Phase III Randomized Double‑Masked Placebo‑Controlled Study of Subcutaneous Satralizumab in Adults with Moderate‑to‑Severe Thyroid Eye Disease

The primary objective of this Phase III, randomized, double-masked, placebo-controlled, multicenter study is to evaluate the **efficacy** of subcutaneous satralizumab compared with placebo at Week 24 based on proptosis response in participants with moderate-to-severe **Thyroid Eye Disease**. Proptosis, or the forward displacement of the eye, is a significant clinical manifestation of Thyroid Eye Disease, and its reduction is crucial for improving patient outcomes and quality of life.

Secondary objectives include:

• Evaluating the efficacy of subcutaneous satralizumab compared with placebo at Week 24 based on overall response.
• Assessing the efficacy based on reduction in the clinical activity score.
• Assessing the efficacy based on change in proptosis from baseline to Week 24.
• Assessing the efficacy based on health-related quality of life using the Graves’ Ophthalmopathy Quality of Life Questionnaire.
• Assessing the efficacy based on reduction/improvement in diplopia.
• Assessing the efficacy based on improvement in orbital pain.
• Evaluating the safety and tolerability of satralizumab.
• Characterizing the satralizumab pharmacokinetic profile.

The clinical trial involves a total of **106 participants** diagnosed with **Moderate-to-Severe Thyroid Eye Disease** (TED). The study population includes both male and female subjects aged 18 years and older. Participants were selected based on their clinical diagnosis of either active or chronic inactive TED, with specific criteria regarding the clinical activity score and proptosis measurements. The trial does not include a vulnerable population. All participants are required to be euthyroid or have mild hypo- or hyperthyroidism, ensuring their background disease is under control. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial aims to evaluate the efficacy of subcutaneous satralizumab compared with placebo, focusing on proptosis response at Week 24.

The clinical trial is a **Phase III**, randomized, double-masked, placebo-controlled, multicenter study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of satralizumab in participants with moderate-to-severe **Thyroid Eye Disease** (TED). The trial aims to assess the efficacy of subcutaneous satralizumab compared with placebo at Week 24, focusing on proptosis response. The study is expected to commence recruitment on January 25, 2024, and conclude by May 4, 2026.

Participants will be randomly assigned to receive either satralizumab or a placebo, with neither the participants nor the investigators aware of the group assignments, ensuring a double-masked design. The trial will include several key visits: an initial screening visit to confirm eligibility based on inclusion criteria such as age, clinical diagnosis of TED, and thyroid status; baseline assessments on Day 1; and subsequent follow-up visits to monitor progress and collect data on primary and secondary endpoints. The primary endpoint is the proportion of participants with active disease achieving a ≥2mm reduction in proptosis from baseline at Week 24. Secondary endpoints include changes in clinical activity score (CAS), proptosis, and quality of life measures.

The expected duration of participant involvement is approximately 24 weeks, with regular follow-up visits scheduled to assess treatment efficacy and safety. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or failure to adhere to the study protocol. Participants will undergo a final end-of-study visit to evaluate overall outcomes and any long-term effects of the treatment. The trial's rigorous design and comprehensive assessment schedule aim to provide robust data on the potential benefits and risks of satralizumab for individuals with moderate-to-severe TED.

The clinical trial involves the evaluation of **Satralizumab**, a humanized anti-IL-6 receptor monoclonal antibody, identified by synonyms such as RO5333787 and SA237. This experimental medication is administered subcutaneously to participants with moderate-to-severe **Thyroid Eye Disease**. The pharmaceutical form, dosage, and specific administration schedule are not detailed in the provided data. Satralizumab is an orphan drug, relabeled for clinical trial use, and is sponsored by Roche Registration GmbH. The trial aims to assess the efficacy of Satralizumab compared to a placebo over a 24-week period, focusing on proptosis response as a primary endpoint.

In addition to Satralizumab, the study includes the use of a **placebo** as a comparator treatment. The placebo is administered in a manner consistent with the experimental drug to maintain the double-masked nature of the trial. The placebo serves as a control to evaluate the true efficacy and safety profile of Satralizumab.

Other non-experimental treatments in the study include auxiliary medications such as **CT-P10**, a protein of other origin, and **Ciclosporin**, a chemical substance. These auxiliary treatments are not the primary focus of the trial but may be used to support the overall treatment regimen. The specific roles and administration details of these auxiliary treatments are not provided in the data.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The study is designed to maintain rigorous standards of clinical research, ensuring the reliability and validity of the trial outcomes.

The efficacy of satralizumab in the treatment of moderate-to-severe **Thyroid Eye Disease** (TED) will be assessed in a Phase III, randomized, double-masked, placebo-controlled, multicenter clinical trial. The primary endpoint for evaluating efficacy is the proportion of participants with active disease achieving a reduction of at least 2 mm in proptosis from baseline at Week 24 in the study eye, without a corresponding deterioration in the fellow eye. Secondary endpoints include the proportion of participants with active disease achieving an overall response at Week 24, defined as a reduction of at least 2 points in the Clinical Activity Score (CAS) and a reduction of at least 2 mm in proptosis from baseline in the study eye, provided there is no deterioration in the fellow eye.

Additional secondary endpoints involve changes in proptosis and CAS from baseline to Week 24, improvements in the Visual Functioning and Appearance sub-scale scores of the Grave's orbitopathy-Quality of Life (GO-QoL) questionnaire, and reductions in diplopia and pain. The efficacy assessments will be conducted at specified timepoints, with the primary analysis occurring at Week 24. The trial will utilize validated scales and questionnaires, such as the CAS and GO-QoL, to measure these parameters. The study is designed to ensure rigorous data collection and analysis to accurately determine the efficacy of satralizumab in comparison to placebo.