Kaul M, Jarvis P, Rozenberg I, Kolbinger F, Di Padova F, Calonder C, Espie P, Rondeau J M, Cebe R, Huber T, Mussmann R, Aassi M, Sligh T S
Novartis Institute for Biomedical Research, Basel, Switzerland.
currently Roche Pharma Research & Early Development, Basel, Switzerland.
J Eur Acad Dermatol Venereol. 2021 May;35(5):1143-1151. doi: 10.1111/jdv.17071. Epub 2021 Jan 5.
Anti-IL-17A IgG/κ monoclonal antibody CJM112 binds both IL-17A and IL-17AF. The purpose of this First-in-Human study was to assess CJM112 effects on safety and efficacy in patients with moderate to severe plaque psoriasis.
This study had two parts: single ascending doses of 5-450 mg subcutaneous (s.c.) CJM112 (SAD) and multi-dose parallel groups of CJM112 15 mg, 50 mg and 150 mg s.c. low frequency or high frequency (MD). SAD/MD were double-blind, randomized and placebo-controlled; MD also included a secukinumab 150 mg s.c. arm as an active comparator. Patients 18-65 years with moderate to severe psoriasis were included in this study. The efficacy outcome was the change in Psoriasis Area Severity Index (PASI) from baseline to Week 4 in the SAD part of the study, and from baseline to Week 12 in the MD part.
96 patients were enrolled in this study (SAD, n = 42; MD, n = 54). In SAD, CJM112 doses from 15 mg and above demonstrated higher PASI responses compared with placebo at Week 12. CJM112 450 mg did not add further efficacy, but efficacy duration was prolonged compared with CJM112 150 mg. CJM112 MD resulted in a dose-dependent decrease in PASI over time to Week 12. CJM112 150 mg high frequency did not exceed the effect of CJM112 150 mg low frequency and had similar efficacy to secukinumab 150 mg. The safety profile of CJM112 was as expected for an antibody targeting IL-17A/IL-17AF.
CJM112 had clinical efficacy in moderate to severe psoriasis and was generally safe and well tolerated in the doses tested. Additional neutralization of IL-17AF did not translate to increased clinical efficacy compared with secukinumab.
抗白细胞介素-17A IgG/κ单克隆抗体CJM112可同时结合白细胞介素-17A和白细胞介素-17AF。这项首次人体研究的目的是评估CJM112对中度至重度斑块状银屑病患者安全性和疗效的影响。
本研究分为两部分：单次递增剂量5 - 450毫克皮下注射CJM112（SAD）以及CJM112 15毫克、50毫克和150毫克皮下注射低频或高频的多剂量平行组（MD）。SAD/MD为双盲、随机且安慰剂对照；MD还包括一个皮下注射司库奇尤单抗150毫克的治疗组作为活性对照。本研究纳入了年龄在18 - 65岁的中度至重度银屑病患者。疗效指标为研究SAD部分从基线至第4周以及MD部分从基线至第12周的银屑病面积和严重程度指数（PASI）变化。
本研究共纳入96例患者（SAD组，n = 42；MD组，n = 54）。在SAD组中，15毫克及以上剂量的CJM112在第12周时与安慰剂相比显示出更高的PASI反应。450毫克的CJM112未进一步增加疗效，但与150毫克的CJM112相比，疗效持续时间延长。CJM112的MD组随着时间推移至第12周PASI呈剂量依赖性下降。150毫克高频的CJM112未超过150毫克低频的CJM112的效果，且与150毫克的司库奇尤单抗疗效相似。CJM112的安全性概况与靶向白细胞介素-17A/白细胞介素-17AF的抗体预期相符。
CJM112在中度至重度银屑病中具有临床疗效，在所测试的剂量下总体安全且耐受性良好。与司库奇尤单抗相比，对白细胞介素-17AF的额外中和并未转化为更高的临床疗效。
