Long-term Evaluation of Safety, Tolerability, Efficacy, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of Empasiprubart in Adults with Multifocal Motor Neuropathy

The primary objective of this study is to evaluate the long-term **safety** and **tolerability** of ARGX-117 in adult participants with **Multifocal Motor Neuropathy** (MMN). This is clinically relevant as it aims to ensure that the treatment is safe for prolonged use, which is crucial for managing a chronic condition like MMN.

Secondary objectives include:

• Evaluating the long-term efficacy of ARGX-117 on muscle strength and/or motor function in adult participants with MMN.
• Assessing the long-term efficacy of ARGX-117 on functional ability, arm and hand function, quality of life (QOL), and fatigue in adult participants with MMN.
• Evaluating the long-term effect of ARGX-117 on health-related productivity and work productivity.
• Assessing the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ARGX-117.

These secondary objectives are significant as they aim to provide a comprehensive understanding of the treatment's impact on various aspects of patient health and daily functioning, which are critical for improving overall patient outcomes in MMN.

The clinical trial involves a total of **17 participants** diagnosed with **Multifocal Motor Neuropathy** (MMN). The study population includes both male and female adults, with an age range that encompasses categories 3 and 4, indicating a broad adult age group. Participants were selected based on their completion of the double-blinded treatment period of the ARGX-117-2002 trial and their eligibility for continued treatment with ARGX-117. The trial population is characterized by individuals who are capable of providing informed consent and complying with protocol requirements, including the ability to read and write. Participants are required to adhere to contraceptive measures consistent with local regulations. The study does not specify particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, highlighting the importance of careful monitoring and ethical considerations throughout the study.

The clinical trial is designed to evaluate the long-term safety and tolerability of **ARGX-117**, a recombinant monoclonal antibody, in adult participants diagnosed with **Multifocal Motor Neuropathy** (MMN). This study is a phase 4, randomized, double-blind, controlled trial, which will include a placebo group to ensure the reliability of the results. The trial is expected to run until August 2027, with recruitment having commenced in May 2023. Participants will be involved in the study for a maximum treatment period of four months, with the investigational medicinal product administered via **intravenous use**.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as the completion of a prior trial phase and the ability to provide informed consent. Following the screening, participants will undergo regular follow-up visits to monitor safety outcomes, including adverse event monitoring and clinical laboratory tests. These visits will also assess secondary endpoints such as changes in grip strength, muscle function, and quality of life measures. The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted to evaluate the long-term effects of the treatment.

Participants are expected to adhere to contraceptive measures during the trial and for a specified period after the last dose of the investigational product. Conditions that may lead to early termination from the study include non-compliance with protocol requirements or the occurrence of significant adverse events. The trial aims to provide comprehensive data on the efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity of **ARGX-117**, contributing valuable insights into its potential as a treatment for MMN.

The clinical trial involves the administration of **ARGX-117**, a recombinant monoclonal antibody, with the active substance **empasiprubart**. This experimental medication is provided in the form of a **concentrate for solution for infusion**. The administration route is **intravenous use**, and the dosing is based on a milligram per kilogram (mg/kg) body weight basis. The maximum treatment period for this medication is set at four weeks. The pharmaceutical form and administration method are designed to ensure optimal delivery and efficacy of the active substance in participants with Multifocal Motor Neuropathy.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in the study. The placebo is designed to match the experimental treatment in appearance and administration method, ensuring blinding of the study. The placebo is referred to as "Placebo to ARGX-117 IV" and does not contain any active substance. The use of a placebo is critical for assessing the true efficacy and safety profile of ARGX-117 by providing a baseline for comparison.

The efficacy of ARGX-117 in the treatment of **Multifocal Motor Neuropathy (MMN)** will be assessed through a series of secondary endpoints. These include the Modified Medical Research Council (mMRC) sum scores, where both the value and change from baseline in the mMRC-10 and mMRC-14 sum scores will be evaluated. The proportion of participants showing a deterioration of at least 2 points in these scores will also be measured. Additionally, grip strength (GS) will be assessed by evaluating values, changes, and percent changes from baseline, as well as the proportion of participants experiencing a decline of more than 30% in GS or a decrease of 8 kilopascals (kPa) or more.

Further efficacy assessments will include changes from baseline in the Rasch-built overall disability scale for MMN (MMN-RODS), and the average time for upper extremity function using the 9-Hole Peg Test (9-HPT). The EQ-5D-5L will be used to determine the proportion of participants by level of severity on each dimension, and changes in the visual analog scale (VAS) will be recorded. The Chronic Acquired Polyneuropathy Patient-Reported Index (CAP-PRI) and the 9-item Fatigue Severity Scale (FSS) will also be utilized to measure changes from baseline.

Patient-reported outcomes will be captured using the Patient Global Impression of Change (PGIC) scale and the Patient Global Impression of Severity (PGIS) for MMN. Work-related and household chore activities will be evaluated through the Health-Related Productivity Questionnaire (HRPQ), focusing on hours lost due to absenteeism and presenteeism. Serum concentrations and pharmacokinetic (PK) parameters for ARGX-117, as well as values and changes in free C2, total C2, and functional complement activity (CH50) over time, will be analyzed. The incidence and prevalence of antidrug antibodies (ADA) against ARGX-117 will also be monitored.