Clinical Trial Results:
A Phase IV Multicenter, Open-Label Study Evaluating B Cell Levels in Infants of Lactating Women With CIS or MS Receiving Ocrelizumab
Summary
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EudraCT number |
2021-000063-79 |
Trial protocol |
ES DE |
Global end of trial date |
13 Jan 2025
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Results information
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Results version number |
v2(current) |
This version publication date |
24 Jul 2025
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First version publication date |
12 Apr 2025
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Other versions |
v1 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MN42989
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04998851 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4058
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Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Jan 2025
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Jan 2025
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
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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Protection of trial subjects |
All study participants were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Sep 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 2
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Country: Number of subjects enrolled |
United Kingdom: 4
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Country: Number of subjects enrolled |
United States: 20
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Worldwide total number of subjects |
26
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EEA total number of subjects |
2
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
8
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Infants and toddlers (28 days-23 months) |
5
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
13
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 13 mother-infant pairs took part in the study across 7 sites in the United States, Spain, and the United Kingdom from 16 September 2021 to 13 January 2025. | |||||||||||||||
Pre-assignment
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Screening details |
Lactating mothers with CIS or MS who, in consultation with their treating physician, chose to continue or start postpartum treatment with commercial ocrelizumab were enrolled in this study. This study included a 60-day treatment and sampling period followed by an 11-month vaccination period. | |||||||||||||||
Period 1
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Period 1 title |
Treatment and Sampling Period (60 days)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Mothers | |||||||||||||||
Arm description |
Lactating mothers initiating ocrelizumab received two doses of 300 milligrams (mg), as an intravenous (IV) infusion on Day 1 and Day 14, and mothers resuming ocrelizumab received a single dose of 600 mg, as an IV infusion on Day 1 at the discretion of the physicians, in accordance with local prescribing information. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Ocrelizumab
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Investigational medicinal product code |
RO4964913
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Mothers initiating, administered ocrelizumab 300 mg, as an IV infusion on Day 1 and Day 14, and mothers resuming ocrelizumab received a single dose of 600 mg, as an IV infusion on Day 1.
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Arm title
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Infants | |||||||||||||||
Arm description |
Infants of mothers who received commercial IV ocrelizumab at the discretion of the physicians, in accordance with local prescribing information were observed until 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. | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Period 2
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Period 2 title |
Vaccination Period (11 Months)
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Mothers | |||||||||||||||
Arm description |
Lactating mothers initiating ocrelizumab received two doses of 300 milligrams (mg), as an intravenous (IV) infusion on Day 1 and Day 14, and mothers resuming ocrelizumab received a single dose of 600 mg, as an IV infusion on Day 1 at the discretion of the physicians, in accordance with local prescribing information. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Ocrelizumab
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Investigational medicinal product code |
RO4964913
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Mothers initiating, administered ocrelizumab, 300 mg, as an IV infusion on Day 1 and Day 14, and mothers resuming ocrelizumab received a single dose of 600 mg, as an IV infusion on Day 1.
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Arm title
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Infants | |||||||||||||||
Arm description |
Infants of mothers who received commercial IV ocrelizumab at the discretion of the physicians, in accordance with local prescribing information were observed until 1 month (+30 days) after the first dose of 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. | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Mothers
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Reporting group description |
Lactating mothers initiating ocrelizumab received two doses of 300 milligrams (mg), as an intravenous (IV) infusion on Day 1 and Day 14, and mothers resuming ocrelizumab received a single dose of 600 mg, as an IV infusion on Day 1 at the discretion of the physicians, in accordance with local prescribing information. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Infants
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Reporting group description |
Infants of mothers who received commercial IV ocrelizumab at the discretion of the physicians, in accordance with local prescribing information were observed until 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Mothers
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Reporting group description |
Lactating mothers initiating ocrelizumab received two doses of 300 milligrams (mg), as an intravenous (IV) infusion on Day 1 and Day 14, and mothers resuming ocrelizumab received a single dose of 600 mg, as an IV infusion on Day 1 at the discretion of the physicians, in accordance with local prescribing information. | ||
Reporting group title |
Infants
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Reporting group description |
Infants of mothers who received commercial IV ocrelizumab at the discretion of the physicians, in accordance with local prescribing information were observed until 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. | ||
Reporting group title |
Mothers
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Reporting group description |
Lactating mothers initiating ocrelizumab received two doses of 300 milligrams (mg), as an intravenous (IV) infusion on Day 1 and Day 14, and mothers resuming ocrelizumab received a single dose of 600 mg, as an IV infusion on Day 1 at the discretion of the physicians, in accordance with local prescribing information. | ||
Reporting group title |
Infants
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Reporting group description |
Infants of mothers who received commercial IV ocrelizumab at the discretion of the physicians, in accordance with local prescribing information were observed until 1 month (+30 days) after the first dose of 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. | ||
Subject analysis set title |
Infants
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Infants of mothers who received commercial IV ocrelizumab at the discretion of the physicians, in accordance with local prescribing information were observed until 1 month (+30 days) after the first dose of 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.
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Subject analysis set title |
Mothers
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Lactating mothers initiating ocrelizumab received two doses of 300 mg, as an IV infusion on Day 1 and Day 14, and mothers resuming ocrelizumab received a single dose of 600 mg, as an IV infusion on Day 1 at the discretion of the physicians, in accordance with local prescribing information.
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End point title |
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 [1] [2] | ||||||||
End point description |
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. Full Analysis Set Infants (FASI) included all the infants of women in the Full Analysis Set Mothers (FASM) population. Number analyzed is the number of participants with data available for analyses.
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End point type |
Primary
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End point timeframe |
At Day 30
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint reports data for the infants only. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No formal statistical analysis was planned for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Estimated Average Oral Daily Infant Dosage (ADID) [3] [4] | ||||||||
End point description |
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. Pharmacokinetic Analysis Set Mothers (PASM) included all mothers in the FASM with a breastmilk sample to allow measurement of ocrelizumab concentration.
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End point type |
Primary
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End point timeframe |
Up to Day 60
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint reports data for the infants only. [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint reports data for the infants only. |
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No statistical analyses for this end point |
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End point title |
Absolute CD19+ B Cell Count in the Infant [5] | ||||||||
End point description |
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). FASI included all the infants of women in the FASM population. Number analyzed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
At Day 30
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Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint reports data for the infants only. |
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No statistical analyses for this end point |
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End point title |
Percentage of CD19+ B Cell in the Infant [6] | ||||||||
End point description |
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). FASI included all the infants of women in the FASM population. Number analyzed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
At Day 30
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Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint reports data for the infants only. |
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No statistical analyses for this end point |
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End point title |
Time of Maximum Concentration (Tmax) of Ocrelizumab in Breastmilk [7] | ||||||||
End point description |
PASM included all mothers in the FASM with a breastmilk sample to allow measurement of ocrelizumab concentration.
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End point type |
Secondary
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End point timeframe |
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
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Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint reports data for the infants only. |
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No statistical analyses for this end point |
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End point title |
Area Under the Milk Concentration-Time Curve (AUC) of Ocrelizumab in Mature Breastmilk [8] | ||||||||
End point description |
PASM included all mothers in the FASM with a breastmilk sample to allow measurement of ocrelizumab concentration.
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End point type |
Secondary
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End point timeframe |
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
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Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint reports data for the infants only. |
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No statistical analyses for this end point |
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End point title |
Average Concentration of Ocrelizumab in Breastmilk (Cmean) [9] | ||||||||
End point description |
PASM included all mothers in the FASM with a breastmilk sample to allow measurement of ocrelizumab concentration.
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End point type |
Secondary
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End point timeframe |
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
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Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint reports data for the infants only. |
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No statistical analyses for this end point |
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End point title |
Maximum Concentration (Cmax) of Ocrelizumab in Breastmilk [10] | ||||||||
End point description |
PASM included all mothers in the FASM with a breastmilk sample to allow measurement of ocrelizumab concentration.
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End point type |
Secondary
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End point timeframe |
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
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Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint reports data for the infants only. |
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No statistical analyses for this end point |
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End point title |
Percentage of Mothers With Adverse Events (AEs) | ||||||||
End point description |
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. Safety Analysis Set Mothers (SAFM) included all mothers who met the eligibility criteria and received any post-partum dose of ocrelizumab.
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End point type |
Secondary
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End point timeframe |
Up to approximately 73.3 weeks
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No statistical analyses for this end point |
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End point title |
Estimated Maximum Oral Daily Infant Dosage (MDID) [11] | ||||||||
End point description |
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. PASM included all mothers in the FASM with a breastmilk sample to allow measurement of ocrelizumab concentration.
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End point type |
Secondary
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End point timeframe |
Up to Day 60
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Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint reports data for the infants only. |
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No statistical analyses for this end point |
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End point title |
Serum Concentration of Ocrelizumab in the Infant at Day 30 [12] | ||||||||
End point description |
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. Pharmacokinetic Analysis Set Infants (PASI) included all infants in the FASI with a serum sample to allow measurement of ocrelizumab concentration. 9999 indicates that the mean and SD were not evaluable as samples were below the limit of quantification (BLQ).
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End point type |
Secondary
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End point timeframe |
At Day 30
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Notes [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint reports data for the infants only. |
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No statistical analyses for this end point |
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End point title |
Average Relative Infant Dose (RID) [13] | ||||||||
End point description |
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. PASM included all mothers in the FASM with a breastmilk sample to allow measurement of ocrelizumab concentration.
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End point type |
Secondary
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End point timeframe |
Up to Day 60
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Notes [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint reports data for the infants only. |
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No statistical analyses for this end point |
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End point title |
Mean Titers of Measles, Immunoglobulin G (IgG) Antibody in Response to MMR Vaccination | ||||||||
End point description |
The immune response to measles, mumps, and rubella (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. Antibody Immune Response Analysis Set of Infants (AIRI) included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. mIU/mL=milli-international units per milliliter.
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End point type |
Secondary
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End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
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No statistical analyses for this end point |
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End point title |
Percentage of Infants With AEs | ||||||||
End point description |
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. Safety Analysis Set Infants (SAFI) included all the infants of women in the FASM population.
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End point type |
Secondary
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End point timeframe |
Up to approximately 73.3 weeks
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No statistical analyses for this end point |
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End point title |
Mean Titers of Rubella, IgG Antibody in Response to MMR Vaccination | ||||||||
End point description |
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. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. Number analyzed are the number of infants with data available for analysis. IU/mL=international units per milliliter.
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End point type |
Secondary
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End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
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No statistical analyses for this end point |
|
|||||||||
End point title |
Mean Titers of Mumps, IgG Antibody in Response to MMR Vaccination | ||||||||
End point description |
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. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. Number analyzed are the number of infants with data available for analysis. RU/mL=relative units per milliliter.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Percentage of Infants With Positive Humoral Response to MMR Vaccination | ||||||||||||||
End point description |
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. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. n = infants with data available for the specified IgG antibody titer.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Percentage of Infants With Positive Humoral Response to DTP Vaccine | ||||||||||||||
End point description |
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. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. Number analyzed are the number of infants with data available for analysis. n = infants with data available for the specified IgG antibody titer.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Mean Titers of Corynebacterium Diphtheriae, IgG Antibody in Response to Diphtheria-Tetanus-Pertussis (DTP) Vaccine | ||||||||
