Targeting IL-6 Receptor Signaling with Satralizumab in Thyroid Eye Disease: Design of the Phase 3 SatraGO-1 and SatraGO-2 Trials.

IF 3.2 3区医学 Q2 OPHTHALMOLOGY

Ophthalmology and Therapy Pub Date : 2025-10-09 DOI:10.1007/s40123-025-01255-3

Daniel Ezra, Atif Collins, Zdenka Haskova, Thomas Kuenzel, Hiroaki Ida, Miriam Triyatni, Christopher Brittain, Oluwatobi Idowu

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引用次数: 0

Abstract

Introduction: Thyroid eye disease (TED) is a rare, autoimmune, orbital inflammatory disorder that is disfiguring, debilitating, and potentially sight-threatening. There is an unmet need for a fast-acting, durable, systemic disease-modifying therapy in active TED, for which current options are associated with relapses and side effects, and for chronic inactive TED, which is largely managed with surgery. Satralizumab is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody that prevents IL-6 from binding to its receptor, thereby reducing proinflammatory and profibrotic signaling. The SatraGO-1 and SatraGO-2 trials evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of satralizumab in participants with active, moderate-to-severe, and chronic inactive TED.

Methods: SatraGO-1 and SatraGO-2 were two identically designed, 72-week, double-masked, placebo-controlled, multicenter, two-stage randomization, phase 3 trials in adults with active, moderate‑to‑severe TED or chronic inactive TED. Participants were randomized 1:1 to receive satralizumab or matching placebo. Based on the proptosis response assessed at week 24, nonresponders received satralizumab every 4 weeks (Q4W), while responders were rerandomized in a 1:1 ratio to receive satralizumab or placebo Q4W through week 44. The primary end point was the proportion of participants with active, moderate-to-severe TED who achieved ≥ 2-mm reduction in proptosis in the study eye from baseline at week 24.

Results: SatraGO-1 and SatraGO-2 enrolled 131 and 127 participants, respectively.

Conclusions: The SatraGO-1 and SatraGO-2 trials investigated IL-6R inhibition via satralizumab in TED. Satralizumab offers a potential disease-modifying treatment option for TED while minimizing safety risks associated with current treatments.

Trial registration: SatraGO-1 (NCT05987423) and SatraGO-2 (NCT06106828).

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靶向IL-6受体信号的Satralizumab治疗甲状腺眼病：SatraGO-1和SatraGO-2期试验设计

简介：甲状腺眼病（TED）是一种罕见的自身免疫性眼窝炎症性疾病，可导致毁容、衰弱和潜在的视力威胁。对于活动性TED和慢性非活动性TED，目前的治疗方案与复发和副作用有关，而对于慢性非活动性TED，主要通过手术治疗，目前对速效、持久、全身性疾病改善治疗的需求尚未得到满足。Satralizumab是一种重组人源化抗白细胞介素-6受体（IL-6R）单克隆抗体，可阻止IL-6与其受体结合，从而减少促炎和促纤维化信号。SatraGO-1和SatraGO-2试验评估了satralizumab在活动性、中重度和慢性非活动性TED患者中的疗效、安全性、药代动力学和药效学。方法：SatraGO-1和SatraGO-2是两项设计相同、为期72周、双盲、安慰剂对照、多中心、两阶段随机化的3期试验，在成人活动性、中重度TED或慢性非活动性TED患者中进行。参与者以1:1的比例随机分配接受satralizumab或匹配的安慰剂。根据第24周评估的预后反应，无应答者每4周接受一次satralizumab (Q4W)，而应答者以1:1的比例重新随机分配到第44周接受satralizumab或安慰剂。主要终点是活动性、中重度TED患者的比例，在第24周时，研究眼的角膜突出比基线降低≥2mm。结果：SatraGO-1和SatraGO-2分别入组131名和127名受试者。结论：SatraGO-1和SatraGO-2试验研究了通过satralizumab对TED患者IL-6R的抑制作用。Satralizumab为TED提供了一种潜在的疾病改善治疗选择，同时最大限度地降低了与当前治疗相关的安全风险。试验注册：SatraGO-1 （NCT05987423）和SatraGO-2 （NCT06106828）。

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来源期刊

Ophthalmology and Therapy OPHTHALMOLOGY-

CiteScore

4.20

自引率

3.00%

发文量

157

审稿时长

6 weeks

期刊介绍： Aims and Scope Ophthalmology and Therapy is an international, open access, peer-reviewed (single-blind), and rapid publication journal. The scope of the journal is broad and will consider all scientifically sound research from preclinical, clinical (all phases), observational, real-world, and health outcomes research around the use of ophthalmological therapies, devices, and surgical techniques. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/series, trial protocols and short communications such as commentaries and editorials. Ophthalmology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. 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