A Study of the Efficacy and Safety of Secukinumab 300 mg in Patients With Thyroid Eye Disease (TED)
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. 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.
This study will have 2 different analysis strategies and corresponding primary, secondary and
 exploratory objective and endpoint definitions.
Inclusion Criteria:

 -  Signed informed consent must be obtained prior to participation in the study.

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

 -  Clinical diagnosis of active, moderate-to-severe TED (not sight threatening) 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 for race and
 gender; 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. 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 corneal decompensation.

 -  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).

 -  Requires immediate surgical ophthalmological intervention or is planning corrective
 surgery/irradiation during the course of the study.

 -  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.

 -  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 this section have to be adhered to.

 -  History of hypersensitivity to any of the study drug constituents.