Efficacy, Safety, and Tolerability of VRDN-003 in Active Thyroid Eye Disease: A Phase 3 Randomized, Double-Masked, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy**, safety, and tolerability of VRDN-003, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor with half-life extension, in participants with active **thyroid eye disease** (TED). The study aims to determine if VRDN-003 affects the signs and symptoms of TED and if the body reacts acceptably to the treatment when administered as a series of subcutaneous injections every 4 or 8 weeks, compared to a placebo. This is clinically relevant as TED is a debilitating condition that can significantly impact a patient's quality of life, and effective treatment options are limited.

The clinical trial involves a total of **49 participants** diagnosed with **thyroid eye disease** (TED). The study population comprises adult males and females aged between 18 and 75 years, all of whom have a clinical diagnosis of TED with a Clinical Activity Score (CAS) of 3 or higher. Participants must exhibit moderate to severe active TED, characterized by eye bulging and at least one additional sign or symptom as specified in the study protocol. The trial includes individuals who have experienced eye-related signs or symptoms within 15 months prior to the first study visit. Both male and female participants are required to use highly effective contraception, and female participants must have a negative pregnancy test at the initial study visit. The trial population was selected based on these criteria to ensure the inclusion of individuals with active TED, and it includes both genders without specific lifestyle considerations mentioned. The study does not provide additional information regarding the general health status or lifestyle habits of the participants.

The clinical trial is a **randomized**, double-masked, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of VRDN-003, an **insulin-like growth factor-1 receptor (IGF-1R) inhibitor**, in participants with active **thyroid eye disease (TED)**. The trial will involve subcutaneous injections of VRDN-003 administered every 4 or 8 weeks, compared to a placebo. The primary objective is to determine the effect of VRDN-003 on the signs and symptoms of TED, as well as its safety and tolerability. The trial is expected to commence recruitment on January 17, 2025, and conclude by November 5, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, clinical diagnosis of TED, and recent onset of eye-related symptoms. The study will include follow-up visits at regular intervals to monitor the participants' response to treatment and any adverse effects. The primary endpoint will be assessed at Week 24, focusing on the percentage of participants achieving an Overall Responder Rate, defined by a reduction in eye bulging and Clinical Activity Score (CAS). Secondary endpoints will evaluate changes in disease severity, symptoms, and the resolution of double vision.

The expected duration of participant involvement is approximately 40 weeks, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. Participants must adhere to the study protocol, including the use of effective contraception and compliance with scheduled visits and assessments. The trial aims to provide valuable insights into the potential benefits and risks of VRDN-003 for individuals with active TED.

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** and is administered via **subcutaneous use**. The dosing regimen for VRDN-003 involves injections given every 4 weeks or every 8 weeks, with a maximum daily dose of 600 mg and a total maximum dose of 4200 mg over a treatment period of up to 40 weeks. The active substance, VRDN-003, is a protein of other origin, specifically designed to target and inhibit IGF-1R, which is implicated in the pathophysiology of active thyroid eye disease (TED). Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol.

The study also includes a **placebo** group, utilizing the TED SC Placebo, which serves as a comparator treatment. The placebo is designed to mimic the administration of the experimental drug without containing any active drug ingredients. This allows for the assessment of the efficacy, safety, and tolerability of VRDN-003 by comparing outcomes between the active treatment group and the placebo group. The placebo is administered in a manner consistent with the experimental treatment to maintain the double-masked nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments.

Efficacy in the clinical trial of VRDN-003 for active **Thyroid Eye Disease (TED)** will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the Overall Responder Rate at Week 24. This is defined as the percentage of participants who achieve a reduction of at least 2 mm in eye bulging and a decrease of at least 2 points in the Clinical Activity Score (CAS), which estimates disease severity and symptoms, compared to baseline measurements taken before the first dose.

Secondary endpoints will evaluate changes in eye bulging, disease severity, and symptoms relative to baseline, as well as the percentage of participants achieving the required reductions in these parameters. Additionally, the study will assess the reduction and resolution of double vision at Week 24. Efficacy assessments will be conducted at specified timepoints, with the primary analysis occurring at Week 24. The study will also monitor safety events and the effects of VRDN-003 on the body throughout the trial.