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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 : September 28, 2018
Information provided by (Responsible Party):

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 for 1 year.

Condition or disease Intervention/treatment Phase
Crigler-Najjar Syndrome Genetic: GNT0003 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 17 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : December 31, 2020
Estimated Study Completion Date : December 31, 2020

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

Primary Outcome Measures :
  1. Incidence of Adverse Events / Serious Adverse Events (Safety) : All Treatment Emergent Adverse Events, all Serious Adverse Events [ Time Frame: 29 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: 14 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: 29 months ]
    • Scale 36-Item Short Form Survey (SF-36 Heath Survey for adults) - score range : 0 worse value : - better value (more favorable health state): 100. Scores represent the percentage of total possible score achieved. The scores from those questions that address each specific area of functional health status (STEP II chart) are then averaged together, for a final score within each of the 8 dimensions measured. (eg pain, physical functioning etc.). Outcome measure : change of quality of Life from baseline to Week 24 and week 48 (after IMP administration).
    • Scale 10- Item Short Form Survey (SF-10 Heath Survey for children) - score range : 1 (worse value) to 6 (more favorable health state). : 100 The SF-10 Health Survey for Children is a parent-completed survey that contains 10 questions adapted from the Child Health Questionnaire. Outcome mesure : change of quality of Life from baseline to Week 24 and week 48 (after IMP administration).

Information from the National Library of Medicine

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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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Responsible Party: Genethon Identifier: NCT03466463     History of Changes
Other Study ID Numbers: GNT-012-CRIG
First Posted: March 15, 2018    Key Record Dates
Last Update Posted: September 28, 2018
Last Verified: September 2018

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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