Evaluation of Personalized Extended Interval Dosing of Natalizumab in Patients with Relapsing-Remitting Multiple Sclerosis

The primary objective of this study is to assess the **feasibility** and validate the **safety** of personalized extended interval dosing of **natalizumab** starting from 6 weeks in a large real-life cohort across the Netherlands. This is clinically relevant as it aims to optimize treatment regimens for patients with relapsing-remitting **multiple sclerosis**, potentially improving patient outcomes and reducing treatment-related risks.

The clinical trial involves participants diagnosed with **Multiple Sclerosis**, specifically focusing on individuals with relapsing-remitting forms of the disease. The study population includes both male and female subjects aged 18 years and older. Participants are required to have received six or more consecutive natalizumab infusions prior to enrollment. The trial does not target a vulnerable population, and participants must have provided written informed consent to partake in the study. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that the study population is representative of a real-life cohort, with no specific lifestyle considerations such as diet or physical activity being highlighted as part of the trial's focus.

The clinical trial is designed to evaluate the feasibility and safety of personalized extended interval dosing of **natalizumab** in patients with relapsing-remitting **multiple sclerosis**. This study is a randomized, double-blind, controlled trial, with an estimated duration from January 2021 to July 2026. Participants will be randomly assigned to receive either Tysabri 300 mg concentrate for solution for infusion, Tyruko 300 mg concentrate for solution for infusion, or Tysabri 150 mg solution for injection in a pre-filled syringe. The trial will involve intravenous infusion or subcutaneous injection, depending on the assigned treatment group.

The sequence of study visits includes an initial screening visit to confirm eligibility based on the inclusion criteria, which require a diagnosis of relapsing-remitting multiple sclerosis according to the 2017 criteria, a history of six or more consecutive natalizumab infusions, and an age of 18 years or older. Participants must provide written informed consent to participate. Following the screening, participants will undergo regular follow-up visits to monitor radiological disease activity, specifically the presence of new or enlarging T2 lesions on brain MRI, which serves as the primary endpoint of the study. The end-of-study visit will occur after two years of participation, at which point the primary endpoint will be assessed.

The expected length of participant involvement is approximately two years, with regular follow-up visits scheduled throughout this period. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, or any other medical reasons deemed necessary by the investigator. The trial aims to provide valuable insights into the safety and efficacy of extended interval dosing of natalizumab, potentially offering a more personalized treatment approach for individuals with relapsing-remitting multiple sclerosis.

The clinical trial involves the administration of **natalizumab**, a monoclonal antibody used in the treatment of **relapsing-remitting multiple sclerosis**. The experimental medication, Tysabri 300 mg, is provided as a **concentrate for solution for infusion**. It is manufactured by Biogen Netherlands B.V. and is administered via **intravenous infusion**. The dosage is set at 300 mg, with a maximum daily and total dose of 300 mg, administered once every six weeks. The pharmaceutical form is a solution for infusion, and the treatment period is limited to one day per administration cycle. Participant compliance is monitored through scheduled visits and infusion records.

Another experimental medication used in the trial is Tyruko 300 mg, also a **concentrate for solution for infusion**. This product is manufactured by Sandoz GmbH and shares the same active substance, **natalizumab**. The administration route is **intravenous infusion**, with a dosage of 300 mg per administration. The maximum daily and total dose is 300 mg, administered once every six weeks, similar to Tysabri. The pharmaceutical form is a solution for infusion, and the treatment period is one day per administration cycle. Compliance is ensured through regular monitoring and documentation of infusion sessions.

The trial also includes Tysabri 150 mg, a **solution for injection in a pre-filled syringe**. This formulation is also produced by Biogen Netherlands B.V. and contains the active substance **natalizumab**. The administration route for this formulation is **subcutaneous injection**. The dosage is 150 mg per injection, with a maximum daily and total dose of 300 mg, administered once every six weeks. The pharmaceutical form is a solution for injection, and the treatment period is one day per administration cycle. Participant adherence is tracked through injection logs and follow-up appointments.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in this trial. The focus is on evaluating the feasibility and safety of personalized extended interval dosing of **natalizumab** in a real-life cohort. The trial does not include pediatric formulations, and all products are classified as non-orphan drugs. The study aims to validate the safety of the extended dosing interval, ensuring that participants receive the correct dosage and adhere to the treatment schedule.

Efficacy in the clinical trial titled "Personalized extended interval dosing of natalizumab in relapsing remitting multiple sclerosis (NEXT-MS)" will be assessed primarily through the evaluation of **radiological disease activity**. This will be determined by the presence of new or enlarging T2 lesions on brain MRI scans after a period of two years. The trial aims to test the feasibility and validate the safety of personalized extended interval dosing of **natalizumab** starting from six weeks in a large real-life cohort across the Netherlands. The primary endpoint is specifically focused on the radiological assessment, which is a critical measure in understanding the progression of relapsing-remitting multiple sclerosis. The trial does not specify secondary endpoints, indicating a concentrated focus on the primary radiological outcomes. The study is designed to provide insights into the efficacy of extended dosing intervals of natalizumab, a treatment already in clinical use, thereby categorizing it as a low-intervention trial.