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

A Two-year Multi-center Phase 3 Study to Investigate the Efficacy and Safety of Secukinumab in Adult Patients With Active, Moderate to Severe Thyroid Eye Disease (ORBIT), With a Randomized, Parallel-group, Double-blind, Placebo-controlled, 16-week Treatment Period, and a Follow-up/Retreatment Period

ClinicalTrials.gov Identifier: NCT04737330

Novartis Reference Number: CAIN457ADE16

Last Update: Feb 14, 2022

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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.

Condition 
Thyroid Eye Disease
Graves Orbitopathy
Phase 
Phase 3
Overall status 
Recruiting
Start date 
Nov 29, 2021
Completion date 
Feb 05, 2025
Gender 
All
Age(s)
18 Years - 80 Years (Adult, Older Adult)

Interventions

Drug
Secukinumab
Secukinumab 300 mg s.c. at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12
Drug
Placebo
Placebo s.c. at Baseline, Weeks 1, Week 2, Week 3, Week 4, Week 8, Week 12
Drug
Secukinumab
Secukinumab 300 mg s.c. at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12
Drug
Placebo
Placebo s.c. at Baseline, Weeks 1, Week 2, Week 3, Week 4, Week 8, Week 12
Drug
Secukinumab
Secukinumab 300 mg s.c. at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12
Drug
Placebo
Placebo s.c. at Baseline, Weeks 1, Week 2, Week 3, Week 4, Week 8, Week 12
Drug
Secukinumab
Secukinumab 300 mg s.c. at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12
Drug
Placebo
Placebo s.c. at Baseline, Weeks 1, Week 2, Week 3, Week 4, Week 8, Week 12

Eligibility 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.

Study Locations

Germany
Novartis Investigative Site
Recruiting
Essen, 45147
-
Germany
Novartis Investigative Site
Recruiting
Freiburg, 79106
-
Germany
Novartis Investigative Site
Recruiting
Mainz, 55131
-
Germany
Novartis Investigative Site
Recruiting
Essen, 45147
-
Germany
Novartis Investigative Site
Recruiting
Freiburg, 79106
-
Germany
Novartis Investigative Site
Recruiting
Mainz, 55131
-
Germany
Novartis Investigative Site
Recruiting
Essen, 45147
-
Germany
Novartis Investigative Site
Recruiting
Freiburg, 79106
-
Germany
Novartis Investigative Site
Recruiting
Mainz, 55131
-
Germany
Novartis Investigative Site
Recruiting
Essen, 45147
-
Germany
Novartis Investigative Site
Recruiting
Freiburg, 79106
-
Germany
Novartis Investigative Site
Recruiting
Mainz, 55131
-
Germany

Contacts

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Novartis Pharmaceuticals
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Novartis Pharmaceuticals
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Novartis Pharmaceuticals
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Novartis Pharmaceuticals
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