Sirolimus vs Corticosteroids in Treatment of Thyroid Eye Disease

Inclusion Criteria:

• The participant want treatment for active thyroid eye disease and is willing to beincluded in the study
• Clinical diagnosis of Graves' disease associated with active TED with a ClinicalActivity Score (CAS) ≥ 4 (on the 7-item scale)
• Moderate-to-severe active TED (not sight-threatening but has an appreciable impact ondaily life), usually associated with one or more of the following: lid retraction ≥ 2mm, moderate or severe soft tissue involvement, exophthalmos ≥ 3 mm above normal forrace and gender, and/or inconstant or constant diplopia
• Onset of active TED symptoms (as determined by participant records) within 9 monthsprior to inculsion
• Participants must be euthyroid with the Graves disease under control or have mildhypo- or hyperthyroidism (defined as free thyroxine and free triiodothyronine levels < 50% above or below the normal limits).
• Does not require immediate surgical ophthalmological intervention and is not planningcorrective surgery/irradiation during the course of the study
• Diabetic participants must have well-controlled stable disease (defined as HbA1C < 9.0% with no new diabetic medication [oral or insulin] or more than a 10% change inthe dose of a currently prescribed diabetic medication within 60 days prior toScreening)
• Women of childbearing potential (including those with an onset of menopause <2 yearsprior to Screening, non-therapy-induced amenorrhea for <12 months prior to Screening,or not surgically sterile [absence of ovaries and/or uterus]) must have a negativeserum pregnancy test at Screening and negative urine pregnancy tests at allprotocol-specified timepoints (i.e., prior to each dose and through Week 48 of theFollow-Up Period); participants who are sexually active with a non-vasectomized malepartner must agree to use 2 reliable forms of contraception during the trial, one ofwhich is recommended to be hormonal, such as an oral contraceptive. Hormonalcontraception must be started at least one full cycle prior to Baseline and continuefor 180 days after the last dose of study drug. Highly effective contraceptive methods (with a failure rate less than 1% per year) when used consistently and correctly,includes implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence or vasectomized partner
• Male participants must be surgically sterile or, if sexually active with a femalepartner of childbearing potential, must agree to use barrier contraceptive method fromScreening through 180 days after the last dose of study drug
• Active Influenza and Pneumococcal vaccines

Exclusion Criteria:

• The participant dont want treatment for active thyroid eye disease or dont want toparticipate in the study
• Decreased vision due to optic neuropathy as defined by a significant decrease in bestcorrected visual acuity, new visual field defect, or color defect secondary to opticnerve involvement within the last 6 months
• Corneal decompensation unresponsive to medical management
• Previous orbital irradiation or surgery for TED Any steroid use (intravenous [IV] ororal) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone for thetreatment of TED. Previous steroid use (IV or oral) with a cumulative dose of <1 gmethylprednisolone or equivalent for the treatment of TED and previous use of steroideye drops is allowed if the corticosteroid was discontinued at least 4 weeks prior toinclusion
• Corticosteroid use for conditions other than TED within 4 weeks prior to inclusion (topical steroids for dermatological conditions and inhaled steroids are allowed)
• Selenium and biotin must be discontinued 3 weeks prior to Screening and must not berestarted during the clinical trial; however, taking a multivitamin that includesselenium and/or biotin is allowed
• Use of any other non-steroid immunosuppressive including agent, new biologic drugswithin 3 months prior to Screening
• Use of an investigational agent for any condition within 60 days prior to inclusion oranticipated use during the course of the trial
• Identified pre-existing ophthalmic disease that, in the judgment of the Investigator,would preclude study participation or complicate interpretation of study results
• Bleeding diathesis that in the judgment of the Investigator would preclude inclusionin the clinical trial
• Malignant condition in the past 12 months (except successfully treated basal/squamouscell carcinoma of the skin)
• Pregnant or lactating women
• Current drug or alcohol abuse, or history of either within the previous 2 years, inthe opinion of the Investigator or as reported by the participant
• Biopsy-proven or clinically suspected inflammatory bowel disease
• Known hypersensitivity to any of the components Sirolimus.
• Any other condition that, in the opinion of the Investigator, would preclude inclusionin the study
• Previous enrollment in this study
• Human immunodeficiency virus (HIV), tuberculosis, hepatitis C or hepatitis Binfections