Evaluating the Efficacy and Safety of Teprotumumab N01 in Patients With Thyroid Eye Disease by FAPI PET/CT and 5.0T-MRI
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- To evaluate the effect of teprotumumab N01 on the response rate in patients with TED
研究概览
简要总结
This is a prospective study designed to evaluate the efficacy and safety of Teprotumumab N01 in patients with Thyroid Eye Disease (TED). Eligible patients will receive Teprotumumab N01 and will be assessed using clinical and imaging parameters before and after treatment, with each patient serving as their own control. The primary endpoint is the overall response rate at Week 24.
详细描述
In this prospective study, patients with thyroid eye disease, treated with Teprotumumab N01 will be recruited. Clinical efficacy will be evaluated by changes in disease activity, ophthalmic findings, visual function, and quality of life. Advanced imaging techniques, including [18F]AlF-NOTA-FAPI-04PET/CT and 5.0-T high-resolution MRI, will be used to assess orbital tissue changes. Safety will be monitored throughout the study by recording adverse events and laboratory findings. The study aims to provide real-world evidence on the effectiveness and safety of Teprotumumab N01 in the management of thyroid eye disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to comply with the study procedures and voluntarily sign the written informed consent form;
- •Male or female subjects aged 18-80 years (inclusive) at screening;
- •Body weight between 45 and 100 kg (inclusive);
- •Meet internationally recognized diagnostic criteria for TED who are receiving teprotumumab N01 treatment；
- •Diagnosed with TED at both the screening and baseline visits;
- •Disease duration of less than 9 months
排除标准
- •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.
研究组 & 干预措施
Experimental arm
Patients with TED who are receiving teprotumumab N01 treatment will be recruited in the study
干预措施: [18F]AlF-NOTA-FAPI-04PET/CT (Diagnostic Test)
Experimental arm
Patients with TED who are receiving teprotumumab N01 treatment will be recruited in the study
干预措施: 5.0-T high-resolution MRI (Diagnostic Test)
结局指标
主要结局
To evaluate the effect of teprotumumab N01 on the response rate in patients with TED
时间窗: weeks 24
The overall response rate is defined as the proportion of subjects achieving a predefined therapeutic response in the study eye. A response is defined as improvement in ≥2 of the following 5 criteria compared with baseline, with no worsening in any criterion in either eye: 1. Clinical Activity Score (CAS) reduction ≥2 points (7-item CAS: eyelid erythema, eyelid edema, conjunctival injection, chemosis, caruncle swelling, spontaneous retrobulbar pain, pain on eye movement; 1 point each); 2. Proptosis reduction ≥2 mm; 3. Palpebral fissure width (height) reduction ≥2 mm; 4. Diplopia improvement (≥1 grade improvement on the Bahn-Gorman subjective diplopia scale \[0-3\]) or improvement in ocular motility ≥8°; 5. Soft tissue involvement improvement ≥2 grades (based on class 2 NOSPECS grading and EUGOGO color atlas evaluation).
To evaluate treatment response using [¹⁸F]AlF-NOTA-FAPI-04 PET/CT in patients with thyroid eye disease
时间窗: Weeks 24 and 48
Response will be assessed using \[¹⁸F\]AlF-NOTA-FAPI-04 PET/CT . These imaging modalities will quantitatively evaluate orbital inflammation, fibroblast activation, and structural changes in the orbit. Imaging-based response will be defined as significant reduction in radiotracer uptake on PET/CT compared with baseline.
To evaluate treatment response using 5.0-T high-resolution magnetic resonance imaging (MRI) in patients with thyroid eye disease
时间窗: Weeks 24 and 48
Response will be assessed using 5.0-T high-resolution magnetic resonance imaging (MRI). These imaging modalities will quantitatively evaluate orbital inflammation, fibroblast activation, and structural changes in the orbit. Imaging-based response will be defined as improvement in anatomical and inflammatory parameters on MRI compared with baseline.
次要结局
- To evaluate the effect of teprotumumab N01 on the response rate in patients with TED(weeks 48)
- To evaluate the recurrence rate of TED after discontinuation of teprotumumab N01.(weeks 48)
- Change in Clinical Activity Score (CAS)(Weeks 24 and 48)
- Improvement in Proptosis(Weeks 24 and 48)
- Improvement in Palpebral Fissure Width (Height)(Weeks 24 and 48)
- Improvement in Diplopia(Weeks 24 and 48)
- Improvement in Ocular Motility(Weeks 24 and 48)
- Improvement in Soft Tissue Involvement(Weeks 24 and 48)
- Change in Best-Corrected Visual Acuity (BCVA)(Weeks 24 and 48)
- Change in Intraocular Pressure (IOP)(Weeks 24 and 48)
- Change in Quality of Life (GO-QoL)(Weeks 24 and 48)
- Changes in Laboratory Biomarkers(Weeks 24 and 48)
- Safety and Tolerability of Teprotumumab N01(From baseline through Week 48)