Evaluating Tocilizumab for Treating Corticosteroid-Resistant Thyroid Eye Disease

Efficacy and Safety of Tocilizumab in Patients With Active Moderate-to-Severe Corticosteroid-Resistant Thyroid Eye Disease: Open, Prospective, Observational Study

This study is testing if Tocilizumab can help people with Graves' Orbitopathy who haven't responded to steroid treatments feel better and improve their quality of life.

Quick facts

• Study type: Observational
• Enrollment: 30 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Medical University of Warsaw (Academic / other)
• Drugs / interventions: tocilizumab
• Locations: 1 site (Warsaw)
• Trial ID: NCT06367517 on ClinicalTrials.gov

What this trial studies

This study aims to assess the efficacy and safety of Tocilizumab as a second or third line treatment for patients suffering from active moderate-to-severe corticosteroid-resistant Graves' Orbitopathy. Graves' Orbitopathy is an autoimmune condition that can severely impact patients' quality of life, and current first-line treatments with glucocorticoids are only effective in a fraction of cases. The study will include 30 patients over approximately four years, focusing on clinical outcomes and adverse events associated with Tocilizumab therapy. The goal is to provide a better management option for patients who do not respond to traditional corticosteroid treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-80 with active, moderate-to-severe Graves' Orbitopathy who have not responded adequately to corticosteroid therapy.

Not a fit: Patients with mild or stable Graves' Orbitopathy or those who have not undergone prior corticosteroid treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new effective option for patients with corticosteroid-resistant Thyroid Eye Disease.

How similar studies have performed: Previous studies have shown promise in using Tocilizumab for similar conditions, indicating potential effectiveness, although long-term outcomes are still being evaluated.

Eligibility criteria

Inclusion Criteria:

* Written informed consent
* Male or female, 18-80 years old
* Patients with active (Clinical Activity Score ≥ 3 in 7-item scale) and moderate-to-severe GO, diagnosed according to the EUGOGO guidelines, after the completion of MP pulse treatment, WITH

  o Deterioration of GO (in 1 or 2 eyes) when two of the following occurred:
* increase in palpebral aperture by at least 2 mm;
* deterioration in CAS by at least 2 points (7-point CAS)
* increase in exophthalmos by at least 2 mm;
* worsening of diplopia (appearance or change in the degree)
* worsening in ocular motility by 8o

  o Incomplete response in both eyes to intravenous methylprednisolone pulse therapy; defined changes smaller than previously defined in any of the mentioned parameters.
* Euthyroid for at least 6-8 weeks (serum free hormone concentrations within 30% of normal range) on either anti-thyroid medications (tyonamides) to control hyperthyroidism or L-thyroxine for replacement therapy for hypothyroidism.
* Negative pregnancy test in women of fertile age.
* All female patients of fertile age must use a reliable contraceptive method to prevent pregnancy during the study period, and at least during a period of six months following the last dose of the investigational medicinal product.

Exclusion Criteria:

* Signs of sight-threatening TED (severe keratopathy, optic neuropathy)
* Pregnant or breastfeeding woman or woman planning to become pregnant during the study
* Patients who could need treatment with radioactive iodine or thyroidectomy during the study
* Treatment with any biological therapy at any time.
* Active infection.
* History of recurrent clinically significant infection or recurrent bacterial infections.
* Positive quantiferon without documentation of treatment for tuberculosis (TB) infection or documentation of no need for such therapy.
* Required management of infections, as follows: currently on any suppressive therapy for a chronic infection, hospitalization for treatment of infection within 60 days before Day 0, use of parenteral antibiotics within 60 days before Day 0, use of oral antibiotics within 30 days before Day 0.
* History of intestinal ulceration or diverticulitis
* Patients with a history of chronic liver disease or liver disorders: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) above 5 times upper limit of normal (ULN)
* HBsAg positive test.
* HBcAb positive test, regardless of HBsAb status, will undergo HBV DNA which, if positive, will be excluded. HbcAb positive, HbsAg negative patients with undetectable HBV DNA will receive antiviral prophylaxis throughout the immunosuppressive therapy.
* Hepatitis C antibody positive test at screening.
* Positive test for Human Immunodeficiency Virus (HIV) antibody at screening or historically. Denied consent to HIV testing.
* Absolute neutrophil count (ANC) \< 2.0 × 109/L or a platelet count \< 100×103/μL
* Alkaline phosphatase and bilirubin\>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin is\<35%).
* Cardiovascular or cerebrovascular disease clinically significant.
* Other serious chronic illness (including uncontrolled diabetes mellitus, renal disease, pulmonary disease, major depression).
* History of sarcoidosis.
* Primary or secondary immunodeficiency.
* History of IgE-mediated or non-IgE-mediated hypersensitivity.
* History of reactions or anaphylactic allergic severe human monoclonal antibodies, humanized or murine.
* Administration of live vaccines given within 30 days prior to administration of (Day 0) or concurrently with tocilizumab (during study).
* Splenectomy.
* Current drug or alcohol abuse or dependence.

Where this trial is running

Warsaw

• Department of Internal Medicine and Endocrinology, Medical University of Warsaw — Warsaw, Poland (Recruiting)

Study contacts

• Principal investigator: Tomasz Bednarczuk, MD, PHD — Medical University of Warsaw
• Study coordinator: Tomasz Bednarczuk, MD, PHD

Conditions Orbitopathy, Graves; Thyroid Eye Disease; Ophthalmopathy; Graves' disease; Graves' orbitopathy; Tocilizumab; Hyperthyroidism