To report the results of OCARINA II (NCT05232825), a Phase III, randomized, open-label, controlled study designed to demonstrate non-inferiority in serum exposure of ocrelizumab (OCR) when administered via subcutaneous (SC) versus intravenous (IV) routes.
OCR is an effective treatment for people with relapsing and primary progressive multiple sclerosis (RMS/PPMS). The currently available formulation is administered IV every 6 months. A novel OCR SC formulation in combination with recombinant human hyaluronidase (rHuPH20) is being developed.
Patients with RMS/PPMS (18‒65 years; Expanded Disability Status Scale score 0–6.5) were randomized (1:1) to receive OCR 600mg IV or 920mg OCR SC (selected based on pharmacokinetic data from the OCARINA I study [NCT03972306]). Study endpoints: comparison of serum OCR area under the concentration-time curve from baseline to Week 12 (AUCW1‒12), MRI lesion activity, number of relapses, immunogenicity, B-cell depletion and safety.
Baseline demographics and disease characteristics were balanced (OCR SC: n=118; 89.0% RMS, 9.3% PPMS; OCR IV: n=118; 89.8% RMS, 10.2% PPMS). At Week (W) 12, the geometric mean ratio (90% CI) for AUCW1‒12 of OCR SC versus IV was 1.29 (1.23‒1.35). OCR SC 920mg resulted in near-complete suppression of MRI and relapse activity up to W24, similar to OCR IV. In both cohorts, treatment with OCR led to rapid and sustained B-cell depletion. The safety profile of OCR SC was consistent with that of OCR IV; both were well tolerated. No new safety concerns were identified in addition to the known risks associated with OCR or SC administration. No OCR-antidrug antibodies or antibodies to rHuPH20 were detected. Data up to W48 will be presented.
Ocrelizumab SC 920mg demonstrated non-inferiority to IV 600mg with respect to AUCW1‒12, and similar clinical and imaging measures. SC administration of ocrelizumab provides treatment flexibility and additional treatment options for patients and healthcare providers.