Graves Ophthalmopathy, Optic Neuropathy, Thyroid Eye Disease, TED
Conditions
Keywords
Dysthyroid optic neuropathy, Orbital decompression, Teprotumumab N01, Intravenous methylprednisolone pulse, Thyroid eye disease
Brief summary
This study aims to evaluate the efficacy and safety of sequential Teprotumumab N01 compared with intravenous methylprednisolone (IVMP) after urgent orbital decompression in patients with dysthyroid optic neuropathy (DON).
Detailed description
This study is designed to evaluate the efficacy and safety of sequential systemic treatment after urgent orbital decompression in patients with dysthyroid optic neuropathy. All eligible participants will undergo standardized urgent orbital decompression. After surgery, participants will be randomized in a 1:1 ratio to receive either sequential Teprotumumab N01 or intravenous methylprednisolone. The study will compare visual function recovery, orbital signs, disease activity, quality of life, rescue treatment, recurrence, and safety between the two treatment groups. The primary outcome is the change from baseline in best-corrected visual acuity at Week 24. Secondary outcomes include changes in visual field mean deviation, Clinical Activity Score, proptosis, diplopia, color vision, Graves' Orbitopathy Quality of Life questionnaire score, rescue treatment, recurrence, and adverse events.
Interventions
DRUGTeprotumumab N01
Teprotumumab N01 will be administered intravenously after urgent orbital decompression. The first infusion will be 10 mg/kg, followed by 20 mg/kg every 3 weeks for 7 additional infusions.
IVMP will be administered after urgent orbital decompression at 0.5 to 1.0 g per day for 3 consecutive days, followed by oral prednisone tapering according to the participant's clinical status and investigator judgment.
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Able and willing to provide written informed consent. * Age 18 to 65 years. * Clinical diagnosis of thyroid eye disease (TED) with dysthyroid optic neuropathy (DON). Diagnosis of DON must meet both of the following criteria: 1. Visual dysfunction not explained by other causes, such as decreased best-corrected visual acuity, visual field defect, abnormal color vision, or relative afferent pupillary defect. 2. Imaging evidence of orbital apex crowding, optic nerve compression, or optic nerve stretching. * The study eye meets the criteria for urgent orbital decompression, defined as either of the following: 1. Poor response after rescue intravenous methylprednisolone for the current dysthyroid optic neuropathy episode, with a cumulative methylprednisolone-equivalent dose of no more than 3.0 g, defined as no improvement or continued deterioration of visual function within 1 to 2 weeks. 2. Contraindication to glucocorticoids or investigator judgment that direct urgent mechanical decompression is required. * Thyroid function is normal or mildly abnormal before enrollment, with free triiodothyronine (FT3) and free thyroxine (FT4) within 50% above or below the normal reference range when possible. * Alanine aminotransferase (ALT) no more than 1.5 times the upper limit of normal, aspartate aminotransferase (AST) no more than 3 times the upper limit of normal, and serum creatinine no more than 1.5 times the upper limit of normal. * For participants with diabetes mellitus, hemoglobin A1c (HbA1c) less than 9.0% and stable antidiabetic treatment within 60 days before enrollment. * For women of childbearing potential, a pregnancy test must be negative before enrollment. * Participants of reproductive potential agree to use effective contraception during the study and for 90 days after the last dose of study treatment. * Able and willing to comply with study treatment and follow-up procedures.
