SIROLIMUS for Thyroid eye disease

Inclusion criteria

• {"criterion_text":"- Clinical diagnosis of Graves` disease associated with active TED with a CAS ≥ 4 for the most severely affected eye\n- 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 average value for race and gender, and/or inconstant or constant diplopia\n- Participants must be euthyroid with the thyroid disease under control or have mild hypo- or hyperthyroidism (defined as free thyroxine [FT4] and free triiodothyronine [FT3] levels < 50% above or below the normal limits). Every effort should be made to correct the mild hypo- or hyperthyroidism promptly and to maintain the euthyroid state for the full duration of the clinical trial.\n- Onset of active TED symptoms within 6 months prior to baseline\n- Women of childbearing potential (including those with an onset of menopause <2 years prior 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 negative serum pregnancy test at screening and negative urine pregnancy tests at each follow up (i.e., prior to each dose and through week 48 of the follow-up period); participants who are sexually active with a non-vasectomized male partner must agree to use a reliable contraception during the trial, such as an oral contraceptive. Hormonal contraception must be started at least one full cycle prior to baseline and continue for 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\n- Male participants must be surgically sterile or, if sexually active with a female partner of childbearing potential, must agree to use barrier contraceptive method from screening through 180 days after the last dose of study drug\n- Must be at least 18 years of age and below 80 years old.\n- Vaccinated according to the national guidelines.\n- Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations."}

Exclusion criteria

• {"criterion_text":"- 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\n- Use of an investigational agent for any condition within 60 days prior to inclusion or anticipated use during the trial\n- Identified pre-existing ophthalmic disease that, in the judgment of the investigator, would preclude study participation or complicate interpretation of study results\n- Bleeding diathesis that in the judgment of the investigator would preclude inclusion in the clinical trial\n- Malignant condition in the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin)\n- Pregnant or lactating women\n- 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\n- Biopsy-proven or diagnosis of inflammatory bowel disease according to ECCO-ESGAR guidelines\n- Known hypersensitivity to any of the components in Sirolimus and Solu-Medrol, including soya beans and peanuts\n- Previous enrolment in this study\n- Ongoing infection with human immunodeficiency virus (HIV), tuberculosis, COVID-19, hepatitis C or hepatitis B\n- Require immediate surgical ophthalmological intervention OR is planning corrective surgery/orbital irradiation during the study\n- Previous infection with tuberculosis, hepatitt B or C virus.\n- Any laboratory values outside the reference range that is of clinical relevance, including but not limited to hematological parameters, electrolytes, liver and kidney function parameters, serum lipid levels.\n- Need to use medications contraindicated according to SmPC of the IMP(s)\n- Any other contraindication listed on the SmPC of the IMP(s)\n- 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.\n- Any reason why, in the opinion of the investigator, the patient should not participate (e.g. not able to comply with study procedures)\n- Uncontrolled diabetes defined as HbA1C > 9.0% and more than a 10% change in the dose of a currently prescribed anti-diabetic medication, or no new anti-diabetic medication within 60 days prior to screening\n- Corneal decompensation unresponsive to medical managemen\n- Previous orbital irradiation or surgery for TED\n- 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 before screening\n- Corticosteroid use for conditions other than TED within 4 weeks prior to inclusion (topical steroids for dermatological conditions and inhaled steroids are allowed)\n- Selenium and biotin must be discontinued at screening and must not be restarted during the clinical trial..\n- Use of any other non-steroid immunosuppressive agent, including biologic drugs within 3 months prior to screening (6 months prior to screening after treatment with rituximab)."}

Primary endpoints

• {"endpoint_text":"- ≥2 point reduction in Clinical Activity Score (CAS) from baseline at week 12.","definition_or_measurement_approach":"Measured as change in Clinical Activity Score (CAS) from baseline; primary outcome assessed at week 12 (≥2 point reduction defines response)."}

Secondary endpoints

• {"endpoint_text":"- ≥ 2 mm reduction from baseline in proptosis in one eye at week 12.","definition_or_measurement_approach":"Measured change in proptosis from baseline in millimetres at week 12 (≥2 mm reduction)."}
• {"endpoint_text":"- ≥ 2 mm reduction from baseline in vertical lid aperture in one eye at week 12.","definition_or_measurement_approach":"Measured change in vertical lid aperture from baseline in millimetres at week 12 (≥2 mm reduction)."}
• {"endpoint_text":"- ≥ 1 class improvement of eye motility from baseline assessed by Gorman score at week 12.","definition_or_measurement_approach":"Improvement in eye motility by at least one class using the Gorman score assessed at week 12."}
• {"endpoint_text":"- Gorman score: 1 = no diplopia, 2 intermittent diplopia, 3 = inconstant (gaze-evoked) diplopia, 4 = constant diplopia in primary or reading position","definition_or_measurement_approach":"Definition of Gorman score categories used to assess diplopia severity/classification."}
• {"endpoint_text":"- ≥ 6 points improvement in GO-QOL score","definition_or_measurement_approach":"Measured change in Graves' Ophthalmopathy Quality of Life (GO-QOL) score; improvement defined as ≥6 points."}

Norway

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

03-03-2026

Processing Time Days

643

Number Of Sites

5

Number Of Participants

70

Primary sponsor

Full Name

Helse Bergen HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway