WBP216，一种新型白细胞介素-6 单克隆抗体，在类风湿关节炎患者中的安全性、耐受性、药代动力学、药效学和疗效：一项 Ia 期随机安慰剂对照研究。

Safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of WBP216, a novel IL-6 monoclonal antibody, in patients with rheumatoid arthritis: A phase Ia randomized placebo-controlled study.

机构信息

Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

出版信息

Front Immunol. 2023 Feb 28;13:1110992. doi: 10.3389/fimmu.2022.1110992. eCollection 2022.

BACKGROUND

WBP216 is a novel human immunoglobulin G1 (IgG1) monoclonal antibody for interleukin (IL)-6. We aimed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a single ascending dose (SAD) of WBP216 in patients with rheumatoid arthritis (RA).

METHODS

In this double-blind, placebo-controlled, SAD, phase Ia study, patients with RA were randomized in a 3:1 (Group A1, 10 mg) and 6:2 (Group A2, 30 mg; Group A3, 75 mg; Group A4, 150 mg; Group A5, 300 mg) ratios to receive either ascending doses of WBP216 or placebo subcutaneously. The primary endpoint was the incidence of adverse events (AEs), while the secondary endpoints were characterization of PK, PD, and immunogenicity of WBP216 and the exploratory endpoints included improvements in RA clinical metrics. All statistical analyses were performed using SAS version 9.2.

RESULTS

A total of 41 subjects (34 females and 7 males) were enrolled in the study. WBP216 was well tolerated in all doses (10-300 mg). Most treatment-emergent AEs (TEAEs; 97.6%) were of grade 1 severity and resolved without any treatment. No subjects experienced TEAEs leading to withdrawal or death during the study. An increase in serum concentration and total IL-6 from baseline was observed, while a substantial decrease in high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) was observed in all the WBP216 groups. Anti-drug antibodies were detected in only one subject after dosing, indicating an acceptable immunogenicity profile. Limited ACR20 and ACR50 response was observed in the WBP216 groups and no response in the placebo group.

CONCLUSION

WBP216 demonstrated a good safety profile and evidence of potential efficacy in the treatment of patients with RA.

CLINICAL TRIAL REGISTRATION

http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier CTR20170306.

背景

WBP216 是一种新型人免疫球蛋白 G1（IgG1）单克隆抗体，用于白细胞介素（IL）-6。我们旨在评估单剂量递增（SAD）WBP216 在类风湿关节炎（RA）患者中的安全性、耐受性、药代动力学（PK）和药效学（PD）。

方法

在这项双盲、安慰剂对照、SAD、I 期研究中，RA 患者以 3:1（A1 组，10mg）和 6:2（A2 组，30mg；A3 组，75mg；A4 组，150mg；A5 组，300mg）的比例随机接受递增剂量的 WBP216 或安慰剂皮下注射。主要终点是不良事件（AE）的发生率，次要终点是 WBP216 的 PK、PD 和免疫原性特征以及探索性终点包括 RA 临床指标的改善。所有统计分析均使用 SAS 版本 9.2 进行。

结果

共有 41 名受试者（34 名女性和 7 名男性）入组研究。所有剂量（10-300mg）的 WBP216 均具有良好的耐受性。大多数治疗后出现的不良事件（TEAEs；97.6%）为 1 级严重程度，无需治疗即可缓解。研究期间，无受试者因 TEAEs 导致退出或死亡。所有 WBP216 组均观察到血清浓度和总 IL-6 从基线升高，而高敏 C 反应蛋白（hs-CRP）和红细胞沉降率（ESR）均显著降低。仅在 1 名受试者在给药后检测到抗药物抗体，表明免疫原性特征可接受。WBP216 组观察到 ACR20 和 ACR50 反应有限，安慰剂组无反应。