Gene Therapy for Severe Crigler Najjar Syndrome
ConditionCrigler-Najjar Syndrome
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age9+
SponsorGenethon
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Sequential
Treatments tested in this trial
GNT0003
GeneticIntravenous infusion, single dose
Treatment groups
17 Participants
are divided into 1 treatment groupGroup A: GNT0003Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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
Time frame
48 weeks2
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.
Time frame
48 weeksSecondary outcomes
1
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)
Time frame
48 weeks2
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
Time frame
48 weeks Source ClinicalTrials.gov