NCT03466463

Brief 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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
17

participants targeted

Target at below P25 for not_applicable

Timeline
47mo left

Started Mar 2018

Longer than P75 for not_applicable

Geographic Reach
3 countries

4 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress68%
Mar 2018Mar 2030

First Submitted

Initial submission to the registry

February 1, 2018

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 15, 2018

Completed
4 days until next milestone

Study Start

First participant enrolled

March 19, 2018

Completed
8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 30, 2026

Completed
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 30, 2030

Expected
Last Updated

March 28, 2023

Status Verified

February 1, 2023

Enrollment Period

8 years

First QC Date

February 1, 2018

Last Update Submit

March 23, 2023

Conditions

Crigler-Najjar Syndrome

Keywords

Crigler-NajjarAdeno Associated Virus

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (2)

  • Change in Health-related quality of Life for Adults from Baseline to Week 48 after GNT0003 administration

    48 weeks

  • Change in Health-related quality of Life for Children from Baseline to Week 48 after GNT0003 administration

    48 weeks

Study Arms (1)

GNT0003

EXPERIMENTAL

2 doses of the IMP assessed in the dose escalation, open-label, phase 1/2 study

Genetic: GNT0003

Interventions

GNT0003GENETIC

Intravenous infusion, single dose

GNT0003

Eligibility Criteria

Age9 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Hopital Antoine BECLERE

Clamart, 92141, France

RECRUITING

ASST Papa Giovanni XXIII

Bergamo, 24127, Italy

RECRUITING

Azienda Ospedaliera Universitaria Federico II

Napoli, 80131, Italy

RECRUITING

AMC

Amsterdam, 1105, Netherlands

RECRUITING

Related Publications (1)

  • 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: 37585628DERIVED

MeSH Terms

Conditions

Crigler-Najjar Syndrome

Condition Hierarchy (Ancestors)

Hyperbilirubinemia, HereditaryMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • LABRUNE Philippe, Prof

    Hopital Antoine Beclere

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Genethon Clinical Development Department

CONTACT

00 33 (0)1 69 47 10 32clinical_development@genethon.fr

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
OTHER
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 1, 2018

First Posted

March 15, 2018

Study Start

March 19, 2018

Primary Completion

March 30, 2026

Study Completion (Estimated)

March 30, 2030

Last Updated

March 28, 2023

Record last verified: 2023-02

Locations

NL(1)FR(1)IT(2)