Optimal Dosage for Subcutaneous Ocrelizumab Uncovered in Phase 1b OCARINA I Trial

New findings from the phase 1b dose-escalation, open-label OCARINA I study (NCT03972306), presented at the 2023 MSMilan, the 9th Joint ECTRIMS-ACTRIMS meeting, October 11–13, in Milan, Italy, showed that a 920 mg dose of subcutaneous ocrelizumab (Ocrevus; Genentech) was the most appropriate dose to use among patients with relapsing or primary progressive multiple sclerosis (MS). These results suggest that the selected dosage was well tolerated and provides a similar exposure to the FDA-approved 600 mg intravenous (IV) dose used in the phase 3 OCARINA II trial (NCT05232825).¹

In the study, 131 patients received at least 1 dose of ocrelizumab 1200 mg or 920 mg. Originally, investigators selected 1200 mg as the candidate for subcutaneous dose based on all of the available data; however, 920 mg was subsequently chosen as the final subcutaneous dose. All told, the median overall ocrelizumab subcutaneous treatment duration was 2 years, with 95% of patients treated for at least 1 year with 3 doses of the therapy. Approximately 92.4% of patients were treated with subcutaneous ocrelizumab for 48 weeks. 

“The candidate dose of 1,200 mg ocrelizumab and the selected ocrelizumab subcutaneous 920 mg dose were generally well tolerated. The overall safety profile observed for ocrelizumab subcutaneous in this study is consistent with the well-established safety profile for ocrelizumab IV,” lead author Scott Newsome, DO, MSCS, FAAN, the director of the Stiff Person Syndrome Center and a professor of neurology at Johns Hopkins Medicine, and colleagues wrote.¹ Newsome and colleagues designed this study to select the appropriate subcutaneous ocrelizumab dose for the subsequent phase 3 trial based on safety, tolerability, and pharmacokinetic data in patients with relapsing or primary progressive MS.

READ MORE: B Cell Suppression Not Correlated With Therapeutic Response in Ocrelizumab-Treated Patients

In this study, investigators recruited adult patients either with relapsing or primary progressive MS between the ages of 18 and 65 years old who had an Expanded Disability Status Scale score between 0.0 and 6.5. These patients were enrolled into 2 separate groups: group A, who was previously treated with ocrelizumab IV, or group B, who was naive to ocrelizumab. In each of the groups, the patients received single ascending doses of subcutaneous ocrelizumab starting from 40 mg, then to 200 mg, 600 mg, and 1200 mg. After dose escalation, new patients in group A were randomized 1:1 to receive either a single 600 mg ocrelizumab IV or the candidate subcutaneous dose.

The researchers originally predicted that the candidate subcutaneous dose of ocrelizumab would result in similar exposure as the 600 mg IV dose, while also demonstrating safety and tolerability. Authors used the area under the concentration-time curve for both formulations to select the subcutaneous ocrelizumab dose. In both cohorts, patients had the option to enter a dose continuation phase receiving the candidate dose, then later the final selected dose for up to 3 years.  

In cohort A (n = 53 subcutaneous ocrelizumab; n = 35 OCR intravenous) and cohort B subcutaneous ocrelizumab (n = 46), most patients were women (cohort A, 72.7%; cohort B, 63.0%). In addition, the mean age at baseline with both cohorts was 45.7 (SD, 10.2) and 39.7 (SD, 9.2) years old, respectively. During the dose escalation phase, subcutaneous ocrelizumab was well tolerated across all doses tested overall. The most common adverse events for patients were injection site reactions with erythema, pain and swelling as the most common symptoms, all of which were either mild or moderate in severity.

“Similar B-cell depletion was achieved with subcutaneous ocrelizumab and IV. No treatment-emergent anti-drug antibodies to ocrelizumab subcutaneous and IV were observed, and antibodies to recombinant human hyaluronidase were low. Patients reported high level of satisfaction with ocrelizumab subcutaneous,” Newsome et al noted.1

Click here for more coverage of MSMilan 2023.

REFERENCES
1. Newsome SD, Goldstick L, Townsend B, et al. Subcutaneous Ocrelizumab in Patients With Multiple Sclerosis: Results of the Phase Ib Dose-Finding OCARINA I Study. Presented at: 2023 MSMilan; October 11-12; Milan, Italy. Abstract P371.