Teprotumumab N01 Versus Methylprednisolone After Urgent Orbital Decompression for Dysthyroid Optic Neuropathy

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат Teprotumumab 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.
• Препарат Intravenous Methylprednisolone (IVMP)
  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.

Первичные конечные точки

• Change in Best-Corrected Visual Acuity (BCVA) From Baseline to Week 24 [Срок оценки: Baseline to Week 24]

Вторичные конечные точки (8)

• Change in BCVA From Baseline to Week 12 [Срок оценки: Baseline to Week 12]
• Change in Visual Field Mean Deviation (VF-MD) Measured by Humphrey Field Analyzer [Срок оценки: Baseline to Weeks 12 and 24]
• Clinical Activity Score (CAS) [Срок оценки: Baseline to Weeks 12 and 24]
• Proptosis Measured by Hertel Exophthalmometry [Срок оценки: Baseline to Weeks 12 and 24]
• Change in Gorman Diplopia Score [Срок оценки: Baseline to Weeks 12 and 24]
• Color Vision Measured by Farnsworth Panel D-15 and Farnsworth-Munsell 100 Hue Tests [Срок оценки: Baseline to Weeks 12 and 24]
• Graves' Orbitopathy Quality of Life Questionnaire Score（GO-QOL） [Срок оценки: Baseline to Weeks 12 and 24]
• Incidence of Adverse Events and Serious Adverse Events [Срок оценки: Baseline to Weeks 12 and 24]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Zhongshan Ophthalmic Center, Sun Yat-sen University — Гуанчжоу

Идентификаторы

NCT: NCT07594912 · yanghs20250429

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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