A Phase I, Multi-Center, Open-Label, Dose Escalation Study of Thrombosomes® in Bleeding Thrombocytopenic Patients in Three Cohorts
Phase: PHASE1
Conditions: Thrombocytopenia, Hematologic Diseases, Bone Marrow Aplasia
Sponsor: Cellphire Therapeutics, Inc.

 
 
 
 
A Phase I, Multi-Center, Open-Label, Dose Escalation Study of Thrombosomes® in Bleeding 
Thrombocytopenic Patients in Three Cohorts  
Cellphire, Inc. 
Clinical Protocol # 2017-1 Version 2.0  
October 18, 2018  
NCT03394755  

Cellphire, Inc. 
 
Thrombosomes® 
 
 
 
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A Phase I, Multi-Center, Open-Label, Dose Escalation Study of 
Thrombosomes® in Bleeding Thrombocytopenic Patients in Three 
Cohorts 
 
Cellphire, Inc. 
Clinical Protocol # 2017-1 
Version 2.0 
October 18, 2018 
 
 
 
  
Printed Name 
Signature 
Function 
Date 
Mike Fitzpatrick, PhD 
 
 
Research/Development 
 
Ruth Biehl 
 
 
Quality 
 
Emily Rossiter 
 
 
Regulatory 
 
Joan Pehta, MD 
 
 
Medical Consultant 
 
 
 
 

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Table of Contents 
Description 
Page 
1.1 
PRINCIPAL INVESTIGATOR & SUB INVESTIGATORS ........................................................ 6 
1.2 
STUDY LOCATION AND TESTING OR OTHER MEDICAL/TECHNICAL 
DEPARTMENTS/INSTITUTIONS INVOLVED IN STUDY ..................................................................... 7 
1.3 
PROGRAM PHASE .............................................................................................................. 9 
1.4 
TIME REQUIRED FOR STUDY COMPLETION ..................................................................... 9 
1.5 
LIST OF ACRONYMS .......................................................................................................... 9 
1.6 
BACKGROUND ................................................................................................................. 12 
1.7 
PRODUCT INFORMATION & INDICATIONS FOR USE ....................................................... 12 
1.8 
OBJECTIVES .................................................................................................................... 13 
1.8.1 
Primary ........................................................................................................................... 13 
1.8.2 
Secondary ....................................................................................................................... 13 
1.9 
STUDY DESIGN ................................................................................................................ 13 
1.9.1 
Introduction ................................................................................................................... 13 
1.9.2 
Methodology ................................................................................................................... 13 
1.9.2.1 
All Cohorts ................................................................................................................... 14 
1.9.2.2 
Additional Hemostatic Therapy:  All Cohorts ............................................................. 15 
1.9.3 
Assessment of Bleeding: Using WHO Bleeding Score ................................................ 16 
1.9.4 
Blinding .......................................................................................................................... 16 
1.9.5 
Duration of Patient Participation and Study .............................................................. 16 
1.9.6 
Patient Compensation ................................................................................................... 16 
1.9.7 
Cohort Study Schedule .................................................................................................. 17 
1.9.8 
Stopping Rules and Procedures for Study .................................................................. 17 
1.9.9 
Safety Endpoints ............................................................................................................ 18 
1.10 
STUDY POPULATION ........................................................................................................ 18 
1.10.1 
Patient Numbers ......................................................................................................... 18 
1.10.2 
Target Population ....................................................................................................... 19 
1.11 
INCLUSION /EXCLUSION CRITERIA ................................................................................ 19 
1.11.1 
Inclusion Criteria ....................................................................................................... 19 
1.11.2 
Exclusion Criteria ...................................................................................................... 20 
1.11.3 
Inclusion of Women and Minorities ......................................................................... 21 

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1.12 
RECRUITMENT PROCESS ................................................................................................. 21 
1.13 
SAMPLE SIZE JUSTIFICATION ......................................................................................... 21 
1.14 
INFORMED CONSENT PROCESS ....................................................................................... 21 
1.15 
 STUDY PROCEDURE ........................................................................................................ 23 
1.15.1 
Measures to Protect Study Patients .......................................................................... 27 
1.15.2 
Receipt and Storage of Thrombosomes .................................................................... 27 
1.15.3 
Drawing Blood Samples from Patients ..................................................................... 28 
1.15.4 
Instructions for Reconstitution and Administration of Thrombosomes ............... 28 
1.15.5 
Blinding of Study Patients ......................................................................................... 29 
1.15.6 
Unscheduled/ Emergency Follow-up Visits .............................................................. 29 
1.15.6.1 
Non-emergent Unscheduled Patient Evaluation (minimum) .................................... 29 
1.15.6.2 
Blood Sampling/Testing ........................................................................................... 29 
1.15.6.3 
AE Evaluation ........................................................................................................... 30 
1.16 
DATA ANALYSIS .............................................................................................................. 30 
1.17 
DATA MANAGEMENT ...................................................................................................... 30 
1.18 
RISK ASSESSMENT ........................................................................................................... 31 
1.18.1 
Foreseeable or Potential Risks .................................................................................. 31 
1.18.2 
Potential Patient Risks for Special Vigilance by Investigator ................................ 31 
1.18.3 
Potential Risks to Study Personnel ........................................................................... 32 
1.18.4 
Risk Management and Emergency Response .......................................................... 32 
1.18.4.1 
Pregnancy .................................................................................................................. 32 
1.18.4.2 
Risk Management ..................................................................................................... 32 
1.18.4.3 
Emergency Care and Treatment ................................................................................ 33 
1.18.5 
Stopping Criteria and DMC Review ........................................................................ 33 
1.18.6 
Potential Benefits ........................................................................................................ 33 
1.19 
STUDY PERSONNEL ......................................................................................................... 33 
1.19.1 
Key Study Personnel .................................................................................................. 33 
1.19.2 
Conflict of Interest ..................................................................................................... 33 
1.20 
MEDICAL MONITORING .................................................................................................. 33 
1.21 
STUDY MONITORING AND AUDITING ............................................................................. 34 
1.22 
STUDY ORGANIZATION AND MANAGEMENT PLAN ........................................................ 34 
1.22.1 
Study Management .................................................................................................... 34 
1.22.2 
Study Timeline ............................................................................................................ 34 

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1.22.3 
Patient Withdrawal .................................................................................................... 34 
1.22.4 
Protocol Modifications ............................................................................................... 35 
1.22.5 
Protocol Deviations .................................................................................................... 36 
1.22.5.1 
Anticipated Deviations .............................................................................................. 36 
1.22.5.2 
Unanticipated Deviations .......................................................................................... 36 
1.22.6 
Adverse Events and Unanticipated Problems ......................................................... 36 
1.22.6.1 
Definition of Terms ................................................................................................... 36 
1.22.6.2 
Relationship to Investigational Product .................................................................... 38 
1.22.6.3 
Severity Assessment ................................................................................................. 39 
1.22.6.4 
Adverse Event Reporting .......................................................................................... 39 
1.22.7 
Study Forms and Recording of Information ........................................................... 40 
1.22.8 
Continuing Review and Reporting ........................................................................... 40 
1.22.9 
Applicable Regulatory Requirements ...................................................................... 41 
1.22.10 
Confidentiality and Disposition of Records ............................................................. 41 
1.22.10.1 
Confidentiality of Study Information ........................................................................ 41 
1.22.10.2 
Confidentiality of Patient Information ...................................................................... 42 
1.22.11 
Security of Investigational Products ......................................................................... 42 
1.22.12 
Shipping of Specimens ............................................................................................... 42 
1.22.13 
Clinical Trial Registration ......................................................................................... 42 
1.22.14 
Investigator Signature Page ...................................................................................... 43 
APPENDIX A- MODIFIED WHO BLEEDING SCORE ..................................................................... 44 
APPENDIX B- FLOW DIAGRAM OF STUDY EVENTS ..................................................................... 46 
APPENDIX C- DEFINITION OF MYOCARDIAL INFARCTION ......................................................... 47 
APPENDIX D- DEFINITION OF ALI ADAPTED FROM NHSN BIOVIGILANCE COMPONENT 
HEMOVIGILANCE MODULE SURVEILLANCE PROTOCOL V2.4 .................................................... 48 
APPENDIX E- DVT AND PE ALGORITHM PAGES FROM ICSI GUIDELINE ................................. 49 
APPENDIX F –  INSTRUCTIONS FOR RECONSTITUTION AND PREPARATION OF THROMBOSOMES 
FOR ADMINISTRATION .................................................................................................................. 51 
Appendix F.1 Supplies and Equipment Required ................................................................. 51 
Appendix F.2 Reconstitution of Thrombosomes ................................................................... 51 
Appendix F.3 Preparation of Doses of Thrombosomes ........................................................ 52 
APPENDIX G –  MODIFIED DEFINITION OF ANAPHYLAXIS .......................................................... 54 
 

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List of Tables 
Description 
Page 
Table 1. Cohort Assignment ..................................................................................................... 14 
Table 2. Patient Cohort Assignment, Dose and Safety Margins ............................................ 15 
Table 3. Proposed Patient Compensation ................................................................................ 17 
Table 4.  Schedule of Events ..................................................................................................... 23 
Table 5. Potential Study Risks .................................................................................................. 31 
Table 6. Requirements Following Patient Withdrawal .......................................................... 35 
Table 7.  Protocol Deviations (Anticipated) ............................................................................. 36 
 

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1.1 Principal Investigator 
Roles and Responsibilities of PI: Eligibility review, evaluate adverse events, adhere to GCP, and supervise staff participation in study. 
 
PI Name 
Institution 
Contact Details 
Jose Cancelas-Perez, MD, PhD 
Hoxworth Blood Center/ University of 
Cincinnati 
Email: cancelje@ucmail.uc.edu 
Phone: 515-558-1324 
Vinod Pullarkat, MD 
City of Hope National Medical Center 
Email: vpullarkat@coh.org 
Phone: 626-256-4673 ext. 83524 
Zbigniew Szczepiorkowski, MD, PhD 
Dartmouth Hitchcock Medical Center 
Email: ziggy@dartmouth.edu 
Phone: 603-650-7171 
Robertson Davenport, MD 
University of Michigan 
Email: rddvnprt@med.umich.edu 
Phone: 734-936-6776 
Maro Ohanian, DO 
The University of Texas/ MD Anderson 
Cancer Center 
Email: MOhanian@mdanderson.org 
Phone: 713-792-2631 
Catherine Broome, MD 
Georgetown University Medical Center 
Email: Catherine.M.Broome@gunet.georgetown.edu 
Phone: 202-444-8240 
Tor Hervig, MD 
Haukeland University Hospital 
Email: tor.audun.hervig@helse-bergen.no 
Phone: +47 55972492 

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1.2 Study Location and Testing or Other Medical/Technical Departments/Institutions Involved in Study 
Institution Name 
Institution Address 
Procedure or Test 
University of Cincinnati Medical Center 
Hematology/Oncology, 234 
Goodman Street, Cincinnati, 
OH, 45219 
Patient Infusion and post-infusion 24 hour observation and 
monitoring 
University of Cincinnati Medical Center 
Clinical Laboratory 
234 Goodman Street, Cincinnati, 
OH, 45219 
All laboratory testing except those tests performed by 
Haemtech Biopharma Services 
Haemtech Biopharma Services 
57 River Road, Essex Junction, 
VT, 05452 
TAT, PF 1+2, TGA 
City of Hope National Medical Center 
1500 E. Duarte Road, Duarte, 
CA 91010 
Patient Infusion and post-infusion 24 hour observation and 
monitoring 
City of Hope National Medical Center, Division 
of Pathology 
1500 E. Duarte Road, Duarte, 
CA 91010 
All laboratory testing except those tests performed by 
Haemtech Biopharma Services 
Dartmouth-Hitchcock Medical Center 
1 Medical Center Drive, 
Lebanon, NH 03756 
Patient Infusion and post-infusion 24 hour observation and 
monitoring 
Dartmouth-Hitchcock Medical Center 
 Dept of Pathology and Laboratory Medicine 
Clinical Laboratory 
1 Medical Center Drive, 
Lebanon, NH 03756 
All laboratory testing except those tests performed by 
Haemtech Biopharma Services 
University of Michigan 
1500 E. Medical Center Drive, 
Ann Arbor, MI 48109 
Patient Infusion and post-infusion 24 hour observation and 
monitoring 
University of Michigan Hospitals- Department 
of Pathology 
1500 E. Medical Center Drive, 
Ann Arbor, MI 48109 
All laboratory testing except those tests performed by 
Haemtech Biopharma Services 
The University of Texas/ MD Anderson Cancer 
Center 
1515 Holcombe Blvd., Houston, 
TX 77030 
Patient Infusion and post-infusion 24 hour observation and 
monitoring 
The University of Texas/ MD Anderson Cancer 
Center, Division of Laboratory Medicine 
1515 Holcombe Blvd., Unit 024, 
Houston, TX 77030 
All laboratory testing except those tests performed by 
Haemtech Biopharma Services 
Georgetown University Medical Center 
3800 Reservoir Road, NW 
Washington, DC 20007 
Patient Infusion and post-infusion 24 hour observation and 
monitoring 

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Dept. of Lab MedStar Georgetown University 
Hospital 
3800 Reservoir Road, NW, 1 
Main Rm M1341Washington, 
DC 20007 
All laboratory testing except those tests performed by 
Haemtech Biopharma Services 
Haukeland University Hospital 
Dept. of Hematology/Immunology and 
Transfusion Medicine 
Postboks 1400, Bergen 
Norway 5021 
Patient Infusion and post-infusion 24 hour observation and 
monitoring 
Haukeland University Hospital 
Dept. of Immunology and Transfusion 
Medicine  
Dept. of Medical Biochemistry and 
Pharmacology 
Postboks 1400, Bergen 
Norway 5021 
All laboratory testing except those tests performed by 
Haemtech Biopharma Services 

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1.3 Program Phase 
The following protocol governs a Phase 1 dose escalation clinical trial. 
1.4 Time Required for Study Completion 
First Patient Treated: Q1 2018 
Last Patient Last Visit: Q2 2019 
1.5 List of Acronyms 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
ALL 
Acute Lymphoblastic Leukemia 
ALT 
Alanine Transaminase 
AML 
Acute Myeloid Leukemia 
aPTT 
Activated Partial Thromboplastin Time 
AST 
Aspartate Aminotransferase 
BARDA 
Biomedical Advanced Research and Development Authority 
BP 
Blood Pressure 
BUN 
Blood Urea Nitrogen 
CAT 
Calibrated Automated Thrombogram 
CBC 
Complete Blood Count 
CBER 
Center for Biologics Evaluation and Research 
CCI 
Corrected Count Increment 
CDC 
Center for Disease Control 
CFR 
Code of Federal Regulations 
CNS 
Central Nervous System 
COR 
Contracting Officer’s Representative (BARDA) 
COX 
Cyclooxygenase 
CPTP 
Clinical Pretest Probability 
CRC 
Clinical Research Center  
CRO 
Clinical Research Organization 
CRF 
Case Report Form 
CSTD 
Closed System Transfer Device 
CTPA 
Computed Tomography Pulmonary Angiogram 
DIC 
Disseminated Intravascular Coagulation 
DMC 
Data Monitoring Committee 
DOT 
Department of Transportation 

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DVT 
Deep Vein Thrombosis 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
FDP 
Fibrin Degradation Products 
GVHD 
Graft-versus-Host Disease 
IND 
Investigational New Drug 
IUD 
Intra-Uterine Device 
EKG 
Electrocardiogram 
GGT 
Gamma Glutamyl Transferase 
HIPAA 
Health Insurance Portability and Accountability Act 
hs 
High sensitivity 
IATA 
International Air Transport Association 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ICSI 
Institute for Clinical Systems Improvement 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IU 
International Unit 
IV 
Intravenous 
LDH 
Lactate Dehydrogenase 
MI 
Myocardial Infarction 
NCI 
National Cancer Institute 
NHSN 
National Healthcare Safety Network 
NIH 
National Institutes of Health 
NZWR 
New Zealand White Rabbit 
OHRP 
Office for Human Research Protections 
PE 
Pulmonary Embolism 
PEF 
Peak Expiratory Flow 
PERC 
Pulmonary Embolism Rule-out Criteria 
PF 
Prothrombin Fragment 
PI 
Principal Investigator 
Plt 
Platelet 
PT 
Prothrombin Time 
RBC 
Red Blood Cell 
RR 
Respiration Rate 
SADR 
Serious Adverse Drug Reaction 
SAE 
Serious Adverse Event 

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SOP 
Standard Operating Procedure 
TAT 
Thrombin Antithrombin 
TEAE 
Treatment Emergent Adverse Event 
TEG 
Thromboelastography 
TGA 
Thrombin Generation Assay 
TIA 
Transient Ischemic Attack 
TGPU 
Thrombin Generation Potency Units 
USP 
United States Pharmacopeia 
VTE 
Venous Thromboembolism 
WFI 
Water for Injection 
WHO 
World Health Organization 
 

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1.6 Background 
Traumatic injury and massive uncontrollable hemorrhage are major public health problems in 
the United States1.  Despite rapid, significant, advances in medicine and technology, 
hemorrhage treatment has in many ways lagged behind other blood product therapies such as 
coagulation factors and plasma proteins.  A systemic hemostatic agent has the potential to fill 
unmet medical needs in non-compressible bleeding such as internal hemorrhage or diffuse 
vascular bleeding.  Thrombosomes® treatment, if proven safe and effective in human trials, 
could assist in the management of blood loss associated with trauma, uncontrolled internal 
bleeding, and/or non- compressible hemorrhage. 
In July of 2016, Cellphire completed a clinical study under an exploratory IND in 15 subjects 
(Thrombosomes n=10 and Control n=5) who received ascending doses of either: 1) 
Thrombosomes ranging from 1/1,000 to 1/10 of the projected minimum effective dosage (~1.89 
x 108 Thrombosomes particles per kg or 330 Thrombin Generation Potency Units (TGPU) per 
kg), or 2) Thrombosomes Control ( the mixture of excipients used to stabilize Thrombosomes 
but without the platelet component). The highest dose achieved was 1.55 x 107 particles per kg 
which has the potential to produce 27 IU of thrombin in-vitro.  
There were no serious adverse events (SAEs) including deaths or stopping rules met on study, no 
decrease of platelet count of 20% or more from baseline, and no clinically significant changes in 
platelet count (change of 5% from baseline combined with post-baseline result outside of normal 
ranges) that occurred during the study.  No statistically significant differences were seen when 
comparing the changes in platelet count between baseline and post-infusion values for subjects in 
Thrombosomes and Control groups.  
Although this study, and more specifically the individual treatment cohorts, contained a small 
number of subjects, which led to high variability in reported AEs, the frequency and nature of 
TEAEs reported in this study are consistent with AEs that are typically observed in a healthy 
volunteer population.  Overall, no clinically significant abnormities were reported after infusion 
of Thrombosomes, and the results were similar between the control and treated cohorts. 
1.7 Product Information & Indications for Use 
Thrombosomes are a lyophilized product prepared from a pool of group O human platelets 
(collected from 5-10 donors) that are being developed for the treatment of uncontrolled 
hemorrhage.  Each vial from each lot of Thrombosomes contains a mean of 1.7 x 109 
Thrombosomes particles per ml and an associated activity of approximately 3400 TGPU per ml 
after rehydration with 10 ml of sterile water for injection.  Based upon efficacy studies in a 
thrombocytopenic New Zealand White Rabbit (NZWR) ear bleed model, the lowest observed 
efficacious dose was (1.89 x 108 particles per kg or 330 TGPU per kg).  Refer to the 
Investigator’s Brochure for additional information. 
 
1 National Highway Traffic Safety Administration Fatality Analysis Reporting System (FARS) 1975-2009 – 
http://nhtsa.gov/FARS 

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1.8 Objectives 
The primary and secondary objectives of this trial, conducted in thrombocytopenic patients 
(platelet count ≥ 5,000/ µL and ≤ 70,000/µL) with modified World Health Organization (WHO) 
Grade 1* or 2 bleeding are:   
1.8.1 
Primary 
• Assess the safety of infusing increasing doses (approximately 5 ml, 10 ml, and 20 ml) of 
allogeneic Thrombosomes which are equivalent to approximately 9.45 x 107 particles/kg or 
165 TGPU per kg, 1.89 x 108 particles/kg or 330 TGPU per kg and 3.78 x 108 particles/kg or 
660 TGPU per kg, respectively. 
1.8.2 
Secondary 
• Assess the effect, on WHO bleeding score, of increasing doses of allogeneic Thrombosomes. 
• Assess the effect of increasing doses of allogeneic Thrombosomes on measures of 
coagulation. 
* Note:  Only a subset of patients with Grade 1 bleeding who have either epistaxis, hematuria, 
oral petechiae, oropharyngeal bleeding, or bleeding at invasive or other wound sites. 
1.9 Study Design 
1.9.1 
Introduction 
This study will require enrollment of patients into three cohorts in order to evaluate, in a dose-
escalation manner, the safety, and preliminary impact on bleeding, and the preliminary effect on 
coagulation measures of increasing doses of allogeneic Thrombosomes.  Data from this study 
will provide information on the safety, and possibly potency of three increasing doses of 
Thrombosomes in order to support the design of future clinical protocols in bleeding patients.  
The proposed starting dose in this protocol is approximately five (5) times the highest dose used 
in a previous dose escalation study in normal healthy volunteers.  For further information 
regarding minimum effective dose, maximum feasible dose and safety margins from previous 
clinical and non-clinical investigations, see the Investigator’s Brochure. 
1.9.2 
Methodology 
This is a Phase 1, multicenter, open-label, dose-escalation study in hospitalized, bleeding, and 
thrombocytopenic patients.  Patients with modified WHO Grade 1 (see note following Table 1. 
Cohort Assignment) or Grade 2 bleeding due to hematology/oncology diseases or bone marrow 
aplasia secondary to cancer chemo/radiotherapy will be enrolled on study and treated with 
allogeneic Thrombosomes (See  
 

