Safety and efficacy of conbercept in neovascular age-related macular degeneration: results from a 12-month randomized phase 2 study: AURORA study.

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.

• Authors: Xiaoxin Li, Gezhi Xu, Yusheng Wang, Xun Xu, Xiaoling Liu, Shibo Tang, Feng Zhang, Junjun Zhang, Luosheng Tang, Quan Wu, Delun Luo, Xiao Ke, AURORA Study Group
• Journal: Ophthalmology (Ophthalmology) Vol. 121 Issue 9 Pg. 1740-7 (Sep 2014) ISSN: 1549-4713 [Electronic] United States
• PMID: 24793528 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Recombinant Fusion Proteins
• Vascular Endothelial Growth Factor A
• KH902 fusion protein

Topics

• Aged
• Angiogenesis Inhibitors (adverse effects, therapeutic use)
• Choroidal Neovascularization (drug therapy, etiology)
• Double-Blind Method
• Female
• Humans
• Intravitreal Injections
• Macular Degeneration (complications)
• Maintenance Chemotherapy
• Male
• Middle Aged
• Neovascularization, Pathologic (drug therapy)
• Recombinant Fusion Proteins (adverse effects, therapeutic use)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors)
• Visual Acuity