Thyroid Eye Disease
Conditions
Interventions
Experimental group:Tetumumab treatment
Sponsors
Department of Ophthalmology, West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily participate in the study and sign the informed consent form 2. Male or female subjects aged between 18~80 years old (inclusive) at screening 3. Diagnosed with thyroid ophthalmopathy before screening, and the CAS score of the affected eye is =1.6 points (using the scoring method, SIR= 60% 3 points); (2) The signal intensity of extraocular muscles was significantly enhanced on the fat inhibition sequence of T1WI enhanced scanning, and the average score of (involved extraocular muscle signal intensity-temporal muscle signal intensity)/temporal muscle signal intensity (SIR) score was >=1.5 points (using the assignment method, SIR= 60% 3 points); (3) The cross-sectional area of the maximum thickening part of the extraocular muscle in the coronal position increased, and the muscle with the largest increase in cross-sectional area was subject to the muscle with the largest increase in cross-sectional area, the > of the inferior rectus muscle was 0.73 mm^2, the superior rectus muscle > was 0.72 mm^2, the medial rectus muscle > was 0.66 mm^2, and the lateral rectus muscle > was 0.74 mm^2 5. Have not received and have not planned to receive any treatment for thyroid eye disease before baseline and have no plans to receive during the study period, including drug therapy (topical or systemic glucocorticoids, traditional immunosuppressants and other biological agents), orbital radiation therapy, or surgical treatment (orbital decompression, strabismus surgery and eyelid retraction correction), etc 6. Normal thyroid function at screening, or mild hyperthyroidism or hypothyroidism (defined as free tetraiodothyronine [FT4] and free triiodothyronine [FT3] levels deviating from the normal reference range of the local research center laboratory by less than 50%), and timely correction of mild hypothyroidism or hyperthyroidism, and maintenance of normal thyroid function during the clinical trial 7. If it is a female subject, it should be a female of childbearing potential who is of no childbearing potential or has a negative blood pregnancy test during the screening period and agrees to take contraceptive measures within 120 days from the screening period to the last dose; In the case of male subjects, they should agree to use contraception from the screening period until 120 days after the last dose
Exclusion criteria
Exclusion criteria: 1. An increase of 2 points in Clinical Activity Score (CAS) from screening to baseline. 2.Best-corrected visual acuity (BCVA) decline due to optic neuropathy, defined as a two-line decrease in vision over the past 6 months, new visual field defects, or color vision impairment secondary to optic nerve involvement. 3.Contraindications to MRI, including absolute contraindications (e.g., pacemakers, cochlear implants; patients with cardiac stents or prosthetic heart valves; presence of ferromagnetic vascular clips; intraocular metallic foreign bodies) and relative contraindications (e.g., ferromagnetic objects within or near the scanning field; metallic dental prostheses precluding nasopharyngeal/oral examination; metallic infusion pumps contraindicating scans of the corresponding area; intrauterine devices precluding pelvic scans; claustrophobia; inability to lie flat for more than 30 minutes; impaired consciousness, severe hypoxia, agitation, or in need of emergency care). 4.Any pre-existing disease, metabolic disorder, abnormal findings on physical examination or clinical laboratory tests that, in the opinion of the investigator, may contraindicate the use of the investigational drug, interfere with interpretation of the study results, or pose a high risk of complications. These include but are not limited to: confirmed or suspected inflammatory bowel disease, coagulation disorders, cerebrovascular accident or transient ischemic attack within 6 months prior to screening, acute myocardial infarction, unstable angina, coronary artery bypass grafting, percutaneous coronary intervention (excluding diagnostic angiography), severe arrhythmias, history of malignancy within the past 5 years (excluding successfully resected and non-metastatic squamous cell carcinoma of the skin, basal cell carcinoma, or in situ carcinoma of the cervix), severe systemic infections, and proptosis not related to TED. 5.Presence of tinnitus or history of other hearing impairment in either ear during screening, or abnormal pure-tone audiometry (defined as an average bone conduction threshold =25 dB at 0.5–1–2–4 kHz, or >=40 dB at any single frequency). 6.Poorly controlled diabetes at screening, defined as hemoglobin A1c (HbA1c) >=9.0%, or initiation of a new diabetes medication (oral or injectable), or dose change >10% of a current diabetes medication within 60 days prior to screening. 7.Poorly controlled hypertension at screening, defined as systolic blood pressure >=160 mmHg or diastolic blood pressure >=100 mmHg; or changes in antihypertensive medication (dosage or type) within 30 days before screening; or evidence of renal artery stenosis or unstable blood pressure (including orthostatic hypotension). 8.Screening 12-lead ECG showing heart rate 100 bpm, evidence of active cardiac disease, or ECG abnormalities that, in the investigator’s opinion, may interfere with interpretation during follow-up. Subjects with QTcF >450 ms (males) or >470 ms (females) should be excluded. 9.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3× upper limit of normal (ULN) at screening, or active hepatitis B infection (defined as positive HBsAg with HBV DNA >1000 IU/mL), or receiving antiviral treatment for hepatitis B. 10.Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2 at screening, calculated by the MDRD formula: GFR = 186 × (serum creatinine in mg/dL)^–1.154 × (age)^–0.203 × 0.742 (if female). Conversion: 1 µmol/L = 0.0113 mg/dL
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Signal intensity ratio (SIR) of the affected extraocular muscles on MRI;Volume of the affected extraocular muscles on MRI; | — |
Secondary
| Measure | Time frame |
|---|---|
| Diplopia Score;Eye movement;Safety; | — |
Countries
China
Contacts
Public ContactWeimin He
Department of Ophthalmology, West China Hospital, Sichuan University
Outcome results
None listed