A randomized, double-blind, parallel controlled phase I clinical trial to determine the equivalence of pharmacokinetics and safety, immunogenicity and tolerability between HS016 and China-licensed adalimumab in healthy male subjects
2022-02-11·Advances in clinical and experimental medicine : official organ Wroclaw Medical University4区 · 医学
Comparative assessment of pharmacokinetic parameters between HS016, an adalimumab biosimilar, and adalimumab (Humira®) in healthy subjects and ankylosing spondylitis patients: Population pharmacokinetic modeling.
4区 · 医学
作者: Xiaofeng Zeng ; Jing Zhang ; Jicheng Yu ; Xiaojie Wu ; Yuancheng Chen ; Jufang Wu ; Xiaoli Yang ; Jingjing Wang ; Guoying Cao
The HS016 is an adalimumab biosimilar related to the immunoglobulin G1 (IgG1) antibody, with a similar amino acid sequence.
To quantify the differences in the pharmacokinetic (PK) parameters of HS016 and adalimumab in healthy individuals and patients with ankylosing spondylitis (AS).
MATERIAL AND METHODS:
The PK data for HS016 and adalimumab were obtained in a randomized, double-blind, phase 1 clinical study in Chinese healthy subjects after a single-dose subcutaneous administration (136 healthy subjects), and in a randomized, double-blind, phase 3 trial of AS patients who received subcutaneous injection of HS016 or adalimumab once every 2 weeks for 24 weeks (366 AS patients).
The time course of HS016 and adalimumab was characterized by a one-compartment model with first-order absorption and elimination kinetics. Age, body weight, creatinine clearance (CLcr) and anti-drug antibody were covariates for the apparent clearance (CL/F); body weight and subject type were significant covariates for the apparent volume of distribution (V/F). The V/F and CL/F were estimated at 11.3 L and 0.0102 L/h. The ratios of the geometric least square (LS) means (HS016 compared to the adalimumab treatment group after multiple doses) in healthy subjects were 97.14 (87.70, 107.59) for the concentration-time curve from time zero to the last measurable concentration (AUC0-t) and 99.14 (90.03, 109.16) for the maximum serum drug concentration within a steady-state dosing interval (Cmax, ss); the ratios (90% confidence interval (90% CI)) in AS patients were 97.03 [84.10; 111.96] for the AUC within the steady-state dose intervals (AUC0-tau) and 99.62 [88.09; 112.68] for Cmax, ss.
The systemic exposure of HS016 was similar to that of adalimumab in healthy subjects and AS patients, demonstrating PK similarity.
2021-12-02·Journal of pharmaceutical sciences3区 · 医学
Physicochemical and functional characterization of HS016, a biosimilar of adalimumab (Humira).
3区 · 医学
作者: Dong Gao ; Lei Nie ; Junjie Yuan ; Feng Hu ; Zhenhua Wu ; Qunhai Lin ; Haibin Wang
The characterization of a biosimilar drug HS016, the reference product adalimumab (Humira), and their biosimilarities were determined using physical chemistry and functional similarity tests. The primary and higher order structures, size and charge variants, glycosylation profiles, and in vitro potency of both antibodies were characterized both for unstressed and stability samples. Slight differences were observed in the relative levels of methionine oxidation, low molecular weight components, terminal lysine variant, high mannoses and galactosylated glycans between HS016 and Humira. However, no differences in antigen binding activity, Fc receptor affinity, antibody-dependent cell-mediated cytotoxicity or complemented-dependent cytotoxicity were found. The primary and higher order structures, physicochemical properties, and biological activity of HS016 and adalimumab were similar.
2021-10-28·Clinical rheumatology3区 · 医学
Evaluation of adalimumab biosimilar candidate (HS016) in Chinese patients with active ankylosing spondylitis based on a health survey: sub-analysis of a phase 3 study.
3区 · 医学
作者: Jinmei Su ; Mengtao Li ; Lan He ; Dongbao Zhao ; Weiguo Wan ; Yi Liu ; Jianhua Xu ; Jian Xu ; Huaxiang Liu ; Lindi Jiang ; Huaxiang Wu ; Xiaoxia Zuo ; Cibo Huang ; Xiumei Liu ; Fen Li ; Zhiyi Zhang ; Xiangyuan Liu ; Lingli Dong ; Tianwang Li ; Haiying Chen ; Jingyang Li ; Dongyi He ; Xin Lu ; Anbin Huang ; Yi Tao ; Yanyan Wang ; Zhuoli Zhang ; Wei Wei ; Xiaofeng Li ; Xiaofeng Zeng
The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to compare the efficacy of HS016 and adalimumab in stratified subgroups at different time points using Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) and short form 36 (SF-36) questionnaires.
We carried out a multicenter, randomized, double-blind, parallel, positive control, phase 3 trial of patients with active AS. They were selected randomly to be subcutaneously administered 40 mg HS016 or adalimumab every 2 weeks for a total treatment period of 24 weeks in a 2:1 ratio. A health surveys were used to assess mental and physical improvements of patients as well as other factors.
HAQ-S revealed that changes in scores from baseline in both groups were time dependent until 14 weeks and that during the first 4 weeks of treatment the changes declined rapidly. The SF-36 health survey revealed that both HS016 and adalimumab produced rapid beneficial effects against AS during the first 2 weeks of therapy, which gradually declined between 2 and 12 weeks and flattened out after 12 weeks until 24 weeks.
This trial demonstrated that both HS016 and adalimumab produced rapid improvements in symptoms during the first 2 weeks of treatment. These findings suggest that HS016 is an alternative economical treatment for Chinese AS patients producing a rapid amelioration of symptoms, aiding them to recover their lifestyle satisfaction.
http://www.chictr.org.cn/enindex.aspx , ChiCTR1900022520, retrospectively registered. Key points • HS016 and adalimumab produced rapid AS symptom improvements during the first 2 weeks followed by a slowdown of improvements until week 4 with afterwards few improvements evaluated by HAQ-S • The improvements according to the short form of the 36 (SF-36) questionnaires revealed similar trends as for HAQ-S • There was no significant difference in HAQ-S and SF-36 scores between HS016 and adalimumab.