A Study of Teprotumumab N01 in Subjects With Active Thyroid Eye Disease

A Multicenter, Randomized, Open-Label, Active-Controlled Phase IV Clinical Study to Evaluate the Efficacy and Safety of Teprotumumab N01 in the Treatment of Active Thyroid Eye Disease

This is a multicenter, randomized, open-label, active-controlled Phase IV clinical trial in participants with active thyroid eye disease (TED). Approximately 92 eligible participants will be randomized to the teprotumumab N01 group and the intravenous glucocorticoid (IVGC) group in a 1:1 ratio on Day 1. The randomization stratification factor is diplopia at baseline (Gorman diplopia score ≥1 vs. Gorman diplopia score = 0).

Inclusion Criteria:

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 45 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;

5. Exophthalmos ≥ 16 mm in the study eye at baseline.

6. Infertile female participants or fertile female participants with negative blood pregnancy test results during the screening period and agree to take contraceptive measures from screening to 120 days after the last dose; male participants should agree to use contraceptive measures from screening to 120 days after the last dose.

Exclusion Criteria:

Key Exclusion Criteria:

Participants to be excluded (Participants meeting any of the following criteria will be regarded as ineligible):

1. The CAS of the study eye at baseline is reduced by ≥ 2 points compared with that at screening, or the proptosis of the study eye at baseline is reduced by ≥ 2 mm compared with that at screening;
2. Participants previously diagnosed with dysthyroid optic neuropathy (DON), or with DON as determined by the investigator at screening;
3. Patients with corneal ulcers that are not relieved after treatment at the investigator's discretion;
4. Scheduled orbital radiotherapy at any time before baseline or during the study, or surgical treatment for TED, including orbital decompression, strabismus surgery, and eyelid surgery;
5. Participants with poorly controlled thyroid function, defined as free triiodothyronine (FT3) or free thyroxine (FT4) deviating from the normal reference range of the local laboratory by more than 50% at screening;
6. Any other pre-existing disease, metabolic disorder, or physical examination or clinical laboratory abnormality that leads to a reasonable suspicion of a disease or condition that contraindicates the use of the investigational drug, affects the interpretation of study results, or places the participant at high risk of treatment complications;
7. History of tinnitus or other hearing impairment in either ear during the screening period; or abnormal pure tone audiometry results (defined as an average bone conduction hearing threshold of ≥ 25 dB at 0.5, 1, 2, and 4 kHz, or a bone conduction hearing threshold of ≥ 40 dB at any frequency);
8. Poorly controlled diabetes mellitus (defined as glycosylated hemoglobin ≥ 8.0% at screening);
9. Cumulative dose of glucocorticoids used to treat TED ≥ 1 g methylprednisolone equivalents at any time before baseline;
10. Oral or intravenous glucocorticoids within 30 days prior to screening;
11. Peribulbar/periorbital injection of glucocorticoids within 90 days prior to screening;
12. Oral or intravenous administration of any other non-steroidal immunosuppressants within 90 days prior to screening;
13. Use of glucocorticoid eye drops/ointments or use of non-steroidal immunosuppressant eye drops within 30 days prior to screening;
14. Received TEPEZZA or Teprotumumab N01 Injection at any time before screening;
15. Received CD20 antibody or interleukin-6 receptor (IL-6R) antibody at any time before screening;
16. Have received any other TED therapeutic drugs under development (including but not limited to biologics targeting IGF-1R, FcRn, and TSHR) at any time before screening;
17. Use of any other monoclonal antibody within 90 days prior to screening;
18. Female participants in pregnancy or lactation.