Clinical trial NCT04998812: A Study Evaluating B Cell Levels In Infants Potentially Exposed To Ocrelizumab During Pregnancy
Official title: A Phase IV Multicenter, Open-Label Study Evaluating B Cell Levels In Infants Potentially Exposed To Ocrelizumab During Pregnancy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Multiple Sclerosis
Clinically Isolated Syndrome
Keywords: ocrelizumab, OCREVUS, placental transfer, pregnancy
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: 70
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 35 pregnant women with singleton pregnancy were enrolled in the study (70 participants in total, including the infants).
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Infants With B Cell Levels (Cluster of Differentiation 19 [CD19+] Cells) Below the Lower Limit of Normal (LLN)
timeFrame: At Week 6 of infant's life
Secondary outcomes:
measure: Absolute CD19+ B Cell Count in the Infant Potentially Exposed to Ocrelizumab During Pregnancy
timeFrame: At Week 6 of infant's life
measure: Percentage of CD19+ B Cell in the Infant Potentially Exposed to Ocrelizumab During Pregnancy
timeFrame: At Week 6 of infant's life
measure: Serum Concentration of Ocrelizumab in the Umbilical Cord Blood at Birth
timeFrame: Within 1 hour after delivery (at birth Day 1)
measure: Serum Concentration of Ocrelizumab in the Infant at Week 6 of Life
timeFrame: At Week 6 of infant's life
measure: Serum Concentration of Ocrelizumab in the Mother
timeFrame: Baseline (gestational Weeks 24-30), gestational Week 35, and at delivery (within 24 hours after delivery) (at birth Day 1)
measure: Percentage of Infants With Adverse Events
timeFrame: Up to 17 months
measure: Percentage of Mothers With Adverse Events
timeFrame: Up to 17 months
measure: Infant Characteristics at Birth: Body Weight
timeFrame: At birth (Day 1)
measure: Infant Characteristics at Birth: Head Circumference
timeFrame: At birth (Day 1)
measure: Infant Characteristics at Birth: Body Length
timeFrame: At birth (Day 1)
measure: Percentage of Pregnancies Resulting in Live Births, Therapeutic Abortions, or Stillbirth
timeFrame: During pregnancy (anytime between 37 to 42 weeks of gestation) and at birth (at Day 1)
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: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Bron
country: France
facility: Hopital Pierre Wertheimer - Hopital Neurologique
city: Paris
country: France
facility: Hôpital de la Pitié Salpétrière
city: Bochum
country: Germany
facility: St. Josef Hospital GmbH
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der TU Dresden
city: Hamburg
country: Germany
facility: MultipEL Studies - Institut für klinische Studien
city: Madrid
country: Spain
facility: Hosp. Clinico San Carlos
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Bern
country: Switzerland
facility: Inselspital Bern
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: