Efficacy and Safety Evaluation of Efgartigimod PH20 SC in Adults with Thyroid Eye Disease: A Phase 3 Randomized, Double-Masked, Placebo-Controlled Study

The primary objective of this Phase 3, randomized, double-masked, placebo-controlled, multicenter study is to evaluate the **efficacy** of efgartigimod PH20 SC compared with placebo PH20 SC at week 24 of the Double Blind treatment period on the proptosis responder rate in adult participants with **Thyroid Eye Disease**. This objective is clinically relevant as proptosis, or the forward displacement of the eye, is a significant symptom of Thyroid Eye Disease, impacting both function and quality of life. Addressing this symptom can lead to improved patient outcomes and quality of life.

Secondary objectives include: - Evaluating the efficacy of efgartigimod PH20 SC compared with placebo PH20 SC. This further assessment of efficacy is crucial to comprehensively understand the therapeutic potential and benefits of efgartigimod in managing Thyroid Eye Disease.

The clinical trial involves a total of **70 participants** diagnosed with **Thyroid Eye Disease (TED)**, specifically those with active, moderate-to-severe TED associated with autoimmune thyroid conditions such as Graves' disease or Hashimoto's thyroiditis. The study population includes both male and female subjects, aged 18 years and older, who are capable of providing informed consent and adhering to protocol requirements. Participants must have experienced the onset of active TED symptoms within 12 months prior to screening and must have normal thyroid function or mild hypo or hyperthyroidism that is promptly corrected and maintained throughout the study. The trial population was selected based on these criteria, ensuring that participants have their baseline disease under control. Additionally, individuals of child-bearing potential are required to use birth control in accordance with local regulations and must have negative pregnancy tests at screening and before receiving the study drug. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating that special considerations are in place to protect these participants during the study.

The clinical trial is a **Phase 3**, randomized, double-masked, placebo-controlled, multicenter study designed to evaluate the efficacy, safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of **efgartigimod** PH20 SC administered by prefilled syringe in adult participants with **Thyroid Eye Disease** (TED). The trial will involve a double-blind treatment period (DBTP) lasting 24 weeks, with the primary endpoint being the percentage of participants who are proptosis responders at week 24. Secondary endpoints include changes in proptosis measurement, total GO-QoL score, and resolution of diplopia at week 24.

Participants will be randomly assigned to receive either efgartigimod or a placebo, both administered subcutaneously. The trial is expected to start recruitment on October 1, 2024, and conclude by September 29, 2027. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and safety, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be at least 18 years old, have a physician's diagnosis of active, moderate-to-severe TED, and have had the onset of active TED symptoms within 12 months before screening. Participants must also have normal thyroid function or mild hypo/hyperthyroidism that is controlled.

The expected length of participant involvement is approximately 48 weeks, including the treatment and follow-up periods. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse events, or withdrawal of consent. The study aims to provide comprehensive data on the therapeutic potential of efgartigimod in managing TED, with a focus on improving proptosis and overall quality of life for affected individuals.

The clinical trial involves the administration of **Efgartigimod**, a solution for injection in a pre-filled syringe. The active substance in this experimental medication is **efgartigimod alfa**, a protein of human monoclonal origin, specifically an anti-FcRn receptor fragment. The pharmaceutical form is a solution intended for subcutaneous administration. The dosing regimen includes a maximum daily dose of 1000 mg, with a total maximum dose of 48000 mg over a treatment period of up to 48 weeks. The medication is provided by ARGENX BV and is identified by the sponsor product code ARGX-113. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

The study also includes a **placebo** control, which is designed to match the experimental treatment in appearance and administration route. The placebo is administered subcutaneously in a similar pre-filled syringe format. This placebo is used to maintain the double-masked nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo serves as a comparator to evaluate the efficacy and safety of efgartigimod in participants with Thyroid Eye Disease. Compliance with the placebo administration will be monitored in the same manner as the experimental treatment to maintain the integrity of the study results.

The efficacy of efgartigimod in the treatment of **Thyroid Eye Disease** will be assessed in a Phase 3, randomized, double-masked, placebo-controlled, multicenter study. The primary endpoint for evaluating efficacy is the percentage of participants who are proptosis responders at week 24 of the Double-Blind Treatment Period (DBTP). Secondary endpoints include the change in proptosis measurement in the study eye from baseline to week 24, the change in the total Graves' Ophthalmopathy Quality of Life (GO-QoL) score from baseline to week 24, and the percentage of participants with a resolution of diplopia at week 24 of the DBTP.

Efficacy parameters will be measured and collected at baseline and at week 24 of the DBTP. The proptosis responder rate will be determined by the percentage of participants achieving a clinically significant reduction in proptosis. Changes in proptosis measurements and GO-QoL scores will be assessed using validated scales and instruments. The resolution of diplopia will be evaluated based on predefined criteria for responder status. Data analysis will focus on comparing the outcomes between the efgartigimod and placebo groups to determine the treatment's efficacy.