Evaluating the Efficacy and Safety of Teprotumumab N01 in Patients With Thyroid Eye Disease.

Exclusion Criteria27

• Poorly controlled thyroid function, defined as FT3 or FT4 deviating by more than 50% from the normal reference range;
• Receipt of radioactive iodine therapy within 3 months prior to screening;
• Thyroid dysfunction-related optic neuropathy, defined as any of the following occurring within the past 6 months due to optic nerve involvement: a decrease in best-corrected visual acuity (BCVA) of ≥2 lines, new visual field defects, or secondary color vision impairment;
• Corneal ulcer without improvement after treatment, as judged by the investigator;
• A decrease in CAS score of ≥2 points at baseline compared with screening;
• Prior treatment at any time before screening with monoclonal antibodies, including but not limited to anti-CD20 antibodies, anti-interleukin-6 antibodies, or anti-IGF-1R antibodies;
• Prior orbital radiotherapy for TED at any time before screening;
• Prior use at any time before screening of oral, injectable, topical, or inhaled glucocorticoids at a cumulative dose ≥1 g methylprednisolone equivalent;
• Receipt within 3 months prior to screening of oral or intravenous glucocorticoids (\<1 g methylprednisolone equivalent), or peribulbar or periocular glucocorticoid injections for TED;
• Use of any other immunosuppressive agents orally or intravenously within 3 months prior to screening;
• Vaccination within 1 month prior to screening;
• Hemoglobin \< 8.5 g/dL, platelet count \< 100 × 10³/µL, white blood cell count \< 3 × 10⁹/L, absolute neutrophil count (ANC) \< 2 × 10⁹/L, or absolute lymphocyte count \< 5 × 10⁸/L;
• Acute or chronic, active or latent, recurrent bacterial, viral, fungal, or other infections, including but not limited to tuberculosis (positive T-SPOT or imaging findings), hepatitis B (HBsAg or HBcAb positive), hepatitis C (anti-HCV or HCV RNA positive), syphilis, herpes simplex, or herpes zoster;
• History of inflammatory bowel disease, gastrointestinal ulcer or diverticulitis, Cushing's disease, osteoporosis, or psychiatric disorders;
• History of immunodeficiency, including HIV infection or AIDS, other acquired or congenital immunodeficiency disorders, or organ transplantation;
• History of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, or Sjögren's syndrome;
• History or current presence of malignancy (except for completely resected skin squamous cell carcinoma, basal cell carcinoma, or localized cervical carcinoma in situ without evidence of metastasis);
• Severe cardiovascular or cerebrovascular disease or related treatment history, including but not limited to stroke, transient ischemic attack, acute myocardial infarction, unstable angina, arrhythmia, heart failure, coronary artery bypass grafting, or percutaneous coronary intervention;
• Severe hepatic or renal insufficiency, defined as liver disease or abnormal liver function with ALT or AST ≥ 1.5 × the upper limit of normal, estimated glomerular filtration rate \< 30 mL/min/1.73 m², or serum creatinine ≥ the upper limit of normal;
• Poorly controlled diabetes mellitus, defined as fasting blood glucose (FBG) ≥ 7.0 mmol/L or HbA1c ≥ 9.0% at screening, or initiation of new antidiabetic medication (oral or injectable) or a change in the dose of current antidiabetic medication by \> 10% within 2 months prior to screening;
• Poorly controlled hypertension, defined as systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg, or adjustment of antihypertensive medication (dose or drug class) within 1 month prior to screening;
• Presence of uncontrolled disease conditions, including but not limited to asthma, psoriasis, or inflammatory bowel disease requiring glucocorticoid treatment at disease onset;
• History of hypersensitivity or allergy to other monoclonal antibodies;
• Alcohol, tobacco, drug, or chemical substance abuse; Alcohol abuse: weekly alcohol intake \> 21 units for men or \> 14 units for women (1 unit = 360 mL beer, or 150 mL wine, or 45 mL distilled spirits/Chinese liquor); Tobacco abuse: smoking index (number of cigarettes per day × years of smoking) \> 400;
• Pregnant or breastfeeding female subjects, or male or female subjects planning pregnancy during the study or within 3 months after study completion, or unwilling to use effective contraception;
• Participation in another interventional clinical trial within 3 months prior to screening (for investigational drugs, within 5 half-lives, whichever is longer; vitamins and minerals excluded), or intention to participate in another clinical trial during the study;
• Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this clinical trial.