重组人源化抗狂犬病病毒单克隆抗体混合物SYN023（扎默罗维单抗和马佐雷维单抗注射液）与狂犬病疫苗联合用于世界卫生组织III类狂犬病暴露后人群的疗效和安全性：一项随机、双盲、阳性对照的III期临床试验。

The efficacy and safety of SYN023 (Zamerovimab and Mazorelvimab injection), the recombinant humanized anti-rabies virus monoclonal antibody mixture, combined with rabies vaccine in a WHO category III rabies post-exposure population: A randomized, double-blind, positive control, phase III clinical trial.

作者信息

Liu Xiaoqiang, Li Jingyu, Zha Yongxian, Wang Zhengxiong, Jiang Ya, Zhang Xiangyu, Guo Jiangshu, Yu Jiajie, Li Xiangjun, Zhang Qingchao, Reid Caroline, McClain J Bruce, Tsao Eric

机构信息

Vaccine Clinical Research Center, Yunnan Provincial Center for Disease Control and Prevention, Kunming, China.

Yanshan County Center for Disease Control and Prevention, Wenshan Zhuang and Miao Autonomous Prefecture, Yunnan Province, China.

出版信息

Vaccine. 2025 Aug 13;61:127289. doi: 10.1016/j.vaccine.2025.127289. Epub 2025 Jun 5.

DOI:10.1016/j.vaccine.2025.127289

PMID:40479926

Abstract

BACKGROUND

The SYN023-006 study was conducted in WHO Category III rabies-exposed patient populations to assess the safety and efficacy of post-exposure prophylaxis that included either the monoclonal antibody mixture SYN023 or human rabies immunoglobulin (HRIG).

METHODS

This phase 3, double-blind, randomized, controlled trial was conducted at multiple clinical disease control sites in China. Patients were randomized 3:1 (stratified by study site) to wound infiltration with 0.3 mg/kg SYN023 or 20 IU/kg HRIG. All patients received thorough wound washing and 5 doses intramuscular Vero cell rabies vaccine. The composite primary study objective was to demonstrate: 1) superiority of Day 8 geometric mean (GM) concentration of serum rabies virus neutralizing antibodies (RVNA) with SYN023 versus HRIG (protocol-defined superiority margin: GM RVNA ratio 95 % confidence interval [CI] lower limit >1.2) and 2) no rabies in SYN023 recipients. Efficacy was evaluated in the Per-Protocol population. Safety endpoints included solicited and unsolicited adverse events (AEs) analyzed in all patients receiving any study treatment.

TRIAL REGISTRATION

ClinicalTrials.govNCT04644484.

RESULTS

From 23 September 2020 to 26 June 2021, 537 male and 463 female patients were randomized (n = 750 SYN023, n = 250 HRIG). Day 8 GM RVNA was 4.339 IU/mL (standard error [SE]: 1.035) with SYN023 and 0.232 IU/mL (SE: 1.060) with HRIG. The SYN023:HRIG GM RVNA ratio was 18.695 (95 % CI: 16.440, 21.260) indicating superior RVNA with SYN023. No suspected rabies cases or deaths occurred. AEs were generally similar between treatment groups except greater local solicited AEs frequencies with HRIG (SYN023: 165/750 patients [22.0 %]; HRIG: 97/250 [38.8 %]).

CONCLUSION

This study indicates that SYN023, a monoclonal antibody product, may be used as part of rabies post-exposure prophylaxis and provides superior protection sooner after exposure than HRIG.

摘要

背景

SYN023-006研究在世界卫生组织III类狂犬病暴露患者群体中开展，以评估暴露后预防措施（包括单克隆抗体混合物SYN023或人狂犬病免疫球蛋白（HRIG））的安全性和有效性。

方法

这项3期双盲随机对照试验在中国多个临床疾病控制地点进行。患者按3:1随机分组（按研究地点分层），分别用0.3mg/kg SYN023或20IU/kg HRIG进行伤口浸润。所有患者均接受彻底的伤口冲洗和5剂肌内注射的Vero细胞狂犬病疫苗。综合主要研究目标是证明：1）SYN023组血清狂犬病病毒中和抗体（RVNA）第8天几何平均（GM）浓度优于HRIG组（方案定义的优势边际：GM RVNA比值95%置信区间[CI]下限>1.2）；2）SYN023组无狂犬病发生。在符合方案人群中评估疗效。安全性终点包括在所有接受任何研究治疗的患者中分析的预期和非预期不良事件（AE）。

试验注册

ClinicalTrials.govNCT04644484。

结果

2020年9月23日至2021年6月26日，537例男性和463例女性患者被随机分组（n = 750例SYN023，n = 250例HRIG）。SYN023组第8天GM RVNA为4.339IU/mL（标准误[SE]：1.035），HRIG组为0.232IU/mL（SE：1.060）。SYN023:HRIG GM RVNA比值为18.695（95%CI：16.440，21.260），表明SYN023的RVNA更优。未发生疑似狂犬病病例或死亡。治疗组之间AE总体相似，但HRIG组预期局部AE发生率更高（SYN023组：165/750例患者[22.0%]；HRIG组：97/250例[38.8%]）。