Effect of Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of guselkumab on coronary flow reserve (CFR), measured by transthoracic doppler-echocardiography, in participants with moderate-to-severe psoriasis and intermediate cardiovascular risk.

Detailed Description
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Psoriasis is a common chronic inflammatory disease that affects 2 percent (%)-3% of the population and has an impact on physical and emotional health-related quality-of-life that is comparable to major illnesses such as cancer, heart disease and depression. Guselkumab is a fully human immunoglobulin G1 lambda monoclonal antibody that binds to the p19 protein subunit of human interleukin 23 (IL-23) with high specificity and affinity. Binding of guselkumab to the IL-23 p19 subunit blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23 specific intracellular signaling and subsequent cytokine production. Guselkumab is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy. This study aims to investigate the efficacy of guselkumab in reducing surrogate parameters of vascular dysfunction and cardiovascular risk. This study will consist of two Screening Visits (Screening Visit S1 at a maximum of 2 weeks prior to Screening Visit S2, to occur at a minimum of 2 weeks and maximum of 4 weeks prior to Week 0), a Treatment Phase (up to 28 weeks), Final Efficacy Visit 4 weeks later (Week 32), and Final Safety Visit (Week 40). The efficacy assessments will be done locally at the sites and safety will be monitored by assessment of adverse events, clinical laboratory tests, physical examinations, vital signs, and concomitant medication review. The total duration of the study will be 40 weeks.

Official Title
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A Phase 4, Interventional, Single-arm, Open-label Study Evaluating the Effect of Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With Moderate to Severe Plaque Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Guselkumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant has a diagnosis of moderate-to-severe plaque psoriasis (with or without psoriatic arthritis [PsA]) for at least 6 months prior to the first dose of guselkumab at Week 0. Moderate-to-severe plaque psoriasis is defined as having a psoriasis area and severity index (PASI) score greater than or equal to (>=) 12, investigator global assessment (IGA) score >= 3 and involved body surface area (BSA) >= 10 percent (%) at Screening Visit S1 The participant has intermediate cardiovascular risk defined as having a coronary flow reserve (CFR) score >= 2 to less than or equal to (<=) 3.5 (criterion to be assessed by cardiologist at Screening Visit S2 and Week 0) A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test (beta-human chorionic gonadotropin [beta-hCG]) at Screening Visit S1 Within 2 months before the first administration of guselkumab, the participant has a negative QuantiFERON-TB Gold test result, or has a newly identified positive QuantiFERON-TB Gold test result in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated before the first administration of guselkumab The participant has a chest radiograph (posterior-anterior view), taken within 3 months before the first administration of study agent and read by a qualified radiologist, with no evidence of current, active tuberculosis (TB) or old, inactive TB Exclusion Criteria: The participant has a predominantly non-plaque form of psoriasis (example, erythrodermic, guttate, or pustular) The participant has uncontrolled hypertension that needs immediate medical attention (criterion to be assessed by the dermatologist at Screening Visit S1 and by the cardiologist at Screening Phase 2) The participant has taken any prohibited therapies before the planned first dose of guselkumab A female participant is pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within 5 months after the last dose of guselkumab The participant has any clinically significant evidence of cardiac functional or valvular abnormalities, other than intermediate cardiovascular risk defined by CFR score >=2 and <=3.5, observed during the CFR assessment (criterion to be assessed by the dermatologist at Screening Visit S1, and to be confirmed by the cardiologist at Screening Visit S2) The participant has any contraindications to adenosine infusion, or other contraindications listed in the summary of product characteristics (SmPC) (criterion to be assessed by the dermatologist at Screening Visit S1 and confirmed by the cardiologist at Screening Visit S2)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Guselkumab<br>Participants will receive guselkumab 100 milligrams (mg) by subcutaneous injection at Weeks 0, 4, 12, 20 and 28. | Drug: Guselkumab<br>* Guselkumab will be administered by subcutaneous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Coronary Flow Reserve (CFR) at Week 32 | CFR describes the ability of coronary blood flow to increase substantially when required by metabolic demands, which may be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR assessment is conducted via transthoracic ultrasound of the coronary vasculature and provides an integrated measure of flow through both the large epicardial arteries and the coronary microcirculation. | Baseline and Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in CFR at Week 16 | Change from baseline in CFR at Week 16 will be reported. | Baseline and Week 16 | 
| Change from Baseline in Global Longitudinal Strain (GLS) at Weeks 16 and 32 | The GLS will be calculated at systole and diastole. Speckle tracking echocardiography (STE) will be employed for the detection of left-ventricular (LV) myocardial strain. | Baseline and Weeks 16 and 32 | 
| Change from Baseline in carotid-femoral Pulse Wave Velocity (cfPWV) at Weeks 16 and 32 | cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV is calculated as cfPWV= distance (meters)/ transit time (seconds). | Baseline and Weeks 16 and 32 | 
| Change from Baseline in CFR at Weeks 16 and 32 Among Participants with CFR in the Ranges of 2 to 2.49, 2.5 to 3, and 3.01 to 3.5 at Baseline | Change from baseline in CFR at Weeks 16 and 32 among participants with CFR in the ranges of 2 to 2.49, 2.5 to 3, and 3.01 to 3.5 at baseline will be reported. | Baseline and Weeks 16 and 32 | 
| Change from Baseline in CFR at Weeks 16 and 32 Among Nicotine Users and Non-users | Change from baseline in CFR at Weeks 16 and 32 among nicotine users and non-users will be reported. | Baseline and Weeks 16 and 32 | 
| Change from Baseline in GLS at Weeks 16 and 32 Among Nicotine Users and Non-users | Change from baseline in GLS at Weeks 16 and 32 among nicotine users and non-users will be reported. | Baseline and Weeks 16 and 32 | 
| Change from Baseline in cfPWV at Weeks 16 and 32 in Nicotine Users and Non-users | Change from baseline in cfPWV at Weeks 16 and 32 in nicotine users and non-users will be reported. | Baseline and Weeks 16 and 32 | 
| Rate of Adverse Events (AEs) Among Participants Treated with Guselkumab | AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. | Up to Week 40 |