Madhi Shabir A, Simões Eric A F, Acevedo Armando, Novoa Pizarro Jose M, Shepard Julie S, Railkar Radha A, Cao Xin, Maas Brian M, Zang Xiaowei, Krick Andrea, Roadcap Brad, Vora Kalpit A, Aliprantis Antonios O, Lee Andrew W, Sinha Anushua
South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.
Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA.
J Infect Dis. 2025 Mar 17;231(3):e478-e487. doi: 10.1093/infdis/jiae581.
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.
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 1 dose of clesrovimab or placebo. The objectives were to evaluate safety, pharmacokinetics, serum neutralizing antibodies (SNA), and antidrug antibodies (ADA). The incidence of RSV-associated end points (medically attended lower respiratory tract infection, hospitalization, and acute respiratory infection) were also evaluated through 150 days postdose.
The most common adverse event 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 end points were lower in infants treated with clesrovimab compared with placebo.
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. NCT03524118.
Clesrovimab是一种研究性单克隆抗体，其半衰期延长，靶向呼吸道合胞病毒（RSV）融合蛋白的IV位点，用于预防婴儿RSV疾病。
在这项1b/2a期双盲研究中，183名2周龄至8个月龄的健康早产和足月婴儿在5个组（早产20、50、75或100mg；足月100mg）内按4:1随机分组，接受1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）和抗药物抗体（ADA）。还通过给药后150天评估RSV相关终点（就医的下呼吸道感染、住院和急性呼吸道感染）的发生率。
至第14天最常见的不良事件是易激惹；未报告与治疗相关的严重不良事件。Clesrovimab血清浓度显示几何平均表观半衰期为44.9天。接受clesrovimab的参与者中，51名（36.7%）产生了ADA，对药代动力学无明显影响。在第150天，SNA滴度呈剂量依赖性增加。与安慰剂相比，接受clesrovimab治疗的婴儿中RSV相关终点的发生率较低。
Clesrovimab总体耐受性良好，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。临床试验注册编号：NCT03524118。
