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

Chronic Plaque Psoriasis Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02690701
• Other study ID #: CAIN457AUS02
• Status: Completed
• Phase: Phase 4
• Start date: February 10, 2016
• Est. completion date: February 19, 2018

Study information

• Verified date: July 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: February 19, 2018
• Est. primary completion date: April 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Plaque Psoriasis
• Inflammation
• Psoriasis

Intervention

Drug:
• Secukinumab 300 mg
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.

Biological:
• Placebo
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.

Locations

Country	Name	City	State
United States	Novartis Investigative Site	Buffalo	New York
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Exton	Pennsylvania
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Rockville	Maryland
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	Santa Ana	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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)	baseline, 12 weeks
Secondary	Change in Adiponectin Total	Change from baseline in Adiponectin to measure adiposity	baseline, 12 weeks
Secondary	Change in Apolipoprotein B	Change from baseline in Apolipoprotein B levels, a marker predictive of diabetes	baseline, 12 weeks
Secondary	Change in CRP	Change from baseline in C reactive protein (CRP), a measure of inflammation	baseline, 12 weeks
Secondary	Change in Cholesterol	Change from baseline in Cholesterol level	baseline, 12 weeks
Secondary	Change in Fetuin A	Change from baseline in Fetuin A, a marker predictive of diabetes	baseline, 12 weeks
Secondary	Change in Ferritin	Change from baseline in Ferritin, a marker predictive of diabetes	baseline, 12 weeks
Secondary	Change in GlycA	Change from baseline in glycoprotein acetylation (GlycA), a marker of inflammation	baseline, 12 weeks
Secondary	Change in HDL Cholesterol	Change from baseline in High Density Lipoprotein (HDL) Cholesterol, a cardiometabolic biomarker	baseline, 12 weeks
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	baseline, 12 weeks
Secondary	HDL Particle Total	Change from baseline in High Density Lipoprotein (HDL) Cholesterol Particle Total	baseline, 12 weeks
Secondary	HDL Size	Change from baseline in High Density Lipoprotein (HDL) Cholesterol size	baseline, 12 weeks
Secondary	HOMA-IR	Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) Insulin [uIU/mL (mU/L)] x Glucose (mg/dL) = HOMA-IR	baseline, 12 weeks
Secondary	Change in IL-2 Receptor A	Interleukin-2 Receptor A (IL-2RA) is a marker predictive of diabetes	baseline, 12 weeks
Secondary	Change in IL-18	Interleukin-18 (IL-18) is a marker predictive of diabetes	baseline, 12 weeks
Secondary	Change in IL-6	Interleukin 6 (IL-6) is a marker of inflammation	baseline, 12 weeks
Secondary	Change in Intermediate-Density Lipoprotein (IDL) Particle	Intermediate-density lipoprotein (IDL) particle is a marker of cardiometabolic function	baseline, 12 weeks
Secondary	Change LDL Cholesterol	Change from baseline in Low-Density Lipoprotein (LDL) Cholesterol as a marker of cardiometabolic function	baseline, 12 weeks
Secondary	Change in Leptin	Change from baseline in Leptin a marker of adiposity	baseline, 12 weeks
Secondary	LDL Particle Total	Change from baseline in Low Density Lipoprotein (LDL) Cholesterol Particle Total	baseline, 12 weeks
Secondary	LDL Size	Change from baseline in Low Density Lipoprotein (LDL) Cholesterol size	baseline, 12 weeks
Secondary	Change in Triglycerides	Triglycerides are a marker of cardiometabolic function	baseline, 12 weeks
Secondary	Change in TNF-a	Change in Tumor necrosis factor (TNF, tumor necrosis factor alpha, TNFa is a marker of inflammation Also written as TNF-alpha	baseline, 12 weeks
Secondary	Change VLDL Particle Total	Change in Very-low-density lipoprotein (VLDL) cholesterol level	baseline, 12 weeks
Secondary	VLDL Size	Change from baseline in Very Low Density Lipoprotein (VLDL) Cholesterol size	baseline, 12 weeks
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).	week 12
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	week 12
Secondary	Psoriasis Area and Severity Index 100 (PASI100)	Percentage of participants with PASI100 response (yes, no) PASI100 response = complete clearing of psoriasis	week 12
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)	week 12
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	baseline, 12 weeks

External Links

•   A Plain Language Trial Summary is available on novartisclinicatrials.com