Chronic Plaque Psoriasis
Conditions
Keywords
psoriasis, plaque psoriasis, secukinumab, AIN457, biologic, monoclonal antibody, aortic vascular inflammation
Brief summary
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.
Interventions
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.
BIOLOGICALPlacebo
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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aortic Vascular Inflammation as Measured by FDG-PET/CT | baseline, 12 weeks | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Apolipoprotein B | baseline, 12 weeks | Change from baseline in Apolipoprotein B levels, a marker predictive of diabetes |
| Change in CRP | baseline, 12 weeks | Change from baseline in C reactive protein (CRP), a measure of inflammation |
| Change in Cholesterol | baseline, 12 weeks | Change from baseline in Cholesterol level |
| Change in Fetuin A | baseline, 12 weeks | Change from baseline in Fetuin A, a marker predictive of diabetes |
| Change in Ferritin | baseline, 12 weeks | Change from baseline in Ferritin, a marker predictive of diabetes |
| Change in GlycA | baseline, 12 weeks | Change from baseline in glycoprotein acetylation (GlycA), a marker of inflammation |
| Change in HDL Cholesterol | baseline, 12 weeks | Change from baseline in High Density Lipoprotein (HDL) Cholesterol, a cardiometabolic biomarker |
| Change in HDL Function (Cholesterol Efflux) | baseline, 12 weeks | Change from baseline in High Density Lipoprotein (HDL) Cholesterol (cholesterol efflux) , a cardiometabolic biomarker Ratio of the pleated serum to removal of Cholesterol |
| HDL Particle Total | baseline, 12 weeks | Change from baseline in High Density Lipoprotein (HDL) Cholesterol Particle Total |
| HDL Size | baseline, 12 weeks | Change from baseline in High Density Lipoprotein (HDL) Cholesterol size |
| HOMA-IR | baseline, 12 weeks | Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) Insulin \[uIU/mL (mU/L)\] x Glucose (mg/dL) = HOMA-IR |
| Change in IL-2 Receptor A | baseline, 12 weeks | Interleukin-2 Receptor A (IL-2RA) is a marker predictive of diabetes |
| Change in IL-18 | baseline, 12 weeks | Interleukin-18 (IL-18) is a marker predictive of diabetes |
| Change in IL-6 | baseline, 12 weeks | Interleukin 6 (IL-6) is a marker of inflammation |
| Change in Adiponectin Total | baseline, 12 weeks | Change from baseline in Adiponectin to measure adiposity |
| Change LDL Cholesterol | baseline, 12 weeks | Change from baseline in Low-Density Lipoprotein (LDL) Cholesterol as a marker of cardiometabolic function |
| Change in Leptin | baseline, 12 weeks | Change from baseline in Leptin a marker of adiposity |
| LDL Particle Total | baseline, 12 weeks | Change from baseline in Low Density Lipoprotein (LDL) Cholesterol Particle Total |
| LDL Size | baseline, 12 weeks | Change from baseline in Low Density Lipoprotein (LDL) Cholesterol size |
| Change in Triglycerides | baseline, 12 weeks | Triglycerides are a marker of cardiometabolic function |
| Change in TNF-α | baseline, 12 weeks | Change in Tumor necrosis factor (TNF, tumor necrosis factor alpha, TNFα is a marker of inflammation Also written as TNF-alpha |
| Change VLDL Particle Total | baseline, 12 weeks | Change in Very-low-density lipoprotein (VLDL) cholesterol level |
| VLDL Size | baseline, 12 weeks | Change from baseline in Very Low Density Lipoprotein (VLDL) Cholesterol size |
| Area and Severity Index 75 (PASI 75) | week 12 | 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). |
| Psoriasis Area and Severity Index 90 (PASI 90) | week 12 | Percentage of participants with PASI90 response (yes, no) PASI90 response = at least a 90& improvement (reduction) in PASI score compared to baseline |
| Psoriasis Area and Severity Index 100 (PASI100) | week 12 | Percentage of participants with PASI100 response (yes, no) PASI100 response = complete clearing of psoriasis |
| Investigator's Global Assessment Modified 2011 (IGA Mod 2011) Score of 0 or 1 | week 12 | 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) |
| Dermatology Life Quality Index (DLQI) Total Score | baseline, 12 weeks | 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 |
| Change in Intermediate-Density Lipoprotein (IDL) Particle | baseline, 12 weeks | Intermediate-density lipoprotein (IDL) particle is a marker of cardiometabolic function |
Countries
United States
Participant flow
Recruitment details
Randomized Set consisted of all 91 participants who were randomly assigned to a treatment group
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab Eligible participants 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 | 46 |
| Placebo Eligible participants received placebo once weekly at Baseline, Weeks 1, 2, 3, and 4 followed by a dose after four weeks at Week 8; participants were switched to once weekly secukinumab 300 mg at Weeks 12, 13, 14, 15, and 16 followed by monthly dosing through Week 48 | 45 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 | Adverse Event | 2 | 2 |
| Treatment Period 1 | Withdrawal by Subject | 0 | 1 |
| Treatment Period 2 | Adverse Event | 2 | 0 |
| Treatment Period 2 | Lack of Efficacy | 1 | 0 |
| Treatment Period 2 | Lost to Follow-up | 0 | 2 |
| Treatment Period 2 | Protocol Violation | 0 | 1 |
| Treatment Period 2 | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Secukinumab | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 39 Participants | 80 Participants |
| Race/Ethnicity, Customized Asian | 6 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 36 Participants | 36 Participants | 72 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Female | 13 Participants | 17 Participants | 30 Participants |
| Sex: Female, Male Male | 33 Participants | 28 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 45 | 0 / 91 |
| other Total, other adverse events | 21 / 46 | 18 / 45 | 39 / 91 |
| serious Total, serious adverse events | 5 / 46 | 0 / 45 | 5 / 91 |
Outcome results
Primary
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)
Time frame: baseline, 12 weeks
Population: Full Analysis Set (FAS) included all participants assigned medication. Patients inappropriately randomized (eg, IRT was called in error for randomization of a screen failed patient) were excluded from this analysis set. Following intent-to-treat principle, participants were analyzed according to treatment they were assigned to at randomization
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Aortic Vascular Inflammation as Measured by FDG-PET/CT | Baseline | 1.6615 target to background ratio (TBR) | Standard Deviation 0.3738 |
| Secukinumab | Aortic Vascular Inflammation as Measured by FDG-PET/CT | Change from Baseline at Week 12 | 0.0143 target to background ratio (TBR) | Standard Deviation 0.2552 |
| Placebo | Aortic Vascular Inflammation as Measured by FDG-PET/CT | Baseline | 1.6333 target to background ratio (TBR) | Standard Deviation 0.33228 |
| Placebo | Aortic Vascular Inflammation as Measured by FDG-PET/CT | Change from Baseline at Week 12 | 0.0655 target to background ratio (TBR) | Standard Deviation 0.28086 |
Comparison: Statistical analysis (Analysis of Covariance) of change from baseline in target to background ratio for regions of the aorta at Week 12 (Full Analysis Set)p-value: 0.371295% CI: [-0.169, 0.064]ANCOVA
Secondary
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).
