A Study on the Combined Use of Tocilizumab and Flupentixol-Melitracen in the Treatment of Thyroid-Associated Ophthalmopathy

NCT06927375 | Recruiting Phase 4

• 1 other identifier: SH9H-2024-T313-2
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Thyroid-associated ophthalmopathy (TAO) is a serious, progressive, vision-threatening autoimmune disease that can be categorized into mild, moderate, and severe stages based on severity. The activity of TAO is commonly evaluated using the Clinical Activity Score (CAS). Tocilizumab serves as a second-line treatment option for patients with moderate to severe active TAO. Additionally, it is common for TAO patients to experience anxiety, which may exacerbate their condition and negatively impact prognosis. Therefore, we have designed this randomized controlled study to evaluate the impact of Flupentixol Melitracen (Lepan) on the treatment outcomes of participants receiving Tocilizumab (Actemra).

Conditions

Thyroid-Associated Ophthalmopathy

Keywords

Thyroid Eye Disease; Graves Orbitopathy; Thyroid Associated Ophthalmopathy; TAO; TED

Outcome Measures

Primary Outcomes (1)

• comprehensive score

  The comprehensive score has a maximum of 30 points. It is calculated as follows：the half score of TED-QoL (Thyroid Eye Disease Quality of Life questionnaire) (15 points), plus the higher value of CAS (Clinical Activity Score) between the two eyes (7 points). Additionally, one point is added for each symptom present in the participant: tearing, photophobia, dry eye, blurred vision. Also included are diplopia score (3 points) and restricted eye movement score (1 point). The study investigates changes in the comprehensive score before and after treatment in two groups.

  week12

Secondary Outcomes (8)

• Go-qol

  week 12

• TED-QoL

  week 12

• CAS Decrease by ≥2 Points

  week 12

• CAS Change Value

  week 12

• Diplopia Improvement

  week 12

Study Arms (2)

Tocilizumab combined with Flupentixol Melitracen

EXPERIMENTAL

Drug: Tocilizumab(400mg) combined with Flupentixol Melitracen(0.5mg:10mg)

Tocilizumab

ACTIVE COMPARATOR

Drug: Tocilizumab(400mg)

Interventions

Tocilizumab(400mg) combined with Flupentixol Melitracen(0.5mg:10mg) DRUG

Tocilizumab (Actemra) is administered via intravenous infusion at a dose of 400 mg at Weeks 0, 4, and 8. Flupentixol/Melitracen is given orally at a dose of 0.5 mg/10 mg twice daily for 8 consecutive weeks starting from Week 0.

Also known as: study group

Tocilizumab combined with Flupentixol Melitracen

Tocilizumab(400mg) DRUG

Tocilizumab (Actemra) is administered via intravenous infusion at a dose of 400 mg at Weeks 0, 4, and 8.

Also known as: control group

Tocilizumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 18 and 80 years (inclusive).
• Meets internationally recognized diagnostic criteria for TED with the more severely affected eye in moderate to severe active phase. Meeting any one of the following criteria qualifies as moderate to severe: an exophthalmos ≥2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm. A Clinical Activity Score (CAS) of ≥3 or a score of 2 combined with MRI evidence indicating active disease is defined as active.
• Normal thyroid function within one month prior to enrollment: including those currently taking antithyroid drugs or not requiring medication, with FT3 and FT4 levels within normal range and TSH either normal or decreased.
• HAMA (Hamilton Anxiety Rating Scale) score of ≥14.
• Voluntary participation and provision of informed consent.

You may not qualify if:

• Severe cardiac, hepatic, or renal insufficiency (including myocardial ischemia or myocardial infarction, arrhythmias, and heart failure; ALT, AST ≥ 3 times the upper limit of normal; eGFR \< 60 ml/min/1.73 m²).
• communicable disease.
• Pregnancy or planning to become pregnant.
• Currently breastfeeding.
• Received radioactive iodine treatment or hepatitis vaccination within three months prior to enrollment.
• Received systemic immunotherapy for TAO, including oral or intravenous glucocorticoids, other immunosuppressants, or orbital radiotherapy within one month prior to enrollment.
• Planning to undergo other treatments during the course of this study.
• Severe mental disorders that affect compliance.
• Presence of other clinically significant or unstable systemic diseases.
• Patients who are unlikely to complete the entire course of treatment.

Sponsors & Collaborators

• Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University: lead

Study Sites (1)

Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200011, China

RECRUITING

MeSH Terms

Conditions

Graves Ophthalmopathy

Interventions

tocilizumab; flupentixol, melitracen drug combination; Control Groups

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Yingli Lu

  Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

  STUDY CHAIR

• Qin Li

  Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yingli Lu

CONTACT

（021）+86 13636352507; luyingli2008@126.com

qin li

CONTACT

(021) +86 13564691094

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician，head of Endocrinology department

Study Record Dates

• First Submitted: April 7, 2025
• First Posted: April 15, 2025
• Study Start: December 12, 2024
• Primary Completion: November 12, 2025
• Study Completion: March 12, 2026
• Last Updated: April 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)