Back to resultsEffect of Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With Moderate to Severe Plaque Psoriasis (G-CARE)
Primary Purpose
Psoriasis
Status
Terminated
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Guselkumab
Sponsored by
About this trial
This is an interventional treatment trial for Psoriasis
Eligibility Criteria
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)
Sites / Locations
- Universitatsklinikum Frankfurt
- Universitätsklinikum Leipzig AÖR
- Attikon Hospital
- Ospedale San Giovanni di Dio
- Azienda Ospedaliera di Padova
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Guselkumab
Arm Description
Participants will receive guselkumab 100 milligrams (mg) by subcutaneous injection at Weeks 0, 4, 12, 20 and 28.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Change from Baseline in CFR at Week 16
Change from baseline in CFR at Week 16 will be reported.
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.
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).
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05125679
Brief Title
Effect of Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With Moderate to Severe Plaque Psoriasis
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
Terminated (A strategic decision was made not to further execute the study. This decision was not based on a safety concern)
Study Start Date
November 23, 2021 (Actual)
Primary Completion Date
July 28, 2023 (Actual)
Study Completion Date
July 28, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen-Cilag Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Guselkumab
Arm Type
Experimental
Arm Description
Participants will receive guselkumab 100 milligrams (mg) by subcutaneous injection at Weeks 0, 4, 12, 20 and 28.
Intervention Type
Drug
Intervention Name(s)
Guselkumab
Intervention Description
Guselkumab will be administered by subcutaneous injection.
Primary Outcome Measure Information:
Title
Change from Baseline in Coronary Flow Reserve (CFR) at Week 32
Description
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.
Time Frame
Baseline and Week 32
Secondary Outcome Measure Information:
Title
Change from Baseline in CFR at Week 16
Description
Change from baseline in CFR at Week 16 will be reported.
Time Frame
Baseline and Week 16
Title
Change from Baseline in Global Longitudinal Strain (GLS) at Weeks 16 and 32
Description
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.
Time Frame
Baseline and Weeks 16 and 32
Title
Change from Baseline in carotid-femoral Pulse Wave Velocity (cfPWV) at Weeks 16 and 32
Description
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).
Time Frame
Baseline and Weeks 16 and 32
Title
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
Description
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.
Time Frame
Baseline and Weeks 16 and 32
Title
Change from Baseline in CFR at Weeks 16 and 32 Among Nicotine Users and Non-users
Description
Change from baseline in CFR at Weeks 16 and 32 among nicotine users and non-users will be reported.
Time Frame
Baseline and Weeks 16 and 32
Title
Change from Baseline in GLS at Weeks 16 and 32 Among Nicotine Users and Non-users
Description
Change from baseline in GLS at Weeks 16 and 32 among nicotine users and non-users will be reported.
Time Frame
Baseline and Weeks 16 and 32
Title
Change from Baseline in cfPWV at Weeks 16 and 32 in Nicotine Users and Non-users
Description
Change from baseline in cfPWV at Weeks 16 and 32 in nicotine users and non-users will be reported.
Time Frame
Baseline and Weeks 16 and 32
Title
Rate of Adverse Events (AEs) Among Participants Treated with Guselkumab
Description
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.
Time Frame
Up to Week 40
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen-Cilag Ltd Clinical Trial
Organizational Affiliation
Janssen-Cilag Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Universitatsklinikum Frankfurt
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitätsklinikum Leipzig AÖR
City
Leipzig
ZIP/Postal Code
4103
Country
Germany
Facility Name
Attikon Hospital
City
Athens
ZIP/Postal Code
12462
Country
Greece
Facility Name
Ospedale San Giovanni di Dio
City
Cagliari
ZIP/Postal Code
09123
Country
Italy
Facility Name
Azienda Ospedaliera di Padova
City
Padova
ZIP/Postal Code
35128
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical- trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency
Learn more about this trial
Effect of Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With Moderate to Severe Plaque Psoriasis
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