Gene Therapy for Severe Crigler Najjar Syndrome (CareCN)

• ClinicalTrials.gov Identifier: NCT03466463
• Recruitment Status: Recruiting
• First Posted: March 15, 2018
• Last Update Posted: June 2, 2021
• Sponsor: Genethon
• Information provided by (Responsible Party): Genethon

Study Description

Brief Summary:

This is a Phase 1/2, multinational, open-label, escalating-dose 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.

Condition or disease	Intervention/treatment	Phase
Crigler-Najjar Syndrome	Genetic: GNT0003	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase I/II, Open Label, Escalating Dose 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
• Actual Study Start Date: March 19, 2018
• Estimated Primary Completion Date: June 20, 2022
• Estimated Study Completion Date: December 27, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of Adverse Events / Serious Adverse Events (Safety) : All Treatment Emergent Adverse Events, all Serious Adverse Events [ Time Frame: 12 months ]

   Incidence of AE/SAE evaluated by changes in laboratory parameters, vital signs, physical examination, reported from baseline to each visit, evaluated for each dose and for the study as a whole. 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.

2. Decrease of total Serum bilirubin level after interruption of daily phototherapy (Efficacy) [ Time Frame: 4 months ]
   Serum total bilirubin ≤ 300 µmol/L, 7 days after interruption of daily phototherapy occuring at week 16 after the administration of GNT0003.

Secondary Outcome Measures :

1. Quality of life assessment [ Time Frame: 60 months ]
   - Scale 36-Item Short Form Survey (SF-36 Health Survey for adults). Outcome measure: change of quality of life from Baseline to Week 24, Week 48 and yearly up to 48 months after IMP administration.
2. Quality of life assessment [ Time Frame: 60 months ]
   - Scale 10-Item Short Form Survey (SF-10 Health Survey for children). Outcome measure: change of quality of life from Baseline to Week 24, Week 48 and yearly up to 48 months after IMP administration.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Genethon Clinical Development Department; 00 33 (0)1 69 47 10 32; clinical_development@genethon.fr

Locations

France

Hopital Antoine BECLERE; Recruiting

Clamart, France, 92141

Contact 00 33 (0)1 45 37 42 72 philippe.labrune@abc.aphp.fr

Principal Investigator: Philippe LABRUNE, MD,PHD

Italy

ASST Papa Giovanni XXIII; Recruiting

Bergame, Italy, 24127

Contact 00390352674959 ldantiga@asst-pg23.it

Principal Investigator: Lorenzo D'Antiga, MD, PHD

Azienda Ospedaliera Universitaria Federico II; Recruiting

Napoli, Italy, 80131

Contact 00390816132361 brunetti@tigem.it

Principal Investigator: Nicola Brunetti-Pierri, MD, PHD

Netherlands

AMC; Recruiting

Amsterdam, Netherlands, 1105

Contact 0031-641476782 u.h.beuers@amc.uva.nl

Principal Investigator: Ulrich Beuers, MD, PHD

Sponsors and Collaborators

Genethon

Investigators

• Principal Investigator: LABRUNE Philippe, Prof; Hopital Antoine Beclere

More Information

• Responsible Party: Genethon
• ClinicalTrials.gov Identifier: NCT03466463
• Other Study ID Numbers: GNT-012-CRIG
• First Posted: March 15, 2018
• Last Update Posted: June 2, 2021
• Last Verified: June 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Genethon:

Crigler-Najjar; Adeno Associated Virus

Additional relevant MeSH terms:

Cardiomyopathies; Crigler-Najjar Syndrome; Syndrome; Disease; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Hyperbilirubinemia, Hereditary; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases