Clinical trial NCT05199103: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Graves Orbitopathy
Keywords: Graves disease
proptosis
antithymocyte globulin
Lead sponsor: Medical University of Silesia
Sponsor class: OTHER
First posted: 2022-01-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: ≥2 point change in Clinical Activity Score from baseline
timeFrame: Week 6, 12, 24, 48
measure: change in proptosis
timeFrame: 48 weeks
measure: a diplopia response
timeFrame: 48 weeks
measure: change of distant best-corrected visual acuity
timeFrame: Week 6, 12, 24, 48
measure: change of mean retinal sensitivity
timeFrame: Week 6, 12, 24, 48
Secondary outcomes:
measure: changes in CD4/CD8 ratio
timeFrame: Week 6, 12, 24, 48
measure: changes in TSH-receptor antibodies level
timeFrame: Week 6, 12, 24, 48
measure: increase in 1 degree amplitude in Pattern visual evoked potential (VEP) by 1 µV
timeFrame: Week 6, 12, 24, 48
Other outcomes:
Locations:
city: Katowice
country: Poland
facility: Department of Internal Medicine and Oncological Chemotherapy, Medical Faculty in Katowice, Medical University of Silesia
state: Silesia
Study officials:
affiliation: Medical University of Silesia
name: Jerzy Chudek, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
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.