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Appendix A- Modified WHO Bleeding Score).  Patients with WHO Grade 0, 3, or 4 bleeding do 
not meet eligibility criteria for enrollment. The protocol will require three cohorts of patients 
consisting of 8 patients in each cohort for a total of 24 patients (See Table 1. Cohort 
Assignment). 
Table 1. Cohort Assignment 
 
Cohort 
1 
2 
3 
Total 
 
n 
n 
n 
n 
WHO Grade 1*or 2 
8 
8 
8 
24 
Note:  *Only a subset of patients with Grade 1 bleeding who have either epistaxis, hematuria, 
oral petechiae, oropharyngeal bleeding, or bleeding at invasive or other wound sites. 
1.9.2.1 
All Cohorts 
Informed consent will be obtained from thrombocytopenic (platelet count ≥ 5,000/ µL and £ 
70,000 per µl) patients who are actively bleeding or are at risk of active bleeding within the 4 
weeks of initial screening.  Patients are eligible who have had a documented bleeding episode(s) 
within the previous 4 days of screening.  If they pass screening, they will be enrolled and 
infused.  Patients who are not actively bleeding, but who are at risk for active bleeding based on 
medical history and prognosis (projected clinical course) within 4 weeks from their initial 
screening, will be monitored for active bleeding.  If the patient was not actively bleeding at the 
time of screening, but bleeding occurs within 4 days (+ 6 hours) of initial screening, the patient 
does not need to be rescreened, but must have a WHO bleeding assessment and a CBC at 
baseline. If the patient was not actively bleeding at the time of screening, but bleeding occurs 
greater than 4 days and within 4 weeks of initial screening, the patient will be rescreened, 
enrolled and infused.  Patients who are not infused within 4 weeks of initial screening are 
withdrawn from study.  Patients who were withdrawn from study may be re-entered into study if 
they were: 1) previously not infused with Thrombosomes, and 2) meet all the enrollment 
requirements of study. All enrolled patients will be assigned to cohorts based on order of 
enrollment and timing of infusion of Thrombosomes.  
All enrolled patients with active bleeding of modified WHO Grade 1 (subset of patients with 
either epistaxis, hematuria, oral petechiae, oropharyngeal bleeding, or bleeding at invasive or 
other wound sites) or Grade 2 bleeding will receive Thrombosomes.  Grades 0, 3, or 4 bleeding 
are not inclusion criteria for enrollment. Active bleeding is defined as to occur within 4 days of 
infusion. If the patient progresses to grade 3 or 4 bleeding during that time, they will be excluded 
from the study and will not be infused. Doses will be adjusted per weight of each patient.  The 
starting dose for patients in Cohort 1 will be approximately 5 ml of Thrombosomes or 
approximately 9.45 x 107 particles/kg or 165 TGPU per kg by IV infusion.  The dose for patients 
in Cohort 2 will be approximately 10 ml of Thrombosomes or approximately 1.89 x 108 
particles/kg or 330 TGPU per kg by IV infusion.  The dose for patients in Cohort 3 will be one 
dose of approximately 20 ml of Thrombosomes or approximately 3.78 x 108 particles/kg or 660 
TGPU per kg by IV infusion.  See Table 2.   

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Pre-infusion, infusion (Day 1), and post-infusion follow up through Day 30 (+2 days) will be 
performed as outlined in Table 4 below. Patients require observation at a minimum through the 
completion of Visit 4 (6 hours post-infusion). Patients may be admitted and observed overnight 
at the discretion of the PI. If the subject is an in-patient on Days 3-5, he/she should be assessed 
and samples collected as described in Table 4. 
All patients in each cohort will be evaluated for any signs of AEs, serious adverse events (SAEs) 
and serious adverse drug reactions (SADRs) after infusion.  
Patient infusions cannot occur on the same day. Once an enrolled patient has been infused, 
he/she must reach Day 4 without a suspension or stopping rule (1.9.8 
Stopping Rules and 
Procedures for Study) event being reported prior to a subsequent patient being infused.  In 
addition, there will be at least a two-week interval between cohorts to allow an independent Data 
Monitoring Committee (DMC) to review all patients’ accumulated safety data after visit Day 6 
from Cohort 1 and then again after the last patient from Cohort 2 has completed visit Day 6 in 
order to recommend whether the study should advance to the next cohort. Refer to Appendix B- 
Flow Diagram of Study Events. 
 
