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Thyroid Eye DiseasePhase 3ORBITNCT04737330

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

A Phase 3 study testing Secukinumab in people with Thyroid Eye Disease and Graves Orbitopathy, run by Novartis Pharmaceuticals at 5 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Thyroid Eye Disease, Graves Orbitopathy
What is being tested?
Secukinumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
28 participants
Where
5 sitesGermany
Study dates
29 Nov 2021to 16 May 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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.
Show all 18Show fewer
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Germany5 sites

  • Novartis Investigative Site

    Essen, 45147

  • Novartis Investigative Site

    Frankfurt, 60318

  • Novartis Investigative Site

    Freiburg im Breisgau, 79106

  • Novartis Investigative Site

    Göttingen, 37075

  • Novartis Investigative Site

    Mainz, 55131

Other trials in Germany

About this study

Official title: 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

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.

Read the detailed description

This study consisted of the following 3 periods:

  1. Screening period (Week -6 to Baseline): Participants' eligibility was assessed during the Screening period, which occurred for a maximum of 6 weeks.
  2. Treatment period (Baseline to Week 16): Eligible participants were randomized in a 1:1 ratio to one of the following double-blinded treatment arms:
  • Arm 1: Secukinumab 300 mg s.c. at Baseline, Week 1, 2, 3, 4, 8, 12
  • Arm 2: Placebo s.c. at Baseline, Week 1, 2, 3, 4, 8, 12 Participants were stratified according to current smoking status (up to 20% smokers per arm) since smoking has a well-known impact on treatment efficacy in TED.
  1. Follow-up/open-label retreatment period (Week 16 up to Week 108):
  • Proptosis responders (see definition below) at Week 16 were followed for relapse up to Week 68. If these participants relapsed, they were offered a course of open-label secukinumab at the time of relapse (see "proptosis relapsers" definition below).
  • Proptosis non-responders (see definition below) at Week 16 were offered the option of open-label secukinumab treatment (with maintenance of blind to initial randomized treatment) for a duration of 16 weeks, i.e., up to Week 32 with last dose at Week 28, as follows:
  • Open-label secukinumab 300 mg s.c. at Week 16, 17, 18, 19, 20, 24 and 28. Thereafter (i.e., from Week 32), participants were followed up for a further 24 weeks to assess the relapse rate.
  • For participants who were proptosis non-responders and who did not receive open-label secukinumab treatment, a follow-up visit 8 weeks after the Week 16 visit needed to be scheduled per protocol. At this follow-up visit, the assessments associated with the Week 24 visit (for responders) were to be performed.
  • Proptosis relapsers (see definition below) during the follow-up period (from Week 16 onward to Week 68) were offered the option of retreatment with open-label secukinumab for a duration of 16 weeks (with maintenance of blind to initial randomized treatment) at the time of relapse as follows:
  • Open-label secukinumab 300 mg s.c. at time of relapse, then at 1, 2, 3, 4, 8 and 12 weeks since time of relapse. Thereafter, participants were followed up for a further 24 weeks (i.e., 40 weeks after start of retreatment) to assess rate of relapse and safety.
  • For participants not receiving open-label secukinumab treatment a follow-up visit 8 weeks after the Week 16 visit were to be scheduled per protocol, if not yet completed. At this follow-up visit, the assessments associated with the Week 24 visit (for responders) were to be performed.

Definitions of proptosis responder, non-responder and relapser:

  • Proptosis responders: Participants achieving response in reduction of proptosis at Week 16 defined as follows: reduction of >= 2 mm from Baseline in the study eye without deterioration (>= 2 mm increase) of proptosis in the fellow eye.
  • Proptosis non-responders: Participants not achieving response in reduction of proptosis at Week 16 with "response" defined as follows: reduction of >= 2 mm from Baseline in the study eye without deterioration (>= 2 mm increase) of proptosis in the fellow eye.
  • Proptosis relapsers: Participants who were "proptosis responders" as defined above, and then relapsed based on proptosis at any time during the 52-week follow-up period with relapse defined as follows: increase in proptosis of >= 2 mm compared to Week 16 in the study eye or deterioration of proptosis (>= 2 mm increase) in the fellow eye at any time during 52-week follow-up period.

In case of worsening of the disease, participants were allowed to receive alternative treatment for TED at the discretion of the investigator and were discontinued from the study treatment.

