Long-term Safety, Tolerability, and Efficacy of Subcutaneous Efgartigimod PH20 in Chronic Inflammatory Demyelinating Polyneuropathy: An Open-label Extension Study

The primary objective of this study is to assess the long-term **safety** and tolerability of efgartigimod PH20 SC, a formulation co-formulated with recombinant human hyaluronidase PH20 for subcutaneous administration, in patients with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). This objective 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 CIDP.

Secondary objectives include:

• Determining the long-term efficacy of the treatment.
• Evaluating the **immunogenicity** by assessing anti-drug antibodies (ADA) of efgartigimod and rHuPH20.
• Assessing the **pharmacokinetics** (PK) of efgartigimod PH20 SC.
• Evaluating the **pharmacodynamic** (PD) effect, specifically total immunoglobulin G (IgG) levels.
• Evaluating additional patient-reported outcomes (PROs), including quality of life and satisfaction with treatment.
• Exploring self-administration of the treatment.
• Exploring administration of the treatment by caregivers.

The clinical trial involves a total of **148 participants** diagnosed with **Chronic Inflammatory Demyelinating Polyneuropathy**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on their previous involvement in the ARGX-113-1802 trial, with eligibility contingent upon completion of specific trial stages or deterioration during the trial. The trial also includes individuals who were offered participation due to early termination of the previous trial. Women of childbearing potential are required to have a negative pregnancy test and must use an acceptable method of contraception. The trial population is considered vulnerable, and participants are expected to comply with the trial protocol, including attending required visits. The study does not specify particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the long-term safety, tolerability, and efficacy of **efgartigimod alfa** in patients with **Chronic Inflammatory Demyelinating Polyneuropathy** (CIDP). This is a Phase 4, open-label extension study following the ARGX-113-1802 trial. The trial employs a randomized, double-blind, controlled methodology to ensure the reliability and validity of the results. The estimated duration of the trial is from May 29, 2020, to May 31, 2027, with participants expected to be involved for a maximum treatment period of 336 days.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as completion of the Week-48 visit of Stage B of the ARGX-113-1802 trial or deterioration during Stage B. Follow-up visits will occur regularly to monitor the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), as well as to assess efficacy through various clinical scores and measurements. Blood samples will be collected at each visit to evaluate laboratory parameters and immunogenicity. The end-of-study visit will conclude the participant's involvement, with assessments to ensure safety and gather final data on the trial endpoints.

The expected length of participant involvement is contingent upon their response to treatment and adherence to the trial protocol. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or non-compliance with study procedures. The primary endpoints focus on the incidence of TEAEs and SAEs, while secondary endpoints include changes in clinical scores, immunogenicity, pharmacokinetics, and patient-reported outcomes. The trial aims to provide comprehensive data on the long-term use of efgartigimod alfa in managing CIDP, contributing valuable insights into its therapeutic potential.

The clinical trial involves the administration of **efgartigimod alfa**, an experimental medication, to evaluate its long-term safety, tolerability, and efficacy in patients with **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)**. The investigational product, known as ARGX-113, is provided in two pharmaceutical forms: a **solution for injection** and a **solution for injection in a pre-filled syringe**. Both forms are intended for **subcutaneous** administration. The maximum daily dose of efgartigimod alfa is 1000 mg, with a total maximum dose of 336,000 mg over a treatment period of 336 days. The active substance, efgartigimod alfa, is a protein of non-chemical origin, specifically a human monoclonal antibody fragment targeting the FcRn receptor.

The solution for injection is manufactured by ARGEN-X BVBA and is not formulated for pediatric use. The administration of this form is conducted subcutaneously, with the dosing schedule designed to ensure participant compliance and safety. Monitoring of participant adherence to the dosing regimen is a critical component of the trial protocol.

The solution for injection in a pre-filled syringe is produced by ARGENX BV and is also administered subcutaneously. This form includes a device component, although it does not possess a CE mark. The pre-filled syringe is designed to facilitate ease of administration and improve dosing accuracy. As with the other form, participant compliance is closely monitored to ensure adherence to the prescribed dosing schedule.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The trial is focused solely on the evaluation of efgartigimod alfa in its specified forms and dosages. The study's primary objective is to assess the long-term safety and tolerability of efgartigimod PH20 SC, which is efgartigimod co-formulated with recombinant human hyaluronidase PH20 for subcutaneous administration.

The efficacy of the clinical trial investigating the long-term safety, tolerability, and efficacy of **efgartigimod** PH20 SC in patients with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) will be assessed through several secondary endpoints. These include changes from baseline over time in various scores and measurements: the Adjusted INCAT score, MRC Sum score, 24-item I-RODS disability scores, mean grip strength assessed by Martin vigorimeter, and TUG score. Additionally, the percentage of patients without clinical deterioration over time, defined by an adjusted INCAT increase of ≥1 point compared to baseline, will be evaluated.

Further assessments will include immunogenicity, with the percentage of patients with and titers of binding antibodies (BAb) towards efgartigimod, and the presence of neutralizing antibodies (NAb) against efgartigimod. Pharmacokinetic parameters will be evaluated by measuring efgartigimod serum concentrations during the first 48-week treatment cycle. Pharmacodynamic assessments will involve changes from baseline over time of serum IgG levels (total). These efficacy, immunogenicity, pharmacokinetic, and pharmacodynamic endpoints are assessed at every study visit.

Additional patient-reported outcomes will be measured, including changes from baseline over time in the Health-related quality-of-life questionnaire (EQ-5D-5L), Brief Pain Inventory – Short Form (BPI-SF), 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9), Rasch-transformed-Fatigue Severity Scale (RT-FSS), and Hospital Anxiety and Depression Scale (HADS). Patient-reported outcomes are assessed at every study visit, except for visit 2 (week 4). The percentage of patients performing self-administration and those with treatment administered by a caregiver over time will also be recorded.