Antithymocyte Globulin as a Second Line Therapy in Graves Orbitopathy
Primary Purpose
Graves Orbitopathy
Status
Recruiting
Phase
Not Applicable
Locations
Poland
Study Type
Interventional
Intervention
rabbit anti-thymocyte globulin
Sponsored by
About this trial
This is an interventional treatment trial for Graves Orbitopathy focused on measuring Graves disease, proptosis, antithymocyte globulin
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis of Graves' disease associated with active thyroid eye disease and a clinical activity score of ≥ 3
- Euthyroid or with mild hypo- or hyperthyroidism defined as free thyroxine (FT4) and free triiodothyronine (FT3) levels less than 50% above or below the normal limits
- previous ineffective treatment (partial response, recurrence or progression of symptoms) with moderate-to-high doses of glucocorticoids (at least 4.5 g of methylprednisolone)
Exclusion Criteria:
- hypersensitivity to rabbit proteins or to any product excipients
- active acute or chronic infections
- latent tuberculosis
- leucopenia below 3000/μl
- lymphopenia below 400/μl
- thrombocytopenia below 75000/μl
- coagulation disorders
- active malignancy and pregnancy
Sites / Locations
- Department of Internal Medicine and Oncological Chemotherapy, Medical Faculty in Katowice, Medical University of SilesiaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rabbit antithymocyte globulin (rATG)
Arm Description
Outcomes
Primary Outcome Measures
≥2 point change in Clinical Activity Score from baseline
change in proptosis
a diplopia response
change of distant best-corrected visual acuity
change of mean retinal sensitivity
Secondary Outcome Measures
changes in CD4/CD8 ratio
changes in TSH-receptor antibodies level
increase in 1 degree amplitude in Pattern visual evoked potential (VEP) by 1 µV
Full Information
NCT ID
NCT05199103
First Posted
December 27, 2021
Last Updated
January 14, 2022
Sponsor
Medical University of Silesia
1. Study Identification
Unique Protocol Identification Number
NCT05199103
Brief Title
Antithymocyte Globulin as a Second Line Therapy in Graves Orbitopathy
Official Title
Single-centre, Safety and Efficacy, Open-label Study Evaluating Antithymocyte Globulin Treatment in Subjects With Graves Orbitopathy
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2020 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Silesia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The overall objective of the study is to evaluate the safety and efficacy of rabbit antithymocyte globulin in the treatment of Graves orbitopathy (GO) after ineffective treatment with moderate-to-high doses of glucocorticoids.
Detailed Description
This is a prospective interventional, single-center study examining the safety and efficacy of rabbit antithymocyte globulin (rATG) in adult patients with active moderate-to-severe GO after ineffective treatment with moderate-to-high doses of glucocorticoids. All enrolled participants will receive 0.8 - 1.0 mg/kg of rATG (cumulative dose of 150-200 mg given intravenously in two or three divided doses, 24 hours apart) after premedication with methylprednisolone i.v. (in total dose of 375 mg), 1 mg of antihistaminic agent clemastine and 1000 mg paracetamol i.v.
In order to assess efficacy and safety of the treatment, patients will be evaluated at baseline and at 6, 12, 24 and 48 weeks. Baseline and subsequent evaluation will involve medical history, physical examination, including detailed eye examination, laboratory assessment (thyroid-stimulating hormone [TSH], flow cytometry, TSH-receptor antibodies, CBC) and orbital magnetic resonance imaging (MRI).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graves Orbitopathy
Keywords
Graves disease, proptosis, antithymocyte globulin
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Rabbit antithymocyte globulin (rATG)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
rabbit anti-thymocyte globulin
Intervention Description
0.8 - 1.0 mg/kg of rATG (cumulative dose of 150-200 mg given intravenously in two or three divided doses, 24 hours apart) after premedication with methylprednisolone i.v. (in total dose of 375 mg), 1 mg of antihistaminic agent clemastine and 1000 mg paracetamol i.v.
Primary Outcome Measure Information:
Title
≥2 point change in Clinical Activity Score from baseline
Time Frame
Week 6, 12, 24, 48
Title
change in proptosis
Time Frame
48 weeks
Title
a diplopia response
Time Frame
48 weeks
Title
change of distant best-corrected visual acuity
Time Frame
Week 6, 12, 24, 48
Title
change of mean retinal sensitivity
Time Frame
Week 6, 12, 24, 48
Secondary Outcome Measure Information:
Title
changes in CD4/CD8 ratio
Time Frame
Week 6, 12, 24, 48
Title
changes in TSH-receptor antibodies level
Time Frame
Week 6, 12, 24, 48
Title
increase in 1 degree amplitude in Pattern visual evoked potential (VEP) by 1 µV
Time Frame
Week 6, 12, 24, 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis of Graves' disease associated with active thyroid eye disease and a clinical activity score of ≥ 3
Euthyroid or with mild hypo- or hyperthyroidism defined as free thyroxine (FT4) and free triiodothyronine (FT3) levels less than 50% above or below the normal limits
previous ineffective treatment (partial response, recurrence or progression of symptoms) with moderate-to-high doses of glucocorticoids (at least 4.5 g of methylprednisolone)
Exclusion Criteria:
hypersensitivity to rabbit proteins or to any product excipients
active acute or chronic infections
latent tuberculosis
leucopenia below 3000/μl
lymphopenia below 400/μl
thrombocytopenia below 75000/μl
coagulation disorders
active malignancy and pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gabriela Handzlik, Ph.D.
Phone
322591202
Ext
0048
Email
ghandzlik@sum.edu.pl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jerzy Chudek, Prof.
Organizational Affiliation
Medical University of Silesia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Internal Medicine and Oncological Chemotherapy, Medical Faculty in Katowice, Medical University of Silesia
City
Katowice
State/Province
Silesia
ZIP/Postal Code
40-029
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabriela Handzlik
Phone
322591202
Ext
0048
Email
ghandzlik@sum.edu.pl
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35615718
Citation
Sarnat-Kucharczyk M, Swierkot M, Handzlik G, Kulawik G, Jagoda K, Grochola-Malecka I, Fryzewska J, Mrukwa-Kominek E, Chudek J. Antithymocyte Globulin as Second-Line Therapy in Graves Orbitopathy-Preliminary Results From a Prospective Single-Center Study. Front Endocrinol (Lausanne). 2022 May 9;13:871009. doi: 10.3389/fendo.2022.871009. eCollection 2022.
Results Reference
derived
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Antithymocyte Globulin as a Second Line Therapy in Graves Orbitopathy
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