Transcript SUPPORT-1

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.
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Conflict of Interest
 Clinical Advisory Board, Ischemix
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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%
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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)
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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)
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Safety and Efficacy of CMX-2043 in
Subjects Undergoing PCI and PeriOperative Reperfusion Treatment
The SUPPORT 1 Study
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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
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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
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SUPPORT-1 Sites and Investigators
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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
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SUPPORT-1 Baseline Characteristics
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SUPPORT I: Arteries Stented Per Rx Group
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Primary Endpoint:
24 Hr CK-MB Change from Baseline
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24 Hr CK-MB Change From Baseline (ng/mL)
p = 0.05
p=0.05
vs. Placebo
CMX-2043 treatment
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24 Hr Troponin T Change from Baseline
CMX-2043 treatment
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24 Hr Peri-Procedural MI by CK-MB >X3 ULN
p=0.024
vs. Placebo
CMX-2043 treatment
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24 Hr Peri-Procedural MI by Troponin T >X3 ULN
p=0.050
vs. Placebo
CMX-2043 treatment
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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
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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
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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
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