SUPPORT-1

Report
A Prospective Randomized Trial of CMX2043, a Lipoic Acid-Based Cytoprotectant,
In Patients Undergoing Elective PCI:
Primary Results of the SUPPORT-1 Trial
Mitchell W. Krucoff, C.K. Ponde, Jagdish Hiremath, Mullasari Ajit,
Eddison Ramsaran, Manesh R. Patel, Alan S. Lader,
F. Howard Schneider, Reinier Beeuwkes, C. Michael Gibson, and
James E. Tcheng.
20090417
Conflict of Interest
 Clinical Advisory Board, Ischemix
20090417
Incidence & Implications of Peri-Procedural MI:
A Controversy of Definitions & Pathophysiology
Incidence: 3.6-17.8%
 Resolute All Comers
 2,121 patients
3 yr mortality: 2-8%
20090417
PCI: A Human Laboratory for Cytoprotection
 PCI produces enzymatic
events
 Selected protein elevations
(CPK-MB, Troponin)
represent myocellular
necrosis
 PCI as a laboratory for RCT
of cytoprotective strategies
has FDA predicate (vitamin
B6 metabolite pyridoxal-5’phosphate monohydrate (MC1) in the MC-1 to Eliminate
Necrosis and Damage
(MEND-1)
20090417
CMS-2043: A Novel Molecular Entity to Inhibit
Ischemic Apoptosis
• Reactive oxygen species (ROS)
anti-oxidant, AND
• Activates Akt (Ak mouse
thymoma = Protein kinase B) via
tyrosine kinase (TK)
20090417
Safety and Efficacy of CMX-2043 in
Subjects Undergoing PCI and PeriOperative Reperfusion Treatment
The SUPPORT 1 Study
20090417
SUPPORT-1: Study Design
 Phase IIa Safety & Efficacy: CMX-2043
 Prospective, randomized 3:1
• 3 doses (0.8, 1.6 & 2.4 mg/kg) vs placebo
 Multi-center (N=6)
 Elective PCI Patients
• WNL biomarkers & Non-acute ECG
• Receiving single stent of ≥ 18 mm or multiple stents
 Primary Outcome Measures:
• Incidence of CK-MB elevation <24 hours following
PCI
• Change in cardiac biomarkers <24 hrs following PCI
CK-MB, Troponin T
 Secondary Outcome Measure: MI as >X3 peak CPK
20090417
SUPPORT-1 Exclusion Criteria
 Acute/unstable angina
 MI within 14 days
 Coagulopathy
 Clinical valvular disease
 Clinical peripheral vascular disease
 TIA, stroke or IC bleed within 90 days
 Creatinine level ≥ 1.5 times ULN
20090417
SUPPORT-1 Sites and Investigators
20090417
SUPPORT I: Patient Accrual/Randomization
Total patients
enrolled
N=142
0.8 mg/Kg
N= 36
1.6 mg/Kg
N= 35
2.4 mg/Kg
N= 36
Placebo
N= 35
0.8 mg/Kg
(100%)
1.6 mg/Kg
(97.1 %)
2.4 mg/Kg
(100%)
Placebo
(100%)
1 subject withdrawn
20090417
SUPPORT-1 Baseline Characteristics
20090417
SUPPORT I: Arteries Stented Per Rx Group
20090417
Primary Endpoint:
24 Hr CK-MB Change from Baseline
20090417
24 Hr CK-MB Change From Baseline (ng/mL)
p = 0.05
p=0.05
vs. Placebo
CMX-2043 treatment
20090417
24 Hr Troponin T Change from Baseline
CMX-2043 treatment
20090417
24 Hr Peri-Procedural MI by CK-MB >X3 ULN
p=0.024
vs. Placebo
CMX-2043 treatment
20090417
24 Hr Peri-Procedural MI by Troponin T >X3 ULN
p=0.050
vs. Placebo
CMX-2043 treatment
20090417
SUPPORT-1 Adverse Events Summary
0.8 mg/kg
1.6 mg/kg
2.4 mg/kg
Placebo
(N = 36)
(N = 35)
(N = 36)
(N = 34)
Any AEs
7 ( 19.44%)
14 ( 40.00%)
11 ( 30.56%)
10 ( 29.41%)
Drug Related AEs
0 ( 0.00%)
3 ( 8.57%)
1 ( 2.78%)
2 ( 5.88%)
Serious AEs
1 ( 2.78%)
2 ( 5.71%)
1 ( 2.78%)
0 ( 0.00%)
AEs leading to Study
discontinuation
0 ( 0.00%)
1 ( 2.86%)
0 ( 0.00%)
0 ( 0.00%)
Deaths
0 ( 0.00%)
0 ( 0.00%)
0 ( 0.00%)
0 ( 0.00%)
Category
20090417
SUPPORT I: Limitations
 Serum marker elevations with elective PCI
have biochemical relevance for NME testing
vs. human apoptosis, however the clinical
relevance of these findings is unproven
20090417
SUPPORT I Primary Results: Conclusions
 SUPPORT I was a prospective, randomized,
multicenter Phase IIa dosing study of protection
from PCI-induced myonecrosis by CMX-2043
infusion
 All doses of CMX-2043 studied (0.8, 1.6 and 2.4
mg/kg) appeared safe in this population
 High dose (2.4 mg/kg) infusion of CMX-2043 was
associated with statistically significant reduction
of serum markers of myonecrosis and MI defined
by >3X elevation above ULN
 Results of SUPPORT I suggest the basis for
further study and a Phase III study design
20090417

similar documents