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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Plaque Psoriasis
• Intervention / Treatment: Drug: Secukinumab 300 mg; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Novartis Investigative Site
    • Santa Ana, California, United States, 92701
      • Novartis Investigative Site
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Novartis Investigative Site
  • New York
    • Buffalo, New York, United States, 14221
      • Novartis Investigative Site
    • New York, New York, United States, 10025 1737
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Novartis Investigative Site
    • Portland, Oregon, United States, 97223
      • Novartis Investigative Site
  • Pennsylvania
    • Exton, Pennsylvania, United States, 19341
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75246-1613
      • Novartis Investigative Site
    • Houston, Texas, United States, 77004
      • Novartis Investigative Site
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Secukinumab; 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; 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.; Other Names: AIN457 300 mg
Placebo Comparator: Placebo then Secukinumab; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Gelfand JM, Shin DB, Duffin KC, Armstrong AW, Blauvelt A, Tyring SK, Menter A, Gottlieb S, Lockshin BN, Simpson EL, Kianifard F, Sarkar RP, Muscianisi E, Steadman J, Ahlman MA, Playford MP, Joshi AA, Dey AK, Werner TJ, Alavi A, Mehta NN. A Randomized Placebo-Controlled Trial of Secukinumab on Aortic Vascular Inflammation in Moderate-to-Severe Plaque Psoriasis (VIP-S). J Invest Dermatol. 2020 Sep;140(9):1784-1793.e2. doi: 10.1016/j.jid.2020.01.025. Epub 2020 Feb 21.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2016
• Primary Completion (Actual): April 26, 2017
• Study Completion (Actual): February 19, 2018

Study Registration Dates

• First Submitted: February 19, 2016
• First Submitted That Met QC Criteria: February 19, 2016
• First Posted (Estimate): February 24, 2016

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: monoclonal antibody; psoriasis; AIN457; biologic; plaque psoriasis; secukinumab; aortic vascular inflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Skin Diseases, Papulosquamous; Inflammation; Psoriasis
• Other Study ID Numbers: CAIN457AUS02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No