Clinical Trial of Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations

Study Overview
=================
Brief Summary
-----------------
The purpose of this clinical trial is to examine the safety of gene therapy for Lebers Congenital Amaurosis (LCA) caused by RPE65 mutations using a recombinant adeno-associated virus serotype 2 (rAAV2) vector carrying the human RPE65 (hRPE65) gene. Recently, three independent short-term gene therapy studies in humans with LCA due to RPE65 mutations were published, suggesting that subretinal delivery of rAAV virus carrying the RPE65 gene is safe. As a secondary outcome, improvement in visual function was observed in seven of the first nine treated patients. The proposed study is a similar open label, Phase I clinical trial of uniocular subretinal rAAV2-hRPE65 administration to individuals with RPE65-associated retinal disease. Two cohorts of three subjects each and one cohort of four subjects will be included in this trial. Cohort 1 and 2 will consist of individuals 18 years of age and older and Cohorts 3 will consist of individuals 8 years of age and older. In cohort 2, a larger volume of vector will be administered. Enrollment in Cohort 3 will begin only after confirming the safety of rAAV2-hRPE65 administration in the older group of participants.

Official Title
-----------------
Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-hRPE65) Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations

Conditions
-----------------
Leber Congenital Amaurosis

Intervention / Treatment
-----------------
* Genetic: rAAV2-hRPE65


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Retinal disease caused by homozygous or compound heterozygote RPE65 mutations; Clinical diagnosis of Leber congenital amaurosis (LCA) with severely impaired visual and retinal function, and best corrected visual acuity of 20/50 or worse in the study eye; Ability to perform tests of visual and retinal function; Good general health; Ability to comply with research procedures; Specific for Cohort 1 and 2: 18 years of age and older; Specific for Cohort 3: Over 8 years of age; Exclusion Criteria: Immune deficiency or use of immunosuppressive medications; Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints (for example, glaucoma or ocular media opacities); Complicating systemic diseases; Impaired coagulation or use of anti-platelet agents within 7 days prior to study agent administration; Pregnancy or breastfeeding; Individuals (males and females) of childbearing potential who are unwilling to use effective contraception for 1 year following agent administration and barrier contraception for 3 months following agent administration; Any other condition that would prevent a subject from completing follow-up examinations during the course of the study; Any other condition that, in the opinion of the investigator, makes the subject unsuitable for the study; Current or recent participation in any other research protocol involving investigational agents or therapies, including recent (within past 6 months) receipt of an investigational biologic therapeutic agent. Subjects will not be excluded based on their gender, race or ethnicity.

Ages Eligible for Study
-----------------
Minimum Age: 8 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rAAV2-hRPE65<br> | Genetic: rAAV2-hRPE65<br>* Uniocular subretinal injections; relative doses: Cohort 1 - basic (lowest) viral dose; Cohort 2 - higher (1.5 times basic) viral dose; Cohort 3 - patients 8-17 years of age will receive basic viral dose; patients 18 years of age and over will receive higher dose;<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measure is ocular and systemic safety of the treatment. |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual function, as quantified before and after vector administration. |  | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Leber congenital amaurosis, LCA, RPE65, RPE65-associated Leber congenital amaurosis, Retinal disease due to RPE65 mutations