Evaluation of Batoclimab Efficacy and Safety in Patients with Graves' Disease: An Open-label, Proof-of-Concept Study

The primary objective of this study is to evaluate the effects of **batoclimab** on thyroid hormone levels in participants with Graves' disease (GD), specifically by assessing the reduction of free triiodothyronine (FT3) and free thyroxine (FT4) at Week 24. This is clinically relevant as GD is characterized by the overproduction of thyroid hormones, and managing these levels is crucial for controlling the disease and preventing complications.

Secondary objectives include:

• Investigating the effects of batoclimab on thyroid hormone levels in participants with GD by assessing the reduction of FT3 and FT4 and changes in antithyroid drug (ATD) usage at Week 24.
• Evaluating the effects of batoclimab on thyroid hormone levels in participants with GD by assessing the reduction of FT3 and FT4 at Week 24 and ATD treatment.

The clinical trial involves participants diagnosed with **Grave's disease**, focusing on both male and female subjects aged 18 years and older. The study population includes individuals with serologically confirmed active hyperthyroidism due to Grave's disease, characterized by specific thyroid hormone levels. Participants must have been on antithyroid drugs (ATD) for at least 12 weeks prior to the screening, with a minimum starting dose of 20 mg of methimazole or carbimazole, or 100 mg of propylthiouracil. The trial includes a vulnerable population, although the total number of participants is not provided by the sponsor. The selection criteria ensure that participants have a documented elevated stimulatory TSH-R-Ab level and meet specific laboratory values for TSH, FT3, and FT4. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the **safety** and **efficacy** of **batoclimab** in participants diagnosed with **Graves' disease**. This is an open-label, therapeutic exploratory trial categorized as Phase II, with a primary objective to assess the effects of batoclimab on thyroid hormone levels, specifically the reduction of FT3 and FT4 at Week 24. The trial is expected to run from March 2023 to August 2025, with a maximum treatment period of 24 weeks for each participant. Participants will receive batoclimab as a **solution for injection** administered subcutaneously.

The trial will include a series of study visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as age (≥18 years), serologically confirmed Graves' disease, and active hyperthyroidism. Participants must have been on an antithyroid drug (ATD) for at least 12 weeks prior to the screening. The primary endpoint is the proportion of participants achieving normalization of FT3 and FT4 without an increase in ATD dose by Week 24. Secondary endpoints include the proportion of participants achieving normalization with reduced ATD dose and those off ATD treatment by Week 24.

Participants will be involved in the study for a duration of up to 24 weeks, with regular follow-up visits to monitor thyroid hormone levels and assess the safety and efficacy of the treatment. The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted. Conditions that may lead to early termination from the study include adverse reactions to the treatment or failure to adhere to the study protocol. The trial is not classified as low intervention, and the investigational product is not an orphan drug. The study aims to provide valuable insights into the therapeutic potential of batoclimab for managing Graves' disease.

The clinical trial involves the administration of **Batoclimab**, a solution for injection, as the experimental medication. Batoclimab, also known by its sponsor product code IMVT-1401, is a human monoclonal antibody targeting the human FcRn receptor. It is administered subcutaneously. The maximum daily dose is 680 mg, with a total maximum dose of 12,240 mg over a treatment period of 24 weeks. The pharmaceutical form is a solution for injection, and the active substance is derived from a protein of other origin. The administration schedule is designed to ensure participant compliance, with regular monitoring to assess adherence to the dosing regimen.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the safety and efficacy of Batoclimab in participants with Graves' Disease. The trial aims to investigate the effects of Batoclimab on thyroid hormone levels, specifically the reduction of FT3 and FT4, at Week 24. Compliance with the dosing schedule is monitored throughout the study to ensure accurate assessment of the drug's effects.

The efficacy of Batoclimab in the treatment of **Graves' Disease** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of participants who, at Week 24, achieve normalization of FT3 and FT4 levels without an increase in antithyroid drug (ATD) dose compared to baseline, or have FT3 and/or FT4 levels below the lower limit of normal (LLN). Secondary endpoints include the proportion of participants who achieve normalization of FT3 and FT4 at Week 24 with an ATD dose that is ≤50% of the baseline ATD dose by Week 24, and the proportion of participants who are off ATD treatment and achieve normalization of FT3 and FT4, or have FT3 and/or FT4 below the LLN at Week 24.

The efficacy parameters will be measured at the specified timepoint of Week 24. The assessment of thyroid hormone levels, specifically FT3 and FT4, will be conducted to evaluate the therapeutic effect of Batoclimab. The trial is designed as a proof-of-concept, open-label study, focusing on the safety and efficacy of Batoclimab in participants with Graves' Disease. The trial is categorized as a Phase II therapeutic exploratory trial, with an estimated end date of August 31, 2025.