Multiple Sclerosis (MS) or Clinically Isolated Syndrome (CIS) [in line with the locally approved indications] MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10071068 Term: Clinically isolated syndrome System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • An informed consent form (ICF) for participation of the maternal subject and her unborn (for collection of blood samples, infant demographics and AE data) is signed and dated by the subject. Where applicable, the written ICF with respect to the infant is also signed and dated by the holder of parental rights as designated by the maternal subject • Able and willing to comply with the study protocol, in the Investigator’s judgment • Age 18-40 years, inclusive, at screening • Have a diagnosis of MS or CIS (in line with the locally approved indications) • Currently pregnant with singleton pregnancy at gestational week =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Last exposure to ocrelizumab >6 months before the woman’s LMP or later than the first trimester (i.e.after gestational week 13) • Gestational age at enrolment >26 weeks • Non-singleton pregnancy • Received last dose of ocrelizumab at a different posology other than per the local prescribing information • Social circumstances that may preclude a woman from participating in the study Exclusions related to obstetric and gynecological health • Lack of access to ultrasound pre-natal care as part of standard clinical practice • Women in whom aneuploid disorders or genetic disorders that cause major congenital malformations have been detected during first trimester prenatal screening (e.g.ultrasound, amniocentesis, genetic testing, nuchal translucency screening, chorionic villus sampling),or in whom any fetal anomalies have been detected during the morphology scan at around or before gestational week 18-20 • Documented history of disorders associated with adverse pregnancy outcomes, including but not limited to: o History of preterm birth (gestational age 35 kilograms per square meter • 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. The woman may be re-screened and included if condition resolves significant and uncontrolled disease, such as cardiovascular (including cardiac arrhythmia and hypertension), pulmonary (including obstructive pulmonary disease), neurological, psychiatric, renal, hepatic, endocrine (e.g. diabetes, thyroid disorders), or gastrointestinal or any other significant 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 (except basal cell and in situ squamous cell carcinomas of the skin). Women with in situ carcinoma of the cervix of the uterus, even if excised and resolved with documented clean margins on pathology, are excluded from the study • Prior or current history of alcohol or drug abuse, or current use of tobacco Exclusions Related to Laboratory Findings • Any abnormal screening laboratory value that is clinically relevant will be retested only once in order to rule out any progressive or uncontrolled underlying condition. The last value before study entry must meet study criteria • Women with positive screening tests for hepatitis B, determined by a positive HBsAg result (current infection) or positive HBcAb titers (previous infection) will be excluded. Wom
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate whether infants potentially exposed to ocrelizumab during pregnancy present with postpartum B cell depletion;Secondary Objective: • To evaluate B cell levels in infants potentially exposed to ocrelizumab during pregnancy • To evaluate whether there is placental transfer of ocrelizumab from the mother to the infant • To evaluate whether infants potentially exposed to ocrelizumab during pregnancy are able to mount humoral immune responses to clinically relevant vaccines • To evaluate the levels of ocrelizumab in the mother during pregnancy • To evaluate the safety of ocrelizumab in the mother, and the safety of infants potentially exposed to ocrelizumab • To evaluate pregnancy and neonatal outcomes;Primary end point(s): 1. Proportion of infants with B cell levels (CD19+ cells, absolute counts) below the lower limit of normal (LLN), measured at week 6 (±7 days) post-partum;Timepoint(s) of evaluation of this end point: 1. At Week 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. B cell levels (CD19+ cells, absolute counts and percentage of lymphocytes) measured at week 6 (±7 days) post-partum 2. Serum concentration of ocrelizumab in the umbilical cord blood at birth 3. Serum concentration of ocrelizumab in the infant at week 6 (±7 days) post-partum 4. Mean titers of antibody immune response(s) to vaccination to common childhood immunizations with full or partial doses given prior to 1 year, measured 1 month after the first dose of MMR vaccine or at month 13 (±14 days) in case MMR vaccine is not planned to be administered 5. Proportion of infants with positive humoral response (seroprotective titers; as defined for the individual vaccine) to vaccines measured 1 month after the first dose of MMR vaccine, or at month 13 (±14 days) in case MMR vaccine is not planned to be administered 6. Serum concentration of ocrelizumab in the mother during the second trimester, the third trimester, and at delivery 7. Rate and nature of adverse events (AEs) in the mother throughout the study, including changes in clinical and laboratory results 8. Rate and nature of AEs in the infant throughout the study, including infections and hospitalizations 9. Proportion of pregnancies resulting in live births (term and preterm, with and without congenital anomalies), therapeutic abortions, or stillbirths 10. Infant characteristics at birth, including but not limited to body weight, head circumference and length;Timepoint(s) of evaluation of this end point: 1. At Week 6 2. Within 1 hour after delivery 3. At Week 6 4-5. 1 month after the first dose of MMR vaccine, or at month 13 in case MMR vaccine is not planned to be administered 6. At Weeks 26, 36, and within 24 hours after delivery 7.-8. Throughout the study 9.-10. At birth | — |
Countries
Australia, Canada, France, Germany, Italy, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed