Slide 1: ALLSTAR: Intracoronary Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration
Intracoronary ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration (ALLSTAR): A Randomized, placebo - controlled, double - blind trial Timothy D. Henry, Dean J. Kereiakes, Glenn Kowalchuk, Frank Aguirre, Konstantinos Malliaris, Anthony DeMaria, Gary Francis, Thomas J. Povsic, Richard Schat
Slide 2: Disclosures
Disclosures Trial Sponsors : Capricor, Inc.; NIH/NHLBI (Phase I - 1RC3HL103356 ARRA grant ) Funded in part by California Institute for Regenerative Medicine (CIRM; Phase 2) Co - PIs Timothy D. Henry & Raj Makkar Steering Committee Anthony DeMaria, MD – Chair Gary S. Francis, MD Frank Aguirre, MD Tho
Slide 3: Introduction
Introduction • Previous trials have demonstrated potential benefit of stem cell therapy in patients with recent MI • Phase 1 data with autologous cardiosphere - derived cells (CDCs) demonstrated scar size reduction and evidence for myocardial regeneration • Allogenic CDCs (CAP - 1002) are equivalent
Slide 4: Rationale for Using CDCs to Treat Post MI Cardiomyopathy
Rationale for Using CDCs to Treat Post MI Cardiomyopathy Pathophysiology CDCs Oxidative/ nitrosative stress Anti - oxidative Inflammation Anti - inflammatory Apoptosis Anti - apoptotic Remodeling Anti - remodeling Loss of cardiomyocytes Regenerative • Diverse effects of CDCs support their potential
Slide 5: CADUCEUS: Phase I Autologous CDCs
CADUCEUS: Phase I Autologous CDCs • Cedars - Sinai & Johns Hopkins • Recent MI • LVEF 25 - 45% following successful PCI • 2:1 allocation to autologous CDCs or routine care • Dose escalation 12.5 - 25M • cMRI at baseline, 6, 12 months Scar Mass (g) Viable Mass (g) Makkar RR, et al., Lancet. 2012 Mall
Slide 6: ALLSTAR Trial Design
* Funded by CIRM ALLSTAR Trial Design * Funded by NIH ARRA RC3 Phase 1 DSMB Review Phase 2 (2:1)
Slide 7: Key ALLSTAR Eligibility Criteria
Key ALLSTAR Eligibility Criteria Inclusion Criteria • History of STEMI or NSTEMI w/in 12 mo • Successful PCI (TIMI flow = 3) in infarct related artery • LVEF < 45% • LV infarct size > 15% of LV mass in qualifying infarct - related region (by MRI core lab) • No further revascularization needed • Age
Slide 8: ALLSTAR Open Label Phase I Efficacy
ALLSTAR Open Label Phase I Efficacy 15% reduction in scar size at one year 4% improvement in EF at one year
Slide 9: ALLSTAR Phase II Efficacy Endpoints
ALLSTAR Phase II Efficacy Endpoints • Primary efficacy endpoint : % change from baseline in infarct size ( cMRI as a % of LV mass) at 12 months • Secondary efficacy endpoint : absolute and % change from baseline in LV structure and function, clinical function, and cardiac biomarkers at 6 and 12 mont
Slide 10: ALLSTAR Phase II Enrollment & Baseline Characteristics
245 pts screened 95 randomized to CDCs 47 randomized to PBO 90 pts followed matched (n=77); unmatched (n=13) 45 pts followed matched (n=45); unmatched (n=0) 103 excluded 5 not infused 90 infused 44 infused CAP - 1002 (N = 90) Placebo (N = 44) Sex, male 84.4% 86.4% Age [mean (SD)] 54.8 (11.25) 53.8 (
Slide 11: Interim Analysis
Interim Analysis • Pre - specified interim analysis – after all subjects observed ≥ 6 months – All data for 134 treated subjects (Primary Cohort, n=121; Exploratory Cohort, n=13) • Given low probability that treatment effect would be observed in primary 12 month efficacy analysis, all subjects were
Slide 12: Change in Scar Size by MRI
Change in Scar Size by MRI Matched Primary mITT Population p = 0.63 p = 0.39 p = 0.39 p = 0.63 Unmatched Exploratory CAP - 1002 & Placebo mITTs p = 0.22 p = 0.01
Slide 13: LV Volumes
LV Volumes “Matched” LVESV LVEDV p = 0.11 p = 0.52 p = 0.30 p = 0.86 “Unmatched” p = 0.004 p = 0.10 p = 0.0005 p = 0.009
Slide 14: NT-proBNP
NT - proBNP “Matched” p = 0.053 p = 0.16 “Unmatched” p = 0.47 p = 0.06
Slide 15: Overall Outcomes (all CAP-1002 vs placebo)
Overall Outcomes (all CAP - 1002 vs placebo, 6 months) Deltas from Baseline to 6 months. Post hoc analysis, Mann - Whitney tests, 2 - tailed Δ LVEDV Δ LVESV Δ NT - proBNP p = 0.0206 p = 0.0259 p = 0.0115
Slide 16: Safety and Clinical Events
Safety and Clinical Events Safety • No primary safety endpoint events were observed during the study • No significant treatment group difference in SAE rates Clinical Events (adjudicated) Clinical Events [n (%)] CAP - 1002 (N = 90) Placebo (N = 44) p - value Death 0(0.0) 0(0.0) -- Non - fatal MI 3 (
Slide 17: Conclusions
Conclusions • No significant difference in scar size based on 6 or 12 month MRI • Signs of improvement in LV volumes and BNP • Very low clinical events - favoring the treatment group • Challenges – Recruitment of patients with large anterior MI – MRI endpoint dropout and variability • To be investig
Slide 18: Acknowledgments
Acknowledgments • Cedars - Sinai Medical Center – R. Makkar & T. Henry (17)* • Linder Center for Research & Education – D. Kereiakes (11) • Prairie Education and Research – F. Aguirre (11) • Sanger Heart & Vascular Institute – G. Kowalchuk (10) • Scripps Green Hospital – R. Schatz (9)* • Minneapolis