A Prospective, Double-Blind, Randomized, Placebo-controlled Clinical Trial of Intracoronary Infusion of Mesenchymal Precursor Cells (MPC) in the Treatment of Patients With ST-Elevation Myocardial Infarction
Phase: PHASE2
Conditions: Acute Myocardial Infarction
Sponsor: Mesoblast, Inc.

 
Official Title: 
A prospective, double blind, randomized, placebo-controlled clinical trial of 
intracoronary infusion of immunoselected, bone marrow-derived Stro3 
mesenchymal precursor cells (MPC) in the treatment of patients with 
STelevation myocardial infarction 
NCT Number: 
 
NCT01781390 
 
Document Date: 
 
Protocol Version 10: 04 May 2017 
 
 
 
 
 
 
 

The AMICI Trial 
 
 
Allogeneic Mesenchymal precursor cell Infusion  
In myoCardial Infarction  
 
A prospective, double blind, randomized, placebo-controlled clinical trial of intracoronary 
infusion of immunoselected, bone marrow-derived Stro3 mesenchymal precursor cells (MPC) in 
the treatment of patients with ST-elevation myocardial infarction 
 
Protocol Number ANG.AMI-IC001 
 
Protocol Version: 10.0 
(Applicable to all participating countries except The Netherlands and Sweden) 
 
Protocol Date:  04 May 2017 
 
Replaces:  Protocol Version 9.0 (October 11, 2016) 
EudraCT Number: 2010-020497-41 
 
 
 
 
Sponsor: 
Mesoblast, Inc. 
 
505 Fifth Ave., 3rd Floor 
 
New York, NY10017 
 
USA 
 
Confidentiality Statement 
 
The confidential information in this document is provided to you as an investigator, potential 
investigator or consultant for review by you, your staff and applicable Independent Ethics 
Committee/Institutional Review Board (IEC/IRB). It is understood that the information shall not 
be disclosed to others without written authorization from Mesoblast Inc. except to the extent 
necessary to obtain informed consent from those persons to whom the drug may be administered. 
 
 

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TABLE OF CONTENTS 
 
 
LIST OF TABLES .............................................................................................................6 
LIST OF FIGURES ...........................................................................................................6 
1. 
GENERAL INFORMATION ....................................................................................7 
1.1 
Study Administrative Structure ........................................................................7 
1.2 
Sponsor Approval Page ....................................................................................9 
1.3 
Investigator Approval Page ............................................................................10 
1.4 
Contacts in Case of Emergency ......................................................................11 
1.5 
Study Synopsis................................................................................................12 
1.6 
Assessments and Procedures ..........................................................................24 
1.7 
Glossary of Abbreviations ..............................................................................28 
2. 
INTRODUCTION ....................................................................................................31 
2.1 
Myocardial Infarction:  The clinical risk remains high post the acute event ..31 
2.2 
Allogeneic Mesenchymal Cells ......................................................................32 
 
33 
 
.33 
 
34 
 
 
35 
 
 
36 
2.4 
Cardiac Magnetic Resonance Imaging (cMRI):  Assessment of Myocardial  
Ischemia, Viability, and Microvascular Obstruction ......................................39 
2.4.1 
Myocardium at Risk (Area of Ischemia) .........................................39 
2.4.2 
Infarct Size .......................................................................................39 
2.4.3 
Infarct Size to Area at Risk Ratio ....................................................40 
2.4.4 
Microvascular Obstruction (MVO)..................................................40 
 
40 

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2.6 
Rationale .........................................................................................................41 
3. 
STUDY HYPOTHESIS ............................................................................................43 
4. 
STUDY OBJECTIVES ............................................................................................43 
4.1 
Primary Objective ...........................................................................................43 
4.2 
Secondary Objectives .....................................................................................43 
4.3 
Study Design ...................................................................................................44 
5. 
SELECTION AND WITHDRAWAL OF SUBJECTS .........................................46 
 
47 
5.1.1 
Inclusion Criteria .............................................................................47 
5.1.2 
Exclusion Criteria ............................................................................48 
5.2 
Subject Withdrawal ........................................................................................49 
5.3 
Withdrawal Procedures ...................................................................................49 
5.4 
Early Termination of Study ............................................................................50 
5.4.1 
Data Safety and Monitoring Board Overview .................................50 
5.4.2 
Executive Steering Committee ........................................................51 
5.4.3 
Clinical Event Committee ................................................................51 
6. 
STUDY PROCEDURES ..........................................................................................52 
6.1 
Study Visits .....................................................................................................52 
6.1.1 
Enrollment and Eligibility................................................................52 
6.2 
Study Monitoring ............................................................................................60 
6.3 
Follow-up/Lost to Follow-up ..........................................................................60 
7. 
STUDY TREATMENTS ..........................................................................................61 
7.1 
Study Infusion Continuation and Halt Guidelines ..........................................61 
7.2 
Definition of Adverse Event of TIMI 1 or 0 flow ..........................................61 
7.3 
Investigational Agent ......................................................................................61 
7.3.1 
Investigational Agent Labeling ........................................................61 
 
62 
 
62 

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7.3.4 
Investigational Agent/Control Agent Handling and Accountability62 
7.4 
Control Agent .................................................................................................62 
7.4.1 
Description of Control Agent...........................................................62 
7.5 
Blinding and Randomization ..........................................................................63 
7.5.1 
Un-blinding Procedure .....................................................................64 
7.5.2 
Concomitant Therapy.......................................................................64 
8. 
ASSESSMENT OF EFFICACY ..............................................................................64 
8.1 
Primary Efficacy Endpoint .............................................................................64 
8.2 
Secondary Efficacy Endpoints ........................................................................65 
8.3 
Clinical Endpoints ..........................................................................................66 
9. 
ASSESSMENT OF SAFETY...................................................................................67 
9.1 
Safety Endpoints .............................................................................................67 
9.2 
Adverse Events ...............................................................................................68 
9.3 
Definitions ......................................................................................................68 
9.4 
Relationship to Study Product ........................................................................69 
9.5 
Relationship to Study Procedure ....................................................................69 
9.6 
Severity of Adverse Events ............................................................................69 
9.7 
Procedures for Adverse Event Reporting .......................................................70 
9.8 
Protocol- Specified Serious Adverse Events ..................................................70 
9.9 
Reporting Requirements .................................................................................71 
9.10 
Pregnancy Reporting ......................................................................................73 
10. ASSESSMENT OF FEASIBILITY ........................................................................73 
10.1 
Feasibility Endpoint ........................................................................................73 
11. STATISTICAL CONSIDERATION ......................................................................73 
11.1 
Introduction .....................................................................................................73 
11.2 
Statistical Methods ..........................................................................................73 
11.3 
General Considerations ...................................................................................74 
11.4 
Analysis Populations ......................................................................................74 

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11.4.1 
Safety Population .............................................................................75 
11.4.2 
Intent-to-Treat Population ................................................................75 
11.4.3 
Per-Protocol Population ...................................................................75 
11.4.4 
Full Analysis Population ..................................................................75 
11.5 
Determination of Sample Size ........................................................................75 
11.6 
Background, Demographic and Concomitant Medications ............................75 
11.7 
Protocol Deviations ........................................................................................75 
11.8 
Efficacy and Feasibility Analyses ..................................................................76 
11.9 
Safety Analyses ..............................................................................................76 
11.10 Timing of Planned Analyses ..........................................................................77 
12. QUALITY CONTROL AND QUALITY ASSURANCE .....................................77 
13. REGULATORY OBLIGATIONS ..........................................................................77 
13.1 
Institutional Review Board (IRB)/ Ethics Committee (EC) Approval ...........77 
13.2 
Protocol Compliance ......................................................................................78 
13.3 
Changes to the Protocol ..................................................................................78 
13.4 
Informed Consent ...........................................................................................78 
13.5 
Source Documents ..........................................................................................78 
13.6 
Case Report Form Completion .......................................................................78 
13.7 
Financial Disclosures ......................................................................................79 
13.8 
Termination of the Study ................................................................................79 
13.9 
Retention of Essential Documents ..................................................................79 
13.10 Confidentiality ................................................................................................79 
14. REFERENCES .........................................................................................................80 
 
 
 

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LIST OF TABLES 
Table 1:  Emergency Contact Information.........................................................................11 
Table 2:  Schedule of Assessments and Procedures ..........................................................24 
.33 
  
38 
 
 
LIST OF FIGURES 
Figure 1:  Cellular and Molecular Mechanisms Follow Myocardial Infarction ................32 
Figure 2:  Randomization/Withdrawal...............................................................................49 
 
 
 

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1. 
GENERAL INFORMATION 
1.1 
Study Administrative Structure  
 
Protocol Title: A prospective, double blind, randomized, placebo-controlled clinical trial of 
intracoronary infusion of immunoselected, bone marrow-derived Stro3 mesenchymal precursor 
cells (MPC) in the treatment of patients with ST-elevation myocardial infarction 
 
 
Protocol Number: 
 
ANG.AMI-IC001 
 
Protocol Version: 
 
10.0 
 
Protocol Date:  
 
 
04 May 2017 
 
Short Title 
AMICI: Allogeneic Mesenchymal precursor cell Infusion  
in myoCardial Infarction  
Study Sponsor 
Mesoblast, Inc. 
505 Fifth Ave, 3rd floor 
New York , NY10017 
USA 
Phone:  212-880-2060 
Fax:212-880-2061 
EU Legal Representative 
Mesoblast UK Limited 
5 New Street Square 
London, EC4A 3TW 
United Kingdom 
Australian Sponsor 
Mesoblast Limited 
Level 38, 55 Collins St. 
Melbourne, VIC 3000 
Australia 
Phone:   +61 3 9639 6036 
Fax:  +61 3 9639 6030 
Sponsor’s Responsible 
Medical Officer 
, MD, MSc 
Sponsor’s Contact 
, MD, MSc 
Data Safety Monitoring Board 
 
, M.D.  

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Coordinating Investigator 
, MD, FACC 
 
 
 
 
United States of America 
Ph: 
 
Fax: 
 
 
MPC Manufacturer and 
Supplier 
 
 
 
 
USA 
 
 
 
 
 
Belgium 
 
 
 
 
Contract Research 
Organization 
 
 
 
 
USA 
Phone: 
 
Fax: 
 
Central Clinical Laboratories 
 
 
 
 USA 
 
 
USA 
Imaging Core Lab 
 
 
 
 
USA 
Phone:
 
Fax: 
 
 
 

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1.2 
Sponsor Approval Page 
 
Allogeneic Mesenchymal precursor cell Infusion  
in myoCardial Infarction  
 
 
A prospective, double blind, randomized, placebo-controlled clinical trial of intracoronary 
infusion of immuno-selected bone marrow-derived Stro3 mesenchymal precursor cells (MPC) in 
the treatment of patients with ST-elevation myocardial infarction 
 
 
Protocol Number:  
 
ANG.AMI-IC001 
 
Protocol Version: 
 
10.0 
 
Protocol Date:  
 
04 May 2017 
 
EudraCT Number: 
 
2010-020497-41 
 
Sponsor:  
 
 
Mesoblast, Inc. 
 
 
 
 
505 Fifth Ave., 3rd Floor  
 
 
 
 
New York, NY 10017 
USA 
 
 
 
Mesoblast, Inc. Approval: 
 
 
 
___________________________ 
 MD, MSc 
 
 
 

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1.3 
Investigator Approval Page 
 
Allogeneic Mesenchymal precursor cell Infusion  
in myoCardial Infarction  
 
 
A prospective, double blind, randomized, placebo-controlled clinical trial of intracoronary 
infusion of immuno-selected bone marrow-derived Stro3 mesenchymal precursor cells (MPC) in 
the treatment of patients with ST-elevation myocardial infarction 
 
Protocol Number:  
 
ANG.AMI-IC001 
 
Protocol Version: 
 
10.0  
 
Protocol Date:  
 
04 May 2017 
 
Sponsor:  
 
 
Mesoblast, Inc. 
 
 
 
 
505 Fifth Ave., 3rd Floor  
 
 
 
 
New York, NY 10017 
USA 
 
Investigator’s Name: 
 
 
Address: 
 
 
Telephone Number: 
 
 
I, the Site Investigator named above, by signing below acknowledge the receipt of this 
protocol in its entirely and agree to conduct this study according to this protocol, Good 
Clinical Practices and all applicable code of federal regulations (CFRs) and guidelines. 
 
 
___________________________ 
___________________________ 
_______________ 
Investigator’s Printed Name 
Signature 
 
 
 
Date  
 

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1.5 
Study Synopsis 
Protocol Title 
A prospective, double blind, randomized, placebo-controlled 
clinical trial of intracoronary infusion of immunoselected, bone 
marrow-derived Stro3 mesenchymal precursor cells (MPC) in the 
treatment of patients with ST-elevation myocardial infarction 
Sponsor 
Mesoblast, Inc. 
505 Fifth Ave., 3rd Floor 
New York, NY 10017 
USA 
Study Phase 
2 
Investigators and 
Clinical Sites 
Approximately 25 clinical sites 
Indication 
De novo anterior wall myocardial infarction due to a lesion or 
occlusion of the left anterior descending (LAD) coronary artery. 
Study Hypothesis 
MPCs when administered intracoronary immediately after 
successful PCI with stenting in patients with first time acute 
anterior STEMI will result in amelioration of the early post-event 
inflammatory response and subsequent fibrotic scarring as well as 
promote the process of neo-angiogenesis in tissue where an 
ischemic condition exists or is developing.  The net result will be: 
 decreased infarct size by short term protection of at-risk 
myocardium 
 increased long term salvage of myocardium resulting in 
decreased adverse left ventricular (LV) remodeling. 
Objectives 
Primary Objective: 
 To determine the safety and feasibility of intracoronary 
allogeneic, immuno-selected, bone marrow-derived Stro3 
MPC delivery in the treatment of subjects with STEMI 
undergoing PCI of the LAD coronary artery. 
Secondary Objectives: 
 To explore a dose-response effect of intracoronary 
delivered MPC in the treatment of subjects with an anterior 
wall STEMI on LV remodelling, microvascular 
obstruction, and the relationship between time from onset 
of ischemic symptoms to primary PCI. 
 To determine the effect of intracoronary delivery of MPC 
on infarct size reduction in the treatment of subjects with 
STEMI undergoing primary  PCI of the LAD coronary 
artery. 
 
 
 
 
 

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Study Design 
This is a prospective, double-blind, randomized, placebo-
controlled study that will enroll approximately 105 subjects with 
de novo anterior STEMI due to a lesion involving LAD coronary 
artery who undergo primary PCI at approximately 25 clinical 
study sites.  
 
This study will compare two doses of MPCs and a placebo control 
group.  Study subjects will be randomly assigned in 1:1:1 fashion 
to receive either 12.5 Million or 25 Million MPCs or placebo 
(saline). Each group will have approximately 35 subjects. 
 
Potential subjects will be approached by a site investigator prior to 
PCI and must sign an informed consent form before initiation of 
the cardiac catheterization procedure in order to participate in this 
trial.  Following successful and uneventful PCI and stenting of the 
culprit LAD lesion, the subjects will be randomized.  The 
randomization and treatment assignment will be obtained from an 
interactive voice-response system (IVRS/interactive web response 
system (IWRS)). The following stratification for duration of 
cardiac ischemia will be performed to ensure balanced 
randomization across the treatment groups: 
 ≤2 hours 
 >2 hours to ≤6 hours 
 >6 to ≤12 hours. 
 
Eligible subjects will receive intracoronary delivery of the 
assigned treatment infused via a microcatheter into the stented 
culprit artery.  The subjects randomized to MPCs will be infused 
at an infusion rate of 2 ml/min over approximately 60 minutes, 
including line flush [2.5x105 MPCs/min (12.5 M), 5.0x105 
MPCs/min (25 M)].  The subjects randomized to placebo will be 
infused placebo solution at 2 mL/min over approximately 
60 minutes, including line flush (0 MPCs/min).  The MPC product 
(12.5M and 25M MPCs) and the placebo solution will be diluted 
in 100mL 0.9% saline solution prior to infusion.  The Sponsor will 
provide all sites with blinded treatment cryovials, which contain 
the different doses of MPCs or placebo solution.   
 
An intracoronary (IC) bolus of glyceryl trinitrate (GTN)/ 
nitroglycerin (NTG) (100-200 mcg) should be administered (blood 
pressure permitting) prior to the Thrombolysis in Myocardial 
Infarction (TIMI) flow assessment during the investigational agent 
infusion period as well as after completion of the investigational 
agent infusion and immediately prior to the final coronary 

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angiographic imaging. 
 
After approximately 50% of the intracoronary infusion of 
investigational agent has been completed, an angiographic 
determination of coronary flow will be performed.  The following 
guidelines will be used to determine if the remaining 
investigational agent should be infused: 
 The study infusion should be continued if either TIMI 2 or 
TIMI 3 flow is present in the absence of ALL of the 
following: 
o Sustained hypotension not responsive to fluid 
administration; 
o Clinical signs/symptoms indicating an acute 
cerebrovascular event; 
o Re-elevation of ST-segments if previously resolved with 
PCI; 
o Onset of the subject’s symptoms of myocardial ischemia 
unresponsive to appropriate interventions; 
o Two episodes of sustained ventricular tachycardia 
(VT)/ventricular fibrillation (VF) requiring cardioversion 
(infusion can continue if a single episode of sustained 
VT/VF requiring cardioversion occurred). 
 
If for any reason, the site investigator withdraws a randomized 
subject prior to infusion of the investigational agent, the reason for 
early termination and data from the screening visit will be entered 
into the eCRF by the study site.  The subject will not remain in the 
study.  If for any reason, a subject’s study infusion is halted due to 
safety considerations, the subject will remain in the study. A 
subject who prematurely withdraws from the study, post-study 
infusion, will remain in the study.   
 
Evaluation for safety will be performed for up to 24 months post 
infusion. Subjects will undergo cardiac magnetic resonance 
imaging (cMRI) and 2-D echocardiography (ECHO), Holter 
monitoring, clinical evaluation and laboratory testing. 
 
cMRI, ECHO monitoring will be performed at 2-7 days post 
infusion of  study agent (MPCs or Placebo), as well as at Day 30 
and at Month 6 after the procedure. Holter monitoring will be 
performed at 14 and 30 days, 3 and 6 months after the procedure. 
Clinical evaluation and laboratory testing will be performed at 6, 
12, 18 and 24 hours post infusion of study agent (MPCs or 
Placebo), during the index hospitalization as well as at 14 and 

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30 days and 3, 6, 12, 18 and 24 months after the procedure as 
outlined in Table 2 Schedule of Assessments and Procedures. 
 
An independent Data Safety Monitoring Board (DSMB) will 
review all relevant acute peri-procedural data, serious adverse 
events (SAE),other adverse events (AE), and efficacy data (if 
requested) periodically dependent on subject enrollment, and 
advise the Executive Steering Committee (ESC) regarding the 
progression of the study.  
 
The ESC will consist of the Coordinating Investigator, site 
investigators and representatives of and advisors to the Sponsor. 
 
A Clinical Events Committee (CEC) will review appropriate 
source documents and adjudicate (blinded per a priori procedure) 
all major adverse cardiovascular and cerebrovascular events  
(MACCE) defined as cardiovascular death, non-fatal myocardial 
infarction, non-fatal stroke, or cardiac hospitalization due to heart 
failure.  Target vessel (or other vessel) revascularization post 
index cardiac catheterization and new or worsening heart failure 
during the index hospitalization will be tracked as “Adverse 
Events of Special Interest” rather than MACCE. 
 
Subjects, Site personnel, Investigators will remain blinded until 
after all safety follow-up is completed. The DSMB may choose to 
be unblinded. 
 
The DSMB safety reviews to assess the frequency of total 
MACCE will be performed after the initial 15, 30, 60, and 
90 subjects have been observed at Day 30 post the index cardiac 
catheterization.  
 
The final safety analysis will be performed at 24 months for all 
patients.    
Population 
Subjects age 18 and above who have been successfully treated 
within 12 hours of the onset of ischemic symptoms with standard 
care for a de novo STEMI (PCI and stent placement) involving the 
LAD coronary artery.   
Efficacy Endpoints 
Primary Efficacy Endpoint: 
 The primary efficacy endpoint is the change in LV end-
systolic volume (LVESV) as assessed by cardiac MRI 
from baseline to 6 months post investigational agent 
infusion in each MPC treatment group compared with the 
Placebo group. 

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Secondary Efficacy Endpoints: 
 The change in LVESV as assessed by 2D-
echocardiography from baseline to 6 months post 
investigational agent infusion. 
 The change in relative infarct size as assessed by late 
contrast enhancement MRI (% infarct volume/total LV 
tissue volume) from baseline to 6 months post 
investigational agent infusion. 
 Additional functional efficacy endpoints will be assessed 
with the following diagnostic studies: 
o Cardiac MRI at 2-4 days, 30 days and at Month 6.  
o LVEF 
o LVESV 
o LVEDV 
o Left ventricular wall thickness and thickening in all 
segments including infarct area 
o Regional wall motion score 
o Myocardial microvascular obstruction measured as 
reduced signal intensity in the region of interest 
o MI size measured in the region of interest as late 
contrast enhancement 
o Myocardial salvage index 
o 2D echocardiogram at 2-4 days, 30days and at Month 6. 
o LVEF  
o LVESV 
o LVEDV 
o Cardiac dimensions (LVESD/ LVEDD) 
o Regional wall motion score index 
 If there is no difference between the MPC groups (using a 
test with alpha= 0.1) in the effect on LVESV then the 
pooled MPC group will be compared to the Placebo group 
for all functional parameters. 
o A subset analysis that corresponds to the stratification 
used during randomization will be performed. 
Stratification will be based on the following categories 
defined as time from onset of AMI symptoms to PCI: 
o 
≤2 hours  
o 
>2 to ≤6 hours  
o 
>6 to ≤12 hours. 
 In addition, a subset analysis will be evaluated at the 
following ischemia duration time points: 
o ≤6 hours  
o >6 to ≤12 hours  
 

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 NT-Pro-BNP serum levels (as a biomarker for heart failure) 
at baseline, days 2-4 and 30,  and months 3, 6, 12 and 24 
 Score changes for TIMI Flow Grade and TIMI Myocardial 
Perfusion Grade assessments at the following day 0 time 
points: 
o pre-PCI,  
o immediately post-PCI,  
o after approximately 50% of intracoronary infusion 
of investigational agent, 
o at completion of intracoronary infusion of 
investigational agent.   
Safety Endpoints 
All safety end points will be assessed from subject randomization 
through up to 24 months post investigational agent infusion: 
 SAE /AE rates 
 Occurrence of MACCE events including: 
o 
Cardiovascular death 
o 
Non-fatal myocardial infarction 
o 
Non-fatal stroke 
o 
Cardiac hospitalization due to heart failure 
 Target vessel (or other vessel) revascularization post index 
cardiac catheterization and new or worsening heart failure 
during the index hospitalization will be tracked as 
“Adverse Events of Special Interest”. 
 Total number of subjects with documented ventricular 
arrhythmia (sustained and non-sustained VT/VF) 
throughout the study period. 
 Angina pectoris as defined by Canadian Cardiovascular 
Society (CCS) clinical clarification. 
 New York Heart Association (NYHA) Class. 
 Telemetry/48 hour Holter monitoring (during hospital 
admission and at 14 and 30 days, 3 and 6 months follow-up 
time points) with assessment of occurrence of ventricular 
arrhythmia.  
 TIMI Flow Grade and TIMI Myocardial Perfusion Grade 
following intracoronary infusion of the MPC cell solution 
compared with placebo 
 Physical examinations, monitoring of vital signs (heart 
rate, respiratory rate, BP, and temperature). 
 Results of clinical laboratory tests (hematology, serum 
chemistry, inflammatory markers), and immunogenicity 
assays; (flow cytometry Class I and Class II HLA percent 
reactivity % with specificity, antibovine and antimurine 
antibody analysis). 

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AE will be collected after a subject has been randomized. The AE 
will be graded according to the protocol as “mild”, “moderate”, 
“severe” and will be classified with the Medical Dictionary for 
Regulatory Activities. 
 
An independent DSMB will review all safety and relevant clinical 
data at regular intervals in accordance with their charter. Based on 
its findings, the DSMB will make recommendations regarding 
study continuation, enrollment and/or study modification(s). 
Feasibility Endpoint 
Feasibility of the infusion of the investigational agent will 
monitored by measurement of TIMI flow and perfusion 
measurements prior to, during (after approximately 50% of total 
investigational agent volume infused) and following the 
investigational agent infusion after successful PCI and stenting.   
Clinical Endpoints 
Clinical Endpoints will be assessed throughout the index  
hospitalization as well as at outpatient visits at 14 and 30 days, and 
at 3, 6, 12, 18 and 24 months after the index cardiac 
catheterization procedure, including: 
 Occurrence of MACCE including: 
o Cardiovascular death 
o Non-fatal myocardial infarction 
o Non-fatal stroke 
o Cardiac hospitalization due to heart failure 
 Target vessel (or other vessel) revascularization post index 
cardiac catheterization and new or worsening heart failure 
during the index hospitalization will be tracked as 
“Adverse Events of Special Interest”. 
 Total number of subjects with documented ventricular 
arrhythmia (sustained and non-sustained VT/VF) 
throughout the study period. 
 Angina pectoris as defined by Canadian Cardiovascular 
Society (CCS) clinical clarification. 
 Functional status will be classified by the NYHA criteria. 
Planned Analysis of 
Efficacy and Safety 
 
The primary efficacy analysis for LVESV will be performed using 
cMRI collected data. The secondary efficacy analyses for LVESV 
will be performed using ECHO data alone, as well as ECHO data 
as a substitute for missing cMRI data at baseline and/or at 
Month 6.   
 
In the latter case, a regression equation will be determined 
between measurements for LVESV-cMRI and LVESV-ECHO 
over a range of values. Whenever appropriate and based on 
LVESV-ECHO values generated using the regression equation, a 
LVESV-ECHO “corrected” value will be determined and used as 

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a replacement for missing value for LVESV-cMRI. 
 
When all enrolled subjects have completed the study through Visit 
9 (Month 6), an unblinded analysis of the safety and primary and 
secondary efficacy endpoints will be conducted.  
 
The primary and secondary efficacy analyses will be performed 
using data collected through Visit 9 (Month 6).  Safety analyses 
will be performed on all available data through Visit 12 
(Month 24) at the time of conduct of the efficacy analysis.  In 
addition, the final safety analysis will be performed at 24 months 
for all patients. 
 
No additional efficacy data will be collected beyond Visit 9 
(Month 6) except for cardiac biomarkers.   
 
 
Blinded Study Personnel and Participants 
Subjects, Site personnel, Investigators will remain blinded until 
after all safety follow-up is completed. The DSMB may choose to 
be unblinded. 
 
Unblinded Study Personnel 
Pre-specified unblinded clinical operations and biometrics team 
members at both the vendor and sponsor will have access to the 
unblinded efficacy results.  
 
These pre-specified unblinded team members will be identified 
prior to the analysis being conducted and they will not have any 
operational responsibility for the conduct of the study.  
 
An independent unblinded statistician from 
 will support 
the DSMB by providing Open and Closed Reports to the DSMB 
independent statistician based on the best available data and other 
information to the DSMB. 
Inclusion Criteria 
Subjects will be entered into this study only if they meet ALL of 
the following criteria: 
1. Willing and able to understand and sign the Informed 
Consent Form (ICF). 
2. Males or females > 18 years. 
3. Clinical symptoms consistent with AMI (pain, etc.) for a 
maximum of 12 hours from onset of symptoms to 
completion of PCI. 
4. De novo anterior AMI 
 
 

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5. Successful revascularization of the culprit lesion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6. If a female subject is of childbearing potential (i.e. not 
amenorrheic for 12 or more months and/or not surgically 
sterile), the subject must be willing to use a highly 
effective method of contraception (oral, injectable or 
implanted hormonal methods of contraception, placement 
of an intrauterine device [IUD] or intrauterine system 
[IUS], condom or occlusive cap with spermicidal 
foam/gel/film/cream/suppository, male sterilization, or true 
abstinence) for at least 16 weeks after investigational agent 
infusion. 
7. Must be willing and able to return for required follow-up 
visits. 
Exclusion Criteria 
 
 
 
 
 
Subjects will not be enrolled into this study if they meet ANY of 
the following criteria: 
1. Prior MI, known cardiomyopathy, or hospital admission 
for heart failure (HF). 
2. Significant valvular disease (mitral or aortic valve 
regurgitation 3/4 classification as defined by ESC/ACC 
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3. Unsuccessful revascularization of culprit artery defined as 
TIMI 1 or 0 flow or residual diameter stenosis of ≥ 20% by 
on line QCA analysis. 
4. Need for staged treatment of coronary artery disease, or 
other interventional or surgical procedures to treat heart 
disease 
 
 
 
 
 
 
 
 
 
 
 
  
5. Cardiogenic shock or hemodynamic instability within 
24 hours prior to randomization, 
 
 
 
 
 
 
 
 
 
 
 
8. Prior PCI involving the LAD. 
9. Malignancy within last 3 years from screening. The subject 
has had an active malignancy, within the past 3 years 
except for cervical carcinoma in situ or non-melanoma skin 
cancer that has been definitively treated. 
 
11. Pacemaker, ICD or any other contraindication for cMRI.  
This is inclusive of patients with an MRI compatible 
device that was implanted prior to the potential qualifying 
event. 
 
 
 
 
 
 
 
 
 
15. Known hypersensitivity to any radiographic contrast  
16. Known hypersensitivity to dimethyl sulfoxide (DMSO), 

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18. Prior participation in any other investigational drug trial in 
the past 30 days.  
19. Pregnant or lactating women. 
 
 
 
 
 
 
Number of Treatment 
Arms 
 
Eligible subjects will be randomized to one of three (3) parallel 
treatment arms:  one of two (2) doses of investigational MPC 
agent or (saline) control. Subjects randomized to MPC product 
will be treated with either 12.5 million or 25 million cell dose. 
Investigational Agent 
The investigational MPC product is STRO-3 selected allogeneic 
MPCs, which are derived from adult bone marrow mononucleated 
cells that are culture-expanded and subsequently cryopreserved.  
 
  
Route of 
Administration 
All subjects will receive investigational agent or placebo, 
suspended/dissolved in 100 mL 0.9% saline via intracoronary 
infusion following successful primary PCI. 
Duration of Treatment 
Subjects will receive treatment post successful PCI and stenting of 
the culprit LAD lesion. 
Follow up Schedule 
Each subject will be followed for up to 2 years after study 
intervention and will have assessments at screening, during study 
procedure, post procedure during hospitalization, 14 and 30 days, 
and again at 3, 6, 12, 18, and 24 months after intracoronary study 
treatment infusion.  Refer to Table 2 Schedule of Assessments and 
Procedures. 
Statistical Analysis 
AE will be summarized descriptively by treatment group, using 
the incidence and frequency of subjects reporting any AE. The AE 
will be graded according to the protocol as “mild”, “moderate”, 
“severe” and will be classified with the Medical Dictionary for 
Regulatory Activities. 
 
All treatment-emergent AE (TEAE) will be presented by severity 
grade and by relationship to study therapy.  Vital signs and clinical 
laboratory data will be summarized descriptively (mean, median, 
standard deviation, minimum, maximum) overall, and by 
treatment group. In addition, clinically significant changes in vital 

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signs, laboratory parameters, and physical examination findings 
will be reported as appropriate and summarized. 
 
The following stratification for duration of cardiac ischemia will 
be performed to ensure balanced randomization across the 
treatment groups: 
 ≤2 hours 
 >2 hours to ≤6 hours 
 >6 to ≤12 hours 
To detect a change from baseline to Month 6 treatment effect of 
10.0 ml for LVESV (SD 14 ml), 
 
 as 
well as published clinical data1- 3, 58, 59, with a two-sided 5% 
significance level and a power of  80%, a sample size of 
105  subjects will be necessary, given the observed dropout rate of 
approximately 4%. Of these, approximately 70 will receive MPCs 
(35 to receive 12.5 M MPC and 35 to receive 25M MPC) and 
35 will receive placebo and act as control subjects.  

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f. 
Hepatic Function Profile (total protein, albumin, total bilirubin, direct bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphatase) 
g. Urine Pregnancy testing  at screening; serum pregnancy testing at follow-up study visits 
h. Target Day 3 (+/- 1 day) post study  infusion 
i. 
Performed daily 
j. 
During infusion of the Investigational Agent, TIMI flow and perfusion measurements should be evaluated and recorded prior to IA infusion, when 
approximately 50% of the Investigational Agent has been infused, and immediately post investigational agent infusion. 
k. AE/SAE assessments should be collected from time of randomization 
l. 
12 lead ECG should be measured on Day 2 and prior to hospital discharge 
m. 2D echo will be performed through 6 month follow-up period only. 2D echo will be performed without contrast 
n. For subjects that receive Investigational agent and discontinue prior to Visit 9 (Month 6) cardiac MRI will not  be obtained as part of the early termination 
visit. 
o. Only for subjects that receive Investigational agent and discontinue prior to Visit 10 (Month 12) 
p. cMRI will be performed through 6 month follow-up period only. Please refer to the study imaging manual for details on MRI contrast agents. 
q. To be performed only if all inclusion/exclusion criteria are adequately satisfied.  
r. 
An ET visit will include the following tests: Physical examination, record of concomitant medications, vital signs measurement, 12-lead ECG, basic 
metabolic profile, non-fasting lipid profile, hs C-reactive protein, hepatic function profile, CBC with differential and platelets, Flow cytometry anti-HLA 
Class I and Class II antibodies for subjects discontinued prior to visit 10 (Month 12), Anti-murine and Anti-bovine antibodies, NT-Pro BNP, serum 
pregnancy testing, Canadian Cardiovascular society Angina Classification , NYHA classification and NYHA classification. cMRI and ECHo are not 
required at an ET visit.   
  
 

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1.7 
Glossary of Abbreviations 
ACC 
American College of Cardiology 
AE  Adverse event 
ALT  Alanine aminotransferase 
AMI  Acute myocardial infarction 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
BLA 
Biologics license application 
BMI 
Body mass index 
BP  Blood Pressure 
BUN 
Blood urea nitrogen 
CABG 
Coronary artery bypass graft 
CBC 
Complete blood count 
CCS 
Canadian Cardiovascular Society 
CEC 
Clinical Events Committee 
CHF 
Congestive heart failure 
CFR 
Coronary flow reserve 
CK  Creatine kinase 
CK-MB  Creatine kinase MB fraction 
cMRI  Cardiac magnetic resonance imaging 
CO2   Carbon dioxide 
COPD 
Chronic obstructive pulmonary disease 
CRF 
Case report form 
CRA 
Clinical Research Associate 
CRO 
Clinical Research Organization 
CV 
Cardiovascular 
DMSO 
Dimethyl sulfoxide 
DNA 
Deoxyribonucleic acid 
DSMB 
Data and Safety Monitoring Board 
EC 
Ethics Committee 
ECG  Electrocardiogram 
eCRF 
Electronic case report form 
EF 
Ejection fraction 
ESC 
Executive Steering Committee 
FDA 
Food and Drug Administration 
FEV 
Forced Expiratory Volume 
FU 
Follow-up 
GCP  Good Clinical Practice 
GMP 
Good Manufacturing Practice 
GFR 
Glomerular Filtration Rate 
GTN 
Glyceryl trinitrate 
HF 
Heart Failure 
HIPAA 
Health Insurance Portability and Accountability Act 

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HLA 
Human Leukocyte Antigen 
HR  Heart rate 
IB 
Investigator brochure 
IC 
Intracoronary 
ICD  Implantable cardioverter defibrillator 
ICF  Informed consent 
IEC 
Independent Ethics Committee 
IND 
Investigational new drug 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IV 
Intravenous 
IVRS  Interactive voice response system 
IWRS 
Interactive web response system 
LAD  Left anterior descending 
LBBB  Left bundle branch block 
LVAD 
Left ventricular assist device 
LVEDD 
Left ventricular end-diastolic dimension 
LVEDV 
Left ventricular end-diastolic volume 
LVEF 
Left ventricular ejection fraction 
LVESD 
Left ventricular end-systolic dimension 
LVESV 
Left ventricular end-systolic volume 
Mab 
Monoclonal antibody 
MACCE 
Major adverse cardiac and cerebrovascular events 
MB 
Subunits of creatine kinase 
 
  
MI 
Myocardial infarction 
MPC  Mesenchymal precursor cell 
MSC 
Mesenchymal stem cell 
NT-Pro-BNP 
N-terminal pro-brain natriuretic peptide, type B 
NQWMI 
NTG 
Non-Q wave myocardial infarction 
Nitroglycerin 
NYHA 
New York Heart Association 
PBMCs 
Peripheral blood mononuclear cells 
PCI 
Percutaneous coronary intervention 
PCR 
Polymerase chain reaction 
PHI 
PPP 
Protected health information 
Per-Protocol Population 
PSP 
Peak systolic pressure 
PTE 
Per Treatment Evaluable 
QCA 
Quantitative coronary analysis 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SOC 
System organ class 
STEMI 
ST-elevation myocardial infarction 

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SUSAR 
Suspected unexpected serious adverse event reaction 
TEAEs  Treatment emergent adverse events 
TIA 
Transient ischemic attack (cerebral) 
TIMI 
Thrombolysis In Myocardial Infarction 
TTE 
Transthoracic echocardiogram 
UADE 
Unanticipated adverse device effect 
VF 
Ventricular fibrillation 
VT 
Ventricular tachycardia 
 

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2. 
INTRODUCTION 
2.1 
Myocardial Infarction:  The clinical risk remains high post the acute event  
A recent update of US Medicare records was published that evaluated data involving 350,509 
acute myocardial infarction (MI) hospitalization in patients >65 years who were discharged alive 
after their event.3  Within the first year post the index event, 25.9% of the MI patients died with 
50.5% re-hospitalized.  In the month after a MI, the likelihood of death was 21 times higher and 
the likelihood of hospitalization was 12 times higher than among the general Medicare-age 
population.  Similar one year mortality data have been published for patients post STEMI treated 
in Canada.4   Clearly, despite important advances in standard of care therapies, there remains a 
large unmet clinical need to reduce death and re-hospitalization post MI.  Stem cell therapy, 
especially with allogeneic cells, represents an innovative opportunity to explore early therapeutic 
approaches that would be adjunctive to coronary artery revascularization of the culprit lesion 
with the goal of reducing post MI adverse myocardial remodeling and major adverse 
cardiovascular events.5-10  
 
In patients with acute ST-segment elevation myocardial infarctions (STEMI), there is a 
progression of myocardial injury that begins with the onset of cardiac ischemia and continues 
past the time of coronary reperfusion.11  The adage that “Time is Tissue” remains a basic 
approach to patients with STEMI with the emphasis on timeliness of reperfusion therapy.  The 
2013 ACCF/AHA STEMI Management Guidelines state that “for patients with STEMI, an ideal 
first-medical contact to device time goal is 90 minutes or less”.12  This equates to a goal of onset 
of ischemic symptoms to device time of <120 minutes. When this cannot be achieved, the 
Guidelines further emphasize that “Reperfusion therapy should be administered to all eligible 
patients with STEMI with symptom onset within the prior 12 hours”.  Because the 
pathophysiologic processes that include necrosis and apoptosis evolve over time, it is important 
to consider the duration of myocardial ischemia as an important variable in subsequent analyses 
of the natural history of myocardial infarctions with and without specific interventions.13-16 
 
Over the past decade, much investigation in acute myocardial ischemia has centered on the 
evaluation of the processes that result in induction of inflammatory cytokines as well as their 
effect on acute and chronic cardiac remodeling post-infarction.17-21   During the acute phase of 
myocardial ischemia, physiologic insults (increased mechanical stretch, oxidative stress, and 
hypoxia) occur that rapidly induce cytokines (e.g., TNF-α and/or IL-6) leading to 
enhanced/accelerated myocyte necrosis and apoptosis resulting in decreased left ventricular LV 
function and clinical compromise.17  This is followed by cytokine amplification with 
transmigration of macrophages and neutrophils.  During the chronic phase post-MI, the 

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established biological activity, consistent characterisation, enhanced purity and potency, and are 
immediately available (“off the shelf”) for allogeneic use.  
 
Please refer to the Investigator’s Brochure (IB) for further information. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 

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2.4 
Cardiac Magnetic Resonance Imaging (cMRI):  Assessment of Myocardial 
Ischemia, Viability, and Microvascular Obstruction 
Cardiac magnetic resonance imaging (cMR) is a useful validated tool to assess multiple 
structural and physiologic parameters in the setting of acute STEMI as well as its long term 
follow-up. 2,3,32-34  The following are the cMRI assessments that will be performed in the AMICI 
trial. 
 
2.4.1 
Myocardium at Risk (Area of Ischemia) 
Ischemic volume will be measured by the edematous volume using T2-weighted images and a 
triple inversion recovery fast spin echo sequences protocol. 35,36 
 
2.4.2 
Infarct Size 
The size of infarcted myocardium will be measured as the volume of tissue exhibiting late 
contrast enhancement. 32,37   
 

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2.4.3 
Infarct Size to Area at Risk Ratio 
This reflects the percent of the myocardium at risk that ultimately is infarcted. It is calculated as 
the ratio of the volume of infarcted myocardium (late contrast enhancement) to the volume of 
edematous myocardium (the ischemic volume determined by T-2 weighted images). 
 
2.4.4 
Microvascular Obstruction (MVO) 
After completion of the primary PCI for acute STEMI, restoration of blood flow at both the 
epicardial coronary artery level (as assessed by angiographic TIMI Flow Grade) and myocardial 
(tissue) level yields the best clinical outcomes. 32,38  This points to the critical role of the 
myocardial microvasculature in determining outcomes despite the relief of epicardial stenosis 
(even in the presence of TIMI 3 flow).  Cardiac MRI evaluation of MVO is conducted by 
assessment for lack of late contrast-enhanced myocardial imaging (i.e. central dark zone) after 
revascularized STEMI within the infarction. 37  
 
It is important to emphasize that studies using radiologic contrast angiography have 
demonstrated that restoration of epicardial flow does not necessarily lead to restoration of tissue 
level or microvascular perfusion. 39  The TIMI Myocardial Perfusion Grade (TMPG) has been 
shown to be a multivariate predictor of mortality in acute STEMI at 2 years of follow-up.  It 
permits risk stratification even within epicardial TIMI grade 3 flow.  Indeed, despite achieving 
epicardial patency with normal TIMI grade 3 flow, those STEMI patients whose 
microvasculature fails to open have a 7-fold increase in mortality compared with those patients 
with both TIMI grade 3 flow in the epicardial artery and no evidence of microvascular 
obstruction.  Among acute STEMI patients undergoing primary PCI, post-PCI TMPG correlates 
with cMR measurements of MVO and infarct size.39  The combined use of both metrics in a 
comprehensive assessment of microvascular integrity and infarct size following STEMI adds to 
an improved understanding of future therapeutic strategies. 
 
 
 
 
 
 
 
 
 
 

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2.6 
Rationale  
Healing of an MI is complicated by the need for viable myocytes at the peri-infarct margin to 
undergo compensatory hypertrophy in order to increase pump function in response to the loss of 
infarcted tissue.40,41  This initiates a process termed “cardiac remodeling,” which is characterized 
by apoptotic loss of hypertrophied myocytes, expansion of the initial infarct area, progressive 
collagen replacement, that collectively result in the development of heart failure.42-45  The 
Sponsor has recently advanced the hypothesis that hypertrophied cardiac myocytes undergo 
apoptosis because the endogenous capillary network cannot provide the compensatory increase 
in perfusion required for cell survival. 46 
 
Vascular network formation is the end result of a complex process that begins in the prenatal 
period with induction of vasculogenesis. Cells that can differentiate into endothelial and smooth 
muscle elements also exist in adult bone marrow47-49 and can induce vasculogenesis in ischemic 
tissues.50-52  The Sponsor has identified a specific population of MPCs derived from human adult 
bone marrow which has phenotypic and functional characteristics of vascular pericyte precursor 
cells that provide the building blocks necessary for arteriogenesis. Since recent observations 
have suggested that a second compensatory response of viable cardiomyocytes is to proliferate 
and regenerate following injury, 53,54 it is theoretically possible that further increase in the infarct 
bed capillary network through regulated neovascularization could result in increased regenerative 
capacity of the heart leading to improvement in myocardial function. 
 
Administration of MPCs resulted in significant improvement in several key parameters of 
myocardial function in rodents following AMI55  In particular, epicardial injection of MPCs 
resulted in a dose-dependent arteriogenesis at the infarct border zone.  This arteriogenesis was 
coupled with echocardiographic improvement in EF as well as restoration of near normal 
contractility and LV end-diastolic pressure.  Additionally, MPCs have been shown to secrete 
cytokines in a paracrine manner that could augment their direct trans differentiation  
potential.56,57  
 
The use of the ‘off-the-shelf’ allogeneic MPCs derived from healthy donors with the Sponsor’s 
proprietary process requires no cell culture and can be infused directly following recanulation of 
the involved artery and reperfusion of the infarcted tissue during a time period of myocardial  

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infarction.  The use of allogeneic donor cells obviates the need for second catheterization, 
hospitalization or anesthetic for treatment.  Therapy can be provided without the delay 
necessitated by days or weeks of cell culture, commonly observed with the use of mesenchymal 
stem cells obtained from bone marrow. 
 
No clinical efficacy studies of allogeneic MPCs in cardiovascular indications have been 
completed to date, but in an ongoing phase 2 study HF-AB002 (conducted by the sponsor), a 
scheduled interim analysis was performed after all study subjects had a minimum of 12 months 
of follow-up.  In this interim review of data for the Phase 2 study, transendocardial injections of 
MPCs in subjects with chronic heart failure was found to be feasible and safe. Treatment of 
subjects with allogeneic MPCs was not associated with a clinically significant immune response. 
Treatment was associated with significant reduction of MACCE and heart failure disease-
specific endpoints, with the latter demonstrating a positive effect of 150 M MPC.  Beneficial 
effects were also seen on LV remodeling and functional exercise capacity with this dose of 
MPCs. The results show a positive effect of MPCs on clinically relevant findings of heart failure 
treatment response.  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 

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3. 
STUDY HYPOTHESIS 
MPCs when administered intracoronary immediately after successful PCI with stenting in 
patients with first time acute anterior STEMI will result in amelioration of the early post-event 
inflammatory response and subsequent fibrotic scarring as well as promote the process of neo-
angiogenesis in tissue where an ischemic condition exists or is developing.  The net result will 
be: 
 decreased infarct size by short term protection of at-risk myocardium 
 increased long term salvage of myocardium resulting in decreased adverse left ventricular 
(LV) remodeling. 
 
4. 
STUDY OBJECTIVES 
4.1 
Primary Objective 
The primary objective of this study is to determine the safety and feasibility of intracoronary 
allogeneic, immuno-selected, bone marrow-derived Stro3 MPC delivery in the treatment of 
subjects with STEMI undergoing primary percutaneous coronary intervention of the LAD 
coronary artery. 
 
4.2 
Secondary Objectives 
 To explore a dose-response effect of intracoronary delivered MPC in the treatment of 
subjects with an anterior wall STEMI on LV remodelling, microvascular obstruction, and 
the relationship between time from onset of ischemic symptoms to primary PCI. 
 To determine the effect of intracoronary delivery of allogeneic immunoselected, bone 
marrow-derived MPC on infarct size reduction in the treatment of subjects with STEMI 
undergoing primary PCI of the LAD coronary artery.  
 
 
 

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4.3 
Study Design  
This is a prospective, double blind, randomized, placebo-controlled, dose finding study that will 
enroll approximately 105 subjects with de novo anterior STEMI due to a lesion involving LAD 
coronary artery who undergo primary PCI at approximately 25 clinical study sites.   
 
This study will compare two doses of MPCs and a placebo control group.  Study subjects will be 
randomly assigned in 1:1:1 fashion to receive either 12.5 M or 25 M MPCs or placebo (saline). 
Each group will have approximately 35 subjects. 
 
Potential subjects will be approached by the site investigator prior to PCI and must sign an 
informed consent form before initiation of the cardiac catheterization procedure in order to 
participate in this trial.  Following successful and uneventful PCI and stenting of the culprit LAD 
lesion, the subjects will be randomized.  The randomization and treatment assignment will be 
obtained from an IVRS/ IWRS.  The following stratification for duration of cardiac ischemia will 
be performed to ensure balanced randomization across the treatment groups: 
 ≤2 hours 
 >2 hours to ≤6 hours 
 >6 to ≤12 hours. 
 
Eligible subjects will receive intracoronary delivery of the assigned treatment infused via a 
microcatheter into the stented culprit artery.  The subjects randomized to MPCs will be infused at 
an infusion rate of 2 ml/min over approximately 60 minutes, including line flush  
[2.5x105 MPCs/min (12.5 M), 5.0x105 MPCs/min (25 M)].  The subjects randomized to placebo 
will be infused placebo solution at 2 mL/min over approximately 60 minutes, including line flush 
(0 MPCs/min).  Due to the presence of a catheter in the coronary arteries for this period of time, 
anticoagulants should be given as clinically indicated.  The MPC product (12.5M and  
25M MPCs) and the placebo solution will be diluted in 100mL 0.9% saline solution prior to 
infusion.  The Sponsor will provide all sites with blinded treatment cryobags or cryovials, which 
contain the different doses of MPCs or placebo solution.   
 
An IC bolus of GTN/ NTG (100-200mcg) should be administered (blood pressure permitting) 
prior to TIMI flow assessments during the investigational agent infusion period as well as after 
completion of the investigational agent infusion and immediately prior to the final coronary 
angiographic imaging. 
 

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After approximately 50% of the intracoronary infusion of investigational agent has been 
completed, an angiographic determination of coronary flow will be performed.  The following 
guidelines will be used to determine if the remaining investigational agent should be infused:  
 The study infusion should be continued if either TIMI 2 or TIMI 3 flow is present in the 
absence of ALL of the following: 
o Sustained hypotension not responsive to fluid administration; 
o Clinical signs/symptoms indicating an acute cerebrovascular event; 
o Re-elevation of ST-segments if previously resolved with PCI; 
o Onset of the subject’s symptoms of myocardial ischemia unresponsive to appropriate 
interventions; 
o Two episodes of sustained ventricular tachycardia/ventricular fibrillation requiring 
cardioversion (infusion can continue if a single episode of sustained VT/VF requiring 
cardioversion occurred). 
 
If for any reason, the site investigator withdraws a randomized subject prior to infusion of the 
investigational agent, the reason for early termination and data from the screening visit will be 
entered into the eCRF by the study site.  The subject will not remain in the study.  If for any 
reason, a subject’s study infusion is halted due to safety considerations, the subject will remain in 
the study.  A subject who prematurely withdraws from the study post study infusion will remain 
in the study. 
 
Evaluation for safety will be performed for up to 24 months post infusion. Subjects will undergo 
cardiac magnetic resonance imaging (cMRI) and 2-D echocardiography (ECHO), Holter 
monitoring, clinical evaluation and laboratory testing. 
 
cMRI, ECHO monitoring will be performed at 2-7 days post infusion of study agent (MPC or 
Placebo), as well as at Day 30 and at Month 6 after the procedure. Holter monitoring will be 
performed at 14 and 30 days, 3 and 6 months after the procedure.  Clinical evaluation and 
laboratory testing will be performed at 6, 12, 18 and 24 hours post infusion of study agent (MPC 
or Placebo), during the index hospitalization as well as at 14 and 30 days and 3, 6, 12, 18 and 
24 months after the procedure as outlined in Table 2 Schedule of Assessments and Procedures. 
 
An independent DSMB will review all relevant acute peri-procedural data, SAE, other AE, and 
efficacy data (if requested) periodically dependent on subject enrollment and advise the ESC 
regarding the progression of the study.  The ESC will consist of the Principal Investigator, site 
investigators and representatives of and advisors to the Sponsor. 
 

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A CEC will review appropriate source documents and adjudicate (blinded per a priori procedure) 
all MACCE defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or 
cardiac hospitalization due to heart failure.  Target vessel (or other vessel) revascularization post 
index cardiac catheterization and new or worsening heart failure during the index hospitalization 
will be tracked as “Adverse Events of Special Interest” rather than MACCE. 
 
Blinded Study Personnel and Participants 
Subjects, Site personnel, Investigators will remain blinded until after all safety follow-up is 
completed.  The DSMB may choose to be unblinded. 
 
Unblinded Study Personnel 
Pre-specified unblinded clinical operations and biometrics team members at both the vendor and 
sponsor will have access to the unblinded efficacy results.  
 
These pre-specified unblinded team members will be identified prior to the analysis being 
conducted and they will not have any operational responsibility for the conduct of the study.  
 
An independent unblinded statistician from 
 will support the DSMB by providing Open 
and Closed Reports to the DSMB independent statistician based on the best available data and 
other information to the DSMB. 
 
The DSMB safety reviews to assess the frequency of total MACCE will be performed after the 
initial 15, 30, 60, and 90 subjects have been observed at Day 30 post the index cardiac 
catheterization. The final safety analysis will be performed at 24 months for all patients. 
 
5. 
SELECTION AND WITHDRAWAL OF SUBJECTS  
The study population will consist of an ‘all-comers’ subject population with a de novo anterior 
AMI who are undergoing primary PCI with stent placement within 12 hours after onset of 
symptoms, who meet all the inclusion and none of the exclusion study criteria.  Enrollment and 
treatment is anticipated to include approximately 105 subjects at approximately 25 clinical sites.  
The subjects will be of any race and of either gender.  
 
 

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5.1.1 
Inclusion Criteria  
Subjects will be entered into this study only if they meet ALL of the following criteria: 
1. Willing and able to understand and sign the Informed Consent Form (ICF). 
2. Males or females ≥ 18 years. 
3. Clinical symptoms consistent with AMI (pain, etc.) for a maximum of 12 hours from 
onset of symptoms to percutaneous coronary intervention (PCI). 
4. De novo anterior Acute Myocardial Infarct (AMI) 
 
 
 
 
 
 
 
 
 
 
5. Successful revascularization of the culprit lesion 
 
 
 
 
 
 
 
 
 
 
  
6. If a female subject is of childbearing potential (i.e., not amenorrheic for 12 or more 
months and/or not surgically sterile), the subject must be willing to use highly effective 
method of contraception (oral, injectable or implanted hormonal methods of 
contraception, placement of an  intrauterine device [IUD] or intrauterine system [IUS], 
condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male 
sterilization, or true abstinence)) for at least 16 weeks after investigational agent infusion. 
7. Must be willing and able to return for required follow-up visits. 
 

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5.1.2 
Exclusion Criteria 
Subjects will not be enrolled into this study if they meet ANY of the following criteria: 
1. Prior MI, known cardiomyopathy, or hospital admission for heart failure (HF). 
2. Significant valvular disease (mitral or aortic valve regurgitation 3/4 classification as 
defined by ESC/ACC guidelines). 
3. Unsuccessful revascularization of culprit artery defined as TIMI 1 or 0 flow or residual 
diameter stenosis of ≥ 20% by on line QCA analysis. 
4. Need for staged treatment of coronary artery disease, or other interventional or surgical 
procedures to treat heart disease 
 
 
 
 
 
 
 
  
5. Cardiogenic shock or hemodynamic instability within 24 hours prior to randomization, 
 
 
 
 
 
 
  
 
 
8. Prior PCI involving the LAD  
9. Malignancy within last 3 years from screening. The subject has had an active 
malignancy, within the past 3 years except for cervical carcinoma in situ, or non-
melanoma skin cancer that has been definitively treated. 
 
11. Pacemaker, ICD or any other contra-indication for cMRI.  This is inclusive of patients 
with an MRI compatible device that was implanted prior to the potential qualifying event. 
 
 
 
 
 
 
  

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18. Prior participation in any other investigational drug trial in the past 30 days.  
 
 
 
 
 
 
5.2 
Subject Withdrawal    
Subjects may withdraw from the study at any time, for any reason, without penalty, or prejudice 
to his or her future medical care.  The investigator also has the right to withdraw subjects from 
the study in the event of intercurrent illness, adverse events, administrative, or other reasons.  
 
5.3 
Withdrawal Procedures 
In all cases, the reason(s) for withdrawal must be recorded on the eCRF.  If a subject prematurely 
withdraws from the study post-study infusion for any reason, the investigator must make every 
effort to perform the evaluations described for the Early Termination visit.  Since the ICF states 
that subjects that prematurely withdraw post study-infusion for any reason may also be contacted 
by telephone for follow-up safety information for up to 24 months post study infusion, unless the 
subject also specifically withdraws consent for this communication all subjects may also be 
contacted by telephone. 
 
Figure 2:  Randomization/Withdrawal 
 

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The randomization number assigned to a withdrawn subject will not be re-used. 
 
Subjects who sign consent and are not randomized will be considered screen failures.   
 
If during the course of the study a subject chooses to revoke his/her written authorization for the 
use and disclosure of Protected Health Information [PHI] (per HIPAA privacy ruling or other 
country and/or region specific law), the subject will then be withdrawn from the study as well 
(i.e., participation in this study is contingent upon an “active” written PHI use, collection, and 
disclosure authorization and only safety data will be collected as required by applicable laws.  
PHI collected prior to the date that the subject revokes his/her written authorization may still be 
used.  In the event of a subject’s withdrawal, the investigator will promptly notify the medical 
monitor or designee and will make every effort to complete the assessments as indicated above 
for subjects who prematurely discontinue from the study.  All withdrawn subjects will be 
followed until resolution of any AEs or until the unresolved AEs are judged by the investigator 
to have stabilized. 
 
5.4 
Early Termination of Study 
If the sponsor, the investigator, or a regulatory authority discover conditions arising during the 
conduct of the study that indicate that the study should be halted or that the study center should 
be closed, this action may be taken after prompt, appropriate consultation between the Sponsor 
and the investigator(s).  Conditions that may warrant termination of the study include, but are not 
limited to, the following: 
 The discovery of an unexpected, serious, or unacceptable risk to the subjects enrolled in 
the study or if, in the sponsor’s judgment there are no further potential benefits to be 
achieved from the study. 
 A decision on the part of the sponsor to suspend or discontinue testing, evaluation or 
development of the investigational product. 
 
Study termination and follow-up will be performed in compliance with the conditions set forth in 
the International Conference on Harmonization of Technical Requirements of Pharmaceuticals 
for Human Use Guideline (ICH E6) and relevant applicable regulations. 
  
5.4.1 
Data Safety and Monitoring Board Overview   
An independent DSMB will be established and is the primary external data and safety group for 
the study.  All members shall have experience and expertise in cardiovascular clinical trials 
and/or stem cell therapy.  DSMB members may not participate in the study as principal or co-

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investigators, study subject physicians or in any other capacity that might compromise their 
privileged position on the DSMB. 
 
The DSMB will periodically review study safety and efficacy data and make recommendations 
to the ESC Chair and Sponsor.  The ESC has the responsibility to accept, reject or to modify 
DSMB recommendations.  A separate charter outlining the operations of the DSMB will be 
developed. The DSMB will meet as specified in the charter. 
 
5.4.2 
Executive Steering Committee 
The ESC will meet periodically by teleconference to monitor subject enrollment, clinical site 
progress, and protocol compliance according to the charter.  The responsibilities of the ESC are 
to: (a) maintain contact with study investigators to stimulate enrollment and ensure high quality 
data; (b) implement major protocol changes in response to the advice of the DSMB and 
agreement of Sponsor; (c) help develop dissemination of the results of the study through 
publications and presentations at major meetings.   
 
5.4.3 
Clinical Event Committee 
The responsibilities of the CEC are to perform a review of appropriate source documents and to 
perform a blinded adjudication of all MACCE defined as cardiovascular death, non-fatal 
myocardial infarction, non-fatal stroke, or cardiac hospitalization due to heart failure.  In 
addition, the CEC will review all cases of target vessel (or other vessel) revascularization post 
index cardiac catheterization and new or worsening heart failure during the index hospitalization.  
These will be designated as “Adverse Events of Special Interest” rather than MACCE. 
 
The CEC committee may also review cardiac events not considered MACCE or “Adverse Events 
of Special Interest” including, but not limited to hospitalization for unstable angina, 
hospitalization for resuscitated cardiac arrest, and transient ischemic attack.  The definition of 
heart failure will be described in the CEC charter.  The individuals who will serve on the 
committee will be independent of the Sponsor, the DSMB, the ESC, the clinical study sites and 
the trial’s investigators.  The committee will consist of cardiologists with prior experience with 
adjudication of cardiac events in clinical trials.  No CEC member will be present during any 
study procedures, and all CEC members will be blinded to the subject treatment assignments.  
The CEC will meet as needed to adjudicate adverse events and outcomes data for each subject 
enrolled.  A charter will be developed to outline the CEC process and procedures.  
 

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6. 
STUDY PROCEDURES  
6.1 
Study Visits 
6.1.1 
Enrollment and Eligibility 
The investigator or his/her designee, such as the study coordinator, will notify the Sponsor or its 
CRO designee of each potential subject, if possible.  Once a subject is determined to be eligible 
and has provided informed consent, the site will call the IVRS for randomization.  Each qualified 
subject will be randomized to one of three parallel treatment arms, 12.5 or 25 x 106 MPCs or to 
the sterile saline control arm.  All subjects will receive a single infusion via intracoronary 
administration at a rate of 2 mL/min for approximately 60 minutes, including line flush.  
 
Evaluations performed at each study visit and visit windows are summarized below.  If a subject 
misses a visit, all efforts should be made to reschedule the missed visit within the allocated visit 
window.  
 
6.1.1.1 Visit 1: Screening/Day of Infusion (Day 0), Pre Study Infusion 
Informed consent will be obtained prior to any study specific procedures.  
 
The following procedures will be performed prior to infusion of the study investigational agent: 
 Informed consent 
 Review of inclusion and exclusion criteria 
 Review of medical and surgical history, including determination of: 
o Medication history, including recent vaccinations and/or immunizations 
o Blood product transfusion history 
o Pregnancy history (females only)  
o Tobacco, drug, alcohol use history 
o Renal disease 
o Pulmonary disease 
 Physical examination to include but not limited to examination of the cardiac, pulmonary, 
neurologic (including but not limited to mental status) and gastrointestinal systems as 
well as the measurement of height, weight, and body mass index (BMI). 
 Recording of concomitant medications including vaccinations 
 Vital signs (BP, temperature, heart rate, and respiratory rate) 
 12 lead ECG 

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 Basic metabolic profile [sodium, potassium, chloride, carbon dioxide (CO2), blood urea 
nitrogen (BUN), glucose, creatinine and calcium, calculated glomerular filtration rate 
(GFR)]  
 Troponin I (or T)  
 Creatine kinase and MB fraction (CK-MB) 
 Non-fasting lipid profile (cholesterol, triglycerides, HDL and LDL) 
 High Sensitive (hs) C-reactive protein (CRP) 
 Hepatic function profile (total protein, albumin, alkaline phosphatase, alanine 
transaminase, aspartate aminotransferase, direct bilirubin, total bilirubin) 
 Complete Blood Count (CBC) with differential and platelets 
 Flow cytometry anti-HLA Class I and Class II antibodies (%PRA) with specificity 
 Anti-murine and anti-bovine antibodies 
 NT-Pro BNP [brain natriuretic peptide, type B] 
 Urine pregnancy test (females not amenorrheic for the previous 12 months and/or not 
surgically sterile) 
 Record details of PCI ( i.e. angiogram findings, stent details) 
 Selective coronary angiogram of target vessel   
 TIMI flow and perfusion measurement 
 QCA analysis of the culprit vessel (to determine diameter residual stenosis and 
procedural success)  
 Randomization 
 Preparation of study investigational agent   
 Commencement of infusion of study investigational agent within 30 minutes after 
completion of PC 
 Killip Class I  
 AE/SAE assessment. 
 
6.1.1.2 Visit 2: Day of Infusion (Day 0), Immediately Post Study Infusion 
 Recording of concomitant medications including vaccinations 
 12 Lead ECG 
 Telemetry monitoring 
 Record study investigational agent infusion details 
 TIMI flow and perfusion measurements  
 AE/SAE assessment. 
 

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6.1.1.3 Visit 3: Six, Twelve, Eighteen Hours Post Study Infusion (± 1 hour) 
 Recording of concomitant medications including vaccinations  
 Vital signs (BP, temperature, heart rate, respiratory rate)  
 Telemetry monitoring 
 Troponin I (or T)  
 Creatine kinase and MB fraction  
 AE/SAE assessment. 
 
6.1.1.4 Visit 4: Twenty-four Hours Post Study Infusion (± 2 hours) 
 Physical examination to include but not limited to examination of the cardiac, pulmonary, 
neurologic (including but not limited to mental status) and gastrointestinal systems as 
well as weight.  New physical examination findings of any system will be noted.  In the 
event of abnormal neurological findings, subjects will require a neurological consult.  
 Recording of concomitant medications including vaccinations Vital signs (BP, 
temperature, heart rate and respiratory rate)  
 12 Lead ECG 
 Telemetry monitoring 
 Troponin I (or T)  
 Creatine kinase and MB fraction  
 AE/SAE assessment. 
 
6.1.1.5 Visit 5: Two thru Seven Days Post Study Infusion 
 Daily physical examination to include but not limited to examination of the cardiac, 
pulmonary, neurologic (including but not limited to mental status) and gastrointestinal 
systems. New physical examination findings of any system will be noted.  In the event of 
abnormal neurological findings, subjects will require a neurological consultation.  
 Recording of concomitant medications including vaccinations  
 Daily vital signs (BP, temperature, heart rate and respiratory rate)  
 12 Lead ECG on Day 2 and prior to hospital discharge 
 Daily telemetry monitoring 
 Daily Troponin I (or T) 
 Daily creatine kinase MB fraction 
 Daily AE/SAE assessment 
 Hospital Discharge on Day 4-7 with outpatient 48 hour Holter monitor 
 The target date for the following assessment is Day 3 post study infusion ±1 day:  

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o Basic Metabolic Profile (sodium, potassium, chloride, carbon dioxide (CO2), blood 
urea nitrogen (BUN), glucose, calculated GFR, creatinine and calcium) 
o hs C-reactive Protein (CRP) 
o Hepatic function profile (total protein, albumin, alkaline phosphatase, alanine 
transaminase, aspartate aminotransferase, direct bilirubin, total bilirubin) 
o CBC with differential and platelets 
o NT-Pro Brain Natriuretic Peptide, type B 
o 2D echocardiogram 
o Cardiac MRI    
o Canadian cardiovascular society angina classification (CCS)  
o NYHA Classification 
o Weight. 
 
6.1.1.6 Visit 6: Fourteen Days Post Study Infusion (± 3 days) 
 Physical examination to include but not limited to examination of the cardiac, pulmonary, 
neurologic (including but not limited to mental status) and gastrointestinal systems as 
well as weight. New physical examination findings of any system will be noted. In the 
event of abnormal neurological findings, subjects will require a neurological consultation.  
 Recording of concomitant medications including vaccinations 
 Vital signs (BP, temperature, heart rate and respiratory rate)  
 Basic metabolic profile (sodium, potassium, chloride, carbon dioxide (CO2), blood urea 
nitrogen (BUN), glucose, calculated GFR, creatinine and calcium)  
 hs C-reactive protein (CRP)  
 Hepatic function profile (total protein, albumin, alkaline phosphatase, alanine 
transaminase, aspartate aminotransferase, direct bilirubin, total bilirubin) 
 CBC with differential and platelets  
 Flow cytometry anti-HLA Class I and Class II antibodies (%PRA) with specificity 
 Anti-murine and anti-bovine antibodies 
 48 hour Holter monitor 
 AE/SAE assessment. 
 
6.1.1.7 Visit 7: Thirty Days Post Study Infusion (± 7 days) 
 Physical examination to include but not limited to examination of the cardiac, pulmonary, 
neurologic (including but not limited to mental status) and gastrointestinal systems as 
well as weight.  New physical examination findings of any system will be noted. In the 
event of abnormal neurological findings, subjects will require a neurological consultation.  

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 Recording of concomitant medications including vaccinations 
 Vital signs (BP, temperature, heart rate and respiratory rate)  
 12 Lead ECG 
 Basic metabolic profile (sodium, potassium, chloride, carbon dioxide (CO2), blood urea 
nitrogen (BUN), glucose, calculated GFR, creatinine and calcium)  
 Non-fasting Lipid Profile 
 hs C-reactive protein (CRP)  
 Hepatic function profile (total protein, albumin, alkaline phosphatase, alanine 
transaminase, aspartate aminotransferase, direct bilirubin, total bilirubin) 
 CBC with differential and platelets  
 Flow cytometry anti-HLA Class I and Class II antibodies (%PRA) with specificity  
 Anti-murine and anti-bovine antibodies 
 NT-Pro BNP [Brain Natriuretic Peptide, type B] 
 2D echocardiogram 
 Cardiac MRI    
 48 hour Holter monitor 
 Canadian cardiovascular society angina classification (CCS)  
 NYHA Classification  
 AE/SAE assessment. 
 
6.1.1.8 Visit 8: Three Months Post Study Infusion (± 7 days) 
 Physical examination to include but not limited to examination of the cardiac, pulmonary, 
neurologic (including but not limited to mental status) and gastrointestinal systems as 
well as weight.  New physical examination findings of any system will be noted. In the 
event of abnormal neurological findings, subjects will require a neurological consultation.  
 Recording of concomitant medications including vaccinations 
 Vital signs (BP, temperature, heart rate and respiratory rate)  
 12 Lead ECG 
 Basic metabolic profile (sodium, potassium, chloride, carbon dioxide (CO2), blood urea 
nitrogen (BUN), glucose, calculated GFR, creatinine and calcium) 
 Non-fasting Lipid Profile 
 hs C-reactive protein (CRP) 
 Hepatic function profile (total protein, albumin, alkaline phosphatase, alanine 
transaminase, aspartate aminotransferase, direct bilirubin, total bilirubin) 
 CBC with differential and platelets 

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 Flow cytometry anti-HLA Class I and Class II antibodies (%PRA) with specificity 
 Anti-murine and anti-bovine antibodies 
 NT-Pro BNP [brain natriuretic peptide, type B] 
 Serum pregnancy test (females not amenorrheic for the previous 12 months and/or not 
surgically sterile) 
 48 hour Holter monitor 
 Canadian cardiovascular society angina classification (CCS)  
 NYHA Classification  
 AE/SAE assessment. 
 
6.1.1.9 Visit 9: Six Months Post Study Infusion (± 14 days) 
 Physical examination to include but not limited to examination of the cardiac, pulmonary, 
neurologic (including but not limited to mental status) and gastrointestinal systems as 
well as weight.  New physical examination findings of any system will be noted.  In the 
event of abnormal neurological findings, subjects will require a neurological consultation.  
 Recording of concomitant medications including vaccinations 
 Vital signs (BP, temperature, heart rate and respiratory rate)  
 12 Lead ECG 
 Basic metabolic profile (sodium, potassium, chloride, carbon dioxide (CO2), blood urea 
nitrogen (bun), glucose, calculated GFR, creatinine and calcium)  
 Non-fasting Lipid Profile 
 hs C-reactive protein (CRP)  
 Hepatic Function profile (total protein, albumin, alkaline phosphatase, alanine 
transaminase, aspartate aminotransferase, direct bilirubin, total bilirubin) 
 CBC with differential and platelets  
 Flow cytometry anti-HLA Class I and Class II antibodies (%PRA) with specificity 
 Anti-murine and anti-bovine antibodies 
 NT-Pro BNP [brain natriuretic peptide, type B] 
 2D Echocardiogram 
 Cardiac MRI  
 48 hour Holter monitor 
 Canadian cardiovascular society angina classification (CCS)  
 NYHA Classification  
 AE/SAE assessment. 
 

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6.1.1.10 Visit 10: Twelve Months Post Study Infusion (± 14 days) 
 Physical examination to include examination of the cardiac, pulmonary, neurologic 
(including but not limited to mental status) and gastrointestinal systems as well as weight.  
New physical examination findings of any system will be noted. In the event of abnormal 
neurological findings, subjects will require a neurological consultation.  
 Recording of concomitant medications including vaccinations 
 Vital signs (BP, temperature, heart rate and respiratory rate)  
 12 Lead ECG 
 Basic metabolic profile (sodium, potassium, chloride, carbon dioxide (CO2), blood urea 
nitrogen (bun), glucose, calculated GFR, creatinine and calcium)  
 Non-fasting Lipid Profile 
 hs C-reactive protein (CRP)  
 Hepatic function profile (total protein, albumin, alkaline phosphatase, alanine 
transaminase, aspartate aminotransferase, direct bilirubin, total bilirubin) 
 CBC with differential and platelets  
 Flow cytometry anti-HLA Class I and Class II antibodies (%PRA) with specificity 
 Anti-murine and anti-bovine antibodies 
 NT-Pro BNP [brain natriuretic peptide, type B]  
 Canadian cardiovascular society angina classification (CCS)  
 NYHA Classification  
 AE/SAE assessment. 
 
6.1.1.11 Visit 11: Eighteen Months Post Study Infusion (± 30 days) 
 Telephone follow-up  
 Recording of concomitant medications including vaccinations 
 AE/SAE assessment. 
 
6.1.1.12 Visit 12: Twenty Four Months Post Study Infusion (± 30 days) 
 Physical examination to include but not limited to examination of the cardiac, pulmonary, 
neurologic (including but not limited to mental status) and gastrointestinal systems as 
well as weight.  New physical examination findings of any system will be noted. In the 
event of abnormal neurological findings, subjects will require a neurological consultation.  
 Recording of concomitant medications including vaccinations 
 Vital signs (BP, temperature, heart rate and respiratory rate)  
 12 Lead ECG 

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 Basic metabolic profile (sodium, potassium, chloride, carbon dioxide (CO2), blood urea 
nitrogen (bun), glucose, calculated GFR, creatinine and calcium)  
 Non-fasting Lipid Profile 
 hs C-reactive protein (CRP)  
 Hepatic function profile (total protein, albumin, alkaline phosphatase, alanine 
transaminase, aspartate aminotransferase, direct bilirubin, total bilirubin) 
 CBC with differential and platelets  
 Anti-murine and anti-bovine antibodies 
 NT-Pro BNP [brain natriuretic peptide, type B]  
 Canadian cardiovascular society angina classification (CCS)  
 NYHA Classification  
 AE/SAE assessment 
 Complete study exit information. 
 
6.1.1.13 Early Termination Visit  
For subjects who are withdrawn from the study post study infusion and prior to completion of the 
study at Month 24, an Early Termination Visit will be scheduled. The following procedures will 
be performed at the Early Termination Visit: 
 Physical examination to include, but not limited to, examination of the cardiac, 
pulmonary, neurologic (including but not limited to mental status), and gastrointestinal 
systems as well as weight. New physical examination findings of any system will be 
noted. In the event of abnormal neurological findings, subjects will require a neurological 
consult.  
 Recording of concomitant medications including vaccinations 
 Vital signs (BP, temperature, heart rate and respiratory rate) 
 12-lead ECG 
 Basic metabolic profile (sodium, potassium, chloride, bicarbonate, BUN, glucose, 
calculated GFR, creatinine, and calcium)  
 Non-fasting Lipid Profile 
 hs C-reactive protein (CRP) 
 Hepatic function profile (total protein, albumin, alkaline phosphatase, ALT, AST, direct 
bilirubin, and total bilirubin) 
 CBC with differential and platelets  
 Flow cytometry anti-HLA Class I and Class II antibodies (PRA%) only for subjects that 
discontinue prior to Visit 10 (Month 12) 

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 Anti-murine and anti-bovine antibodies 
 NT-Pro BNP [brain natriuretic peptide, type B]  
 Serum pregnancy testing 
 Canadian Cardiovascular Society Angina Classification 
 NYHA Classification   
 Adverse event and SAE assessment. 
 
6.2 
Study Monitoring 
All aspects of the study should be conducted in accordance with Good Clinical Practice (GCP) as 
described in ICH E6 and all other applicable regulations.  
 
The Sponsor and/or its designated CRO will monitor the study.  Monitoring will be performed by 
qualified individuals designated by the Sponsor and in accordance with the protocol, GCP and 
standard operating procedures for compliance with applicable regulations. The investigators 
agree to allow the monitors direct access to source documents. 
 
In addition, the study may be evaluated by representatives from regulatory agencies, who will 
also be allowed access to study documents.  The investigators will promptly notify the Sponsor 
or its designee of any audits or inspections they have scheduled with any regulatory 
agency/authority. 
 
6.3 
Follow-up/Lost to Follow-up 
Vigorous attempts will be made to obtain follow-up evaluations for all study subjects who are 
enrolled in the study.  
 
If necessary, appointment reminders will be sent by mail by the study coordinator before the 
scheduled follow-up visit and telephone contact will be attempted in the event that a study 
subject fails to attend a scheduled follow-up visit.  
 
A minimum of three telephone calls will be made to the subject and if no response, a certified 
letter will be sent to the subject in an attempt to obtain follow-up information. 
 

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7. 
STUDY TREATMENTS  
7.1 
Study Infusion Continuation and Halt Guidelines  
Procedure-related cardiac arrhythmias will be handled according to current 2004 
ACC/AHA/ESC practice guidelines for management of subjects with ventricular arrhythmias 
and the prevention of sudden cardiac death will be implemented.   
 
After approximately 50% of the intracoronary infusion of investigational agent has been 
completed, an angiographic determination of coronary flow will be performed.  The following 
guidelines will be used to determine if the remaining investigational agent should be infused:  
1. The study infusion should be continued if either TIMI 2 or TIMI 3 flow is present in the 
absence of ALL of the following: 
2. Sustained hypotension not responsive to fluid administration; 
3. Clinical signs/symptoms indicating an acute cerebrovascular event; 
4. Re-elevation of ST-segments if previously resolved with PCI; 
5. Onset of the patient’s symptoms of myocardial ischemia unresponsive to appropriate 
interventions; 
6. Two episodes of sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) 
requiring cardioversion (infusion can continue if a single episode of sustained VT/VF 
requiring cardioversion occurred). 
 
If TIMI flow is 1 or 0 at this assessment, regardless of associated symptoms listed above, the 
infusion of investigational agent must be terminated.  
 
7.2 
Definition of Adverse Event of TIMI 1 or 0 flow 
If the study infusion procedure is terminated due to a TIMI 1 or 0 flow in the absence of 
clinically evident symptoms, this must be reported as an AE. The appropriate term to record in 
the CRF is ‘Cardiac procedure complication. 
 
7.3 
Investigational Agent  
7.3.1 
Investigational Agent Labeling 
The content of the coded treatment cryovials (MPC and saline placebo) will not be known to the 
participating centers, subject representatives of the Sponsor, or data management organization, 
and the code will not be broken until after the database of the study has been locked by the CRO. 
 

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7.3.4 
Investigational Agent/Control Agent Handling and Accountability 
All study product accountability records including records of randomization assignment will be 
maintained by the investigator or qualified designee, stored in a secure location and reviewed 
during monitoring visits by the assigned CRA/monitor.  
 
 
   
 
 
 
   
 
7.4 
Control Agent 
7.4.1 
Description of Control Agent 
The control placebo agent is sterile saline.  In addition to the coded MPC agent, the coded study 
placebo agent will also be provided by the Sponsor and prepared in similar volume and similar 

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cryovials, as applicable, as the MPC product so as to help make it as indistinguishable from the 
investigational MPC product as best as possible.  
 
7.5 
Blinding and Randomization  
This is a double blinded study.  Each subject will be blinded to his/her assigned treatment.   
Study blinding will be maintained as described below. 
 
Blinded Study Personnel and Participants 
Subjects, Site personnel, Investigators will remain blinded until after all safety follow-up is 
completed. The DSMB may choose to be unblinded. 
 
Unblinded Study Personnel 
Pre-specified unblinded clinical operations and biometrics team members at both the vendor and 
sponsor will have access to the unblinded efficacy results.  
 
These pre-specified unblinded team members will be identified prior to the analysis being 
conducted and they will not have any operational responsibility for the conduct of the study.  
 
An independent unblinded statistician from the CRO will support the DSMB by providing Open 
and Closed Reports to the DSMB independent statistician based on the best available data and 
other information to the DSMB. 
 
Subjects that are admitted within a maximum of 12 hours after onset of ischemic cardiac 
symptoms who are experiencing a de novo anterior MI and qualify based on inclusion/exclusion 
criteria will be approached for enrollment.  Eligible subjects will be randomized to receive one of 
three possible intracoronary treatments:  Investigational product at 12.5 M or 25.0 M allogeneic 
MPCs or saline placebo control. 
 
Randomization will occur after informed consent has been obtained and the PCI with stenting of 
the culprit LAD coronary artery lesion has been successfully completed (residual TIMI Flow 
Grade 3 or 2, residual diameter stenosis <20% by QCA, uncomplicated primary PCI).   
 
The randomization and treatment assignment will be obtained from an IVRS/ IWRS.  
 
 
 

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The following stratification for duration of cardiac ischemia will be performed to ensure 
balanced randomization across the treatment groups: 
 ≤2 hours 
 >2 hours to ≤6 hours 
 >6 to ≤12 hours. 
 
After randomization has been performed, each subject will receive a unique identification 
number that will include site and subject identifiers. 
 
7.5.1 
Un-blinding Procedure 
The study blind should not be broken except in a medical emergency (where knowledge of the 
test material received would affect the treatment of the emergency) for regulatory requirement 
(e.g., suspected unexpected serious adverse reactions (SUSARs)), and for the unblinded analysis 
of efficacy and preliminary safety once all subjects have completed the 6-month visit. If an 
emergency un-blinding becomes necessary, the investigator should notify the Sponsor or 
Medical Monitor, as soon as possible. 
 
