Clinical Research Directory

Study to Assess Linsitinib in Participants With Moderate to Severe Active Thyroid Eye Disease (TED)

The goal of this clinical trial is to evaluate the efficacy, safety, and tolerability of linsitinib in participants with moderate to severe Thyroid Eye Disease (TED).

Prophylactic Treatment of Graves Ophthalmopathy (GO) in Newly Diagnosed Graves' Disease (GD) With Atorvastatin (ATORGO)

Graves' disease is an autoimmune condition that causes an overactive thyroid. Some people with Graves' disease develop thyroid eye disease, also called Graves' orbitopathy, which can cause swelling around the eyes, eye discomfort, double vision, changes in appearance, and, in severe cases, problems with vision. The purpose of this study is to find out whether atorvastatin, a commonly used cholesterol-lowering medicine, can reduce the risk of developing active thyroid eye disease in adults who have recently been diagnosed with Graves' disease. A total of 554 participants will be randomly assigned to one of two groups. One group will receive atorvastatin 40 mg once daily for 12 months in addition to standard treatment for Graves' disease. The other group will receive standard treatment for Graves' disease alone. Participants will be followed for 18 months. During the study, participants will have regular assessments of their thyroid disease and their eyes. Blood samples and questionnaires about symptoms and quality of life will also be collected. The researchers will compare the two groups to determine whether atorvastatin reduces the development of active thyroid eye disease.

A Phase 2b, Study of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED)

The overall objective is to study the safety, pharmacokinetics and efficacy of linsitinib (a small molecule IGF-1R inhibitor) administered orally twice daily (BID) vs. placebo, at 24 weeks in the treatment of subjects with active, moderate to severe thyroid eye disease (TED).

Study of Atorvastatin and Its Effects in Clinical and Radiological Aspects in Patients With Moderate-to-Severe Thyroid Eye Disease

The trial tests the hypothesis that, in adults with active, moderate-to-severe Graves' orbitopathy, 24 weeks of oral atorvastatin 20 mg daily added to a standard 12-week course of intravenous methylprednisolone produces a greater reduction in extraocular muscle size than intravenous methylprednisolone alone, and that any such reduction is accompanied by lower expression of TSH receptor, IGF-1 receptor, PDGF receptor, PI3K/AKT and miR-155 transcripts, and higher expression of miR-146a. The prespecified direction for miR-146a follows its reported suppression in CD4+ T cells in active disease \[26\]. Reported directions of change are compartment-specific and not unanimous, so the transcript analyses are exploratory.

Tofacitinib for Glucocorticoid-Resistant Moderate-to-Severe Thyroid Eye Disease

Thyroid Eye Disease (TED), also known as Graves' orbitopathy, is an autoimmune condition that causes inflammation and tissue expansion behind the eyes, leading to bulging eyes (proptosis), double vision, and pain. Currently, intravenous glucocorticoids (steroids) are the standard first-line treatment. However, approximately 20-30% of patients do not respond to steroids, or cannot tolerate their side effects. This study aims to evaluate the safety and efficacy of Tofacitinib, an oral medication known as a Janus kinase (JAK) inhibitor, as a rescue therapy for these difficult-to-treat cases. Tofacitinib works by blocking specific signaling pathways (JAK-STAT) that drive inflammation and fibrosis in the eye socket. In this study, patients with moderate-to-severe active TED who are resistant to or intolerant of steroids will receive Tofacitinib tablets (5 mg twice daily) for 24 weeks. The researchers will assess whether the treatment can effectively reduce eye bulging and improve clinical activity scores.

A Study of the Efficacy and Safety of Secukinumab 300 mg in Patients With Thyroid Eye Disease (TED)

Thyroid eye disease (TED) is a rare autoimmune, inflammatory disorder of the orbit and represents the most common extra-thyroidal manifestation of Graves' disease (GD). Several lines of evidence suggest an important role of interleukin-17A (IL-17A) in the pathogenesis of TED; increased levels of IL-17A have been detected in the serum and tears of patients with TED and IL-17A levels correlate with clinical activity of the disease. T-helper 17 cells (Th17 cells) (as well as other cellular sources of IL-17A, e.g., Tc17 cells) have been shown to infiltrate the orbital tissue of affected patients, producing IL-17A. IL-17A stimulates fibroblast activation, leading to retrobulbar tissue expansion and orbital fibrosis, which causes significant functional impairment. Secukinumab is a recombinant high-affinity fully human monoclonal anti-IL-17A antibody currently approved for the treatment of 3 inflammatory/ autoimmune diseases: moderate to severe plaque psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) (ankylosing spondylitis (AS) and non-radiographic axSpA). The purpose of this study was to demonstrate the efficacy and safety of secukinumab 300 mg subcutaneous (s.c.) in adults with active, moderate to severe TED.

Development of a Non-Invasive Prognostic Test for Graves Orbitopathy

The aim of this research project is to develop a non-invasive, simple, robust, and sensitive prognostic test that can identify hyperthyroidism patients who are at risk of developing Graves' Orbitopathy. This phase of the study is a research phase in which we analyze blood samples and tear fluid using standard laboratory equipment and software. The aim is to identify biomarkers that can detect patients at risk of developing Graves' Orbitopathy. Offering more personalized advice, treatment, and follow-up could potentially prevent the clinical consequences or limit their severity.

Extension Study of Two Doses of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED)

The overall study objective is to continue to assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of linsitinib in subjects who were enrolled in the prior VGN-TED-301 through Week 24. These subjects include VGN-TED-301 Week 24 proptosis non-responders or subjects who relapse during the Follow-Up Period of VGN-TED-301.