Antithymocyte Globulin as a Second Line Therapy in Graves Orbitopathy

Not Applicable

• Conditions: Graves Orbitopathy
• Interventions: Drug: rabbit anti-thymocyte globulin

• Registration Number: NCT05199103
• Lead Sponsor: Medical University of Silesia

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).

Study Timeline

• Study Start: 2020-01-01
• Study First Submitted: 2021-12-27
• Status Verified: 2022-01
• Study First Submitted QC: 2022-01-14
• Last Update Submitted: 2022-01-14
• Study First Posted: 2022-01-20
• Last Update Posted: 2022-01-20
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rabbit antithymocyte globulin (rATG)	rabbit anti-thymocyte globulin	-

Primary Outcome Measures

Name	Time	Method
≥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

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

Trial Locations

Locations (1)

Department of Internal Medicine and Oncological Chemotherapy, Medical Faculty in Katowice, Medical University of Silesia; 🇵🇱 Katowice, Silesia, Poland