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目的观察不同剂量重组人源抗狂犬病病毒单克隆抗体(recombinated human rabies immunoglobin,rhRIG)注射液人体单次给药的安全性。方法采用随机、单盲、安慰剂平行对照的方法,对成功筛选的48名健康受试者按照随机数字表进行分组,共分低、中、高3个rhRIG单次给药组(10、20、40 IU/kg),每组12人,每个剂量组均按3∶1设1个安慰剂(rhRIG的赋形剂)平行对照组,每组4人,依次经上臂三角肌(≤2 ml)、臀大肌(≤10 ml)和大腿外侧肌肉(剩余药液)进行肌肉注射。分别在筛选期(入组用药前14 d内)、用药后7、14和42 d记录不良事件(adverseevent,AE)、严重不良事件(serious adverse events,SAE)、局部反应、全身反应的发生情况,并进行生命体征、实验室(血常规、尿常规、血生化)、心电图、胸片、腹部B超检查。结果不同剂量rhRIG组中共发生7例次AE,分别为谷氨酸氨基转移酶、天门冬氨酸氨基转移酶和谷氨酰转肽酶升高、血白细胞下降、上呼吸道感染、宫外孕,其中宫外孕判断为SAE。上述AE均判断与试验药物无关或可能无关。对照组未发生任何AE/SAE。所有受试者用药后生命体征均未见异常改变。结论受试者单次肌肉注射10～40 IU/kg rhRIG后耐受性良好。
Objective To observe the safety of single dose of recombinated human rabies immunoglobin (rhRIG) injection at different doses. Methods A randomized, single-blind and placebo-controlled parallel method was used to divide the 48 healthy subjects successfully into three groups according to a random number table: low, middle and high rhRIG single administration groups (10, 20, , 40 IU / kg in each group, 12 in each group. Each dose group was given a placebo (rhRIG excipient) parallel control group at 3: 1, 4 in each group, followed by the upper arm deltoid (≤2 ml), gluteus maximus (≤10 ml), and lateral thigh muscles (remaining fluid) for intramuscular injection. The incidences of adverse events (AE), serious adverse events (SAE), local reactions, and systemic reactions were recorded at the screening stage (within 14 days before enrollment) and at 7, 14 and 42 days after treatment , And the vital signs, laboratory (blood, urine, blood biochemistry), ECG, chest X-ray, abdominal B-ultrasound. Results A total of 7 AE events were observed in different doses of rhRIG group, including glutamate aminotransferase, aspartate aminotransferase and glutamyl transpeptidase, decreased white blood cell count, upper respiratory tract infection and ectopic pregnancy, of which ectopic pregnancy Judge as SAE. The above-mentioned AEs are judged to be unrelated to the test drug or may not be relevant. No AE / SAE occurred in the control group. All subjects showed no abnormal changes in vital signs after treatment. Conclusion The subjects were well tolerated with a single intramuscular injection of 10 to 40 IU / kg rhRIG.