Time frame: week 12
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Area and Severity Index 75 (PASI 75) | 84.8 percentage of participants |
| Placebo | Area and Severity Index 75 (PASI 75) | 0.0 percentage of participants |
Secondary
Change in Adiponectin Total
Change from baseline in Adiponectin to measure adiposity
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in Adiponectin Total | Baseline | 18799.0 ng/mL | Standard Deviation 18608.48 |
| Secukinumab | Change in Adiponectin Total | Change from Baseline at Week 12 | 1594.90 ng/mL | Standard Deviation 15146.84 |
| Placebo | Change in Adiponectin Total | Baseline | 19475.00 ng/mL | Standard Deviation 18343 |
| Placebo | Change in Adiponectin Total | Change from Baseline at Week 12 | -1076.40 ng/mL | Standard Deviation 14565.6 |
Secondary
Change in Apolipoprotein B
Change from baseline in Apolipoprotein B levels, a marker predictive of diabetes
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in Apolipoprotein B | Baseline | 0.1014 ng/mL | Standard Deviation 0.04651 |
| Secukinumab | Change in Apolipoprotein B | Change from Baseline at Week 12 | 0.0020 ng/mL | Standard Deviation 0.06331 |
| Placebo | Change in Apolipoprotein B | Change from Baseline at Week 12 | 0.0017 ng/mL | Standard Deviation 0.04835 |
| Placebo | Change in Apolipoprotein B | Baseline | 0.1033 ng/mL | Standard Deviation 0.04451 |
Secondary
Change in Cholesterol
Change from baseline in Cholesterol level
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in Cholesterol | Baseline | 179.350 mg/dL | Standard Deviation 30.01243 |
| Secukinumab | Change in Cholesterol | Change from Baseline at Week 12 | 10.6000 mg/dL | Standard Deviation 30.27379 |
| Placebo | Change in Cholesterol | Baseline | 178.707 mg/dL | Standard Deviation 38.92573 |
| Placebo | Change in Cholesterol | Change from Baseline at Week 12 | -8.4878 mg/dL | Standard Deviation 35.18247 |
Secondary
Change in CRP
Change from baseline in C reactive protein (CRP), a measure of inflammation
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in CRP | Baseline | 6.1525 mg/L | Standard Deviation 8.23016 |
| Secukinumab | Change in CRP | Change from Baseline at Week 12 | -1.0016 mg/L | Standard Deviation 9.45281 |
| Placebo | Change in CRP | Baseline | 7.8676 mg/L | Standard Deviation 7.5986 |
| Placebo | Change in CRP | Change from Baseline at Week 12 | 1.1622 mg/L | Standard Deviation 15.84088 |
Secondary
Change in Ferritin
Change from baseline in Ferritin, a marker predictive of diabetes
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in Ferritin | Baseline | 111.953 ng/mL | Standard Deviation 91.17931 |
| Secukinumab | Change in Ferritin | Change from Baseline at Week 12 | -6.1006 ng/mL | Standard Deviation 60.71995 |
| Placebo | Change in Ferritin | Baseline | 122.040 ng/mL | Standard Deviation 114.8715 |
| Placebo | Change in Ferritin | Change from Baseline at Week 12 | -17.118 ng/mL | Standard Deviation 63.86703 |
Secondary
Change in Fetuin A
Change from baseline in Fetuin A, a marker predictive of diabetes
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in Fetuin A | Baseline | 988677.800781 ng/mL | Standard Deviation 488494.3491043 |
| Secukinumab | Change in Fetuin A | Change from Baseline at Week 12 | 90810.212003 ng/mL | Standard Deviation 444791.4700461 |
| Placebo | Change in Fetuin A | Baseline | 1169947.724848 ng/mL | Standard Deviation 79644.6884632 |
| Placebo | Change in Fetuin A | Change from Baseline at Week 12 | 45731.298018 ng/mL | Standard Deviation 452743.5932412 |
Secondary
Change in GlycA
Change from baseline in glycoprotein acetylation (GlycA), a marker of inflammation
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in GlycA | Baseline | 413.860 μmol/L | Standard Deviation 65.34929 |
