Gene Therapy for Severe Crigler Najjar Syndrome

Genethon17 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Crigler-Najjar Syndrome

Interventions

Eligibility

Sex: ALLMin age: 9 Years

Medical Language ↔ Plain English

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

Locations (4)

Hopital Antoine BECLERE

Clamart, France

RECRUITING

ASST Papa Giovanni XXIII

Bergamo, Italy

RECRUITING

Azienda Ospedaliera Universitaria Federico II

Napoli, Italy

RECRUITING

AMC

Amsterdam, Netherlands

RECRUITING

Outcomes

Primary Outcomes

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 weeks

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 weeks

Secondary Outcomes

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 weeks

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

Gene Therapy for Severe Crigler Najjar Syndrome

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts