E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neurotrophic Keratitis |
cheratite neurotrofica |
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E.1.1.1 | Medical condition in easily understood language |
degenerative disease of the cornea |
malattia degenerativa della cornea |
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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 | PT |
E.1.2 | Classification code | 10069732 |
E.1.2 | Term | Neurotrophic keratopathy |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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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 |
• In the first 24 patients, to determine the safety, tolerability and PK profile of REC 0/0559 (MT8) given as 1 drop 4 times a day (QID) of escalating doses up to 50 µg/mL. • To determine the efficacy and safety of MT8 given as 1 drop QID at 5, 25, and 50 µg/mL during 8 weeks and select the dose with the best benefit risk ratio. |
Per i primi 24 pazienti, determinare la sicurezza, la tollerabilità e il profilo PK di REC 0/0559 (MT8) somministrato in 1 goccia 4 volte al giorno (QID) in dosi crescenti fino a 50 µg/ml. |
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E.2.2 | Secondary objectives of the trial |
Not applicable |
non applicabile |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Be a male or female aged = 18 years 2. Have Stage 2 moderate (PED) or Stage 3 severe (corneal ulcer) NK involving only 1 eye (study eye) and of at least 2 weeks duration. 3. Have no objective clinical evidence of improvement in the PED or corneal ulceration within the 2 weeks before the Screening Visit despite use of conventional non-surgical treatment. 4. Have decreased corneal sensitivity (= 4cm using the Cochet-Bonnet aesthesiometer) within the area of the PED or corneal ulcer and outside of the area of the defect in at least one corneal quadrant. 5. Have a BCDVA score = 75 ETDRS letters in the study eye, due to NK. |
1. Essere un maschio o una femmina di età =18 anni 2. Avere NK di stadio 2 moderato (PED) o di stadio 3 grave (ulcera corneale) che coinvolge solo 1 occhio (occhio di studio) da almeno 2 settimane. 3. Non avere avuto evidenze cliniche oggettive di miglioramento della PED o dell'ulcerazione corneale nelle 2 settimane precedenti la visita di screening nonostante l'uso di un trattamento non chirurgico convenzionale. 4. Sensibilità corneale ridotta (= 4 cm utilizzando l’estesiometro di Cochet-Bonnet) all’interno dell’area del PED o dell’ulcera corneale e fuori dall’area del difetto in almeno un quadrante corneale. 5. Punteggio BCDVA = 75 lettere su ETDRS nell’occhio dello studio, a causa della NK. |
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E.4 | Principal exclusion criteria |
Individuals meeting any of the following criteria at the Screening Visit are ineligible to participate in this study. For the study eye: 1. Have severe blepharitis and/or severe meibomian gland disease in the study eye. 2. Have severe vision loss in the study eye with no potential for visual improvement in the opinion of the investigator as a result of the study treatment. 3. Have evidence of corneal ulceration/melting involving the posterior third of the corneal stroma, or perforation in the study eye. 4. Have a history of corneal transplantation in the study eye. 5. Have had prior surgical procedures for the treatment of NK (except amniotic membrane transplantation, 6. Have an uncontrolled glaucoma at the Screening Visit 7. Have Stage 2 or 3 NK or perforation. 8. Have had prior treatment with Oxervate (cenegermin eye drops).
