• Cardiology Clinical Trials
• Lipid Disorders

Higher levels of high density lipoprotein cholesterol (HDL-C) have been associated with a reduction in risk of cardiovascular disease, largely through its reverse transport of cholesterol, anti-inflammatory and anti-oxidative properties. CSL-111 is a reconstituted HDL that is similar to native HDL. It is isolated from human plasma, with appropriate donor screening and purification steps to minimize the risk of disease transmission. The findings from the Effect of Reconstituted High-Density Lipoprotein on Atherosclerosis: Safety and Efficacy (ERASE) trial (Tardif et al. JAMA. 2007 doi:10.1001/jama.297.15.jpc70004) were presented by Jean-Claude Tardif, MD, of the Montreal Heart Institute.

Patients with recent acute coronary syndrome (ACS) were randomly assigned to either 4 weekly infusions of CSL-111 (40 mg/kg or 80 mg/kg) or volume-matched placebo. Patients were assessed via intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA) at baseline and follow-up. The primary endpoint was the percentage change in atheroma volume as measured by IVUS. Secondary efficacy endpoints included nominal change in plaque volume on IVUS, change in plaque characterization on IVUS, and change in coronary score of QCA. The original statistical analysis plan was to compare the differences between all 3 treatment groups, but the safety review committee recommended stopping the 80 mg/kg arm because of observed liver function test abnormalities. The statistical plan and protocol were therefore amended to adjust the primary analysis to the change from baseline to final assessment within the active treatment group.

Twelve (12) patients were randomly assigned to the 80 mg/kg group (before the treatment group was discontinued), 60 to placebo, and 111 to CSL-111 40 mg/kg. Patients treated with CSL-111 40 mg/kg had a statistically significant reduction in the median percent and nominal changes in atheroma volume compared with baseline (p<0.001), but these changes were not significant when compared to placebo. The change in plaque composition characterization and change in coronary score (p=0.03) were significantly different between the treatment groups.

Thirty-three percent (33%) of the 80 mg/kg group had an ALT >10 times the upper limit of normal, compared with 0.9% in the 40 mg/kg group. Dr. Tardif noted that the liver enzyme elevations were transient, returned to normal after CSL-111 discontinuation, and there was no evidence of hepatic dysfunction/failure. The most common adverse events in the 80 mg/kg group were fatigue (25%) and diarrhea (16.7%), and the most frequent adverse events in the 40 mg/kg group were hypotension (13.8%) and fatigue (10.1%).

Dr. Tardif concluded by saying that, although the clinical significance of these findings is not fully understood, the compound demonstrated great promise in this small, proof-of-concept study.

• © 2007 MD Conference Express