Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial
| العنوان: | Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial |
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| المؤلفون: | Cora M. Pierce, Steven D. Schwartz, Thomas W. Chalberg, Ian J. Constable, Mark S. Blumenkranz, Mariapia A. Degli-Esposti, Aaron L. Magno, Matthew E. Wikstrom, Chooi May Lai, Elizabeth Rakoczy, Martyn A. French |
| المصدر: | The Lancet. 386:2395-2403 |
| بيانات النشر: | Elsevier BV, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Visual acuity, genetic structures, Genetic Vectors, Visual Acuity, Angiogenesis Inhibitors, Article, Adenoviridae, law.invention, Randomized controlled trial, law, Ranibizumab, Ophthalmology, medicine, Clinical endpoint, Humans, Aged, Aged, 80 and over, Vascular Endothelial Growth Factor Receptor-1, medicine.diagnostic_test, business.industry, Genetic Therapy, General Medicine, Diabetic retinopathy, Macular degeneration, medicine.disease, Fluorescein angiography, Choroidal Neovascularization, Recombinant Proteins, eye diseases, Clinical trial, Wet Macular Degeneration, Female, Injections, Intraocular, medicine.symptom, business, medicine.drug |
| الوصف: | Summary Background Neovascular, or wet, age-related macular degeneration causes central vision loss and represents a major health problem in elderly people, and is currently treated with frequent intraocular injections of anti-VEGF protein. Gene therapy might enable long-term anti-VEGF therapy from a single treatment. We tested the safety of rAAV.sFLT-1 in treatment of wet age-related macular degeneration with a single subretinal injection. Methods In this single-centre, phase 1, randomised controlled trial, we enrolled patients with wet age-related macular degeneration at the Lions Eye Institute and the Sir Charles Gairdner Hospital (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 × 10 10 vector genomes (vg; low-dose rAAV.sFLT-1 group) or 1 × 10 11 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. Findings From Dec 16, 2011, to April 5, 2012, we enrolled nine patients 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 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 generally 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. Interpretation rAAV.sFLT-1 was safe and well tolerated. These results support ocular gene therapy as a potential long-term treatment option for wet age-related macular degeneration. Funding National Health and Medical Research Council of Australia, Richard Pearce Bequest, Lions Save Sight Foundation, Brian King Fellowship, and Avalanche Biotechnologies, Inc. |
| تدمد: | 0140-6736 0149-4805 |
| DOI: | 10.1016/s0140-6736(15)00345-1 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3fd2f2d4c9d66b1e7e8d0828f89ba92c https://doi.org/10.1016/s0140-6736(15)00345-1 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3fd2f2d4c9d66b1e7e8d0828f89ba92c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 01406736 01494805 |
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| DOI: | 10.1016/s0140-6736(15)00345-1 |