PLASMA Trial: A Dose-Response Study of A-002 In Subjects With Stable Coronary Artery Disease

PLASMA Trial: Phospholipase Levels And Serological Markers of Atherosclerosis: A Dose-Response Clinical Pharmacology Study of A-002 In Subjects With Stable Coronary Artery Disease

The study will be conducted at up to 80 centers worldwide and will be a double-blind randomized parallel group placebo controlled study among subjects with stable coronary artery disease (CAD). Subjects will be randomized to receive either placebo tablets or one of 4 orally active doses of A-002. The duration of study drug therapy will be 8 weeks.

A-002 represents a novel therapy for the treatment of atherosclerosis and coronary artery disease (CAD). Through the inhibition of activity A-002 may provide multifunctional activity directed against key facets of the disease process, namely a) inflammation, b) atherogenic lipid profiles and c) the atherosclerotic process. Non-clinical and clinical data from recent studies have demonstrated the benefit of early and aggressive anti-inflammatory therapy to reduce cardiovascular risk. Recent clinical studies have provided a strong association between levels and cardiovascular event risk. The proposed Phase 2 clinical pharmacology study (Study No. AN-CVD-2221) will examine the effects of 4 different doses of A-002 compared with placebo, on enzyme levels and activity after 8 weeks of treatment. In addition, the effect of treatment on inflammatory markers of cardiovascular risk (C-reactive protein [CRP]), lipid levels and lipoprotein subclasses and other soluble biomarkers (e.g., ICAM-1, VCAM-1, TNF, MCP-1 etc) will also be assessed.

Inclusion Criteria:

Subjects are eligible for inclusion if they meet the following inclusion criteria:

• Men and women > 18 years of age
• Written informed consent from the subject
• Stable CAD
• Stable medical condition, will be compliant and able to comply with the requirements of the protocol

Exclusion Criteria:

• Subjects must NOT meet any of the following exclusion criteria:
• Planned CABG
• Hospitalization for acute coronary syndrome if troponin level is >0.1 ng/mL in the preceding 6 weeks
• Hospitalization for ST-segment acute myocardial infarction (STEMI) in the preceding 12 weeks
• Subjects with chronic inflammatory disease (e.g., RA), inflammatory bowel disease, recent (12 weeks) systemic or localized infection (the latter requiring clinical intervention), or major surgery
• hs-CRP >15 mg/L repeated on at least 2 occasions >24 hours apart due to non-cardiovascular systemic inflammatory conditions (e.g., rheumatoid disease)
• Acute or chronic heart failure as defined by the NYHA classification as functional Class III or Class IV