Ocrelizumab in Breastmilk

Study Overview
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Brief Summary
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The goal of the current project is to measure the levels of ocrelizumab in the breastmilk of women with multiple sclerosis (MS) and clinically isolated syndrome (CIS) who are postpartum, and to collect information on 12-month infant development outcomes (length, weight, head circumference, infections) in their offspring. This study will fill a significant unmet need as many women with MS at high risk for postpartum relapses are not effectively treated for their MS in the postpartum period due to lack of information about the presence, concentration and effects of medications in breastmilk.

Detailed Description
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Levels of ocrelizumab in breastmilk will be serially evaluated across one drug half-life from women with MS and CIS who are postpartum and lactating at the time of the infusion (whether or not they plan to continue to breastfeed their baby after the infusion). The timeline for breastmilk sample is dependent on infusion schedule and dosing if receiving 600mg infusion x1, collection will occur: before infusion and at 8H, 24H, 7D, 20D, 30D, 60D, and 90D post infusion; if receiving 300mg infusion x2 collection will occur: before infusion 1, at 8H, 24H, 7D, and 14D (before infusion 2) after infusion 1 and after infusion 2 at 8H, 24H, 7D, 20D, 30D, 60D, and 90D in 20. Blood samples to determine serum concentration of ocrelizumab will be collected, when possible, at the 24-hour, 14 day (if receiving 300mg infusion x2), and 20D timepoint(s). Both women continuing to breastfeed their infant post-infusion and those that chose to discontinue will be included in the study. In order to ensure broad collaboration as well as rapid recruitment, samples will be collected from patients fitting eligibility criteria upon referral to our study by other investigators.

Official Title
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Monoclonal Antibodies in Mothers' Milk and Infants: Ocrelizumab in Breastmilk

Conditions
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Multiple Sclerosis, Clinically Isolated Syndrome

Intervention / Treatment
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* Drug: Ocrelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women between the ages of 18 and 64 that carry a diagnosis of Clinically Isolated Syndrome or Multiple Sclerosis (based on the 2010 McDonald Criteria). Participants must be pregnant, contemplating pregnancy or postpartum at the time of enrollment. Participants must be receiving treatment with ocrelizumab infusion between 2 and 36 weeks postpartum (300mg x2 or 600mg x1). Participants must be willing to provide breastmilk samples before and after their first and, if applicable, second ocrelizumab infusions postpartum. A signed informed consent and HIPAA authorization form is required for participation. Exclusion Criteria: Patients unable to provide informed consent. Patients unable or unwilling to provide breast milk samples for analysis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ocrelizumab<br>Women receiving treatment for multiple sclerosis with ocrelizumab infusion between 2 and 36 weeks postpartum. | Drug: Ocrelizumab<br>* Receiving either 1infusion (600mg) or 2 infusions (300mg).<br>* Other names: ocrevus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine levels of ocrelizumab in the breastmilk of women with MS | Levels of ocrelizumab (μg/mL) in the breastmilk of women at the selected timepoints before and after infusion (hour 8, hour 24, day 7, day 20, day 30, day 60, and day 90). If receiving two infusions the samples will be as follows: pre-infusion, hour 8, hour 24, day 7, and day 14 after infusion 1(prior to infusion 2); then post infusion 2, at hour 8, hour 24, day 7, day 20, day 30, day 60, and day 90. This outcome will be measured by breastmilk concentration (μg/mL), average breastmilk concentration (CAVE, determined using pharmacokinetic methods), maximum concentration of ocrelizumab in breastmilk (CMAX), absolute average ocrelizumab dose to the infant in a 24-hour period, maximum ocrelizumab dose to the infant in a 24-hour period, average relative infant dose (RIDAVE), and maximum relative infant dose (RIDMAX). | 12 months | 
| Determine time to peak levels of ocrelizumab in the breastmilk of women with MS. | Based on analysis of levels of ocrelizumab (μg/mL) in the breastmilk of women at the selected timepoints before and after infusion (hour 8, hour 24, day 7, day 20, day 30, day 60, and day 90). If receiving two infusions the samples will be as follows: pre-infusion, hour 8, hour 24, day 7, and day 14 after infusion 1(prior to infusion 2); then post infusion 2, at hour 8, hour 24, day 7, day 20, day 30, day 60, and day 90. The average peak level of ocrelizumab concentration will be determined. | 12 months | 
| Determine predictors of ocrelizumab levels in breastmilk. | The following predictors will be assessed in relation to level of detectable ocrelizumab in breastmilk: ocrelizumab dosing (300 vs. 600mg), maternal age and parity, introduction of solid foods, and other clinical factors. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Obtain information on newborn adjusted length until 12 months of life. | Newborn adjusted length (in cm) will be collected by manual review of infant medical records at all visits occurring in the first 12 months of life. | 12 months | 
| Obtain information on newborn weight until 12 months of life. | Newborn weight (in kg) will be collected by manual review of infant medical records at all visits occurring in the first 12 months of life. | 12 Months | 
| Obtain information on newborn head circumference until 12 months of life. | Newborn head circumference (in cm) will be collected by manual review of infant medical records at all visits occurring in the first 12 months of life. | 12 Months | 
| Obtain information on newborn infections until 12 months of life. | Newborn infections will be collected by manual review of infant medical records at all visits occurring in the first 12 months of life. | 12 Months | 
| Obtain information on newborn vaccines until 12 months of life. | Newborn vaccine completed and scheduled vaccines will be collected by manual review of infant medical records at all visits occurring in the first 12 months of life. | 12 Months | 
| Obtain information on newborn developmental milestones until 12 months of life. | The Ages and Stages Questionnaire, third edition, (ASQ-3) will be completed by participating mothers at the following timepoints postpartum, to determine the developmental age of infants: 2 months, 4 months, 6 months, 8 months, 10 months and 12 months. The questionnaire scores 5 areas of development: Communication, Gross Motor, Fine Motor, Problem Solving and Personal-Social. Cumulative scores range from 0 to 60. Higher scores indicate more positive outcomes. Each version of the ASQ-3 has different cutoff scores that indicate whether the child's development appears to be on schedule, requires monitoring or requires further assessment. (Above and Monitoring Ranges indicate on schedule infant development for age). | 12 Months |