Crigler-Najjar Syndrome
Conditions
Keywords
Crigler-Najjar, Adeno Associated Virus
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.
Interventions
GENETICGNT0003
Intravenous infusion, single dose
Sponsors
Genethon
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Health-related quality of Life for Adults from Baseline to Week 48 after GNT0003 administration | 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 | 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 |
Countries
France, Italy, Netherlands
Contacts
Primary ContactGenethon Clinical Development Department
Outcome results
None listed