Multiple Sclerosis (MS) or Clinically Isolated Syndrome (CIS) [in line with the locally approved indications] MedDRA version: 20.0 Level: PT Classification code 10071068 Term: Clinically isolated syndrome System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis 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 for participation of the maternal subject and her infant (for collection of blood, infant demographic and AE data) is signed and dated by the subject. Where applicable, the written Informed Consent form with respect to the infant is also signed and dated by the holder of parental rights as designated by the maternal subject • Woman is able and willing to comply with the study protocol, according to the judgment of the Investigator, in particular: 1] Woman is willing to breastfeed (either exclusively, or with formula supplementation) for at least 60 days after the first post-partum ocrelizumab infusion (this decision is to be taken prior to and independent from study participation) 2] Woman is willing to provide breastmilk samples before and after their first and, if applicable, second post-partum ocrelizumab infusion • Woman is between 18 and 40 years of age at screening • Woman has a diagnosis of MS or CIS (in line with the locally approved indications) • Woman has delivered a term singleton infant (>=37 weeks gestation) • Infant is between 2-24 weeks of life • For women who received commercial ocrelizumab (OCREVUS) before enrolment: documentation that last exposure ocrelizumab occurred more than 3 months before the last menstrual period (LMP) (i.e. excluded a potential fetal exposure) and was given at the approved dose of 2x300 mg or 1x600 mg • Woman agrees to use acceptable contraceptive methods during the study Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusions related to the mother • Woman received last dose of ocrelizumab 3 months prior to the LMP in the context of a study or registry sponsored by Roche Exclusions related to the infant • Infant is >24 weeks of life at the time of the mother’s first dose of ocrelizumab • Infant has any abnormality that may interfere with breastfeeding or milk absorption, including but not limited to cleft palate and/or lip, congenital diaphragmatic hernia and esophageal atresia • Infant has an active infection. Infant may be included once the infection resolves • Infant has at least one documented brief resolved unexplained event (BRUE), as defined by the 2016 Guidelines of the American Academy of Pediatrics Exclusions Related to Laboratory Findings • Mother with any abnormal screening laboratory value that is clinically relevant should 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 • Mother with positive screening tests for hepatitis B, determined by a positive hepatitis B surface antigen (HBsAg) result (current infection) or positive hepatitis B core antibody (HBcAb) titers (previous infection) will be excluded. Women with documented history of hepatitis B virus (HBV) vaccination or positive hepatitis B surface antibody (HBsAb) titers are eligible
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate whether infants of lactating women with CIS or MS receiving ocrelizumab post-partum present with B cell depletion • To evaluate the exposure to ocrelizumab in infants of lactating women with CIS or MS receiving ocrelizumab post-partum;Secondary Objective: • To evaluate B cell levels in infants of lactating women with CIS or MS receiving ocrelizumab post-partum • To evaluate transfer of ocrelizumab into breastmilk of lactating women with CIS or MS receiving ocrelizumab post-partum • To evaluate the maximum exposure to ocrelizumab in infants of lactating women with CIS or MS receiving ocrelizumab post-partum • To evaluate whether there is transfer of ocrelizumab from the mother to the infant via breastmilk • To evaluate whether infants of lactating women with CIS or MS receiving ocrelizumab post-partum are able to mount humoral immune responses to clinically relevant vaccines • To evaluate the safety of ocrelizumab in lactating women with CIS or MS receiving ocrelizumab post-partum and in their respective infants;Primary end point(s): 1. Proportion of infants with B cell levels (CD19+ cells, absolute counts in blood) below the lower limit of normal (LLN), measured 30 (±2) days after the mother’s first ocrelizumab post-partum infusion 2. Estimated average oral daily infant dosage (ADID), calculated as the ocrelizumab average milk concentration over 60 days multiplied by an estimated infant milk intake of 150 mL/kg/day;Timepoint(s) of evaluation of this end point: 1. At 30 days after the mother’s first ocrelizumab post-partum infusion 2. Over 60 days after the mother’s first ocrelizumab post-partum infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. 30 days after the mother’s first ocrelizumab post-partum infusion 2. For 1x600 mg: before infusion and at 24 hours (Day 1), 7 days, 30 days and 60 days post-infusion; For 2x300 mg: before infusion 1 and at 24 hours (Day 1), 7 days, 14 days, 15 days (24 hours after infusion 2), 21 days, 30 days and 60 days post-infusion 1 3-4. Over 60 days after the mother’s first ocrelizumab post-partum infusion 5. 30 days after the mother’s first ocrelizumab post-partum infusion 6-7. 1 month after the first dose of MMR vaccine or at month 13 in case MMR vaccine is not planned to be administered 8-9. Throughout the study and approximately until the infant’s month 13 of life;Secondary end point(s): 1. B cell levels (CD19+ cells, absolute counts and percentage of lymphocytes) measured 30 (±2) days after the mother’s first ocrelizumab post-partum infusion 2. Area under the milk concentration-time curve (AUC) of ocrelizumab in mature breastmilk (i.e. milk produced after day 14 post-partum) over 60 days after the first post-partum ocrelizumab infusion 3. Average and peak ocrelizumab milk concentration as well as time to reach peak milk concentration, measured over 60 days after the mother’s first postpartum ocrelizumab infusion 4. Estimated maximum oral daily infant dosage (MDID) calculated as the peak ocrelizumab milk concentration multiplied by an estimated infant milk intake of 150 mL/kg/day measured over 60 days after the mother’s first post-partum ocrelizumab infusion 5. Serum concentration of ocrelizumab in the infant measured 30 (±2) days after the mother’s first ocrelizumab post-partum infusion 6. Mean titers of antibody immune response(s) to vaccination against 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 7. Proportion of infants with positive humoral response (ser | — |
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