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.
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 IBI311 in inactive moderate to severe TAO patients.
The aim of this clinical study is to:
1. To evaluate the efficacy of IBI311 treatment in patients with inactive moderate to severe TAO. 2. To observe the safety of IBI311 treatment in patients with inactive moderate to severe TAO.
Diagnosed with TAO by Bartley criteria.
Moderate to severe patients defined by EUGOGO.
CAS <3 (on the 7-item scale) for the study eye.
Participant with intractable diplopia, or incomplete closure of both eyes, or requiring further surgical intervention.
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).
Parallel
IBI311
DrugIBI311 is a fully human anti-IGF-1R mAb. IBI311 will be provided in single-dose 500-mg glass vials as a Injection solution containing.
Follew-up
Other interventionrecived follow-up every six months
Percentage of participants who were diplopia responders after 4 times and at the end of the treatment
Diplopia responders were defined as percentage of participants with ≥ 1 class improvement of eye motility from baseline assessed by Gorman score. Gorman score: 1 = no diplopia, 2 =intermittent diplopia, 3 = inconstant (gaze-evoked) diplopia, 4 = constant diplopia in primary or reading position.
Percentage of participants who were proptosis responders after 4 times and and the end of the treatment
Proptosis responders were defined as subjects whose exophthalmos in the study eye decreased by ≥2 mm compared to the baseline, and whose exophthalmos in the contralateral eye did not deteriorate (increase by ≥2 mm) at the end of the treatment.
Incidence and characterization of nonserious treatment emergent adverse events (TEAEs) during the treatment
Percentage of participants who were ATA categorical responders after 4 times and at the end of the treatment
Participants whose baseline ATA score of the study eye was \>4, with a reduction of ≥1 grade in the ATA score, while there was no corresponding deterioration in the contralateral eye (≥1 grade deterioration). The denominator is the number of subjects with a baseline ATA score grade \>4.
Change of GO-QoL from baseline after 4 times and at the end of the treatment
Changes of the visual field in the dark areas from baseline after 4 times and at the end of the treatment
MR Imaging changes of orbital contents compared with the baseline after 4 times and at the end of the treatment
Including: exophthalmos, the volume of the lacrimal gland/optic nerve/extraocular muscle/retroorbital adipose tissue/lacrimal gland, edema, inflammation, blood perfusion, fibrosis, and fatty changes
Percentage of participants who underwent surgery throughout the study period
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