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Completed

NCT Number: NCT04998812

A 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.

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Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Clinically Isolated Syndrome Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Nervous System Diseases

Age range

18 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

Hopital Pierre Wertheimer - Hopital Neurologique, Bron, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ocrelizumab

Drug

Post-partum dosing and treatment duration are at the discretion of the physicians, in accordance with local clinical practice and local labelling.

Primary outcomes

  1. Percentage of Infants With B Cell Levels (Cluster of Differentiation 19 [CD19+] Cells) Below the Lower Limit of Normal (LLN)

    Time frame: At Week 6 of infant's life

    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.

Secondary outcomes

  1. Absolute CD19+ B Cell Count in the Infant Potentially Exposed to Ocrelizumab During Pregnancy

    Time frame: At Week 6 of infant's life

  2. Percentage of CD19+ B Cell in the Infant Potentially Exposed to Ocrelizumab During Pregnancy

    Time frame: At Week 6 of infant's life

  3. Serum Concentration of Ocrelizumab in the Umbilical Cord Blood at Birth

    Time frame: Within 1 hour after delivery (at birth, Day 1)

    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.

  4. Serum Concentration of Ocrelizumab in the Infant at Week 6 of Life

    Time frame: At Week 6 of infant's 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.

  5. Serum Concentration of Ocrelizumab in the Mother

    Time frame: Baseline (gestational Weeks 24-30), gestational Week 35, and at delivery (within 24 hours after delivery) (at birth, Day 1)

    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.

  6. Percentage of Infants With Adverse Events

    Time frame: Up to approximately 71 weeks

    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.

  7. Percentage of Mothers With Adverse Events

    Time frame: Up to approximately 87.6 weeks

    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.

  8. Infant Characteristics at Birth: Body Weight

    Time frame: At birth (Day 1)

    Day 1 refers to the time an infant's birth.

  9. Infant Characteristics at Birth: Head Circumference

    Time frame: At birth (Day 1)

    Day 1 refers to the time an infant's birth.

  10. Infant Characteristics at Birth: Body Length

    Time frame: At birth (Day 1)

    Day 1 refers to the time an infant's birth.

  11. Percentage of Pregnancies Resulting in Live Births, Therapeutic Abortions, or Stillbirth

    Time frame: During pregnancy (anytime between 37 to 42 weeks of gestation) and at birth (at Day 1)

    Pregnancy outcomes analysed included live births (term and preterm, presence of congenital anomalies) and elective/therapeutic abortions and stillbirths.

  12. Mean Titers of Measles, Immunoglobin G (IgG) Antibody in Response to MMR Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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.

  13. Mean Titers of Mumps, IgG Antibody in Response to MMR Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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.

  14. Mean Titers of Rubella, IgG Antibody in Response to MMR Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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.

  15. Percentage of Infants With Positive Humoral Response to MMR Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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.

  16. Mean Titers of Corynebacterium Diphtheriae, IgG Antibody in Response to Diphtheria-Tetanus-Pertussis (DTP) Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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.

  17. Mean Titers of Bordetella Pertussis, IgG Antibody in Response to DTP Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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).

  18. Mean Titers of Tetanus Toxoid, IgG Antibody in Response to DTP Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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.

  19. Percentage of Infants With Positive Humoral Response to DTP Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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).

  20. Mean Titers of Antibody Immune Responses to Haemophilus Influenzae Type B (Hib) Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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.

  21. Percentage of Infants With Positive Humoral Response to Hib Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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.

  22. Mean Titers of Antibody Immune Responses to Hepatitis B Virus (HBV) Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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.

  23. Percentage of Infants With Positive Humoral Response to HBV Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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.

  24. Mean Titers of Antibody Immune Responses to 13-valent Pneumococcal Conjugate (PCV-13) Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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.

  25. Percentage of Infants With Positive Humoral Response to PCV-13 Vaccination

    Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)

    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.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Collaborators

  • Illingworth Research Group
  • Laboratory Corporation of America
  • PPD Development, LP

Registry information

Official study title

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

Acronym: MINORE

Important dates

Study start
2022
Primary completion
2024
Study completion
2025
First posted
Aug 10, 2021
Registry last updated
Apr 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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