依替莫福昔治疗新生血管性年龄相关性黄斑变性的有效性和安全性：一项II期试验

IF 4.6 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-08-14 DOI:10.1016/j.xops.2025.100913

Tong Li MD, PhD , Shiqi Yang MD, PhD , Qinghuai Liu MD , Yanping Song MS , Jianping Tong MD , Wenbin Wei MD , Weiqi Chen BS , Hong Dai MD , Wei Wang MS , Miaoqin Wu MD , Guohong Zhou MD , Xuan Xiao MD , Jinglin Zhang MD , Rongrong Zhu MS , Haoyu Li MS , Yafang Wang PhD , Xiaoyu Chen PhD , Shujie Lu MS , Haiwei Du PhD , Han Han-Zhang PhD , Xiaodong Sun MD, PhD

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引用次数: 0

摘要

目的：本研究旨在评价高剂量efdamrofusp （IBI302，靶向VEGF和补体C3b/4b）个体化给药间隔治疗新生血管性年龄相关性黄斑变性（nAMD）患者的疗效和安全性。设计一项多中心、随机、双盲、主动对照、非劣效性的II期试验。共纳入132名抗vegf naïve或先前接受过nAMD治疗的参与者。方法将符合条件的受试者按1:1:1的比例随机分为IBI302 6.4 mg、IBI302 8.0 mg和afliberept 2.0 mg。注射4个月后，根据第20周的疾病活度评估，每8周（Q8W）或每12周（Q12W）给药一次Efdamrofusp α组。afliberept 2.0 mg组在3个月后给予Q8W注射。主要终点是最佳矫正视力（BCVA）从基线到第40周的平均变化。预定的非劣效距为4个字母。结果从基线到第40周，最小二乘平均值（标准误差）变化为：IBI302 6.4 mg组+10.5（1.5）个字母，IBI302 8.0 mg组+9.2（1.5）个字母，afliberept 2.0 mg组+9.7（1.5）个字母。IBI302 6.4 mg与aflibercept 2.0 mg的估计差异为+0.8(80%置信区间：-1.9至3.6，非劣效性试验：P = 0.0115), IBI302 8.0 mg与aflibercept 2.0 mg的估计差异为-0.5（-3.3至2.2，非劣效性试验：P = 0.0123）。IBI302组中超过80%的参与者在第20周后服用Q12W，并维持他们的方案直到研究结束。在接受IBI302 6.4 mg， 37.8%接受IBI302 8.0 mg， 23.3%接受阿伯西普2.0 mg的受试者中，有36.4%的受试者报告了研究中出现的治疗不良事件（teae）。在IBI302组中，最常见的眼部TEAE是结膜出血（6.4 mg组为9.1%，8.0 mg组为11.1%），而在afliberept 2.0 mg组中，白内障（7.0%）是最常见的眼部TEAE。结论给药至Q12W时，sefdamrofusp 6.4和8.0 mg与afliberept 2.0 mg Q8W相比，视觉增益不差。此外，IBI302组耐受性良好。这些发现表明，延长给药间隔的大剂量IBI302可以为nAMD患者提供持续的视觉益处。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。

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Efficacy and Safety of Efdamrofusp Alfa with Personalized Dosing Intervals in Neovascular Age-Related Macular Degeneration: A Phase II Trial

Purpose

This study aims to evaluate the efficacy and safety of high-dose efdamrofusp alfa (IBI302, targeting VEGF and complement C3b/4b) with personalized dosing intervals in patients with neovascular age-related macular degeneration (nAMD).

Design

A multicenter, randomized, double-masked, active-controlled, noninferiority phase II trial.

Participants

A total of 132 anti-VEGF naïve or previously treated participants with nAMD were enrolled.

Methods

Eligible participants were randomized (1:1:1) to receive IBI302 6.4 mg, IBI302 8.0 mg, or aflibercept 2.0 mg. Efdamrofusp alfa groups were dosed every 8 weeks (Q8W) or every 12 weeks (Q12W), based on disease activity assessment at week 20, after 4 monthly injections. The aflibercept 2.0-mg group was dosed Q8W, after 3 monthly injections.

Main Outcome Measures

The primary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to week 40. The prespecified noninferiority margin was 4 letters.

Results

The least squares mean (standard error) changes in BCVA from baseline to week 40 were +10.5 (1.5) letters with IBI302 6.4 mg, +9.2 (1.5) letters with IBI302 8.0 mg, and +9.7 (1.5) letters with aflibercept 2.0 mg. The estimated differences were +0.8 (80% confidence interval: –1.9 to 3.6, noninferiority test: P = 0.0115) for IBI302 6.4 mg versus aflibercept 2.0 mg and –0.5 (–3.3 to 2.2, noninferiority test: P = 0.0123) for IBI302 8.0 mg versus aflibercept 2.0 mg. Over 80% of participants in IBI302 groups were dosed Q12W after week 20 and maintained their regimens until the end of study. Treatment-emergent adverse events (TEAEs) in the study eye were reported in 36.4% of participants receiving IBI302 6.4 mg, 37.8% receiving IBI302 8.0 mg, and 23.3% receiving aflibercept 2.0 mg. The most common ocular TEAE was conjunctival hemorrhage (9.1% for 6.4 mg and 11.1% for 8.0 mg) in both IBI302 groups, whereas cataract (7.0%) was the most frequent ocular TEAE in the aflibercept 2.0-mg group.

Conclusions

Efdamrofusp alfa 6.4 and 8.0 mg dosed up to Q12W demonstrated noninferior visual gain to aflibercept 2.0 mg Q8W. Moreover, IBI302 groups were well tolerated. These findings suggested that high-dose IBI302 with extended dosing intervals could provide sustained visual benefits for patients with nAMD.