A Study to Evaluate B Cell Levels in Infants Potentially Exposed to Ocrelizumab During Pregnancy - The MINORE Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

10 Nov 2021 → 14 Jul 2025

Decision date (initial)

2024-04-26

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2024-510974-25-00

EudraCT number

2021-000062-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Safety

To evaluate whether infants potentially exposed to ocrelizumab during pregnancy present with postpartum B-cell depletion

Secondary objectives 6

1. To evaluate B cell levels in infants potentially exposed to ocrelizumab during pregnancy
2. To evaluate whether there is placental transfer of ocrelizumab from the mother to the infant
3. To evaluate whether infants potentially exposed to ocrelizumab during pregnancy are able to mount humoral immune responses to clinically relevant vaccines
4. To evaluate the levels of ocrelizumab in the mother during pregnancy
5. To evaluate the safety of ocrelizumab in the mother, and the safety of infants potentially exposed to ocrelizumab
6. To evaluate pregnancy and neonatal outcomes

Conditions and MedDRA coding

Multiple Sclerosis (MS) or Clinically Isolated Syndrome (CIS) [in line with the locally approved indications]

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age 18−40 years, inclusive, at screening.
2. Have a diagnosis of MS or CIS (in line with the locally approved indications)
3. Currently pregnant with singleton pregnancy at gestational week ≤ 30 at enrolment
4. Documentation that first (12-week) and second (18 to 20-week) obstetric ultrasound (prenatal screening) has been conducted before enrolment
5. 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 (up to gestational week 13 inclusive)

Exclusion criteria 6

1. Last exposure to ocrelizumab >6 months before the woman’s LMP or later than the first trimester (i.e., after gestational week 13)
2. Gestational age at enrolment >30 weeks
3. Non-singleton pregnancy
4. Received last dose of ocrelizumab at a different posology other than per the local prescribing information
5. Social circumstances, that may preclude a woman from participating in the study
6. Additional exclusions related to obstetric and gynecological health, general health, laboratory findings, and medications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Proportion of infants with B-cell levels (CD19+ cells, absolute counts) below the lower limit of normal (LLN), measured at week 6 of life

Secondary endpoints 10

1. 1. B-cell levels (CD19+ cells, absolute counts and percentage of lymphocytes) measured at week 6 of life
2. 2. Serum concentration of ocrelizumab in the umbilical cord blood at birth
3. 3. Serum concentration of ocrelizumab in the infant at week 6 of life
4. 4. Mean titers of antibody immune response(s) to vaccination to common childhood vaccinations with full or partial doses given prior to 1 year, which include responses to diphtheria, tetanus, pertussis, Hib, PCV-13, MMR, and HBV
5. 5. Proportion of infants with positive humoral response (seroprotective titers; as defined for the individual vaccine) to vaccines
6. 6. 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)
7. 7. Rate and nature of adverse events (AEs) in the mother throughout the study, including changes in clinical and laboratory results
8. 8.Rate and nature of AEs in the infant throughout the study, including infections and hospitalizations
9. 9. Proportion of pregnancies resulting in live births (term and preterm, with and without congenital anomalies), therapeutic abortions, or stillbirths
10. 10. Infant characteristics at birth, including but not limited to body weight, head circumference and length

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 4

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications