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
{"title":"Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study.","authors":"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","doi":"10.1002/acn3.52229","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Interpretation: </strong>Subcutaneous ocrelizumab may provide patients with multiple sclerosis with an additional treatment option.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Clinical and Translational Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/acn3.52229","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.