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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.
 
ClinicalTrials.gov Identifier: NCT03466463
Recruitment Status : Recruiting
First Posted : March 15, 2018
Last Update Posted : March 12, 2020
Sponsor:
Information provided by (Responsible Party):
Genethon

Tracking Information
First Submitted Date  ICMJE February 1, 2018
First Posted Date  ICMJE March 15, 2018
Last Update Posted Date March 12, 2020
Actual Study Start Date  ICMJE March 19, 2018
Estimated Primary Completion Date October 20, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • Incidence of Adverse Events / Serious Adverse Events (Safety) : All Treatment Emergent Adverse Events, all Serious Adverse Events [ Time Frame: 12 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.
  • Decrease of total Serum bilirubin level after interruption of daily phototherapy (Efficacy) [ Time Frame: 4 months ]
    Serum total bilirubin ≤ 300 µmol/L, 7 days after interruption of daily phototherapy occuring at week 16 after the administration of GNT0003.
Original Primary Outcome Measures  ICMJE
 (submitted: March 8, 2018)
  • 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.
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • Quality of life assessment [ Time Frame: 60 months ]
    - Scale 36-Item Short Form Survey (SF-36 Health Survey for adults). Outcome measure: change of quality of life from Baseline to Week 24, Week 48 and yearly up to 48 months after IMP administration.
  • Quality of life assessment [ Time Frame: 60 months ]
    - Scale 10-Item Short Form Survey (SF-10 Health Survey for children). Outcome measure: change of quality of life from Baseline to Week 24, Week 48 and yearly up to 48 months after IMP administration.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2018)
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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gene Therapy for Severe Crigler Najjar Syndrome
Official Title  ICMJE 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
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 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Crigler-Najjar Syndrome
Intervention  ICMJE Genetic: GNT0003
Intravenous infusion, single dose
Study Arms  ICMJE Experimental: GNT0003
2 doses of the IMP assessed in a dose escalation, open-label, phase 1/2 study
Intervention: Genetic: GNT0003
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 8, 2018)
17
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 27, 2026
Estimated Primary Completion Date October 20, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 9 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Genethon Clinical Development Department 00 33 (0)1 69 47 10 32 clinical_development@genethon.fr
Listed Location Countries  ICMJE France,   Italy,   Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03466463
Other Study ID Numbers  ICMJE GNT-012-CRIG
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genethon
Study Sponsor  ICMJE Genethon
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: LABRUNE Philippe, Prof Hopital Antoine Beclere
PRS Account Genethon
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP