Integrated Biomarker And Imaging Study - 2

Completed

Phase 2 Results

Trial Description

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.

Detailed Description

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.

Conditions

Interventions

  • SB-480848 (darapladib)Drug
    Intervention Desc: SB-480848 is available as enteric-coated, free-base micronized tablet
    ARM 1: Kind: Experimental
    Label: Non-ACS and ACS subjects without evidence of MN: SB-480848
    Description: 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
    ARM 2: Kind: Experimental
    Label: Subjects with ACS and evidence of MN:SB-480848
    Description: Enrolled subjects (subjects with ACS and evidence of myocardial necrosis) will receive 160mg of SB-480848 once daily with food for 52 weeks
  • SB-480848 matching placebo Drug
    Intervention Desc: Placebo is available as enteric-coated, free-base micronized tablet
    ARM 1: Kind: Experimental
    Label: Non-ACS and those ACS subjects without evidence of MN: placebo
    Description: 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
    ARM 2: Kind: Experimental
    Label: Subjects with ACS and evidence of MN: placebo
    Description: Enrolled subjects (subjects with ACS and evidence of myocardial necrosis) will receive SB-480848 matching placebo once daily with food for 52 weeks

Trial Design

  • Allocation: Randomized
  • Masking: Double-Blind
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary IVUS (Intravascular Ultrasound) -based palpography and high sensitivity C-reactive protein.
Secondary Endothelial function plaque volume by quantitative coronary angiography and intravascular ultrasound circulating biomarkers.
Primary IVUS (Intravascular Ultrasound) -based palpography and high sensitivity C-reactive protein
Secondary Endothelial function plaque volume by quantitative coronary angiography and intravascular ultrasound circulating biomarkers
Primary Mean circulating high sensitivity C- Reactive Protein (HS-CRP) levels at Week 52. Week 52
Primary 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. Baseline and Week 52
Secondary Circulating HS-CRP at the end of week 26. Week 26
Secondary Mean Lipoprotein Phospholipase A2 (Lp-PLA2) activity at the end of week 26 and week 52 Week 26 and Week 52
Secondary Change from Baseline in plaque volume as IVUS-Grey Scale Assessments at Week 52 Baseline and Week 52
Secondary Change from Baseline in Percent obstruction volume as IVUS-Grey Scale Assessments at Week 52 Baseline and Week 52
Secondary Change from Baseline in necrotic core volume as intravenous Ultrasound-Virtual Histology (IVUS-VH) assessments at Week 52 Baseline and Week 52
Secondary Change from Baseline in necrotic core as a percent of IVUS-VH plaque at the end of week 52. Baseline and Week 52
Secondary Mean Interlukin 6 (IL-6) levels as circulating biomarkers associated with inflammatory burden at Week 26 and Week 52 Week 26 and Week 52
Secondary 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
Secondary Mean Myeloperoxidase (MPO) levels as circulating biomarkers associated with inflammatory burden at Week 26 and Week 52 Week 26 and Week 52
Secondary Mean sCD40L levels as circulating biomarkers associated with inflammatory burden at Week 26 and Week 52 Week 26 and Week 52
Secondary 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
Secondary 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
Secondary 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
Secondary Change from Baseline in vessel volume and lumen volume as IVUS-Grey Scale Assessments at Week 52. Baseline and Week 52
Secondary 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
Secondary Change from Baseline in fibrous tissue volume and fibro-fatty volume as IVUS-VH assessments at Week 52 Baseline and Week 52
Secondary 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

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