A Randomized, Double-blind, Placebo-controlled, Multicenter, Exploratory Evaluation of Surrogate Markers of Cardiovascular Risk in Patients With Active Chronic Plaque-type Psoriasis Treated for up to 52 Weeks With Subcutaneous (s.c.) Secukinumab (300 mg or 150 mg).
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 151
- 试验地点
- 1
- 主要终点
- Flow Mediated Dilation (FMD) at Week 12 Followed by Secukinumab 300 mg vs Pooled Placebo Treatment
研究概览
简要总结
The purpose of this study was to explore the effect of treatment with 300 mg or with 150 mg secukinumab (administered weekly for 4 weeks followed by four-weekly administration) on endothelial dysfunction and arterial stiffness after 12 weeks and for up to 52 weeks in subjects with chronic plaque-type psoriasis. Furthermore soluble biomarkers were assessed to evaluate the influence of secukinumab on cardiovascular risk. Magnetic resonance imaging (MRI) was performed in a sub-population to assess the treatment effect on arterial vessel wall morphometry in atherosclerosis prone vascular beds.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Chronic moderate to severe plaque type psoriasis for at least 6 months prior to randomization with a Psoriasis Area and Severity Index (PASI) score ≥ 10 at randomization.
- •Inadequate response, intolerance or contraindication to cyclosporine, methotrexate and psoralen plus ultraviolet A light treatment (PUVA) as documented in the patient's medical history or reported by the patient or determined by the investigator at screening. Relative contraindications such as interference of patient's lifestyle with the treatment are accepted.
排除标准
- •Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttata psoriasis) at screening or randomization.
- •Ongoing use of prohibited psoriasis and non-psoriasis treatments.
研究组 & 干预措施
300 mg secukinumab
300 mg secukinumab every week for 4 weeks followed by 300 mg secukinumab every 4 weeks until week 48 (last injection)
干预措施: Secukinumab (Drug)
150 mg secukinumab
150 mg secukinumab every week for 4 weeks followed by 150 mg secukinumab every 4 weeks until week 48 (last injection)
干预措施: Secukinumab (Drug)
Placebo followed by 300 mg secukinumab
Placebo until week 12 followed by 300 mg secukinumab every week for 4 weeks followed by 300 mg secukinumab every 4 weeks until week 48 (last injection)
干预措施: Placebo (Other)
Placebo followed by 150 mg secukinumab
Placebo until week 12 followed by 150 mg secukinumab every week for 4 weeks followed by 150 mg secukinumab every 4 weeks until week 48 (last injection)
干预措施: Placebo (Other)
结局指标
主要结局
Flow Mediated Dilation (FMD) at Week 12 Followed by Secukinumab 300 mg vs Pooled Placebo Treatment
时间窗: Week 12
Flow Mediated Dilation (FMD) is non-invasive method evaluated by Doppler Ultrasound test, to assess endothelial function. FMD was calculated as the percent maximal deviation from the baseline arterial diameter (D):FMD = 100\*\[(D maximum - D baseline) / D baseline\]. Here, arterial diameter (brachial artery) was measured at rest (1 minute), during inflation of the distal cuff to 100 millimeter of mercury (mmHg) for 4.5 minutes and for 4.5 minutes following deflation.
次要结局
- Change From Baseline in Flow Mediated Dilation (FMD) at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Aortic Augmentation Index at Heart Rate of 75 (AIx-75) at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Pulse Wave Velocity (PWV) at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Average Wall Area Assessed as a Measure of Total Plaque Burden at Week 12(Baseline, Week 12)
- Change From Baseline in Average Wall Area Assessed as a Measure of Total Plaque Burden at Week 52(Baseline, Week 52)
- Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in S-100 Protein B (Total) at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Chemokine (C-c Motif) Ligand 5 (CCL5), Monocyte Chemoattractant Protein 1 (MCP-1) and Macrophage Inflammatory Proteins (MIP) 1 Alpha and 1 Beta at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Fasting Insulin at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Homeostatic Model Assessment (HOMA) Beta-cell Function at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Homeostatic Model Assessment (HOMA) Insulin Resistance at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Hemoglobin A1c (Glycated Hemoglobin) at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Sex Hormone-binding Globulin (SHBG) at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Triglycerides, Total Cholesterol, Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Apolipoprotein A-1 (ApoA-1) and Apolipoprotein B (ApoB) at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Adiponectin at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)
- Change From Baseline in Leptin at Week 4, 12, 24 and 52(Baseline, Week 4, 12, 24 and 52)