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

Sponsor

Lions Eye Institute, Perth, Western Australia (Other)

Overall Status

Completed

CT.gov ID

NCT01494805

Collaborator

Adverum Biotechnologies, Inc. (Industry)

Enrollment

Location

Arms

Actual Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Macular Degeneration Age-related Maculopathies Age-related Maculopathy Maculopathies,Age-related Maculopathy,Age-related Retinal Degeneration Retinal Neovascularization Eye Diseases	Biological: rAAV.sFlt-1 Biological: rAAV.sFlt-1 Other: Control (ranibizumab alone)	Phase 1/Phase 2

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Dec 1, 2011

Actual Primary Completion Date :

May 1, 2017

Actual Study Completion Date :

Aug 1, 2017

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Low Dose rAAV.sFlt-1

Biological: rAAV.sFlt-1

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

Experimental: High Dose rAAV.sFlt-1

Biological: rAAV.sFlt-1

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

Active Comparator: Control - ranibizumab only

Other: Control (ranibizumab alone)

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

Outcome Measures

Primary Outcome Measures

No sign of unresolved ophthalmic complications, toxicity or systemic complications as measured by laboratory tests from 1 month post injection [Primary endpoint at 1 month]
Ocular examination: Ocular inflammation Intraocular pressure Visual acuity Retinal bleeding Abnormal laboratory data

Secondary Outcome Measures

Maintenance or improvement of vision without the necessity of ranibizumab re-injections [Up to 3 years]
Best-corrected visual acuity CNV lesion Foveal thickness

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;