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

Evaluating the Efficacy and Safety of Teprotumumab N01 in Patients With Thyroid Eye Disease by FAPI PET/CT and 5.0T-MRI

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.

Study Overview

• Status: Recruiting
• Conditions: Thyroid Eye Disease
• Intervention / Treatment: Diagnostic test: [18F]AlF-NOTA-FAPI-04PET/CT; Diagnostic test: 5.0-T high-resolution MRI

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lingge Suo; Phone Number: 86-010-82264935; Email: suolingge_1019@126.com
• Study Contact Backup: Name: Yi Wang; Phone Number: 86-13439150508; Email: wangyieye@126.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University Third Hospital
    • Contact: Lingge Suo; Phone Number: 86-010-82264935; Email: suolingge_1019@126.com
    • Contact: Yi Wang; Phone Number: 86-13439150508; Email: wangyieye@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to comply with the study procedures and voluntarily sign the written informed consent form;
2. Male or female subjects aged 18-80 years (inclusive) at screening;
3. Body weight between 45 and 100 kg (inclusive);
4. Meet internationally recognized diagnostic criteria for TED who are receiving teprotumumab N01 treatment；
5. Diagnosed with TED at both the screening and baseline visits;
6. Disease duration of less than 9 months

Exclusion Criteria:

1. Poorly controlled thyroid function, defined as FT3 or FT4 deviating by more than 50% from the normal reference range;
2. Receipt of radioactive iodine therapy within 3 months prior to screening;
3. 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;
4. Corneal ulcer without improvement after treatment, as judged by the investigator;
5. A decrease in CAS score of ≥2 points at baseline compared with screening;
6. 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;
7. Prior orbital radiotherapy for TED at any time before screening;
8. Prior use at any time before screening of oral, injectable, topical, or inhaled glucocorticoids at a cumulative dose ≥1 g methylprednisolone equivalent;
9. Receipt within 3 months prior to screening of oral or intravenous glucocorticoids (<1 g methylprednisolone equivalent), or peribulbar or periocular glucocorticoid injections for TED;
10. Use of any other immunosuppressive agents orally or intravenously within 3 months prior to screening;
11. Vaccination within 1 month prior to screening;
12. 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;
13. 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;
14. History of inflammatory bowel disease, gastrointestinal ulcer or diverticulitis, Cushing's disease, osteoporosis, or psychiatric disorders;
15. History of immunodeficiency, including HIV infection or AIDS, other acquired or congenital immunodeficiency disorders, or organ transplantation;
16. History of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, or Sjögren's syndrome;
17. 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);
18. 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;
19. 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;
20. 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;
21. 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;
22. Presence of uncontrolled disease conditions, including but not limited to asthma, psoriasis, or inflammatory bowel disease requiring glucocorticoid treatment at disease onset;
23. History of hypersensitivity or allergy to other monoclonal antibodies;
24. 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;
25. 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;
26. 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;
27. Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental arm; Patients with TED who are receiving teprotumumab N01 treatment will be recruited in the study

