Ocrelizumab dose selection for treatment of pediatric relapsing–remitting multiple sclerosis: results of the OPERETTA I study

Background: The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS). Methods: Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period. Primary endpoints: pharmacokinetics, pharmacodynamics (CD19+ B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change. Results: A total of 23 patients (cohort 1: n = 6, age 10-12 years, BW 27.0-39.0 kg; cohort 2: n = 17, age 11-17 years, BW 42.1-108.4 kg) were enrolled. Median treatment duration was 120 (range, 24-193) weeks at the primary analysis cutoff (October 5, 2023). Overall, the pharmacokinetic data were within the range observed at 600 mg in adult patients with MS; however, the exposure at 300 mg in patients < 40 kg was lower than with 600 mg in patients ≥ 40 kg. Shifting the cutoff to 35 kg would provide better exposure to patients with 35-40 kg body weight. Sustained, near-complete B-cell depletion was observed. The safety profile was consistent with that in adults. EDSS scores remained stable; no clinical relapses were observed. Conclusion: A dosing regimen of 300 mg ocrelizumab for patients < 35 kg, and 600 mg for patients ≥ 35 kg (every 24 weeks), was selected for the phase 3 OPERETTA II trial (NCT05123703). Trial registration: ClinicalTrials.gov: NCT04075266.