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

Phase 4

Completed

• Conditions: Chronic Plaque Psoriasis
• Interventions: Drug: Secukinumab 300 mg; Biological: Placebo

• Registration Number: NCT02690701
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-02-10
• Study First Submitted: 2016-02-19
• Study First Submitted QC: 2016-02-19
• Study First Posted: 2016-02-24
• Primary Completion: 2017-04-26
• Study Completion: 2018-02-19
• Disposition First Submitted: 2018-02-26
• Disposition First Submitted QC: 2018-02-26
• Disposition First Posted: 2018-02-28
• Results First Submitted: 2019-02-19
• Status Verified: 2019-07
• Results First Submitted QC: 2019-07-08
• Results First Posted: 2019-07-09
• Last Update Submitted: 2020-12-09
• Last Update Posted: 2021-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 91

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Secukinumab	Secukinumab 300 mg	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
Placebo then Secukinumab	Placebo	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
LDL Size	baseline, 12 weeks	Change from baseline in Low Density Lipoprotein (LDL) Cholesterol size
Change in Adiponectin Total	baseline, 12 weeks	Change from baseline in Adiponectin to measure adiposity
Change in Apolipoprotein B	baseline, 12 weeks	Change from baseline in Apolipoprotein B levels, a marker predictive of diabetes
Change in Cholesterol	baseline, 12 weeks	Change from baseline in Cholesterol level
Change in Ferritin	baseline, 12 weeks	Change from baseline in Ferritin, a marker predictive of diabetes
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
Change VLDL Particle Total	baseline, 12 weeks	Change in Very-low-density lipoprotein (VLDL) cholesterol level
Change in HDL Cholesterol	baseline, 12 weeks	Change from baseline in High Density Lipoprotein (HDL) Cholesterol, a cardiometabolic biomarker
HDL Particle Total	baseline, 12 weeks	Change from baseline in High Density Lipoprotein (HDL) Cholesterol Particle Total
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-6	baseline, 12 weeks	Interleukin 6 (IL-6) is a marker of inflammation
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 in CRP	baseline, 12 weeks	Change from baseline in C reactive protein (CRP), a measure of inflammation
Change in GlycA	baseline, 12 weeks	Change from baseline in glycoprotein acetylation (GlycA), a marker of inflammation
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 Size	baseline, 12 weeks	Change from baseline in High Density Lipoprotein (HDL) Cholesterol size
Change in Fetuin A	baseline, 12 weeks	Change from baseline in Fetuin A, a marker predictive of diabetes
Change in IL-18	baseline, 12 weeks	Interleukin-18 (IL-18) is a marker predictive of diabetes
Change LDL Cholesterol	baseline, 12 weeks	Change from baseline in Low-Density Lipoprotein (LDL) Cholesterol as a marker of cardiometabolic function
Change in Triglycerides	baseline, 12 weeks	Triglycerides are a marker of cardiometabolic function
Psoriasis Area and Severity Index 100 (PASI100)	week 12	Percentage of participants with PASI100 response (yes, no) PASI100 response = complete clearing of psoriasis
Change in IL-2 Receptor A	baseline, 12 weeks	Interleukin-2 Receptor A (IL-2RA) is a marker predictive of diabetes
Change in Intermediate-Density Lipoprotein (IDL) Particle	baseline, 12 weeks	Intermediate-density lipoprotein (IDL) particle is a marker of cardiometabolic function
VLDL Size	baseline, 12 weeks	Change from baseline in Very Low Density Lipoprotein (VLDL) Cholesterol size
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
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)
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).
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

Trial Locations

Locations (1)

Novartis Investigative Site; 🇺🇸 Salt Lake City, Utah, United States