E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Crigler Najjar syndrome in patients requiring daily phototherapy (= 6h/day) |
Sindrome di Crigler-Najjar grave in pazienti che necessitano di fototerapia giornaliera (= 6 ore/giorno) |
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E.1.1.1 | Medical condition in easily understood language |
Crigler-Najjar Syndrome |
Sindrome di Crigler-Najjar |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
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 | 10011386 |
E.1.2 | Term | Crigler-Najjar syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 |
- Safety: To assess safety and tolerability of a single intravenous administration of GNT0003 in patients with severe Crigler-Najjar syndrome requiring phototherapy - Efficacy: To assess efficacy of a single intravenous administration of GNT0003 in patients with severe Crigler-Najjar syndrome measured by the serum bilirubin level and the need of phototherapy |
- Sicurezza: valutare la sicurezza e la tollerabilità di una singola somministrazione endovenosa di GNT0003 in pazienti con sindrome di Crigler-Najjar grave che necessitano di fototerapia - Efficacia: valutare l'efficacia di una singola somministrazione endovenosa di GNT0003 in pazienti con sindrome di Crigler-Najjar grave, misurata dal livello di bilirubina totale nel siero e dalla necessità di fototerapia |
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E.2.2 | Secondary objectives of the trial |
- To measure the effect of the UGT1A1 transgene expression on the serum total bilirubin level, the bilirubin/albumin ratio - To measure the effect of UGT1A1 transgene expression by determining presence of bilirubin conjugates in bile - To evaluate the quality of life of patients - To measure the immune responses to the UGT1A1 transgene product and AAV capsid proteins |
- Misurare l'effetto dell'espressione del transgene UGT1A1 sul livello di bilirubina totale nel siero e il rapporto bilirubina/albumina - Misurare l'effetto dell'espressione del transgene UGT1A, determinando la presenza di bilirubina diretta nella bile - Valutare la qualità di vita dei pazienti - Misurare l'immuno risposta al prodotto del transgene UGT1A1 e alle proteine del capside degli AAV |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Patients with severe Crigler-Najjar syndrome requiring phototherapy [2] Molecular confirmation of mutations in the UGT1A1 gene by DNA sequencing |
[1] Pazienti con sindrome di Crigler-Najjar grave, che necessitano di fototerapia [2] Conferma molecolare delle mutazioni nel gene UGT1A1 nella sequenza del DNA |
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E.4 | Principal exclusion criteria |
[1] Fibrosis score = 3 (METAVIR) or 10 kPa [2] Patients who underwent liver transplantation |
[1] Score di fibrosi = 3 (METAVIR) o 10 kPA [2] Pazienti che hanno subito un trapianto di fegato
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E.5 End points |
E.5.1 | Primary end point(s) |
-Safety: Safety and tolerability, measured by the incidence of adverse event (AE) or serious adverse event (SAE) evaluated by changes in laboratory parameters, vital signs and in the physical examination from baseline to each visit, will be evaluated for each dose and for the study as a whole - Efficacy: Serum total bilirubin = 300 µmol/L, 7 days after interruption of daily phototherapy occuring at week 16 after the administration of GNT0003
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- Sicurezza: per ogni dose e per lo studio nel suo insieme, verranno valutate la sicurezza e la tollerabilità, misurate con l'incidenza di eventi avversi (EA) o di eventi avversi gravi (EAG) valutati mediante il cambiamento dei parametri di laboratorio, dei parametri vitali e dell’esame fisico dalla visita baseline a ogni visita. - Efficacia: Bilirubina totale nel siero = 300 µmol/L, 7 giorni dopo l’interruzione della fototerapia giornaliera, avvenuta alla settimana 16 dopo la somministrazione di GNT0003
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Primary Safety endpoint: from Baseline to each visit - Primary Efficacy endpoint: week 16 + 7 days |
- Endpoint di sicurezza primario: dalla visita baseline a ogni visita - Endpoint di efficacia primario: settimana 16 + 7 giorni
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E.5.2 | Secondary end point(s) |
1. Change in bilirubin/albumin ratio from baseline to each visit 2. Quality of life assessment: Change in 36-Item Short Form Survey (SF-36) and 10-item Short-Form Survey (SF10) score from baseline to W24 and W48
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1. Cambiamento del rapporto bilirubina/albumina dalla visita baseline a ogni visita successiva 2. Valutazione della qualità della vita: cambiamenti nel punteggio dello Short Form Health Survey (SF-36 e SF-10), questionari sulla qualità della vita del paziente, dalla terapia pregene fino alla S24 e S48. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Endpoint 1: from baseline to each visit Secondary Endpoint 2: from baseline to W24 and W48
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End point secondario 1: dalla visita baseline a ogni visita End point secondario 2: dalla visita baseline alla S24 e S48
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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 | Yes |
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) | 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 | 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 | 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.8.2.4 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | 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 | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |