Slide 1: PreSERVE-AMI: Randomized Trial of Intracoronary CD34+ Cells (NBS10) Post STEMI
PreSERVE-AMI: A Randomized, Double-Blind, Placebo Controlled Clinical Trial of Intracoronary Infusion of Autologous CD34+ Cells (NBS10) in Patients with Left Ventricular Dysfunction Post STEMI Arshed Quyyumi1, Dean Kereiakes2, David Shavelle3, Timothy Henry4, Ali Denktas5, Ahmed Abdel-Latif6, Catali
Slide 2: The PreSERVE AMI Study: Funding Sources & Disclosures
The PreSERVE AMI Study: Funding Sources & Disclosures Conflict of Interest Disclosures • Quyyumi: NeoStem Advisory Board member Funding Source • Study funded by NeoStem, Inc. 2
Slide 3: Background
Background • Recent meta-analysis of unselected bone marrow mononuclear cell therapy after STEMI suggest that there may be no impact on LVEF changes and MACE1 • Clinical studies evaluating the therapeutic potential of cells selected for CD34 expression have demonstrated a consistent favorable impact
Slide 4: PreSERVE Study Design
PreSERVE Study Design 4 DESIGN Randomized (1:1), Phase 2, double blind, placebo controlled trial in patients with acute STEMI and low LVEF PRIMARY ENDPOINTS • Incidence rates of SAEs and MACE • Change in myocardial perfusion (RTSS) measured quantitatively by gated SPECT MPI at 6 months KEY SECONDARY
Slide 5: PreSERVE: Eligibility
PreSERVE: Eligibility INCLUSION CRITERIA • Acute ST elevation myocardial infarction. • Stenting within 3 days of chest pain • LVEF ≤48% by CMR or ≤45% by SPECT after 4 days • Wall motion abnormality associated with the target lesion • NYHA heart failure class I, II or III. EXCLUSION CRITERIA • STEMI
Slide 6: PreSERVE Sites
PreSERVE Sites 6 Investigator Name Site Arshed Quyyumi Emory Alejandro Vasquez Heart Center Research Dean Kereiakes The Christ Hospital Marc Klapholz UMDNJ-Newark Kenichi Fujise Univ. Texas - Galveston Nandish Thukral Methodist San Antonio Gary Schaer Rush University Medical Center Robert Iwaoka Pre
Slide 7: PreSERVE: Study Protocol
PreSERVE: Study Protocol 7 1. Patient presents with chest pain + STEMI Day 1 2. Stenting and usual medical Rx Day 1 - 3 5. Patient Bone Marrow Harvested Day 4-9 6. CD34+CXCR4 + immunomagnetic separation Day 5-10 Day 6-11 7. Intracoronary injection: CD34+ Cells/Placebo 3. Enrolled if EF ≤ 48% CMR Day
Slide 8: PreSERVE-AMI patient flow
PreSERVE-AMI Screened (N = 281) • Patients with STEMI and successful stent placement • LVEF ≤ 48% by CMR or ≤ 45% by SPECT measured ≥ 4 days after stent Underwent BM Harvest (n = 96) CD34+ cells infusion (n = 78) CD34+ cells (NBS10; n = 100) Underwent BM harvest (n = 88) Placebo infusion (n = 83) Pl
Slide 9: Baseline Characteristics
Baseline Characteristics 9 Treated NBS10 (N=78) Placebo (N=83) P-value* Demographics Age; mean ± SD 57.1 ± 10.1 56.4 ± 10.1 0.65 Female; n (%) 12 (15%) 17 (20%) 0.4 Race; White, n (%) 56 (72%) 62 (75%) 0.87 CV Risk Factors Hypertension (%) 53 (68%) 56 (67%) 0.80 Diabetes (%) 27 (35%) 19 (23%) 0.1 Hy
Slide 10: PreSERVE Status
PreSERVE Status • One year follow-up completed for all subjects in December 2014 • Median follow-up time: 18 months • Primary endpoints and key secondary endpoints after all subjects completed 6 months follow-up (one year median follow-up) presented at AHA 10
Slide 11: PreSERVE: Cardiac Death
