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: the lack of head-to-head studies of temumab and glucocorticoids.
The aim of this clinical study is to:
1. To evaluate the efficacy of IBI311 treatment in patients with active moderate to severe TAO in the initial treatment. 2. To observe the safety of IBI311 treatment in patients with active moderate to severe TAO in the initial treatment. 3. Head-to-head comparison of sequential hormone therapy and IBI311 therapy in patients with active moderate to severe TAO in the initial 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.
Have not received glucocorticoid treatment for TAO in the past.
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 10-mL glass vials as a Injection solution containing.
Glucocorticoids
Drug500mg methylprednisolone was intravenously injected once a day for 3 consecutive days. The next treatment was carried out with an interval of 2 weeks for a total of 8 times.
Percentage of participants who were overall treatment responders ater 4 times and at the end of treatment
Subjects in the study eye with a reduction of ≥2 mm in exophthalmos and a reduction of ≥2 points in the clinical activity score (CAS) from baseline, and no deterioration in the contralateral eye (an increase of ≥2 mm in exophthalmos or an increase of ≥2 points in CAS)
Percentage of participants who were CAS categorical responders after 4 times and at the end of the treatment
The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore "equivocal" redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no inflammatory symptoms) to 7 (most inflammatory symptoms). CAS categorical responders were defined as subjects whose CAS in the study eyes decreased to 0 or 1 (with no or minimal inflammatory symptoms)
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 intervention observation period -1.
Incidence and characterization of nonserious treatment emergent adverse events (TEAEs) during the treatment
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
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