The primary endpoint analysis was planned to be performed once all participants had reached Week 40, which included the primary efficacy endpoint (Week 16), efficacy of retreatment for initial non-responders and relapse rates during 24 weeks of follow-up.

The final analysis was planned to be performed when the last participant had reached the end of trial.

The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) expressed different preferences regarding the primary and secondary objectives and endpoints and their ordering. Therefore, this study intended to have 2 different analysis strategies and corresponding primary, secondary objective and endpoint definitions; Plan A was intended for submission in Europe (EU) and other applicable countries and Plan B was intended for submission in the United States (US) and other applicable countries. As the study was early terminated, only Plan A analysis was conducted.

Being tested
Secukinumab, Placebo
Keywords
TED, Bulging eyes, Exophthalmos
Medical subject headings
Graves Ophthalmopathy, Exophthalmos

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SecukinumabDrug

    Also called AIN457

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

  • PlaceboDrug

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

Study groups in NCT04737330
Study groupRoleWhat they receive
Secukinumab 300 mgActive comparatorSecukinumab 300 mg subcutaneous (s.c.) injection at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12
Receives: Drug: Secukinumab
PlaceboPlacebo comparatorPlacebo subcutaneous (s.c.) injection at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline, Week 16

  2. 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.

    Measured: Baseline, Week 16

Secondary outcomes (17)

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

    The percentage of participants achieving response in reduction of clinical activity score (CAS) at Week 16 was defined as follows: reduction of >= 2 points from Baseline in the study eye without deterioration (>= 2 points increase) of CAS in the fellow eye. Due to premature study discontinuation, purely descriptive analyses were performed for the secondary endpoint.

    Measured: Baseline, Week 16

  2. Plan A - 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, purely descriptive analyses were performed for the secondary endpoint.

    Measured: Baseline, Week 16

  3. Plan A - Percentage of Participants Achieving Response in Diplopia

    The percentage of participants achieving response in diplopia at Week 16 was defined as follows: Baseline diplopia > 0 and a reduction of >= 1 grade with no corresponding deterioration (>= 1 grade worsening) in the fellow eye at Week 16. Due to premature study discontinuation, purely descriptive analyses were performed for the secondary endpoint.

    Measured: Baseline, Week 16

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

    Thyroid Eye Disease (TED) activity was assessed using the CAS at the frequency indicated in the study schedule based on the following signs and symptoms in accordance with the European Group on Graves' Orbitopathy (EUGOGO) guideline:

    • Symptoms
    • Spontaneous retrobulbar pain
    • Pain on attempted upward or downward gaze
    • Signs
    • Redness of eyelids
    • Redness of conjunctiva
    • Swelling of caruncle or plica
    • Swelling of eyelids
    • Swelling of conjunctiva (chemosis)

    For each item present, 1 point is given. The sum of these points is the CAS score, i.e., minimum score of 0 and maximum score of 7.

    • Inactive TED: CAS < 3.
    • Active TED: CAS >= 3.

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

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

    Proptosis measurements were performed at the frequency indicated in the study schedule. The same Hertel instrument, and the same outer intercanthal distance, were to be used for each measurement. The mean of measurements (change from baseline in millimeters (mm) of proptosis, calculated as: (Post-Baseline value - Baseline value) / Baseline value * 100)) for each group were presented. Due to premature study discontinuation, purely descriptive analyses were performed for the secondary endpoint.

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

  6. Plan A - Percentage of Participants With Improvement in EUGOGO Disease Severity

    Thyroid Eye Disease (TED) activity was assessed using the CAS at the frequency indicated in the study schedule based on the following signs and symptoms in accordance with the European Group on Graves' Orbitopathy (EUGOGO) guideline. Improvement in EUGOGO disease severity was categorized: Mild, Moderate to severe and Sight threatening.

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

  7. Plan A - Graves' Ophthalmopathy Quality of Life Questionnaire (GO-QOL) Score (Score 1: Visual Functioning) Over Time

    The Graves' ophthalmopathy quality of life questionnaire (GO-QOL) contains 8 questions on visual functioning and 8 questions on appearance; answers on each subscale are transformed to scores ranging from 0 (worst) to 100 (best). Due to premature study discontinuation, purely descriptive analyses were performed for the secondary endpoint.

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

  8. Plan A - Graves' Ophthalmopathy Quality of Life Questionnaire (GO-QOL) Score (Score 2: Psychosocial Functioning) Over Time

    The Graves' ophthalmopathy quality of life questionnaire (GO-QOL) contains 8 questions on visual functioning and 8 questions on appearance; answers on each subscale are transformed to scores ranging from 0 (worst) to 100 (best). Due to premature study discontinuation, purely descriptive analyses were performed for the secondary endpoint.

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

  9. Plan A - Number of Participants With Adverse Events

    The distribution of adverse events during Plan A study treatment period was done via the analysis of frequencies for Adverse Event (AEs) and Serious Adverse Event (SAEs), through the monitoring of relevant clinical and laboratory safety parameters.

    Measured: From first dose of study treatment until Week 16

  10. Plan B - Percentage of Participants Achieving Response in Reduction of Clinical Activity Score (CAS)

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

    Measured: Baseline, Week 16

  11. Plan B - Percentage of Participants Achieving Overall Response

    The percentage of participants achieving overall response was defined as follows: >= 2 points reduction in 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, only Plan A was conducted (Plan B was not initiated) for the secondary endpoint.

    Measured: Baseline, Week 16

  12. Plan B - Percentage of Participants Achieving Response in Diplopia

    The percentage of participants achieving response in diplopia at Week 16 was defined as follows: Baseline diplopia > 0 and a reduction of >= 1 grade with no corresponding deterioration (>= 1 grade worsening) in the fellow eye at Week 16. Due to premature study discontinuation, only Plan A was conducted (Plan B was not initiated) for the secondary endpoint.

    Measured: Baseline, Week 16

  13. Plan B - Mean Change From Baseline to Week 16 in Clinical Activity Score (CAS) in the Study Eye.

    Due to premature study discontinuation, only Plan A was conducted (Plan B was not initiated) for the secondary endpoint.

    Measured: Baseline, Week 16

  14. Plan B - Mean Change From Baseline to Week 16 in Proptosis in the Study Eye.

    Proptosis is the protrusion of the eyeball. Exophthalmos means the same, and this term is usually used when describing proptosis due to Grave's disease. Due to premature study discontinuation, only Plan A was conducted (Plan B was not initiated) for the secondary endpoint.

    Measured: Baseline, Week 16

  15. Plan B - Mean Change From Baseline to Week 16 in the Graves' Ophthalmopathy Quality of Life Questionnaire (GO-QOL) Score (Score 1: Visual Functioning)

    The Graves' ophthalmopathy quality of life questionnaire (GO-QOL) contains 8 questions on visual functioning and 8 questions on appearance; answers on each subscale are transformed to scores ranging from 0 (worst) to 100 (best). Due to premature study discontinuation, only Plan A was conducted (Plan B was not initiated) for the secondary endpoint.

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

  16. Plan B - Mean Change From Baseline to Week 16 in the Graves' Ophthalmopathy Quality of Life Questionnaire (GO-QOL) Score (Score 2: Psychosocial Functioning)

    The Graves' ophthalmopathy quality of life questionnaire (GO-QOL) contains 8 questions on visual functioning and 8 questions on appearance; answers on each subscale are transformed to scores ranging from 0 (worst) to 100 (best). Due to premature study discontinuation, only Plan A was conducted (Plan B was not initiated) for the secondary endpoint.

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

  17. Plan B - Number of Participants With Adverse Events

    Due to premature study discontinuation, only Plan A was conducted (Plan B was not initiated) for the secondary endpoint.

    Measured: From first dose of study treatment until Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2021
  2. Study start29 Nov 2021
  3. Primary completion16 May 2023
  4. Study completion16 May 2023

Why it stopped: Analysis of blinded patient data showed a very low probability of the study meeting the primary efficacy endpoints. No safety concerns were identified

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04737330
Sponsor's protocol ID
CAIN457ADE16
Other IDs
2020-001611-24
Acronym
ORBIT
Status last verified
Apr 2026
First submitted
20 Nov 2020
Last updated
15 Apr 2026
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Secukinumab in people with Thyroid Eye Disease and Graves Orbitopathy, run by Novartis Pharmaceuticals at 5 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plan A - Percentage of Participants Achieving Overall Response (time frame: Baseline, Week 16). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04737330.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2026.

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