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

• Status: Not yet recruiting
• Trial end date: 2025-01-25
• Target enrollment: 0
• Participant gender: All

Summary

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. 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 is to demonstrate the efficacy and safety of secukinumab 300 mg s.c. in adults with active, moderate to severe TED.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals

Criteria

Inclusion Criteria:

• Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed.

• Male or non-pregnant, non-lactating female patients ≥ 18 years of age.

• Clinical diagnosis of active, moderate to severe TED (not sight threatening) in the study eye at Baseline associated with 2 or more of the following: Lid retraction ≥ 2 mm; Moderate or severe soft tissue involvement; Exophthalmos ≥ 3 mm above normal; Inconstant or constant diplopia

• Onset of TED symptoms fewer than 12 months prior to Baseline.

• CAS ≥ 4 (on a 7-point scale, with a score of ≥ 3 indicating active TED) in the more severely affected (study) eye at Screening and Baseline. Note: Proptosis is the primary qualifier for selection of the study eye. In case both eyes show a similar degree of proptosis, other inflammatory signs and symptoms (CAS) should be taken into account by the investigator for the selection of the study eye.

• Peripheral euthyroidism or mild hypo-/hyperthyroidism defined as free T3 (fT3) and free T4 (fT4) < 30% above/below normal limits at Screening. Every effort should be made to correct the mild hypo-/hyperthyroidism promptly and to maintain the euthyroid state until the end of this study.

• Orbital MRI assessment available confirming the diagnosis of TED for patients initially presenting with hypo- or euthyroidism (without treatment for hyperthyroidism) before or at the time of TED diagnosis (to rule out other potential causes of orbital signs and symptoms).

Exclusion Criteria:

• Improvement in CAS of ≥ 2 points and/or improvement in proptosis of ≥ 2 mm in the study eye between Screening and Baseline.

• Signs of sight-threatening TED defined by optic neuropathy or severe corneal injury.

• Patients, in the opinion of the investigator, requiring immediate or urgent medical treatment with glucocorticoids for TED.

• Patients requiring immediate surgical ophthalmological intervention or planning corrective surgery/irradiation during the course of the study.

• Decreased best corrected visual acuity (BCVA) as defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect or color defect within the last 6 months.

• Any other ophthalmic and/or orbital disease or condition that might interfere with the assessment of TED.

• Previous orbital radiotherapy.

• Previous ophthalmological/orbital surgery for TED (e.g., orbital decompression).

• Previous use of biological agents for the treatment of TED.

• Previous use of systemic, non-biologic, immunomodulatory agents for the treatment of TED (e.g., mycophenolate or cyclosporine).

• Previous exposure to secukinumab or other biologic drugs directly targeting IL-17A or the IL-17 receptor (e.g., ixekizumab, brodalumab).

• Previous treatment with rituximab, tocilizumab or teprotumumab.

• Previous use of systemic corticosteroids for the treatment of TED, except for oral corticosteroids with a cumulative dose equivalent to < 1 g oral prednisone/prednisolone if the corticosteroid was discontinued at least 4 weeks prior to Baseline.

• Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 or investigational agents (e.g., CAMPATH, anti CD4, anti-CD5, anti-CD3, anti-CD19).

• Use of other investigational drugs within 5 half-lives of enrollment or within 30 days, whichever is longer.

• Previous or ongoing use of prohibited treatments. Respective washout periods detailed in the study protocol have to be adhered to.

• History of hypersensitivity to any of the study drug constituents. Other protocol specified exclusion criteria apply.