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 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.