Cerenis Therapeutics, the biopharmaceutical company, has announced that its Phase IIb CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis REgression?) study did not reach its primary endpoint in post-Acute Coronary Syndrome (ACS) patients.
The Phase IIb efficacy and safety trial randomized 507 patients with ACS at 53 centers in the US, Canada, France and The Netherlands. The trial, conducted by Principal Investigator Jean-Claude Tardif, MD, FRCPC, FACC of the Montreal Heart Institute, was a double-blind, randomized, placebo-controlled dose-ranging study to assess the efficacy of CER-001 at three doses to regress coronary atherosclerotic plaque as measured by intravascular ultrasound (IVUS). CHI SQUARE is the largest clinical trial to-date testing an HDL mimetic.
Cerenis reported that CER-001 demonstrated a dose-dependent mobilization of cholesterol in post-ACS patients with a potency consistent with the prior Phase I study in healthy volunteers. The study did not meet its primary endpoint of reducing Total Atheroma Volume (TAV) versus placebo in the modified Intention to Treat (mITT) population (n= 417). The reduction in the Total Atheroma Volume versus baseline as measured by IVUS was statistically significant.
In an independent and blinded analysis performed by Stephen Nicholls, MBBS, PhD, FACC of the South Australian Health & Medical Research Institute (SAHMRI), the reduction in TAV versus baseline in the mITT population (n= 369) was also statistically significant but did not reach statistical significance when compared with placebo for the primary clinical endpoint. In the modified Per Protocol (mPP) population (n=295), one CER-001 dose level did reach nominal statistical significance versus placebo for reductions in both TAV and PAV (Percent Atheroma Volume). Cerenis anticipates that the full CHI SQUARE results will be presented at an upcoming international scientific meeting and will be published expeditiously.
Dr. Tardif commented, "I look forward to the publication of the study results in a scientific journal."
Dr. Nicholls added, "The apparent demonstration of benefit at one dose level versus placebo in our analysis is encouraging. CER-001 warrants further study in clinical trials to evaluate its potential benefits for patients with cardiovascular disease."
John F. Paolini, MD, PhD, FACC, Chief Medical Officer of Cerenis, said, "While we are disappointed that the primary end point in CHI-SQUARE was not met, the magnitude of the reduction in TAV versus baseline is consistent with what had been seen in the prior IVUS trial with the earlier-generation HDL-mimetic ETC-216 (apoA-Imilano) reported by Esperion in 2003. Furthermore, we are pleased with the demonstrated safety profile seen in all studies performed thus far."
Jean-Louis Dasseux, PhD, MBA, and CEO of Cerenis, concluded: "In all preclinical and clinical studies to date, CER-001 has been shown to perform the functions of natural HDL and the steps of the Reverse Lipid Transport Pathway with a high degree of potency. We are undertaking a detailed review of all the data to further understand these results and to determine the best path forward for CER-001. We remain confident that CER-001 has the potential to be demonstrated to be a clinically valuable pre-beta HDL mimetic, and that CER-001 will be shown to offer an important benefit for patients suffering from cardiovascular disease."
CER-001 is an engineered complex of recombinant human apoA-I, the major structural protein of HDL, and phospholipids. It has been designed to mimic the structure and function of natural, nascent HDL, also known as pre-beta HDL. Its mechanism of action is to increase apoA-I and the number of HDL particles transiently, to stimulate the removal of excess cholesterol and other lipids from tissues including the arterial wall and to transport them to the liver for elimination through a process called Reverse Lipid Transport.
About CHI SQUARE
The Can HDL Infusions Significantly Quicken Atherosclerosis REgression (CHI SQUARE) Study (CER-001-CLIN-002) was a Phase II multi-center, double-blind ascending dose, placebo-controlled, dose-finding IVUS-imaging trial in patients immediately post Acute Coronary Syndrome (ACS). It involved 53 study sites in the United States, Canada, France, and the Netherlands. 507 subjects presenting with an Acute Coronary Syndrome (STEMI, non STEMI or Unstable Angina) in whom coronary angiography was clinically indicated and planned were randomized in a 3:1 ratio to receive 6 weekly infusions of CER-001 (low, middle, or high dose) or placebo after a baseline IVUS examination. A follow-up IVUS examination was conducted approximately 3 weeks after last dose of study drug. The primary endpoint for this study was the nominal change in Total Atheroma Volume in patients treated with CER-001 versus placebo.