To report results of the OCARINA I (NCT03972306) Phase Ib, dose-escalation study that assessed ocrelizumab (OCR) safety, tolerability and pharmacokinetic data in patients with relapsing and primary progressive multiple sclerosis (RMS/PPMS), to select the appropriate OCR subcutaneous (SC) dose for OCARINA II.

OCR intravenous (IV) 600mg every 6 months is approved for the treatment of RMS/PPMS. A novel OCR SC formulation utilizing recombinant human hyaluronidase (rHuPH20) is being developed.

Patients with RMS/PPMS (18–65 years; Expanded Disability Status Scale score 0–6.5) were enrolled in OCR IV-pretreated (A) or OCR-naive (B) groups. Following dose escalation, new patients in group A were randomized (1:1) to receive either a single 600mg OCR IV or the selected candidate SC dose predicted to achieve the same area under the concentration-time curve as the 600mg IV dose.

Baseline demographics and disease characteristics were balanced (Group A: n=53 OCR SC, n=35 OCR IV; Group B: n=46 OCR SC). The candidate SC was 1,200mg. Subsequently, based on all available data, the final selected SC dose was 920mg. Median treatment duration with OCR SC 1,200mg or 920mg was 96 weeks, with 94.7% receiving ≥3 doses. Of patients receiving 1,200mg or 920mg OCR (n=131), 77.9% and 23.7% experienced local injection reactions (IR) and systemic IRs, respectively. No antidrug antibodies to OCR were reported, and incidence of antibodies to rHuPH20 was low (1/87, group A; 2/45, group B). OCR SC treatment led to rapid and sustained B-cell depletion, similar to OCR IV. Most patients (93.9%) were satisfied with the SC procedure. New additional safety data will be presented.

The selected ocrelizumab SC 920mg dose was well tolerated and is expected to provide similar exposure to the approved ocrelizumab IV dose, which is being assessed in the OCARINA II Phase III (NCT05232825) study.