A Study Evaluating B Cell Levels In Infants Potentially Exposed To Ocrelizumab During Pregnancy
- Conditions
- Clinically Isolated SyndromeMultiple Sclerosis
- Interventions
- Registration Number
- NCT04998812
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 70
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pregnant Women with CIS or MS Ocrelizumab Pregnant women with CIS or MS (in line with the locally approved indications) receiving commercial ocrelizumab up to 6 months before the LMP or during the first trimester of pregnancy (up to gestational week 13), due to accidental exposure, or in whom a decision to treat with ocrelizumab was taken as part of routine clinical practice.
- Primary Outcome Measures
Name Time Method Percentage of Infants With B Cell Levels (Cluster of Differentiation 19 [CD19+] Cells) Below the Lower Limit of Normal (LLN) At Week 6 of infant's life 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.
- Secondary Outcome Measures
Name Time Method Percentage of CD19+ B Cell in the Infant Potentially Exposed to Ocrelizumab During Pregnancy At Week 6 of infant's life Absolute CD19+ B Cell Count in the Infant Potentially Exposed to Ocrelizumab During Pregnancy At Week 6 of infant's life Serum Concentration of Ocrelizumab in the Umbilical Cord Blood at Birth Within 1 hour after delivery (at birth Day 1) 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.
Serum Concentration of Ocrelizumab in the Infant at Week 6 of Life At Week 6 of infant's 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.
Serum Concentration of Ocrelizumab in the Mother Baseline (gestational Weeks 24-30), gestational Week 35, and at delivery (within 24 hours after delivery) (at birth Day 1) 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.
Percentage of Infants With Adverse Events Up to 17 months 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.
Percentage of Mothers With Adverse Events Up to 17 months 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.
Infant Characteristics at Birth: Body Weight At birth (Day 1) Day 1 refers to the time an infant's birth.
Infant Characteristics at Birth: Head Circumference At birth (Day 1) Day 1 refers to the time an infant's birth.
Infant Characteristics at Birth: Body Length At birth (Day 1) Day 1 refers to the time an infant's birth.
Percentage of Pregnancies Resulting in Live Births, Therapeutic Abortions, or Stillbirth During pregnancy (anytime between 37 to 42 weeks of gestation) and at birth (at Day 1) Pregnancy outcomes analysed included live births (term and preterm, presence of congenital anomalies) and elective/therapeutic abortions and stillbirths.
Mean Titers of Antibody Immune Responses to Measles, Mumps, and Rubella (MMR) Vaccination Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13) The immune response to MMR vaccine will be 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 is not planned to be administered. This is to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines.
Percentage of Infants With Positive Humoral Response to MMR Vaccination Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13) Percentage of infants with positive humoral response (seroprotective titers as defined for the individual vaccine) will be presented for each immunoglobulin G (IgG) antibody titer. Seroprotective titer based on vaccine tests for MMR vaccine are as follows: Anti-Measles Vir IgG(-70)CL: ≥ 120 milli-international units/milliliter (mIU/mL); Anti-MumpsAT Vir iGG(-70)CL: ≥ 17 units per milliliters (U/mL); Anti-Rub Vir IgG(-70)RUOCL: ≥ 10 international units/milliliters (IU/mL).
Mean Titers of Antibody Immune Responses to Diphtheria-Tetanus-Pertussis (DTP) Vaccine Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13) The immune response to DTP vaccine will be 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 is not planned to be administered. This is to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines.
Percentage of Infants With Positive Humoral Response to DTP Vaccine Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13) Percentage of infants with positive humoral response (seroprotective titers as defined for the individual vaccine) will be presented for each IgG antibody titer. Seroprotective titer based on vaccine tests for DTP vaccine are as follows: Anti-Diphtheria IgG(-70)CL and Anti-Tetanus Toxoid IgG(-70)RUO: ≥ 0.01 IU/mL; Bordetella pertussis antibodies, IgG: \> 1.04 cut-off index (COI).
Mean Titers of Antibody Immune Responses to Haemophilus Influenzae Type B (Hib) Vaccine Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13) The immune response to Hib vaccine will be 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 is not planned to be administered. This is to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines.
Percentage of Infants With Positive Humoral Response to Hib Vaccine Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13) Percentage of infants with positive humoral response (seroprotective titers as defined for the individual vaccine) will be presented for each IgG antibody titer. Seroprotective titer based on vaccine tests for Hib vaccine are as follows: Hib, IgG: ≥ 0.15 µg/mL.
Mean Titers of Antibody Immune Responses to Hepatitis B Vaccine (HBV) Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13) The immune response to HBV vaccine will be 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 is not planned to be administered. This is to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines.
Percentage of Infants With Positive Humoral Response to HBV Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13) Percentage of infants with positive humoral response (seroprotective titers as defined for the individual vaccine) will be presented for each IgG antibody titer. Seroprotective titer based on vaccine tests for HBV vaccine are as follows: Anti-HBs: ≥ 10 mIU/mL.
Mean Titers of Antibody Immune Responses to 13-valent Pneumococcal Conjugate Vaccine (PCV-13) Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13) The immune response to PCV-13 vaccine will be 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 is not planned to be administered. This is to evaluate whether infants can mount humoral immune responses to clinically relevant vaccines.
Percentage of Infants With Positive Humoral Response to PCV-13 Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13) Percentage of infants with positive humoral response (seroprotective titers as defined for the individual vaccine) will be presented for each IgG antibody titer. Seroprotective titer based on vaccine tests for PCV-13 vaccine are as follows: 13 Valent anti-pneumococcal antibody panel: ≥ 0.35 µg/mL.
Trial Locations
- Locations (12)
Inselspital Bern
🇨🇭Bern, Switzerland
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Hosp. Clinico San Carlos
🇪🇸Madrid, Spain
University Of Colorado
🇺🇸Aurora, Colorado, United States
Hopital Pierre Wertheimer - Hopital Neurologique
🇫🇷Bron, France
Hôpital de la Pitié Salpétrière
🇫🇷Paris, France
St. Josef Hospital GmbH
🇩🇪Bochum, Germany
Universitätsspital Basel
🇨🇭Basel, Switzerland
University of California San Francisco
🇺🇸San Francisco, California, United States
Universitaetsklinikum Carl Gustav Carus an der TU Dresden
🇩🇪Dresden, Germany
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
MultipEL Studies - Institut für klinische Studien
🇩🇪Hamburg, Germany