Diagnostic test: [18F]AlF-NOTA-FAPI-04PET/CT; [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.; Diagnostic test: 5.0-T high-resolution MRI; 5.0-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: 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);; Proptosis reduction ≥2 mm;; Palpebral fissure width (height) reduction ≥2 mm;; Diplopia improvement (≥1 grade improvement on the Bahn-Gorman subjective diplopia scale [0-3]) or improvement in ocular motility ≥8°;; Soft tissue involvement improvement ≥2 grades (based on class 2 NOSPECS grading and EUGOGO color atlas evaluation).	weeks 24
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.	Weeks 24 and 48
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.	Weeks 24 and 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	weeks 48
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: CAS increase ≥2 points;; Proptosis increase ≥2 mm;; Palpebral fissure width (height) increase ≥2 mm;; New-onset diplopia or worsening diplopia (≥1 grade increase on the Bahn-Gorman scale) or increased limitation of ocular motility ≥8°;; Soft tissue involvement worsening ≥2 grades (based on class 2 NOSPECS and EUGOGO color atlas evaluation).	weeks 48
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: Spontaneous retrobulbar pain; Pain on attempted up- or down-gaze; Redness of the eyelids; Redness of the conjunctiva; Swelling of the eyelids; Chemosis; 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.	Weeks 24 and 48
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.	Weeks 24 and 48
Improvement in Palpebral Fissure Width (Height)	Response rate, defined as a reduction ≥2 mm in the study eye without an increase ≥2 mm in the contralateral eye.	Weeks 24 and 48
Improvement in Diplopia	Diplopia was evaluated using the Bahn-Gorman subjective diplopia scoring system. The grading criteria were defined as follows: Grade 0: No diplopia; Grade 1: Intermittent diplopia, occurring in the primary gaze position under conditions of fatigue or upon awakening; Grade 2: Inconstant (nonpersistent) diplopia, elicited only at extreme gaze positions; Grade 3: Constant diplopia, present in the primary gaze or reading position. Scores were assigned based on the participants' subjective reports. An improvement of ≥1 grade was considered clinically meaningful.	Weeks 24 and 48
Improvement in Ocular Motility	Ocular motility limitation in the horizontal and vertical directions was assessed using the corneal light reflex method. Under ambient room lighting, the examiner directed a penlight toward the participant's eyes and observed the tested eye along the visual axis. Participants were instructed to move the eye in the four cardinal directions (adduction, abduction, elevation, and depression), while the examiner evaluated the position of the corneal light reflex on the corneal surface in each gaze position.An ocular rotation of 45°, 30°, and 15° was estimated when the reflex was located at the limbus, midway between the limbus and the pupillary margin, and at the pupillary margin, respectively.The degree of movement limitation in each gaze direction was recorded sequentially for each eye.	Weeks 24 and 48
Improvement in Soft Tissue Involvement	Soft tissue response rate, defined as improvement ≥2 grades in the study eye without worsening ≥2 grades in the contralateral eye, based on class 2 NOSPECS grading and EUGOGO color atlas evaluation. Class 2 NOSPECS classification was graded as follows: Grade 0: No signs or symptoms; Grade 1 (Mild): Eyelid and conjunctival edema, conjunctival hyperemia, eyelid fullness, orbital fat prolapse, and a palpable lacrimal gland or enlarged extraocular muscle detectable through the lower eyelid; Grade 2 (Moderate): In addition to the above signs, marked conjunctival edema (chemosis) and lagophthalmos; Grade 3 (Severe): More pronounced ocular signs with marked severity. The EUGOGO color atlas evaluation: Severity was assessed by comparison with representative atlas images of eyelid edema, eyelid erythema, conjunctival hyperemia, and chemosis, and graded on a 0-3 ordinal scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe), allowing for standardized and reproducible evaluation.	Weeks 24 and 48
Change in Best-Corrected Visual Acuity (BCVA)	Mean change from baseline in BCVA of the study eye.	Weeks 24 and 48
Change in Intraocular Pressure (IOP)	Mean change from baseline in IOP of the study eye.	Weeks 24 and 48
Change in Quality of Life (GO-QoL)	Mean change from baseline in total Graves' Ophthalmopathy Quality of Life (GO-QoL) score. The Graves' ophthalmopathy-specific quality-of-life (GO-QoL) questionnaire was used to assess disease-specific visual function and psychosocial impact. It comprises two subscales: visual functioning (questions 1-8), evaluating limitations in daily activities such as cycling, driving, walking, reading, watching TV, and hobbies; and appearance/life impact (questions 9-16), assessing perceived changes in appearance, social interactions, self-confidence, and coping behaviors. Each item is scored on a 3-point scale (0 = severely limited/affected, 1 = somewhat limited/affected, 2 = not limited/affected), with subscale scores calculated separately. Subscale scores range from 0 (worst) to 32 (best). Patients were instructed to focus on the past week when responding.	Weeks 24 and 48
Changes in Laboratory Biomarkers	Mean change from baseline in: Thyrotropin receptor antibody (TRAb).	Weeks 24 and 48
Safety and Tolerability of Teprotumumab N01	Incidence of grade ≥3 serious adverse events (SAEs), assessed according to CTCAE version 5.0;; Incidence, number, severity, and relationship of all ocular and systemic adverse events, serious adverse events, and adverse drug reactions, including events related to underlying disease (e.g., thyroid dysfunction, sight-threatening TED) and events potentially related to teprotumumab N01 (e.g., menstrual disorders, infusion reactions, exacerbation of inflammatory bowel disease, hyperglycemia, hearing impairment, sinus bradycardia).	From baseline through Week 48

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Collaborators: Innovent Biologics (Suzhou) Co. Ltd.
• Investigators: Study Chair: Yi Wang, Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: December 21, 2025
• First Submitted That Met QC Criteria: February 13, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Thyroid Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Graves Ophthalmopathy
• Other Study ID Numbers: Teprotumumab N01-TED

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No