Safety, PK, and PD of recombinant anti-interleukin-21 monoclonal antibody in a first-in-human trial
Safety, PK, and PD of recombinant anti-interleukin-21 monoclonal antibody in a first-in-human trial
复制标题
DOI：
10.5414/cp202474
复制
发表时间：
2016-04-01
影响因子：
0.8
通讯作者：
Mouritzen, Ulrik
中科院分区：
文献类型：
--
作者：
Ignatenko, Stanislav;Skrumsager, Birte K.;Mouritzen, Ulrik
目的：这项首次在人体中进行的随机、双盲、安慰剂对照试验评估了NNC0114-0005（一种重组人抗白细胞介素(IL)-21单克隆抗体）治疗类风湿关节炎（RA）的安全性。方法和材料：健康男性受试者（HS = 44）和接受甲氨蝶呤治疗的活动性RA患者（n = 20）随机分为3组：1组为单次静脉或皮下注射NNC0114-0005 （0.0025 - 25 mg/kg）或安慰剂。安全终点、药代动力学和药效学在12周内进行评估。结果：对所有研究参与者进行了分析。21名nnc0114 -0005治疗的参与者（44%）报告了37例ae， 10名安慰剂治疗的参与者（63%）报告了18例ae，没有剂量依赖性。最常见的ae是头痛和鼻咽炎；无注射部位反应。测定了NNC0114-0005的线性药代动力学（平均终末半衰期2 - 3周）。观察剂量依赖性总IL-21（游离IL-21和IL-21- nnc0114 -0005复合物）积累。服用25 mg/kg NNC0114-0005可观察到RA活性降低的初步迹象。结论：单剂量NNC0114-0005 (
Objective: This first-in-human, randomized, double-blind, placebo-controlled trial assessed the safety of NNC0114-0005, a human recombinant anti interleukin (IL)-21 monoclonal antibody, for the treatment of rheumatoid arthritis (RA). Methods and materials: Healthy male subjects (HS = 44)) and patients with active RA treated with methotrexate (n = 20) were randomized 3 : 1 to single IV or SC doses of NNC0114-0005 (0.0025 - 25 mg/kg) or placebo. Safety endpoints, pharmacokinetics, and pharmacodynamics were assessed over 12 weeks. Results: All study participants were analyzed. 37 AEs were reported in 21 NNC0114-0005-treated participants (44%) and 18 AEs in 10 placebo-treated participants (63%), with no dose-dependency. The most common AEs were headache and nasopharyngitis; there were no injection-site reactions. Linear pharmacokinetics of NNC0114-0005 were indicated (mean terminal half-life, 2 - 3 weeks). Dose-dependent total IL-21 (free IL-21 and IL-21-NNC0114-0005 complexes) accumulation was observed. Preliminary signs of reduced RA activity were observed with 25 mg/kg NNC0114-0005. Conclusions: Single doses of NNC0114-0005 (