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

Phase 4TerminatedNCT05125679

Janssen-Cilag Ltd.15 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Psoriasis

Interventions

GuselkumabDRUG

Guselkumab will be administered by subcutaneous injection.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (5)

Universitatsklinikum Frankfurt

Frankfurt, Germany

Universitatsklinikum Leipzig AOR

Leipzig, Germany

Attikon Hospital

Athens, Greece

Ospedale San Giovanni di Dio

Cagliari, Italy

Azienda Ospedaliera di Padova

Outcomes

Primary Outcomes

Change From Baseline in Coronary Flow Reserve (CFR) at Week 32

Change from baseline in CFR at Week 32 were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 micrograms per kilogram per minute (mcg/kg/min; coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest.

Time frame: Baseline (Week 0) and Week 32

Secondary Outcomes

Change From Baseline in CFR at Week 16

Change from baseline in CFR at Week 16 were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest.

Time frame: Baseline (Week 0) and Week 16

Change From Baseline in Absolute Global Longitudinal Strain (GLS) at Week 16

Change from baseline in absolute GLS at Week 16 were reported. GLS is a myocardial deformation analysis that predominantly reflects the function of sub-endocardial longitudinally oriented fibers, which are most prone to ischemic damage and wall stress. The GLS is calculated at systole and diastole. Speckle tracking echocardiography (STE) were employed for the detection of left-ventricular (LV) myocardial strain. GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values.

Data from ClinicalTrials.gov

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Time frame: Baseline (Week 0) and Week 16

Change From Baseline in Absolute GLS at Week 32

Change from baseline in absolute GLS is a myocardial deformation analysis that predominantly reflects the function of sub-endocardial longitudinally oriented fibers, which are most prone to ischemic damage and wall stress. The GLS is calculated at systole and diastole. Speckle tracking echocardiography (STE) were employed for the detection of left-ventricular (LV) myocardial strain. GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values.

Time frame: Baseline (Week 0) and Week 32

Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 16

Change from baseline in cfPWV at Week 16 were reported. cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. cfPWV was calculated as cfPWV = distance (meters) / transit time (seconds).

Time frame: Baseline (Week 0) and Week 16

Change From Baseline in cfPWV at Week 32

Change from baseline in cfPWV at Week 32 were reported. cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. cfPWV was calculated as cfPWV = distance (meters) / transit time (seconds).

Time frame: Baseline (Week 0) and Week 32

Change From Baseline in CFR at Week 16 Among Participants With CFR >=2 to Less Than (<) 2.75 at Baseline

Change from baseline in CFR at Week 16 among participants with CFR \>=2 to \<2.75 at baseline were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest

Time frame: Baseline (Week 0) and Week 16

Change From Baseline in CFR at Week 32 Among Participants With CFR >=2 to <2.75 at Baseline

Change from baseline in CFR at Week 32 among participants with CFR \>=2 to \<2.75 at baseline were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest

Time frame: Baseline (Week 0) and Week 32

Change From Baseline in CFR at Week 16 Among Participants With CFR >=2.75 to <=3.5 at Baseline

Change from baseline in CFR at Week 16 among participants with CFR \>=2.75 to \<=3.5 at baseline were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest

Time frame: Baseline (Week 0) and Week 16

Change From Baseline in CFR at Week 32 Among Participants With CFR >=2.75 to <=3.5 at Baseline

Change from baseline in CFR at Week 32 among participants with CFR \>=2.75 to \<=3.5 at baseline were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest

Time frame: Baseline (Week 0) and Week 32

Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 16

Change from baseline in CFR among nicotine users and non-users at Week 16 were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest

Time frame: Baseline (Week 0) and Week 16

Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 32

Change from baseline in CFR among nicotine users and non-nicotine users at Weeks 32 were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest

Time frame: Baseline (Week 0) and Week 32

Change From Baseline in Absolute GLS Among Nicotine Users and Non-users at Week 16

Change from baseline in absolute GLS among nicotine users and non-nicotine users at Week 16 were reported. GLS is a myocardial deformation analysis that predominantly reflects the function of sub-endocardial longitudinally oriented fibers, which are most prone to ischemic damage and wall stress. The GLS is calculated at systole and diastole. Speckle tracking echocardiography (STE) were employed for the detection of left-ventricular (LV) myocardial strain. GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values.

Time frame: Baseline (Week 0) and Week 16

Change From Baseline in Absolute GLS Among Nicotine Users and Non-users at Week 32

Change from baseline in absolute GLS among nicotine users and non-nicotine users at Week 32 were reported. GLS is a myocardial deformation analysis that predominantly reflects the function of sub-endocardial longitudinally oriented fibers, which are most prone to ischemic damage and wall stress. The GLS is calculated at systole and diastole. Speckle tracking echocardiography (STE) were employed for the detection of left-ventricular (LV) myocardial strain. GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values.

Time frame: Baseline (Week 0) and Week 32

Change From Baseline in cfPWV Among Nicotine Users and Non-users at Week 16

Change from baseline in cfPWV among nicotine users and non-nicotine users at Week 16 were reported. cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. cfPWV was calculated as cfPWV= distance (meters)/ transit time (seconds).

Time frame: Baseline (Week 0) and Week 16

Change From Baseline in cfPWV Among Nicotine Users and Non-users at Week 32

Change from baseline in cfPWV among nicotine users and non-nicotine users at Week 32 were reported. cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. cfPWV was calculated as cfPWV= distance (meters)/ transit time (seconds).

Time frame: Baseline (Week 0) and Week 32

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Number of participants with TEAEs were reported. An adverse event (AE) was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Any AE occurring at or after initial administration study intervention (guselkumab) through the day of last dose within the study phase plus 12 weeks or the date of the Final Safety visit, whichever was the latest, was considered to be TEAE.

Time frame: Week 0 up to 12 weeks post last dose of study drug (up to Week 40)