Safety and Efficacy Study of rAAV.sFlt-1 in Patients With Exudative Age-Related Macular Degeneration

Lions Eye Institute, Perth, Western Australia40 enrolled

Overview

The study will involve approximately 40 subjects aged 55 or above who have exudative age-related macular degeneration (wet AMD). Patients will be randomized to receive one of two doses of rAAV.sFlt-1 or assigned to the control group.

A new treatment for exudative age-related macular degeneration (wet AMD) is being investigated. The purpose of this Phase I/II clinical research study is to examine the baseline safety and efficacy of an experimental study drug to treat a complication of the disease which leads to vision loss. The name of the study drug is rAAV.sFlt-1. This experimental study uses a non-pathogenic virus to express a therapeutic protein within the eye. The therapeutic diminishes the growth of abnormal blood vessels under the retina. The duration of effect is thought to be long-term (years) following a single administration. The clinical research study will look at the baseline safety and efficacy of a single injection of rAAV.sFlt-1 injected directly into the eye. Approximately forty (40) subjects will participate in Australia. The primary endpoint of the study is at one month, with extended follow up for 3 years.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Macular Degeneration Age-related Maculopathies

Interventions

rAAV.sFlt-1BIOLOGICAL

1 x 10\^10 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection

rAAV.sFlt-1BIOLOGICAL

1 x 10\^11 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection

Control (ranibizumab alone)OTHER

Patients will not receive rAAV.sFlt-1, but will be eligible for retreatment with ranibizumab (Lucentis).

Eligibility

Sex: ALLMin age: 55 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age greater than or equal to 55 years; * Subfoveal CNV secondary to AMD and with best corrected visual acuity of 3/60 - 6/9 with 6/60 or better in the other eye; * Fluorescein angiogram of the study eye must show evidence of a leaking subfoveal choroidal neovascular lesion, or CNV currently under active management with anti-VEGF therapy; * Must be a candidate for anti-VEGF intravitreal injections; * No previous retinal treatment of photodynamic therapy or laser; * Able to provide informed consent; * Able to comply with protocol requirements, including follow-up visits. Exclusion Criteria: * Liver enzymes \> 2 X upper limit of normal; * Any prior treatment for AMD in the study / control eye, excluding anti-VEGF injections; * Extensive sub-foveal scarring, extensive geographic atrophy, or thick subretinal blood in the study eye as determined by the investigator; * Significant retinal disease other than sub-foveal CNV AMD;

Outcomes

Primary Outcomes

No sign of unresolved ophthalmic complications, toxicity or systemic complications as measured by laboratory tests from 1 month post injection

1. Ocular examination: * Ocular inflammation * Intraocular pressure * Visual acuity * Retinal bleeding 2. Abnormal laboratory data

Time frame: Primary endpoint at 1 month

Secondary Outcomes

Maintenance or improvement of vision without the necessity of ranibizumab re-injections

1. Best-corrected visual acuity 2. CNV lesion 3. Foveal thickness

Time frame: Up to 3 years