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Completed

NCT Number: NCT04998851

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

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.

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Key information

Conditions

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

Age range

18 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

Hosp. Clinico San Carlos, Madrid, Spain

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Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • 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

Exclusion criteria

related to the Mother:

  • 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

Exclusion criteria

related to the Infant:

  • >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
  • At least one documented brief resolved unexplained event (BRUE), as defined by the 2016 Guidelines of the American Academy of Pediatrics

Treatment and study plan

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.

Primary outcomes

  1. 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

    Time frame: At Day 30

    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.

  2. Estimated Average Oral Daily Infant Dosage (ADID)

    Time frame: Up to Day 60

    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.

Secondary outcomes

  1. Absolute CD19+ B Cell Count in the Infant

    Time frame: At Day 30

    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).

  2. Percentage of CD19+ B Cell in the Infant

    Time frame: At Day 30

    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).

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

    Time frame: 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

  4. Average Concentration of Ocrelizumab in Breastmilk (Cmean)

    Time frame: 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

  5. Maximum Concentration (Cmax) of Ocrelizumab in Breastmilk

    Time frame: 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

  6. Time of Maximum Concentration (Tmax) of Ocrelizumab in Breastmilk

    Time frame: 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

  7. Estimated Maximum Oral Daily Infant Dosage (MDID)

    Time frame: Up to Day 60

    MDID was calculated at the subject level as the peak ocrelizumab milk concentration (μg/mL) multiplied by an estimated infant milk intake of 150 mL/kg/day measured over 60 days after the mother's first postpartum ocrelizumab infusion.

  8. Average Relative Infant Dose (RID)

    Time frame: Up to Day 60

    Average RID over 60 days was calculated as the ADID (mg/kg/day) divided by the maternal dosage (mg/kg/day) over 60 days multiplied by 100.

  9. Serum Concentration of Ocrelizumab in the Infant at Day 30

    Time frame: At Day 30

    Serum concentration of ocrelizumab in the infant measured at Day 30 after the mother's first ocrelizumab postpartum infusion. Concentrations reported as below the lower limit of quantification (LLQ=156 ng/mL) are set to zero for calculation of summary statistics.

  10. Percentage of Mothers With Adverse Events (AEs)

    Time frame: Up to approximately 73.3 weeks after first ocrelizumab dose

    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.

  11. Percentage of Infants With AEs

    Time frame: Up to approximately 73.3 weeks after first ocrelizumab dose administered to mother

    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.

  12. Mean Titers of Measles, Immunoglobin G (IgG) Antibody in Response to Measles, Mumps, and Rubella (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 vaccine 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 vaccine 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 vaccine 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) was 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 RU/mL; Anti-Rub Vir IgG(-70)RUOCL: ≥ 10 IU/mL.

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

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

    The immune response to DTP vaccine 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 Vaccine

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

    The immune response to DTP vaccine 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 Vaccine

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

    The immune response to DTP vaccine 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 Vaccine

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

    The immune response to DTP vaccine 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).

  20. Mean Titers of Haemophilus Influenzae Type B (Hib), IgG Antibody in Response to Hib Vaccine

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

    The immune response to Hib vaccine 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 Vaccine

    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 Hib vaccine are as follows: Hib, IgG: ≥ 0.15 µg/mL.

  22. Mean Titers of Anti-Hepatitis B Surface Antibody in Response to Hepatitis B Virus (HBV) Vaccine

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

    The immune response to HBV vaccine 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.

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

    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 Pneumococcal Capsular Polysaccharide, Serotypes, IgG Antibody in Response to 13-valent Pneumococcal Conjugate Vaccine (PCV-13)

    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 vaccine 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

    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.

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 Of Lactating Women With CIS Or MS Receiving Ocrelizumab

Acronym: SOPRANINO

Important dates

Study start
2021
Primary completion
2024
Study completion
2025
First posted
Aug 10, 2021
Registry last updated
Jan 14, 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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