A Study Evaluating B Cell Levels In Infants Potentially Exposed To Ocrelizumab During Pregnancy (MINORE)

A Phase IV Multicenter, Open-Label Study Evaluating B Cell Levels In Infants Potentially Exposed To Ocrelizumab During Pregnancy

This study will evaluate the potential placental transfer of ocrelizumab in pregnant women with clinically isolated syndrome (CIS) or multiple sclerosis (MS) [in line with the locally approved indications] whose last dose of ocrelizumab was administered any time from 6 months before the last menstrual period (LMP) through to the first trimester (up to gestational week 13) of pregnancy, and the corresponding pharmacodynamic effects (B cell levels) in the infant.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Clinically Isolated Syndrome
• Intervention / Treatment: Drug: Ocrelizumab

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Bron, France, 69003
    • Hopital Pierre Wertheimer - Hopital Neurologique
  • Paris, France, 75013
    • Hopital de la Pitie Salpetriere
• Germany
  • Bochum, Germany, 44791
    • St. Josef Hospital GmbH
  • Hamburg, Germany, 22179
    • MultipEL Studies - Institut für klinische Studien
• Spain
  • Madrid, Spain, 28040
    • Hosp. Clinico San Carlos
• Switzerland
  • Basel, Switzerland, 4031
    • Universitatsspital Basel
  • Bern, Switzerland, 3010
    • Inselspital Bern
• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Illinois
    • Chicago, Illinois, United States, 60611-4296
      • The Ken and Ruth Davee department of Neurology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of MS or CIS (in line with the locally approved indications)
• Currently pregnant with singleton pregnancy at gestational week ≤30 at enrolment
• Documentation that first and second obstetric ultrasound has been conducted before enrolment during the screening period
• Documentation that the last exposure to ocrelizumab occurred up to 6 months before the LMP before the woman became pregnant OR during the first trimester of pregnancy

Exclusion Criteria:

• Last exposure to ocrelizumab >6 months before the woman's LMP or later than the first trimester of pregnancy
• Gestational age at enrolment >30 weeks
• Non-singleton pregnancy
• Received the last dose of ocrelizumab at a different posology other than per the local prescribing information
• Lack of access to ultrasound pre-natal care as part of standard clinical practice
• Prior or current obstetric/gynecological conditions associated with adverse pregnancy outcomes
• Pre-pregnancy body mass index >35 kg/m2
• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
• Prior or current history of primary or secondary immunodeficiency, or woman in an otherwise severely immunocompromised state
• Significant and uncontrolled disease that may preclude a woman from participating in the study
• Women with known active malignancies or being actively monitored for recurrence of malignancy including solid tumors and hematological malignancies
• Prior or current history of alcohol or drug abuse, or current use of tobacco
• Positive screening tests for hepatitis B
• Treatment with drugs known to have teratogenic effects
• Planned treatment with interferons, glatiramer acetate, or pulsed corticosteroids as a bridging therapy after the last ocrelizumab dose and throughout pregnancy
• Treatment with disease-modifying therapies for MS within their respective half-lives prior to the last ocrelizumab dose or prior to the LMP
• Treatment with natalizumab within 12 weeks prior to the LMP
• Treatment with teriflunomide within the last two years, unless measured plasma concentrations are <0.02 mg/L. If levels are >0.02 mg/L or not known, an accelerated elimination procedure is required
• Treatment with any investigational agent within 6 months or five half-lives of the investigational drug prior to the last ocrelizumab dose or prior to the LMP

