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

A Multicenter, Randomized, Double-Masked Phase II Study Evaluating the Efficacy and Safety of IBI311 in Subjects With Inactive or Active Thyroid Eye Disease

This is a multicenter, randomized, double-masked phase II study evaluating the efficacy and safety of IBI311 in subjects with inactive or active thyroid eye disease. Approximately 36 subjects meeting the study eligibility criteria will be randomly assigned to the 3-10 mg group, 3-20 mg group, 10 mg group, or 20 mg group on day 1 in a 1:1:2:2 ratio. Dose conversion of the 3-10 mg or 3-20 mg group was performed at week 12. Active and inactive TED was a stratification factor in this study. Active and inactive TED subjects were enrolled in a 1:1 ratio.

Key Inclusion Criteria:

1. Written informed consent.

2. Male or female subject between the ages of 18 and 80 years at screening.

3. Weight between 50 kg and 100 kg.

4. 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.

5. Exophthalmos ≥ 20 mm in the study eye at baseline.

6. 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:

1. Baseline CAS decreased by ≥ 2 points, or baseline proptosis decreased by ≥ 2 mm as compared with screening.
2. 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;
3. Corneal ulcers with no relief after treatment as determined by the investigator;
4. TED patients who need immediate corticosteroid therapy, orbital radiotherapy, or orbital decompression;
5. 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;
6. 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.
7. 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);
8. 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%);
9. Systemic use of glucocorticoids ≤ 30 days prior to screening;
10. Periorbital use of glucocorticoids ≤ 90 days prior to screening;
11. Systemic use of immunosuppressants ≤ 90 days prior to screening;
12. Use glucocorticoid eye drops or immunosuppressive eye drops ≤ 30 days prior to screening

12. 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.