Results from a single-center, phase 1, randomized controlled clinical trial show that ocular gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration was found to be safe and well tolerated.
The study enrolled patients with wet age-related macular degeneration at the Lions Eye Institute and the Sir Charles Gairdner Hospital in Nedlands, WA, Australia. Eligible patients had to be aged 65 years or older, have age-related macular degeneration secondary to active subfoveal choroidal neovascularisation, with best corrected visual acuity (BCVA) of 3/60–6/24 and 6/60 or better in the other eye. Patients were randomly assigned (3:1) to receive either 1 × 1010 vector genomes (vg; low-dose rAAV.sFLT-1 group) or 1 × 1011 vg (high-dose rAAV.sFLT-1 group), or no gene-therapy treatment (control group). Randomisation was done by sequential group assignment. All patients and investigators were unmasked. Staff doing the assessments were masked to the study group at study visits. All patients received ranibizumab at baseline and week 4, and rescue treatment during follow-up based on prespecified criteria including BCVA measured on the Early Treatment Diabetic Retinopathy Study (EDTRS) scale, optical coherence tomography, and fluorescein angiography. The primary endpoint was ocular and systemic safety.
This trial is registered with ClinicalTrials.gov, number NCT01494805.
The study was conducted from Dec 16, 2011, to April 5, 2012, with nine patients being enrolled, of whom eight were randomly assigned to receive either intervention (three patients in the low-dose rAAV.sFLT-1 group and three patients in the high-dose rAAV.sFLT-1 group) or no treatment (two patients in the control group). Subretinal injection of rAAV.sFLT-1 was found to be highly reproducible. No drug-related adverse events were noted; procedure-related adverse events (subconjunctival or subretinal haemorrhage and mild cell debris in the anterior vitreous) were reported as mild and self-resolving. There was no evidence of chorioretinal atrophy. Clinical laboratory assessments generally remained unchanged from baseline. Four (67%) of six patients in the treatment group required zero rescue injections, and the other two (33%) required only one rescue injection each.
The authors note that rAAV.sFLT-1 was found to be safe and well tolerated, supporting ocular gene therapy as a potential long-term treatment option for wet age-related macular degeneration.
This work has been supported by National Health and Medical Research Council of Australia, Richard Pearce Bequest, Lions Save Sight Foundation, Brian King Fellowship, and Avalanche Biotechnologies, Inc.
Source: The Lancet
How does it work? More info on Avalanche Biotechnologies, Inc.’s webpage. (Not an endorsement or an advertisement!)
Featured image – (c) Avalanche Biotechnologies, Inc.