Study to Evaluate the Effect of Secukinumab Compared to Placebo on Aortic Vascular Inflammation in Subjects With Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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This study evaluated the effect of secukinumab compared to placebo on aortic vascular inflammation in adult patients who have moderate to severe plaque psoriasis that is poorly controlled by current psoriasis treatments.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Effect of Secukinumab on Aortic Vascular Inflammation and Cardiometabolic Biomarkers After 12 Weeks of Treatment, Compared to Placebo, and up to 52 Weeks of Treatment With Secukinumab in Adult Subjects With Moderate to Severe Chronic Plaque-type Psoriasis

Conditions
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Chronic Plaque Psoriasis

Intervention / Treatment
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* Drug: Secukinumab 300 mg
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Males and females at least 18 years of age with moderate to severe plaque psoriasis Exclusion Criteria: Forms of psoriasis other than chronic plaque psoriasis Previous exposure to IL-17A or IL-17 receptor targeting agents. Other active or ongoing disease that may interfere with evaluation of psoriasis or places the patient at unacceptable risk Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Secukinumab<br>Eligible patients received secukinumab 300 mg once weekly at Baseline, Weeks 1, 2, 3 and 4 followed by monthly dosing starting at Week 8 through Week 48 inclusive | Drug: Secukinumab 300 mg<br>* Secukinumab 300 mg was provided in 1 mL prefilled syringes of 150 mg. Each dose of 300 mg secukinumab consisted of two secukinumab 150 mg injections once weekly for 5 weeks (Baseline, Weeks 1, 2, 3 and 4), followed by dosing every four weeks starting at Week 8 through Week 48 inclusive. The patients (or caregivers) self-injected each dose at the study site under the supervision of site personnel when injections occurred on days of study visits. The injections not occurring on days of study visits were done by the patients (or caregivers) at home.<br>* Other names: AIN457 300 mg;|
| Placebo Comparator: Placebo then Secukinumab<br>Eligible patients received placebo doses once weekly at Baseline, Weeks 1, 2, 3 and 4 followed by a dose after four weeks at Week 8. Beginning with the Week 12 dose, participants were switched to treatment with secukinumab 300 mg and were dosed once weekly at Weeks 12, 13, 14, 15 and 16 followed by monthly dosing through Week 48 inclusive. | Biological: Placebo<br>* Placebo was provided in 1 mL prefilled syringe. Each placebo dose consisted of two placebo injections once weekly for five weeks (Baseline, Weeks 1, 2, 3, 4), then after four weeks at Week 8. At Week 12, patients were switched to receive 300 mg secukinumab once weekly for five weeks (Weeks 12, 13, 14, 15, 16) followed by monthly dosing through Week 48 inclusive. The patients (or caregivers) self-injected each dose at the study site under the supervision of site personnel when injections occured on days of study visits. The injections not occurring on days of study visits were done by the patients (or caregivers) at home.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aortic Vascular Inflammation as Measured by FDG-PET/CT | Change from baseline in the target to background ratio from the whole aorta. Effect of secukinumab 300 mg subcutaneous (sc) compared to placebo on aortic vascular inflammation with respect to the change from baseline in the target (arterial vascular uptake) to background (venous blood pool) ratio from the aorta. The primary analysis time point was at Week 12. Increased aortic vascular inflammation as measured by (18F) fluorodeoxyglucose positron emission tomography with computer assisted tomography (FDG-PET/CT) | baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Adiponectin Total | Change from baseline in Adiponectin to measure adiposity | baseline, 12 weeks | 
| Change in Apolipoprotein B | Change from baseline in Apolipoprotein B levels, a marker predictive of diabetes | baseline, 12 weeks | 
| Change in CRP | Change from baseline in C reactive protein (CRP), a measure of inflammation | baseline, 12 weeks | 
| Change in Cholesterol | Change from baseline in Cholesterol level | baseline, 12 weeks | 
| Change in Fetuin A | Change from baseline in Fetuin A, a marker predictive of diabetes | baseline, 12 weeks | 
| Change in Ferritin | Change from baseline in Ferritin, a marker predictive of diabetes | baseline, 12 weeks | 
| Change in GlycA | Change from baseline in glycoprotein acetylation (GlycA), a marker of inflammation | baseline, 12 weeks | 
| Change in HDL Cholesterol | Change from baseline in High Density Lipoprotein (HDL) Cholesterol, a cardiometabolic biomarker | baseline, 12 weeks | 
| Change in HDL Function (Cholesterol Efflux) | Change from baseline in High Density Lipoprotein (HDL) Cholesterol (cholesterol efflux) , a cardiometabolic biomarker Ratio of the pleated serum to removal of Cholesterol | baseline, 12 weeks | 
| HDL Particle Total | Change from baseline in High Density Lipoprotein (HDL) Cholesterol Particle Total | baseline, 12 weeks | 
| HDL Size | Change from baseline in High Density Lipoprotein (HDL) Cholesterol size | baseline, 12 weeks | 
| HOMA-IR | Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) Insulin [uIU/mL (mU/L)] x Glucose (mg/dL) = HOMA-IR | baseline, 12 weeks | 
| Change in IL-2 Receptor A | Interleukin-2 Receptor A (IL-2RA) is a marker predictive of diabetes | baseline, 12 weeks | 
| Change in IL-18 | Interleukin-18 (IL-18) is a marker predictive of diabetes | baseline, 12 weeks | 
| Change in IL-6 | Interleukin 6 (IL-6) is a marker of inflammation | baseline, 12 weeks | 
| Change in Intermediate-Density Lipoprotein (IDL) Particle | Intermediate-density lipoprotein (IDL) particle is a marker of cardiometabolic function | baseline, 12 weeks | 
| Change LDL Cholesterol | Change from baseline in Low-Density Lipoprotein (LDL) Cholesterol as a marker of cardiometabolic function | baseline, 12 weeks | 
| Change in Leptin | Change from baseline in Leptin a marker of adiposity | baseline, 12 weeks | 
| LDL Particle Total | Change from baseline in Low Density Lipoprotein (LDL) Cholesterol Particle Total | baseline, 12 weeks | 
| LDL Size | Change from baseline in Low Density Lipoprotein (LDL) Cholesterol size | baseline, 12 weeks | 
| Change in Triglycerides | Triglycerides are a marker of cardiometabolic function | baseline, 12 weeks | 
| Change in TNF-α | Change in Tumor necrosis factor (TNF, tumor necrosis factor alpha, TNFα is a marker of inflammation Also written as TNF-alpha | baseline, 12 weeks | 
| Change VLDL Particle Total | Change in Very-low-density lipoprotein (VLDL) cholesterol level | baseline, 12 weeks | 
| VLDL Size | Change from baseline in Very Low Density Lipoprotein (VLDL) Cholesterol size | baseline, 12 weeks | 
| Area and Severity Index 75 (PASI 75) | Percentage of participants with PASI75 response (yes, no) PASI75 response = at least a 75% improvement (reduction) in PASI score compared to baseline Psoriasis Area and Severity Index ( PASI) is a tool for measuring the severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). | week 12 | 
| Psoriasis Area and Severity Index 90 (PASI 90) | Percentage of participants with PASI90 response (yes, no) PASI90 response = at least a 90& improvement (reduction) in PASI score compared to baseline | week 12 | 
| Psoriasis Area and Severity Index 100 (PASI100) | Percentage of participants with PASI100 response (yes, no) PASI100 response = complete clearing of psoriasis | week 12 | 
| Investigator's Global Assessment Modified 2011 (IGA Mod 2011) Score of 0 or 1 | percentage of participants with IGA mod 2011 score of 0 or 1 (yes, no) Investigator's Global Assessment modified 2011 (IGA mod 2011) score of 0 or 1 Statistical analysis (Cochran-Mantel-Haenszel test) of Novartis Investigator's Global Assessment Modified 2011 0 or 1 response by visit (Non-responder Imputation) | week 12 | 
| Dermatology Life Quality Index (DLQI) Total Score | Change from baseline in the DLQI total score Summary of analysis of change from baseline in DLQI at Week 12 and statistical analysis (using Analysis of Covariance) of change from baseline in DLQI at Week 12 The higher the score, the more quality of life is impaired. 0 - 1 no effect at all on patient's life 2 - 5 small effect on patient's life 6 - 10 moderate effect on patient's life 11 - 20 very large effect on patient's life 21 - 30 extremely large effect on patient's life | baseline, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriasis, plaque psoriasis, secukinumab, AIN457, biologic, monoclonal antibody, aortic vascular inflammation