Gene Therapy for Severe Crigler Najjar Syndrome (CareCN)

• ClinicalTrials.gov Identifier: NCT03466463
• Recruitment Status: Recruiting
• First Posted: March 15, 2018
• Last Update Posted: March 28, 2023
• Sponsor: Genethon
• Information provided by (Responsible Party): Genethon

Tracking Information

• First Submitted Date: February 1, 2018
• First Posted Date: March 15, 2018
• Last Update Posted Date: March 28, 2023
• Actual Study Start Date: March 19, 2018
• Estimated Primary Completion Date: March 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 23, 2023)

• 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
• 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.

Original Primary Outcome Measures (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.

Current Secondary Outcome Measures (submitted: March 23, 2023)

• 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)
• 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

Original Secondary Outcome Measures (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: Gene Therapy for Severe Crigler Najjar Syndrome
• 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Crigler-Najjar Syndrome

Intervention

Genetic: GNT0003

Intravenous infusion, single dose

Study Arms

Experimental: GNT0003

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

Intervention: Genetic: GNT0003

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 8, 2018): 17
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 30, 2030
• Estimated Primary Completion Date: March 30, 2026 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 9 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Genethon Clinical Development Department; 00 33 (0)1 69 47 10 32; clinical_development@genethon.fr

• Listed Location Countries: France, Italy, Netherlands

Administrative Information

• NCT Number: NCT03466463
• Other Study ID Numbers: 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: Not Provided
• Current Responsible Party: Genethon
• Original Responsible Party: Same as current
• Current Study Sponsor: Genethon
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: LABRUNE Philippe, Prof; Hopital Antoine Beclere

• PRS Account: Genethon
• Verification Date: February 2023