Antithymocyte Globulin as a Second Line Therapy in Graves Orbitopathy

Study Overview
=================
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).

Official Title
-----------------
Single-centre, Safety and Efficacy, Open-label Study Evaluating Antithymocyte Globulin Treatment in Subjects With Graves Orbitopathy

Conditions
-----------------
Graves Orbitopathy

Intervention / Treatment
-----------------
* Drug: rabbit anti-thymocyte globulin


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rabbit antithymocyte globulin (rATG)<br> | Drug: rabbit anti-thymocyte globulin<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ≥2 point change in Clinical Activity Score from baseline |  | Week 6, 12, 24, 48 | 
| change in proptosis |  | 48 weeks | 
| a diplopia response |  | 48 weeks | 
| change of distant best-corrected visual acuity |  | Week 6, 12, 24, 48 | 
| change of mean retinal sensitivity |  | Week 6, 12, 24, 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in CD4/CD8 ratio |  | Week 6, 12, 24, 48 | 
| changes in TSH-receptor antibodies level |  | Week 6, 12, 24, 48 | 
| increase in 1 degree amplitude in Pattern visual evoked potential (VEP) by 1 µV |  | Week 6, 12, 24, 48 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Graves disease, proptosis, antithymocyte globulin