Safety, Tolerability, and Pharmacokinetics of MEDI8897, the Respiratory Syncytial Virus Prefusion F-Targeting Monoclonal Antibody with an Extended Half-Life, in Healthy Adults.
Safety, Tolerability, and Pharmacokinetics of MEDI8897, the Respiratory Syncytial Virus Prefusion F-Targeting Monoclonal Antibody with an Extended Half-Life, in Healthy Adults.
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DOI：
10.1128/aac.01714-16
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发表时间：
2017-03
影响因子：
4.9
通讯作者：
Dubovsky F
中科院分区：
文献类型：
--
作者：
Griffin MP;Khan AA;Esser MT;Jensen K;Takas T;Kankam MK;Villafana T;Dubovsky F
预防婴儿呼吸道合胞病毒（RSV）疾病是一个主要的公共卫生优先事项，但没有批准的疫苗。帕利珠单抗是一种单克隆抗体，可提供RSV预防，但需要每月注射5次，仅批准用于RSV发病率和死亡率最高的婴儿。因此，在健康婴儿中预防RSV疾病仍然存在显著未满足的医疗需求。MEDI 8897是一种重组人RSV单克隆抗体，其Fc区经过修饰，可延长其半衰期，正在开发用于所有婴儿的RSV预防。在这项1期、首次人体、安慰剂对照研究中，136名健康成年人被随机分配到5个队列中的1个队列中接受单剂量MED 8897（n = 102）或安慰剂（n = 34）（300、1，000或3，000 mg静脉注射或100或300 mg肌内注射[i. m]）并被监测了360天。MEDI 8897的平均半衰期在各剂量组中为85至117天，并且在300-mg i. m.给药率为77%。i.m.给药后至最大浓度的时间给药时间为5至9天。在安慰剂（15.2%）和MEDI 8897（13.7%）接受者中检测到相似比例的抗药抗体（ADA）应答。MEDI 8897的安全性特征与安慰剂的安全性特征相似。这些结果支持i.m.在一些实施方案中，本发明提供了在婴儿的目标群体中施用单剂量的MEDI 8897以在RSV季节期间提供保护的方法。(This研究已在ClinicalTrials.gov注册，标识符为NCT 02114268。）
Prevention of respiratory syncytial virus (RSV) illness in infants is a major public health priority, but there is no approved vaccine. Palivizumab is a monoclonal antibody that provides RSV prophylaxis but requires 5 monthly injections and is approved only for infants who experience the greatest morbidity and mortality from RSV. Thus, there remains a significant unmet medical need for prevention of RSV disease in healthy infants. MEDI8897 is a recombinant human RSV monoclonal antibody with a modified Fc region that extends its half-life and is being developed as RSV prophylaxis for all infants. In this phase 1, first-in-human, placebo-controlled study, 136 healthy adults were randomized to receive a single dose of MEDI8897 (n = 102) or placebo (n = 34) in 1 of 5 cohorts (300, 1,000, or 3,000 mg intravenously or 100 or 300 mg intramuscularly [i.m.]) and were monitored for 360 days. The mean half-life of MEDI8897 was 85 to 117 days across dose groups, and bioavailability after 300-mg i.m. dose administration was 77%. Time to maximum concentration following i.m. dosing was 5 to 9 days. Antidrug antibody (ADA) responses were detected in a similar proportion of placebo (15.2%) and MEDI8897 (13.7%) recipients. The safety profile of MEDI8897 was similar to that of the placebo. These results support clinical studies of the i.m. administration of a single dose of MEDI8897 in the target population of infants to provide protection for the duration of the RSV season. (This study has been registered at ClinicalTrials.gov under identifier NCT02114268.)