Efficacy Assessment of Ublituximab in Combination with Cetirizine, Dexamethasone, Paracetamol, Methylprednisolone, and Diphenhydramine in Relapsing Multiple Sclerosis

The primary objective of this study is to assess the **efficacy** of a modified regimen of ublituximab in patients with **relapsing multiple sclerosis**, as measured by the presence of T1 Gd-enhancing lesions. This is clinically relevant as T1 Gd-enhancing lesions are indicative of active inflammation and disease activity in multiple sclerosis, and their reduction could signify a decrease in disease progression and activity.

Secondary objectives include:

• Assessing the proportion of participants free of T1 Gd-enhancing lesions, which provides additional insight into the treatment's impact on disease activity.
• Evaluating the tolerability of ublituximab infusions, which is crucial for understanding the safety profile and patient compliance with the treatment regimen.
• Assessing treatment satisfaction in participants treated with ublituximab, which can influence adherence and overall treatment success.

The clinical trial involves a total of **150 participants** diagnosed with **relapsing 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 multiple sclerosis according to the 2017 Revised McDonald criteria, and an Expanded Disability Status Scale (EDSS) score of 5.5 or less at screening. The trial includes individuals who are either treatment-naïve or have previously discontinued a disease-modifying therapy, provided they meet the necessary washout requirements. Participants are required to be neurologically stable prior to the first dose of ublituximab. Female participants of childbearing potential must agree to use a medically acceptable method of contraception throughout the study and for a specified period after the last dose. The trial population also includes vulnerable groups, ensuring a comprehensive assessment of the treatment's efficacy across diverse demographics. Lifestyle factors such as diet and physical activity are not specified, but participants must have IgG and absolute lymphocyte counts at required levels during screening.

The clinical trial is designed to evaluate the efficacy of a modified regimen of **ublituximab** in patients with **relapsing multiple sclerosis**. This study is a phase 3b, randomized, double-blind, controlled trial. The trial is expected to commence recruitment on February 20, 2025, and conclude by November 25, 2026. The primary objective is to assess the efficacy of ublituximab by measuring the proportion of participants with no change or reduction in the number of T1 Gd-enhancing lesions from baseline to Week 48. Secondary endpoints include the proportion of participants free of T1 Gd-enhancing lesions at Week 48, the incidence of infusion-related reactions (IRRs), Treatment Satisfaction Questionnaire for Medication (TSQM-9) scores at Weeks 24 and 48, and the pharmacokinetics of ublituximab.

Participants will be involved in the study for a maximum of 48 weeks. 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 EDSS score of ≤ 5.5. Participants must be neurologically stable and meet specific laboratory criteria. Following the screening, participants will undergo regular follow-up visits to monitor efficacy and safety, with assessments at Weeks 24 and 48. The end-of-study visit will occur at Week 48, where final evaluations will be conducted.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for the participant's safety. The trial will utilize a double-blind design to ensure unbiased results, with neither participants nor investigators aware of the treatment assignments. The study will employ a controlled methodology, with a placebo or standard treatment group for comparison. The trial will adhere to rigorous scientific standards to ensure the validity and reliability of the findings.

The clinical trial involves the administration of several **experimental medications** and auxiliary treatments. **Ublituximab** is the primary investigational product, administered as a **concentrate for solution for infusion**. It is a recombinant chimeric monoclonal antibody against CD20, with a maximum daily dose of 600 mg and a total dose of 1050 mg over a treatment period of 48 weeks. The route of administration is **intravenous infusion**. This product is identified by the sponsor product code TG-1101 and is not a pediatric formulation.

**Cetirizine** is used as an auxiliary treatment in the form of a **tablet**. It is administered **orally** with a maximum daily dose of 10 mg and a total dose of 20 mg over a 24-week period. This medication is of chemical origin and is not a pediatric formulation.

**Dexamethasone** is another auxiliary treatment, also in **tablet** form, administered **orally**. The maximum daily dose is 20 mg, with a total dose of 40 mg over 24 weeks. It is of chemical origin and not formulated for pediatric use.

**Paracetamol** is provided as a **tablet** for **oral** administration. The maximum daily dose is 500 mg, with a total dose of 1000 mg over a 24-week period. This medication is of chemical origin and is not a pediatric formulation.

**Methylprednisolone** is administered as a **solution for injection**. The maximum daily dose is 125 mg, with a total dose of 250 mg over 24 weeks. It is of chemical origin and not formulated for pediatric use.

**Diphenhydramine** is used in **tablet** form for **oral** administration. The maximum daily dose is 50 mg, with a total dose of 100 mg over a 24-week period. This medication is of chemical origin and is not a pediatric formulation.

**Gadobutrol** is administered as a **solution for injection**. The maximum daily dose is 0.1 mmol/kg, with a total dose of 0.1 mmol/kg over a 48-week period. It is of chemical origin and not formulated for pediatric use.

All medications are monitored for participant compliance, and dosing schedules are adhered to as per the trial protocol. The trial aims to evaluate the efficacy of the modified regimen of ublituximab, with auxiliary treatments provided to manage symptoms and support the primary investigational product.

The efficacy of the clinical trial evaluating a modified regimen of **ublituximab** will be assessed through several primary and secondary endpoints. The primary endpoint is the proportion of participants with no change or reduction in the number of T1 Gd-enhancing lesions from baseline to Week 48. Secondary endpoints include the proportion of participants free of T1 Gd-enhancing lesions at Week 48, the proportion of participants experiencing infusion-related reactions (IRRs) as reported by the investigator, and Treatment Satisfaction Questionnaire for Medication (TSQM-9) scores at Week 24 and Week 48. Additionally, the pharmacokinetics of **ublituximab** will be evaluated.

Measurements will be collected at specified timepoints, including baseline, Week 24, and Week 48, to ensure comprehensive assessment of the treatment's efficacy. The use of validated scales and patient-reported outcomes will be integral to the evaluation process. The trial is designed to provide robust data on the efficacy of **ublituximab** in reducing T1 Gd-enhancing lesions, which are indicative of disease activity in patients with relapsing forms of multiple sclerosis (RMS).