Phase I clinical trial of pharmacokinetics and safety comparison between the generic and the original bevacizumab
10.3760/cma.j.cn114015-20220218-00138
- VernacularTitle:仿制与原研贝伐珠单抗药代动力学和安全性比对的Ⅰ期临床试验
- Author:
Xiuhua REN
1
;
Hengyi YU
;
Yinian FANG
;
Donglin ZHANG
;
Qian CHEN
;
Yongfang LEI
;
Dong LIU
;
Zhelong LIU
Author Information
1. 华中科技大学同济医学院附属同济医院Ⅰ期临床试验研究室，武汉 430030
- Publication Type:Journal Article
- Keywords:
Vascular endothelial growth factor;
Antibodies, monoclonal;
Bevacizumab;
Equivalence trial;
Pharmacokinetics;
Safety
- From:
Adverse Drug Reactions Journal
2022;24(6):300-307
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To compare the pharmacokinetics and safety of single intravenous injection of the generic bevacizumab injection WBP264 and the original bevacizumab injection Avastin ? in healthy male volunteers. Methods:The study was designed as a randomized, double-blind, single dose, parallel, and controlled phase I clinical trial. Healthy male volunteers who were recruited publicly were randomized into the trial group (intravenous infusion of WBP264) and the control group (intravenous infusion of Avastin ?), and the dose was 3 mg/kg. Peripheral venous blood was collected within 30 minutes before administration, 45 minutes after onset of the administration, immediately after finishing the administration, 2.5, 3.5, 5.5, 9.5, 13.5, 24, 48 hours and on the 5th, 8th, 15th, 22nd, 29th, 36th, 43rd, 57th, 71st, 85th, and 99th days after the administration. The plasma concentration was measured by enzyme-linked immunosorbent assay, the plasma concentration-time curve and its semilogarithmic plot were plotted, and the pharmacokinetic parameters such as the area under the plasma concentration-time curve [including AUC from time zero to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞)], peak concentration ( Cmax), time to peak ( Tmax), plasma elimination half-life ( t1/2), clearance rate (CL), and apparent volume of distribution (Vd) were calculated. When the 90% confidence intervals ( CI) of the geometric mean ratio of AUC 0-t, AUC 0-∞, and Cmax between the trial group and the control group were between 0.80-1.25, it indicated that pharmacokinetics of WBP264 and Avastin ? were similar. The physical examination, vital signs detection, electrocardiogram, and laboratory tests were performed on the subjects, the occurrence of adverse events (AEs) and the severity classification were recorded, and correlation between the AEs and the trial drug was evaluated. The anti-drug antibody and its neutralizing antibody were detected before administration and on the 8th, 15th, 29th, 43rd, 71st, and 99th days after administration to evaluate the immunogenicity of the drug. Results:A total of 78 subjects were recruited, 39 in the trial group and 39 in the control group. In the trial group, 2 cases withdrew from the trial (1 case did not take the drug and 1 case withdrew for personal reason after taking the drug). Seventy-seven cases were in the safety analysis set and 76 cases in the pharmacokinetic analysis set. The differences in age, height, weight, and body mass index between the 2 groups were not significant (all P>0.05). The plasma concentration-time curves of bevacizumab between the trial group and the control group were similar. The geometric mean ratios (90% CI) of AUC 0-t, AUC 0-∞, and Cmax were 1.04 (0.98-1.10), 1.03 (0.98-1.10), and 1.09 (1.03-1.14), respectively. The differences in the incidence of overall AEs [89.5% (34/38) vs. 87.2% (34/39)] and the incidence of AEs possibly related to the trial drug [86.8% (33/38) vs. 79.5% (31/39)] between the trial group and the control group were not significant (all P>0.05). Only one case of AE in the trial group was grade 3 in severity and was assessed as being not related to the drug, and the rest were grade 1-2, with grade 1 AEs accounting for the vast majority. The difference in the positive rate of anti-drug antibody between the trial group and the control group was not significant [10.5% (4/38) vs. 10.3% (4/39), P>0.05]. The neutralizing antibody test was negative in the patients with positive anti-drug antibody. Conclusion:The pharmacokinetics and safety of WBP264 and Avastin ? are similar.