Table 2. Patient Cohort Assignment, Dose and Safety Margins 
Cohort 
No. of 
Infusions 
Target 
Mean 
Particles 
per kg 
Target 
Mean 
TGPU 
per kg 
Estimated Total Vol. Infused 
based on a 70kg patient and 
a mean Thrombosomes conc. 
of 1.61 x 109 particles per ml 
with an associated 2800 
TGPU per ml1 
Safety Margin2  
Particles 
infused 
per kg 
TGPU 
infused 
per kg 
1 
(Patients 
1-8) 
1 
9.45 x 
107 
165 
4.1 ml 
300 
301 
2 
(Patients 
9-16) 
1 
1.89 x 
108 
330 
8.2 ml 
150 
150 
3 
(Patients 
17-24) 
1 
3.78 x 
108 
660 
16.4ml 
75 
75 
1Doses will be adjusted per weight of each patient, Estimated Total Volume Infused based on a 
70kg patient and a mean Thrombosomes concentration of 1.7 x 109 particles per ml with an 
associated 3400 TGPU. Example Total Dose in ml = (Weight in kg X (desired Dose in particle 
count or TGPU, specific for each cohort))/ Thrombosomes particle count or TGPU per ml 
provided with each lot of Thrombosomes. EXAMPLE for Cohort 1: 70 X (9.45 x 107)/1.7 x 109 per 
ml = 5.5ml 
2Safety margin based on the single acute toxicity study in NZWR (MPI 1542-001) 
1.9.2.2 
Additional Hemostatic Therapy:  All Cohorts 
This product is not expected to increase the platelet corrected count increment (CCI). The 
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restricted.  However, at any time, if the patient’s clinical bleeding remains unchanged or 
deteriorates with additional or worsening bleeding, the patient’s physician(s) may transfuse the 
patient with blood products, hemostatic agents, or coagulation factors without limitation.  The 
study patient will be followed for safety data for 30 (+2) days post-infusion of the dose of 
Thrombosomes.   
1.9.3 
Assessment of Bleeding: Using WHO Bleeding Score 
Use of the WHO (World Health Organization) Bleeding Assessment will provide a standardized 
approach, across multiple clinical sites, in order to determine study eligibility, for assessing a 
patient’s bleeding during the clinical trial, and for assessing the effect of Thrombosomes (if any) 
on bleeding.  Study personnel conducting the assessment will be trained on the assessment and 
will be authorized by the PI to perform the assessment.  This authorization will be documented 
on the Authorities and Responsibilities Log.  The location of bleeding for all bleeding sites will 
be assessed by WHO grade during study at screening, (re-screening, if applicable) baseline, 1 
hour, 6 hours, 24 hours post-infusion and 6 days post-infusion. In some instances, a bleeding site 
may not be able to be reassessed post-infusion due to the need for an invasive procedure or other 
procedure that would add additional risk for the subject.  The protocol does not require subjects 
to undergo medically unnecessary procedures (or risks) only in order to perform post-infusion 
WHO bleeding assessments.  Subjects who are transfused with red cells to treat anemia due to 
their underlying disease (and not because of bleeding) will not be assessed as having WHO grade 
3 bleeding. Anemia from underlying disease will be designated if there is evidence of bone 
marrow suppression indicated by at least two of the following: leukopenia, thrombocytopenia, or 
reticulocytopenia; and absence of WHO grade 2 bleeding in the prior 24 hours. For designation 
of WHO grade 3 bleeding, red cell transfusion must be specifically related to treatment of 
bleeding within 24 hours of onset of bleeding. (see Table 4. Schedule of Events for timing of 
WHO bleeding assessments). The same person must perform assessment of pre-infusion and 1-
hour post-infusion time points. 
To assess bleeding and determine the WHO Bleeding Score, the patient will be interviewed, a 
physical examination will be performed, and the patient’s chart will be reviewed.  The WHO 
Bleeding Score will be determined using Appendix A- Modified WHO Bleeding Score. 
1.9.4 
Blinding 
This is an open-label safety study. 
1.9.5 
Duration of Patient Participation and Study 
The duration of the patient’s participation on the study is expected to be approximately 4-8 
weeks.  The time from first patient first visit to last patient last visit is expected to be 18 months. 
1.9.6 
Patient Compensation 
Patients may or may not be compensated for participation in study. If compensated, the total 
should not exceed $1000.00, for time, parking and transportation costs during visits. See Table 3. 

