NCT lookup
Pull any trial record directly from ClinicalTrials.gov.
Sponsor: Novartis Pharmaceuticals
Conditions: Thyroid Eye Disease, Graves Orbitopathy
Interventions: Secukinumab, Placebo
Countries: Germany
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.
Sex: ALL
Age: 18 Years to 80 Years
Healthy volunteers: No
Study type: INTERVENTIONAL
Key Inclusion Criteria: * Patient had to be able to understand and communicate with the investigator and comply with the requirements of the study and had to give a written, signed and dated informed consent before any study assessment was 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 showed a similar degree of proptosis, other inflammatory signs and symptoms (CAS) were 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 was to 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. Key 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-cluster of differentiation 20 (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 (see Appendix 16.1.1-Protocol Section 6.2.2). Respective washout periods detailed in this section needed to be adhered to. * History of hypersensitivity to any of the study drug constituents. Other protocol defined Inclusion/Exclusion may apply.
- Essen, Germany
- Frankfurt, Germany
- Freiburg im Breisgau, Germany
- Göttingen, Germany
- Mainz, Germany