Clinical Gene Therapy Protocol for the Treatment of Retinal Dystrophy Caused by Defects in RPE65

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety and efficacy of the active substance rAAV-2/4.hRPE65 in patients with Leber Congenital Amaurosis or Congenital severe early-onset retinal degeneration associated with RPE65 mutation.

Official Title
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Prospective Monocentric Open Label Non Randomized Uncontrolled Phase I/II Clinical Gene Therapy Protocol for the Treatment of Retinal Dystrophy Caused by Defects in RPE65

Conditions
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Leber Congenital Amaurosis

Intervention / Treatment
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* Drug: rAAV2/4.hRPE65


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mutations that code for abnormal RPE65 protein Presence of characteristic abnormalities in fundus Dramatic reduction of both rods ans cones ERG responses Low visual acuity <0.32 inform consent signed Exclusion Criteria: Patients with chronic conditions such a haematological, cardiac, renal diseases Patients with, within the past 6 months, a clinically significant cardiac disease or known congestive heart failure, cardiac rhytm and conduction abnormalities Patients with pulmonaty dysfunction Patients with suspected rheumatoid arthritis Patients with current systemic infection........

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rAAV2/4.hRPE65<br>3 cohortes of 3 patients each. All the patients enrolled in the study will receive a single subretinal injection in one eye. The eye, that will be injected, will be the eye with the poorest visual acuity. | Drug: rAAV2/4.hRPE65<br>* One injection in on eye Cohorte 1 : 3 patients will receive one injection of up to 400 microliters of the IMP Cohorte 2 : 3 patients will receive one injection of up to 800 microliters of the IMP. Cohorte 3 : 3 patients under age of eighteen will receive one injection up to 400 or 800 microliters of the IMP.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The drug safety evaluation after administration | Biodistribution : Urine sampling and nasal secretion will be collected at several time points after administration of the gene therapy product during all the duration of hospital stay, an average of 7 days. | After administration of the gene therapy product.The patient will be folloed for the duration of the hospital stay, an average of 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Different efficacy parameters and immune parameters have to be measured to conclude on the overall amelioration of quality of life of enrolled patients | Recording global ERG (electroretinogram) Patient efficacy questionnaire Testing of far and near visual acuity, color vision, pupillometry, microperimetry and dark adaptation. | Between Day -120 and Day-7, Day 5, Day 14, Day 30 Day 60, Day 90, Day 120, Day 180, Day 360 |