Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease closely related to thyroid disease, which leads the incidence of orbital disease in adults and is the most common cause of diffuse toxic goiter (Graves disease, GD). The clinical manifestations of TAO are complex and varied. In severe cases, it may seriously impair visual function, affect daily life, and even cause corneal ulceration, perforation, and blindness. Therefore, a reasonable and effective treatment plan should be chosen according to the degree of TAO. Tetuzumab (IBI311) is a fully human monoclonal insulin-like growth factor-1 receptor inhibitory antibody. It has binding activity against IGF-1R positive cells, can block the binding of IGF-1 and IGF-2 to IGF-1R, and has a dose-dependent effect. It can inhibit the proliferation of HT29 cells caused by the activation of the IGF-1R signaling pathway. Meanwhile, it can dose-dependently inhibit the proliferation of orbital fibroblasts and the secretion of hyaluronic acid (HA) in patients with TAO.
However, there are still significant gaps in the existing research evidence: There is a lack of reports on the efficacy and safety of Tetuzumab (IBI311) in the population after glucocorticoid treatment.
The aim of this clinical study is to:
1. To evaluate the efficacy of IBI311 treatment in patients with active moderate to severe TAO after glucocorticoid treatment. 2. To observe the safety of IBI311 treatment in patients with active moderate to severe TAO after glucocorticoid treatment.
Diagnosed with TAO by Bartley criteria.
Moderate to severe patients defined by EUGOGO.
CAS ≥4 (on the 7-item scale) for the study eye.
participants have received glucocorticoid treatment for TAO in the past，but did not responsive or has an unsatisfactory effect.
Anticipated need for intervention due to sight-threatening complications or other significant and acute deterioration in vision.
Combined with other lesions in the orbit.
Receive orbital radiotherapy or surgical treatment for TED, including orbital decompression, strabismus surgery and eyelid retraction correction.
During the screening period, if either ear has a history of tinnitus or other hearing impairment; Or abnormal pure tone audiometry results (defined as an average bone conduction hearing threshold of ≥25 dB at 0.5, 1, 2, 4 kHz or a bone conduction hearing threshold of ≥40 dB at any frequency).