Preserve: Cardiac Death 11 P ro b abili ty o f sur v iv a l MEDIAN FOLLOW-UP: 18 MONTHS No treatment group deaths to date* mITT Population **P-value calculated using a z-test. ‡P-value calculated using log rank test * As of March 13, 2015 0% 1% 2% 3% 4% 5% 3.6% (N=3) 0% (N=0) Treatment N=78 Control
Slide 12: PreSERVE: Major Adverse Cardiovascular Events
PreSERVE: Major Adverse Cardiovascular Events 12 MACE= Death, MI, CHF Hospitalization, Revascularization Ctrl N=83 <14M N=47 >14M N=31 >20M N=15 Parameter Parameter Estimate (SE)* P-Value‡ Infused CD34+ Dose -1.11E-7 (5.769E-8) 0.055 ‡Multiple regression model with MACE modeled as a function of time
Slide 13: PreSERVE: Serious Adverse Events
PreSERVE: Serious Adverse Events 1.2 0.9 1.1 0.6 0.7 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Control <14M >14M >20M P ro p o rt io n o f e v e n ts (n o rma li z e d b y t o ta l s u b jects ) Tmt SAE frequency normalized by total subjects per group Control (N=83) Treatment (N=78) <14M (N=47) >14M (N=31) >20M (
Slide 14: PreSERVE: Hospitalization during Follow-up
PreSERVE: Hospitalization during Follow- up 14 160.5 165.6 164.4 167.5 167.6 Control N=83 <14M N=46 >14M N=29 >20M N=14 P = 0.04* P = 0.04* *P values based on two sample t- test using Satterthwaite method Tmt N=75 T im e ( d a y s ) A li v e an d O u t o f Hos p ita l Parameter Parameter Estimate (S
Slide 15: PreSERVE: Myocardial Perfusion
PreSERVE: Myocardial Perfusion • Improvement in clinically relevant endpoints not mirrored by change in SPECT perfusion • Results indicate that SPECT myocardial perfusion is not a suitable surrogate 15 SPECT Resting Total Severity Score (RTSS) Change from Baseline to 6 months (mITT) Placebo CD34 P-v
Slide 16: PreSERVE: Left Ventricular Ejection Fraction
4.9 4.1 3.1 5.8 10.2 PreSERVE: Left Ventricular Ejection Fraction Change from Baseline to 6 months (mITT) CMR (SPECT when unavailable) 16 Control (N=80) <14M (N=45) >14M (N=15) >20M (N=13) L V E F c h an g e fro m b a seli n e ( % ) P < 0.05* Tmt (N=73) Parameter Parameter Estimate (SE) P-Value CD34
Slide 17: PreSERVE: Infarct Size
PreSERVE: Infarct Size Change from Baseline to 6 months(CMR only; mITT) -24% -23% -16% -35% -41% -50% -40% -30% -20% -10% 0% 17 Control N=54 <14M N=28 >14M N=17 >20M N=7 P = NS for all dose groups vs control Influence of dose corrected for time to stent Parameter Parameter Estimate (SE) P-Value CD34
Slide 18: PreSERVE Sites
PreSERVE Sites 18 Investigator Name Site Arshed Quyyumi Emory Alejandro Vasquez Heart Center Research Dean Kereiakes The Christ Hospital Marc Klapholz UMDNJ-Newark Kenichi Fujise Univ. Texas - Galveston Nandish Thukral Methodist San Antonio Gary Schaer Rush University Medical Center Robert Iwaoka Pr
Slide 19: Thank you for your attention
Thank you for your attention 19
Slide 20: BACK UP SLIDES
BACK UP SLIDES 20
Slide 21: Time to Cardiac Death (ITT Population)
Time to Cardiac Death (ITT Population) 21 MEDIAN FOLLOW-UP: 18 MONTHS Pro b a b ilit y of surv iva l Days since informed consent 200 400 600 800 1000 1200 P=0.008‡ ‡P-value calculated using log rank test ‡ P-value calculated using log rank test
Slide 22: Time to First Hospitalization (mITT)
Time to First Hospitalization (mITT) 22 MEDIAN FOLLOW-UP: 12 MONTHS Pro b a b ilit y of b e in g a liv e a n d o u t of h o sp ita l >20M >14M Control