A Single-Center, Prospective, Randomized, Open-Label, Parallel-Group Study Comparing Sequential Teprotumumab N01 With Intravenous Methylprednisolone After Urgent Orbital Decompression in Patients With Dysthyroid Optic Neuropathy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in Best-Corrected Visual Acuity (BCVA) From Baseline to Week 24
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •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.
- •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:
- •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.
- •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.
排除标准
- •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.
研究组 & 干预措施
Postoperative Sequential Teprotumumab N01
Participants in this arm will undergo urgent orbital decompression and then receive postoperative sequential Teprotumumab N01.
干预措施: Teprotumumab N01 (Drug)
Postoperative Sequential Intravenous Methylprednisolone
Participants in this arm will undergo urgent orbital decompression and then receive postoperative sequential intravenous methylprednisolone.
干预措施: Intravenous Methylprednisolone (IVMP) (Drug)
结局指标
主要结局
Change in Best-Corrected Visual Acuity (BCVA) From Baseline to Week 24
时间窗: 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.
次要结局
- Change in BCVA From Baseline to Week 12(Baseline to Week 12)
- Change in Visual Field Mean Deviation (VF-MD) Measured by Humphrey Field Analyzer(Baseline to Weeks 12 and 24)
- Clinical Activity Score (CAS)(Baseline to Weeks 12 and 24)
- Proptosis Measured by Hertel Exophthalmometry(Baseline to Weeks 12 and 24)
- Change in Gorman Diplopia Score(Baseline to Weeks 12 and 24)
- Color Vision Measured by Farnsworth Panel D-15 and Farnsworth-Munsell 100 Hue Tests(Baseline to Weeks 12 and 24)
- Graves' Orbitopathy Quality of Life Questionnaire Score（GO-QOL）(Baseline to Weeks 12 and 24)
- Incidence of Adverse Events and Serious Adverse Events(Baseline to Weeks 12 and 24)
研究者
Huasheng Yang
Clinical Professor
Sun Yat-sen University