E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071117 |
E.1.2 | Term | Plaque psoriasis |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of guselkumab on CFR measured by transthoracic dopplerechocardiography, in participants with moderate-to-severe psoriasis and intermediate cardiovascular risk |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the short-term effect of guselkumab on CFR measured by transthoracic dopplere-chocardiography, in participants with moderate-to-severe psoriasis and intermediate cardiovascular risk.
-To evaluate the effect of guselkumab on GLS as a surrogate marker of left ventricular function in participants with moderate-to-severe psoriasis and intermediate cardiovascular risk.
- To evaluate the effect of guselkumab on arterial stiffness in participants with moderate-to-severe psoriasis and intermediate cardiovascular risk.
- To evaluate the effect of guselkumab on CFR among participants in the different CFR categories.
- To evaluate the effect of guselkumab on surrogate CV risk markers among nicotine users and non-users in the participant population.
- To assess the safety and tolerability of guselkumab in participants with moderate-to severe plaque psoriasis and intermediate cardiovascular risk
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Is male or female 18 years of age and above.
- Has a diagnosis of moderate-to-severe plaque psoriasis for at least 6 months prior to the first dose of guselkumab at Week 0. Moderate-to-severe plaque psoriasis is defined as PASI ≥12, IGA ≥3 and involved BSA ≥10% at Screening Visit S1. Participants with a predominantly non-plaque form of psoriasis will not be eligible for inclusion in the study.
-Has intermediate cardiovascular risk defined by CFR ≥2 to ≤3.5.
- Is a candidate for systemic treatment for psoriasis.
- Does not have any abnormalities in physical examination, medical history, clinical
laboratory tests, vital signs, and 12-lead ECG performed at screening that are not consistent with the underlying illness in the study population. This determination must be recorded in the participant’s source documents and initialed by the investigator. The 12-lead ECG must be assessed by the dermatologist at Screening Visit S1.
- Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
For the complete overview of the inclusion criteria, please refer to section 5.1 of the protocol.
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E.4 | Principal exclusion criteria |
- Has low-density lipoprotein >190 mg/dL.
- Has uncontrolled hypertension that needs immediate medication
- Has any clinically significant evidence of cardiac functional or valvular abnormalities, other than intermediate cardiovascular risk defined by CFR ≥2 and ≤3.5, including but not limited to: coronary stenosis, history of any MI or transient ischemic attacks, stroke, cerebrovascular disease, peripheral atherosclerosis, congestive heart failure, chronic pulmonary disease, fast atrial fibrillation, supraventricular arrhythmia, valvular abnormalities, ventricular wall movement abnormalities observed during the CFR assessment
- Has any contraindications to adenosine infusion, including but not limited to asthma with ongoing wheezing, hypersensitivity to adenosine, known or suspected bronchoconstrictive or bronchospastic lung disease, greater than first degree heart block without a pacemaker or sick sinus syndrome, systolic blood pressure <90 mmHg and severe sinus bradycardia, or other contraindications listed in the SmPC.
- Unable or unwilling to abstain from caffeine-or nicotine-containing products including but not limited to smoking, vaping, chewing tobacco, nicotine gum and patches for 12
hours prior to the cardiology assessments.
- Has diabetes or has HbA1c >6.5.
For the complete overview of the inclusion criteria, please refer to section 5.2 of the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in CFR |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change from baseline in CFR at Week 16
- Change from baseline in GLS at Week 32 and change from baseline in GLS at Week 16
- Change from baseline in cfPWV at Week 32 and change from baseline in cfPWV at Week 16.
- Change from baseline in CFR at Week 16 and Week 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 Week 16 and Week 32 among nicotine users and non-users.
- Change from baseline in GLS at Week 16 and Week 32 among nicotine users and non-users.
- Change from baseline in cfPWV at Week 16 and Week 32 in nicotine users and non-users
- Rate of AEs among participants treated with guselkumab.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 27 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |