Pharmacokinetics, Pharmacodynamics, and Safety of Nipocalimab in Healthy Chinese Volunteers: A Single-Dose, Phase I Study.

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Neurology and Therapy Pub Date : 2025-05-19 DOI:10.1007/s40120-025-00763-5

Haiyan Li, Juanfang Liu, Xiaohong Wang, Weilong Zhao, Lili Zhang, Xiaoye Niu, Jingyao Liu, Zhongqi Dong

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Abstract

Introduction: Nipocalimab is a high-affinity, fully human, immunoglobulin G (IgG) 1 monoclonal antibody that inhibits the neonatal Fc receptor. Nipocalimab is under development for the treatment of various IgG autoantibody- and alloantibody-mediated diseases. This study assessed the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose of nipocalimab in healthy Chinese volunteers.

Methods: In this phase I, open-label study, healthy volunteers received single doses of intravenous (IV) nipocalimab at 15, 30, or 45 mg/kg. The primary objective was to assess the PK following a single administration of nipocalimab. Secondary objectives included the PD effects of nipocalimab on change from baseline in total serum IgG levels, safety, and tolerability.

Results: A total of 30 healthy Chinese volunteers (mean age 31.0 years, 93.3% men) received single doses of IV nipocalimab. Following a single infusion of nipocalimab, mean exposure increased as the dose of nipocalimab increased. Maximum serum nipocalimab concentrations increased proportionally with doses, whereas the area under the concentration-time curve increased by greater than a dose-proportional manner. Nipocalimab led to dose-dependent reductions in serum IgG levels from baseline; this decrease was sustained over a longer period of time with higher dose levels. Nipocalimab was generally well tolerated, with an acceptable safety profile, across all three doses; most of the treatment-emergent adverse events (TEAEs) were mild. Higher doses of nipocalimab were not associated with increased frequency of TEAEs.

Conclusion: Our findings add to the evidence on the safety, tolerability, and PD of nipocalimab in the Chinese population, and support for the treatment of pathogenic IgG-mediated diseases in this population.

Trial registration: ClinicalTrials.gov NCT05151692.

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尼波卡利单抗在中国健康志愿者中的药代动力学、药效学和安全性：单剂量I期研究

Nipocalimab是一种高亲和力的全人源免疫球蛋白G (IgG) 1单克隆抗体，可抑制新生儿Fc受体。Nipocalimab正在开发中，用于治疗各种IgG自身抗体和同种抗体介导的疾病。本研究评估了中国健康志愿者单剂量尼波卡利单抗的安全性、药代动力学（PK）和药效学（PD）。方法：在这项I期开放标签研究中，健康志愿者接受单剂量静脉注射（IV） nipocalimab，剂量为15mg /kg、30mg /kg或45mg /kg。主要目的是评估单次给药nipocalimab后的PK。次要目标包括尼波卡利单抗对PD的影响，从基线到血清总IgG水平的变化，安全性和耐受性。结果：共有30名健康的中国志愿者（平均年龄31.0岁，男性占93.3%）接受了单次静脉注射尼波卡利单抗。单次输注尼波卡利单抗后，平均暴露量随着尼波卡利单抗剂量的增加而增加。尼波卡利单抗血清最大浓度随剂量成比例增加，而浓度-时间曲线下面积的增加大于剂量成比例。尼波卡利单抗导致血清IgG水平较基线呈剂量依赖性降低；在较高的剂量水平下，这种下降持续的时间更长。Nipocalimab在所有三种剂量中耐受性良好，具有可接受的安全性；大多数治疗后出现的不良事件（teae）是轻微的。较高剂量的尼波卡利单抗与teae发生频率的增加无关。结论：我们的研究结果为尼波卡利单抗在中国人群中的安全性、耐受性和PD提供了证据，并为在中国人群中治疗致病性igg介导疾病提供了支持。试验注册：ClinicalTrials.gov NCT05151692。

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来源期刊

Neurology and Therapy CLINICAL NEUROLOGY-

CiteScore

5.40

自引率

8.10%

发文量

103

审稿时长

6 weeks

期刊介绍： Aims and Scope Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice. Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. 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