Evaluation of Postpartum B-Cell Depletion in Infants Exposed to Ocrelizumab In Utero in Mothers with Multiple Sclerosis or Clinically Isolated Syndrome

The primary objective of this study is to evaluate whether infants potentially exposed to **ocrelizumab** during pregnancy present with postpartum B-cell depletion. This is clinically relevant as B-cell depletion in infants could have significant implications for their immune system development and function, potentially affecting their ability to respond to infections and vaccinations.

Secondary objectives include: - Evaluating B cell levels in infants potentially exposed to ocrelizumab during pregnancy. - Assessing whether there is placental transfer of ocrelizumab from the mother to the infant. - Determining if infants potentially exposed to ocrelizumab during pregnancy can mount humoral immune responses to clinically relevant vaccines. - Measuring the levels of ocrelizumab in the mother during pregnancy. - Evaluating the safety of ocrelizumab in the mother and the safety of infants potentially exposed to ocrelizumab. - Assessing pregnancy and neonatal outcomes.

The clinical trial involves a total of **19 participants** who are being studied to evaluate whether infants potentially exposed to ocrelizumab during pregnancy present with postpartum B-cell depletion. The study population consists of individuals aged **18 to 40 years**, inclusive, who have been diagnosed with **Multiple Sclerosis (MS)** or **Clinically Isolated Syndrome (CIS)**, in accordance with locally approved indications. Participants are currently pregnant with a singleton pregnancy at gestational week 30 or less at the time of enrollment. The trial includes both male and female subjects, although the focus is on pregnant women. Participants were selected based on specific criteria, including documentation of prenatal screenings and exposure to ocrelizumab up to six months before the last menstrual period or during the first trimester of pregnancy. The trial population is considered vulnerable due to the inclusion of pregnant women. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **Phase IV**, multicenter, open-label study aimed at evaluating B-cell levels in infants potentially exposed to **ocrelizumab** during pregnancy. The primary objective is to assess whether such exposure results in postpartum B-cell depletion. The trial will involve participants diagnosed with **Multiple Sclerosis (MS)** or **Clinically Isolated Syndrome (CIS)**, who are currently pregnant with a singleton pregnancy at gestational week 30 or less at enrollment. The study will not administer any investigational medicinal product, and participants may resume their standard of care treatment with ocrelizumab after birth, though this is not a protocol requirement. The trial is expected to conclude by April 2025, with recruitment having commenced in April 2022.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, diagnosis, and pregnancy status. Follow-up visits will be scheduled to monitor the health of both the mother and infant, with specific assessments conducted at week 6 of the infant's life to measure B-cell levels and serum concentrations of ocrelizumab. The end-of-study visit will occur after the final assessments are completed. The expected duration of participant involvement is from enrollment until the infant reaches one year of age, with conditions for early termination including withdrawal of consent or significant adverse events.

The trial will measure primary and secondary endpoints, including the proportion of infants with B-cell levels below the lower limit of normal and various serum concentrations of ocrelizumab. Additional endpoints will assess the immune response to vaccinations and the rate and nature of adverse events in both the mother and infant. The study aims to provide valuable data to inform post-approval activities related to ocrelizumab exposure during pregnancy.

The clinical trial involves the administration of **Ocrevus**, a pharmaceutical product containing the active substance **ocrelizumab**. Ocrevus is formulated as a **concentrate for solution for infusion** and is intended for intravenous administration. The product is supplied in a concentration of 300 mg per infusion. The administration route is via **infusion**, and the dosing schedule is designed to ensure a maximum daily dose of one unit, with a total treatment period not exceeding one day. The product is manufactured by Roche Registration GmbH and is not a pediatric formulation. The active substance, ocrelizumab, is a protein of non-specific origin, classified under the ATC code L04AA36.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of Ocrevus to evaluate its effects. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The study aims to assess the potential postpartum B-cell depletion in infants exposed to ocrelizumab during pregnancy, as part of the Phase IV, multicenter, open-label MINORE study.

The efficacy of the clinical trial titled "A Phase IV, Multicenter, Open-Label Study Evaluating B-Cell Levels in Infants Potentially Exposed to Ocrelizumab During Pregnancy – The MINORE Study" will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the proportion of infants with B-cell levels, specifically **CD19+ cells**, with absolute counts below the lower limit of normal, measured at week 6 of life. This endpoint is crucial for determining the potential impact of prenatal exposure to ocrelizumab on infant B-cell levels.

Secondary endpoints include a comprehensive evaluation of B-cell levels, both in absolute counts and as a percentage of lymphocytes, also measured at week 6 of life. Additionally, the study will assess the serum concentration of ocrelizumab in the umbilical cord blood at birth and in the infant at week 6 of life. The study will also evaluate the mean titers of antibody immune responses to common childhood vaccinations, such as diphtheria, tetanus, pertussis, Hib, PCV-13, MMR, and HBV, and the proportion of infants with positive humoral responses to these vaccines. Furthermore, the serum concentration of ocrelizumab in the mother during pregnancy and at delivery will be measured, alongside the rate and nature of adverse events in both the mother and infant throughout the study. The study will also document the proportion of pregnancies resulting in live births, therapeutic abortions, or stillbirths, and assess infant characteristics at birth, including body weight, head circumference, and length.