Gene Therapy for Crigler Najjar Syndrome

CareCN: A phase I/II, open label, escalating dose study to evaluate safety and efficacy of an intravenous injection of GNT0003 (Adeno-associated Viral Vector expressing the UGT1A1 transgene) in patients with severe Crigler-Najjar syndrome requiring phototherapy - CareCN

Status

Active, not recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-000506-37-FR

Enrollment

Registered

2018-01-18

Start date

Unknown

Completion date

Unknown

Last updated

2024-10-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

severe Crigler Najjar syndrome in patients requiring phototherapy MedDRA version: 20.0 Level: PT Classification code 10011386 Term: Crigler-Najjar syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

Interventions

Product Name: rAAV8-hUGT1A1 Product Code: GNT0003 Pharmaceutical Form: Concentrate for solution for infusion

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Patients with severe Crigler-Najjar syndrome requiring phototherapy 2. Molecular confirmation of mutation in the UGT1A1 gene by DNA sequencing Are the trial subjects under 18? yes Number of subjects for this age range: 9 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1

Exclusion criteria

Exclusion criteria: 1. Fibrosis score = 3 (METAVIR) or 10 PKa 2. Patients who underwent liver transplantation

Design outcomes

Primary

Measure	Time frame
Main Objective: - 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;Secondary Objective: - 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;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;Timepoint(s) of evaluation of this end point: - Primary Safety endpoint: from Baseline to each visit - Secondary Safety endpoint: week 16 + 7 days	—

Measure

Time frame

Main Objective: - 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;Secondary Objective: - 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;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;Timepoint(s) of evaluation of this end point: - Primary Safety endpoint: from Baseline to each visit - Secondary Safety endpoint: week 16 + 7 days

—

Secondary

Measure	Time frame
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 ;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	—

Countries

France, Italy, Netherlands

Contacts

Public ContactGeraldine HONNET

Genethon

clinical_development@genethon.fr0033169 47 29 64

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026