Synermore Biologics Co., Ltd., 6F-6, No. 5, Aly.22, Ln. 513, Ruiguang Rd, Neihu Dist, Tapei 11492, Taiwan.
Diagnostic Medicine/Pathobiology Department, Kansas State University, Manhattan, Kansas, United States of America, Present address: 1800 Denison Avenue, Manhattan, Kansas 66506, USA.
Vaccine. 2021 Sep 24;39(40):5822-5830. doi: 10.1016/j.vaccine.2021.08.066. Epub 2021 Sep 3.
SYN023-002 is a randomized, blinded, controlled study comparing rabies virus neutralizing activity (RVNA) and safety of SYN023, a monoclonal anti-rabies antibody mixture, to human-serum derived anti-rabies immunoglobulin (RIG) when administered with commercially available vaccines to healthy adult volunteers.
Participants were randomized among 4 treatment groups (SYN023 + Imovax, SYN023 + RabAvert, HyperRab + Imovax, HyperRab + RabAvert). On Day 0, subjects received 1 dose of RIG (0.3 mg/kg SYN023 or 20 IU/mL HyperRab) and their first of 5 vaccine doses. The primary objective was to compare cumulative RVNA between SYN023 and HyperRab recipients. Secondary objectives were to compare safety and to assess SYN023 pharmacokinetics and immunogenicity.
All 164 randomized subjects initiated treatment and were included in safety analyses. At least 34 subjects/treatment group received all treatment and had complete RVNA results, thus were included in the primary endpoint analysis. Mean RVNAs were approximately ten-fold higher in SYN023 recipients compared to HyperRab recipients until Day 14. From Day 14 onwards, mean RVNA was lower in SYN023 recipients, but remained above the RVNA level widely considered adequate (≥0.5 IU/mL) through Day 112 (study end). The point estimate of the cumulative RVNA (83.22% SYN023/HyperRab), but not the lower CI bound (90% CI: 66.06%, 104.83%), fell within the protocol-defined similarity margin. Each RIG + vaccine regimen appeared safe with mostly mild AEs and no serious or severe related events observed. Except injection site pain (22% HyperRab recipients vs. 6% SYN023 recipients), treatment-related AEs incidences were similar between RIGs. Anti-SYN023 antibodies were observed but had no apparent effects on PK or safety.
SYN023 administered with commercially available vaccines provides adequate antibody coverage beginning earlier than other commercially available RIGs with an acceptable safety profile. Some suppression of vaccine response occurred, but RVNA levels ≥ 0.5 IU/mL were maintained throughout the relevant period.
ClinicalTrials.gov #NCT02956746.
Synermore biologics.
SYN023-002 是一项随机、双盲、对照研究，比较了狂犬病病毒中和抗体（RVNA）和安全性，研究对象为接受市售疫苗的健康成年志愿者，使用 SYN023（一种单克隆抗狂犬病抗体混合物）与市售的人血清来源狂犬病免疫球蛋白（RIG）。
参与者按 4 种治疗组（SYN023+Imovax、SYN023+RabAvert、HyperRab+Imovax、HyperRab+RabAvert）随机分组。第 0 天，受试者接受 1 剂 RIG（0.3mg/kg SYN023 或 20IU/mL HyperRab）和第 1 剂 5 剂疫苗中的第 1 剂。主要目标是比较 SYN023 和 HyperRab 接受者的累积 RVNA。次要目标是比较安全性，并评估 SYN023 的药代动力学和免疫原性。
所有 164 名随机受试者均开始接受治疗，并纳入安全性分析。至少 34 名/治疗组的受试者接受了所有治疗，并完成了完整的 RVNA 结果，因此被纳入主要终点分析。与 HyperRab 接受者相比，SYN023 接受者的 RVNA 平均高出约 10 倍，直到第 14 天。从第 14 天开始，SYN023 接受者的 RVNA 较低，但在第 112 天（研究结束）之前，RVNA 仍保持在被广泛认为足够的 RVNA 水平（≥0.5IU/mL）之上。累积 RVNA 的点估计值（83.22%SYN023/ HyperRab），但不是较低的 CI 下限（90%CI：66.06%，104.83%），符合方案规定的相似性范围。每种 RIG+疫苗方案似乎都安全，主要为轻度不良反应，未观察到严重或严重相关事件。除注射部位疼痛（22% HyperRab 接受者 vs. 6% SYN023 接受者）外，RIG 相关不良反应发生率相似。观察到抗-SYN023 抗体，但对 PK 或安全性无明显影响。
与市售疫苗联合使用 SYN023 可提供早期、足够的抗体覆盖，优于其他市售的 RIG，安全性良好。疫苗反应出现一定程度的抑制，但在整个相关期间均维持 RVNA 水平≥0.5IU/mL。
ClinicalTrials.gov #NCT02956746。
Synermore biologics。
