Evaluation of Safety and Tolerability of VRDN-003 in Patients with Thyroid Eye Disease: A Randomized, Double-Masked, Controlled Study

The primary objective of this study is to evaluate the **safety** and **tolerability** of VRDN-003 when administered as a series of subcutaneous injections every 4 weeks or every 8 weeks in participants with **thyroid eye disease** (TED) of any duration. This is clinically relevant as it aims to determine if the body reacts acceptably to VRDN-003, which is an **insulin-like growth factor-1 receptor (IGF-1R) inhibitor** with half-life extension. Understanding the safety and tolerability of this treatment is crucial for its potential use in managing TED, a condition that can significantly impact patients' quality of life.

The clinical trial involves **208 participants** diagnosed with **thyroid eye disease** (TED). The study population comprises adult males and females aged between 18 and 75 years. Participants were selected based on their clinical diagnosis of TED, and the investigator's assessment that they may benefit from the investigational drug VRDN-003. Both male and female subjects are included, and all participants must agree to use highly effective contraception throughout the study. Female participants are required to have a negative pregnancy test at the first study visit. The trial includes individuals from a vulnerable population, and lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The study aims to evaluate the safety and tolerability of VRDN-003 when administered as subcutaneous injections every 4 or 8 weeks.

The clinical trial is designed to evaluate the **safety** and tolerability of VRDN-003, an **insulin-like growth factor-1 receptor (IGF-1R) inhibitor**, in participants with **thyroid eye disease** (TED). This is a Phase III, randomized, double-masked, controlled study. Participants will receive subcutaneous injections of VRDN-003 or a placebo every 4 or 8 weeks. The trial aims to assess the rate of treatment-emergent adverse events through Week 24 as the primary endpoint, with secondary endpoints including changes in eye bulging and safety event rates through Week 52.

The trial will commence with a screening visit to confirm eligibility based on criteria such as age (18-75 years), clinical diagnosis of TED, and agreement to use effective contraception. Female participants must have a negative pregnancy test at the first study visit. Following the screening, eligible participants will be randomized to receive either VRDN-003 or placebo. Study visits will occur at regular intervals to monitor safety, efficacy, and any adverse events. The end-of-study visit will conclude the participant's involvement, which is expected to last up to 52 weeks.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial is estimated to end by January 31, 2027, with recruitment starting on June 3, 2025. The study is not categorized as low intervention and is conducted under the regulatory framework for a Category 2 trial. The investigational product, VRDN-003, is administered as an injection, with a maximum daily dose of 600 mg and a total dose not exceeding 2100 mg over a 20-week treatment period.

The clinical trial involves the administration of **VRDN-003**, an **Insulin-like growth factor-1 receptor (IGF-1R) inhibitor** with half-life extension, developed by Viridian Therapeutics, Inc. This experimental medication is provided in the form of an injection. The active substance, VRDN-003, is a protein of other origin. The medication is administered via subcutaneous injection, targeting the layer of fat between the skin and muscle. The dosing schedule for VRDN-003 involves administration every 4 weeks or every 8 weeks, with a maximum daily dose of 600 mg and a total maximum dose of 2100 mg over a treatment period of up to 20 weeks. The primary objective of the trial is to evaluate the safety and tolerability of VRDN-003 in participants with thyroid eye disease (TED).

In addition to the experimental treatment, a placebo, referred to as TED SC Placebo, is utilized in the study. The placebo is designed to mimic the administration of the experimental drug without containing the active substance. The pharmaceutical form, dosage, and route of administration for the placebo are not specified in the available data. The use of a placebo allows for a controlled comparison to assess the effects of VRDN-003 in the study population.

Efficacy in the clinical trial of VRDN-003 for the treatment of **Thyroid Eye Disease (TED)** will be assessed using specific endpoints. The primary endpoint focuses on the rate of safety events, specifically Treatment Emergent Adverse Events, occurring through Week 24 after the initiation of treatment with VRDN-003. Secondary endpoints include changes in eye bulging at Week 24 compared to baseline measurements taken before the first dose, as well as the rate of safety events through Week 52.

Measurements for these endpoints will be collected at specified timepoints, with the primary assessment occurring at Week 24 and additional evaluations extending to Week 52. The trial will utilize a randomized, double-masked, controlled design to ensure the reliability and validity of the data collected. The efficacy parameters will be analyzed to determine the impact of VRDN-003 on the progression and symptoms of TED, providing insights into its potential therapeutic benefits.