Virginia Commonwealth University School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia, United States of America.
PLoS One. 2021 May 6;16(5):e0247357. doi: 10.1371/journal.pone.0247357. eCollection 2021.
Endogenous serine protease inhibitors are associated with anti-inflammatory and pro-survival signaling mediated via Low-density lipoprotein receptor-related protein 1 (LRP1) signaling. SP16 is a short polypeptide that mimics the LRP1 binding portion of alpha-1 antitrypsin.
A pilot phase I, first-in-man, randomized, double blind, placebo-controlled safety study was conducted to evaluate a subcutaneous injection at three dose levels of SP16 (0.0125, 0.05, and 0.2 mg/kg [up to 12 mg]) or matching placebo in 3:1 ratio in healthy individuals. Safety monitoring included vital signs, laboratory examinations (including hematology, coagulation, platelet function, chemistry, myocardial toxicity) and electrocardiography (to measure effect on PR, QRS, and QTc).
Treatment with SP16 was not associated with treatment related serious adverse events. SP16 was associated with mild-moderate pain at the time of injection that was significantly higher than placebo on a 0-10 pain scale (6.0+/-1.4 [0.2 mg/kg] versus 1.5+/-2.1 [placebo], P = 0.0088). No differences in vital signs, laboratory examinations and electrocardiography were found in those treated with SP16 versus placebo.
A one-time treatment with SP16 for doses up to 0.2 mg/kg or 12 mg was safe in healthy volunteers.
内源性丝氨酸蛋白酶抑制剂与通过低密度脂蛋白受体相关蛋白 1（LRP1）信号转导介导的抗炎和促生存信号有关。SP16 是一种短肽，模拟α-1 抗胰蛋白酶的 LRP1 结合部分。
进行了一项 I 期、首次人体、随机、双盲、安慰剂对照的安全性研究，以评估三种剂量水平的 SP16（0.0125、0.05 和 0.2mg/kg[最高 12mg]）或匹配安慰剂的皮下注射，健康个体中以 3:1 的比例随机分配。安全性监测包括生命体征、实验室检查（包括血液学、凝血、血小板功能、化学、心肌毒性）和心电图（测量对 PR、QRS 和 QTc 的影响）。
SP16 治疗与治疗相关的严重不良事件无关。SP16 与注射时的轻度至中度疼痛相关，与安慰剂相比，疼痛评分在 0-10 疼痛量表上显著更高（6.0+/-1.4[0.2mg/kg]与 1.5+/-2.1[安慰剂]，P=0.0088）。与安慰剂相比，接受 SP16 治疗的患者在生命体征、实验室检查和心电图方面没有差异。
单次使用 SP16 治疗剂量高达 0.2mg/kg 或 12mg 在健康志愿者中是安全的。
