THIAMAZOLE for Graves' disease | Graves' orbitopathy

Inclusion criteria

• {"criterion_text":"-1. Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form\n-2. A diagnosis of Graves’ disease based on the presence of hyperthyroidism associated with detectable anti-thyrotropic hormone (TSH) receptor autoantibodies (TRAb). Patients must be euthyroid under control on stable medical regimen and every effort will be made to maintain the euthyroid status for the entire duration of the clinical trial.\n-3. Duration of Graves’ disease shorter than 18 months\n-4. A moderate-to-severe GO, defined as the presence of at least two of the following criteria in the most affected eye: an exophthalmos ≥3 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm; active GO (see below)\n-5. Active GO: CAS ≥ 3 out of 7 points in the most affected eye. Taking into account severity (moderate-to-severe) and activity (CAS ≥ 3/7) of GO, patients are eligible for methylprednisolone treatment according to clinical practice.\n-6. Duration of GO shorter than 18 months\n-7. AST, ALT and CPK levels ≤ 3 times the upper value of normal range\n-8. Absolute neutrophil count >1000 cells/L\n-9. Women of childbearing potential (WOCBP, namely not in menopause or in menopause since less than two years; in all other instances women will be considered as non-WOCBP) and men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year (as indicated in Appendix) for at least 6 and 7,5 months, respectively, after the last dose of the investigational drug (see also 2014_09_HMA_CTFG_Contraception.pdf, namely the “2014 CTFG Recommendations related to contraception and pregnancy testing in clinical trials”)\n-10. Male and female patients of age 18-75 years"}

Exclusion criteria

• {"criterion_text":"-1. Optic neuropathy or sight threatening GO of any type\n-2. Previous therapy for Graves’ disease with radioiodine or thyroidectomy\n-3. Corticosteroids or other immunosuppressive treatment for GO or other reasons in the last 3 months.\n-4. Previous surgical treatment and/or radiotherapy for GO.\n-5. Contraindications to GC: hypersensitivity to the active substance or to any of the excipients; uncontrolled hypertension, uncontrolled diabetes; history of peptic ulcer; urinary infections, glaucoma, systemic fungal infections, systemic infections unless appropriate therapy is employed, idiopathic thrombocytopenic purpura, cerebral edema associated with malaria.\n-6. Contraindications to RAI.\n-7. Previous or current glucocorticoid-related psychosis.\n-8. Use of medications interfering with GC or increasing the risk of GC-related adverse events (see prohibited therapies)\n-9. Acute or chronic liver disease\n-10. Contraindications to MMI: hypersensitivity to the active substance or to any of the excipients; breastfeeding\n-11. Contraindications of any kind to perform thyroidectomy\n-12. Relevant Malignancy\n-13. Recent (≤1 year) history of alcoholism or drug abuse\n-14. Mental illness that prevent patients from comprehensive, written informed consent\n-15. Pregnancy or breastfeeding"}

Primary endpoints

• {"endpoint_text":"-Response rate 24 weeks after inclusion: -Comparison of overall GO outcome determined using a composite evaluation as indicated below. The evaluation will be performed by a unblinded ophthalmologist and will be documented in the CRF, including the following items: -Lid aperture in mm - CAS (5 items) -Exophthalmos in mm using a Hertel exophthalmometer -Eye ductions -Visual acuity using the Snellen chart in log10","definition_or_measurement_approach":"Composite evaluation performed by an unblinded ophthalmologist at 24 weeks, documented in the CRF, including lid aperture (mm), Clinical Activity Score (CAS, 5 items), exophthalmos measured with a Hertel exophthalmometer (mm), eye ductions, and visual acuity using the Snellen chart expressed in log10."}

Italy

Earliest CTIS Part Ii Submission Date

26-09-2024

Latest Decision Or Authorization Date

19-11-2024

Processing Time Days

54

Number Of Sites

1

Number Of Participants

52

Primary sponsor

Full Name

Azienda Ospedaliero Universitaria Pisana

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy