Sirolimus vs Corticosteroids in Treatment of Thyroid Eye Disease

NCT04936854 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 234527
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether Sirolimus is more effective and burdened with less side effects than conventional treatment with corticosteroids in patients with active thyroid eye disease.

Conditions

Thyroid-Associated Ophthalmopathy

Keywords

Thyroid eye disease; Graves' Orbitopathy; Immunosuppressive Agents; Exophthalmos; Sirolimus

Outcome Measures

Primary Outcomes (1)

• Percentage of participants who were CAS categorical responders at week 12

  CAS categorical responders were defined as participants with a reduction of ≥ 2 CAS points. The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (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 inflammatory symptoms) to 7 (most inflammatory symptoms).

  Week 12

Secondary Outcomes (3)

• Percentage of participants who were proptosis responders at week 12

  Week 12

• Percentage of participants who were eyelid retraction responders at week 12

  Week 12

• Percentage of participants who were diplopia responders at week 12

  Baseline, up to Week 12

Study Arms (2)

Sirolimus

ACTIVE COMPARATOR

Patients with active thyroid eye disease will receive 2 mg Sirolimus (two 1 mg tablets) on the first day, followed by 0,5 mg Sirolimus (half 1 mg tablet) per day for 12 weeks.

Drug: Sirolimus 1 mg Oral Tablet

Corticosteroids

ACTIVE COMPARATOR

Patients with active thyroid eye disease will receive 500 mg Methylprednisolone intravenously once a week for 6 weeks, followed by 250 mg once a week for 6 weeks.

Drug: Methylprednisolone

Interventions

Sirolimus 1 mg Oral Tablet DRUG

2 mg Sirolimus (two 1 mg tablets) on the first day, followed by 0,5 mg Sirolimus (half 1 mg tablet) per day for 12 weeks.

Also known as: Rapamycin, Rapamune

Sirolimus

Methylprednisolone DRUG

500 mg Methylprednisolone intravenously once a week for 6 weeks, followed by 250 mg once a week for 6 weeks. Total period of treatment 12 weeks.

Also known as: Solu-Medrol

Corticosteroids

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant want treatment for active thyroid eye disease and is willing to be included in the study
• Clinical diagnosis of Graves' disease associated with active TED with a Clinical Activity Score (CAS) ≥ 4 (on the 7-item scale)
• Moderate-to-severe active TED (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
• Onset of active TED symptoms (as determined by participant records) within 9 months prior to inculsion
• Participants must be euthyroid with the Graves disease under control or have mild hypo- 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 planning corrective 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 in the dose of a currently prescribed diabetic medication within 60 days prior to Screening)
• 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 all protocol-specified timepoints (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 2 reliable forms of contraception during the trial, one of which is recommended to be hormonal, 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
• 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
• Active Influenza and Pneumococcal vaccines

You may not qualify if:

• The participant dont want treatment for active thyroid eye disease or dont want to participate in the study
• Decreased vision due to optic neuropathy as defined by a significant decrease in best corrected visual acuity, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months
• Corneal decompensation unresponsive to medical management
• Selenium and biotin must be discontinued 3 weeks prior to Screening and must not be restarted during the clinical trial; however, taking a multivitamin that includes selenium and/or biotin is allowed
• Use of any other non-steroid immunosuppressive including agent, new biologic drugs within 3 months prior to Screening
• Identified pre-existing ophthalmic disease that, in the judgment of the Investigator, would preclude study participation or complicate interpretation of study results
• Malignant condition in the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin)
• Pregnant or lactating women
• 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
• Biopsy-proven or clinically suspected inflammatory bowel disease
• Known hypersensitivity to any of the components Sirolimus.
• Previous enrollment in this study
• Human immunodeficiency virus (HIV), tuberculosis, hepatitis C or hepatitis B infections

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (1)

Department of Ophthalmology Haukeland University Hospital

Bergen, Hordaland, 5021, Norway

RECRUITING

Related Publications (3)

• Roos JCP, Murthy R. Sirolimus (rapamycin) for the targeted treatment of the fibrotic sequelae of Graves' orbitopathy. Eye (Lond). 2019 Apr;33(4):679-682. doi: 10.1038/s41433-019-0340-3. Epub 2019 Feb 12.

  PMID: 30755726 BACKGROUND

• Chang S, Perry JD, Kosmorsky GS, Braun WE. Rapamycin for treatment of refractory dysthyroid compressive optic neuropathy. Ophthalmic Plast Reconstr Surg. 2007 May-Jun;23(3):225-6. doi: 10.1097/IOP.0b013e3180500d57.

  PMID: 17519662 BACKGROUND

• Roos JCP, Eglitis V, Murthy R. Inhibition of Fibrotic Contraction by Sirolimus (Rapamycin) in an Ex Vivo Model of Thyroid Eye Disease. Ophthalmic Plast Reconstr Surg. 2021 Jul-Aug 01;37(4):366-371. doi: 10.1097/IOP.0000000000001876.

  PMID: 33237667 BACKGROUND

MeSH Terms

Conditions

Graves Ophthalmopathy; Exophthalmos

Interventions

Sirolimus; Tablets; Methylprednisolone; Methylprednisolone Hemisuccinate

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Hans O Ueland, MD Phd

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hans O ueland, MD PhD

CONTACT

+47 55 97 57 19; uela@helse-bergen.no

Eyvind Rødahl, MD PhD

CONTACT

+47 55 97 41 10; erod@helse-bergen.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The treatment will be allocated by the investigator trough the procedure with sealed envelopes, thereafter the investigator will enroll patients and assign patients to treatment. The treatment options will be conceal to prevent participants knowing until final trial analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2021
• First Posted: June 23, 2021
• Study Start: January 1, 2023
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 22, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)