Gene Therapy for Severe Crigler Najjar Syndrome (CareCN)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Crigler-Najjar Syndrome
• Intervention / Treatment: Genetic: GNT0003

• Study Type: Interventional
• Enrollment (Anticipated): 17
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Genethon Clinical Development Department; Phone Number: 00 33 (0)1 69 47 10 32; Email: clinical_development@genethon.fr

Study Locations

• France
  • Clamart, France, 92141
    • Recruiting
    • Hôpital Antoine Béclère
    • Contact: Phone Number: 00 33 (0)1 45 37 42 72; Email: philippe.labrune@abc.aphp.fr
    • Principal Investigator: Philippe LABRUNE, MD,PHD
• Italy
  • Bergame, Italy, 24127
    • Recruiting
    • Asst Papa Giovanni XXIII
    • Contact: Phone Number: 00390352674959; Email: ldantiga@asst-pg23.it
    • Principal Investigator: Lorenzo D'Antiga, MD, PHD
  • Napoli, Italy, 80131
    • Recruiting
    • Azienda Ospedaliera Universitaria Federico II
    • Contact: Phone Number: 00390816132361; Email: brunetti@tigem.it
    • Principal Investigator: Nicola Brunetti-Pierri, MD, PHD
• Netherlands
  • Amsterdam, Netherlands, 1105
    • Recruiting
    • AMC
    • Contact: Phone Number: 0031-641476782; Email: u.h.beuers@amc.uva.nl
    • Principal Investigator: Ulrich Beuers, MD, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GNT0003; 2 doses of the IMP assessed in the dose escalation, open-label, phase 1/2 study	Genetic: GNT0003; Intravenous infusion, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Genethon
• Investigators: Principal Investigator: LABRUNE Philippe, Prof, Hôpital Antoine Béclère

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2018
• Primary Completion (Anticipated): March 30, 2026
• Study Completion (Anticipated): March 30, 2030

Study Registration Dates

• First Submitted: February 1, 2018
• First Submitted That Met QC Criteria: March 8, 2018
• First Posted (Actual): March 15, 2018

Study Record Updates

• Last Update Posted (Actual): March 28, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Adeno Associated Virus; Crigler-Najjar
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Hyperbilirubinemia, Hereditary; Syndrome; Cardiomyopathies; Crigler-Najjar Syndrome
• Other Study ID Numbers: GNT-012-CRIG

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No