- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04737330
A Study of the Efficacy and Safety of Secukinumab 300 mg in Patients With Thyroid Eye Disease (TED) (ORBIT)
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Essen, Germany, 45147
- Novartis Investigative Site
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Frankfurt, Germany, 60318
- Novartis Investigative Site
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Freiburg, Germany, 79106
- Novartis Investigative Site
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Gottingen, Germany, 37075
- Novartis Investigative Site
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Mainz, Germany, 55131
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Investigational Arm
Investigational Arm - Secukinumab 300 mg s.c. at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12
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Secukinumab 300 mg s.c. at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12
Other Names:
|
Placebo Comparator: Control Arm - placebo
Control arm - placebo s.c. at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12
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Placebo s.c. at Baseline, Weeks 1, Week 2, Week 3, Week 4, Week 8, Week 12
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plan A - Proportion of participants achieving overall response
Time Frame: 16 weeks
|
Overall Response is defined as a ≥ 2-point reduction in clinical activity score (CAS) AND ≥ 2 mm reduction in proptosis from Baseline in study eye, provided there is no corresponding deterioration in CAS or proptosis (≥ 2 point or 2 mm increase, respectively) in the fellow eye
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16 weeks
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Plan B - Proportion of patients achieving response in reduction of proptosis
Time Frame: 16 weeks
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Reduction of proptosis is defined as reduction of ≥ 2 mm from Baseline in the study eye without deterioration (≥ 2 mm increase) of proptosis in the fellow eye.
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16 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plan A - Proportion of patients achieving response in reduction of clinical activity score (CAS)
Time Frame: 16 weeks
|
Reduction of CAS at Week 16 defined as reduction of ≥ 2 points from Baseline in the study eye without deterioration (≥ 2 point increase) of CAS in the fellow eye.
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16 weeks
|
Plan A - Proportion of patients achieving response in reduction of proptosis
Time Frame: 16 weeks
|
Reduction of proptosis is defined as reduction of ≥ 2 mm from Baseline in the study eye without deterioration (≥ 2 mm increase) of proptosis in the fellow eye.
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16 weeks
|
Plan A - Proportion of patients achieving response in diplopia
Time Frame: 16 weeks
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Proportion of participants with Baseline diplopia > 0 and a reduction of ≥ 1 grade with no corresponding deterioration (≥ 1 grade worsening) in the fellow eye at Week 16.
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16 weeks
|
Plan A - Mean change from Baseline to Week 16 in CAS in the study eye
Time Frame: 16 weeks
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Average change in clinical activity score (CAS)
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16 weeks
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Plan A - Mean change from Baseline to Week 16 in proptosis in the study eye
Time Frame: 16 weeks
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Average change in proptosis in study eye.
Proptosis is protrusion of the eyeball.
Exophthalmos means the same, and this term is usually used when describing proptosis due to Grave's disease
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16 weeks
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Plan A - Proportion of patients with improvement in EUGOGO disease severity
Time Frame: 16 weeks
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TED disease severity will be assessed at the frequency indicated in the study schedule based on the signs and symptoms in accordance with the European Group of Graves' Orbitopathy (EUGOGO) guideline (Bartalena et al 2016)
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16 weeks
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Plan A - Mean change from Baseline to Week 16 in GO-QoL score
Time Frame: 16 weeks
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Average change in the Graves' ophthalmopathy quality of life questionnaire (GO-QOL) score.
The 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).
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16 weeks
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Plan A - Number of participants with Adverse Events
Time Frame: Through study completion, up to two years
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Adverse Events (AEs) are any untoward sign or symptom that occurs during Plan A study treatment period
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Through study completion, up to two years
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Plan B - Proportion of patients achieving response in reduction of CAS
Time Frame: 16 weeks
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Reduction of CAS is defined as reduction of ≥ 2 points from Baseline in the study eye without deterioration (≥ 2 point increase) of CAS in the fellow eye
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16 weeks
|
Plan B - Proportion of patients achieving overall response
Time Frame: 16 weeks
|
Proportion of participants with ≥ 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.
|
16 weeks
|
Plan B - Proportion of patients achieving response in diplopia
Time Frame: 16 weeks
|
Proportion of participants with Baseline diplopia > 0 and a reduction of ≥ 1 grade with no corresponding deterioration (≥ 1 grade worsening) in the fellow eye at Week 16
|
16 weeks
|
Plan B - Mean change from Baseline to Week 16 in CAS in the study eye.
Time Frame: 16 weeks
|
Average change in clinical activity score (CAS)
|
16 weeks
|
Plan B - Mean change from Baseline to Week 16 in proptosis in the study eye.
Time Frame: 16 weeks
|
Average change in proptosis in study eye.
Proptosis is protrusion of the eyeball.
Exophthalmos means the same, and this term is usually used when describing proptosis due to Grave's disease
|
16 weeks
|
Plan B - Mean change from Baseline to Week 16 in GO-QoL score
Time Frame: 16 weeks
|
Average change in the Graves' ophthalmopathy quality of life questionnaire (GO-QOL) score.
The 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).
|
16 weeks
|
Plan B - Number of participants with Adverse Events
Time Frame: Through study completion, up to two years
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Adverse Events (AEs) are any untoward sign or symptom that occurs during Plan B study treatment period
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Through study completion, up to two years
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Study Director Novartis Pharmaceuticals, Sponsor GmbH
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CAIN457ADE16
- 2020-001611-24 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
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
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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