A Study Evaluating B Cell Levels In Infants Of Lactating Women With CIS Or MS Receiving Ocrelizumab

Multiple Sclerosis Clinical Trial

— SOPRANINO  

Official title:

A Phase IV Multicenter, Open-Label Study Evaluating B Cell Levels In Infants Of Lactating Women With CIS Or MS Receiving Ocrelizumab

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04998851
• Other study ID #: MN42989
• Secondary ID: 2021-000063-79
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: September 16, 2021
• Est. completion date: February 26, 2025

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: February 26, 2025
• Est. primary completion date: March 29, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Clinically Isolated Syndrome
• Multiple Sclerosis

Intervention

Drug:
• Ocrelizumab
Women will receive the ocrelizumab dose regimen as per the locally-approved label. The ocrelizumab dose will be administered as an initial split dose of two 300 mg infusions separated by 14 days or a single 600 mg infusion according to the local prescribing information.

Locations

Country	Name	City	State
Germany	St. Josef Hospital GmbH	Bochum
Germany	Universitaetsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Spain	Hosp. Clinico San Carlos	Madrid
United Kingdom	Queen Mary University of London	London
United States	University Of Colorado	Aurora	Colorado
United States	Brigham and Womens Hospital	Boston	Massachusetts
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis	Owosso	Michigan
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,  Germany,  Spain,  United Kingdom, 

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)		Day 30 after the mother's first post-partum ocrelizumab infusion
Primary	Estimated average oral daily infant dosage (ADID)		Over 60 days after the mother's first post-partum ocrelizumab infusion
Secondary	B cell levels (CD19+ cells) in the infant		Day 30 after the mother's first post-partum ocrelizumab infusion
Secondary	Area under the milk concentration-time curve (AUC) of ocrelizumab in mature breastmilk		Over 60 days after the mother's first post-partum ocrelizumab infusion
Secondary	Average ocrelizumab milk concentration		Over 60 days after the mother's first post-partum ocrelizumab infusion
Secondary	Peak ocrelizumab milk concentration		Over 60 days after the mother's first post-partum ocrelizumab infusion
Secondary	Time to reach peak ocrelizumab milk concentration		Over 60 days after the mother's first post-partum ocrelizumab infusion
Secondary	Estimated maximum oral daily infant dosage (MDID)		Over 60 days after the mother's first post-partum ocrelizumab infusion
Secondary	Serum concentration of ocrelizumab in the infant		Day 30 after the mother's first post-partum ocrelizumab infusion
Secondary	Mean titers of antibody immune responses to Mumps, Measles and Rubella vaccination		1 month after the first or second dose of measles, mumps, and rubella (MMR) vaccine, or at Month 13, in case MMR vaccine is not planned to be administered
Secondary	Proportion of infants with positive humoral response (seroprotective titers; as defined for the individual vaccine) to Measles, Mumps and Rubella vaccines		1 month after the first or second dose of measles, mumps, and rubella (MMR) vaccine, or at Month 13, in case MMR vaccine is not planned to be administered
Secondary	Mean titers of antibody immune responses to Diphtheria-Tetanus-Pertussis Vaccine		1 month after the first or second dose of measles, mumps, and rubella (MMR) vaccine, or at Month 13, in case MMR vaccine is not planned to be administered
Secondary	Proportion of infants with positive humoral response to Diphtheria-Tetanus-Pertussis Vaccine		1 month after the first or second dose of measles, mumps, and rubella (MMR) vaccine, or at Month 13, in case MMR vaccine is not planned to be administered
Secondary	Mean titers of antibody immune responses to Haemophilus influenzae type B Vaccine		1 month after the first or second dose of measles, mumps, and rubella (MMR) vaccine, or at Month 13, in case MMR vaccine is not planned to be administered
Secondary	Proportion of infants with positive humoral response to Haemophilus influenzae type B Vaccine		1 month after the first or second dose of measles, mumps, and rubella (MMR) vaccine, or at Month 13, in case MMR vaccine is not planned to be administered
Secondary	Mean titers of antibody immune responses to Hepatitis B Vaccine		1 month after the first or second dose of measles, mumps, and rubella (MMR) vaccine, or at Month 13, in case MMR vaccine is not planned to be administered
Secondary	Proportion of infants with positive humoral response to Hepatitis B Vaccine		1 month after the first or second dose of measles, mumps, and rubella (MMR) vaccine, or at Month 13, in case MMR vaccine is not planned to be administered
Secondary	Mean titers of antibody immune responses to Pneumococcal conjugate Vaccine		1 month after the first or second dose of measles, mumps, and rubella (MMR) vaccine, or at Month 13, in case MMR vaccine is not planned to be administered
Secondary	Proportion of infants with positive humoral response to Pneumococcal conjugate Vaccine		1 month after the first or second dose of measles, mumps, and rubella (MMR) vaccine, or at Month 13, in case MMR vaccine is not planned to be administered
Secondary	Rate and nature of adverse events in the infant		Baseline up to 16 months
Secondary	Rate and nature of adverse events in the mother		Baseline up to 16 months