Thyroid Eye Disease (TED) in patients with Graves' Diease.
Conditions
Interventions
Trade Name: Solu-Medrol
Pharmaceutical Form: Powder and solvent for solution for injection
Trade Name: Rapamune
Pharmaceutical Form: Tablet
Sponsors
Helse Bergen HF, Haukeland University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Clinical diagnosis of Graves` disease associated with active TED with a CAS = 4 for the most severely affected eye 2. Moderate-to-severe active TED according to EUGOGO`s classification (not sight-threatening but has an appreciable impact on daily life), usually associated with one or more of the following: lid retraction = 2 mm, moderate or severe soft tissue involvement, exophthalmos = 3 mm above normal for race and gender, and/or inconstant or constant diplopia 3. Onset of active TED symptoms within 6 months prior to baseline 4. Participants must be euthyroid with the baseline disease under control or have mild hypo- or hyperthyroidism (defined as free thyroxine [FT4] and free triiodothyronine [FT3] levels =65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: 1. Decreased vision due to optic neuropathy as defined by a significant decrease in best corrected visual acuity, new visual field defect, or colour defect secondary to optic nerve involvement within the last 6 months 2. Require immediate surgical ophthalmological intervention OR is planning corrective surgery/irradiation during the course of the study 3. Uncontrolled diabetes defined as HbA1C > 9.0% and more than a 10% change in the dose of a currently prescribed diabetic medication, or no new anti-diabetic medication within 60 days prior to Screening 4. Corneal decompensation unresponsive to medical management 5. Previous orbital irradiation or surgery for TED 6. Any steroid use (intravenous [IV] or oral) with a cumulative dose equivalent to = 1 g of methylprednisolone for the treatment of TED. Previous steroid use (IV or oral) with a cumulative dose of <1 g methylprednisolone or equivalent for the treatment of TED and previous use of steroid eye drops is allowed if the corticosteroid was discontinued at least at screening. 7. Corticosteroid use for conditions other than TED within 4 weeks prior to inclusion (topical steroids for dermatological conditions and inhaled steroids are allowed) 8. Selenium and biotin must be discontinued at screening and must not be restarted during the clinical trial; however, taking a multivitamin that includes selenium and/or biotin is allowed 9. Use of any other non-steroid immunosuppressive including agent, new biologic drugs within 3 months prior to screening 10. Use of an investigational agent for any condition within 60 days prior to inclusion or anticipated use during the course of the trial 11. Identified pre-existing ophthalmic disease that, in the judgment of the investigator, would preclude study participation or complicate interpretation of study results 12. Bleeding diathesis that in the judgment of the investigator would preclude inclusion in the clinical trial 13. Malignant condition in the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin) 14. Pregnant or lactating women 15. Current drug or alcohol abuse, or history of either within the previous 2 years, in the opinion of the investigator or as reported by the participant 16. Biopsy-proven or diagnose of inflammatory bowel disease according to ECCO-ESGAR guidelines 17. Known hypersensitivity to any of the components Sirolimus and Solu-medrol, including soya beans and peanuts. 18. Previous enrolment in this study 19. Ongoing Human immunodeficiency virus (HIV), tuberculosis, COVID-19, hepatitis C or hepatitis B infections 20. Previous tuberculosis, hepatitt C or B. 21. Any laboratory values outside the reference range that is of clinical relevance, including but not limited to hematological parameters, clinical blood chemistry, liver and kidney function parameters, serum lipids levels. 22. Need to use medications contraindicated according to SmPC of the IMP(s). 23. Any other contraindication listed on the SmPC of the IMP(s). 24. Participation in another clinical trial that might affect the current study or that there should be minimum 90 days between participation in another intervention trial. 25. Any reason why, in the opinion of the investigator, the patient should not participate (e.g. not able to comply with study procedures).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether treatment with Sirolimus in patients with active TED is more effective, and gives less metabolic complications than the established treatment with intravenous corticosteroids;Secondary Objective: Not applicable.;Primary end point(s): •=2 point reduction in Clinical Activity Score (CAS) from baseline at week 12. The CAS is a 7-item description of clinical symptoms and signs indicating orbital inflammation. These are: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active inflammatory phase of TED; 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active inflammatory phase of TED (ignore "equivocal" redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1 = present; 0 = absent) and scores for each item are summed for total score of 0 (no clinical activity) to 7 (most clinical activity). ;Timepoint(s) of evaluation of this end point: Endpoint evaluation after week 12. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • = 2 mm reduction from baseline in proptosis in one eye at week 12. • = 2 mm reduction from baseline in vertical lid aperture in one eye at week 12. • = 1 class improvement of eye motility from baseline assessed by Gorman score at week 12. Gorman score: 1 = no diplopia, 2 intermittent diplopia, 3 = inconstant (gaze-evoked) diplopia, 4 = constant diplopia in primary or reading position. • participants with serious adverse effects after 6 months • participants with minor adverse effects after 6 months • = 6 points improvement in GO-QOL score ;Timepoint(s) of evaluation of this end point: Efficacy endpoint evaluation after week 12. Safety endpoint evaluation after 6 months. | — |
Countries
Norway
Contacts
Public ContactHans Olav Ueland
Helse Bergen HF, Haukeland University Hospital
Outcome results
None listed