DalCor Pharmaceuticals has randomised the first patient in the Phase lll dal-GenE clinical trial, a cardiovascular outcomes study of dalcetrapib in patients with acute coronary syndrome (ACS) and the AA genotype in the ADCY9 gene.
To be led by the Montreal Heart Institute (MHI), Canada, the global, double-blind, randomised, placebo-controlled, multi-centre clinical trial will be conducted at 1,000 sites in 33 countries.
MHI’s Biobank was also involved in this pharmacogenomic research.
The trial expects to include 5,000 patients recently hospitalised with ACS and who express the AA genotype at variant rs1967309 in the ADCY9 gene, determined by an investigational companion diagnostic test developed by Roche Molecular Systems (RMS).
The main endpoint of the study is the time to first occurrence of any component of the composite of cardiovascular death, myocardial infarction (heart attack) and stroke.
Around 20% of the general population currently harbour the AA genotype.
DalCor chief executive officer Robert McNeil said: "We believe that targeting a genetically specific patient population with dalcetrapib has the potential to dramatically reduce cardiovascular risk in this select patient population.
"Success would represent a major breakthrough in an important therapeutic area that has seen a tremendous amount of interest.
"This trial represents a major step forward in cardiovascular medicine, opening new doors and creating therapeutic options for patients of specific genetic composition suffering from heart disease, and who can benefit from the compound.
"We expect to complete the trial in the first half of 2020."
The company stated that dalcetrapib is one of four CETP inhibitors to have reached full-scale development, with more than 17,000 patients participating in dalcetrapib clinical trials.
In 2012, investigators at the MHI, led by professors Jean-Claude Tardif and Marie-Pierre Dubé, found a link between the effects of dalcetrapib in altering CV events and the polymorphism at the rs1967309 location in the adenylate cyclase type 9 (ADCY9) gene.
Patients with the AA genotype had a 39% reduction in CV events when treated with dalcetrapib compared to placebo, while GG patients had a 27% increase and AG patients had a neutral effect.
The analysis was conducted in 5,749 patients and additional analyses of other studies also demonstrated reduced atherosclerosis in the AA population when treated with dalcetrapib.