Evaluation of Efgartigimod Alfa PH20 SC Efficacy and Safety 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 (DBTP) on the proptosis responder rate in adult participants with **Thyroid Eye Disease**. Proptosis, or the forward displacement of the eye, is a significant clinical feature of Thyroid Eye Disease, and its reduction is a critical therapeutic goal, as it can alleviate symptoms and improve quality of life for patients.

Secondary objectives include:

• To evaluate the efficacy of efgartigimod PH20 SC compared with placebo PH20 SC.

The clinical trial for **Thyroid Eye Disease (TED)** involves a total of 59 participants. The study population includes both male and female subjects, aged 18 years and older, who are in general good health with controlled thyroid function or mild hypo or hyperthyroidism. Participants were selected based on their ability to provide informed consent and adhere to protocol requirements. The trial specifically targets individuals with active, moderate-to-severe TED associated with autoimmune thyroid conditions such as Graves' disease or Hashimoto's thyroiditis, with the first onset of symptoms occurring within 12 months prior to screening. Participants are required to use birth control in accordance with local regulations, and those of child-bearing potential must have negative pregnancy tests at screening and before receiving the study drug. The trial does not include vulnerable populations, and lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

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 aims to compare the effects of efgartigimod PH20 SC with a placebo at week 24 of the Double-Blind Treatment Period (DBTP) on the proptosis responder rate. The study is expected to commence recruitment on October 1, 2024, and conclude by October 29, 2027.

Participants will be involved in the study for a maximum treatment period of 48 weeks. The trial includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age, disease severity, and thyroid function; regular follow-up visits to monitor treatment effects and safety; and an end-of-study visit to assess final outcomes. The primary endpoint is the percentage of participants who are proptosis responders at week 24, with secondary endpoints including changes in proptosis measurement, total GO-QoL score, and resolution of diplopia.

Inclusion criteria require participants to be at least 18 years old, capable of providing informed consent, and diagnosed with active, moderate-to-severe TED associated with autoimmune thyroid conditions. Participants must have experienced the first onset of active TED symptoms within 12 months before screening and have normal or controlled thyroid function. Exclusion criteria are not specified in the provided data. Participants are expected to adhere to birth control measures and undergo pregnancy testing if applicable. Conditions that may lead to early termination from the study include non-compliance with protocol requirements or adverse events that compromise participant safety.

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 is 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 solution form, ensuring that the study remains double-masked. This allows for an unbiased comparison of the efficacy and safety of efgartigimod against the placebo. The placebo is specifically formulated for use in this trial and does not contain any active pharmaceutical ingredients. The use of a placebo is critical in evaluating the true therapeutic effects of efgartigimod in participants with Thyroid Eye Disease.

The efficacy of efgartigimod PH20 SC in the treatment of **Thyroid Eye Disease** will be assessed in a Phase 3, randomized, double-masked, placebo-controlled, multicenter clinical trial. 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 will be analyzed to compare the efficacy of efgartigimod PH20 SC with placebo PH20 SC, with the primary focus on the proptosis responder rate at the specified timepoint.