Clinical trial NCT01494805: Safety and Efficacy Study of rAAV.sFlt-1 in Patients With Exudative Age-Related Macular Degeneration
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Macular Degeneration
Age-related Maculopathies
Age-related Maculopathy
Maculopathies,Age-related
Maculopathy,Age-related
Retinal Degeneration
Retinal Neovascularization
Eye Diseases
Keywords: 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
Lead sponsor: Lions Eye Institute, Perth, Western Australia
Sponsor class: OTHER
Collaborators: name: Adverum Biotechnologies, Inc.
First posted: 2011-12-19
Enrollment: 40
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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;

Primary outcomes:
measure: No sign of unresolved ophthalmic complications, toxicity or systemic complications as measured by laboratory tests from 1 month post injection
timeFrame: Primary endpoint at 1 month
Secondary outcomes:
measure: Maintenance or improvement of vision without the necessity of ranibizumab re-injections
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Nedlands
country: Australia
facility: Lions Eye Institute
state: Western Australia
Study officials:
affiliation: Lions Eye Institute
name: Ian Constable, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Constable IJ, Pierce CM, Lai CM, Magno AL, Degli-Esposti MA, French MA, McAllister IL, Butler S, Barone SB, Schwartz SD, Blumenkranz MS, Rakoczy EP. Phase 2a Randomized Clinical Trial: Safety and Post Hoc Analysis of Subretinal rAAV.sFLT-1 for Wet Age-related Macular Degeneration. EBioMedicine. 2016 Dec;14:168-175. doi: 10.1016/j.ebiom.2016.11.016. Epub 2016 Nov 10.
citation: Rakoczy EP, Lai CM, Magno AL, Wikstrom ME, French MA, Pierce CM, Schwartz SD, Blumenkranz MS, Chalberg TW, Degli-Esposti MA, Constable IJ. Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial. Lancet. 2015 Dec 12;386(10011):2395-403. doi: 10.1016/S0140-6736(15)00345-1. Epub 2015 Sep 30.