E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Corneal lesions with associated moderate to severe limbal stem cell deficiency due to ocular burns |
Lesiones corneales con deficiencia asociada de moderada a severa de células madre limbales debido a quemaduras oculares |
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E.1.1.1 | Medical condition in easily understood language |
corneal damage due to ocular burns |
Daño corneal debido a quemaduras oculares |
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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 long term safety of one or two implants with Holoclar in patients suffering from moderate to severe LSCD secondary to ocular burns. |
Demostrar la seguridad a largo plazo de uno o dos implantes con Holoclar en pacientes con moderada a grave DCML secundaria a quemaduras oculares. |
|
E.2.2 | Secondary objectives of the trial |
1)To evaluate the long-term efficacy of one or two ACLSCT(s), the degree of superficial corneal neo-vascularization and corneal epithelial stability, clinical symptoms, conjunctival inflammation, visual acuity, quality of life, tear secretion compared to baseline (i.e. before the first ACLSCT) and long term efficacy based on clinical judgment of the investigator; 2) To evaluate safety and clinical outcomes (i.e. superficial corneal neo-vascularization, epithelial defects, visual acuity, conjunctival inflammation, and symptoms) after keratoplasty in patients previously treated with Holoclar. |
1) Evaluar la eficacia a largo plazo de uno o dos ACLSCT, el grado de neo-vascularización superficial de la córnea y la estabilidad epitelial de la córnea, los síntomas clínicos, la inflamación conjuntival, la agudeza visual, la calidad de vida, la secreción lagrimal comparados con el valor inicial (es decir, antes del primer ACLSCT) y la eficacia a largo plazo según el juicio clínico del investigador; 2) Evaluar la seguridad y los resultados clínicos (es decir, la neo-vascularización superficial de la córnea, los defectos epiteliales, la agudeza visual, la inflamación conjuntival y los síntomas) después de la queratoplastia en pacientes tratados previamente con Holoclar. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All patients (adults and pediatrics) who completed the HOLOCORE core study and who consent to roll over to the present extension study at the end of the HOLOCORE follow-up. |
Todos los pacientes (adultos y pediátricos) que completaron el Estudio principal HOLOCORE y que consienten pasar al presente estudio de extensión al final del seguimiento de HOLOCORE. |
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E.4 | Principal exclusion criteria |
No specific exclusion criterion is considered for this study, except for patients dropping out from the HOLOCORE study or withdrawing consent. |
No se ha considerado un criterio de exclusión específico para este estudio, except para los pacientes que abandonan el estudio HOLOCORE o retiran su consentimiento. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients reporting Treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), Adverse Event of Special Interest in accordance with the Risk Management Plan for Holoclar (AESI), including glaucoma and blepharitis. |
Porcentaje de pacientes que reporten acontecimientos adversos emergentes del tratamiento (AAETs), acontecimientos adversos relacionados con el tratamiento (AARTs), acontecimientos adversos de especial interés de acuerdo con el Plan de gestión de riesgos para Holoclar (AAEIs), incluidos el glaucoma y la blefaritis. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All study duration |
Toda la duración del Estudio |
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E.5.2 | Secondary end point(s) |
Percentage of patients with successful transplantation at Visit 3 (success is defined on the basis of the degree of "superficial corneal neovascularization" and "epithelial defects") |
Porcentaje de pacientes con trasplante exitoso en la visita 3 (el éxito se define en base al grado de "neovascularización corneal superficial" y a los "defectos epiteliales") |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 months after patient inclusion (or ” 24 months from the last Holoclar treatment” ) |
12 meses tras la inclusion del paciente (o "24 meses desde el ultimo tratamiento 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 | 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) | 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 |
Seguimiento de Pacientes que recibieron HOLOCLAR en el protocolo HOLOCORE |
Follow up of patients who received HOLOCLAR in HOLOCORE protocol. |
|
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
| 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 | 1 |
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 | 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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LVLS |
Última visita del ultimo paciente |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
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 | 9 |