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Le persone che soddisfano uno dei seguenti criteri durante la visita di screening non sono ammissibili a partecipare a questo studio. Per l'occhio in studio: 1. Avere grave blefarite e / o grave malattia della ghiandola di Meibomio nell'occhio dello studio. 2. Grave perdita della vista nell’occhio dello studio senza potenziale miglioramento visivo secondo il parere dello sperimentatore a seguito del trattamento dello studio. 3. Evidenza di ulcera/fusione corneale che interessa il terzo posteriore dello stroma corneale, o perforazione nell’occhio dello studio. 4. Precedente trapianto di cornea nell’occhio dello in studio. 5. Hanno avuto precedenti procedure chirurgiche per il trattamento di NK (ad eccezione del trapianto di membrana amniotica, 6. Avere un glaucoma incontrollato durante la visita di screening 7. Avere Stage 2 o 3 NK o perforazione. 8. Hanno avuto un precedente trattamento con Oxervate (collirio cenegermin). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the percentage of patients achieving complete corneal healing of persistent epithelial defects (PED) or corneal ulcer at Week 8, defined as no corneal fluorescein staining in the area of the PED or corneal ulcer as assessed by an independent central reading centre. |
L’endpoint primario di questo studio è la percentuale di pazienti che raggiungono la guarigione completa della cornea da difetti epiteliali persistenti (Persistent Epithelial Defect, PED) o da ulcera corneale alla settimana 8, definita come assenza di colorazione corneale da fluoresceina nell’area del PED o dell’ulcera corneale secondo la valutazione effettuata da una struttura di lettura indipendente centrale. |
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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) |
• Percentage of patients who achieve a 5-, 10-, and 15-letter mean improvement in best corrected distance visual acuity (BCDVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) chart at Week 8 compared to baseline (in all patients and in patients with a central location of the PED or corneal ulcer, respectively). • Percentage of patients achieving complete corneal healing of PED or corneal ulcer at Week 8, defined as no corneal fluorescein staining in the area of the PED or corneal ulcer as assessed by the investigator. • Time to complete corneal healing of PED or corneal ulcer defined as no corneal fluorescein staining in the area of the PED or corneal ulcer as assessed by an independent central reading. • Time to complete corneal healing of PED or corneal ulcer defined as no corneal fluorescein staining in the area of the PED or corneal ulcer as assessed by the investigator. • Percentage of patients having deterioration of the disease at Week 8 (defined as increase in lesion size = 1 mm as assessed by the investigator, or mean decrease in BCDVA by > 5 letters compared to baseline, or progression in lesion depth to corneal melting or perforation, or onset of infection). • Mean change in BCDVA from baseline to Week 8 in all patients and in patients with a central location of the PED or corneal ulcer, respectively. • Percentage of patients with improvement in corneal sensitivity from baseline as measured by Cochet-Bonnet aesthesiometer at Week 8.
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- Percentuale di pazienti che raggiungono un miglioramento medio di 5, 10 e 15 lettere alla massima acuità visiva corretta (Best Corrected Distance Visual Acuity, BCDVA) misurata mediante la tavola ETDRS (Early Treatment Diabetic Retinopathy Study) alla settimana 8 rispetto al basale (in tutti i pazienti e nei pazienti con una posizione centrale del PED o dell’ulcera corneale, rispettivamente). - Percentuale di pazienti che raggiungono la guarigione completa del PED o dell'ulcera corneale alla settimana 8, definita come assenza di colorazione corneale da fluoresceina nell’area del PED o dell’ulcera corneale secondo la valutazione effettuata dallo sperimentatore. -Tempo trascorso fino alla guarigione completa del PED o dell'ulcera corneale definita come assenza di colorazione corneale da fluoresceina nell’area del PED o dell’ulcera corneale secondo la valutazione effettuata presso una struttura di lettura centrale indipendente. - Percentuale di pazienti con deterioramento della malattia alla settimana 8 (definita come aumento della dimensione della lesione = 1 mm secondo la valutazione dello sperimentatore o riduzione media della BCDVA di > 5 lettere rispetto al basale o progressione della profondità della lesione fino alla fusione o alla perforazione corneale o insorgenza di infezione). -Variazione media della BCDVA dal basale alla settimana 8 in tutti i pazienti e nei pazienti con una posizione centrale del PED o dell’ulcera corneale, rispettivamente. - Percentuale di pazienti con miglioramento della sensibilità corneale dal basale alla settimana 8 misurata con estesiometro di Cochet-Bonnet. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
France |
Germany |
Hungary |
Italy |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |