CMAB008（一种英夫利昔单抗生物类似药）在健康受试者和中重度活动性类风湿关节炎患者中的群体药代动力学研究。
Population Pharmacokinetics of CMAB008 (an Infliximab Biosimilar) and Remicade in Healthy Subjects and Patients with Moderately to Severely Active Rheumatoid Arthritis.
机构信息
Department of Rheumatology and Immunology, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, People's Republic of China.
Mabpharm Limited, Taizhou, People's Republic of China.
出版信息
Adv Ther. 2023 Mar;40(3):1005-1018. doi: 10.1007/s12325-022-02396-8. Epub 2023 Jan 6.
INTRODUCTION
CMAB008 is a monoclonal antibody developed as a biosimilar to infliximab (Remicade, Janssen). The pharmacokinetic characteristics of CMAB008 and Remicade in healthy subjects and patients with moderately to severely active rheumatoid arthritis (RA) were investigated using a population modeling approach, and the pharmacokinetic similarity of CMAB008 to Remicade was assessed.
METHODS
The population pharmacokinetic model was developed on the basis of intensive pharmacokinetic data from a phase 1 study in healthy male subjects and combined intensive and sparse pharmacokinetic data from a phase 3 study in patients with RA.
RESULTS
A two-compartment model with first-order elimination adequately described CMAB008 and Remicade concentration data in healthy subjects and patients with RA. The analysis of covariates identified anti-drug antibody (ADA), neutralizing antibody (NAB), real-time body weight (BWT), and real-time albumin (ALB) as significant covariates on clearance, and BWT was also a significant covariate for the central volume of distribution. The treatment type (CMAB008 versus Remicade) and the study population (healthy subjects versus patients with RA) were not identified as significant covariates on the pharmacokinetics of infliximab, demonstrating pharmacokinetic similarity between CMAB008 and Remicade in both study populations. The effect of BWT and ALB changes on exposures to infliximab was within the acceptable range, suggesting that the 3 mg/kg regimen is appropriate in clinical practice for patients with RA and BTW and ALB distribution within the range evaluated in the current analysis.
CONCLUSIONS
The pharmacokinetic characteristics were similar between CMAB008 and Remicade in healthy subjects and patients with RA. CMAB008 can be considered bioequivalent to Remicade.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov identifiers NCT04779892, NCT03478111.
简介
CMAB008 是一种单克隆抗体，作为英夫利昔单抗（Remicade，杨森）的生物类似药开发。采用群体建模方法研究了 CMAB008 和 Remicade 在健康受试者和中重度活动性类风湿关节炎（RA）患者中的药代动力学特征，并评估了 CMAB008 与 Remicade 的药代动力学相似性。
方法
该群体药代动力学模型基于健康男性受试者的 1 期研究中的密集药代动力学数据以及 RA 患者的 3 期研究中的密集和稀疏药代动力学数据进行开发。
结果
CMAB008 和 Remicade 在健康受试者和 RA 患者中的浓度数据用两室模型和一级消除过程来描述。协变量分析确定了抗药物抗体（ADA）、中和抗体（NAB）、实时体重（BWT）和实时白蛋白（ALB）是清除率的显著协变量，BWT 也是中央分布容积的显著协变量。治疗类型（CMAB008 与 Remicade）和研究人群（健康受试者与 RA 患者）并未被确定为英夫利昔单抗药代动力学的显著协变量，表明 CMAB008 和 Remicade 在两个研究人群中具有相似的药代动力学。英夫利昔单抗暴露量受 BWT 和 ALB 变化的影响在可接受范围内，表明在当前分析中评估的范围内，RA 患者的 BWT 和 ALB 分布下，3mg/kg 剂量方案在临床实践中是合适的。
结论
CMAB008 和 Remicade 在健康受试者和 RA 患者中的药代动力学特征相似。CMAB008 可被认为与 Remicade 生物等效。
临床试验注册
ClinicalTrials.gov 标识符 NCT04779892、NCT03478111。
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