An International, Multicenter, Randomized, Placebo-controlled, Parallel-group, 1 Year Treatment, Integrated Biomarkers and Imaging Study in Subjects With Angiographically Documented Coronary Heart Disease (CHD) to Examine the Effects of the Novel Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Inhibitor SB-480848 on Intermediate Cardiovascular Endpoints, Patient Safety and Tolerability
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 336
- 试验地点
- 1
- 主要终点
- Mean Circulating High Sensitivity C- Reactive Protein (Hs-CRP) Levels at Week 52.
研究概览
简要总结
IBIS-2 is a study using SB-480848 versus placebo in subjects with angiographically documented coronary heart disease. Endpoints include coronary imaging, endothelial function, biomarkers, safety and tolerability.
详细描述
Integrated Biomarker and Imaging Study -2 (IBIS-2): An International, Multicenter, Randomized, Placebo-controlled, Parallel-group, 1 Year Treatment, Integrated Biomarkers and Imaging Study in Subjects with Angiographically Documented Coronary Heart Disease (CHD) to Examine the Effects of the Novel Lipoprotein-associated Phospholipase A2 (Lp-PLA2) inhibitor SB-480848 on Intermediate Cardiovascular Endpoints, Patient Safety and Tolerability.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Subjects with ACS and evidence of MN:SB-480848
Enrolled subjects (subjects with ACS and evidence of myocardial necrosis) will receive 160mg of SB-480848 once daily with food for 52 weeks
干预措施: SB-480848 (Drug)
Subjects with ACS and evidence of MN: placebo
Enrolled subjects (subjects with ACS and evidence of myocardial necrosis) will receive SB-480848 matching placebo once daily with food for 52 weeks
干预措施: SB-480848 matching placebo (Drug)
Non-ACS and ACS subjects without evidence of MN: SB-480848
Enrolled subjects (non-ACS subjects and those ACS subjects without evidence of myocardial necrosis) will receive 160mg of SB-480848 once daily with food for 52 weeks
干预措施: SB-480848 (Drug)
Non-ACS and those ACS subjects without evidence of MN: placebo
Enrolled subjects (non-ACS subjects and those ACS subjects without evidence of myocardial necrosis) will receive SB-480848 matching placebo once daily with food for 52 weeks
干预措施: SB-480848 matching placebo (Drug)
结局指标
主要结局
Mean Circulating High Sensitivity C- Reactive Protein (Hs-CRP) Levels at Week 52.
时间窗: Week 52
hs-CRP is a pentameric protein that is rapidly upregulated in response to inflammation and tissue damage and assessed as circulating biomarkers associated with atherosclerosis and cardiovascular risk. Last Observation Carried Forward (LOCF) data was reported. Only data from 3 months onwards was carried forward. hs-CRP has a skewed distribution and values were log transformed before analysis. The statistics was calculated on the log transformed data and back transformed. The adjusted geometric means of hs-CRP levels at Week 52 were reported. The levels were analyzed using analysis of co-variance (ANCOVA), with Acute Coronary Syndrome (ACS) status, pooled country and treatment included as covariates.
Change From Baseline in the Density of Rotterdam Classification (ROC) Grade III/IV Strain Spots/10 Millimeter (mm) Within the Region of Interest (ROI) on IVUS Grey Scale Based Palpography at the End of Week 52.
时间窗: Baseline and Week 52
The ROC grade III/IV strain spots per 10 millimetre (mm) within the ROI on intravascular ultrasound (IVUS) grey scale based palpography were assessed and change from Baseline at end of 52 was reported. Change from Baseline was calculated as the density of spots at the end of study minus the density of spots recorded at Baseline. If either value was considered missing then the change from Baseline value was missing for the participant. Between treatment group comparisons of change from Baseline were analyzed using ANCOVA adjusting for ACS status, pooled country, Baseline value, matched segment length and treatment. Adjusted means and associated standard errors for each treatment group were presented. The baseline value for each participant was defined as the last value prior to the first dose of study drug.
次要结局
- Circulating Hs-CRP at the End of Week 26.(Week 26)
- Change From Baseline in Plaque Volume as IVUS-Grey Scale Assessments at Week 52(Baseline and Week 52)
- Change From Baseline in Necrotic Core Volume as Intravenous Ultrasound-Virtual Histology (IVUS-VH) Assessments at Week 52(Baseline and Week 52)
- Mean Lipoprotein Phospholipase A2 (Lp-PLA2) Activity at the End of Week 26 and Week 52(Week 26 and Week 52)
- Change From Baseline in Percent Obstruction Volume as IVUS-Grey Scale Assessments at Week 52(Baseline and Week 52)
- Mean Levels of Oxidized Non-esterified Fatty Acids (Ox-NEFA) as Target Circulating Biomarkers at the End of Week 26 and Week 52(Week 26 and Week 52)
- Change From Baseline in Vessel Volume and Lumen Volume as IVUS-Grey Scale Assessments at Week 52.(Baseline and Week 52)
- Change From Baseline in Necrotic Core as a Percent of IVUS-VH Plaque at the End of Week 52.(Baseline and Week 52)
- Mean Interlukin 6 (IL-6) Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52(Week 26 and Week 52)
- Mean Intercellular Adhesion Molecule-1 (ICAM-1) Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52(Week 26 and Week 52)
- Mean Myeloperoxidase (MPO) Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52(Week 26 and Week 52)
- Mean sCD40L Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52(Week 26 and Week 52)
- Mean Matrix Metaloproteinases-9 (MMP-9) Levels as Circulating Biomarkers Associated With Plaque Instability at Week 26 and Week 52.(Week 26 and Week 52)
- Mean Levels of Oxidised Phospholipids/ Apolipoprotein B100 (oxPL/apoB) Ratio as Target Circulating Biomarkers at the End of Week 26 and Week 52.(Week 26 and Week 52)
- Change From Baseline in Mean Plaque Area, Mean Vessel Area, and Mean Lumen Area as IVUS-Grey Scale Assessments at Week 52.(Baseline and Week 52)
- Change From Baseline in Fibrous Tissue and Fibro-fatty as a Percent of IVUS-VH Plaque as IVUS-VH Assessments at Week 52(Baseline and Week 52)
- Change From Baseline in Fibrous Tissue Volume and Fibro-fatty Volume as IVUS-VH Assessments at Week 52(Baseline and Week 52)