Evaluation of Human (scFv)2-Fab Fusion Protein Against CD40L in Moderate-to-Severe Thyroid Eye Disease: An Open-Label, Long-Term Follow-Up Study

The primary objective of this clinical trial is to evaluate the **efficacy** of Lu AG22515 on proptosis in patients with moderate-to-severe **Thyroid Eye Disease** (TED). Proptosis, or the forward displacement of the eye, is a significant clinical manifestation of TED that can lead to complications such as exposure keratopathy and optic neuropathy. Assessing the impact of Lu AG22515 on proptosis is crucial for determining its potential therapeutic benefit in managing this condition.

The clinical trial involves a total of **7 participants** diagnosed with **active, moderate-to-severe Thyroid Eye Disease (TED)**. The study population includes both male and female subjects, with an age range corresponding to category code 3, which typically represents adults. Participants were selected based on specific criteria, including the presence of Graves' disease-associated TED symptoms with ophthalmologic symptom onset less than 12 months prior to the baseline visit. The trial population is characterized by proptosis of at least 3 millimeters above normal for race and sex, as measured using the Hertel exophthalmometer, and a Clinical Activity Score of 3 or higher in the most severe eye at the screening visit. Participants must be euthyroid or have mild hypo- or hyperthyroidism, with free thyroxin and/or free triiodothyronine levels not exceeding normal limits by more than 50%. The trial includes a vulnerable population, although specific lifestyle considerations such as diet or physical activity are not detailed in the provided data.

The clinical trial is designed as an **interventional**, open-label, single-group, long-term follow-up study to evaluate the efficacy of Lu AG22515 in patients with moderate-to-severe **Thyroid Eye Disease** (TED). The primary objective is to assess the change in proptosis from baseline to Week 24 using the Hertel exophthalmometer. Secondary endpoints include pharmacokinetics, safety, and immunogenicity assessments. The trial is set to commence recruitment on July 1, 2024, and is estimated to conclude by July 30, 2026, with a maximum treatment period of 168 days.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as the presence of Graves’ disease-associated TED symptoms and specific ophthalmologic measurements. The baseline visit will establish initial proptosis levels and other relevant health metrics. Follow-up visits will occur at regular intervals to monitor changes in proptosis, collect pharmacokinetic data, and assess safety through laboratory tests, vital signs, and ECG parameters. The end-of-study visit will finalize data collection and evaluate the presence of anti-Lu AG22515 antibodies.

Participant involvement is expected to last approximately 24 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. The investigational product, Lu AG22515, is administered as a **solution for infusion**. The trial is conducted under the sponsorship of H. Lundbeck A/S, with adherence to regulatory standards for clinical research. The study is not classified as a low-intervention trial and is categorized as a Phase 3 therapeutic exploratory trial, focusing on efficacy, safety, tolerability, and pharmacokinetic/pharmacodynamic endpoints.

The clinical trial involves the administration of an **experimental medication** known as Lu AG22515, which is a **human (scFv)2-Fab fusion protein against CD40L**. This investigational product is provided in the form of a **solution for infusion**. The pharmaceutical formulation is designed for intravenous administration, allowing for direct delivery into the bloodstream. The dosing regimen for Lu AG22515 is structured to accommodate a maximum treatment period of 168 days. The specific dosage in milligrams is not predetermined, as the trial does not specify a maximum daily or total dose amount. The investigational product is developed by H. Lundbeck A/S and is not classified as a pediatric formulation.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus remains solely on evaluating the efficacy of Lu AG22515 in patients with moderate-to-severe **Thyroid Eye Disease**. The trial is designed as an interventional, open-label, single-group, long-term follow-up study. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol and to assess the therapeutic impact of the investigational product on TED proptosis.

The efficacy of Lu AG22515 in patients with moderate-to-severe Thyroid Eye Disease (TED) will be assessed primarily through changes in **proptosis** from Baseline to Week 24. Proptosis will be measured using the Hertel exophthalmometer, a standard tool for assessing eye protrusion, at both the Screening Visit and the Baseline Visit. The primary endpoint focuses on the reduction of proptosis in the trial eye, providing a direct measure of the treatment's impact on this specific symptom of TED.

Secondary endpoints will include pharmacokinetic parameters such as Cmax, tmax, Ctrough, AUC, CL, V, and t½, which will be used to evaluate the exposure to Lu AG22515. Safety assessments will involve monitoring treatment-emergent adverse events (TEAEs), changes from Baseline in clinical safety laboratory test values, vital signs, weight, and ECG parameter values. Additionally, the presence of anti-Lu AG22515 antibodies (ADAs) will be evaluated to assess immunogenicity. These comprehensive assessments will be conducted throughout the trial to ensure a thorough evaluation of both efficacy and safety.