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.
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；
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;
Single group
[18F]AlF-NOTA-FAPI-04PET/CT
Diagnostic test\[¹⁸F\]AlF-NOTA-FAPI-04 PET/CT is used as a molecular imaging intervention in Thyroid Eye Disease to noninvasively assess fibroblast activation protein expression in orbital tissues. It enables evaluation of disease activity, orbital involvement, and treatment response by providing quantitative functional imaging beyond conventional anatomical modalities.
5.0-T high-resolution MRI
Diagnostic test5.0-T high-resolution MRI is used as an imaging intervention in Thyroid Eye Disease to provide detailed anatomical visualization of the orbit, including extraocular muscles, orbital fat, optic nerve, and soft tissues. It allows precise assessment of disease extent, structural changes, and treatment-related morphological responses.
To evaluate the effect of teprotumumab N01 on the response rate in patients with TED
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
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
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.
To evaluate the effect of teprotumumab N01 on the response rate in patients with TED
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 the recurrence rate of TED after discontinuation of teprotumumab N01.
The recurrence rate is defined as the proportion of subjects who relapse at Week 48 among those who achieved a response at Week 24. Recurrence is defined as the occurrence of dysthyroid optic neuropathy (DON), or worsening of ≥2 of the following 5 criteria compared with Week 24 in either eye: 1. CAS increase ≥2 points; 2. Proptosis increase ≥2 mm; 3. Palpebral fissure width (height) increase ≥2 mm; 4. New-onset diplopia or worsening diplopia (≥1 grade increase on the Bahn-Gorman scale) or increased limitation of ocular motility ≥8°; 5. Soft tissue involvement worsening ≥2 grades (based on class 2 NOSPECS and EUGOGO color atlas evaluation).
Change in Clinical Activity Score (CAS)
Proportion of subjects with Clinical Activity Score reduction ≥2 points or Clinical Activity Score \<3. The original Clinical Activity Score evaluates seven inflammatory parameters, each scored as 1 point if present and 0 if absent, yielding a total score ranging from 0 to 7: 1. Spontaneous retrobulbar pain 2. Pain on attempted up- or down-gaze 3. Redness of the eyelids 4. Redness of the conjunctiva 5. Swelling of the eyelids 6. Chemosis 7. Inflammation of the caruncle and/or plica A CAS ≥ 3/7 is generally considered indicative of active disease, suggesting ongoing inflammation that may respond to immunosuppressive or anti-inflammatory therapy.
Improvement in Proptosis
Proptosis response rate, defined as a reduction ≥2 mm in the study eye without an increase ≥2 mm in the contralateral eye.
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Peking University Third Hospital
Lead sponsor
Innovent Biologics (Suzhou) Co. Ltd.
Collaborator
