A Study of IBI311 in Subjects With Inactive or Active Thyroid Eye Disease

Key Inclusion Criteria:

• Written informed consent.
• Male or female subject between the ages of 18 and 80 years at screening.
• Weight between 50 kg and 100 kg.
• Moderate-to-severe active TED:

• CAS ≥ 3 in the study eye at screening and baseline;
• Usually associated with at least two of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, exophthalmos ≥ 3 mm above normal, and/or inconstant or constant diplopia;
• ≤ 12 months since the onset of active TED symptoms according to subjects' chief complaint or medical record at screening;

Inactive TED:

• According to subjects' chief complaint or medical record at screening, initial diagnosis of TED > 12 months but < 10 years prior to screening.
• CAS ≤ 2 in both eyes at screening and baseline and CAS ≤ 2 in both eyes for at least 6 months prior to screening or all of the following at least 6 months prior to screening: a. no progression in proptosis; b. no progression in diplopia; c. no new inflammatory TED symptoms.
• Exophthalmos ≥ 3 mm above normal.
• Exophthalmos ≥ 20 mm in the study eye at baseline.
• Female subjects should be fertile women who are sterile or have a negative blood pregnancy test during the screening period and who agree to take contraceptive measures within 120 days from the screening period to the last medication; Male subjects should agree to use contraception from the screening period to 120 days after the last dose.

Key Exclusion Criteria:

Subjects will be ineligible for study participation if they meet any of the following criteria:

• Baseline CAS decreased by ≥ 2 points, or baseline proptosis decreased by ≥ 2 mm as compared with screening.
• Visual function impairment due to optic neuropathy, defined as ≥ 2 lines of vision loss, new visual field defect, or color vision impairment secondary to optic nerve involvement within the past 180 days;
• Corneal ulcers with no relief after treatment as determined by the investigator;
• TED patients who need immediate corticosteroid therapy, orbital radiotherapy, or orbital decompression;
• At any time prior to baseline or during the study period planned to receive orbital radiation therapy or TED surgery, including orbital decompression, strabismus surgery, and eyelid retraction correction;
• Poorly controlled thyroid function, which was defined as free triiodothyronine (FT3) or free tetraiodothyronine (FT4) deviated more than 50% from the normal reference range of the local research center laboratory at screening.
• Either ear had a history of tinnitus or other hearing impairment; or abnormal pure tone audiometry (defined as mean bone conduction threshold [0.5, 1, 2, 4 kHz] ≥25 dB or any bone conduction threshold ≥ 40 dB);
• Poorly controlled diabetes at screening, defined as HbA1C ≥ 9.0% at screening, or any new medication for diabetes within 60 days prior to screening, or any dose adjustment for diabetes drugs > 10%);
• Systemic use of glucocorticoids ≤ 30 days prior to screening;
• Periorbital use of glucocorticoids ≤ 90 days prior to screening;
• Systemic use of immunosuppressants ≤ 90 days prior to screening;
• Use glucocorticoid eye drops or immunosuppressive eye drops ≤ 30 days prior to screening

• Use IBI311 or TEPEZZA at any time prior to screening; 13 Use CD20 antibody ≤ 1 year prior to screening, or IL-6R antibody ≤ 180 days prior to screening; 14. Subjects had participated in other interventional clinical trials ≤ 90 days prior to screening, or attempting to participate in other clinical trials during the study period.