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

Hadassah Medical Center

Status and phase

Completed

Phase 1

Conditions

Leber Congenital Amaurosis

Treatments

Genetic: rAAV2-hRPE65

Study type

Interventional

Funder types

Other

Identifiers

NCT00821340

RPE65-HMO-CTIL

Details and patient eligibility

About

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.

Enrollment

3 patients

Sex

All

Ages

8+ years old

Volunteers

No Healthy Volunteers

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.