Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study
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, an...
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Wiley
2024-12-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.52229 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Scott D. Newsome |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e982d8dc5ce04519af3c9fb26edbdfd0 |
| institution | OA Journals |
| issn | 2328-9503 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
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| series | Annals of Clinical and Translational Neurology |
| spelling | doaj-art-e982d8dc5ce04519af3c9fb26edbdfd02025-08-20T01:58:23ZengWileyAnnals of Clinical and Translational Neurology2328-95032024-12-0111123215322610.1002/acn3.52229Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I studyScott D. Newsome0Lawrence Goldstick1Derrick S. Robertson2James D. Bowen3Robert T. Naismith4Ben Townsend5Catarina Figueiredo6Heidemarie Kletzl7Mylene Giraudon8Oscar Bortolami9Dusanka Zecevic10Caroline Giacobino11Susanne Clinch12Yun‐An Shen13Gurpreet Deol-Bhullar14Robert A. Bermel15Johns Hopkins University School of Medicine Baltimore Maryland USAUniversity of Cincinnati Waddell Center for Multiple Sclerosis Cincinnati Ohio USACollege of Medicine University of South Florida Tampa Florida USAMultiple Sclerosis Center Swedish Neuroscience Institute Seattle Washington USADepartment of Neurology, Neuroimmunology Section Washington University St. Louis Missouri USAF. Hoffmann‐La Roche Ltd Basel SwitzerlandF. Hoffmann‐La Roche Ltd Basel SwitzerlandF. Hoffmann‐La Roche Ltd Basel SwitzerlandF. Hoffmann‐La Roche Ltd Basel SwitzerlandIQVIA RDS Milan ItalyF. Hoffmann‐La Roche Ltd Basel SwitzerlandF. Hoffmann‐La Roche Ltd Basel SwitzerlandRoche Products Ltd Welwyn Garden City UKGenentech, Inc. South San Francisco California USAHoffmann‐La Roche Limited Mississauga Ontario CanadaDepartment of Neurology, Mellen Center for Multiple Sclerosis Cleveland Clinic Cleveland Ohio USAAbstract 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.https://doi.org/10.1002/acn3.52229 |
| spellingShingle | 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 Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study Annals of Clinical and Translational Neurology |
| title | Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study |
| title_full | Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study |
| title_fullStr | Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study |
| title_full_unstemmed | Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study |
| title_short | Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study |
| title_sort | subcutaneous ocrelizumab in multiple sclerosis results of the phase 1b ocarina i study |
| url | https://doi.org/10.1002/acn3.52229 |
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