Clinical trial NCT04387110: Ocrelizumab in Breastmilk
Official title: Monoclonal Antibodies in Mothers' Milk and Infants: Ocrelizumab in Breastmilk
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Clinically Isolated Syndrome
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2020-05-13
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study participants will be identified via self referral from study advertisements (via the National MS Society and clinicaltrials.gov) or referred by clinician at the UCSF MS Center.

Clinicians outside of UCSF will also be invited to refer eligible patients to the study by providing study team contact information.

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Determine levels of ocrelizumab in the breastmilk of women with MS
timeFrame: 12 months
measure: Determine time to peak levels of ocrelizumab in the breastmilk of women with MS.
timeFrame: 12 months
measure: Determine predictors of ocrelizumab levels in breastmilk.
timeFrame: 12 months
Secondary outcomes:
measure: Obtain information on newborn adjusted length until 12 months of life.
timeFrame: 12 months
measure: Obtain information on newborn weight until 12 months of life.
timeFrame: 12 Months
measure: Obtain information on newborn head circumference until 12 months of life.
timeFrame: 12 Months
measure: Obtain information on newborn infections until 12 months of life.
timeFrame: 12 Months
measure: Obtain information on newborn vaccines until 12 months of life.
timeFrame: 12 Months
measure: Obtain information on newborn developmental milestones until 12 months of life.
timeFrame: 12 Months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Riley Bove, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Genentech. (2011). Prescribing Information. [PDF File]. Retrieved from https://www.gene.com/download/pdf/ocrevus_prescribing.pdf
citation: Matro R, Martin CF, Wolf D, Shah SA, Mahadevan U. Exposure Concentrations of Infants Breastfed by Women Receiving Biologic Therapies for Inflammatory Bowel Diseases and Effects of Breastfeeding on Infections and Development. Gastroenterology. 2018 Sep;155(3):696-704. doi: 10.1053/j.gastro.2018.05.040. Epub 2018 May 30.
citation: Hale TW, Rowe HE. Medications and mothers' milk. 16th ed. Amarillo (TX): Hale Publishing; 2014
citation: Krysko KM, LaHue SC, Anderson A, Rutatangwa A, Rowles W, Schubert RD, Marcus J, Riley CS, Bevan C, Hale TW, Bove R. Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions. Neurol Neuroimmunol Neuroinflamm. 2019 Nov 12;7(1):e637. doi: 10.1212/NXI.0000000000000637. Print 2020 Jan.