Ocrelizumab in Breastmilk

NCT04387110 | Completed FDA Drug

• 1 other identifier: 17-22422
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis; Clinically Isolated Syndrome

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Obtain information on newborn adjusted length until 12 months of life.

  12 months

• Obtain information on newborn weight until 12 months of life.

  12 Months

• Obtain information on newborn head circumference until 12 months of life.

  12 Months

• Obtain information on newborn infections until 12 months of life.

  12 Months

• Obtain information on newborn vaccines until 12 months of life.

  12 Months

Study Arms (1)

Ocrelizumab

Women receiving treatment for multiple sclerosis with ocrelizumab infusion between 2 and 36 weeks postpartum.

Drug: Ocrelizumab

Interventions

Ocrelizumab DRUG

Receiving either 1infusion (600mg) or 2 infusions (300mg).

Also known as: ocrevus

Ocrelizumab

Eligibility Criteria

• Age: 18 Years - 64 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• Patients unable to provide informed consent.
• Patients unable or unwilling to provide breast milk samples for analysis.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Related Publications (4)

• Genentech. (2011). Prescribing Information. [PDF File]. Retrieved from https://www.gene.com/download/pdf/ocrevus_prescribing.pdf

  BACKGROUND

• 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.

  PMID: 29857090 BACKGROUND

• Hale TW, Rowe HE. Medications and mothers' milk. 16th ed. Amarillo (TX): Hale Publishing; 2014

  BACKGROUND

• 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.

  PMID: 31719115 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Breastmilk-Breastmilk will be serially sampled prior to and after the first infusion(s) postpartum according to the following schedule: * 600mg infusion x1: before infusion and at 8H, 24H, 7D, 20D, 30D, 60D, and 90D post * 300mg infusion x2: 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 Blood (serum)- Samples will be collected to determine maternal serum concentration of ocrelizumab relative to breastmilk samples at the following timepoints: * 600mg infusion x1: 24H and 20D post infusion * 300mg infusion x2: 24H and 14D (post infusion 1) and 24H and 20D (post infusion 2)

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ocrelizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Riley Bove, MD, MSc

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2020
• First Posted: May 13, 2020
• Study Start: August 7, 2020
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2022
• Last Updated: December 16, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)