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

The primary objective of this study is to evaluate the **efficacy** of batoclimab, administered subcutaneously at a dose of 680 mg once a week for 12 weeks followed by 340 mg once a week for another 12 weeks, compared to placebo. The primary endpoint is the proptosis responder rate at Week 24 in participants with active **Thyroid Eye Disease**. This is clinically relevant as proptosis, or bulging of the eyes, is a significant symptom of Thyroid Eye Disease, and its reduction can lead to improved patient outcomes and quality of life.

Secondary objectives include evaluating the efficacy of batoclimab compared to placebo as assessed by various clinical measures:

• 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)
• Motility

The clinical trial for **Thyroid Eye Disease** involves a total of 25 participants. The study population includes both male and female subjects, aged 18 years and older, who have been diagnosed with active, moderate to severe Thyroid Eye Disease (TED). Participants are required to have a Clinical Activity Score (CAS) of 4 or higher in either eye and must exhibit clinical 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 course of the study. The trial also considers vulnerable populations, ensuring a comprehensive evaluation of the treatment's efficacy.

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 is structured as a Phase 3 study, with the primary objective of assessing the proptosis responder rate at Week 24. Participants will receive **Batoclimab** 680 mg subcutaneously once a week for 12 weeks, followed by 340 mg subcutaneously once a week for an additional 12 weeks, compared to a placebo. The trial is expected to conclude by December 31, 2025, with recruitment having commenced on January 5, 2023.

The study involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, clinical diagnosis of TED, and thyroid status. Participants must be 18 years or older, have moderate to severe active TED, and meet specific proptosis and anti-TSHR-Ab criteria. The trial excludes those requiring immediate surgical intervention or planning corrective surgery during the study. Following the screening, participants will undergo regular follow-up visits to monitor treatment effects and safety, culminating in an end-of-study visit at Week 24 to assess the primary and secondary endpoints.

Participant involvement is anticipated to last approximately 24 weeks, aligning with the treatment period. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or any protocol deviations that compromise the integrity of the trial. 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 changes in Clinical Activity Score (CAS), seroconversion rates, and improvements in diplopia and quality of life measures. The trial's design ensures rigorous assessment of **Batoclimab**'s efficacy and safety in treating active TED.

The clinical trial involves the administration of **Batoclimab**, a solution for injection, as the experimental medication. Batoclimab is a human monoclonal antibody targeting the human FcRn receptor, with the active substance name **BATOCLIMAB**. It is also known by synonyms such as HL161BKN, HBM-9161, and RVT-1401. The pharmaceutical form of Batoclimab is a solution for injection, and it is administered via subcutaneous injection. The dosing regimen for Batoclimab involves an initial dose of 680 mg administered once weekly for the first 12 weeks, followed by a reduced dose of 340 mg once weekly for the subsequent 12 weeks. The maximum daily dose is 680 mg, with a total maximum dose of 12,240 mg over the 24-week treatment period. The medication is provided by Immunovant Sciences GmbH.

The study also includes a **placebo** treatment, which is identical in appearance to the investigational medicinal product (IMP) but contains no active substance. The placebo is administered in the same pharmaceutical form and via the same route as Batoclimab, ensuring blinding of the study. The placebo serves as a control to evaluate the efficacy of Batoclimab in treating participants with active Thyroid Eye Disease (TED). The administration schedule for the placebo mirrors that of Batoclimab, with weekly subcutaneous injections over the 24-week study period.

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) ≤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 changes in proptosis, total GO-QOL score, and motility from baseline to Week 24.

Efficacy parameters will be measured at baseline and at Week 24 using validated clinical scales and laboratory tests. The study will employ a quadruple-masked, placebo-controlled design to ensure unbiased assessment of outcomes. The treatment regimen involves administering Batoclimab 680 mg subcutaneously once a week for 12 weeks, followed by 340 mg weekly for another 12 weeks, with efficacy assessments conducted at the end of the 24-week treatment period. The analysis will focus on comparing the efficacy outcomes between the Batoclimab and placebo groups to determine the therapeutic benefit of Batoclimab in managing active TED.