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

Study Overview
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Brief Summary
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This study will evaluate the potential placental transfer of ocrelizumab in 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.

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

Conditions
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Multiple Sclerosis, Clinically Isolated Syndrome

Intervention / Treatment
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* Drug: Ocrelizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Women with CIS or MS<br>Women with CIS or MS (in line with the locally approved indications) receiving commercial ocrelizumab up to 6 months before the LMP or during the first trimester of pregnancy (up to gestational week 13), due to accidental exposure, or in whom a decision to treat with ocrelizumab was taken as part of routine clinical practice. | Drug: Ocrelizumab<br>* Post-partum dosing and treatment duration are at the discretion of the physicians, in accordance with local clinical practice and local labelling.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of infants with B cell levels (CD19+ cells) below the lower limit of normal (LLN) |  | Week 6 of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B cell levels (CD19+ cells) in the infant |  | Week 6 of life | 
| Serum concentration of ocrelizumab in the umbilical cord blood at birth |  | Within 1 hour after delivery | 
| Serum concentration of ocrelizumab in the infant |  | Week 6 of life | 
| Serum concentration of ocrelizumab in the mother |  | During the second trimester (week 26), third trimester (week 36) and at delivery (within 24 hours after delivery) | 
| Rate and nature of adverse events in the infant |  | Baseline up to 17 months | 
| Rate and nature of adverse events in the mother |  | Baseline up to 17 months | 
| Infant characteristics at birth (body weight) |  | At birth | 
| Infant characteristics at birth (head circumference) |  | At birth | 
| Infant characteristics at birth (body length) |  | At birth | 
| Proportion of pregnancies resulting in live births, therapeutic abortions, or stillbirth |  | At birth | 
| Mean titers of antibody immune responses to Measles, Mumps, and Rubella (MMR) Vaccination |  | Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered | 
| Proportion of infants with positive humoral response to Measles, Mumps, and Rubella (MMR) Vaccination |  | Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered | 
| Mean titers of antibody immune responses to Diphtheria-Tetanus-Pertussis Vaccine |  | Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered | 
| Proportion of infants with positive humoral response to Diphtheria-Tetanus-Pertussis Vaccine |  | Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered | 
| Mean titers of antibody immune responses to Haemophilus influenzae type B Vaccine |  | Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered | 
| Proportion of infants with positive humoral response to Haemophilus influenzae type B Vaccine |  | Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered | 
| Mean titers of antibody immune responses to Hepatitis B Vaccine |  | Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered | 
| Proportion of infants with positive humoral response to Hepatitis B Vaccine |  | Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered | 
| Mean titers of antibody immune responses to Pneumococcal conjugate Vaccine |  | Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered | 
| Proportion of infants with positive humoral response to Pneumococcal conjugate Vaccine |  | Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ocrelizumab, OCREVUS, placental transfer, pregnancy