CClinicalTrials.gg
RecruitingNCT03466463CareCNUpdated Mar 28, 2023

Gene Therapy for Severe Crigler Najjar Syndrome

An interventional study of GNT0003 in Crigler-Najjar Syndrome, sponsored by Genethon. Recruiting at 4 sites in 3 countries. Open to participants aged 9 Years and older. Per ClinicalTrials.gov, last updated 2023-03-28.

Sponsored by Genethon · Not applicable, Interventional, and Other

Phase
Not applicable
Study type
Interventional
Enrollment
17
Allocation
Not applicable
Ages
9 Years and older
Sex
All
01

Study 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.
02

Conditions studied

  • Crigler-Najjar Syndrome

Keywords

  • Crigler-Najjar
  • Adeno Associated Virus
03

Who can participate

Ages eligible
9 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Not applicable
Primary purpose
Other
Allocation
Not applicable
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
17 participants (estimated)

Study arms

  • Experimental
    GNT0003

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

    Genetic: GNT0003

Interventions

  • GeneticGNT0003

    Intravenous infusion, single dose

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: 48 weeks

  2. 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.

    Time frame: 48 weeks

Secondary outcomes

  1. 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)

    Time frame: 48 weeks

  2. 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

    Time frame: 48 weeks

06

Study locations

4 of 4 sites recruiting
  • Hopital Antoine BECLERE
    Clamart, 92141, France
    Recruiting
  • ASST Papa Giovanni XXIII
    Bergame, 24127, Italy
    • · Contact · ldantiga@asst-pg23.it · 00390352674959
    • Lorenzo D'Antiga, MD, PHD · Principal investigator
    Recruiting
  • Azienda Ospedaliera Universitaria Federico II
    Napoli, 80131, Italy
    • · Contact · brunetti@tigem.it · 00390816132361
    • Nicola Brunetti-Pierri, MD, PHD · Principal investigator
    Recruiting
  • AMC
    Amsterdam, 1105, Netherlands
    Recruiting
07

Registry details

Key details

Study ID
NCT03466463
Lead sponsor
Genethon
Responsible party
Sponsor
First posted
Mar 15, 2018
Start date
Mar 19, 2018
Primary completion
Mar 30, 2026 (estimated)
Completion
Mar 30, 2030 (estimated)
Last update
Mar 28, 2023

Study contacts

Genethon Clinical Development Department
Contact
clinical_development@genethon.fr
00 33 (0)1 69 47 10 32
LABRUNE Philippe, Prof
principal investigator · Hopital Antoine Beclere

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion