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

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

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.

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.