Efficacy and Safety of Tocilizumab for TAO

Efficacy and Safety of Tocilizumab for Patients With Thyroid-associated Ophthalmopathy

This study aims to evaluate the efficacy and safety of tocilizumab treating Thyroid Associated Ophthalmopathy.

Study Overview

• Status: Withdrawn
• Conditions: Thyroid Associated Ophthalmopathy; Tocilizumab
• Intervention / Treatment: Drug: Tocilizumab

Detailed Description

Thyroid Associated Ophthalmopathy(TAO) is one of autoimmune orbital diseases characterized by enlargement of the extraocular muscles and increase in fatty or/and orbit connective tissue volume affecting the appearance and visual function of the eyes. In TAO pathogenesis, orbital fibroblasts are activated by autoantibodies against the thyrotropin receptor TSHR and the insulin-like growth factor-1 receptor. The fibroblasts then secrete interleukin-6 (IL-6), macrophage chemoattractant protein-1, and transforming growth factor-ß. In orbital preadipocyte fibroblasts, IL-6 increases expression of the thyrotropin receptor TSHR, and the orbital volume is relative to IL-6 mRNA expression. Thus, IL-6 may have several roles in the pathogenesis of TAO. Tocilizumab, a recombinant humanized IgG1 monoclonal antibody against IL-6 receptors, is FDA-approved for the treatment of rheumatoid arthritis, giant cell arteritis and juvenile idiopathic arthritis with a good toleration. The investigators carry this perspective cohort study to evaluate the efficacy of tocilizumab in TAO.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Zhongshan Ophthalmic Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

Age 18-70 years old

• Clinical diagnosis of Thyroid-associated ophthalmopathy
• Euthyroid status at least 1 months before baseline.
• No previous specific therapy for TAO, except for local measures
• Written informed consent is obtained

Exclusion criteria:

• Uncontrolled diabetes or hypertension
• Renal or hepatic insufficiency.
• Infectious diseases (HIV, HBV,TB and so on)
• History of mental/psychiatric disorder
• Other ocular diseases or fundus diseases.
• Any previous systemic medications or surgery for the treatment of TAO
• Pregnant or lactating females.
• Intolerability of tocilizumab

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tocilizumab; administrated with tocilizumab (8mg/kg) every four weeks	Drug: Tocilizumab; Tocilizumab (8mg/kg) every 4 wekks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
volume and signal intensity of each extraocular muscles and soft tissue in MRI images	The volume and signal intensity of each extraocular muscles and soft tissue are analyzed in the MRI slides of each patients. each part of each extraocular muscles and soft tissue were measured three times and two trained performers will do this assignment respectively.	month 1，month 3，month 6
Clinical Activity Score	Spontaneous orbital pain. Gaze evoked orbital pain. Eyelid swelling that is considered to be due to active (inflammatory phase) GO. Eyelid erythema. Conjunctival redness that is considered to be due to active (inflammatory phase) GO (ignore "equivocal" redness). Chemosis. Inflammation of caruncle or plica	month 1，month 3，month 6
eyelid aperture	For the assessment of eyelid aperture, the same millimeter ruler should be used by the same observer. When performed this assessment, participants should relax their eyes and keep looking ahead and the observers should keep the ruler perpendicular to their eyelid.	month 1，month 3，month 6
exophthalmos	For the assessment of exophthalmos, the same Hertel instrument and ideally the same observer should be used on each occasion. Additionally the same intercanthal distance (ICD) should be used on each occasion.	month 1，month 3，month 6
eyelid lag	For the assessment of eyelid aperture, the same millimeter ruler should be used by the same observer. Lid lag is defined that the lid margin distance in downgaze. The upper eyelid positions above (recorded '+') or below (recorded '-') the superior limbus will be measured in millimeters.	month 1，month 3，month 6
retraction of the upper and lower eyelids	For the assessment of eyelid aperture, the same millimeter ruler should be used by the same observer. The upper eyelid positions above (recorded '+') or below (recorded '-') the superior limbus and the lower eyelid positions above (recorded '+') or below (recorded '-') the posterior limbus will be measured in millimeters on the primary position with relaxed status.	month 1，month 3，month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ocular motility	The head of each participant is adjusted to fix on the modified perimeter and set the visual axis of the examined eye on the center of the optimal visual target in visual chart. The other eye should be covered. The participantshould move the examined eye to follow the movement of the visual target until he/she cannot identify the exact visual target in vertical and horizontall directions respectively. And the extreme scales of these four directions (upgaze, downgaze, abduction and adduction) for each eye are obtained.	month 1，month 3，month 6
Graves' Ophthalmopathy Quality of Life Scale	The Graves' Ophthalmopathy Quality of Life (GO-QOL) questionnaire [4]includes visual functioning and psychosocial functioning. A raw score of each part is calculated by adding each score of 8 question, namely 1, 2, or 3 for each question which means marked, mild, or absent limitation, the final score ranging from 0 (full limitation) to 100 (no limitation) is calculated as the following rule: (raw score - 8) ÷ 16 × 100]. GO-QOL will be completed at screening, week 0, week 4 and week 12. The data will also be recorded to assess activity of TAO and impact on quality of life respectively. The GO-QOL is a 16-item self-administered questionnaire used to assess the perceived effects of TAO by the patients on their daily physical and psychosocial functioning.	month 1，month 3，month 6
inflammatory markers changes	Serum inflammatory markers （systemic）including neutrophil, lymphocyte, platelet, monocyte, WBC, NLR, PLR, MLR, SII,SIRI, PIV, WMR and others.	month 1，month 3，month 6

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Dan Liang, Zhongshan Ophthalmic Center, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2023
• Primary Completion (Actual): September 23, 2023
• Study Completion (Actual): September 23, 2023

Study Registration Dates

• First Submitted: September 22, 2023
• First Submitted That Met QC Criteria: October 11, 2023
• First Posted (Actual): October 18, 2023

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 23, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: tocilizumab; Thyroid Associated Ophthalmopathy
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Eye Diseases; Graves Ophthalmopathy; Thyroid Diseases
• Other Study ID Numbers: 2023TAOIL-6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No