Gene Therapy for Severe Crigler Najjar Syndrome

Crigler-Najjar Syndrome Clinical Trial

— CareCN  

Official title:

A Phase I/II, Open Label, Study to Evaluate Safety and Efficacy of an Intravenous Injection of GNT0003 (AAV Vector Expressing the UGT1A1 Transgene) in Patients With Severe Crigler-Najjar Syndrome Requiring Phototherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03466463
• Other study ID #: GNT-012-CRIG
• Status: Recruiting
• Phase: N/A
• Start date: March 19, 2018
• Est. completion date: March 30, 2030

Study information

• Verified date: February 2023
• Source: Genethon
• Contact: Genethon Clinical Development Department
• Phone: 00 33 (0)1 69 47 10 32
• Email: clinical_development[@]genethon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1/2, multinational, open-label, study to evaluate the safety and efficacy of an intravenous infusion of GNT0003 in patients with Crigler-Najjar aged ≥10 years and requiring phototherapy. Patients will received a single administration of GNT0003 and will be followed for safety and efficacy of approximately 60 months (5 years):

• a follow-up of approximately 12 months (48 weeks)

• a long term follow-up of approximately 48 months (4 years), in order to be in line with the latest EMEA Guideline on follow-up of patients administered with gene therapy medicinal products, released on 22 Oct.2009 by the Committee for medicinal products for human use.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 17
• Est. completion date: March 30, 2030
• Est. primary completion date: March 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 9 Years and older

Eligibility

Inclusion Criteria:

• Patients with severe Crigler-Najjar syndrome resulting from a molecular confirmation of mutations in the UGT1A1 gene and requiring phototherapy

• Male or female at least 9 years at the date of signature of informed consent

• Patient able to give informed assent and/or consent in writing

Exclusion Criteria:

• Patients who underwent liver transplantation

• Patients with chronic hepatitis B or C

• Patients infected with Human immunodeficiency virus (HIV)

• Patients with significant underlying liver disease

• Patients with significant encephalopathy

• Participation in any other investigational trial during this trial

• Patients unable or unwilling to comply with the protocol requirements

Related Conditions & MeSH terms

• Cardiomyopathies
• Crigler-Najjar Syndrome
• Syndrome

Intervention

Genetic:
• GNT0003
Intravenous infusion, single dose

Locations

Country	Name	City	State
France	Hopital Antoine BECLERE	Clamart
Italy	ASST Papa Giovanni XXIII	Bergame
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Netherlands	AMC	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
Genethon

Countries where clinical trial is conducted

France,  Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients having received the selected dose of GNT0003 with serum bilirubin = 300µmol/L within 48 meeks after GNT0003 administration and without phototherapy from week 16	Decrease of total Serum bilirubin level after interruption of daily phototherapy (Efficacy); change in serum total biliirubin from baseline to week 48	48 weeks
Primary	Incidence of Treatment Emergent Adverse Events or Treatement Serious Adverse Events	Incidence of AE/SAE evaluated by changes in laboratory parameters, vital signs, physical examination, reported from baseline to each visit study. Clinically relevant abnormal findings on Laboratory values, Vital Signs, Physical findings will be reported as Adverse Events.; Incidence and Severity of Adverse Events for each body system will be presented for each dose level and summarized overall.	48 weeks
Secondary	Change in Health-related quality of Life for Adults from Baseline to Week 48 after GNT0003 administration	Quality of Life outcome measure: change of quality of life from Baseline to Week 48 after GNT0003 administration.; Scale 36-Item Short Form Survey (SF-36 Health Survey) for adults: from 0 (negative to health) to 100 (positive to health)	48 weeks
Secondary	Change in Health-related quality of Life for Children from Baseline to Week 48 after GNT0003 administration	Quality of Life outcome measure: change of quality of life from Baseline to Week 48 after GNT0003 administration.; PedsQL 4.0 Generic Core Scale for pediatrics: 0-100 scale where higher scores indicate better health-related quality of life	48 weeks