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
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 5
- 主要终点
- Change From Baseline in Coronary Flow Reserve (CFR) at Week 32
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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)
研究组 & 干预措施
Guselkumab
Participants will receive guselkumab 100 milligrams (mg) by subcutaneous injection at Weeks 0, 4, 12, 20 and 28.
干预措施: Guselkumab (Drug)
结局指标
主要结局
Change From Baseline in Coronary Flow Reserve (CFR) at Week 32
时间窗: Baseline (Week 0) and 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.
次要结局
- Change From Baseline in CFR at Week 16(Baseline (Week 0) and Week 16)
- Change From Baseline in Absolute Global Longitudinal Strain (GLS) at Week 16(Baseline (Week 0) and Week 16)
- Change From Baseline in Absolute GLS at Week 32(Baseline (Week 0) and Week 32)
- Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 16(Baseline (Week 0) and Week 16)
- Change From Baseline in cfPWV at Week 32(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(Baseline (Week 0) and Week 16)
- Change From Baseline in CFR at Week 32 Among Participants With CFR >=2 to <2.75 at Baseline(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(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(Baseline (Week 0) and Week 32)
- Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 16(Baseline (Week 0) and Week 16)
- Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 32(Baseline (Week 0) and Week 32)
- Change From Baseline in Absolute GLS Among Nicotine Users and Non-users at Week 16(Baseline (Week 0) and Week 16)
- Change From Baseline in Absolute GLS Among Nicotine Users and Non-users at Week 32(Baseline (Week 0) and Week 32)
- Change From Baseline in cfPWV Among Nicotine Users and Non-users at Week 16(Baseline (Week 0) and Week 16)
- Change From Baseline in cfPWV Among Nicotine Users and Non-users at Week 32(Baseline (Week 0) and Week 32)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Week 0 up to 12 weeks post last dose of study drug (up to Week 40))