7.5.2 
Concomitant Therapy 
All subjects will receive standard post-therapy care guided by standard practices at the study 
center.  In the event of procedure-related cardiac arrhythmias, current ACC/AHA/ESC practice 
guidelines for management of subjects with ventricular arrhythmias and the prevention of sudden 
cardiac death will be implemented.  All other investigational agents or therapies are prohibited 
for the duration of this study. 
 
All concomitant medications administered to study subjects will be recorded on the eCRF. 
 
8. 
ASSESSMENT OF EFFICACY  
Feasibility of the infusion of the investigational agent will monitored by measurement of TIMI 
flow and perfusion prior to, during, and following the investigational agent infusion after 
successful PCI and stenting. 
 
8.1 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the change in LVESV as assessed by cardiac MRI from 
baseline to 6 months post investigational agent infusion for each MPC treatment group compared 
with control. 
 

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8.2 
Secondary Efficacy Endpoints 
 The change in LVESV as assessed by 2D-echocardiography from baseline to 6 months 
post investigational agent infusion. 
 The change in relative infarct size as assessed by late contrast enhancement MRI 
(% infarct volume/total LV tissue volume) from baseline to 6 months post investigational 
agent infusion. 
 Additional functional efficacy endpoints will be assessed with the following diagnostic 
studies: 
o Cardiac MRI at 2-4 days, 30 days and at Month 6. 
 LVEF 
 LVESV 
 LVEDV  
 Left ventricular wall thickness and thickening in all segments including 
infarct area 
 Regional wall motion score 
 Myocardial MVO measured as reduced signal intensity in the region of 
interest 
 MI size measured in the region of interest as late contrast enhancement 
 Myocardial salvage index 
o 2D echocardiogram at 2-4 days, 30 days and at Month 6. 
 LVEF  
 LVESV 
 LVEDV 
 Cardiac dimensions (LVESD/ LVEDD) 
 Regional wall motion score index 
o If neither MPC arm is found to be better than the placebo arm and there is no 
difference between the MPC groups (using the ANCOVA test with alpha=.1) in 
the effect on LVESV then the pooled MPC group will be compared to the placebo 
group for all functional parameters. 
o A subset analysis that corresponds to the stratification used during randomization 
will be performed. Stratification will be based on the following following 
categories defined as time from onset of AMI symptoms to PCI: 
 ≤2 hours 
 >2 hours to ≤6 hours 
 >6 to ≤12 hours. 

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o In addition, a subset analysis will be evaluated at the following ischemia duration 
time points: 
 ≤6 hours  
 >6 to ≤12 hours. 
o NT-Pro-BNP serum levels (as measurement biomarker  for heart failure) at 
baseline, days 2-4 and 30 and months 3 6, 12 and 24 
o Score changes for TIMI Myocardial Flow Grade and Perfusion assessments at the 
following day 0 time points: 
 pre-PCI,  
 immediately post-PCI,  
 after approximately 50% of intracoronary infusion of investigational 
agent,  
 at completion of intracoronary infusion of investigational agent.   
 
8.3 
Clinical Endpoints 
Clinical Endpoints will be assessed throughout the index hospitalization as well as at outpatient 
visits at 14 and 30 days, and at 3, 6, 12, 18 and 24 months after the index cardiac catheterization 
procedure, including:  
  
 Occurrence of MACCE: 
o Cardiovascular death 
o Non-fatal myocardial infarction 
o Non-fatal stroke 
o Cardiac hospitalization due to heart failure 
 Target vessel (or other vessel) revascularization post index cardiac catheterization and 
new or worsening heart failure during the index hospitalization will be tracked as 
“Adverse Events of Special Interest”. 
 Total number of subjects with documented ventricular arrhythmia (sustained and non-
sustained VT/VF) throughout the study period. 
 Angina pectoris as defined by CCS clinical clarification. 
 Functional status will be classified by the NYHA criteria. 
 
 

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9. 
ASSESSMENT OF SAFETY 
9.1 
Safety Endpoints 
All safety endpoints will be assessed from subject randomization through up to 24 months post 
investigational agent infusion: 
 SAE / AE rates 
 Occurrence of MACCE including: 
o Cardiovascular death 
o Non-fatal myocardial infarction 
o Non-fatal stroke 
o Cardiac hospitalization due to heart failure 
 Target vessel (or other vessel) revascularization post index cardiac catheterization and 
new or worsening heart failure during the index hospitalization will be tracked as 
“Adverse Events of Special Interest”. 
 Total number of subjects with documented ventricular arrhythmia (sustained and non-
sustained VT/VF) throughout the study period. 
 Angina pectoris as defined by CCS clinical clarification. 
 NYHA Class. 
 Telemetry/48 hour Holter monitoring (during hospital admission and at 14 and 30 days, 3 
and 6 months follow-up time points) with assessment of occurrence of ventricular 
arrhythmia.  
 TIMI flow and perfusion measurements following intracoronary infusion of the MPC cell 
solution compared with placebo. 
 Physical examinations, monitoring of vital signs (heart rate, respiratory rate, BP, and 
temperature). 
 Results of clinical laboratory tests (hematology, serum chemistry, inflammatory 
markers), and immunogenicity assays; (flow cytometry Class I and Class II HLA percent 
reactivity % with specificity, antibovine and antimurine antibody analysis). 
 
AE will be collected after a subject has been randomized. The AE will be graded according to 
the protocol as “mild”, “moderate”, “severe” and will be classified according to MedDRA. 
 
An independent DSMB will review all safety and relevant clinical data at regular intervals in 
accordance with their charter. Based on its findings, the DSMB will make recommendations 
regarding study continuation, enrollment and/or study modification(s). 
 

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The primary safety analysis will be performed on the following safety and feasibility parameters 
up to 30 days post-treatment: 
 TIMI flow prior to, during (approximately 50% of total infusion of investigational agent) 
and following infusion of investigational agent after successful PCI. 
 SAE/AE rates.  
 Results of clinical laboratory tests (including hematology, serum chemistry, 
inflammatory markers, flow cytometry anti-HLA Class I and Class II percent reactivity 
with specificity, antibovine and antimurine antibody analysis). 
 Infusion procedure monitoring of vital signs (heart rate, respiratory rate, BP, and 
temperature. 
 
9.2 
Adverse Events  
Each AE should be assessed by the investigator to establish its seriousness, severity and causality 
(relationship to the investigational product).  
 
9.3 
Definitions 
Adverse Event (AE) is defined as any untoward medical occurrence in a subject who was 
treated with an investigational product, and does not necessarily have a causal relationship with 
the treatment.  An AE can therefore be any unfavorable and unintended sign, symptom, or 
disease, whether or not related to the investigational product.  
 
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that:  
 results in death,  
 is life-threatening,  
 requires inpatient hospitalization or prolongation of existing hospitalization,  
 results in persistent or significant disability/incapacity,  
 is a congenital anomaly/birth defect, or 
 is medically important* 
* “Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience, when based on appropriate 
medical judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition.” (CFR 312.32). 
 
Expectedness: An SAE is considered “unexpected” if it is not listed in the IB or is not listed at 
the specificity or severity that has been observed. The Sponsor is responsible for assessing 
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Suspected Unexpected Serious Adverse Event reactions (SUSAR) is defined as a SAE event 
occurring in a subject in an interventional study that is assessed as both causally related to the 
suspect product under clinical investigation and unexpected per the IB. 
 
9.4 
Relationship to Study Product 
For each AE, the relationship to the study drug must be recorded as either related (there is a 
reasonable possibility of a causal relationship between the event and the investigational agent) or 
not related (there is not a reasonable possibility of a causal relationship between the event and 
the investigational agent). In general, a causal relationship will be assigned when facts, evidence, 
or arguments exist to support the causal relationship.  
 
When assessing a relationship between investigational agent and an adverse event, the following 
parameters are to be considered: 
 The causal relationship is reasonable on the basis of clinical judgment and given the 
currently available data. 
 A temporal relationship exists between treatment with the investigational agent or 
protocol-specified procedures and the AE. 
 A biologic plausibility of relationship is present. 
 Any underlying concurrent illness and/or therapies the subject has received are 
considered. 
 
9.5 
Relationship to Study Procedure 
For each AE, the relationship to the Investigational Agent delivery procedure must be recorded 
as either related (there is a reasonable possibility of a causal relationship between the event and 
the study procedure) or not related (there is not a reasonable possibility of a causal relationship 
between the event and the study procedure). 
 
9.6 
Severity of Adverse Events 
The intensity of each event will be rated by the investigator or if needed using the following per 
protocol severity classifications: 
 
 

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Severity 
 
 
 
 
Definition 
 
Mild:  
AEs are transient, require no special treatment, and do not interfere with subject’s 
daily activities. 
Moderate:  
AEs introduce a low level of inconvenience or concern to the subject and may 
interfere with daily activities, but are usually ameliorated by simple therapeutic 
measures. 
Severe:  
AEs interrupt a subject’s usual daily activities and typically require systemic drug 
therapy or other treatment. A severe AE is not necessarily serious; for instance, a 
migraine headache lasting for several hours may be considered severe but not 
serious.  Action taken will be categorized as none, study drug discontinued, dose 
modified, required concomitant medication, required procedure, or other. 
 
9.7 
Procedures for Adverse Event Reporting 
AE will be collected only after a subject has been randomized.  
 
All AE (including MACCE), will be recorded by the investigator or designee as part of the study 
participant’s medical history records and on the appropriate case report form.  The investigator 
or designee will evaluate the relationship of the AE to both the investigational agent and study 
procedure as related, not related, or unknown, and will record the findings, including all pertinent 
details of the event on the eCRF. 
 
The investigator will take appropriate measures to ensure the subject’s well-being and document 
these interventions on the appropriate eCRF. The DSMB will review these events. 
 
To maintain a consistent and thorough approach to the collection, documentation and assessment 
of AE, it is essential that investigators provide the Sponsor with the highest level of medical 
understanding of each event.  This means that when describing an event, medical diagnosis is 
preferred to a list of symptoms.  If a diagnosis can be made, which organizes or explains multiple 
symptoms or a cascade of events, the diagnosis will become the AE and should replace multiple 
symptoms in the eCRF and study records. 
 
9.8 
Protocol- Specified Serious Adverse Events 
For the purposes of this study, SAE that are primary endpoint events will not be reported 
individually in an expedited manner.  These protocol-specified SAE will be monitored by the 
DSMB.  The DSMB will monitor the occurrence of MAACE, all-cause mortality and adverse 

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events of special interest (target vessel revascularization and new or worsening HF during the 
index hospitalization) throughout the study. The DSMB will review all safety data periodically in 
a blinded fashion and may request unblinding of the data, as needed.  If aggregate analysis 
indicates that the events are occurring more frequently in the MPC treatment group this will be 
reported as appropriate (e.g. IND safety report, CIOMs, etc.).  
 
The following is a list of events that will not be reported in an expedited manner: 
 Death (Cardiovascular/Non-Cardiovascular/Unknown) 
 Myocardial infarction 
 Hospitalization for Unstable Angina 
 Hospitalization for other angina/chest pain 
 Hospitalization for heart failure 
 Percutaneous or Surgical Coronary Revascularization 
 Percutaneous or Peripheral Arterial Revascularization 
 Transient Ischemic Attack 
 Stroke. 
 
9.9 
Reporting Requirements  
All SAE reported or observed during the trial, whether protocol defined or not and whether or 
not attributable to the investigational agent, must be reported to 
 within 24 hours of the 
knowledge of the occurrence (this refers to any AE that meets any of the aforementioned serious 
criteria).  To report the SAE, the investigator or designee will complete the SAE form 
electronically in the eCRF.  When the form is completed, 
 Safety personnel will be 
notified electronically and will retrieve the form.  If the event meets serious criteria, and it is not 
possible to access the eCRF, the investigator or designee will send an e-mail to 
Safety 
at 
 or call the 
 SAE hotline (phone number 
listed below) and fax the completed paper SAE form to 
 (fax number listed below) with 
24 hours of awareness.  When the eCRF becomes available, the SAE information must be 
entered within 24 hours of the system becoming available.  
 Safety personnel are 
available for SAE reporting on a 24-hour basis.  Reports are reviewed during normal business 
hours of the receiving office.   
 
 

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Safety Contact Information: 
 Clinical Safety 
 
 
 USA 
 SAE hotline – North America/Asia Pacific: 
  
Facsimile: 
 
e-mail: 
 
 SAE hotline – Europe/Israel: 
Telephone: 
 
Facsimile: 
 
e-mail: 
  
 
The investigator must continue to follow the subject until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the 
subject dies.  Within 24 hours of receipt of follow-up information, the investigator or designee 
must update the SAE form electronically in the EDC system for the study and submit any 
supporting documentation (e.g., subject discharge summary or autopsy reports) to 
 
Safety personnel via fax or e-mail.  If it is not possible to access the eCRF, refer to the 
procedures outlined above for initial reporting of SAEs.   
 
The Sponsor and/or designated CRO personnel will be available to answer questions and to assist 
site personnel in documenting SAEs and completing the SAE eCRF. 
 
All SAE that are considered unexpected and related to the study product will be reported by the 
Sponsor or its designee as a 15-day report to the Regulatory Authorities as applicable and to all 
participating investigators.  
 
SAEs that are considered unexpected, related to the study and are life threatening or result in 
death will be reported by the Sponsor or its designee to the regulatory authorities as applicable, 
and to all participating investigators as a 7-day report.  
 