| Secukinumab | Change in GlycA | Change from Baseline at Week 12 | 0.5152 μmol/L | Standard Deviation 59.46394 |
| Placebo | Change in GlycA | Baseline | 439.622 μmol/L | Standard Deviation 60.44873 |
| Placebo | Change in GlycA | Change from Baseline at Week 12 | -1.5420 μmol/L | Standard Deviation 40.25958 |
Secondary
Change in HDL Cholesterol
Change from baseline in High Density Lipoprotein (HDL) Cholesterol, a cardiometabolic biomarker
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in HDL Cholesterol | Baseline | 43.3000 mg/dL | Standard Deviation 10.20357 |
| Secukinumab | Change in HDL Cholesterol | Change from Baseline at Week 12 | -0.7500 mg/dL | Standard Deviation 8.80195 |
| Placebo | Change in HDL Cholesterol | Baseline | 43.0732 mg/dL | Standard Deviation 12.52276 |
| Placebo | Change in HDL Cholesterol | Change from Baseline at Week 12 | -1.1220 mg/dL | Standard Deviation 8.10924 |
Secondary
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
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in HDL Function (Cholesterol Efflux) | Baseline | 0.9535 ratio | Standard Deviation 0.18986 |
| Secukinumab | Change in HDL Function (Cholesterol Efflux) | Change from Baseline at Week 12 | 0.1473 ratio | Standard Deviation 0.23262 |
| Placebo | Change in HDL Function (Cholesterol Efflux) | Baseline | 1.0456 ratio | Standard Deviation 0.17819 |
| Placebo | Change in HDL Function (Cholesterol Efflux) | Change from Baseline at Week 12 | 0.0541 ratio | Standard Deviation 0.21902 |
Secondary
Change in IL-18
Interleukin-18 (IL-18) is a marker predictive of diabetes
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in IL-18 | Baseline | 1259.45 pg/mL | Standard Deviation 1910.327 |
| Secukinumab | Change in IL-18 | Change from Baseline at Week 12 | 34555.1 pg/mL | Standard Deviation 231199.6 |
| Placebo | Change in IL-18 | Baseline | 1308.47 pg/mL | Standard Deviation 2454.672 |
| Placebo | Change in IL-18 | Change from Baseline at Week 12 | -627.77 pg/mL | Standard Deviation 1874.377 |
Secondary
Change in IL-2 Receptor A
Interleukin-2 Receptor A (IL-2RA) is a marker predictive of diabetes
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in IL-2 Receptor A | Baseline | 25.5554 pg/mL | Standard Deviation 59.47232 |
| Secukinumab | Change in IL-2 Receptor A | Change from Baseline at Week 12 | -3.3606 pg/mL | Standard Deviation 38.52458 |
| Placebo | Change in IL-2 Receptor A | Baseline | 21.0665 pg/mL | Standard Deviation 61.46295 |
| Placebo | Change in IL-2 Receptor A | Change from Baseline at Week 12 | -1.1162 pg/mL | Standard Deviation 6.31189 |
Secondary
Change in IL-6
Interleukin 6 (IL-6) is a marker of inflammation
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in IL-6 | Baseline | 5.6477 pg/mL | Standard Deviation 20.81242 |
| Secukinumab | Change in IL-6 | Change from Baseline at Week 12 | 0.1334 pg/mL | Standard Deviation 29.35524 |
| Placebo | Change in IL-6 | Baseline | 1.6658 pg/mL | Standard Deviation 1.50954 |
| Placebo | Change in IL-6 | Change from Baseline at Week 12 | -0.0900 pg/mL | Standard Deviation 1.78692 |
Secondary
Change in Intermediate-Density Lipoprotein (IDL) Particle
Intermediate-density lipoprotein (IDL) particle is a marker of cardiometabolic function
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in Intermediate-Density Lipoprotein (IDL) Particle | Baseline | 284.350 nmol/mL | Standard Deviation 179.6482 |
| Secukinumab | Change in Intermediate-Density Lipoprotein (IDL) Particle | Change from Baseline at Week 12 | 47.0500 nmol/mL | Standard Deviation 167.6253 |
| Placebo | Change in Intermediate-Density Lipoprotein (IDL) Particle | Baseline | 271.049 nmol/mL | Standard Deviation 155.7413 |
| Placebo | Change in Intermediate-Density Lipoprotein (IDL) Particle | Change from Baseline at Week 12 | 2.3902 nmol/mL | Standard Deviation 160.6046 |
Secondary
Change in Leptin
