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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04998851




Registration number
NCT04998851
Ethics application status
Date submitted
6/08/2021
Date registered
10/08/2021
Date last updated
26/10/2023

Titles & IDs
Public title
A Study Evaluating B Cell Levels In Infants Of Lactating Women With CIS Or MS Receiving Ocrelizumab
Scientific title
A Phase IV Multicenter, Open-Label Study Evaluating B Cell Levels In Infants Of Lactating Women With CIS Or MS Receiving Ocrelizumab
Secondary ID [1] 0 0
2021-000063-79
Secondary ID [2] 0 0
MN42989
Universal Trial Number (UTN)
Trial acronym
SOPRANINO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 0 0
Clinically Isolated Syndrome 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ocrelizumab

Experimental: Women with CIS or MS - Lactating women with CIS or MS (in line with the locally approved indications) who decided together with their treating physician to continue on, or start treatment with, OCREVUS (ocrelizumab) post-partum. Women resuming treatment with ocrelizumab post-partum will be included only if the last exposure to ocrelizumab occurred more than 3 months before the last menstrual period to exclude any interference between fetal exposure and exposure via lactation.


Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of infants with B cell levels (CD19+ cells) below the lower limit of normal (LLN)
Timepoint [1] 0 0
Day 30 after the mother's first post-partum ocrelizumab infusion
Primary outcome [2] 0 0
Estimated average oral daily infant dosage (ADID)
Timepoint [2] 0 0
Over 60 days after the mother's first post-partum ocrelizumab infusion
Secondary outcome [1] 0 0
B cell levels (CD19+ cells) in the infant
Timepoint [1] 0 0
Day 30 after the mother's first post-partum ocrelizumab infusion
Secondary outcome [2] 0 0
Area under the milk concentration-time curve (AUC) of ocrelizumab in mature breastmilk
Timepoint [2] 0 0
Over 60 days after the mother's first post-partum ocrelizumab infusion
Secondary outcome [3] 0 0
Average ocrelizumab milk concentration
Timepoint [3] 0 0
Over 60 days after the mother's first post-partum ocrelizumab infusion
Secondary outcome [4] 0 0
Peak ocrelizumab milk concentration
Timepoint [4] 0 0
Over 60 days after the mother's first post-partum ocrelizumab infusion
Secondary outcome [5] 0 0
Time to reach peak ocrelizumab milk concentration
Timepoint [5] 0 0
Over 60 days after the mother's first post-partum ocrelizumab infusion
Secondary outcome [6] 0 0
Estimated maximum oral daily infant dosage (MDID)
Timepoint [6] 0 0
Over 60 days after the mother's first post-partum ocrelizumab infusion
Secondary outcome [7] 0 0
Serum concentration of ocrelizumab in the infant
Timepoint [7] 0 0
Day 30 after the mother's first post-partum ocrelizumab infusion
Secondary outcome [8] 0 0
Mean titers of antibody immune responses to Mumps, Measles and Rubella vaccination
Timepoint [8] 0 0
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 outcome [9] 0 0
Proportion of infants with positive humoral response (seroprotective titers; as defined for the individual vaccine) to Measles, Mumps and Rubella vaccines
Timepoint [9] 0 0
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 outcome [10] 0 0
Mean titers of antibody immune responses to Diphtheria-Tetanus-Pertussis Vaccine
Timepoint [10] 0 0
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 outcome [11] 0 0
Proportion of infants with positive humoral response to Diphtheria-Tetanus-Pertussis Vaccine
Timepoint [11] 0 0
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 outcome [12] 0 0
Mean titers of antibody immune responses to Haemophilus influenzae type B Vaccine
Timepoint [12] 0 0
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 outcome [13] 0 0
Proportion of infants with positive humoral response to Haemophilus influenzae type B Vaccine
Timepoint [13] 0 0
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 outcome [14] 0 0
Mean titers of antibody immune responses to Hepatitis B Vaccine
Timepoint [14] 0 0
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 outcome [15] 0 0
Proportion of infants with positive humoral response to Hepatitis B Vaccine
Timepoint [15] 0 0
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 outcome [16] 0 0
Mean titers of antibody immune responses to Pneumococcal conjugate Vaccine
Timepoint [16] 0 0
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 outcome [17] 0 0
Proportion of infants with positive humoral response to Pneumococcal conjugate Vaccine
Timepoint [17] 0 0
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 outcome [18] 0 0
Rate and nature of adverse events in the infant
Timepoint [18] 0 0
Baseline up to 16 months
Secondary outcome [19] 0 0
Rate and nature of adverse events in the mother
Timepoint [19] 0 0
Baseline up to 16 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
40 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Other
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
14/10/2024
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
Germany
State/province [7] 0 0
Bochum
Country [8] 0 0
Germany
State/province [8] 0 0
Dresden
Country [9] 0 0
Spain
State/province [9] 0 0
Madrid
Country [10] 0 0
United Kingdom
State/province [10] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
PPD
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Laboratory Corporation of America
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Illingworth Research Group
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04998851
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: MN42989 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04998851