Evaluation of Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous vs. Intravenous Ublituximab in Relapsing Multiple Sclerosis

The primary objective of this study is to estimate the geometric mean ratio of the **area under the curve (AUC)** of **ublituximab** when administered subcutaneously compared to intravenous (IV) administration in patients with relapsing forms of **Multiple Sclerosis**. This objective is clinically relevant as it aims to determine the pharmacokinetic equivalence of the subcutaneous formulation to the established IV formulation, potentially offering a more convenient administration route for patients.

Secondary objectives include:

• To assess the pharmacokinetics (PK) of subcutaneous ublituximab.
• To assess the pharmacodynamics (PD) of subcutaneous ublituximab.
• To evaluate the safety profile of subcutaneous ublituximab.
• To assess the radiological effects of subcutaneous ublituximab.

These secondary objectives are crucial for understanding the overall therapeutic profile of subcutaneous ublituximab, including its absorption, distribution, metabolism, and excretion, as well as its biological effects and safety in the target population.

The clinical trial involves a total of **276 participants** diagnosed with **relapsing forms of Multiple Sclerosis**. The study population includes both male and female subjects, aged between **18 and 65 years**. Participants were selected based on specific criteria, including a diagnosis of relapsing forms of Multiple Sclerosis and an Expanded Disability Status Scale (EDSS) score of 5.5 or less at screening. The trial population is characterized by a diverse range of individuals, with no specific lifestyle considerations such as diet or physical activity being highlighted. The study does include a vulnerable population, indicating a careful selection process to ensure the safety and efficacy of the trial outcomes. Female participants of childbearing potential are required to use a highly effective method of contraception during the study period. The trial aims to estimate the geometric mean ratio of the area under the curve (AUC) of ublituximab when administered subcutaneously compared to intravenous administration.

The clinical trial is a **Phase 3**, non-inferiority, randomized, open-label, parallel group, multicenter study designed to evaluate the pharmacokinetics, pharmacodynamics, safety, radiological, and clinical effects of subcutaneous versus intravenous administration of **ublituximab** in patients with relapsing forms of **multiple sclerosis**. The primary objective is to estimate the geometric mean ratio of the area under the curve (AUC) of ublituximab when administered subcutaneously compared to intravenous administration. The trial is expected to commence recruitment on September 8, 2025, and conclude by March 28, 2028.

Participants will be involved in the study for a maximum treatment period of one year. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age (18-65 years), diagnosis of relapsing multiple sclerosis, and an Expanded Disability Status Scale (EDSS) score of ≤ 5.5. Female participants of childbearing potential must agree to use a highly effective method of contraception. Follow-up visits will be scheduled to monitor the pharmacokinetics, pharmacodynamics, and safety of the treatment, as well as to assess any treatment-emergent adverse events. The end-of-study visit will evaluate the overall outcomes and any long-term effects of the treatment.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The study will also monitor secondary endpoints, including the proportion of participants with CD19+ B-cell levels and the incidence of treatment-emergent adverse events. The trial is not classified as a low-intervention study, and it is not designated as an orphan drug trial. The pharmaceutical forms involved include a solution for infusion and a concentrate for solution for infusion, with administration routes being subcutaneous and intravenous, respectively.

The clinical trial involves the administration of **Ublituximab**, a monoclonal antibody, in two different formulations to evaluate its pharmacokinetics, pharmacodynamics, safety, radiological, and clinical effects in patients with **Multiple Sclerosis**. The experimental medication, Ublituximab, is provided in a **solution for infusion** form. This formulation is administered subcutaneously. The dosing schedule and frequency of administration are determined based on the study protocol, with compliance monitored throughout the trial. The pharmaceutical form is a solution for infusion, and the active substance is derived from a protein of other origin. The sponsor product code for this formulation is TG-1101, and it is not a pediatric formulation.

The comparator treatment in the study is also Ublituximab, but in a different pharmaceutical form, a **concentrate for solution for infusion**. This formulation is administered via intravenous administration. The dosing unit is in milligrams, and the administration schedule is aligned with the study's protocol to ensure accurate comparison with the subcutaneous form. The active substance remains the same, with the same origin and characteristics as the experimental formulation. The sponsor product code for this comparator is also TG-1101, and it is similarly not a pediatric formulation. Both formulations are provided by TG Therapeutics, Inc., and are authorized for use in the trial.

The efficacy of the clinical trial will be assessed by evaluating the pharmacokinetics and pharmacodynamics of **ublituximab** when administered subcutaneously compared to intravenous administration in patients with Multiple Sclerosis. The primary objective is to estimate the geometric mean ratio of the area under the curve (AUC) of **ublituximab** for the two administration routes. Secondary endpoints include the proportion of participants with CD19+ B-cell levels and the incidence of treatment-emergent adverse events (TEAEs). These parameters will be measured and collected at specified timepoints throughout the study duration. The trial is designed as a Phase 3, non-inferiority, randomized, open-label, parallel-group, multicenter study. The study will involve the use of validated laboratory tests and clinical assessments to ensure accurate and reliable data collection. The trial is expected to start recruitment in September 2025 and conclude by March 2028.