Change from baseline in Leptin a marker of adiposity
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in Leptin | Baseline | 19913.4 pg/mL | Standard Deviation 21835.66 |
| Secukinumab | Change in Leptin | Change from Baseline at Week 12 | -1886.0 pg/mL | Standard Deviation 11701 |
| Placebo | Change in Leptin | Baseline | 36813.3 pg/mL | Standard Deviation 62138.25 |
| Placebo | Change in Leptin | Change from Baseline at Week 12 | -5595.9 pg/mL | Standard Deviation 17042.08 |
Secondary
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
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in TNF-α | Baseline | 2.3919 pg/mL | Standard Deviation 1.79049 |
| Secukinumab | Change in TNF-α | Change from Baseline at Week 12 | -0.3577 pg/mL | Standard Deviation 1.52948 |
| Placebo | Change in TNF-α | Baseline | 2.8089 pg/mL | Standard Deviation 4.11492 |
| Placebo | Change in TNF-α | Change from Baseline at Week 12 | -0.9818 pg/mL | Standard Deviation 3.85715 |
Secondary
Change in Triglycerides
Triglycerides are a marker of cardiometabolic function
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change in Triglycerides | Baseline | 123.200 mg/dL | Standard Deviation 52.90398 |
| Secukinumab | Change in Triglycerides | Change from Baseline at Week 12 | 11.5000 mg/dL | Standard Deviation 62.56279 |
| Placebo | Change in Triglycerides | Baseline | 125.293 mg/dL | Standard Deviation 79.10633 |
| Placebo | Change in Triglycerides | Change from Baseline at Week 12 | -10.732 mg/dL | Standard Deviation 60.25281 |
Secondary
Change LDL Cholesterol
Change from baseline in Low-Density Lipoprotein (LDL) Cholesterol as a marker of cardiometabolic function
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change LDL Cholesterol | Baseline | 122.475 mg/dL | Standard Deviation 28.8604 |
| Secukinumab | Change LDL Cholesterol | Change from Baseline at Week 12 | 9.9750 mg/dL | Standard Deviation 29.84532 |
| Placebo | Change LDL Cholesterol | Change from Baseline at Week 12 | -6.2927 mg/dL | Standard Deviation 34.42401 |
| Placebo | Change LDL Cholesterol | Baseline | 121.049 mg/dL | Standard Deviation 36.39708 |
Secondary
Change VLDL Particle Total
Change in Very-low-density lipoprotein (VLDL) cholesterol level
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Change VLDL Particle Total | Baseline | 52.9125 nmol/L | Standard Deviation 26.92102 |
| Secukinumab | Change VLDL Particle Total | Change from Baseline at Week 12 | 3.2500 nmol/L | Standard Deviation 28.56421 |
| Placebo | Change VLDL Particle Total | Baseline | 54.5829 nmol/L | Standard Deviation 27.57024 |
| Placebo | Change VLDL Particle Total | Change from Baseline at Week 12 | 3.2024 nmol/L | Standard Deviation 25.40299 |
Secondary
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
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Dermatology Life Quality Index (DLQI) Total Score | Baseline | 12.30 scores on a scale | Standard Deviation 7.65 |
| Secukinumab | Dermatology Life Quality Index (DLQI) Total Score | Change from baseline at Week 12 | -9.4 scores on a scale | Standard Deviation 7.91 |
| Placebo | Dermatology Life Quality Index (DLQI) Total Score | Baseline | 12.6 scores on a scale | Standard Deviation 7.21 |
| Placebo | Dermatology Life Quality Index (DLQI) Total Score | Change from baseline at Week 12 | -0.5 scores on a scale | Standard Deviation 3.97 |
Secondary
HDL Particle Total
Change from baseline in High Density Lipoprotein (HDL) Cholesterol Particle Total
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | HDL Particle Total | Baseline | 29.2875 μmol/L | Standard Deviation 5.38184 |
| Secukinumab | HDL Particle Total | Change from Baseline at Week 12 | -0.1375 μmol/L | Standard Deviation 5.229 |
| Placebo | HDL Particle Total | Baseline | 29.3634 μmol/L | Standard Deviation 6.27442 |
| Placebo | HDL Particle Total | Change from Baseline at Week 12 | -0.1707 μmol/L | Standard Deviation 5.12973 |
Secondary
HDL Size
Change from baseline in High Density Lipoprotein (HDL) Cholesterol size
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | HDL Size | Baseline | 8.9350 nm | Standard Deviation 0.5328 |
| Secukinumab | HDL Size | Change from Baseline at Week 12 | 0.0500 nm | Standard Deviation 0.47932 |
| Placebo | HDL Size | Baseline | 8.9585 nm | Standard Deviation 0.56656 |
| Placebo | HDL Size | Change from Baseline at Week 12 | 0.0073 nm | Standard Deviation 0.34161 |
Secondary
HOMA-IR
Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) Insulin \[uIU/mL (mU/L)\] x Glucose (mg/dL) = HOMA-IR
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | HOMA-IR | Baseline | 3.4901 HOMA-IR units | Standard Deviation 3.02479 |
| Secukinumab | HOMA-IR | Change from Baseline at Week 12 | 0.9563 HOMA-IR units | Standard Deviation 2.23669 |
| Placebo | HOMA-IR | Baseline | 5.5112 HOMA-IR units | Standard Deviation 6.22334 |
| Placebo | HOMA-IR | Change from Baseline at Week 12 | -1.2764 HOMA-IR units | Standard Deviation 5.13505 |
Secondary
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)
Time frame: week 12
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Investigator's Global Assessment Modified 2011 (IGA Mod 2011) Score of 0 or 1 | 78.3 percentage of participants |
| Placebo | Investigator's Global Assessment Modified 2011 (IGA Mod 2011) Score of 0 or 1 | 0.0 percentage of participants |
Secondary
LDL Particle Total
Change from baseline in Low Density Lipoprotein (LDL) Cholesterol Particle Total
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | LDL Particle Total | Baseline | 1236.35 nmol/L | Standard Deviation 317.9542 |
| Secukinumab | LDL Particle Total | Change from Baseline at Week 12 | 114.250 nmol/L | Standard Deviation 294.8695 |
| Placebo | LDL Particle Total | Baseline | 1263.00 nmol/L | Standard Deviation 447.3457 |
| Placebo | LDL Particle Total | Change from Baseline at Week 12 | -111.39 nmol/L | Standard Deviation 343.2109 |
Secondary
LDL Size
Change from baseline in Low Density Lipoprotein (LDL) Cholesterol size
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | LDL Size | Baseline | 21.2200 nm | Standard Deviation 0.74977 |
| Secukinumab | LDL Size | Change from Baseline at Week 12 | -0.0025 nm | Standard Deviation 0.70036 |
| Placebo | LDL Size | Baseline | 21.1171 nm | Standard Deviation 0.76384 |
| Placebo | LDL Size | Change from Baseline at Week 12 | 0.1439 nm | Standard Deviation 0.53807 |
Secondary
Psoriasis Area and Severity Index 100 (PASI100)
Percentage of participants with PASI100 response (yes, no) PASI100 response = complete clearing of psoriasis
Time frame: week 12
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Psoriasis Area and Severity Index 100 (PASI100) | 37.0 percentage of participants |
| Placebo | Psoriasis Area and Severity Index 100 (PASI100) | 0.0 percentage of participants |
Secondary
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
Time frame: week 12
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Psoriasis Area and Severity Index 90 (PASI 90) | 73.9 percentage of participants |
| Placebo | Psoriasis Area and Severity Index 90 (PASI 90) | 0.0 percentage of participants |
Secondary
VLDL Size
Change from baseline in Very Low Density Lipoprotein (VLDL) Cholesterol size
Time frame: baseline, 12 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | VLDL Size | Baseline | 51.5650 nm | Standard Deviation 9.11152 |
| Secukinumab | VLDL Size | Change from Baseline at Week 12 | -0.3950 nm | Standard Deviation 9.30271 |
| Placebo | VLDL Size | Baseline | 50.1195 nm | Standard Deviation 9.51641 |
| Placebo | VLDL Size | Change from Baseline at Week 12 | -0.7927 nm | Standard Deviation 7.72572 |