Efficacy and Safety Evaluation of IMVT-1402 in Adult Patients with Graves' Disease: A Randomized, Double-Blind, Placebo-Controlled Phase 2b Trial

The primary objective of this study is to evaluate the **efficacy** of IMVT-1402 compared to placebo in patients with **Graves' Disease**. This will be assessed by measuring levels of T3 (Total T3 or FT3), FT4, TSH, and ATD at Week 26. The clinical relevance of this objective lies in determining the potential of IMVT-1402 as a therapeutic option for managing Graves' Disease, which is characterized by hyperthyroidism and can lead to significant morbidity if not effectively treated.

Secondary objectives include evaluating the efficacy of IMVT-1402 versus placebo at various time points: Week 2, Week 4, Week 26, Week 52, Week 78, and Week 104. These assessments aim to provide a comprehensive understanding of the treatment's long-term efficacy and its potential benefits over an extended period, which is crucial for chronic conditions like Graves' Disease.

The clinical trial involves a total of **67 participants** diagnosed with **Grave's Disease**. The study population includes both male and female subjects, aged between 18 and 75 years. Participants were selected based on specific inclusion criteria, including a documented prior diagnosis of Grave's Disease and a TSH value of less than 0.1 mIU/L at the screening visit. Additionally, participants must have been on antithyroid drugs (ATD) for a minimum of three months prior to the screening, with specific dosage requirements. The trial population is not limited to any specific lifestyle considerations such as diet or physical activity. The study includes a vulnerable population, ensuring a comprehensive evaluation of the treatment's efficacy across diverse demographic groups.

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** Phase 2b study designed to evaluate the efficacy, safety, and tolerability of IMVT-1402 in adult patients with **Graves' Disease**. The trial aims to assess the efficacy of IMVT-1402 compared to placebo by measuring thyroid function parameters such as T3, FT4, TSH, and ATD at Week 26. The study will involve participants aged 18 to 75 years who have a documented diagnosis of Graves' Disease and meet specific inclusion criteria, including a TSH value of less than 0.1 mIU/L and a stable dose of antithyroid drugs (ATD) prior to randomization.

The trial is expected to last until July 2028, with recruitment starting in June 2025. Participants will be involved in the study for a maximum treatment period of 52 weeks. The study visits will include an initial screening visit to confirm eligibility, followed by randomization. Participants will then attend regular follow-up visits to monitor their thyroid function and overall health. The primary endpoint is the proportion of participants who are euthyroid and off ATD at Week 26. Secondary endpoints include the proportion of participants who maintain euthyroid status and are off ATD at various time points up to Week 104.

Participants will receive either IMVT-1402 or a placebo, administered as a **solution for injection** via **subcutaneous use**. The maximum daily dose of IMVT-1402 is 600 mg, with a total dose not exceeding 31,200 mg over the treatment period. The study will terminate early for any participant who experiences significant adverse effects, fails to adhere to the study protocol, or withdraws consent. The end-of-study visit will occur after the final assessment at Week 52, or earlier if the participant discontinues the study prematurely. The trial is not classified as a low-intervention study and is categorized as a therapeutic exploratory and confirmatory trial.

The clinical trial involves the administration of **IMVT-1402**, an investigational medicinal product, formulated as a **solution for injection**. The active substance, IMVT-1402, is a protein of other origin, developed by Immunovant Sciences GmbH. The medication is administered via **subcutaneous use**. The dosing regimen includes a maximum daily dose of 600 mg, with a total maximum dose of 31,200 mg over a treatment period of up to 52 weeks. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

The study also includes a **placebo** group, where participants receive an injection identical in appearance to the investigational product but containing no active substance. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. This approach allows for an unbiased assessment of the efficacy and safety of IMVT-1402 in comparison to the placebo. The placebo is administered following the same route and frequency as the investigational product to maintain consistency across treatment groups.

The efficacy of IMVT-1402 in the treatment of adult patients with **Graves' Disease** will be assessed through a randomized, double-blind, placebo-controlled, Phase 2b clinical trial. The primary endpoint for evaluating efficacy is the proportion of participants who are euthyroid and off antithyroid drugs (ATD) at Week 26. Secondary endpoints include the proportion of participants who are euthyroid and off ATD at Week 52, as well as those who remain euthyroid, off IMVT-1402, and off ATD for 6 to 12 months following Week 52. Additional secondary endpoints involve the assessment of thyroid-stimulating hormone receptor antibodies (TRAb) status and thyroid hormone levels, specifically T3 (Total T3 or FT3) and FT4, at various timepoints.

Efficacy parameters will be measured and collected at specified intervals, including Weeks 2, 4, 26, 52, 78, and 104. The analysis will focus on the proportion of participants achieving the defined thyroid status and medication criteria at these timepoints. The trial will utilize laboratory tests to assess thyroid hormone levels and TRAb status, ensuring accurate and reliable data collection. The results will be analyzed to determine the efficacy of IMVT-1402 compared to placebo in achieving and maintaining a euthyroid state without the need for ATD.