Phase 3 Randomized Quadruple-Masked Placebo-Controlled Trial of Batoclimab in Active Thyroid Eye Disease Patients

The primary objective of this study is to evaluate the efficacy of **batoclimab** 680 mg administered subcutaneously once a week for 12 weeks, followed by 340 mg subcutaneously once a week for an additional 12 weeks, compared to placebo, in improving the proptosis responder rate at Week 24 in participants with active **Thyroid Eye Disease (TED)**. This is clinically relevant as proptosis, or bulging of the eyes, is a significant symptom of TED that can impact vision and quality of life.

Secondary objectives include evaluating the efficacy of batoclimab compared to placebo through various clinical assessments:

• Proptosis and Clinical Activity Score (CAS)
• CAS alone
• Change in binding anti-TSHR antibodies
• Gorman score for diplopia
• Proptosis alone
• Graves’ ophthalmology-specific quality of life (GO-QOL)
• Ocular motility

The clinical trial for **Thyroid Eye Disease (TED)** involves a total of 64 participants. The study population includes both male and female subjects, aged 18 years and older, who have been clinically diagnosed with active, moderate to severe TED. Participants are required to have a Clinical Activity Score (CAS) of 4 or higher in either eye, with evidence of worsened proptosis. The trial population was selected based on specific inclusion criteria, such as the onset of active TED within 12 months prior to screening and documented evidence of detectable anti-TSHR-Ab. Participants are expected to be euthyroid or have mild hypo- or hyperthyroidism, with their baseline disease under control. The study does not include individuals planning corrective surgery, irradiation, or medical therapy for TED during the trial period. The trial also considers vulnerable populations, ensuring a comprehensive evaluation of the treatment's efficacy across diverse groups.

The clinical trial is a **randomized**, quadruple-masked, placebo-controlled study designed to evaluate the efficacy of **batoclimab** in participants with active **Thyroid Eye Disease (TED)**. The trial involves administering batoclimab at a dose of 680 mg subcutaneously once a week for 12 weeks, followed by 340 mg subcutaneously once a week for another 12 weeks, compared to a placebo. The primary endpoint is the proportion of proptosis responders at Week 24, defined as participants with a ≥ 2 mm reduction in the study eye without deterioration in the fellow eye. Secondary endpoints include various measures of proptosis, clinical activity score (CAS), and quality of life improvements.

The trial is expected to last until December 31, 2025, with recruitment having started on November 23, 2022. Participants will be involved in the study for a total of 24 weeks. The study visits are structured as follows: an initial **screening visit** to confirm eligibility based on criteria such as age, clinical diagnosis of TED, and thyroid status. This is followed by regular **follow-up visits** to monitor the efficacy and safety of the treatment, and an **end-of-study visit** at Week 24 to assess the primary and secondary endpoints.

Participants are expected to remain in the study for the full duration unless they meet conditions for early termination, such as adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial is conducted under strict adherence to ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Batoclimab**, a solution for injection, as the experimental medication. Batoclimab is a human monoclonal antibody targeting the neonatal Fc receptor (FcRn). It is administered via **subcutaneous injection**. The dosing regimen consists of an initial dose of 680 mg once a week for the first 12 weeks, followed by a reduced dose of 340 mg once a week for the subsequent 12 weeks. The total treatment period spans 24 weeks. The maximum daily dose is 680 mg, with a cumulative maximum dose of 12,240 mg over the course of the study. The active substance, Batoclimab, is derived from a protein of other origin and is produced by Immunovant Sciences GmbH. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.

The study also includes a **placebo** group, which serves as the comparator treatment. The placebo is identical in appearance to the investigational medicinal product (IMP) but contains no active substance. It is administered in the same pharmaceutical form and via the same route as Batoclimab, ensuring blinding of the study. The placebo is given subcutaneously once a week, following the same dosing schedule as the experimental group. This design allows for a controlled comparison of the efficacy and safety of Batoclimab in participants with active Thyroid Eye Disease (TED).

The efficacy of Batoclimab in the treatment of **Thyroid Eye Disease (TED)** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of proptosis responders at Week 24, defined as participants achieving a reduction of ≥2 mm in proptosis in the study eye without a deterioration of ≥2 mm in the fellow eye. Secondary endpoints include the proportion of participants with a ≥2 mm reduction in proptosis and a Clinical Activity Score (CAS) of ≤3 at Week 24, the proportion of participants with a CAS of 0 or 1 at Week 24, and the mean change in CAS from baseline to Week 24 in the study eye. Additional secondary endpoints involve the proportion of participants achieving seroconversion of anti-TSHR antibodies, a decrease in Gorman score for diplopia, and improvements in proptosis, total GO-QOL score, and motility in the study eye at Week 24.

Measurements will be conducted at baseline and at Week 24, utilizing validated scales and clinical assessments to ensure accuracy and reliability. The study will employ a randomized, quadruple-masked, placebo-controlled design to minimize bias and ensure the robustness of the efficacy data. The trial is structured to provide a comprehensive evaluation of Batoclimab's impact on TED, with a focus on both clinical and patient-reported outcomes.