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Recruiting NCT03466463

Gene Therapy for Severe Crigler Najjar Syndrome

No phase Interventional Crigler-Najjar Syndrome

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: GNT0003.
Who it may be relevant to
Registry conditions: Crigler-Najjar Syndrome. Basic parameters: from 9 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
France, Italy, Netherlands
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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

Overview

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.

Interventions

  • Genetic GNT0003
    Intravenous infusion, single dose

Primary outcome measures

  • 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 [Time frame: 48 weeks]
  • Incidence of Treatment Emergent Adverse Events or Treatement Serious Adverse Events [Time frame: 48 weeks]
Secondary outcome measures (2)
  • Change in Health-related quality of Life for Adults from Baseline to Week 48 after GNT0003 administration [Time frame: 48 weeks]
  • Change in Health-related quality of Life for Children from Baseline to Week 48 after GNT0003 administration [Time frame: 48 weeks]

Eligibility 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Sequential
Masking
Open label
Primary purpose
Other

Study locations

Italy · 2 centers
  • ASST Papa Giovanni XXIII — Bergamo
  • Azienda Ospedaliera Universitaria Federico II — Naples
France · 1 center
  • Hopital Antoine BECLERE — Clamart
Netherlands · 1 center
  • AMC — Amsterdam

Publications

  • D'Antiga L, Beuers U, Ronzitti G, Brunetti-Pierri N, Baumann U, Di Giorgio A, Aronson S, Hubert A, Romano R, Junge N, Bosma P, Bortolussi G, Muro AF, Soumoudronga RF, Veron P, Collaud F, Knuchel-Legendre N, Labrune P, Mingozzi F. Gene Therapy in Patients with the Crigler-Najjar Syndrome. N Engl J Med. 2023 Aug 17;389(7):620-631. doi: 10.1056/NEJMoa2214084. PMID 37585628

Identifiers

NCT: NCT03466463 · GNT-012-CRIG

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