Exclusion criteria
* Orbital decompression surgery within 6 months before screening. * Bilateral dysthyroid optic neuropathy requiring urgent bilateral orbital decompression at baseline. * Cumulative preoperative methylprednisolone-equivalent dose greater than 3.0 g for the current dysthyroid optic neuropathy episode. * Systemic glucocorticoid treatment for non-thyroid eye disease within 3 months before screening with cumulative methylprednisolone-equivalent dose of 1.0 g or greater. * Tocilizumab or other systemic immunosuppressive treatment within 3 months before screening, or rituximab within 6 months before screening. * Orbital radiotherapy within 3 months before screening. * Previous treatment with teprotumumab. * Other ocular diseases that may significantly affect visual function assessment, including glaucomatous optic neuropathy, macular disease, severe cataract, or non-thyroid eye disease optic neuropathy. * Irreversible optic nerve damage in the study eye with very low potential for visual recovery, as judged by the investigator. * History of definite inner ear disease or clinically significant hearing impairment. * Severe cardiovascular disease. * Severe hepatic or renal disease. * Active infection or clinically significant infectious disease, including active hepatitis, HIV infection, syphilis, or active tuberculosis. * Active gastrointestinal ulcer. * Clinically significant abnormal blood test results, including white blood cell count less than 4.0 × 10\^9/L, platelet count less than 80 × 10\^9/L, hemoglobin less than 110 g/L in males or less than 100 g/L in females. * History of malignancy judged by the investigator to be unsuitable for enrollment. * Pregnancy or breastfeeding. * Known allergy to monoclonal antibodies, methylprednisolone, or any study drug excipient. * Uncontrolled diabetes mellitus or any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Best-Corrected Visual Acuity (BCVA) From Baseline to Week 24 | Baseline to Week 24 | BCVA will be assessed using a Snellen visual acuity chart and converted to logarithm of the minimum angle of resolution (logMAR) units for analysis. Lower logMAR values indicate better visual acuity. A negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in BCVA From Baseline to Week 12 | Baseline to Week 12 | BCVA will be assessed using a Snellen visual acuity chart and converted to logarithm of the minimum angle of resolution (logMAR) units for analysis. Lower logMAR values indicate better visual acuity. A negative change from baseline indicates improvement. |
| Change in Visual Field Mean Deviation (VF-MD) Measured by Humphrey Field Analyzer | Baseline to Weeks 12 and 24 | VF-MD will be measured in decibels using the Humphrey Field Analyzer. Higher or less negative VF-MD values indicate better visual field function. A positive change from baseline indicates improvement. |
| Clinical Activity Score (CAS) | Baseline to Weeks 12 and 24 | CAS will be used to assess disease activity in thyroid eye disease (TED). The 7-item CAS (CAS-7) will be used at baseline and ranges from 0 to 7. The 10-item CAS (CAS-10) will be used during follow-up and ranges from 0 to 10. Higher scores indicate more active inflammation, greater recent disease progression, and worse disease activity. |
| Proptosis Measured by Hertel Exophthalmometry | Baseline to Weeks 12 and 24 | Proptosis will be measured in millimeters using a Hertel exophthalmometer. Higher values indicate greater proptosis. A negative change from baseline indicates improvement. |
| Change in Gorman Diplopia Score | Baseline to Weeks 12 and 24 | Diplopia will be graded using the Gorman diplopia score. Scores range from 0 to 3, where 0 indicates no diplopia, 1 indicates intermittent diplopia, 2 indicates inconstant diplopia, and 3 indicates constant diplopia. Higher scores indicate worse diplopia. A negative change from baseline indicates improvement. |
| Color Vision Measured by Farnsworth Panel D-15 and Farnsworth-Munsell 100 Hue Tests | Baseline to Weeks 12 and 24 | Color vision will be assessed using the Farnsworth Panel D-15 test and the Farnsworth-Munsell 100 Hue test. The Farnsworth Panel D-15 test will be recorded as normal or abnormal color discrimination. The Farnsworth-Munsell 100 Hue test will be recorded using the total error score, with lower scores indicating better color discrimination. A decrease in total error score from baseline indicates improvement. |
| Graves' Orbitopathy Quality of Life Questionnaire Score（GO-QOL） | Baseline to Weeks 12 and 24 | The GO-QOL is a 16-item disease-specific questionnaire designed to measure health-related quality of life in patients with Graves' ophthalmopathy. It comprises two subscales: visual functioning (8 items) and appearance (8 items). Scores for each subscale are transformed to a range of 0 (worst possible quality of life) to 100 (best possible quality of life). A higher score indicates better quality of life. A positive change from baseline indicates improvement. |
| Incidence of Adverse Events and Serious Adverse Events | Baseline to Weeks 12 and 24 | Adverse events and serious adverse events will be recorded throughout the study period. The incidence, severity, seriousness, and relationship to study treatment will be summarized by treatment group. |
Countries
China
Contacts
CONTACTHui jing Ye, M.D, PhD
CONTACTGesang Zhuoma
Outcome results
None listed