Study of efficacy and safety of secukinumab in adult patients with active, moderate to severe thyroid eye disease

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 - ORBIT

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-001611-24-DE

Enrollment

Registered

2020-10-26

Start date

2021-07-26

Completion date

Unknown

Last updated

2021-10-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Active, moderate to severe thyroid eye disease MedDRA version: 20.1 Level: PT Classification code 10060742 Term: Endocrine ophthalmopathy System Organ Class: 10015919 - Eye disorders

Interventions

Trade Name: Cosentyx Product Name: Secukinumab Product Code: AIN457 Pharmaceutical Form: Solution for injection in pre-filled syringe INN or Proposed INN: secukinumab CAS Number: 1229022-83-6 Current

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. 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. 2. Male or non-pregnant, non-lactating female patients = 18 years of age. 3. 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 4. Onset of TED symptoms fewer than 12 months prior to Baseline. 5. 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. 6. Peripheral euthyroidism or mild hypo-/hyperthyroidism defined as free T3 (fT3) and free T4 (fT4) =65 years) yes F.1.3.1 Number of subjects for this age range 7

Exclusion criteria

Exclusion criteria: 1. Improvement in CAS of = 2 points and/or improvement in proptosis of = 2 mm in the study eye between Screening and Baseline. 2. Signs of sight-threatening TED defined by optic neuropathy or severe corneal injury. 3. Patients, in the opinion of the investigator, requiring immediate or urgent medical treatment with glucocorticoids for TED. 4. Patients requiring immediate surgical ophthalmological intervention or planning corrective surgery/irradiation during the course of the study. 5. 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. 6. Any other ophthalmic and/or orbital disease or condition that might interfere with the assessment of TED. 7. Previous orbital radiotherapy. 8. Previous ophthalmological/orbital surgery for TED (e.g. orbital decompression). 9. Previous use of biological agents for the treatment of TED. 10. Previous use of systemic, non-biologic, immunomodulatory agents for the treatment of TED (e.g., mycophenolate or cyclosporine). 11. Previous exposure to secukinumab or other biologic drugs directly targeting IL-17A or the IL-17 receptor (e.g., ixekizumab, brodalumab). 12. Previous treatment with rituximab, tocilizumab or teprotumumab. 13. 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. 14. 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). 15. Use of other investigational drugs within 5 half-lives of enrollment or within 30 days, whichever is longer. 16. Previous or ongoing use of prohibited treatments. Respective washout periods have to be adhered to. 17. History of hypersensitivity to any of the study drug constituents. Other protocol-defined exclusion criteria may apply

Design outcomes

Primary

Measure	Time frame
Main Objective: To demonstrate that secukinumab is superior to placebo with regard to the overall responder rate after 16 weeks of treatment.;Secondary Objective: - To demonstrate that secukinumab is superior to placebo with regard to the CAS responder rate after 16 weeks of treatment. - To demonstrate that secukinumab is superior to placebo with regard to the proptosis responder rate after 16 weeks of treatment. - To demonstrate that secukinumab is superior to placebo with regard to reduction in diplopia after 16 weeks of treatment. - To demonstrate that secukinumab is superior to placebo with regard to reduction in CAS after 16 weeks of treatment. - To demonstrate that secukinumab is superior to placebo with regard to reduction in proptosis after 16 weeks of treatment. - To demonstrate that secukinumab is superior to placebo with regard to improvement in disease severity after 16 weeks of treatment. - To demonstrate that secukinumab is superior to placebo with regard to improvement in GO-QoL after 16 weeks of treatment. - To evaluate the safety of secukinumab compared to placebo.;Primary end point(s): Proportion of patients achieving overall response defined as follows: = 2 point reduction in CAS AND = 2 mm reduction in proptosis from Baseline in the study eye, provided there is no corresponding deterioration in CAS or proptosis (= 2 point or 2 mm increase, respectively) in the fellow eye after 16 weeks of treatment. ;Timepoint(s) of evaluation of this end point: Week 16	—

Measure

Time frame

Main Objective: To demonstrate that secukinumab is superior to placebo with regard to the overall responder rate after 16 weeks of treatment.;Secondary Objective: - To demonstrate that secukinumab is superior to placebo with regard to the CAS responder rate after 16 weeks of treatment. - To demonstrate that secukinumab is superior to placebo with regard to the proptosis responder rate after 16 weeks of treatment. - To demonstrate that secukinumab is superior to placebo with regard to reduction in diplopia after 16 weeks of treatment. - To demonstrate that secukinumab is superior to placebo with regard to reduction in CAS after 16 weeks of treatment. - To demonstrate that secukinumab is superior to placebo with regard to reduction in proptosis after 16 weeks of treatment. - To demonstrate that secukinumab is superior to placebo with regard to improvement in disease severity after 16 weeks of treatment. - To demonstrate that secukinumab is superior to placebo with regard to improvement in GO-QoL after 16 weeks of treatment. - To evaluate the safety of secukinumab compared to placebo.;Primary end point(s): Proportion of patients achieving overall response defined as follows: = 2 point reduction in CAS AND = 2 mm reduction in proptosis from Baseline in the study eye, provided there is no corresponding deterioration in CAS or proptosis (= 2 point or 2 mm increase, respectively) in the fellow eye after 16 weeks of treatment. ;Timepoint(s) of evaluation of this end point: Week 16

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Secondary

Measure	Time frame
Secondary end point(s): - Proportion of patients achieving response in reduction of CAS at Week 16 defined as follows: reduction of = 2 points from Baseline in the study eye without deterioration (= 2 point increase) of CAS in the fellow eye. - Proportion of patients 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. - Proportion of patients achieving response in diplopia at Week 16 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. - Mean change from Baseline to Week 16 in CAS in the study eye. - Mean change from Baseline to Week 16 in proptosis in the study eye. - Proportion of patients with improvement in EUGOGO disease severity between Baseline and Week 16. - Mean change from Baseline to Week 16 in GO QoL score. - Frequency of AEs, TEAEs, AEs resulting in treatment discontinuation, SAEs.;Timepoint(s) of evaluation of this end point: Week 16	—

Measure

Time frame

Secondary end point(s): - Proportion of patients achieving response in reduction of CAS at Week 16 defined as follows: reduction of = 2 points from Baseline in the study eye without deterioration (= 2 point increase) of CAS in the fellow eye. - Proportion of patients 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. - Proportion of patients achieving response in diplopia at Week 16 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. - Mean change from Baseline to Week 16 in CAS in the study eye. - Mean change from Baseline to Week 16 in proptosis in the study eye. - Proportion of patients with improvement in EUGOGO disease severity between Baseline and Week 16. - Mean change from Baseline to Week 16 in GO QoL score. - Frequency of AEs, TEAEs, AEs resulting in treatment discontinuation, SAEs.;Timepoint(s) of evaluation of this end point: Week 16

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Countries

Germany

Contacts

Public ContactMedizinischer Infoservice

Novartis Pharma GmbH

infoservice.novartis@novartis.com+49911273 12100

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026