End point description |
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. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. Number analyzed are the number of infants with data available for analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Mean Titers of Tetanus Toxoid, IgG Antibody in Response to DTP Vaccine | ||||||||
End point description |
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. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. Number analyzed are the number of infants with data available for analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Mean Titers of Bordetella Pertussis, IgG Antibody in Response to DTP Vaccine | ||||||||
End point description |
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. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. Number analyzed are the number of infants with data available for analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Mean Titers of Haemophilus Influenzae Type B (Hib), IgG Antibody in Response to Hib Vaccine | ||||||||
End point description |
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. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. Number analyzed are the number of infants with data available for analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percentage of Infants With Positive Humoral Response to Hib Vaccine | ||||||||
End point description |
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. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. Number analyzed are the number of infants with data available for analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Mean Titers of Anti-Hepatitis B Surface Antibody in Response to Hepatitis B Virus (HBV) Vaccine | ||||||||
End point description |
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. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. Number analyzed are the number of infants with data available for analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percentage of Infants With Positive Humoral Response to HBV Vaccine | ||||||||
End point description |
Percentage of infants with positive humoral response (seroprotective titers as defined for the individual vaccine) was presented for eachthe IgG antibody titer. Seroprotective titer based on vaccine tests for HBV vaccine are as follows: Anti-HBs: ≥ 10 mIU/mL. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. Number analyzed are the number of infants with data available for analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||
End point title |
Mean Titers of Pneumococcal Capsular Polysaccharide (CPS), Serotypes, IgG Antibody in Response to 13-valent Pneumococcal Conjugate Vaccine (PCV-13) | ||||||||||||||||||||||||||||||||||
End point description |
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. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. Number analyzed are the number of infants with data available for analysis.
|
||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||
End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
|
||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||
End point title |
Percentage of Infants With Positive Humoral Response to PCV-13 | ||||||||||||||||||||||||||||||||||
End point description |
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. AIRI included all infants in the SAFI for whom any serum titers of antibody immune response to vaccinations were available. Number analyzed are the number of infants with data available for analysis.
|
||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||
End point timeframe |
Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
|
||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
Mothers and Infants: Up to approximately 73.3 weeks
|
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Adverse event reporting additional description |
SAFM included all mothers who met the eligibility criteria and received any post-partum dose of ocrelizumab. SAFI included all the infants of women in the FASM population.
|
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.1
|
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Reporting groups
|
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Reporting group title |
Mothers
|
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Reporting group description |
Lactating mothers initiating ocrelizumab received two doses of 300 mg, as an IV infusion on Day 1 and Day 14, and mothers resuming ocrelizumab received a single dose of 600 mg, as an IV infusion on Day 1 at the discretion of the physicians, in accordance with local prescribing information. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Infants
|
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Reporting group description |
Infants of mothers who received commercial IV ocrelizumab at the discretion of the physicians, in accordance with local prescribing information were observed until the last visit which was at 1 month (+ 30 days) after the first dose of 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
01 Apr 2022 |
1. A note on referral to sites was added, to allow referral of potentially eligible women to study sites. Women could be referred to study sites; and the possibility of home-based study visits was extended to all visits (conducted by a mobile nurse, and by the investigator using telemedicine [i.e., remotely]).
2. Woman agreed to use acceptable contraceptive methods or alternative methods during the study as described below and, if applicable, upon study treatment discontinuation, as defined by the local prescribing information. |
||
05 Jun 2023 |
1. The secondary objectives were amended to include the evaluation of the relative exposure as measured by the RID to ocrelizumab in infants of lactating women with CIS or MS receiving ocrelizumab postpartum.
2. The sample size was reduced from at least 20 to at least 10 women with CIS or MS.
3. The total length of the study was increased from approximately 2 years to approximately 3 years, due to the extension of the enrolment period from approximately 8 months to approximately 21 months.
4. The list of antibody (Ab) titers of responses to vaccines administered as per local practice, had been updated to detail that the following were included: antimeasles Ab IgG, anti-rubella Ab IgG, anti-mumps Ab IgG, PCV-13 Ab (all serotypes), anti-tetanus toxoid IgG, anti-diphtheria IgG, Bordetella pertussis Ab IgG, hepatitis B surface Ab, Hemophilus influenza B IgG. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |