Efficacy and Safety of Tocilizumab for TAO

Thyroid Associated Ophthalmopathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT06087731
• Other study ID #: 2023TAOIL-6
• Status: Withdrawn
• Phase: Phase 2
• Start date: September 23, 2023
• Est. completion date: September 23, 2023

Study information

• Verified date: April 2023
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 23, 2023
• Est. primary completion date: September 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Eye Diseases
• Graves Ophthalmopathy
• Thyroid Associated Ophthalmopathy
• Thyroid Diseases
• Tocilizumab

Intervention

Drug:
• Tocilizumab
Tocilizumab (8mg/kg) every 4 wekks

Locations

Country	Name	City	State
China	Zhongshan Ophthalmic Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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