Date: 2014-01-02
Type of information: Initiation of preclinical development
phase: 2
Announcement: results
Company: Cerenis Therapeutics (France)
Product: CER-001
Action
mechanism: CER-001 is a complex of recombinant human ApoA-I and phospholipids. It is designed to mimic pre-beta HDL, the "good" cholesterol, to promote the removal of excess cholesterol and other lipids from artery walls and enhance reverse lipid transport.
Disease: secondary prevention of cardiovascular events in patients with acute coronary syndrome
Therapeutic area: Cardiovascular diseases
Country: USA, Canada, France, the Netherlands
Trial
details: The Chi-Square study will assess the effects of CER-001, an ApoA-I-based HDL mimetic, on indices of atherosclerotic plaque progression and regression as assessed by intravascular ultrasound (IVUS) measurements in patients with (ACS). (NCT01201837)
Latest
news: * On January 2, 2014, Cerenis Therapeutics 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).
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.
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.”
* On March 15, 2011, Cerenis Therapeutics has announced the start of the Phase 2 CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis Regression?) study of CER-001 in patients with acute coronary syndrome. This complex of recombinant human ApoA-I, the major structural protein of HDL, and phospholipids has been designed to mimic the structure and function of natural, nascent HDL, also known as pre-beta HDL, which is believed to be protective against atherosclerosis. It is hoped that CER-001 will further reduce cardiovascular events in high-risk patients by promoting removal of cholesterol from the vessel wall.
The double-blind, randomized, placebo-controlled, safety and efficacy study will assess the ability of CER-001 to regress coronary atherosclerotic plaque as measured by intravascular ultrasound (IVUS). The study will include over 500 patients at 50 centers in the US, Canada and Europe, and will evaluate three different dose levels given in six weekly intravenous infusions. CHI SQUARE is the largest clinical trial to-date testing an HDL mimetic.
