A Phase 3 Non-inferiority Study Comparing Subcutaneous versus Intravenous Administration of Frexalimab in Adults with Multiple Sclerosis

The primary objective of this study is to determine the non-inferiority of subcutaneous administration of frexalimab compared to intravenous administration based on pharmacokinetic parameters in adults with multiple sclerosis. 6, 8

Secondary objectives include:

• Characterization of the pharmacokinetics for both subcutaneous and intravenous routes. 6
• Evaluation of safety and tolerability. 4
• Assessment of efficacy regarding disease activity through magnetic resonance imaging and clinical endpoints. 5
• Safety evaluation of the investigational device injector. 4
• Assessment of administration route preference.
• Evaluation of long-term safety and tolerability for subcutaneous administration. 4

This study involves a total of 146 participants diagnosed with multiple sclerosis. The population consists of both male and female patients categorized into two distinct groups. The first group includes individuals with relapsing remitting multiple sclerosis aged 18 to 55 years, who meet specific relapse history or magnetic resonance imaging criteria and possess an Expanded Disability Status Scale score of ≤5.5. The second group comprises patients with non-relapsing secondary progressive multiple sclerosis aged 18 to 60 years, characterized by an EDSS score between 3.0 and 6.5, documented disability progression within the preceding 12 months, and an absence of clinical relapses for at least 24 months. All participants must adhere to local regulations regarding contraception.

This Phase 3, randomized, open-label study is designed to evaluate the pharmacokinetics, safety, and efficacy of subcutaneous administration of frexalimab compared to intravenous administration in adults with multiple sclerosis. The research methodology includes a non-inferiority assessment in Part A, focusing on trough concentration at steady state and the area under the curve through week 24. The study involves a screening visit to assess eligibility based on age, diagnosis, and Expanded Disability Status Scale scores. Following screening, participants undergo scheduled follow-up visits to monitor adverse events, plasma concentrations, and gadolinium-enhancing T1 lesions. The overall study period extends through week 96, with additional annual assessments for certain parameters. Participant involvement is expected to continue until the end-of-study visit, although conditions may lead to early termination from the study.

The experimental medication is frexalimab, provided as a solution for injection. The study evaluates the administration of a 1800 mg dose via subcutaneous or intravenous routes.

Efficacy and pharmacokinetic assessments in participants with multiple sclerosis include several parameters. Primary endpoints for the non-inferiority assessment consist of the area under the curve over the interval from week 20 to week 24 and the trough concentration at steady state through week 24.

Secondary efficacy and pharmacokinetic parameters involve the following:

• Frexalimab plasma concentrations, Cmax, and Tmax measured until week 24.
• The total number of gadolinium-enhancing T1 lesions evaluated at week 12, week 24, week 48, and week 96, with subsequent yearly assessments.
• The time to onset of confirmed disability progression confirmed over 3 months, monitored until week 96.
• The percentage of participants preferring subcutaneous administration over intravenous administration, assessed via items 13 and 14 of the Patient Experience Survey Questionnaire at week 48 for those transitioning from intravenous to subcutaneous administration.