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Efficacy and Safety of Tocilizumab for TAO

Primary Purpose

Tocilizumab, Thyroid Associated Ophthalmopathy

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tocilizumab
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tocilizumab focused on measuring Thyroid Associated Ophthalmopathy, tocilizumab

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Zhongshan Ophthalmic CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

tocilizumab

Arm Description

administrated with tocilizumab (8mg/kg) every four weeks

Outcomes

Primary Outcome Measures

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.
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
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.
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.
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.
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.

Secondary Outcome Measures

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.
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.
inflammatory markers changes
Serum inflammatory markers (systemic)including neutrophil, lymphocyte, platelet, monocyte, WBC, NLR, PLR, MLR, SII,SIRI, PIV, WMR and others.

Full Information

First Posted
September 22, 2023
Last Updated
October 11, 2023
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT06087731
Brief Title
Efficacy and Safety of Tocilizumab for TAO
Official Title
Efficacy and Safety of Tocilizumab for Patients With Thyroid-associated Ophthalmopathy
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 17, 2023 (Actual)
Primary Completion Date
May 1, 2026 (Anticipated)
Study Completion Date
May 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tocilizumab, Thyroid Associated Ophthalmopathy
Keywords
Thyroid Associated Ophthalmopathy, tocilizumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
tocilizumab
Arm Type
Experimental
Arm Description
administrated with tocilizumab (8mg/kg) every four weeks
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Intervention Description
Tocilizumab (8mg/kg) every 4 wekks
Primary Outcome Measure Information:
Title
volume and signal intensity of each extraocular muscles and soft tissue in MRI images
Description
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.
Time Frame
month 1,month 3,month 6
Title
Clinical Activity Score
Description
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
Time Frame
month 1,month 3,month 6
Title
eyelid aperture
Description
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.
Time Frame
month 1,month 3,month 6
Title
exophthalmos
Description
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.
Time Frame
month 1,month 3,month 6
Title
eyelid lag
Description
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.
Time Frame
month 1,month 3,month 6
Title
retraction of the upper and lower eyelids
Description
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.
Time Frame
month 1,month 3,month 6
Secondary Outcome Measure Information:
Title
ocular motility
Description
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.
Time Frame
month 1,month 3,month 6
Title
Graves' Ophthalmopathy Quality of Life Scale
Description
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.
Time Frame
month 1,month 3,month 6
Title
inflammatory markers changes
Description
Serum inflammatory markers (systemic)including neutrophil, lymphocyte, platelet, monocyte, WBC, NLR, PLR, MLR, SII,SIRI, PIV, WMR and others.
Time Frame
month 1,month 3,month 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dan Liang
Phone
(86)-87330402
Email
liangdan@gzzoc.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dan Liang
Organizational Affiliation
Zhongshan Ophthalmic Center, Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zhongshan Ophthalmic Center
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dan Liang
Phone
(86)-87330402
Email
liangdan@gzzoc.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Efficacy and Safety of Tocilizumab for TAO

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