Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China.
Clin Pharmacol Drug Dev. 2022 Sep;11(9):1028-1035. doi: 10.1002/cpdd.1135. Epub 2022 Jul 2.
This study aimed to evaluate the pharmacokinetics (PK), safety, and immunogenicity of the infliximab biosimilar CMAB008 compared to the reference product (Remicade) in healthy Chinese male subjects to provide the basis for the similarity evaluation of the 2 drugs. In this phase I randomized, double-blind, parallel-controlled, single-dose study, a total of 90 subjects were randomized 1:1 to receive CMAB008 or infliximab reference product with single intravenous injections (5 mg/kg). Blood samples were collected at designed time points for PK and immunogenicity assessment. If the 90%CI of the geometric mean ratio of area under the plasma concentration-time curve from 0 to the time of the last observation, maximum observed plasma concentration, area under the plasma concentration-time curve from 0 to infinity was completely within the range of 80% to 125%, the PK bioequivalence was established. Other PK parameters including time to maximum plasma concentration half-life time, clearance, apparent volume of distribution, and last measurable concentration time point were also assessed. Adverse events (AEs) were recorded. Serum concentration-time profiles were similar across the 2 groups, and PK parameters were comparable in the 2 groups. The 90%CI of the geometric mean ratio of test to reference was within the predefined bioequivalence range of 80% to 125%. The AEs occurred similarly in 2 groups. One serious AE (rhabdomyolysis, grade 3) occurred in the test group. The total positive rates of antidrug antibody and neutralizing antibodies in the test group (85.7% and 5.6%, respectively) were numerically lower than infliximab reference product group (90.9% and 15%, respectively). The PK profile of the 2 groups is statistically equivalent. The preliminary safety and immunogenicity evaluation of the 2 drugs are comparable.
这项研究旨在评估英夫利昔单抗生物类似药 CMAB008 在中国健康男性受试者中的药代动力学（PK）、安全性和免疫原性，并与参比产品（Remicade）进行比较，为这两种药物的相似性评价提供依据。在这项 I 期随机、双盲、平行对照、单次给药研究中，共有 90 名受试者按 1:1 随机分为 CMAB008 组或英夫利昔单抗参比产品组，单次静脉注射（5mg/kg）。设计时间点采集血样进行 PK 和免疫原性评估。如果受试制剂和参比制剂的 AUC0-t，Cmax，AUC0-∞几何均值比的 90%CI 完全在 80%125%范围内，则可判定 PK 生物等效。还评估了其他 PK 参数，包括达峰时间（Tmax）、半衰期（t1/2）、清除率（CL）、表观分布容积（Vz/F）和最后可测量浓度时间点（Tlast）。记录不良事件（AE）。两组的血清浓度-时间曲线相似，两组的 PK 参数也相似。受试制剂和参比制剂的 AUC0-t，Cmax，AUC0-∞几何均值比的 90%CI 在 80%125%的预设生物等效范围内。两组的 AE 发生率相似。试验组发生 1 例严重不良事件（横纹肌溶解症，3 级）。试验组的抗药抗体和中和抗体总阳性率（分别为 85.7%和 5.6%）略低于英夫利昔单抗参比产品组（分别为 90.9%和 15%）。两组的 PK 特征在统计学上等效。两种药物的初步安全性和免疫原性评价结果相当。
