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

NCT04737330 | Terminated Phase 3 Results

• 2 other identifiers: CAIN457ADE162020-001611-24
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 5

Brief 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. 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.

Conditions

Thyroid Eye Disease; Graves Orbitopathy

Keywords

TED; Bulging eyes; Exophthalmos

Outcome Measures

Primary Outcomes (2)

• Plan A - Percentage of Participants Achieving Overall Response

  The percentage of participants achieving overall response was defined as follows: \>= 2 points reduction in clinical activity score (CAS) AND \>= 2 mm reduction in proptosis from Baseline in the study eye, provided there was no corresponding deterioration in CAS or proptosis (\>= 2 point or 2 mm increase, respectively) in the fellow eye after 16 weeks of treatment. Due to premature study discontinuation, purely descriptive analyses were performed for the primary endpoint.

  Baseline, Week 16

• Plan B - Percentage of Participants Achieving Response in Reduction of Proptosis

  The percentage of participants achieving response in reduction of proptosis at Week 16 was defined as follows: reduction of \>= 2 mm from Baseline in the study eye without deterioration (\>= 2 mm increase) of proptosis in the fellow eye. Due to premature study discontinuation, only Plan A was conducted (Plan B was not initiated) for the primary endpoint.

  Baseline, Week 16

Secondary Outcomes (17)

• Plan A - Percentage of Participants Achieving Response in Reduction of Clinical Activity Score (CAS)

  Baseline, Week 16

• Plan A - Percentage of Participants Achieving Response in Reduction of Proptosis

  Baseline, Week 16

• Plan A - Percentage of Participants Achieving Response in Diplopia

  Baseline, Week 16

• Plan A - Mean Change From Baseline to Week 16 in Clinical Activity Score (CAS) in the Study Eye

  Baseline, Week 2, Week 4, Week 8, Week 12, Week 16

• Plan A - Mean Change From Baseline to Week 16 in Millimeters (mm) of Proptosis in the Study Eye

  Baseline, Week 2, Week 4, Week 8, Week 12, Week 16

Study Arms (2)

Secukinumab 300 mg

ACTIVE COMPARATOR

Secukinumab 300 mg subcutaneous (s.c.) injection at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12

Drug: Secukinumab

Placebo

PLACEBO COMPARATOR

Placebo subcutaneous (s.c.) injection at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12

Drug: Placebo

Interventions

Secukinumab DRUG

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

Also known as: AIN457

Secukinumab 300 mg

Placebo DRUG

Placebo s.c. at Baseline, Weeks 1, Week 2, Week 3, Week 4, Week 8, Week 12

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Frankfurt, 60318, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Göttingen, 37075, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Graves Ophthalmopathy; Exophthalmos

Interventions

secukinumab

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2020
• First Posted: February 3, 2021
• Study Start: November 29, 2021
• Primary Completion: May 16, 2023
• Study Completion: May 16, 2023
• Last Updated: April 15, 2026
• Results First Posted: January 9, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (5)