Background Clesrovimab is an investigational monoclonal antibody with an extended half-life targeting site IV of the respiratory syncytial virus (RSV) fusion protein for the prevention of RSV disease in infants. Methods In this phase 1b/2a, double-blind study,183 healthy preterm and full-term infants 2 weeks to 8 months of age were randomized 4:1 within 5 panels (preterm: 20, 50, 75 or 100-mg, full-term: 100 mg) to receive one dose of clesrovimab or placebo. The objectives were to evaluate safety, pharmacokinetics, serum neutralizing antibodies (SNA), and anti-drug antibodies (ADA). The incidence of RSV-associated endpoints [medically-attended lower respiratory tract infection (MALRI), hospitalization, and acute respiratory infection (ARI)] were also evaluated through 150 days postdose. Results The most common adverse event (AE) through day 14 was irritability; no treatment-related serious AEs were reported. Clesrovimab serum concentrations displayed a geometric mean apparent half-life of 44.9 days. Of participants receiving clesrovimab, 51 (36.7%) developed ADA with no apparent impact in pharmacokinetics. SNA titers increased in a dose-dependent manner at day 150. The incidences of RSV-associated endpoints were lower in infants treated with clesrovimab compared with placebo. Conclusion Clesrovimab was generally well tolerated and exhibited an extended half-life compared to typical IgG1 antibodies supporting its ongoing development in late-stage trials. Clinical Trial Registration Clinicaltrials.gov, NCT03524118

中文翻译：

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半衰期延长 RSV 中和抗体 clesrovimab 在健康早产儿和足月儿中的 1b/2a 期单剂量递增研究


背景 Clesrovimab 是一种研究性单克隆抗体，具有延长的半衰期靶向呼吸道合胞病毒 （RSV） 融合蛋白的位点 IV，用于预防婴儿 RSV 疾病。方法 在这项 1b/2a 期双盲研究中，183 名 2 周至 8 月龄的健康早产儿和足月儿以 4：1 的比例随机分为 5 组 （早产儿：20、50、75 或 100 毫克，足月：100 毫克） 接受一剂 clesrovimab 或安慰剂。目的是评估安全性、药代动力学、血清中和抗体 （SNA） 和抗药抗体 （ADA）。还评估了给药后 150 天内 RSV 相关终点 [就医下呼吸道感染 （MALRI）、住院和急性呼吸道感染 （ARI）] 的发生率。结果 第 14 天最常见的不良事件 （AE） 是易激惹;未报告与治疗相关的严重 AE。Clesrovimab 血清浓度显示几何平均表观半衰期为 44.9 天。在接受 clesrovimab 治疗的参与者中，51 例 （36.7%） 发生 ADA，对药代动力学没有明显影响。SNA 滴度在第 150 天以剂量依赖性方式增加。与安慰剂相比，接受 clesrovimab 治疗的婴儿 RSV 相关终点的发生率较低。结论 Clesrovimab 通常耐受性良好，与典型的 IgG1 抗体相比，半衰期延长，支持其在后期试验中的持续开发。临床试验注册 Clinicaltrials.gov， NCT03524118