The purpose of this study was to explore the effect of treatment with 300 mg or with 150 mg secukinumab (administered weekly for 4 weeks followed by four-weekly administration) on endothelial dysfunction and arterial stiffness after 12 weeks and for up to 52 weeks in subjects with chronic plaque-type psoriasis. Furthermore soluble biomarkers were assessed to evaluate the influence of secukinumab on cardiovascular risk. Magnetic resonance imaging (MRI) was performed in a sub-population to assess the treatment effect on arterial vessel wall morphometry in atherosclerosis prone vascular beds.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
151
300 mg secukinumab
Placebo followed by 300 mg secukinumab
Placebo followed by 150 mg secukinumab
150 mg secukinumab
Novartis Investigative Site
Augsburg, Germany
Novartis Investigative Site
Berlin, Germany
Novartis Investigative Site
Berlin, Germany
Novartis Investigative Site
Bielefeld, Germany
Novartis Investigative Site
Bochum, Germany
Novartis Investigative Site
Bonn, Germany
Novartis Investigative Site
Darmstadt, Germany
Novartis Investigative Site
Dresden, Germany
Novartis Investigative Site
Duisburg, Germany
Novartis Investigative Site
Essen, Germany
...and 13 more locations
Flow Mediated Dilation (FMD) at Week 12 Followed by Secukinumab 300 mg vs Pooled Placebo Treatment
Flow Mediated Dilation (FMD) is non-invasive method evaluated by Doppler Ultrasound test, to assess endothelial function. FMD was calculated as the percent maximal deviation from the baseline arterial diameter (D):FMD = 100\*\[(D maximum - D baseline) / D baseline\]. Here, arterial diameter (brachial artery) was measured at rest (1 minute), during inflation of the distal cuff to 100 millimeter of mercury (mmHg) for 4.5 minutes and for 4.5 minutes following deflation.
Time frame: Week 12
Change From Baseline in Flow Mediated Dilation (FMD) at Week 4, 12, 24 and 52
FMD is non-invasive method evaluated by Doppler Ultrasound test, to assess endothelial function. FMD was calculated as the percent maximal deviation from the baseline arterial diameter (D):FMD = 100\*\[(D maximum - D baseline) / D baseline\]. Here, arterial diameter (brachial artery) was measured at rest (1 minute), during inflation of the distal cuff to 100 mmHg for 4.5 minutes and for 4.5 minutes following deflation. A positive change in FMD constitutes an improvement in endothelial function.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Aortic Augmentation Index at Heart Rate of 75 (AIx-75) at Week 4, 12, 24 and 52
Pulse wave analysis was performed on the central aortic pressure waveform as derived by SphygmoCor XCEL from the brachial pressure waveform recorded in a partially-inflated blood pressure cuff around the upper arm. The waveform derivation employs a validated generalized transfer function to convert a brachial waveform to a central waveform and has been shown to produce measurement results corresponding to measurements using intra-arterial pressure catheters. The augmentation index is derived from the waveform by determining the percentage of the central pulse pressure during systole due to wave reflection. AIx was heart-rate corrected to calculate the AIx at a heart rate of 75 bpm, i.e. AIx-75.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Pulse Wave Velocity (PWV) at Week 4, 12, 24 and 52
Regional arterial pulse wave velocity (PWV) was directly related to arterial stiffness and was defined as the time it takes for the blood pressure wave to travel from a proximal site to a distal site (relative to the heart) divided by the distance (PWV = ∆distance/∆time \[m/s\]). The foot of the arterial pulse wave was being recorded by using the SphygmoCor XCEL device. XCEL simultaneously measures the pressure waveform at the femoral site (using a partially inflated custom blood pressure cuff) and the carotid site (using hand-held applanation tonometry). The foot-to-foot time between the two pressure waveforms was the time interval used in the PWV calculation.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Average Wall Area Assessed as a Measure of Total Plaque Burden at Week 12
Magnetic resonance imaging (MRI) was used to evaluate vessel wall morphometry to determine plaque burden. As a measure of plaque burden, average wall area was computed by subtracting vessel lumen area from total vessel area. Exploratory 3.0 Tesla MRI technique was applied to assess structure and function of the carotid and the aorta. A 2D axial dark blood T1, T2, proton density weighted spin echo based images and time of flight images were acquired from the bilateral carotid arteries as well as the descending aorta.
