新生儿 Fc 受体抑制剂 Rozanolixizumab 的安全性、耐受性、药代动力学和药效学:健康日本人、中国人和白人参与者的种族敏感性研究。

IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Clinical Pharmacology in Drug Development Pub Date : 2024-11-21 DOI:10.1002/cpdd.1484
Assem El Baghdady, Rocío Lledó-García, Maryam Gayfieva, Romana Lowcock, Shikiko Watanabe, Jagdev Sidhu, Denisa Wilkes
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引用次数: 0

摘要

Rozanolixizumab是一种抗人类新生儿Fc受体的人源化免疫球蛋白(Ig)G4单克隆抗体,可减少IgG,包括致病性IgG自身抗体。以前的临床研究已对罗扎尼珠单抗的安全性和耐受性进行了评估,研究对象主要是白人。与白人参与者相比,我们评估了健康的日本和中国参与者单剂量使用罗扎尼珠单抗的安全性、耐受性、药代动力学和药效学。这项双盲、单中心、基于英国的 1 期研究将 65 名参与者随机分为罗扎尼单抗 4 mg/kg(仅限日本和白人参与者)、7 mg/kg 或 10 mg/kg。所有治疗突发不良事件(TEAEs)的严重程度均为轻度至中度;未出现严重TEAEs、严重TEAEs或导致停药的TEAEs。日本和中国参试者的 TEAE 发生率与白人参试者相当。日本和中国参试者的罗扎尼单抗全身暴露量低于白种人参试者,这是因为中国和日本参试者体重较轻导致实际用药剂量较低,这表明体重并不是罗扎尼单抗药代动力学的相关预测因素。所有三个种族的患者都表现出剂量依赖性的IgG下降,IgG在第10天左右达到最低值,到第56天逐渐恢复到基线水平。这些数据支持罗扎尼珠单抗以往临床研究的安全性数据适用于日本人和中国人。
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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Neonatal Fc Receptor Inhibitor Rozanolixizumab: An Ethnic Sensitivity Study in Healthy Japanese, Chinese, and White Participants.

Rozanolixizumab is an anti-human neonatal Fc receptor humanized immunoglobulin (Ig) G4 monoclonal antibody that reduces IgG, including pathogenic IgG autoantibodies. Rozanolixizumab safety and tolerability have been assessed in previous clinical studies with predominantly White participants. We assessed safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of rozanolixizumab in healthy Japanese and Chinese participants compared with White participants. This double-blind, single-center, UK-based, Phase 1 study randomized 65 participants to rozanolixizumab 4 mg/kg (Japanese and White participants only), 7  mg/kg, or 10 mg/kg. All treatment-emergent adverse events (TEAEs) were mild to moderate in severity; no severe TEAEs, serious TEAEs, or TEAEs leading to discontinuation occurred. Incidences of TEAEs in Japanese and Chinese participants were comparable to those in White participants. Japanese and Chinese participants had lower systemic rozanolixizumab exposure relative to Caucasian participants, attributable to lower actual doses administered due to lower body weight in Chinese and Japanese participants, indicating that body weight is not a relevant predictor of rozanolixizumab pharmacokinetics. All 3 ethnicities demonstrated dose-dependent IgG reductions, with IgG nadir achieved around Day 10 and gradual return to baseline levels by Day 56. These data support the applicability of safety data from previous clinical studies of rozanolixizumab to individuals of Japanese and Chinese ethnicity.

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来源期刊
CiteScore
3.70
自引率
10.00%
发文量
154
期刊介绍: Clinical Pharmacology in Drug Development is an international, peer-reviewed, online publication focused on publishing high-quality clinical pharmacology studies in drug development which are primarily (but not exclusively) performed in early development phases in healthy subjects.
期刊最新文献
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Neonatal Fc Receptor Inhibitor Rozanolixizumab: An Ethnic Sensitivity Study in Healthy Japanese, Chinese, and White Participants. The Safety, Tolerability, and Pharmacokinetics of Active Ingredients From Hydroxysafflor Yellow A in Healthy Chinese Volunteers. Pharmacokinetics and Bioequivalence of Two Formulations of Montelukast Sodium Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions. Osimertinib Efficacy and Safety in Treating Epidermal Growth Factor Receptor Mutation-Positive Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis. Issue Information
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