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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-001611-24 | EudraCT Number |
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Analysis of blinded patient data showed a very low probability of the study meeting the primary efficacy endpoints. No safety concerns were identified
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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.
This study consisted of the following 3 periods:
Screening period (Week -6 to Baseline):
Participants' eligibility was assessed during the Screening period, which occurred for a maximum of 6 weeks.
Treatment period (Baseline to Week 16):
Eligible participants were randomized in a 1:1 ratio to one of the following double-blinded treatment arms:
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.
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:
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:
Definitions of proptosis responder, non-responder and relapser:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Placebo | Placebo Comparator | Placebo subcutaneous (s.c.) injection at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Secukinumab | Drug | Secukinumab 300 mg s.c. at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Key Inclusion Criteria:
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:
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.
Key Exclusion Criteria:
Other protocol defined Inclusion/Exclusion may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Essen | 45147 | Germany | |||
| Novartis Investigative Site |
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| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on www.novctrd.com | View source |
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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
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Eligible participants were randomized in a 1:1 ratio to one of the following double-blinded treatment arms: Secukinumab 300 mg (arm 1) and Placebo (arm 2).
This study was conducted at 5 centers in Germany.
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| ID | Title | Description |
|---|---|---|
| FG000 | Secukinumab 300 mg | Secukinumab 300 mg subcutaneous (s.c.) injection at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12 |
| FG001 | Placebo | Placebo subcutaneous (s.c.) injection at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period (Baseline to Week 16) |
|
| |||||||||||||||||||||
| Follow-up Period (Week 16 to Week 108) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Secukinumab 300 mg | Secukinumab 300 mg subcutaneous (s.c.) injection at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12 |
| BG001 | Placebo | Placebo subcutaneous (s.c.) injection at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Full Analysis Set (FAS) | Posted | Count of Participants | Participants | Baseline, Week 16 |
|
Adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 16) and for the follow-up/open-label re-treatment period, including AEs in follow up for all patients who received at least one dose of Secukinumab during the entire study up to a maximum of 108 weeks.
The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Secukinumab 300 mg (Double-blind) | Secukinumab 300 mg (Double-blind): Double-blind treatment period (from first dose of study treatment until Week 16) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Graves' disease | Endocrine disorders | MedDRA (24.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (24.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | + 1 862 778 8300 | Novartis.email@Novartis.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 15, 2022 | Apr 10, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 25, 2023 | Apr 10, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D049970 | Graves Ophthalmopathy |
| D005094 | Exophthalmos |
| ID | Term |
|---|---|
| D015785 | Eye Diseases, Hereditary |
| D005128 | Eye Diseases |
| D006111 | Graves Disease |
| D009916 | Orbital Diseases |
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| ID | Term |
|---|---|
| C555450 | secukinumab |
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| Placebo | Drug | Placebo s.c. at Baseline, Weeks 1, Week 2, Week 3, Week 4, Week 8, Week 12 |
|
| Baseline, Week 16 |
| 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. | Baseline, Week 16 |
| 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. | Baseline, Week 16 |
| 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:
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.
| 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 | 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. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 |
| 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. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 |
| 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. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 |
| 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. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 |
| 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. | From first dose of study treatment until Week 16 |
| 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. | Baseline, Week 16 |
| 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. | Baseline, Week 16 |
| 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. | Baseline, Week 16 |
| 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. | Baseline, Week 16 |
| 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. | Baseline, Week 16 |
| 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. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 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. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 |
| 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. | From first dose of study treatment until Week 16 |
| Frankfurt |
| 60318 |
| Germany |
| Novartis Investigative Site | Freiburg im Breisgau | 79106 | Germany |
| Novartis Investigative Site | Göttingen | 37075 | Germany |
| Novartis Investigative Site | Mainz | 55131 | Germany |
| NOT COMPLETED |
|
|
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Smoking History | Count of Participants | Participants |
|
| Placebo |
Placebo subcutaneous (s.c.) injection at Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12 |
|
|
| Primary | 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. | Full Analysis Set (FAS). Due to premature study discontinuation, only Plan A was conducted (no data collected for Plan B, as Plan B was not initiated). | Posted | Baseline, Week 16 |
|
|
| Secondary | 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. | Full Analysis Set (FAS) | Posted | Count of Participants | Participants | Baseline, Week 16 |
|
|
|
| Secondary | 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. | Full Analysis Set (FAS) | Posted | Count of Participants | Participants | Baseline, Week 16 |
|
|
|
| Secondary | 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. | Full Analysis Set (FAS) | Posted | Count of Participants | Participants | Baseline, Week 16 |
|
|
|
| Secondary | 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:
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.
| Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included. | Posted | Mean | Standard Deviation | Unit on a scale | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 |
|
|
|
| Secondary | 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. | Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included. | Posted | Mean | Standard Deviation | millimeters (mm) | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 |
|
|
|
| Secondary | 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. | Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included. | Posted | Count of Participants | Participants | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 |
|
|
|
| Secondary | 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. | Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included. | Posted | Mean | Standard Deviation | Unit on a scale | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 |
|
|
|
| Secondary | 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. | Full Analysis Set (FAS). Only participants with a value at both Baseline and post-baseline visit included. | Posted | Mean | Standard Deviation | Unit on a scale | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 |
|
|
|
| Secondary | 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. | Safety Analysis Set (SAF) | Posted | Count of Participants | Participants | From first dose of study treatment until Week 16 |
|
|
|
| Secondary | 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. | Full Analysis Set (FAS). Due to premature study discontinuation, only Plan A was conducted (no data collected for Plan B, as Plan B was not initiated). | Posted | Baseline, Week 16 |
|
|
| Secondary | 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. | Full Analysis Set (FAS). Due to premature study discontinuation, only Plan A was conducted (no data collected for Plan B, as Plan B was not initiated). | Posted | Baseline, Week 16 |
|
|
| Secondary | 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. | Full Analysis Set (FAS). Due to premature study discontinuation, only Plan A was conducted (no data collected for Plan B, as Plan B was not initiated). | Posted | Baseline, Week 16 |
|
|
| Secondary | 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. | Full Analysis Set (FAS). Due to premature study discontinuation, only Plan A was conducted (no data collected for Plan B, as Plan B was not initiated). | Posted | Baseline, Week 16 |
|
|
| Secondary | 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. | Full Analysis Set (FAS). Due to premature study discontinuation, only Plan A was conducted (no data collected for Plan B, as Plan B was not initiated). | Posted | Baseline, Week 16 |
|
|
| Secondary | 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. | Full Analysis Set (FAS). Due to premature study discontinuation, only Plan A was conducted (no data collected for Plan B, as Plan B was not initiated). | Posted | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 |
|
|
| Secondary | 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. | Full Analysis Set (FAS). Due to premature study discontinuation, only Plan A was conducted (no data collected for Plan B, as Plan B was not initiated). | Posted | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 |
|
|
| Secondary | 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. | Safety Analysis Set (SAF). Due to premature study discontinuation, only Plan A was conducted (no data collected for Plan B, as Plan B was not initiated). | Posted | From first dose of study treatment until Week 16 |
|
|
| 0 |
| 14 |
| 1 |
| 14 |
| 12 |
| 14 |
| EG001 | Placebo (Double-blind) | Secukinumab matching placebo (Double-blind): Double-blind treatment period (from first dose of study treatment until Week 16) | 0 | 14 | 1 | 14 | 12 | 14 |
| EG002 | Any Secukinumab 300 mg (Entire Study) | All events reported from the beginning of the study up until the end of follow-up/open-label retreatment period (from first dose of study treatment up to Week 108) | 0 | 26 | 1 | 26 | 23 | 26 |
| Endocrine ophthalmopathy | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (24.0) | Systematic Assessment |
|
| Thyroid dermatopathy | Endocrine disorders | MedDRA (24.0) | Systematic Assessment |
|
| Chalazion | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Conjunctival hyperaemia | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Conjunctival oedema | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Diplopia | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Erythema of eyelid | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Eye swelling | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Metamorphopsia | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Ocular discomfort | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Pupillary reflex impaired | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Swelling of eyelid | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Visual field defect | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Injection site haematoma | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Injection site pruritus | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Injection site swelling | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Swelling | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Borrelia infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Blood thyroid stimulating hormone decreased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Glycosylated haemoglobin increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Haematocrit decreased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Red blood cell count decreased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Thyroxine free decreased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Tri-iodothyronine increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Meningioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Horner's syndrome | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Acute stress disorder | Psychiatric disorders | MedDRA (24.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (24.0) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006042 | Goiter |
| D013959 | Thyroid Diseases |
| D004700 | Endocrine System Diseases |
| D006980 | Hyperthyroidism |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| Missing |
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| Missing |
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| Missing |
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| Change from BL at Week 4 |
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| Change from BL at Week 8 |
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| Change from BL at Week 12 |
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| Change from BL at Week 16 |
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| Change from BL at Week 4 |
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| Change from BL at Week 8 |
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| Change from BL at Week 12 |
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| Change from BL at Week 16 |
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| Moderate to severe |
|
| Sight threatening |
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| Week 2 |
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| Week 4 |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 2 |
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| Week 4 |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 2 |
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| Week 4 |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| AE leading to study treatment discontinuation |
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| Serious adverse event (SAE) |
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| Study treatment related SAE |
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| SAE leading to study treatment discontinuation |
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