipendenti; 4. Stabilità dell’LSCD, intesa come durata della malattia di almeno 24 mesi (12 mesi per i minori) al momento della visita di screening e presenza di epitelio continuo alla colorazione con fluoresceina classificato come inesistente o in tracce. 5. Presenza di grave compromissione dell’acuità visiva definita da uno score dopo la miglior correzione (ovvero la miglior acuità visiva corretta) uguale o inferiore a 1/10° (o 20/200) secondo la tavola di Snellen (cecità legale); 6. Assenza di altra controindicazione clinica al trapianto ACLSC secondo il giudizio del ricercatore; 7. Un atteggiamento collaborativo a seguire le procedure dello studio (tutori in caso di minorenni).
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E.4 | Principal exclusion criteria |
1. LSCD of mild degree (i.e. below 2 quadrants of neo-vessel invasion ), due to a recent burn (less than 24 months before screening for adults and 12 months for minors), or secondary to medical conditions other than burns (i.e.radiotherapy); 2. Severe ocular inflammation according to the Efron Grading Scale for Contact Lens Complications. Patient can be re-screened after appropriate treatment; 3. Presence of eyelids malposition; 4. Conjunctival scarring with fornix shortening; 5. Tear secretion deficiency, determined by Schirmer's test (<5 mm/ 5 min); 6. Corneal anaesthesia and conjunctival anaesthesia or severe hypoesthesia; |
1. LSCD di lieve entità (ovvero invasione neovascolare in meno di 2 quadranti) dovuto ad un’ustione recente (meno di 24 mesi prima dello screening per gli adulti e 12 per i minori) o secondario a condizioni mediche che non siano ustioni (ovvero la radioterapia); 2. Grave infiammazione oculare secondo la scala graduata di Efron per le complicanze da lenti a contatto. Il paziente può essere sottoposto nuovamente allo screening dopo un trattamento adeguato; 3. Presenza di malposizione delle palpebre; 4. Cicatrici congiuntivali con accorciamento del fornice; 5. Grave deficit di secrezione lacrimale diagnosticato mediante il test di Schirmer di tipo I (<5 mm/ 5 min.); 6. Anestesia corneale e congiuntivale o ipoestesia severa; |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Percentage of patients with a success of transplantation (success is defined on the basis of the degree of "superficial corneal neovascularization" and "epithelial defects") |
Percentuale di pazienti con un successo di trapianto (il successo del trapianto si definisce in base al grado di “neovascolarizzazione corneale superficiale" e di “difetti epiteliali”. ) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 months from the first Holoclar treatment |
12 mesi dopo il primo trattamento con Holoclar |
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E.5.2 | Secondary end point(s) |
Percentage of patients with clinical success after one or two ACLSCTs (same definition of success as primary endpoint) |
Percentuale di pazienti con successo clinico dopo uno o due ACLSCT (stessa definizione dell'endpoint primario) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 months after the last treatment with Holoclar |
12 mesi dopo l'ultimo trattemento con Holoclar |
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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 | Yes |
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) | No |
E.7.1.1 | First administration to humans | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
studio prospettico |
prospective trial |
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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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |