Clinically Isolated Syndrome, Multiple Sclerosis
Conditions
Keywords
ocrelizumab, OCREVUS, placental transfer, pregnancy
Brief summary
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.
Interventions
DRUGOcrelizumab
Post-partum dosing and treatment duration are at the discretion of the physicians, in accordance with local clinical practice and local labelling.
Sponsors
Hoffmann-La Roche
PPD Development, LP
Laboratory Corporation of America
Illingworth Research Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
35 pregnant women with singleton pregnancy were enrolled in the study (70 participants in total, including the infants).
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Infants With B Cell Levels (Cluster of Differentiation 19 [CD19+] Cells) Below the Lower Limit of Normal (LLN) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 Umbilical Cord Blood at Birth | 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. |
| Serum Concentration of Ocrelizumab in the Infant at Week 6 of Life | 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. |
| Serum Concentration of Ocrelizumab in the Mother | 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. |
| Percentage of Infants With Adverse Events | 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. |
| Percentage of Mothers With Adverse Events | 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. |
| Infant Characteristics at Birth: Body Weight | At birth (Day 1) | Day 1 refers to the time an infant's birth. |
| Infant Characteristics at Birth: Head Circumference | At birth (Day 1) | Day 1 refers to the time an infant's birth. |
| Infant Characteristics at Birth: Body Length | At birth (Day 1) | Day 1 refers to the time an infant's birth. |
| Percentage of Pregnancies Resulting in Live Births, Therapeutic Abortions, or Stillbirth | 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. |
| Mean Titers of Measles, Immunoglobin G (IgG) Antibody in Response to MMR Vaccination | 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. |
| Mean Titers of Mumps, IgG Antibody in Response to MMR Vaccination | 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. |
| Mean Titers of Rubella, IgG Antibody in Response to MMR Vaccination | 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. |
| Percentage of Infants With Positive Humoral Response to MMR Vaccination | 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. |
| Mean Titers of Corynebacterium Diphtheriae, IgG Antibody in Response to Diphtheria-Tetanus-Pertussis (DTP) Vaccination | 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. |
| Mean Titers of Bordetella Pertussis, IgG Antibody in Response to DTP Vaccination | 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). |
| Mean Titers of Tetanus Toxoid, IgG Antibody in Response to DTP Vaccination | 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. |
| Percentage of Infants With Positive Humoral Response to DTP Vaccination | 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). |
| Mean Titers of Antibody Immune Responses to Haemophilus Influenzae Type B (Hib) Vaccination | 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. |
| Percentage of Infants With Positive Humoral Response to Hib Vaccination | 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. |
| Mean Titers of Antibody Immune Responses to Hepatitis B Virus (HBV) Vaccination | 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. |
| Percentage of Infants With Positive Humoral Response to HBV Vaccination | 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. |
| Mean Titers of Antibody Immune Responses to 13-valent Pneumococcal Conjugate (PCV-13) Vaccination | 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. |
| Percentage of Infants With Positive Humoral Response to PCV-13 Vaccination | 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. |
Countries
France, Germany, Spain, Switzerland, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
35 pregnant women (with singleton pregnancy) were enrolled in the study across 10 centers in the United States, Germany, France, Switzerland and Spain from 13 April 2022 to 14 July 2025. An Informed Consent Form (ICF) for participation of the maternal subject and her unborn was signed and dated by the subject. Where applicable, the written ICF with respect to the infant was also signed and dated by the holder of parental rights as designated by the maternal subject.
Pre-assignment details
Pregnant women with clinically isolated syndrome (CIS) or multiple sclerosis (MS) who were exposed accidentally or as part of routine clinical practice to commercial ocrelizumab up to 6 months before the last menstrual period (LMP) or during the first trimester of pregnancy were enrolled & potential placental transfer of ocrelizumab in infants was observed.
Participants by arm
| Arm | Count |
|---|---|
| Women Pregnant 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 enrolled. Ocrelizumab was not administered after enrollment in the study until the infant's birth. | 35 |
| 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 until the last visit which was at 1 month (+ 30 days) after the first dose of measles, mumps, and rubella (MMR) vaccine (if first dose is administered at 11 months of age or later) or 1 month (+ 30 days) after second dose of MMR vaccine (if first dose is administered before 11 months of age), or at Month 13 of chronological age (+ 30 days) if MMR vaccine is not planned to be administered. | 35 |
| Total | 70 |
Baseline characteristics
| Characteristic | Infants | Women | Total |
|---|---|---|---|
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adults (18-64 years) | 0 Participants | 35 Participants | 35 Participants |
| Age, Customized Children (2-11 years) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized From 65-84 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Newborns (0-27 days) | 35 Participants | 0 Participants | 35 Participants |
| Age, Customized Preterm newborn infants (gestational age <37 weeks) | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not reported | 35 Participants | 35 Participants | 70 Participants |
| Sex: Female, Male Female | 22 Participants | 35 Participants | 57 Participants |
| Sex: Female, Male Male | 13 Participants | 0 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 28 / 35 | 26 / 35 |
| serious Total, serious adverse events | 6 / 35 | 3 / 35 |
Outcome results
Primary
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.
Time frame: At Week 6 of infant's life
Population: FASI included all infants born to women in the FASW who were potentially exposed to ocrelizumab during pregnancy. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infants | Percentage of Infants With B Cell Levels (Cluster of Differentiation 19 [CD19+] Cells) Below the Lower Limit of Normal (LLN) | 0 percentage of participants |
Secondary
Absolute CD19+ B Cell Count in the Infant Potentially Exposed to Ocrelizumab During Pregnancy
Time frame: At Week 6 of infant's life
Population: FASI included all infants born to women in the FASW who were potentially exposed to ocrelizumab during pregnancy. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infants | Absolute CD19+ B Cell Count in the Infant Potentially Exposed to Ocrelizumab During Pregnancy | 1170.00 cells per microliter (cells/µL) |
Secondary
Infant Characteristics at Birth: Body Length
Day 1 refers to the time an infant's birth.
Time frame: At birth (Day 1)
Population: FASI included all infants born to women in the FASW who were potentially exposed to ocrelizumab during pregnancy. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Infants | Infant Characteristics at Birth: Body Length | 51.58 cm | Standard Deviation 2.15 |
Secondary
Infant Characteristics at Birth: Body Weight
Day 1 refers to the time an infant's birth.
Time frame: At birth (Day 1)
Population: FASI included all infants born to women in the FASW who were potentially exposed to ocrelizumab during pregnancy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Infants | Infant Characteristics at Birth: Body Weight | 3.46 kilogram (kg) | Standard Deviation 0.43 |
Secondary
Infant Characteristics at Birth: Head Circumference
Day 1 refers to the time an infant's birth.
Time frame: At birth (Day 1)
Population: FASI included all infants born to women in the FASW who were potentially exposed to ocrelizumab during pregnancy. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Infants | Infant Characteristics at Birth: Head Circumference | 35.08 centimeter (cm) | Standard Deviation 1.15 |
Secondary
Mean Titers of Antibody Immune Responses to 13-valent Pneumococcal Conjugate Vaccine (PCV-13)
The immune response to PCV-13 vaccine 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.
Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Secondary
Mean Titers of Antibody Immune Responses to Diphtheria-Tetanus-Pertussis (DTP) Vaccine
The immune response to DTP vaccine 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.
Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Secondary
Mean Titers of Antibody Immune Responses to Haemophilus Influenzae Type B (Hib) Vaccine
The immune response to Hib vaccine 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.
Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Secondary
Mean Titers of Antibody Immune Responses to Hepatitis B Vaccine (HBV)
The immune response to HBV vaccine 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.
Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Secondary
Mean Titers of Antibody Immune Responses to Measles, Mumps, and Rubella (MMR) Vaccination
The immune response to MMR vaccine 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.
Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Secondary
Percentage of CD19+ B Cell in the Infant Potentially Exposed to Ocrelizumab During Pregnancy
Time frame: At Week 6 of infant's life
Population: FASI included all infants born to women in the FASW who were potentially exposed to ocrelizumab during pregnancy. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infants | Percentage of CD19+ B Cell in the Infant Potentially Exposed to Ocrelizumab During Pregnancy | 19.20 percentage of cells |
Secondary
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.
Time frame: Up to 17 months
Secondary
Percentage of Infants With Positive Humoral Response to DTP Vaccine
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 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 cut-off index (COI).
Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Secondary
Percentage of Infants With Positive Humoral Response to HBV
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 HBV vaccine are as follows: Anti-HBs: ≥ 10 mIU/mL.
Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Secondary
Percentage of Infants With Positive Humoral Response to Hib Vaccine
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.
Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Secondary
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) will be presented for each immunoglobulin G (IgG) antibody titer. Seroprotective titer based on vaccine tests for MMR vaccine are as follows: Anti-Measles Vir IgG(-70)CL: ≥ 120 milli-international units/milliliter (mIU/mL); Anti-MumpsAT Vir iGG(-70)CL: ≥ 17 units per milliliters (U/mL); Anti-Rub Vir IgG(-70)RUOCL: ≥ 10 international units/milliliters (IU/mL).
Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Secondary
Percentage of Infants With Positive Humoral Response to PCV-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 PCV-13 vaccine are as follows: 13 Valent anti-pneumococcal antibody panel: ≥ 0.35 µg/mL.
Time frame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Secondary
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.
Time frame: Up to 17 months
Secondary
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.
Time frame: During pregnancy (anytime between 37 to 42 weeks of gestation) and at birth (at Day 1)
Population: Safety analysis set women (SAFW) included all enrolled pregnant women who were exposed to ocrelizumab either 0-6 months before the LMP or in the first trimester of pregnancy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infants | Percentage of Pregnancies Resulting in Live Births, Therapeutic Abortions, or Stillbirth | Live Births | 100 percentage of pregnancies |
| Infants | Percentage of Pregnancies Resulting in Live Births, Therapeutic Abortions, or Stillbirth | Congenital Anomalies | 8.6 percentage of pregnancies |
| Infants | Percentage of Pregnancies Resulting in Live Births, Therapeutic Abortions, or Stillbirth | Therapeutic Abortions | 0 percentage of pregnancies |
| Infants | Percentage of Pregnancies Resulting in Live Births, Therapeutic Abortions, or Stillbirth | Stillbirth | 0 percentage of pregnancies |
| Infants | Percentage of Pregnancies Resulting in Live Births, Therapeutic Abortions, or Stillbirth | Preterm | 0 percentage of pregnancies |
Secondary
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.
Time frame: At Week 6 of infant's life
Population: FASI included all infants born to women in the FASW who were potentially exposed to ocrelizumab during pregnancy. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infants | Serum Concentration of Ocrelizumab in the Infant at Week 6 of Life | 0.00 ng/mL |
Secondary
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.
Time frame: Baseline (gestational Weeks 24-30), gestational Week 35, and at delivery (within 24 hours after delivery) (at birth Day 1)
Population: FASW included all enrolled pregnant women who were exposed to ocrelizumab either 0-6 months before the LMP or in the first trimester of pregnancy. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Infants | Serum Concentration of Ocrelizumab in the Mother | Baseline - Gestational Weeks 24-30 | 0.00 ng/mL |
| Infants | Serum Concentration of Ocrelizumab in the Mother | Gestational Week 35 | 0.00 ng/mL |
| Infants | Serum Concentration of Ocrelizumab in the Mother | At Delivery | 0.00 ng/mL |
Secondary
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.
Time frame: Within 1 hour after delivery (at birth Day 1)
Population: FASI included all infants born to women in the FASW who were potentially exposed to ocrelizumab during pregnancy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infants | Serum Concentration of Ocrelizumab in the Umbilical Cord Blood at Birth | 0.00 nanograms/milliliter (ng/mL) |