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Gene Therapy for Severe Crigler Najjar Syndrome (CareCN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03466463
Recruitment Status : Recruiting
First Posted : March 15, 2018
Last Update Posted : March 28, 2023
Information provided by (Responsible Party):

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.

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

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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, 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 : March 30, 2026
Estimated Study Completion Date : March 30, 2030

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

Primary Outcome Measures :
  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 [ Time Frame: 48 weeks ]
    Decrease of total Serum bilirubin level after interruption of daily phototherapy (Efficacy); change in serum total biliirubin from baseline to week 48

  2. Incidence of Treatment Emergent Adverse Events or Treatement Serious Adverse Events [ Time Frame: 48 weeks ]

    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.

Secondary Outcome Measures :
  1. Change in Health-related quality of Life for Adults from Baseline to Week 48 after GNT0003 administration [ Time Frame: 48 weeks ]

    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)

  2. Change in Health-related quality of Life for Children from Baseline to Week 48 after GNT0003 administration [ Time Frame: 48 weeks ]

    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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   9 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   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:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03466463

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Contact: Genethon Clinical Development Department 00 33 (0)1 69 47 10 32

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Hopital Antoine BECLERE Recruiting
Clamart, France, 92141
Contact    00 33 (0)1 45 37 42 72   
Principal Investigator: Philippe LABRUNE, MD,PHD         
ASST Papa Giovanni XXIII Recruiting
Bergame, Italy, 24127
Contact    00390352674959   
Principal Investigator: Lorenzo D'Antiga, MD, PHD         
Azienda Ospedaliera Universitaria Federico II Recruiting
Napoli, Italy, 80131
Contact    00390816132361   
Principal Investigator: Nicola Brunetti-Pierri, MD, PHD         
AMC Recruiting
Amsterdam, Netherlands, 1105
Contact    0031-641476782   
Principal Investigator: Ulrich Beuers, MD, PHD         
Sponsors and Collaborators
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Principal Investigator: LABRUNE Philippe, Prof Hopital Antoine Beclere
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Responsible Party: Genethon Identifier: NCT03466463    
Other Study ID Numbers: GNT-012-CRIG
First Posted: March 15, 2018    Key Record Dates
Last Update Posted: March 28, 2023
Last Verified: February 2023

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Genethon:
Adeno Associated Virus
Additional relevant MeSH terms:
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Crigler-Najjar Syndrome
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Hyperbilirubinemia, Hereditary
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases