Bakker A B H, Python C, Kissling C J, Pandya P, Marissen W E, Brink M F, Lagerwerf F, Worst S, van Corven E, Kostense S, Hartmann K, Weverling G J, Uytdehaag F, Herzog C, Briggs D J, Rupprecht C E, Grimaldi R, Goudsmit J
Crucell Holland BV, Leiden, The Netherlands.
Vaccine. 2008 Nov 5;26(47):5922-7. doi: 10.1016/j.vaccine.2008.08.050. Epub 2008 Sep 17.
Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cannot be provided due to limited availability of human or equine rabies immunoglobulin (HRIG and ERIG, respectively). We report first clinical data from two phase I studies evaluating a monoclonal antibody cocktail CL184 against rabies. The studies included healthy adult subjects in the USA and India and involved two parts. First, subjects received a single intramuscular dose of CL184 or placebo in a double blind, randomized, dose-escalation trial. Second, open-label CL184 (20IU/kg) was co-administered with rabies vaccine. Safety was the primary objective and rabies virus neutralizing activity (RVNA) was investigated as efficacy parameter. Pain at the CL184 injection site was reported by less than 40% of subjects; no fever or local induration, redness or swelling was observed. RVNA was detectable from day 1 to day 21 after a single dose of CL184 20 or 40IU/kg. All subjects had adequate (>0.5IU/mL) RVNA levels from day 14 onwards when combined with rabies vaccine. CL184 appears promising as an alternative to RIG in PEP.
由于人用或马用狂犬病免疫球蛋白（分别为HRIG和ERIG）的供应有限，作为狂犬病暴露后预防（PEP）一部分的即时被动免疫预防往往无法提供。我们报告了两项评估抗狂犬病单克隆抗体鸡尾酒CL184的I期研究的首批临床数据。这些研究纳入了美国和印度的健康成年受试者，分为两个部分。首先，在一项双盲、随机、剂量递增试验中，受试者接受单次肌肉注射CL184或安慰剂。其次，开放标签的CL184（20IU/kg）与狂犬病疫苗联合给药。安全性是主要目标，狂犬病病毒中和活性（RVNA）作为疗效参数进行研究。不到40%的受试者报告CL184注射部位疼痛；未观察到发热或局部硬结、发红或肿胀。在单次注射20或40IU/kg CL184后的第1天至第21天可检测到RVNA。与狂犬病疫苗联合使用时，所有受试者从第14天起RVNA水平均足够（>0.5IU/mL）。CL184作为PEP中RIG的替代品似乎很有前景。
