Concentration of ofatumumab in the breast milk of lactating women with relapsing forms of multiple sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

10 Dec 2024 → ongoing

Decision date (initial)

2024-06-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

Quantification of ofatumumab concentration in breast milk of lactating women with RMS who have initiated or re-initiated ofatumumab treatment post-partum

Secondary objectives 3

1. Evaluate other PK parameters of ofatumumab in breast milk and plasma of lactating women with RMS who have initiated or re-initiated ofatumumab treatment post-partum
2. Estimation of relative infant dose of ofatumumab
3. Evaluate safety data collected in lactating women receiving ofatumumab and their breastfed infants.

Conditions and MedDRA coding

Relapsing forms of Multiple Sclerosis (RMS)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Written informed consent must be obtained before any study assessment is performed.
2. 2. Participant is female with a relapsing form of MS and at least 18 years of age at the time of providing consent.
3. 3. Participant must be postpartum at the time of enrollment, plan to be exclusively breastfeeding and willing to provide breast milk samples.
4. 4. Participant has delivered term infant (at least 37 weeks gestation).
5. 5. Participant must plan to initiate or re-initiate or have initiated or re-initiated treatment with ofatumumab between 2 to 24 weeks postpartum. The decision to be treated with ofatumumab and to breastfeed is made in accordance with the treating physician and must be completely independent of the decision to participate in this study.

Exclusion criteria 14

1. 1. Use of any investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline, whichever is longer.
2. 10. Prior or current history of primary or secondary immunodeficiency, or participant in an otherwise severely immunocompromised state.
3. 2. Participant taking medications prohibited by the protocol (see Section 6.6.2) at screening.
4. 3. Pregnant woman, confirmed by positive serum pregnancy test during screening.
5. 4. Females of childbearing potential should use effective contraception as per local label.
6. 5. Participant has history of chronic alcohol abuse or drug abuse in the last year.
7. 6. Participant has any medical, obstetrical, psychiatric or other medical condition that, in the opinion of the Investigator, can jeopardize or would compromise the subject’s ability to participate in this study or confound the study assessment.
8. 7. Participant has history of breast implants, breast augmentation, or breast reduction surgery.
9. 8. Participant has received anti-CD20 agents during the second and third trimesters of pregnancy.
10. 9. Active infections, including mastitis (participant may be included once the infection is resolved).
11. 11. Participant with active hepatitis B disease prior to the initiation or re-initiation of ofatumumab. (Participant with positive hepatitis B serology should consult a liver disease expert before the start of treatment and should be monitored and managed following local medical standards to prevent hepatitis B reactivation.)
12. 12. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
13. 13. Any contraindication as per local label.
14. 14. Participant who has an infant with any abnormality that may interfere with breastfeeding or confound the study assessment in the opinion of the Investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The concentration of ofatumumab in breast milk at the following timepoints: (pre-dose) on the day of the second (or any subsequent) maintenance dose, then 7, 14, 21 and (pre-dose) 28 days after the second (or any subsequent) maintenance dose.

Secondary endpoints 7

1. Proportion of participants with at least 1 sample with quantifiable ofatumumab concentrations in breast milk
2. Maximum concentration (Cmax) of ofatumumab in breast milk over 28 days after the second (or any subsequent) maintenance dose.
3. The exposure (area under the curve (AUC) of ofatumumab in milk over 28 days (from the second or any subsequent maintenance dose to the next maintenance dose after initiation or re-initiation of ofatumumab post-partum)
4. Milk/Plasma (M/P) ratio of ofatumumab at 28 days after the second or any subsequent maintenance dose.
5. Estimated relative infant dose (RID, %) over 28 days after the lactating mother receives second or subsequent maintenance dose
6. Rate and nature of adverse events in the mothers treated with ofatumumab up to 12 months after ofatumumab treatment initiation/re-initiation
7. Rate and nature of serious adverse events and any infections in the breast-fed infants of mothers up to 12 months after ofatumumab treatment initiation/re-initiation

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 8

Locations

4 EU/EEA countries · 16 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

Documents 41 files

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

Application history

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