Sheng Xiao-Yan, Liu Zhi-Yan, Zhao Jing, Song Lei, Zhao Wen-Ming, Zhao Xia, Cui Yi-Min
Department of Pharmacy, Peking University First Hospital, Beijing, China.
Department of Cardiology, Peking University First Hospital, Beijing, China.
Platelets. 2022 Nov 17;33(8):1185-1191. doi: 10.1080/09537104.2022.2073344. Epub 2022 May 13.
The thrombopoietin mimetic peptide for injection is a second-generation thrombopoietin receptor agonist (TPO-RA) used in the treatment of patients with immune thrombocytopenia. The aim of the present study was to assess the safety, tolerance, pharmacokinetic and pharmacodynamic properties of thrombopoietin mimetic peptide for injection in Chinese healthy volunteers. A randomized, placebo-controlled, double-blind, dose-escalation study was conducted in healthy Chinese subjects aged 18-50 years. Thirty subjects received single subcutaneous injection of 0.3 μg/kg, 1.0 μg/kg, 2.0 μg/kg thrombopoietin mimetic peptide or placebo. Thrombopoietin mimetic peptide was safe and well tolerated at doses of 0.3-2.0 μg/kg. There was no significant change in mean platelet count (PLT) from baseline at the 0.3 μg/kg or placebo groups. The mean PLT of subjects in the 1.0 μg/kg and 2.0 μg/kg groups peaked at day 12 (± 1), began to decline around day 17, and returned to the baseline level at day 28 (± 1). Platelet aggregation rates of the three dose groups showed no significant change before and after administration. Serum concentrations of thrombopoietin mimetic peptide in all subjects were below the quantization limit. This was the first study to demonstrate that subcutaneous injection of thrombopoietin mimetic peptide at doses of 0.3-2.0 μg/kg was safe and well tolerated in Chinese healthy subjects. As a second-generation TPO-RA, thrombopoietin mimetic peptide is effective at improving PLT after single subcutaneous injection at dose of ≥1 μg/kg.What is the context?● Immune thrombocytopenia (ITP) is a rare, serious autoimmune disorder characterized by low platelet count (PLT) without an alternate cause. The treatment goal of ITP is to increase the platelet count to a safe level that can stop active bleeding and reduce the risks of future bleeding.● Thrombopoietin receptor agonists (TPO-RAs, e.g. eltrombopag, avatrombopag, hetrombopag, and romiplostim) have shown high response rates in stimulating platelet production and reducing the risk of bleeding. TPO-RAs provide ITP patients with well-tolerated, long-term treatment choices.What is new?● The thrombopoietin mimetic peptide for injection is a new TPO-RAs developed by Shandong Quangang Pharmaceutical Co., Ltd. (China).● This study showed that thrombopoietin mimetic peptide is effective at improving PLT after a single subcutaneous injection.● The thrombopoietin mimetic peptide is safe and well-tolerated in Chinese healthy subjects.What is the impact?● This study provides evidence for the further development potential of the thrombopoietin mimetic peptide.
注射用血小板生成素模拟肽是一种第二代血小板生成素受体激动剂（TPO-RA），用于治疗免疫性血小板减少症患者。本研究的目的是评估注射用血小板生成素模拟肽在中国健康志愿者中的安全性、耐受性、药代动力学和药效学特性。对18至50岁的中国健康受试者进行了一项随机、安慰剂对照、双盲、剂量递增研究。30名受试者接受了单次皮下注射0.3μg/kg、1.0μg/kg、2.0μg/kg的血小板生成素模拟肽或安慰剂。血小板生成素模拟肽在0.3-2.0μg/kg剂量下安全且耐受性良好。0.3μg/kg组或安慰剂组的平均血小板计数（PLT）与基线相比无显著变化。1.0μg/kg和2.0μg/kg组受试者的平均PLT在第12（±1）天达到峰值，在第17天左右开始下降，并在第28（±1）天恢复到基线水平。三个剂量组的血小板聚集率在给药前后均无显著变化。所有受试者的血小板生成素模拟肽血清浓度均低于定量限。这是第一项证明皮下注射0.3-2.0μg/kg剂量的血小板生成素模拟肽在中国健康受试者中安全且耐受性良好的研究。作为第二代TPO-RA，血小板生成素模拟肽在≥1μg/kg剂量单次皮下注射后可有效提高PLT。
背景是什么？
● 免疫性血小板减少症（ITP）是一种罕见的严重自身免疫性疾病，其特征是血小板计数（PLT）低且无其他原因。ITP的治疗目标是将血小板计数提高到安全水平，以停止活动性出血并降低未来出血的风险。
● 血小板生成素受体激动剂（TPO-RAs，如艾曲泊帕、阿伐曲泊帕、海曲泊帕和罗米司亭）在刺激血小板生成和降低出血风险方面显示出高反应率。TPO-RAs为ITP患者提供了耐受性良好的长期治疗选择。
新发现是什么？
● 注射用血小板生成素模拟肽是山东泉港药业有限公司（中国）研发的一种新型TPO-RAs。
● 本研究表明，血小板生成素模拟肽单次皮下注射后可有效提高PLT。
● 血小板生成素模拟肽在中国健康受试者中安全且耐受性良好。
有何影响？
● 本研究为血小板生成素模拟肽的进一步开发潜力提供了证据。
