This trial is active, not recruiting.

Condition leber congenital amaurosis
Treatment aav2-hrpe65v2
Phase phase 1/phase 2
Sponsor Spark Therapeutics
Start date November 2010
End date November 2026
Trial size 12 participants
Trial identifier NCT01208389, 10-007752, AAV2-hRPE65v2-102


The study is a follow-on to a Phase 1 dose-escalation and safety study.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Primary purpose treatment
Masking no masking
Administration of study agent (AAV2-hRPE65v2) to the previously, uninjected contralateral eye:
One time, subretinal administration of 1.5E11 vg AAV2-hRPE65v2 vector to the contralateral, previously uninjected eye.

Primary Outcomes

Adverse events as a measure of safety and tolerability
time frame: 15 years

Secondary Outcomes

Visual acuity
time frame: 15 years
Visual field
time frame: 15 years
Pupillary light response
time frame: 15 years
Mobility testing
time frame: 15 years
Full-field light threshold sensitivity testing
time frame: 15 years
Contrast sensitivity
time frame: 15 years

Eligibility Criteria

All participants at least 8 years old.

Inclusion Criteria: - Prior participation in Phase 1 study with unilateral, subretinal administration of AAV2-hRPE65v2. - Visual acuity equal to or greater than light perception. - Sufficient viable retinal cells in contralateral, previously uninjected eye, as determined by non-invasive means, such as optical coherence tomography (OCT) and/or ophthalmoscopy. Must have either: 1) an area of retina within the posterior pole of > 100 µm shown on OCT; 2) ≥ 3 disc areas of retina without atrophy or pigmentary degeneration within the posterior pole; or 3) remaining visual field within 50 degrees of fixation. - Willingness to adhere to protocol and long-term follow-up as evidenced by written informed consent or parental permission and subject assent (where applicable). Exclusion Criteria: - Unable or unwilling to meet requirements of the study. - Participation in any other study of an investigational drug within the past six months. - Use of retinoid compounds or precursors that could potentially interact with the biochemical activity of the RPE65 enzyme; individuals who discontinue use of these compounds for 18 months may become eligible. - Prior intraocular surgery within six months. - Known sensitivity to medications planned for use in the peri-operative period. - Pre-existing eye conditions, such as glaucoma, or complicating systemic diseases that would preclude the planned surgery or could interfere with the interpretation of study. Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter ocular function. Examples are malignancies whose treatment could affect central nervous system function (for example: radiation treatment of the orbit; leukemia with CNS/optic nerve involvement). Subjects with diabetes or sickle cell disease would be excluded if they had any manifestation of advanced retinopathy (e.g. macular edema or proliferative changes). Also excluded would be subjects with immunodeficiency (acquired or congenital) as there could be susceptibility to opportunistic infection (such as CMV retinitis). - Individuals of childbearing potential who are pregnant or unwilling to use effective contraception for four months following vector administration. - Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study and, in the opinion of the investigator, makes the potential subject unsuitable for the study. - Subjects will NOT be excluded based on their gender, race, or ethnicity.

Additional Information

Official title A Follow-On Study to Evaluate the Safety of Re-Administration of Adeno-Associated Viral Vector Containing the Gene for Human RPE65 [AAV2-hRPE65v2] to the Contralateral Eye in Subjects With Leber Congenital Amaurosis (LCA) Previously Enrolled in a Phase 1 Study
Principal investigator Albert M Maguire, MD
Description The study is a follow-on to a Phase 1 dose-escalation and safety study (closed to enrollment as of June 2009). Up to twelve adults and children with molecular diagnosis of LCA2, who have participated in the earlier Phase 1 study, and who meet all study eligibility criteria, will receive AAV2-hRPE65v2 vector in the previously uninjected, contralateral eye to evaluate the safety of bilateral, sequential subretinal administration of AAV2-hRPE65v2.
Trial information was received from ClinicalTrials.gov and was last updated in March 2017.
Information provided to ClinicalTrials.gov by Spark Therapeutics.