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

Psoriasis Clinical Trial

— G-CARE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05125679
• Other study ID #: CR109033
• Secondary ID: 2020-004061-39CN
• Status: Terminated
• Phase: Phase 4
• Start date: November 23, 2021
• Est. completion date: July 28, 2023

Study information

• Verified date: August 2023
• Source: Janssen-Cilag Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: July 28, 2023
• Est. primary completion date: July 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• Guselkumab
Guselkumab will be administered by subcutaneous injection.

Locations

Country	Name	City	State
Germany	Universitatsklinikum Frankfurt	Frankfurt
Germany	Universitätsklinikum Leipzig AÖR	Leipzig
Greece	Attikon Hospital	Athens
Italy	Ospedale San Giovanni di Dio	Cagliari
Italy	Azienda Ospedaliera di Padova	Padova

Sponsors (1)

Lead Sponsor	Collaborator
Janssen-Cilag Ltd.

Countries where clinical trial is conducted

Germany,  Greece,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from Baseline in CFR at Week 16	Change from baseline in CFR at Week 16 will be reported.	Baseline and Week 16
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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