A Study Evaluating B Cell Levels In Infants Of Lactating Women With CIS Or MS Receiving Ocrelizumab

NCT04998851 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: MN429892021-000063-79
• Study Type: interventional
• Target: 26
• Locations: 3 countries
• Sites: 8

Brief Summary

This study will evaluate the pharmacokinetics of ocrelizumab in the breastmilk of lactating women with clinically isolated syndrome (CIS) or multiple sclerosis (MS) \[in line with the locally approved indications\] treated with ocrelizumab, by assessing the concentration of ocrelizumab in mature breastmilk, as well as the corresponding exposure and pharmacodynamic effects (blood B cell levels) in the infants.

Conditions

Multiple Sclerosis; Clinically Isolated Syndrome

Keywords

ocrelizumab, OCREVUS, breastmilk transfer, breast milk transfer, lactation

Outcome Measures

Primary Outcomes (2)

• Percentage of Infants With B Cell Levels (Cluster of Differentiation 19 [CD19+] Cells) Below the Lower Limit of Normal (LLN) Measured at Day 30 After the Mother's First Ocrelizumab Postpartum Infusion

  Infant blood samples were collected at Day 30 after the mothers received their first postpartum ocrelizumab infusion (regardless of whether women receive a 600 mg or a 2x300 mg dose). The percentage of infants with B cell levels below LLN are reported with the two-sided Clopper Pearson 95% confidence interval (CI). B-cell reference ranges by week of life (absolute and percentage counts) are defined by Borriello et al. 2022.

  At Day 30

• Estimated Average Oral Daily Infant Dosage (ADID)

  ADID was calculated as the arithmetic mean of the mother's daily ocrelizumab milk concentration (micrograms/milliliters \[µg/mL\]) over 60 days post-ocrelizumab infusion 1 multiplied by an estimated infant milk intake of 150 milliliters/kilograms/day (mL/kg/day) and based on the weight \[kilograms (kg)\] recorded at the Day 30 visit. Ocrelizumab concentrations reported as below the lower limit of quantification \[LLQ=160 nanograms/millilitres (ng/mL)\] are imputed to zero for the calculation ADID.

  Up to Day 60

Secondary Outcomes (25)

• Absolute CD19+ B Cell Count in the Infant

  At Day 30

• Percentage of CD19+ B Cell in the Infant

  At Day 30

• Area Under the Milk Concentration-Time Curve (AUC) of Ocrelizumab in Mature Breastmilk

  One 600 mg infusion: before infusion and at 24 hours (Day 1), Days 7, 30 and 60 post-infusion; Two 300 mg infusions: before infusion 1 and at 24 hours (Day 1), Days 7, 14, 15 (24 hours after infusion 2), 21, 30 and 60 post-infusion 1

• Average Concentration of Ocrelizumab in Breastmilk (Cmean)

  One 600 mg infusion: before infusion and at 24 hours (Day 1), Days 7, 30 and 60 post-infusion; Two 300 mg infusions: before infusion 1 and at 24 hours (Day 1), Days 7, 14, 15 (24 hours after infusion 2), 21, 30 and 60 post-infusion 1

• Maximum Concentration (Cmax) of Ocrelizumab in Breastmilk

  One 600 mg infusion: before infusion and at 24 hours (Day 1), Days 7, 30 and 60 post-infusion; Two 300 mg infusions: before infusion 1 and at 24 hours (Day 1), Days 7, 14, 15 (24 hours after infusion 2), 21, 30 and 60 post-infusion 1

Study Arms (1)

Women with CIS or MS

EXPERIMENTAL

Lactating women with CIS or MS (in line with the locally approved indications) who decided together with their treating physician to continue on, or start treatment with, OCREVUS (ocrelizumab) post-partum. Women resuming treatment with ocrelizumab post-partum will be included only if the last exposure to ocrelizumab occurred more than 3 months before the last menstrual period to exclude any interference between fetal exposure and exposure via lactation.

