Safety and Tolerability Assessment of VRDN-001, an IGF-1R Inhibitor, in Patients with Thyroid Eye Disease

The primary objective of this study is to confirm the **safety** and **tolerability** of VRDN-001, a humanized monoclonal antibody directed against the **insulin-like growth factor-1 receptor (IGF-1R)**, in participants with **thyroid eye disease (TED)**. This will be assessed by administering five intravenous infusions of 10 mg/kg every three weeks, regardless of the duration of TED. The clinical relevance of this objective lies in ensuring that VRDN-001 can be safely administered to patients, potentially offering a new therapeutic option for managing TED, a condition that can significantly impact quality of life.

The clinical trial involves a total of **142 participants** diagnosed with **thyroid eye disease** (TED). The study population comprises adult males and females aged over 18 to 75 years. Participants were selected based on their clinical diagnosis of TED, with or without proptosis, and any Clinical Activity Score (CAS) ranging from 0 to 7. The trial includes both male and female subjects, with specific considerations for female participants to have a negative serum pregnancy test at screening and subsequent negative urine tests before each dose of the study medication. Male participants are required to be surgically sterile or agree to use an acceptable method of contraception. The trial population includes a vulnerable group, indicating that additional ethical considerations are in place to ensure participant safety and compliance with regulatory standards. Lifestyle factors such as diet and physical activity were not specified in the available data.

The clinical trial is designed to evaluate the **safety** and **tolerability** of VRDN-001, a humanized monoclonal antibody targeting the **insulin-like growth factor-1 receptor (IGF-1R)**, in participants diagnosed with **thyroid eye disease (TED)**. This study is structured as a randomized, controlled trial with a double-blind methodology to ensure unbiased results. Participants will receive five intravenous infusions of VRDN-001 at a dosage of 10 mg/kg every three weeks. The trial is expected to span a total duration of approximately 52 weeks, with the primary endpoint being the incidence rate of treatment-emergent adverse events (TEAEs) through Week 15, and secondary endpoints including changes in proptosis and TEAE incidence through Week 52.

Study visits are sequenced to include an initial screening visit, where eligibility is confirmed based on criteria such as age (18 to 75 years), clinical diagnosis of TED, and negative pregnancy tests for females. Following the screening, participants will attend regular follow-up visits coinciding with each infusion to monitor safety and efficacy parameters. The end-of-study visit will occur after the final infusion and will include comprehensive assessments to evaluate the long-term effects of the treatment. The expected length of participant involvement is approximately 12 months, with conditions for early termination including significant adverse reactions or withdrawal of consent.

The clinical trial involves the administration of **VRDN-001**, an experimental medication classified as an **Insulin-like growth factor-1 receptor (IGF-1R) inhibitor**. This investigational product is provided in the pharmaceutical form of a **concentrate for solution for infusion**. The active substance, VRDN-001, is a protein of other origin, developed by Viridian Therapeutics, Inc. The medication is administered via **intravenous infusion**. Participants receive a dosage of 10 mg/kg, with a maximum total dose of 50 mg/kg, delivered in five infusions every three weeks over a maximum treatment period of 12 weeks. The study aims to evaluate the safety and tolerability of VRDN-001 in individuals diagnosed with thyroid eye disease (TED).

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus remains solely on the administration of VRDN-001. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol. The trial is designed to confirm the safety profile of VRDN-001 when administered under the specified conditions, with no pediatric formulation involved. The investigational product is not classified as an orphan drug.

Efficacy in the clinical trial of VRDN-001, a humanized monoclonal antibody targeting the **insulin-like growth factor-1 receptor (IGF-1R)**, will be assessed using both primary and secondary endpoints. The primary endpoint is the incidence rate of Treatment Emergent Adverse Events (TEAEs) through Week 15. Secondary endpoints include the change from baseline in proptosis in the study eye, measured by exophthalmometer at Week 15, and the incidence rate of TEAEs through Week 52. These efficacy parameters will be collected and analyzed at specified timepoints to evaluate the therapeutic impact of VRDN-001 in participants with thyroid eye disease (TED). The study involves administering 5 intravenous infusions of 10 mg/kg of VRDN-001 every three weeks, with the efficacy assessments scheduled to align with these treatment intervals.