Evaluation of Ofatumumab Concentration in Breast Milk of Lactating Women with Relapsing Multiple Sclerosis Receiving Ofatumumab Therapy

The primary objective of this study is the **quantification** of ofatumumab concentration in the breast milk of lactating women with relapsing forms of multiple sclerosis (RMS) who have initiated or re-initiated ofatumumab treatment post-partum. This is clinically relevant as it provides critical information on the transfer of ofatumumab into breast milk, which is essential for understanding the potential exposure of breastfed infants to the medication.

Secondary objectives include:

• Evaluating other pharmacokinetic (PK) parameters of ofatumumab in breast milk and plasma of lactating women with RMS who have initiated or re-initiated ofatumumab treatment post-partum.
• Estimating the relative infant dose of ofatumumab.
• Evaluating safety data collected in lactating women receiving ofatumumab and their breastfed infants.

The clinical trial involves a total of **11 participants** who are exclusively **female** and have been diagnosed with **Relapsing forms of Multiple Sclerosis (RMS)**. The study population consists of lactating women who are at least 18 years of age and have delivered a term infant, defined as at least 37 weeks of gestation. Participants are required to be postpartum and plan to exclusively breastfeed, as the trial aims to quantify the concentration of ofatumumab in breast milk. The trial population was selected based on specific criteria, including the initiation or re-initiation of ofatumumab treatment between 2 to 24 weeks postpartum, in consultation with their treating physician. The study does not include male subjects and focuses on a vulnerable population, given the postpartum status of the participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is a **phase IV**, prospective, multicenter, open-label study designed to evaluate the concentration of **ofatumumab** in the breast milk of lactating women with relapsing forms of **multiple sclerosis** (RMS) who have initiated or re-initiated treatment with ofatumumab postpartum. The primary objective is to quantify the concentration of ofatumumab in breast milk at specific time points, including pre-dose on the day of the second or any subsequent maintenance dose, and at 7, 14, 21, and pre-dose 28 days after the second or any subsequent maintenance dose. Secondary endpoints include the proportion of participants with quantifiable ofatumumab concentrations in breast milk, maximum concentration (Cmax), area under the curve (AUC), milk/plasma (M/P) ratio, estimated relative infant dose (RID), and the rate and nature of adverse events in both mothers and breast-fed infants up to 12 months after treatment initiation or re-initiation.

The trial is expected to commence recruitment on May 15, 2024, and conclude by February 2, 2026. Participants will be involved in the study for a maximum of 12 months. The study includes several key visits: an inclusion (screening) visit to confirm eligibility, followed by regular follow-up visits to collect breast milk samples and monitor health outcomes, and an end-of-study visit to assess final outcomes and any adverse events. Participants must be postpartum, exclusively breastfeeding, and willing to provide breast milk samples. They must have delivered a term infant and plan to initiate or re-initiate treatment with ofatumumab between 2 to 24 weeks postpartum. The decision to treat with ofatumumab and to breastfeed must be made independently of the study.

Participants may be terminated early from the study if they withdraw consent, experience significant adverse events, or if the investigator deems it necessary for safety reasons. The study is not a low-intervention trial and does not involve a pediatric formulation. The investigational product, Kesimpta 20 mg solution for injection in a pre-filled syringe, is administered via subcutaneous use. The trial is conducted under the sponsorship of Novartis Ireland Limited, with the product authorized for use in Norway. The study is designed to provide critical data on the safety and pharmacokinetics of ofatumumab in lactating women, contributing to the understanding of its use in this specific population.

The clinical trial involves the administration of **ofatumumab**, marketed under the name Kesimpta, which is a **solution for injection** provided in a pre-filled syringe. The pharmaceutical form is specifically designed for **subcutaneous use**. Each syringe contains a dosage of 20 mg of ofatumumab. The maximum daily dose is set at 20 mg, with a total maximum dose of 300 mg over the course of the treatment. The treatment period is limited to a maximum of 12 months. The administration of the drug is facilitated by an autoinjector device, known as Delta-04, which is assembled with the pre-filled syringe to form a pre-filled pen intended for single use. This device does not possess a CE mark.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the quantification of ofatumumab concentration in the breast milk of lactating women with relapsing forms of multiple sclerosis who have initiated or re-initiated ofatumumab treatment post-partum. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

Efficacy in this clinical trial will be assessed by measuring the concentration of **ofatumumab** in breast milk of lactating women with relapsing forms of multiple sclerosis. The primary endpoint involves quantifying the concentration of ofatumumab at specific timepoints: pre-dose on the day of the second or any subsequent maintenance dose, and then at 7, 14, 21, and pre-dose 28 days after the second or any subsequent maintenance dose. Secondary endpoints include the proportion of participants with at least one sample showing quantifiable ofatumumab concentrations in breast milk, the maximum concentration (Cmax) of ofatumumab over 28 days, and the area under the curve (AUC) of ofatumumab in milk over the same period. Additional secondary endpoints are the milk/plasma (M/P) ratio of ofatumumab at 28 days, the estimated relative infant dose (RID, %) over 28 days, and the rate and nature of adverse events in mothers and serious adverse events or infections in breast-fed infants up to 12 months after treatment initiation or re-initiation. These parameters will be collected and analyzed to evaluate the efficacy of ofatumumab in the context of its concentration in breast milk and its potential effects on both mothers and infants.