anti-CD19单克隆抗体的安全性和耐受性,读出- 551,在学科系统性硬化症:第一阶段,随机、安慰剂对照、单剂量升级研究。
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Schiopu E, Chatterjee年代,许V,福罗,Cimbora D,智利的K,姚明W,李J, streich K,麦基弗K,白色B, Katz E, Drappa J,肌肉萎缩,Herbst R
anti-CD19单克隆抗体的安全性和耐受性,读出- 551,在学科系统性硬化症:第一阶段,随机、安慰剂对照、单剂量升级研究。
关节炎Res其他。2016年6月7日,18 (1):131。doi: 10.1186 / s13075 - 016 - 1021 - 2。
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27267753 (在PubMed]
- 文摘
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背景:系统性硬化症(SSc)是一种临床异构,危及生命的疾病,其特征是纤维化microvasculopathy和自身免疫。广泛的临床前和临床数据表明B细胞SSc的发病机理。读出- 551是一个临床实验的人源化单克隆抗体,目标B细胞表面抗原CD19和调节依赖抗体,细胞B细胞的细胞毒性。本临床研究评估的安全性和耐受性,药物动力学和药效学读出和SSc - 551科目。方法:这个阶段我多中心、随机、双盲、安慰剂对照、单剂量升级研究了成年受试者与有限或弥漫性皮肤SSc。单一静脉注射剂量的读出- 551管理,安全性和耐受性进行了评估。读出- 551药物动力学(PK)、药效学和免疫原性也评估。安全评估包括不良事件的发生率和临床和实验室结果的变化。读出- 551血清浓度,对循环的影响和组织B细胞和浆细胞(pc)和反麻醉品的抗体进行了分析。修改Rodnan皮肤评分(夫人)和肺功能测试被用来探索读出- 551的临床效果。 RESULTS: The study enrolled 28 subjects with SSc (mean age, 47.3 years; 67.9 % female). Twenty-four received a single dose of MEDI-551 (0.1-10.0 mg/kg) and four received placebo. Treatment-emergent adverse events (TEAEs) occurred in 95.8 % of subjects in the MEDI-551 group and in 75.0 % of subjects in the placebo group; the majority of TEAEs were mild or moderate in severity. Two serious adverse events were considered possibly related to the study drug. One death, deemed not related to the study drug, occurred in a MEDI-551-treated subject. MEDI-551 exhibited linear PK in the dose range of 1.0 to 10.0 mg/kg, and more rapid clearance at lower doses. Dose-dependent depletion of circulating B cells and plasma cells was observed. MRSS assessments suggest a possible clinical effect of MEDI-551 on affected skin. CONCLUSIONS: A single escalating dose of MEDI-551 was tolerable and safe in this subject population. B cell depletion was achieved and was dose dependent. A signal of clinical effect was observed. Based on these results, further investigation of MEDI-551 as a disease-modifying treatment for SSc is warranted. TRIAL REGISTRATION: www.clinicaltrials.gov identifier, NCT00946699 ; registered 23 July 2009.
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