Infusions of the novel agent CSL-111, which acutely raises levels of high-density lipoprotein cholesterol, may reduce the volume of coronary artery plaque in patients with a recent episode of acute coronary syndrome, according to results from a late-breaking phase II trial presented at the scientific session of the American College of Cardiology.

CSL-111 is a patented biologic product consisting of apolipoprotein A-I purified from human plasma that is reconstituted to form a particle that chemically and biologically resembles human high-density lipoprotein cholesterol. A 40 mg/kg dose of CSL-111 results in an approximately 50-percent elevation in blood high-density cholesterol levels, which remain above normal for one week.

The Effect of Reconstituted HDL on Atherosclerosis - Safety and Efficacy (ERASE) trial was a phase II, randomized, blinded, placebo-controlled study conducted at 17 sites throughout Canada and coordinated by the Montreal Heart Institute. The trial examined whether four infusions of CSL-111, given at weekly intervals to patients with a recent episode of ACS, could reduce the volume of plaque in the coronary arteries.

Arterial assessment was performed using intravascular ultrasound and quantitative coronary angiography before and two to three weeks after treatment.
A total of 183 patients received placebo, 40 mg/kg or 80 mg/kg CSL-111. The higher dosage of CSL-111 was discontinued early because of transient liver function test abnormalities. The 40mg/kg dose was safe and generally well tolerated.

The presentation was based on data from 145 patients who had two sequential ultrasound procedures. There was a reduction in coronary plaque volume after infusions of CSL-111 of 3.4 percent and after placebo of 1.6 percent, which were not statistically significantly different. However, when compared with baseline, the reduction for patients infused with CSL-111 was statistically significant, but this was not the case in the placebo group.

Other assessments of plaque, such as characterization indexes or changes in plaque that are different than volume measurements, on ultrasound and coronary score on quantitative angiography, were significantly different between CSL-111 and placebo.

Interestingly, the difference in coronary score between patients who had 4 weeks of CSL-111 and those given placebo was similar to those observed after two years of statin treatment compared with no statin.

"Overall, these results strongly suggest that CSL-111 is biologically active, and that short term infusions of CSL-111 result in a rapid, favorable effect on coronary atherosclerotic plaque," said Jean-Claude Tardif, MD, of the Montreal Heart Institute, University of Montreal, and lead author of the study. "These data strongly support the conduct of further clinical studies to assess whether CSL-111 will provide a clinical benefit to patients with ACS."