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RECRUITING

NCT07547930

PHASE2

Tofacitinib for Glucocorticoid-Resistant Moderate-to-Severe Thyroid Eye Disease

Sponsor: The First Affiliated Hospital of Xiamen University

View on ClinicalTrials.gov

Summary

Thyroid Eye Disease (TED), also known as Graves' orbitopathy, is an autoimmune condition that causes inflammation and tissue expansion behind the eyes, leading to bulging eyes (proptosis), double vision, and pain. Currently, intravenous glucocorticoids (steroids) are the standard first-line treatment. However, approximately 20-30% of patients do not respond to steroids, or cannot tolerate their side effects. This study aims to evaluate the safety and efficacy of Tofacitinib, an oral medication known as a Janus kinase (JAK) inhibitor, as a rescue therapy for these difficult-to-treat cases. Tofacitinib works by blocking specific signaling pathways (JAK-STAT) that drive inflammation and fibrosis in the eye socket. In this study, patients with moderate-to-severe active TED who are resistant to or intolerant of steroids will receive Tofacitinib tablets (5 mg twice daily) for 24 weeks. The researchers will assess whether the treatment can effectively reduce eye bulging and improve clinical activity scores.

Official title: A Single-Arm, Open-Label, Exploratory Study of Tofacitinib in Patients With Glucocorticoid-Resistant or Intolerant Moderate-to-Severe Active Thyroid Eye Disease

Key Details

Gender

All

Age Range

18 Years - 75 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2026-04-24

Completion Date

2027-12-30

Last Updated

2026-04-29

Healthy Volunteers

Conditions

Thyroid Eye Disease, TED Graves Ophthalmopathy Graves Orbitopathy

Interventions

DRUG

Tofacitinib

5 mg tablet administered orally twice daily (BID) for a continuous period of 24 weeks.

Inclusion Criteria: 1. Age and Gender: Male or female participants aged 18 to 75 years (inclusive). 2. Diagnosis: Clinical diagnosis of Graves' orbitopathy (GO) consistent with EUGOGO criteria. 3. Severity: Moderate-to-severe GO as defined by EUGOGO guidelines (impact on daily life, but not sight-threatening). 4. Activity: Active disease, defined as a Clinical Activity Score (CAS) \>=3 points (on the 7-point scale). 5. Refractory Status (Must meet ONE of the following):Glucocorticoid-Resistant: Failure to respond (no significant improvement in proptosis or CAS) after receiving a cumulative dose of at least 3g of intravenous methylprednisolone (or equivalent).Glucocorticoid-Intolerant: Documented contraindications to high-dose systemic glucocorticoids (e.g., uncontrolled diabetes mellitus, severe osteoporosis, glaucoma, severe psychiatric disorders) or history of severe adverse events leading to discontinuation. 6. Thyroid Function: Euthyroid or mild hypothyroidism/hyperthyroidism maintained on stable antithyroid drugs or thyroxine replacement therapy for at least 4 weeks prior to baseline. 7. Contraception: Women of childbearing potential must agree to use effective contraception during the study period and for at least 4 weeks after the last dose of the study drug. 8. Consent: Willing and able to provide written informed consent and comply with study procedures. Exclusion Criteria: * 1.Sight-Threatening Disease: Presence of Dysthyroid Optic Neuropathy (DON) or severe corneal breakdown requiring immediate surgical intervention. 2.Chronic/Inactive Disease: Fibrotic or burnout stage of GO with a Clinical Activity Score (CAS) \< 3. 3.Prior Orbital Treatment:Orbital radiotherapy at any time.Orbital surgical decompression at any time.Strabismus surgery or eyelid surgery within 3 months prior to baseline. 4.Concomitant Immunomodulation: Use of other biologic agents (e.g., Teprotumumab, Rituximab, Tocilizumab) within 3 months prior to baseline. 5.Active Infection Risk (Critical for JAK Inhibitors):Active tuberculosis (TB) or untreated latent TB.Active or chronic Hepatitis B or Hepatitis C infection.Human Immunodeficiency Virus (HIV) infection.History of disseminated herpes zoster or herpes simplex.Any severe active infection requiring hospitalization or IV antibiotics within 4 weeks of baseline. 6.Thrombosis Risk: History of venous thromboembolism (VTE), including deep vein thrombosis (DVT) or pulmonary embolism (PE), or known coagulation disorders. 8.Malignancy: History of any malignancy within the past 5 years (except adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix). 9.Laboratory Abnormalities:Absolute Neutrophil Count (ANC) \< 1.0 \*10\^9/L and/or Absolute Lymphocyte Count (ALC) \< 0.5 \*10\^9/L and /or Hemoglobin \< 90 g/L and/or AST or ALT \> 2\* Upper Limit of Normal (ULN) and/or Estimated Glomerular Filtration Rate (eGFR) \< 60 mL/min/1.73 m²

Locations (1)

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China