Pharmacokinetic, Safety, Tolerability, Immunogenicity and Pharmacodynamic Evaluation of Subcutaneous Ocrelizumab in Pediatric Relapsing‑Remitting Multiple Sclerosis

The primary objective is to assess the pharmacokinetic profile of subcutaneous ocrelizumab in children and adolescents with relapsing‑remitting multiple sclerosis, providing essential data for dose optimization in this population. Secondary objectives include: evaluation of safety and tolerability of the subcutaneous formulation; characterization of the pharmacodynamic impact on circulating CD19⁺ B‑cell counts; and determination of the immunogenicity of ocrelizumab in combination with recombinant human hyaluronidase (rHuPH20). These endpoints aim to clarify the therapeutic risk‑benefit profile and inform clinical management of pediatric RRMS.

The trial enrolled 12 participants diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) who were children and adolescents, encompassing both female and male subjects and classified as a vulnerable population. Eligible individuals weighed at least 25 kg, met pediatric diagnostic criteria (IPMSSG 2012, McDonald 2017 or 2024), had received all recommended childhood vaccinations, and exhibited an Expanded Disability Status Scale score between 0 and 5.5 at screening. Participants were required to demonstrate neurologic stability for a minimum of 30 days prior to screening and between screening and baseline, and to comply with contraception requirements. No specific lifestyle factors such as diet or physical activity were stipulated in the provided information.

The study is an open‑label, single‑arm Phase IV trial evaluating subcutaneous ocrelizumab 920 mg in children and adolescents diagnosed with Relapsing‑Remitting Multiple Sclerosis. The primary objective is to characterize the pharmacokinetic profile after the first injection, with secondary objectives including safety, tolerability, immunogenicity, pharmacodynamic effects, and biomarker assessments. Enrollment is planned from August 2026 to July 2029, and participants will remain in the study until the end‑of‑study visit, which follows the final scheduled assessments. Study visits are sequenced as follows: a screening visit to confirm eligibility criteria (body weight ≥ 25 kg, EDSS 0‑5.5, stable disease, required vaccinations, and contraception compliance); a baseline visit on the day of the first subcutaneous dose; periodic follow‑up visits for collection of blood samples to determine peak concentration (Cmax) and area under the curve (AUCτ), monitoring of adverse events, vital signs, ECG, laboratory tests, CD19⁺ B‑cell counts, and anti‑drug antibodies; and an end‑of‑study visit to complete the PK and safety evaluations. Participant involvement spans the entire interval from screening through the end‑of‑study assessment, encompassing all scheduled dosing and evaluation periods.

The investigational product is Ocrevus, a solution for injection containing the monoclonal antibody ocrelizumab. Each dose consists of 920 mg administered by the subcutaneous route. The formulation is supplied as a single‑use vial for injection, and dosing follows the schedule defined in the study protocol, with administration performed by qualified personnel and documented in the trial records to ensure compliance.

No additional non‑experimental treatments, such as standard‑of‑care therapy, placebo, or active comparator, are incorporated into this open‑label study; participants receive only the study medication as described.

Drug administration is recorded in the electronic case report form, and adherence is monitored through site‑based verification of dose preparation, injection timing, and completion of the required observation period after each administration.

The study will evaluate pharmacokinetic exposure by determining the peak serum concentration (Cmax) and the area under the concentration‑time curve over a dosing interval (AUCτ) following the first subcutaneous injection of ocrelizumab. Blood samples will be collected at predefined timepoints after dosing, and drug concentrations will be quantified using a validated analytical assay; pharmacokinetic parameters will be derived from the resulting concentration‑time profiles.

Pharmacodynamic and immunogenicity assessments will include measurement of the CD19+ B cell count in peripheral blood, performed by flow cytometry, and detection of treatment‑emergent anti‑drug antibodies using a validated immunoassay. Changes from baseline in selected vital signs, electrocardiogram findings, and clinical laboratory test results will be recorded. Adverse events will be captured throughout the study and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. The incidence of study‑treatment discontinuation due to adverse events, as well as the relationship between anti‑drug antibody status, pharmacokinetics, and safety, will be analyzed.