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

Multiple Sclerosis Clinical Trial

— MINORE  

Official title:

A Phase IV Multicenter, Open-Label Study Evaluating B Cell Levels In Infants Potentially Exposed To Ocrelizumab During Pregnancy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04998812
• Other study ID #: MN42988
• Secondary ID: 2021-000062-14
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: April 13, 2022
• Est. completion date: April 21, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 44
• Est. completion date: April 21, 2025
• Est. primary completion date: April 8, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Clinically Isolated Syndrome
• Multiple Sclerosis

Intervention

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

Locations

Country	Name	City	State
France	Hopital Pierre Wertheimer - Hopital Neurologique	Bron
France	Hôpital de la Pitié Salpétrière	Paris
Germany	St. Josef Hospital GmbH	Bochum
Germany	Universitaetsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	MultipEL Studies - Institut für klinische Studien	Hamburg
Spain	Hosp. Clinico San Carlos	Madrid
Switzerland	Universitätsspital Basel	Basel
United States	University Of Colorado	Aurora	Colorado
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of California San Francisco	San Francisco	California

Sponsors (4)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Illingworth Research Group, Laboratory Corporation of America, PPD

Countries where clinical trial is conducted

United States,  France,  Germany,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of infants with B cell levels (CD19+ cells) below the lower limit of normal (LLN)		Week 6 of life
Secondary	B cell levels (CD19+ cells) in the infant		Week 6 of life
Secondary	Serum concentration of ocrelizumab in the umbilical cord blood at birth		Within 1 hour after delivery
Secondary	Serum concentration of ocrelizumab in the infant		Week 6 of life
Secondary	Serum concentration of ocrelizumab in the mother		During the second trimester (week 26), third trimester (week 36) and at delivery (within 24 hours after delivery)
Secondary	Rate and nature of adverse events in the infant		Baseline up to 17 months
Secondary	Rate and nature of adverse events in the mother		Baseline up to 17 months
Secondary	Infant characteristics at birth (body weight)		At birth
Secondary	Infant characteristics at birth (head circumference)		At birth
Secondary	Infant characteristics at birth (body length)		At birth
Secondary	Proportion of pregnancies resulting in live births, therapeutic abortions, or stillbirth		At birth
Secondary	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, or at Month 13 of age if the MMR vaccine is not planned to be administered
Secondary	Proportion of infants with positive humoral response to Measles, Mumps, and Rubella (MMR) Vaccination		Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered
Secondary	Mean titers of antibody immune responses to Diphtheria-Tetanus-Pertussis Vaccine		Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered
Secondary	Proportion of infants with positive humoral response to Diphtheria-Tetanus-Pertussis Vaccine		Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered
Secondary	Mean titers of antibody immune responses to Haemophilus influenzae type B Vaccine		Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered
Secondary	Proportion of infants with positive humoral response to Haemophilus influenzae type B Vaccine		Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered
Secondary	Mean titers of antibody immune responses to Hepatitis B Vaccine		Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered
Secondary	Proportion of infants with positive humoral response to Hepatitis B Vaccine		Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered
Secondary	Mean titers of antibody immune responses to Pneumococcal conjugate Vaccine		Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered
Secondary	Proportion of infants with positive humoral response to Pneumococcal conjugate Vaccine		Up to 1 month after the first or second dose of MMR vaccine, or at Month 13 of age if the MMR vaccine is not planned to be administered