Clinical trial NCT04998851: A Study Evaluating B Cell Levels In Infants Of Lactating Women With CIS Or MS Receiving Ocrelizumab
Official title: A Phase IV Multicenter, Open-Label Study Evaluating B Cell Levels In Infants Of Lactating Women With CIS Or MS Receiving Ocrelizumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Clinically Isolated Syndrome
Keywords: ocrelizumab, OCREVUS, breastmilk transfer, breast milk transfer, lactation
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
name: Laboratory Corporation of America
name: Illingworth Research Group
First posted: 2021-08-10
Enrollment: 26
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Woman is between 18 and 40 years of age at screening
* Woman is willing to breastfeed 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)
* Woman is willing to provide breastmilk samples
* Woman has a diagnosis of MS or CIS (in line with the locally approved indications)
* Woman has delivered a healthy term singleton infant (≥37 weeks gestation)
* Infant is between 2-24 weeks of age at the time of the mother's first post-partum dose of ocrelizumab
* For women who received commercial ocrelizumab (OCREVUS) before enrolment: documentation that last exposure to ocrelizumab occurred more than 3 months before the last menstrual period (LMP) and was given at the approved dose of 2 x 300 mg or 1 x 600 mg
* Woman agrees to use acceptable contraceptive methods during the study

Exclusion Criteria related to the Mother:

* Hypersensitivity to ocrelizumab or to any of its excipients
* Received last dose of ocrelizumab \<3 months before the LMP or during pregnancy
* Active infections (may be included once the infection is treated and is resolved; women with bilateral mastitis infection should not have samples collected until the infection is completely resolved)
* Prior or current history of primary or secondary immunodeficiency, or woman in an otherwise severely immunocompromised state
* Known active malignancies, or being actively monitored for recurrence of malignancy
* History of breast implants, breast augmentation, breast reduction surgery or mastectomy
* Prior or current history of chronic alcohol abuse or drug abuse
* Positive screening tests for hepatitis B
* Treatment with a DMT for CIS or MS during pregnancy and/or first weeks post-partum, with the exception of formulations of interferon-beta, glatiramer acetate or pulsed corticosteroids
* Treatment with drugs known to transfer to the breastmilk and with established or potential deleterious effects for the infant
* Treatment with any investigational agent within 6 months or five half-lives of the investigational drug prior to the LMP

Exclusion Criteria related to the Infant:

* \>24 weeks of life at the time of the mother's first dose of ocrelizumab
* Any abnormality that may interfere with breastfeeding or milk absorption
* Active infection (may be included once the infection resolves)
* Infant has any other medical condition or abnormality that, in the opinion of the investigator, could compromise the infant's ability to participate in this study, including interference with the interpretation of study results
* At least one documented brief resolved unexplained event (BRUE), as defined by the 2016 Guidelines of the American Academy of Pediatrics

Primary outcomes:
measure: 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
timeFrame: At Day 30
measure: Estimated Average Oral Daily Infant Dosage (ADID)
timeFrame: Up to Day 60
Secondary outcomes:
measure: Absolute CD19+ B Cell Count in the Infant
timeFrame: At Day 30
measure: Percentage of CD19+ B Cell in the Infant
timeFrame: At Day 30
measure: Area Under the Milk Concentration-Time Curve (AUC) of Ocrelizumab in Mature Breastmilk
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
measure: Average Concentration of Ocrelizumab in Breastmilk (Cmean)
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
measure: Maximum Concentration (Cmax) of Ocrelizumab in Breastmilk
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
measure: Time of Maximum Concentration (Tmax) of Ocrelizumab in Breastmilk
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
measure: Estimated Maximum Oral Daily Infant Dosage (MDID)
timeFrame: Up to Day 60
measure: Average Relative Infant Dose (RID)
timeFrame: Up to Day 60
measure: Serum Concentration of Ocrelizumab in the Infant at Day 30
timeFrame: At Day 30
measure: Percentage of Mothers With of Adverse Events (AEs)
timeFrame: Up to 16 months
measure: Number of AEs in Infants
timeFrame: Up to 16 months
measure: Mean Titers of Antibody Immune Responses to Measles, Mumps, and Rubella (MMR) Vaccination
timeFrame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
measure: Percentage of Infants With Positive Humoral Response to MMR Vaccination
timeFrame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
measure: Mean Titers of Antibody Immune Responses to Diphtheria-Tetanus-Pertussis (DTP) Vaccine
timeFrame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
measure: Percentage of Infants With Positive Humoral Response to DTP Vaccine
timeFrame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
measure: Mean Titers of Antibody Immune Responses to Haemophilus Influenzae Type B (Hib) Vaccine
timeFrame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
measure: Percentage of Infants With Positive Humoral Response to Hib Vaccine
timeFrame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
measure: Mean Titers of Antibody Immune Responses to Hepatitis B Vaccine (HBV)
timeFrame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
measure: Percentage of Infants With Positive Humoral Response to HBV
timeFrame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
measure: Mean Titers of Antibody Immune Responses to 13-valent Pneumococcal Conjugate Vaccine (PCV-13)
timeFrame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
measure: Percentage of Infants With Positive Humoral Response to PCV-13
timeFrame: Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: University Of Colorado
state: Colorado
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Owosso
country: United States
facility: Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis
state: Michigan
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der TU Dresden
city: London
country: United Kingdom
facility: Queen Mary University of London
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: