E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
severe Crigler Najjar syndrome in patients requiring phototherapy |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 |
|
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 |
|
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 |
|
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 mutation in the UGT1A1 gene by DNA sequencing
|
|
E.4 | Principal exclusion criteria |
1. Fibrosis score ≥ 3 (METAVIR) or 10 PKa
2. Patients who underwent liver transplantation |
|
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 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Primary Safety endpoint: from Baseline to each visit
- Primary Safety endpoint: week 16 + 7 days |
|
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
|
|
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 |
|
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 | 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 | 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 | No |
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
|
|
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 | 2 |
E.8.9.1 | In the Member State concerned days | |
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 | 2 |