A Multi-center, Randomized , Double Blind, Placebo-controlled, Study of the Safety, Tolerability, and Effects on Arterial Structure and Function of ACZ885 in Patients With Clinically Evident Atherosclerosis and Either T2DM or IGT
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 189
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events, Serious Adverse Events and Death
研究概览
简要总结
This study will evaluate the effect of ACZ885 on vascular function in patients with documented atherosclerotic disease and T2DM or IGT.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with known atherosclerotic disease and documented diagnosis of T2DM for ≤ 14 years OR IGT
- •HbA1c between 6.0% and 10.0%
- •On stable statin therapy or statin intolerant
- •Patients who are eligible and able to participate in the study
排除标准
- •Contraindications to MRI
- •NYHA class IV Heart Failure
- •NYHA class I - III heart failure with acute exacerbation in 3 months prior to screening
- •Patients with type 1 diabetes
- •Acute infections
- •HsCRP > 30 mg/dL
- •Aortic aneurysm ≥5cm
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Placebo
subcutaneous (SQ) monthly
干预措施: Placebo (Drug)
ACZ885
150 mg SQ monthly
干预措施: ACZ885 (Drug)
结局指标
主要结局
Number of Participants With Adverse Events, Serious Adverse Events and Death
时间窗: 12 months
Participants were monitored for adverse events, serious adverse events and death throughout the study.
Change From Baseline in Plaque Burden (Aortic Vessel Wall Area and Carotid Vessel Wall Area)
时间窗: baseline, 3 months, 12 months
For assessment of atherosclerotic plaque burden of the aorta, vessel wall images of the aorta were acquired with an ECG gated double-inversion recovery (black blood) fast spin echo sequence applied breath-holding. Using an oblique sagittal image of the aorta as a pilot, serial axial images were acquired to cover a section of the descending thoracic aorta. The midpoint of the right pulmonary artery in cross section was used as the anatomical reference for the first slice in baseline and follow-up scans. For assessment of the atherosclerotic plaque burden in the carotids, vessel wall images were acquired with an axial ECG gated PD (proton density) weighted black blood sequence. The carotid bifurcation was used as the anatomical reference for all three imaging time points (baseline, 12 weeks, 48 weeks) with axial slice planes acquired below the bifurcation region. The mean values reported here for the carotid are reported for the proximal common carotid region.
Change From Baseline in Aortic Distensibility
时间窗: baseline, 3 months, 12 months
Two axial, ECG-gated, steady state free precession (SSFP) 'cine' images were acquired during breath-hold to determine aortic distensibility. The first image was obtained at the level of the right pulmonary artery through the ascending and proximal descending aorta and the second through the distal aorta below the diaphragm. Imaging of the aorta also enabled evaluation of the plaque burden and additional vascular function measures.
次要结局
- Change From Baseline in High Sensitivity C-reactive Protein (hsCRP)(baseline, 3 months, 12 months)
- Change From Baseline in Aortic Strain(baseline, 3 months, 12 months)
- Change From Baseline in Hemoglobin A1c (HbA1c)(baseline, 3 months, 12 months)
- Pharmacokinetics: ACZ885 Serum Concentrations(pre-dose, 0.167 day post dose 1, 7 days post dose 1, 14 days post dose 1, every 30 days post each dose from doses 1 through 12, 60 days post dose 12, 90 days post dose 12)
- Change From Baseline in Pulse Wave Velocity and Pulse Wave Velocity Error(baseline, 3 months, 12 months)
- Change From Baseline in Plaque Composition(baseline, 3 months, 12 months)
- Change From Baseline in Beta Cell Function (HOMA-B)(baseline, 3 months, 12 months)
- Change From Baseline in 2 Hour Glucose Post Oral Glucose Tolerance Test (OGTT)(baseline, 3 months, 12 months)
- Change From Baseline in Fasting Plasma Glucose(baseline, 3 months, 12 months)
- Change From Baseline Insulin Resistance (HOMA-IR)(baseline, 3 months, 12 months)