Time frame: Baseline, Week 12
Change From Baseline in Average Wall Area Assessed as a Measure of Total Plaque Burden at Week 52
Magnetic resonance imaging (MRI) was used to evaluate vessel wall morphometry to determine plaque burden. As a measure of plaque burden, average wall area was computed by subtracting vessel lumen area from total vessel area. Exploratory 3.0 Tesla MRI technique was applied to assess structure and function of the carotid and the aorta. A 2D axial dark blood T1, T2, proton density weighted spin echo based images and time of flight images were acquired from the bilateral carotid arteries as well as the descending aorta.
Time frame: Baseline, Week 52
Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) at Week 4, 12, 24 and 52
High sensitivity C-reactive protein (hsCRP), a soluble biomarker of systemic inflammation was determined in fasting blood samples to evaluate the effect of secukinumab on systemic inflammation.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in S-100 Protein B (Total) at Week 4, 12, 24 and 52
S100 calcium-binding protein B (S100B-protein), a soluble biomarker of systemic inflammation was determined in fasting blood samples to evaluate the effect of secukinumab on systemic inflammation.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Chemokine (C-c Motif) Ligand 5 (CCL5), Monocyte Chemoattractant Protein 1 (MCP-1) and Macrophage Inflammatory Proteins (MIP) 1 Alpha and 1 Beta at Week 4, 12, 24 and 52
Chemokine (c-c motif) ligand 5 (CCL5), Monocyte chemoattractant protein 1 (MCP-1) and Macrophage inflammatory proteins (MIP) 1 alpha (1A) and 1 beta (1B), soluble biomarkers of systemic inflammation were determined in fasting blood samples to evaluate the effect of secukinumab on systemic inflammation.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 4, 12, 24 and 52
Fasting plasma glucose (FPG), a soluble biomarker of Dysglycemia was determined in fasting blood samples to evaluate the effect of secukinumab on systemic inflammation.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Fasting Insulin at Week 4, 12, 24 and 52
Fasting Insulin, a soluble biomarker of Dysglycemia was determined in fasting blood samples to evaluate the effect of secukinumab on Dysglycemia.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Homeostatic Model Assessment (HOMA) Beta-cell Function at Week 4, 12, 24 and 52
Homeostatic Model Assessment (HOMA) beta-cell function, a soluble biomarker of Dysglycemia was determined in fasting blood samples to evaluate the effect of secukinumab on Dysglycemia.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Homeostatic Model Assessment (HOMA) Insulin Resistance at Week 4, 12, 24 and 52
HOMA insulin resistance, a soluble biomarker of Dysglycemia was determined in fasting blood samples to evaluate the effect of secukinumab on Dysglycemia.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Hemoglobin A1c (Glycated Hemoglobin) at Week 4, 12, 24 and 52
Hemoglobin A1c (glycated hemoglobin), a soluble biomarker of Dysglycemia was determined in fasting blood samples to evaluate the effect of secukinumab on Dysglycemia.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Sex Hormone-binding Globulin (SHBG) at Week 4, 12, 24 and 52
Sex hormone-binding globulin (SHBG), a soluble biomarker of Dysglycemia was determined in fasting blood samples to evaluate the effect of secukinumab on Dysglycemia.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Triglycerides, Total Cholesterol, Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Apolipoprotein A-1 (ApoA-1) and Apolipoprotein B (ApoB) at Week 4, 12, 24 and 52
Triglycerides, Total cholesterol, Low density lipoprotein (LDL), High density lipoprotein (HDL), Apolipoprotein A-1 (ApoA-1) and Apolipoprotein B (ApoB), soluble biomarkers of impaired lipid metabolism were determined in fasting blood samples to evaluate the effect of secukinumab on impaired lipid metabolism.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Adiponectin at Week 4, 12, 24 and 52
Adiponectin, a soluble biomarker of impaired lipid metabolism was determined in fasting blood samples to evaluate the effect of secukinumab on systemic inflammation.
Time frame: Baseline, Week 4, 12, 24 and 52
Change From Baseline in Leptin at Week 4, 12, 24 and 52
Leptin, a soluble biomarker of impaired lipid metabolism was determined in fasting blood samples to evaluate the effect of secukinumab on systemic inflammation.
Time frame: Baseline, Week 4, 12, 24 and 52
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