TY - JOUR
T1 - RNAi-Based Treatment for Neovascular Age-Related Macular Degeneration by Sirna-027
AU - Kaiser, Peter K.
AU - Symons, R. C.Andrew
AU - Shah, Syed Mahmood
AU - Quinlan, Edward J.
AU - Tabandeh, Homayoun
AU - Do, Diana V.
AU - Reisen, Gail
AU - Lockridge, Jennifer A.
AU - Short, Brian
AU - Guerciolini, Roberto
AU - Nguyen, Quan Dong
N1 - Funding Information:
Supported by Sirna Therapeutics, Inc , San Franciso, California. The Cole Eye Institute, the employer of Dr Kaiser, and the Johns Hopkins University, the employer of Drs Symons, Shah, Quinlan, Do, and Nguyen, have received research grant support from Allergan and Sirna Therapeutics, Inc . Drs Kaiser and Quinlan served on the Scientific Advisory Board of Allergan. Drs Lockridge and Guerciolini and Ms Reisen were employees of Sirna Therapeutics, Inc. Dr Short is an employee of Allergan, Inc. Involved in design and conduct of the study (P.K.K., R.G., Q.D.N.); Collection, management, analysis, and interpretation of the data (P.K.K., R.C.A.S., S.M.S., E.J.Q., H.T., D.V.D., G.R., J.A.L., B.S., R.G., Q.D.N.); and Preparation, review, or approval of the manuscript (P.K.K., R.C.A.S., S.M.S., E.J.Q., H.T., D.V.D., G.R., J.A.L., B.S., R.G., Q.D.N.). The study received institutional review board approval at both the Wilmer Eye Institute, Johns Hopkins University, and the Cole Eye Institute, Cleveland Clinics. All study sites were compliant with the Health Insurance Portability and Accountability Act of 1996. Before determination of eligibility for enrollment, patients provided written, informed consent for study participation. The study was posted to http://www.clinicaltrials.gov (identified no. NCT00363714 ).
PY - 2010/7
Y1 - 2010/7
N2 - Purpose: To assess the safety, tolerability, pharmacokinetics, and dose-limiting toxicity of single intravitreal injection of Sirna-027, a small interfering RNA targeting vascular endothelial growth factor receptor-1, in patients with choroidal neovascularization (CNV) resulting from neovascular age-related macular degeneration (AMD). Secondary objectives included assessment of anatomic changes in retinal thickness, size of CNV, and changes in visual acuity. Design: Prospective, open-label, single-dose, dose-escalation phase 1 study. Methods: Twenty-six eyes of 26 patients with a median age of 82 years and CNV resulting from AMD who had previous treatments with other therapies were treated at 2 academic retinal practices. Patients received a single dose of Sirna-027 (100, 200, 400, 800, 1200, or 1600 μg/eye). Blood was sampled for pharmacokinetic analysis at 1, 4, and 24 hours after injection and on day 7. Patients underwent ophthalmic examinations including visual acuity, fluorescein angiography, and optical coherence tomography at screening and days 7, 14, 28, and 84. The main outcome measures were adverse reactions and dose-limiting toxicities. Results: Intravitreal injection of a single dose of Sirna-027 from 100 to 1600 μg was well tolerated in patients with AMD, with no dose-limiting toxicity found. Adverse events were mild to moderate in severity. Adjusted mean foveal thickness decreased within 2 weeks after study treatment. The decrease was most pronounced in the 100- and 200-μg doses. Conclusions: A single intravitreal dose of Sirna-027 up to 1600 μg/eye was well tolerated in patients with CNV resulting from neovascular AMD that had been refractory to other therapies. Stabilization or improvement in visual acuity and foveal thickness was observed. No dose-response or dose-limiting effects were noted.
AB - Purpose: To assess the safety, tolerability, pharmacokinetics, and dose-limiting toxicity of single intravitreal injection of Sirna-027, a small interfering RNA targeting vascular endothelial growth factor receptor-1, in patients with choroidal neovascularization (CNV) resulting from neovascular age-related macular degeneration (AMD). Secondary objectives included assessment of anatomic changes in retinal thickness, size of CNV, and changes in visual acuity. Design: Prospective, open-label, single-dose, dose-escalation phase 1 study. Methods: Twenty-six eyes of 26 patients with a median age of 82 years and CNV resulting from AMD who had previous treatments with other therapies were treated at 2 academic retinal practices. Patients received a single dose of Sirna-027 (100, 200, 400, 800, 1200, or 1600 μg/eye). Blood was sampled for pharmacokinetic analysis at 1, 4, and 24 hours after injection and on day 7. Patients underwent ophthalmic examinations including visual acuity, fluorescein angiography, and optical coherence tomography at screening and days 7, 14, 28, and 84. The main outcome measures were adverse reactions and dose-limiting toxicities. Results: Intravitreal injection of a single dose of Sirna-027 from 100 to 1600 μg was well tolerated in patients with AMD, with no dose-limiting toxicity found. Adverse events were mild to moderate in severity. Adjusted mean foveal thickness decreased within 2 weeks after study treatment. The decrease was most pronounced in the 100- and 200-μg doses. Conclusions: A single intravitreal dose of Sirna-027 up to 1600 μg/eye was well tolerated in patients with CNV resulting from neovascular AMD that had been refractory to other therapies. Stabilization or improvement in visual acuity and foveal thickness was observed. No dose-response or dose-limiting effects were noted.
UR - http://www.scopus.com/inward/record.url?scp=77953909544&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953909544&partnerID=8YFLogxK
U2 - 10.1016/j.ajo.2010.02.006
DO - 10.1016/j.ajo.2010.02.006
M3 - Article
C2 - 20609706
AN - SCOPUS:77953909544
SN - 0002-9394
VL - 150
SP - 33-39.e2
JO - American journal of ophthalmology
JF - American journal of ophthalmology
IS - 1
ER -