Xiaoxin Li1, Gezhi Xu2, Yusheng Wang3, Xun Xu4, Xiaoling Liu5, Shibo Tang6, Feng Zhang7, Junjun Zhang8, Luosheng Tang9, Quan Wu10, Delun Luo10, Xiao Ke10. 1. Department of Ophthalmology, Peking University People's Hospital, Beijing, China. Electronic address: dr_lixiaoxin@126.com. 2. Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China. 3. Department of Ophthalmology, Xijing Hospital of the Fourth Military Medical University, Xian, Shanxi, China. 4. Department of Ophthalmology, Shanghai First People's Hospital, Shanghai, China. 5. Department of Ophthalmology, Optometry and Ophthalmology Hospital of Wenzhou Medical College, Wenzhou, Fujian, China. 6. Department of Ophthalmology, Zhongshan Ophthalmic Center, Sun-Yat University, Guangzhou, Guangdong, China. 7. Department of Ophthalmology, Peking Tongren Hospital, Beijing, China. 8. Department of Ophthalmology, Sichuan University West China Hospital, Chengdu, Sichuan, China. 9. Department of Ophthalmology, Second Affiliated Hospital of Xiangya Medical College, Changsha, Hunan, China. 10. Department of Clinical Research, Chengdu Kanghong Biotechnology, Inc., Chengdu, China.
Abstract
PURPOSE: To assess the safety and efficacy of multiple injections of 0.5 and 2.0 mg conbercept using variable dosing regimens in patients with neovascular age-related macular degeneration (AMD). DESIGN: Randomized, double-masked, multicenter, controlled-dose, and interval-ranging phase 2 clinical trial divided into a 3-month loading phase followed by a maintenance phase. PARTICIPANTS: Patients with choroidal neovascularization secondary to AMD with lesion sizes of 12 disc areas or less and a best-corrected visual acuity (BCVA) letter score of between 73 and 24 were enrolled. METHODS: Patients were randomized 1:1 to receive either 0.5 or 2.0 mg intravitreal conbercept for 3 consecutive monthly does. After the third dose, each group was reassigned randomly again to monthly (Q1M group) or as-needed (pro re nata [PRN] group) treatment without changing the drug assignment. MAIN OUTCOME MEASURES: The primary end point was the mean change in BCVA from baseline to month 3, with secondary end points being the mean change in BCVA, mean change in central retinal thickness (CRT), and safety at month 12. RESULTS:We enrolled 122 patients. At the primary end point at month 3, mean improvements in BCVA from baseline in the 0.5- and 2.0-mg groups were 8.97 and 10.43 letters, respectively. At month 12, mean improvements in BCVA from baseline were 14.31, 9.31, 12.42, and 15.43 letters for the 0.5-mg PRN, 0.5-mg Q1M, 2.0-mg PRN, and 2.0-mg Q1M regimens, respectively. At month 12, mean reductions in CRT in the 4 regimens were 119.8, 129.7, 152.1, and 170.8 μm, respectively. There were no significant differences for the pairwise comparisons between all study groups. The difference in the number of injections between the 2 PRN groups was not statistically significant. Treatment with conbercept generally was safe and well tolerated. CONCLUSIONS: The significant gains in BCVA at 3 months were the same or better at 12 months in all conbercept dosing groups of neovascular AMD patients. During the 12 months, repeated intravitreal injections of conbercept were well tolerated in these patients. Future clinical trials are required to confirm its long-term efficacy and safety.
RCT Entities:
PURPOSE: To assess the safety and efficacy of multiple injections of 0.5 and 2.0 mg conbercept using variable dosing regimens in patients with neovascular age-related macular degeneration (AMD). DESIGN: Randomized, double-masked, multicenter, controlled-dose, and interval-ranging phase 2 clinical trial divided into a 3-month loading phase followed by a maintenance phase. PARTICIPANTS: Patients with choroidal neovascularization secondary to AMD with lesion sizes of 12 disc areas or less and a best-corrected visual acuity (BCVA) letter score of between 73 and 24 were enrolled. METHODS:Patients were randomized 1:1 to receive either 0.5 or 2.0 mg intravitreal conbercept for 3 consecutive monthly does. After the third dose, each group was reassigned randomly again to monthly (Q1M group) or as-needed (pro re nata [PRN] group) treatment without changing the drug assignment. MAIN OUTCOME MEASURES: The primary end point was the mean change in BCVA from baseline to month 3, with secondary end points being the mean change in BCVA, mean change in central retinal thickness (CRT), and safety at month 12. RESULTS: We enrolled 122 patients. At the primary end point at month 3, mean improvements in BCVA from baseline in the 0.5- and 2.0-mg groups were 8.97 and 10.43 letters, respectively. At month 12, mean improvements in BCVA from baseline were 14.31, 9.31, 12.42, and 15.43 letters for the 0.5-mg PRN, 0.5-mg Q1M, 2.0-mg PRN, and 2.0-mg Q1M regimens, respectively. At month 12, mean reductions in CRT in the 4 regimens were 119.8, 129.7, 152.1, and 170.8 μm, respectively. There were no significant differences for the pairwise comparisons between all study groups. The difference in the number of injections between the 2 PRN groups was not statistically significant. Treatment with conbercept generally was safe and well tolerated. CONCLUSIONS: The significant gains in BCVA at 3 months were the same or better at 12 months in all conbercept dosing groups of neovascular AMDpatients. During the 12 months, repeated intravitreal injections of conbercept were well tolerated in these patients. Future clinical trials are required to confirm its long-term efficacy and safety.