Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study.

IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Annals of Clinical and Translational Neurology Pub Date : 2024-10-26 DOI:10.1002/acn3.52229
Scott D Newsome, Lawrence Goldstick, Derrick S Robertson, James D Bowen, Robert T Naismith, Ben Townsend, Catarina Figueiredo, Heidemarie Kletzl, Mylene Giraudon, Oscar Bortolami, Dusanka Zecevic, Caroline Giacobino, Susanne Clinch, Yun-An Shen, Gurpreet Deol-Bhullar, Robert A Bermel
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Abstract

Objective: Subcutaneous ocrelizumab is being developed to provide treatment flexibility and additional choice to patients with multiple sclerosis. OCARINA I (NCT03972306) is an open-label, multicenter, Phase 1b, dose-finding study to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of subcutaneous ocrelizumab and to select a dose for the Phase 3 OCARINA II study (NCT05232825).

Methods: Patients with relapsing or primary progressive multiple sclerosis (aged 18-65 years; Expanded Disability Status Scale score 0.0-6.5) were enrolled into two groups: previously treated with intravenous ocrelizumab (Group A) or naïve to ocrelizumab (Group B). Patients received single ascending doses of subcutaneous ocrelizumab up to 1200 mg. Following dose escalation, new patients in Group A were randomized (1:1) to receive a single 600 mg intravenous ocrelizumab dose or the candidate subcutaneous dose, which was predicted to result in similar exposure as the 600 mg intravenous dose while being safe and well tolerated. The area under the concentration-time curve for both formulations was used to select the subcutaneous ocrelizumab dose. Patients in all cohorts could enter a dose-continuation phase.

Results: Eighty-eight and 47 patients were enrolled into Group A and B, respectively; most patients were female (72.7%/63.0%), and mean age at baseline was 45.7 and 39.7 years, respectively. Subcutaneous ocrelizumab was well tolerated across all doses tested. The 920 mg subcutaneous ocrelizumab dose was selected for the OCARINA II study based on pharmacokinetic and safety data.

Interpretation: Subcutaneous ocrelizumab may provide patients with multiple sclerosis with an additional treatment option.

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皮下注射奥克雷珠单抗治疗多发性硬化症:OCARINA I 1b 期研究结果。
目的:正在开发的皮下注射奥柯利珠单抗为多发性硬化症患者提供了治疗的灵活性和更多选择。OCARINA I(NCT03972306)是一项开放标签、多中心、1b期、剂量摸底研究,旨在调查皮下注射奥柯利珠单抗的药代动力学、安全性、耐受性和免疫原性,并为3期OCARINA II研究(NCT05232825)选择剂量:复发性或原发性进展多发性硬化症患者(年龄18-65岁;扩展残疾状态量表评分0.0-6.5分)分为两组:曾接受过静脉注射奥柯利珠单抗治疗的患者(A组)或对奥柯利珠单抗无经验的患者(B组)。患者接受单次递增剂量的皮下注射奥柯利珠单抗,最高剂量为 1200 毫克。剂量递增后,A 组新患者被随机(1:1)分配接受单次 600 毫克静脉注射奥柯利珠单抗剂量或候选皮下注射剂量。两种制剂的浓度-时间曲线下面积用于选择奥柯利珠单抗的皮下注射剂量。所有组群的患者均可进入剂量持续阶段:A组和B组分别有88名和47名患者入组;大多数患者为女性(72.7%/63.0%),基线平均年龄分别为45.7岁和39.7岁。皮下注射奥克雷珠单抗的耐受性在所有测试剂量中都很好。根据药代动力学和安全性数据,OCARINA II研究选择了920毫克的皮下注射奥柯利珠单抗剂量:解读:皮下注射奥柯利珠单抗可为多发性硬化症患者提供额外的治疗选择。
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来源期刊
Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)
CiteScore
9.10
自引率
1.90%
发文量
218
审稿时长
8 weeks
期刊介绍: Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.
期刊最新文献
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