Background:
CER
-
001 is a negatively charged, engineered
pre
-

HDL mimetic
containing apolipoprotein A
-
I and sphingomyelin.
Preliminary
studies
demonstrated favorable effects of CER
-
001 on cholesterol efflux and vascular
inflammation.
In a
post
hoc
re
-
analy
sis
of a previously completed study of
intravenous infusion of
CER
-
001 3 mg/kg in patients with a high
coronary
plaque
burden
promoted regression as assessed by intravascular ultrasound (IVUS)
.
Objective:
To determine the effect of infusing CER
-
001 on cor
onary atherosclerosis
progression in statin
-
treated patients.
Design:
A double
-
blind, randomized, multicenter trial evaluated the effect of ten
weekly intravenous in
fusions of CER
-
001 3 mg/kg (n=135) or placebo (n=137
) in
patients with an acute coronary
syndrome
(ACS)
and
baseline
percent atheroma
volume (PAV) >30%
in the proximal segment
of an epicardial artery
by IVUS
.
Settings and participants:
34 academic and community hospitals in Australia,
Hungary, The Netherlands and United States in patients wit
h ACS presenting for
coronary angiography.
Intervention:
Participants were randomized to receive weekly CER
-
001 3 mg/kg or
placebo for ten weeks, in addition to statins.
Main outcome measures:
The primary efficacy measure was the nominal change in
percent
atheroma volume (PAV) from baseline to day
78
measured by serial
intravascular ultrasonography (IVUS) imaging. The secondary efficacy measures
were nominal change in normalized total atheroma volume (TAV) and percentage of
Nicholls et al
5
patients demonstrating plaque re
gression. Safety and tolerability were also
evaluated.
Results:
Among
293
treated patients,
29
% had statin use prior to the index ACS and
272 had evaluable imaging at follow
-
up. The placebo and CER
-
001 groups had
similar post
-
treatment
median
levels of LDL
-
C (74 vs 79 mg/dL (P=0.15) and HDL
-
C
(43 vs 44 mg/dL, P=0.66). The primary efficacy measure,
PAV, decreased 0.41
%
with placebo (P=0.005 compared with baseli
ne), but not with CER
-
001 (
-
0.09
%,
P=0.67 compared with baseline; between group differences P=0.15)
. Similar
percentages of patients in the placebo and CER
-
001 groups demonstrated
regression of PAV (57.7% vs. 53.3%, P=0.49). Infusions were well tolerated with no
differences in clinical and laboratory adverse events observed between treatment
groups.
Co
nclusion:
Infusion of CER
-
001 did not promote
regression of coronary
atherosclerosis in statin
-
treated patients with
ACS
and high plaque burden.
(Funded by
Cerenis Pharmaceuticals
, ClinicalTrials.gov identifier
–
NCT
2484378)