A phase I study evaluating the safety, pharmacokinetics, and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis
A phase I study evaluating the safety, pharmacokinetics, and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis
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DOI：
10.1111/j.0022-202x.2004.23448.x
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发表时间：
2004-12-01
影响因子：
6.5
通讯作者：
Mascelli, MA
中科院分区：
文献类型：
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作者：
Kauffman, CL;Aria, N;Mascelli, MA
抗人IL-12p40亚单位的人单抗(抗IL-12p40)的潜在治疗活性已在体外和体内得到证实，这为银屑病的首次人类研究奠定了基础。这项第一阶段的非随机开放标签研究评估了单次、递增、静脉(IV)剂量的抗IL-12p40在中到重度寻常型牛皮癣患者中的短期安全性、药代动力学和临床反应。18名受试者至少有3%的体表面积受累，分为四个剂量组(0.1、0.3、1.0和5.0 mg/kg)。在16wk的随访期中，在基线和特定时间点监测安全性、药代动力学和临床反应(例如，牛皮癣面积和严重程度指数(PASI))。抗IL-12p40抗体耐受性良好。没有相关的严重不良事件或输液反应的报道，大多数不良事件都是轻微的。IV抗IL-12p40的药物动力学呈线性，平均终端半衰期约为24天。在四个剂量组中观察到与临床反应的速度和程度呈剂量依赖关系。18名受试者中有12名(67%)在服用研究药剂后8至16周内PASI至少改善了75%。在大多数受试者中，银屑病皮损的显著和持续的浓度依赖性改善被观察到。
The potential therapeutic activity of a human monoclonal antibody to the human interleukin-12 p40 subunit (anti-IL-12p40) has been established both in vitro and in vivo, warranting a first-in-human investigation in psoriasis. This phase 1, first-in-human, non-randomized, open-label study evaluated the short-term safety, pharmacokinetics, and clinical response of single, ascending, intravenous (IV) doses of anti-IL-12p40 in subjects with moderate-to-severe psoriasis vulgaris. Eighteen subjects with at least 3% body surface area involvement were enrolled in four dose groups (0.1, 0.3, 1.0, and 5.0 mg per kg). Safety, pharmacokinetics, and clinical response (e.g., Psoriasis Area and Severity Index (PASI)) were monitored at baseline and at specific time points over a 16-wk follow-up period. Anti-IL-12p40 was generally well tolerated. No related serious adverse events or infusion reactions were reported, and most adverse events were mild. IV anti-IL-12p40 yielded linear pharmacokinetics, with a mean terminal half-life of approximately 24 d. Dose-dependent associations with both the rate and extent of clinical response were observed across the four dose groups. Twelve of 18 subjects (67%) achieved at least a 75% improvement in PASI between 8 and 16 wk after study agent administration. Significant and sustained concentration-dependent improvements in psoriatic lesions were observed in most subjects.