Efficacy and Safety Evaluation of Intravenous LASN01 in Thyroid Eye Disease: A Phase 2 Randomized, Double-Masked, Placebo-Controlled Study

The primary objective of this study is to evaluate the **safety** and **efficacy** of two dose levels of LASN01 administered intravenously in patients with **Thyroid Eye Disease** (TED). This is clinically relevant as it aims to determine the potential therapeutic benefits and risks associated with LASN01, which could lead to improved treatment options for individuals affected by TED.

Secondary objectives include assessing changes in TED-related clinical parameters following intravenous administration of LASN01 at either low or high doses in patients with TED. This evaluation is crucial for understanding the broader impact of LASN01 on disease progression and patient outcomes.

The clinical trial involves a total of **13 participants** diagnosed with **Thyroid Eye Disease** (TED). The study population includes both male and female subjects who are **18 years of age or older**. Participants are required to have a clinical diagnosis of Graves' disease associated with moderate-to-severe active TED, with symptoms present for less than 15 months. The trial excludes individuals with a history of medical or surgical treatment for TED, except for specific exceptions such as local supportive measures, mycophenolate, and oral or injectable steroids. Participants must not have undergone orbital radiation or surgery in the study eye. Female participants must be nonpregnant, nonlactating, and either surgically sterile for at least six months or agree to use a highly effective method of contraception, while male participants must be surgically sterile or agree to use a highly effective method of contraception. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

The clinical trial is a **randomized**, double-masked, placebo-controlled study designed to evaluate the efficacy and safety of LASN01 in patients with **Thyroid Eye Disease** (TED). The trial will involve two dose levels of LASN01 administered intravenously. The study is expected to commence recruitment on March 13, 2024, and conclude by October 31, 2025. Participants will be involved in the study for a maximum treatment period of 48 weeks. The trial will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes.

Inclusion criteria for the study require participants to be adults aged 18 years or older with a clinical diagnosis of Graves' disease associated with active TED, and they must have moderate-to-severe active TED with symptoms present for less than 15 months. Exclusion criteria include any previous medical or surgical treatment for TED in the study eye, history of orbital radiation, or surgery in the study eye. Female participants must be nonpregnant and nonlactating, or agree to use effective contraception, while male participants must be surgically sterile or agree to use effective contraception.

The primary endpoints of the study are to assess changes in proptosis in the study eye compared to baseline and to evaluate the safety and tolerability of LASN01 compared with placebo. Secondary endpoints include changes in TED-related clinical parameters and pharmacokinetic parameters such as maximum plasma concentration, time to peak concentration, and half-life of LASN01. Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it necessary for their safety.

The clinical trial involves the administration of **LASN01**, an experimental medication formulated as a **solution for injection**. The active substance, LASN01, is a protein of other origin, developed by LASSEN THERAPEUTICS 1 INC. The medication is administered via **intravenous infusion**. The dosing regimen includes a maximum daily dose of 600 mg, with a total maximum dose of 7800 mg over a treatment period of 48 weeks. The trial aims to evaluate the safety and efficacy of two dose levels of LASN01 in patients with **thyroid eye disease**.

In addition to the experimental treatment, the study utilizes **Sodium Chloride 0.9% Intravenous Infusion BP** as a comparator treatment. This non-experimental treatment is a **solution for infusion** containing the active substance sodium chloride, a chemical compound. Manufactured by BAXTER HEALTHCARE LTD., it is administered through **intravenous infusion**. The maximum daily dose is 60 ml, with a total maximum dose of 780 ml over the same 48-week treatment period.

Furthermore, **Water for Injections BP** is used as a placebo in the study. This product, produced by HAMELN PHARMA LTD, is an **injection** containing water for injection as the active substance, classified under specified substance group 1. It is also administered via **intravenous infusion**. The dosing schedule mirrors that of LASN01, with a maximum daily dose of 600 mg and a total maximum dose of 7800 mg over 48 weeks.

Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the treatment protocols. The study is designed to maintain rigorous standards for evaluating the therapeutic potential and safety profile of LASN01 in the target patient population.

The efficacy of LASN01 in patients with **Thyroid Eye Disease** (TED) will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint focuses on evaluating changes in proptosis in the study eye compared to baseline, utilizing an Exophthalmometer for measurement. This tool is essential for accurately assessing the degree of eye protrusion, a key symptom of TED.

Secondary efficacy endpoints include a comprehensive assessment of TED-related clinical parameters. These parameters encompass changes in proptosis, Clinical Activity Score (CAS), lid retraction, lid aperture, lagophthalmos, Von Graefe’s sign, and diplopia in the study eye compared to baseline. Additionally, pharmacokinetic (PK) parameters will be evaluated by measuring serum LASN01 concentration at specified timepoints. These PK parameters include maximum plasma concentration (Cmax), time to peak concentration (Tmax), area under the curve (AUC), clearance volume (CL), terminal phase volume (Vz), and half-life (t1/2).