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

Hoffmann-La Roche70 enrolled

Overview

This study will evaluate the potential placental transfer of ocrelizumab in pregnant 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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Multiple Sclerosis Clinically Isolated Syndrome

Interventions

OcrelizumabDRUG

Post-partum dosing and treatment duration are at the discretion of the physicians, in accordance with local clinical practice and local labelling.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 40 Years

Medical Language ↔ Plain English

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

Locations (11)

University of California San Francisco

San Francisco, California, United States

University Of Colorado

Aurora, Colorado, United States

The Ken and Ruth Davee department of Neurology

Chicago, Illinois, United States

Outcomes

Primary Outcomes

Percentage of Infants With B Cell Levels (Cluster of Differentiation 19 [CD19+] Cells) Below the Lower Limit of Normal (LLN)

The event rate (percentage of infants with B cell levels below LLN) and corresponding Clopper Pearson 95% CI were reported. B-cell reference ranges by week of life (absolute counts) are defined by Borriello et al. 2022.

Time frame: At Week 6 of infant's life

Secondary Outcomes

Absolute CD19+ B Cell Count in the Infant Potentially Exposed to Ocrelizumab During Pregnancy

Time frame: At Week 6 of infant's life

Percentage of CD19+ B Cell in the Infant Potentially Exposed to Ocrelizumab During Pregnancy

Time frame: At Week 6 of infant's life

Serum Concentration of Ocrelizumab in the Umbilical Cord Blood at Birth

Serum ocrelizumab concentrations were measured in the umbilical cord blood at birth (within 1 hour after delivery) to evaluate whether there was placental transfer of ocrelizumab from the mother to the infant. At delivery, blood samples from the umbilical cord were collected. Ocrelizumab serum concentration below the lower limit of quantification (LLOQ = 156 ng/ml) was set to zero.

Time frame: Within 1 hour after delivery (at birth, Day 1)

Serum Concentration of Ocrelizumab in the Infant at Week 6 of Life

Serum ocrelizumab concentrations were measured were measured at 6 weeks of the infants life to evaluate whether there was placental transfer of ocrelizumab from the mother to the infant. Serum samples from the infant were collected.

Time frame: At Week 6 of infant's life

Serum Concentration of Ocrelizumab in the Mother

Serum concentration of ocrelizumab in the mother during pregnancy (time frame of blood sampling: Week 24-30, Week 35) and at delivery (time frame of blood sampling: within 24 hours after delivery). Ocrelizumab serum concentration below the lower limit of quantification (LLOQ = 156 ng/ml) was set to zero.

Data from ClinicalTrials.gov

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Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Hopital Pierre Wertheimer - Hopital Neurologique

Bron, France

Hôpital de la Pitié Salpétrière

Paris, France

St. Josef Hospital GmbH

Bochum, Germany

MultipEL Studies - Institut für klinische Studien

Hamburg, Germany

Hosp. Clinico San Carlos

Madrid, Spain

Universitätsspital Basel

Basel, Switzerland

...and 1 more locations

Time frame: Baseline (gestational Weeks 24-30), gestational Week 35, and at delivery (within 24 hours after delivery) (at birth, Day 1)

Percentage of Infants With Adverse Events

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. Percentages have been rounded off.

Time frame: Up to approximately 71 weeks

Percentage of Mothers With Adverse Events

Time frame: Up to approximately 87.6 weeks

Infant Characteristics at Birth: Body Weight

Day 1 refers to the time an infant's birth.

Time frame: At birth (Day 1)

Infant Characteristics at Birth: Head Circumference

Day 1 refers to the time an infant's birth.

Time frame: At birth (Day 1)

Infant Characteristics at Birth: Body Length

Day 1 refers to the time an infant's birth.

Time frame: At birth (Day 1)

Percentage of Pregnancies Resulting in Live Births, Therapeutic Abortions, or Stillbirth

Pregnancy outcomes analysed included live births (term and preterm, presence of congenital anomalies) and elective/therapeutic abortions and stillbirths.

Time frame: During pregnancy (anytime between 37 to 42 weeks of gestation) and at birth (at Day 1)

Mean Titers of Measles, Immunoglobin G (IgG) Antibody in Response to MMR Vaccination

The immune response to MMR vaccination 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. mIU/mL=milli-international units per milliliter.