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pregnant Women with CIS or MS; Pregnant women with CIS or MS (in line with the locally approved indications) receiving commercial ocrelizumab up to 6 months before the LMP or during the first trimester of pregnancy (up to gestational week 13), due to accidental exposure, or in whom a decision to treat with ocrelizumab was taken as part of routine clinical practice.	Drug: Ocrelizumab; Post-partum dosing and treatment duration are at the discretion of the physicians, in accordance with local clinical practice and local labelling.
No Intervention: Infants; Infants born to women receiving commercial ocrelizumab IV either 0-6 months before the LMP or during the first trimester of pregnancy (up to gestational week 13) due to accidental exposure, or in whom a decision to treat with ocrelizumab was taken as part of routine clinical practice were observed up to month 13 of age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Infants With B Cell Levels (Cluster of Differentiation 19 [CD19+] Cells) Below the Lower Limit of Normal (LLN)	The event rate (percentage of infants with B cell levels below LLN) and corresponding Clopper Pearson 95% CI were reported. B-cell reference ranges by week of life (absolute counts) are defined by Borriello et al. 2022.	At Week 6 of infant's life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute CD19+ B Cell Count in the Infant Potentially Exposed to Ocrelizumab During Pregnancy		At Week 6 of infant's life
Percentage of CD19+ B Cell in the Infant Potentially Exposed to Ocrelizumab During Pregnancy		At Week 6 of infant's life
Serum Concentration of Ocrelizumab in the Infant at Week 6 of Life	Serum ocrelizumab concentrations were measured were measured at 6 weeks of the infants life to evaluate whether there was placental transfer of ocrelizumab from the mother to the infant. Serum samples from the infant were collected.	At Week 6 of infant's life
Infant Characteristics at Birth: Body Weight	Day 1 refers to the time an infant's birth.	At birth (Day 1)
Infant Characteristics at Birth: Head Circumference	Day 1 refers to the time an infant's birth.	At birth (Day 1)
Infant Characteristics at Birth: Body Length	Day 1 refers to the time an infant's birth.	At birth (Day 1)
Percentage of Pregnancies Resulting in Live Births, Therapeutic Abortions, or Stillbirth	Pregnancy outcomes analysed included live births (term and preterm, presence of congenital anomalies) and elective/therapeutic abortions and stillbirths.	During pregnancy (anytime between 37 to 42 weeks of gestation) and at birth (at Day 1)
Serum Concentration of Ocrelizumab in the Umbilical Cord Blood at Birth	Serum ocrelizumab concentrations were measured in the umbilical cord blood at birth (within 1 hour after delivery) to evaluate whether there was placental transfer of ocrelizumab from the mother to the infant. At delivery, blood samples from the umbilical cord were collected. Ocrelizumab serum concentration below the lower limit of quantification (LLOQ = 156 ng/ml) was set to zero.	Within 1 hour after delivery (at birth, Day 1)
Serum Concentration of Ocrelizumab in the Mother	Serum concentration of ocrelizumab in the mother during pregnancy (time frame of blood sampling: Week 24-30, Week 35) and at delivery (time frame of blood sampling: within 24 hours after delivery). Ocrelizumab serum concentration below the lower limit of quantification (LLOQ = 156 ng/ml) was set to zero.	Baseline (gestational Weeks 24-30), gestational Week 35, and at delivery (within 24 hours after delivery) (at birth, Day 1)
Percentage of Infants With Adverse Events	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Percentages have been rounded off.	Up to approximately 71 weeks
Percentage of Mothers With Adverse Events	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Percentages have been rounded off.	Up to approximately 87.6 weeks
Mean Titers of Measles, Immunoglobin G (IgG) Antibody in Response to MMR Vaccination	The immune response to MMR vaccination was assessed 1 month after the first dose of MMR vaccine (if the first dose is administered at 11 months of age or later) or 1 month after the second dose of MMR vaccine (if the first dose is administered before 11 months of age), or at Month 13 of chronological age if MMR vaccine was not planned to be administered. This was to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines. mIU/mL=milli-international units per milliliter.	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Mean Titers of Mumps, IgG Antibody in Response to MMR Vaccination	The immune response to MMR vaccination was assessed 1 month after the first dose of MMR vaccine (if the first dose is administered at 11 months of age or later) or 1 month after the second dose of MMR vaccine (if the first dose is administered before 11 months of age), or at Month 13 of chronological age if MMR vaccine was not planned to be administered. This was to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines. RU/mL=relative units per milliliter.	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Mean Titers of Rubella, IgG Antibody in Response to MMR Vaccination	The immune response to MMR vaccination was assessed 1 month after the first dose of MMR vaccine (if the first dose is administered at 11 months of age or later) or 1 month after the second dose of MMR vaccine (if the first dose is administered before 11 months of age), or at Month 13 of chronological age if MMR vaccine was not planned to be administered. This was to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines. IU/mL=international units per milliliter.	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Percentage of Infants With Positive Humoral Response to MMR Vaccination	Percentage of infants with positive humoral response (seroprotective titers as defined for the individual vaccine) are presented for each IgG antibody titer. Seroprotective titer based on vaccine tests for MMR vaccine are as follows: Anti-Measles Vir IgG(-70)CL: ≥ 120 mIU/mL; Anti-MumpsAT Vir iGG(-70)CL: ≥ 17 U/mL; Anti-Rub Vir IgG(-70)RUOCL: ≥ 10 IU/mL. Percentages have been rounded off.	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Mean Titers of Corynebacterium Diphtheriae, IgG Antibody in Response to Diphtheria-Tetanus-Pertussis (DTP) Vaccination	The immune response to DTP vaccination was assessed 1 month after the first dose of MMR vaccine (if the first dose is administered at 11 months of age or later) or 1 month after the second dose of MMR vaccine (if the first dose is administered before 11 months of age), or at Month 13 of chronological age if MMR vaccine was not planned to be administered. This was to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines.	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Mean Titers of Bordetella Pertussis, IgG Antibody in Response to DTP Vaccination	The immune response to DTP vaccination was assessed 1 month after the first dose of MMR vaccine (if the first dose is administered at 11 months of age or later) or 1 month after the second dose of MMR vaccine (if the first dose is administered before 11 months of age), or at Month 13 of chronological age if MMR vaccine was not planned to be administered. Cut-off Index (COI) = unitless ratio calculated as the signal intensity of the sample divided by the signal of the assay's cut-off calibrator. It is interpreted as follows: COI < 0.95: Negative;; COI 0.95-1.04: Equivocal;; COI > 1.04: Positive. The assay used has not been standardized against WHO International Units (IU/mL) for Bordetella pertussis IgG and therefore, cannot be converted to IU/mL. Higher COI values = a stronger antibody signal, but are not directly correlated with clinical protection. Positivity was defined using the manufacturer's COI cut-off (>1.04).	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Mean Titers of Tetanus Toxoid, IgG Antibody in Response to DTP Vaccination	The immune response to DTP vaccination was assessed 1 month after the first dose of MMR vaccine (if the first dose is administered at 11 months of age or later) or 1 month after the second dose of MMR vaccine (if the first dose is administered before 11 months of age), or at Month 13 of chronological age if MMR vaccine was not planned to be administered. This was to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines.	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Percentage of Infants With Positive Humoral Response to DTP Vaccination	Percentage of infants with positive humoral response (seroprotective titers as defined for the individual vaccine) was presented for each IgG antibody titer. Seroprotective titer based on vaccine tests for DTP vaccine are as follows: Anti-Diphtheria IgG(-70)CL and Anti-Tetanus Toxoid IgG(-70)RUO: ≥ 0.01 IU/mL; Bordetella pertussis antibodies, IgG: > 1.04 COI. COI = unitless ratio calculated as the signal intensity of the sample divided by the signal of the assay's cut-off calibrator. It is interpreted as follows: COI < 0.95: Negative;; COI 0.95-1.04: Equivocal;; COI > 1.04: Positive. The assay used has not been standardized against WHO international units for Bordetella pertussis IgG and therefore, cannot be converted to IU/mL. Higher COI values = a stronger antibody signal, but are not directly correlated with clinical protection. Positivity was defined using the manufacturer's COI cut-off (>1.04).	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Mean Titers of Antibody Immune Responses to Haemophilus Influenzae Type B (Hib) Vaccination	The immune response to Hib vaccination was assessed 1 month after the first dose of MMR vaccine (if the first dose is administered at 11 months of age or later) or 1 month after the second dose of MMR vaccine (if the first dose is administered before 11 months of age), or at Month 13 of chronological age if MMR vaccine was not planned to be administered. This was to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines.	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Percentage of Infants With Positive Humoral Response to Hib Vaccination	Percentage of infants with positive humoral response (seroprotective titers as defined for the individual vaccine) will be presented for each IgG antibody titer. Seroprotective titer based on vaccine tests for Hib vaccine are as follows: Hib, IgG: ≥ 0.15 µg/mL.	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Mean Titers of Antibody Immune Responses to Hepatitis B Virus (HBV) Vaccination	The immune response to HBV vaccination will be assessed 1 month after the first dose of MMR vaccine (if the first dose is administered at 11 months of age or later) or 1 month after the second dose of MMR vaccine (if the first dose is administered before 11 months of age), or at Month 13 of chronological age if MMR vaccine is not planned to be administered. This is to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines.	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Percentage of Infants With Positive Humoral Response to HBV Vaccination	Percentage of infants with positive humoral response (seroprotective titers as defined for the individual vaccine) was presented for the IgG antibody titer. Seroprotective titer based on vaccine tests for HBV vaccine are as follows: Anti-HBs: ≥ 10 mIU/mL.	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Mean Titers of Antibody Immune Responses to 13-valent Pneumococcal Conjugate (PCV-13) Vaccination	The immune response to PCV-13 vaccination was assessed 1 month after the first dose of MMR vaccine (if the first dose is administered at 11 months of age or later) or 1 month after the second dose of MMR vaccine (if the first dose is administered before 11 months of age), or at Month 13 of chronological age if MMR vaccine was not planned to be administered. This was to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines.	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Percentage of Infants With Positive Humoral Response to PCV-13 Vaccination	Percentage of infants with positive humoral response (seroprotective titers as defined for the individual vaccine) was presented for each IgG antibody titer. Seroprotective titer based on vaccine tests for PCV-13 vaccine are as follows: 13 Valent anti-pneumococcal antibody panel: ≥ 0.35 µg/ml. Percentages have been rounded off.	Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Laboratory Corporation of America; Illingworth Research Group; PPD Development, LP
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2022
• Primary Completion (Actual): April 8, 2024
• Study Completion (Actual): July 14, 2025

Study Registration Dates

• First Submitted: August 6, 2021
• First Submitted That Met QC Criteria: August 6, 2021
• First Posted (Actual): August 10, 2021

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: ocrelizumab, OCREVUS, placental transfer, pregnancy
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Immunologic Factors; Physiological Effects of Drugs; ocrelizumab
• Other Study ID Numbers: MN42988; 2021-000062-14 (EudraCT Number); 2024-510974-25-00 (Registry Identifier: EU CT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No