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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I/II Controlled Dose-escalating Trial to Establish the Baseline Safety and Efficacy of a Single Subretinal Injection of rAAV.sFlt-1 Into Eyes of Patients With Exudative Age-related Macular Degeneration (AMD)

Conditions
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Macular Degeneration, Age-related Maculopathies, Age-related Maculopathy, Maculopathies,Age-related, Maculopathy,Age-related, Retinal Degeneration, Retinal Neovascularization, Eye Diseases

Intervention / Treatment
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* Biological: rAAV.sFlt-1
* Biological: rAAV.sFlt-1
* Other: Control (ranibizumab alone)


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose rAAV.sFlt-1<br> | Biological: rAAV.sFlt-1<br>* 1 x 10^10 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection<br>|
| Experimental: High Dose rAAV.sFlt-1<br> | Biological: rAAV.sFlt-1<br>* 1 x 10^11 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection<br>|
| Active Comparator: Control - ranibizumab only<br> | Other: Control (ranibizumab alone)<br>* Patients will not receive rAAV.sFlt-1, but will be eligible for retreatment with ranibizumab (Lucentis).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| No sign of unresolved ophthalmic complications, toxicity or systemic complications as measured by laboratory tests from 1 month post injection | Ocular examination: Ocular inflammation Intraocular pressure Visual acuity Retinal bleeding Abnormal laboratory data | Primary endpoint at 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maintenance or improvement of vision without the necessity of ranibizumab re-injections | Best-corrected visual acuity CNV lesion Foveal thickness | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age-related Macular Degeneration, AAV, AMD, Wet AMD, Neovascular AMD, Gene Therapy, Ocular, Ocular Gene Therapy, Eye diseases, Macular Degeneration, Retinal Degeneration, Retinal Neovascularization, Wet Macular Degeneration, Retinal Diseases