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

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

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).

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.

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.