Drug: Ocrelizumab

Interventions

Ocrelizumab DRUG

Women will receive the ocrelizumab dose regimen as per the locally-approved label. The ocrelizumab dose will be administered as an initial split dose of two 300 mg infusions separated by 14 days or a single 600 mg infusion according to the local prescribing information.

Women with CIS or MS

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Lactating women with CIS or MS (in line with the locally approved indications) who decided together with their treating physician to continue on, or start treatment with, OCREVUS (ocrelizumab) post-partum. Women resuming treatment with ocrelizumab post-partum will be included only if the last exposure to ocrelizumab occurred more than 3 months before the last menstrual period to exclude any interference between fetal exposure and exposure via lactation.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Woman is between 18 and 40 years of age at screening
• Woman is willing to breastfeed for at least 60 days after the first post-partum ocrelizumab infusion (this decision is to be taken prior to and independent from study participation)
• Woman is willing to provide breastmilk samples
• Woman has a diagnosis of MS or CIS (in line with the locally approved indications)
• Woman has delivered a healthy term singleton infant (≥37 weeks gestation)
• Infant is between 2-24 weeks of age at the time of the mother's first post-partum dose of ocrelizumab
• For women who received commercial ocrelizumab (OCREVUS) before enrolment: documentation that last exposure to ocrelizumab occurred more than 3 months before the last menstrual period (LMP) and was given at the approved dose of 2 x 300 mg or 1 x 600 mg
• Woman agrees to use acceptable contraceptive methods during the study

You may not qualify if:

• Hypersensitivity to ocrelizumab or to any of its excipients
• Received last dose of ocrelizumab \<3 months before the LMP or during pregnancy
• Active infections (may be included once the infection is treated and is resolved; women with bilateral mastitis infection should not have samples collected until the infection is completely resolved)
• Prior or current history of primary or secondary immunodeficiency, or woman in an otherwise severely immunocompromised state
• Known active malignancies, or being actively monitored for recurrence of malignancy
• History of breast implants, breast augmentation, breast reduction surgery or mastectomy
• Prior or current history of chronic alcohol abuse or drug abuse
• Positive screening tests for hepatitis B
• Treatment with a DMT for CIS or MS during pregnancy and/or first weeks post-partum, with the exception of formulations of interferon-beta, glatiramer acetate or pulsed corticosteroids
• Treatment with drugs known to transfer to the breastmilk and with established or potential deleterious effects for the infant
• Treatment with any investigational agent within 6 months or five half-lives of the investigational drug prior to the LMP
• \>24 weeks of life at the time of the mother's first dose of ocrelizumab
• Any abnormality that may interfere with breastfeeding or milk absorption
• Active infection (may be included once the infection resolves)
• Infant has any other medical condition or abnormality that, in the opinion of the investigator, could compromise the infant's ability to participate in this study, including interference with the interpretation of study results

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• PPD Development, LP: collaborator
• Illingworth Research Group: collaborator
• Laboratory Corporation of America: collaborator

Study Sites (8)

University of California San Francisco

San Francisco, California, 94158, United States

Location

University Of Colorado

Aurora, Colorado, 80045, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611-2987, United States

Location

Brigham and Womens Hospital

Boston, Massachusetts, 02115, United States

Location

Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis

Owosso, Michigan, 48867, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Hosp. Clinico San Carlos

Madrid, 28040, Spain

Location

Queen Mary University of London

London, EC1M 6BQ, United Kingdom

Location

MeSH Terms

Conditions

Multiple Sclerosis; Breast Feeding

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; Feeding Behavior; Behavior

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2021
• First Posted: August 10, 2021
• Study Start: September 16, 2021
• Primary Completion: March 29, 2024
• Study Completion: January 13, 2025
• Last Updated: January 14, 2026
• Results First Posted: April 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (6); ES (1); GB (1)