Each investigator must notify the Institutional Review Board (IRB)/ Ethics Committee (EC) 
responsible for reviewing the study at their site of all 15-day or 7-day safety reports required by 
local regulations and shall provide the Sponsor or its designee with written confirmation of said 
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9.10 
Pregnancy Reporting  
If the subject becomes pregnant during the study, the investigator should report the pregnancy to 
the Sponsor, or its representative, within 24 hours of being notified.  
 Safety personnel 
will then forward the Exposure in Utero form to the investigator for completion.  The subject 
should be followed by the investigator until completion of the pregnancy and continue to be 
monitored for duration of the study.  If the pregnancy ends for any reason before the anticipated 
date, the investigator should notify the Sponsor.  At the completion of pregnancy, the 
investigator will document the outcome of pregnancy.  If the outcome of the pregnancy meets the 
criteria for immediate classification as an SAE (i.e., postpartum complication, spontaneous 
abortion, stillbirth, neonatal death, or congenital anomaly), then the investigator should follow 
reporting procedures for an SAE.   
 
10. 
ASSESSMENT OF FEASIBILITY  
10.1 
Feasibility Endpoint 
Feasibility of the infusion of the investigational agent will monitored by measurement of TIMI 
Flow prior to, during (approximately 50% of total investigational agent volume infused), and 
following the investigational agent infusion after successful PCI and stenting. 
 
11. 
STATISTICAL CONSIDERATION  
11.1 
Introduction  
The objective of this study is to determine the safety and feasibility of IC allogeneic immuno-
selected, bone marrow-derived Stro3 MPC delivery in the treatment of subjects with STEMI 
undergoing primary PCI of the LAD coronary artery. 
 
11.2 
Statistical Methods 
The primary efficacy analysis will use an ANCOVA model with baseline LVESV as covariate 
and alpha=0.05 to test for a difference of change in LVESV from baseline to Month 6 between 
each MPC arm separately and the placebo arm.  If neither MPC arm is found to be better than the 
placebo arm and there is no difference between the MPC groups (using the ANCOVA test with 
alpha= 0.1) in the effect on LVESV, then the pooled MPC group will be compared to the placebo 
group for all functional parameters. 
 
All other statistical tests will be considered to be exploratory (post-hoc) unless a pre-specified 
hypothesis exists in the statistical analysis plan (SAP), which will be finalized prior to any 
analysis.  All statistical tests will be two-sided and statistical significance will be assessed with 

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respect to a nominal p-value ≤0.05.  Any deviations from the planned analyses will be 
documented and justified in the final clinical/statistical study report. 
 
The primary efficacy analysis for LVESV will be performed using cMRI collected data.  The 
secondary efficacy analyses for LVESV will be performed using ECHO data alone, as well as 
ECHO data as a substitute for missing cMRI data at baseline and/or at Month 6.   
 
In the latter case, a regression equation will be determined between measurements for LVESV-
cMRI and LVESV-ECHO over a range of values. Whenever appropriate and based on LVESV-
ECHO values generated using the regression equation, a LVESV-ECHO “corrected” value will 
be determined and used as a replacement for missing value for LVESV-cMRI. 
 
When all enrolled subjects have completed the study through Visit 9 (Month 6), an unblinded 
analysis of the safety and primary and secondary efficacy endpoints will be conducted.  
 
The primary and secondary efficacy analyses will be performed using data collected through 
Visit 9 (Month 6). In addition, safety analyses will be performed on all available data through 
Visit 12 (Month 24) at the time of conduct of the efficacy analysis. In addition, the final safety 
analysis will be performed at 24 months for all patients. 
 
No additional efficacy data will be collected beyond Visit 9 (Month 6) except for cardiac 
biomarkers.   
 
11.3 
General Considerations 
All clinical test results will be listed and summarized by treatment and time with appropriate 
descriptive statistics (number of observations, mean, median, standard deviation, minimum, and 
maximum) for continuous measures.  Nominal and ordinal scale measures will be summarized 
with frequency tables, relative risk, and percentages, as appropriate.  
 
11.4 
Analysis Populations 
The four populations, Safety, Intent-to-Treat (ITT), Per Protocol (PPP) and Full Analysis 
Population (FAP), are defined below. 
 

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11.4.1 
Safety Population 
The Safety set will include all ITT subjects who received the study treatment.  In the event that a 
subject receives treatment other than what was assigned, safety analyses will be conducted 
according to the treatment that the subject actually received. 
 
11.4.2 
Intent-to-Treat Population 
The set of Intent-to-Treat (ITT) subjects will include all subjects who are randomly assigned to a 
treatment at screening, regardless of whether or not the subject receives the study treatment. 
 
11.4.3 
Per-Protocol Population 
The PPP will include ITT subjects who do not have major protocol violations, and have at least 
one post-treatment efficacy and safety evaluation. 
 
11.4.4 
Full Analysis Population 
The Full Analysis Population will include all subjects who are randomized, have undergone PCI 
and had infusion of study agent (MPCs or Placebo) initiated. 
 
11.5 
Determination of Sample Size  
To detect a treatment effect of 10.0 ml for LVESV (SD 14 ml), 
 
 as well as published clinical data 
1-3, 58,59, with a two-sided 5% significance level and a power of 80%, a sample size of 
105 subjects will be necessary, given the observed dropout rate of approximately 4%. Of these, 
approximately 70 will receive MPCs (35 to receive 12.5 M MPC and 35 to receive 25M MPC) 
and 35 will receive placebo and act as control subjects.  
 
11.6 
Background, Demographic and Concomitant Medications 
Demographic data, medical history, concomitant disease and concomitant medication will be 
summarized by means of descriptive statistics (n, mean, SD, median, minimum and maximum) 
or frequency tables, stratified by treatment. 
 
11.7 
Protocol Deviations 
Deviations from the protocol including violations of inclusion/exclusion criteria will be assessed 
as “minor” or “major”. Deviations will be defined prior to un-blinding. 
 

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11.8 
Efficacy and Feasibility Analyses 
Where appropriate, 95% confidence intervals for treatment differences in key feasibility 
measures will be constructed. Analysis of covariance (ANCOVA) may be used where 
appropriate to adjust for baseline differences in key continuous feasibility outcome measures and 
also take the site and the time from onset of AMI symptoms to PCI as covariates in the 
ANCOVA model.  For non-normally distributed measures, the Wilcox-Mann-Whitney test or 
analysis of variance ANOVA of rank transformed data may be used as an alternative.  For 
categorical measures, relative risks and nominal 95% confidence intervals will be constructed to 
assess strength of association.  The Cochran-Mantel-Haeszel test (CMH) controlled by site and 
the time from the onset of AMI symptom to PCI will be used for the treatment differences. The 
primary feasibility analysis will be performed on the FA population, and confirmatory based on 
PP population. 
 
The primary and secondary efficacy analyses will be performed on ITT, FA, and PP populations. 
Analysis of clinical endpoints will be performed on all analysis populations. 
 
11.9 
Safety Analyses 
Review of safety tables, listings and figures will be performed by the medical monitor or 
designee.  The safety tables will allow a view of changes from baseline in findings from 12-lead 
ECGs, vital signs, clinical laboratory values, and adverse events. No statistical testing will be 
executed for safety measures. 
 
In this safety study with a limited sample size and projected high subject exclusion rate, the 
safety analysis will be performed on the Safety population.  These analyses will include 
categorization of events per study phase (before and after cell infusion or assigned treatment) and 
event attribution as appropriate to the study phase.  All analyses will include those at baseline, to 
2 weeks post-index procedure.   
 
Safety analyses will be performed on all available data through Visit 12 (Month 24) at the time 
of conduct of the efficacy analysis.  In addition, the final safety analysis will be performed at 
24 months for all patients. 
 
 

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11.10 
Timing of Planned Analyses 
Primary and Secondary Efficacy Analysis:  
Analysis of efficacy will occur once all subjects have completed the 6-month visit.  
 
Feasibility analysis:  
Feasibility analysis based on TIMI flow will be concurrent with the analysis of efficacy 
described above. 
 
Initial Safety Follow Up: 
Preliminary analysis of safety will be concurrent with the analysis of efficacy described above. 
 
Long Term Safety Follow up: 
Analysis of long-term safety will occur once all subjects have completed the 24-month visit. 
 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE  
The Sponsor shall implement and maintain quality control and quality assurance procedures with 
written standard operating procedures to ensure that the study is conducted and data are 
generated, documented, and reported in compliance with the protocol, GCP, and applicable 
regulatory requirements.  This study shall be conducted in accordance with the provisions of the 
Declaration of Helsinki (October 1996) and all revisions thereof, and in accordance with 
applicable regulations and with the ICH guidelines on GCP (ICH E6).  
 
13. 
REGULATORY OBLIGATIONS 
13.1 
Institutional Review Board (IRB)/ Ethics Committee (EC) Approval 
Prior to enrollment of subjects into the study, as required by relevant regulations, the protocol, 
and informed consent form will be reviewed and approved by an appropriate IRB/EC. By 
signing the Statement of Investigator Form (FDA 1572 or equivalent), the investigator assures 
that all aspects of the institutional review will be conducted in accordance with current federal 
regulations and ICH.  A letter documenting the IRB/EC approval must be received by the 
sponsor prior to the initiation of the study.  Amendments to the protocol will be subject to the 
same review and approval requirements as the original protocol.  
 
The investigator shall promptly notify the IRB/EC of any SAE, or any other information that 
may affect the safe use of the drug during the course of the study. 
 

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13.2 
Protocol Compliance 
Except for a change that is intended to eliminate an apparent immediate hazard to a study 
subject, the protocol shall be conducted as described.  Protocol violations must be reported 
immediately to the Sponsor or its representative(s) as well as the governing IRB/EC and relevant 
regulatory authority as required. 
 
13.3 
Changes to the Protocol 
The investigator may not deviate from the protocol without a formal protocol amendment having 
been established and approved by an appropriate IRB/EC, and relevant regulatory authority if 
required, except when necessary to eliminate immediate hazards to the subject or when the 
change(s) involve only logistical or administrative aspects of the study.  Any deviation may 
result in the subject having to be withdrawn from the study and rendering that subject non-
evaluable. 
 
13.4 
Informed Consent 
Each subject must sign the study-specific informed consent form to enroll as a participant in the 
study.  This consent form will comply with all applicable regulations governing the protection of 
human subjects. The basic elements of informed consent are specified in the ICH Guideline for 
GCP (E6). 
 
13.5 
Source Documents 
During the study, the investigator will maintain adequate records for the study, including medical 
records, records detailing the progress of the study for each subject, laboratory reports, study 
worksheets/subject questionnaires, signed informed consent forms, drug disposition records, 
correspondence with the IRB/EC/Competent Authority, AE reports, and information regarding 
subject discontinuation and completion of the study. 
 
13.6 
Case Report Form Completion 
All data obtained during this study should be entered on the eCRFs promptly.  All source 
documents from which eCRF entries are derived should be placed in the subject’s medical 
records.  
 
 

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13.7 
Financial Disclosures 
In accordance with the US Code of Federal regulations, Title 21, Part 54, the investigator will 
provide the Sponsor or its designee sufficient and accurate information on financial interests 
(proprietary or equity interests, payments exclusive of clinical study costs) to allow complete 
disclosure to regulatory authorities.  The investigator shall promptly update this information with 
any relevant changes that occur during the course of the study and for a period of 1 year 
following the completion of the study. 
 
13.8 
Termination of the Study 
If the Investigator, Medical Monitor, ESC or DSMB becomes aware of conditions or events that 
suggest a possible study related hazard to subjects if the study continues, they may recommend 
to the Sponsor that the study be terminated after appropriate consultation between the relevant 
parties.  The decision to terminate the study remains with the Sponsor.  The study may also be 
terminated early at the Sponsor’s discretion in the absence of such a finding. 
 
Conditions that may warrant termination by the Sponsor may include, but are not limited to: 
 The discovery that in the opinion of the Sponsor poses an unexpected, significant, or 
unacceptable risk to the subjects enrolled in the study; 
 A decision on the part of the Sponsor to suspend or discontinue development of the test 
material for any reason. 
 
13.9 
Retention of Essential Documents 
All records and documents pertaining to the study including, but not limited to, those outlined 
above will be maintained by the investigator for at least a period of (or longer depending upon 
the local Regulatory Agency requirements): (a) 2 years after last approval of the product; (b) 
5 years after non-approval of the Biologics License Application (BLA); or (c) 2 years after 
termination of investigational agent development program. In order to avoid any possible errors, 
the investigator will contact the Sponsor prior to the destruction of any study records.  The 
investigator will promptly notify the Sponsor in the event of accidental loss or destruction of any 
study records.   
 
13.10 
 Confidentiality 
All study findings and documents will be regarded as confidential.  The investigator and 
members of his/her research team must not disclose such information without prior written 
approval from the Sponsor. 
 

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14. 
REFERENCES 
1. 
Janssens, S., Dubois, C., Bogaert, J., et al.  Autologous bone marrow-derived stem-
cell transfer in patients with ST-segment elevation myocardial infarction:  double-
blind, randomised controlled trial.  Lancet 2006;367:113-121. 
2. 
Francone M, Bucciarelli-Ducci C, Carbone I, et al.  Impact of primary coronary 
angioplasty delay on myocardial salvage, infarct size, and microvascular damage in 
patients with ST-segment elevation myocardial infarction.  J Am Coll Cardiol 2009; 
54:2145-2153. 
3. 
Mewton, N., et al., Effect of cyclosporine on left ventricular remodeling after 
reperfused myocardial infarction. J Am Coll Cardiol, 2010. 55(12): p. 1200-5. 
4. 
Dharmarajan K,Hsieh A, Lin Z, Bueno H,Ross J,Horwitz L, Barreto-Filho J, Kim N, 
Suter L,Bernheim S, Drye E, and Krumholz H. Hospital readmission performance 
and patterns of readmission: retrospective cohort study of Medicare admissions.  BMJ 
2013;347:f6571 doi: 10.1136/bmj.f6571 (Published 20 November 2013)   
5. 
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