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Gene Therapy for Severe Crigler Najjar Syndrome (CareCN)

Primary Purpose

Crigler-Najjar Syndrome

Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
GNT0003
Sponsored by
Genethon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Crigler-Najjar Syndrome focused on measuring Crigler-Najjar, Adeno Associated Virus

Eligibility Criteria

9 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hopital Antoine BECLERERecruiting
  • ASST Papa Giovanni XXIIIRecruiting
  • Azienda Ospedaliera Universitaria Federico IIRecruiting
  • AMCRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GNT0003

Arm Description

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

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

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)
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

Full Information

First Posted
February 1, 2018
Last Updated
March 23, 2023
Sponsor
Genethon
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1. Study Identification

Unique Protocol Identification Number
NCT03466463
Brief Title
Gene Therapy for Severe Crigler Najjar Syndrome
Acronym
CareCN
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 19, 2018 (Actual)
Primary Completion Date
March 30, 2026 (Anticipated)
Study Completion Date
March 30, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genethon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crigler-Najjar Syndrome
Keywords
Crigler-Najjar, Adeno Associated Virus

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GNT0003
Arm Type
Experimental
Arm Description
2 doses of the IMP assessed in the dose escalation, open-label, phase 1/2 study
Intervention Type
Genetic
Intervention Name(s)
GNT0003
Intervention Description
Intravenous infusion, single dose
Primary Outcome Measure Information:
Title
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
Description
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
Title
Incidence of Treatment Emergent Adverse Events or Treatement Serious Adverse Events
Description
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 Outcome Measure Information:
Title
Change in Health-related quality of Life for Adults from Baseline to Week 48 after GNT0003 administration
Description
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
Title
Change in Health-related quality of Life for Children from Baseline to Week 48 after GNT0003 administration
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
9 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Genethon Clinical Development Department
Phone
00 33 (0)1 69 47 10 32
Email
clinical_development@genethon.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
LABRUNE Philippe, Prof
Organizational Affiliation
Hopital Antoine Beclere
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Antoine BECLERE
City
Clamart
ZIP/Postal Code
92141
Country
France
Individual Site Status
Recruiting
Facility Contact:
Phone
00 33 (0)1 45 37 42 72
Email
philippe.labrune@abc.aphp.fr
First Name & Middle Initial & Last Name & Degree
Philippe LABRUNE, MD,PHD
Facility Name
ASST Papa Giovanni XXIII
City
Bergame
ZIP/Postal Code
24127
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
Phone
00390352674959
Email
ldantiga@asst-pg23.it
First Name & Middle Initial & Last Name & Degree
Lorenzo D'Antiga, MD, PHD
Facility Name
Azienda Ospedaliera Universitaria Federico II
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
Phone
00390816132361
Email
brunetti@tigem.it
First Name & Middle Initial & Last Name & Degree
Nicola Brunetti-Pierri, MD, PHD
Facility Name
AMC
City
Amsterdam
ZIP/Postal Code
1105
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
Phone
0031-641476782
Email
u.h.beuers@amc.uva.nl
First Name & Middle Initial & Last Name & Degree
Ulrich Beuers, MD, PHD

12. IPD Sharing Statement

Learn more about this trial

Gene Therapy for Severe Crigler Najjar Syndrome

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