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 Table 3. Proposed Patient Compensation 
Visit No. 
Type of Contact 
Cohorts 1, 2 and 3 
1 
Screening 
$200 
2 
Infusion Visit 
$200 
9 
Day 6 
$400 
10 
Follow-up 30-day visit 
$200 
 
Total 
$1000 
 
1.9.7 
Cohort Study Schedule 
The assignment of treatment dose will be determined in sequential order, as shown in Table 2.  
Patients in Cohorts 2 through 3 will not receive infusion of study material until all eight patients 
in the previous cohort have received infusion of study treatments and have been observed 
through the completion of follow up visit Day 6, and the study data has been reviewed by one of 
the study investigators, the medical monitor, and the DMC.  The DMC will meet before initiation 
of the study in order to approve a charter that will determine the process and schedule for 
reviewing the safety data, determination of serious adverse events, and the appropriate stopping 
rules for the study.  
1.9.8 
Stopping Rules and Procedures for Study 
Suspension Rules 
If an SAE is reported to the Sponsor that: 
1. the investigator believes is possibly, probably, or definitely related to the use of the product 
(As defined in 1.22.6.1 
Definition of Terms), and  
2. does not meet the stopping rules criteria for SAEs listed below, then the Sponsor will confirm 
relatedness and suspend enrollment and infusion of patients in the study until further 
evaluation of the SAE is completed. The independent DMC will meet ad hoc to review the 
results of the event(s) with the Medical Monitor and PI who treated the patient.  The DMC 
will then determine causality and recommend whether the study should either proceed 
without changes, proceed with modifications, or not proceed. See 1.22.6.4 
Adverse Event 
Reporting for reporting of serious adverse events.  Safety reports will be provided to FDA in 
accordance with 21 CFR 312.32. 
Stopping Rules 

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The Sponsor will stop enrollment into the study if an SAE of death, thrombotic or embolic 
event, acute lung injury or anaphylaxis occurs that is directly (probably or definite) related to the 
product within 48 hours of infusion of Thrombosomes (except for anaphylaxis within 4 hours). 
If the study is stopped, the study will be restarted only after a complete review of the data is 
completed by the medical monitor, all PIs and the independent DMC, and it is determined that 
there is reasonable doubt that the event is related to the product. Safety reports will be provided 
to FDA in accordance with 21 CFR 312.32. 
The following definitions will be used to characterize specific stopping rule SAEs:   
• Thrombotic or embolic event (including myocardial infarction, pulmonary embolism, and 
venous thromboembolism [defined in Appendix C- Definition of Myocardial Infarction and 
Appendix E- DVT and PE Algorithm Pages from ICSI Guideline, respectively], or stroke 
[including transient ischemic attack]).  A minor catheter thrombosis is not included in this 
category, or 
• Pulmonary adverse event of acute lung injury (ALI) (defined in Appendix D- Definition of 
ALI), or 
• Anaphylaxis (defined in Appendix G – Modified Definition of Anaphylaxis) 
An SAE will be considered potentially attributable to the product if there is a high degree of 
certainty that 1) a relationship to a Thrombosomes infusion exists, 2) there is a reasonable 
temporal association, and 3) the event cannot be explained by known characteristics of the 
patient’s clinical state or factors including other therapy.  For an SAE to be considered to be 
definitely related to a Thrombosomes infusion, an association exists between the receipt of an 
investigational product and the event, and an association to other factors has been ruled out (See 
1.22.6.2 
Relationship to Investigational Product for definitions to determine causality). 
1.9.9 
Safety Endpoints 
Primary:  The occurrence and frequency of AEs, SAEs, and thromboembolic events as 
determined by clinical signs and symptoms, physical exam including neurological assessment, 
and laboratory studies.  
Secondary:   
• Describe the effect of increasing doses of allogeneic Thrombosomes on bleeding 
including changes in WHO bleeding grade. 
• Describe the effect of increasing doses of allogeneic Thrombosomes on coagulation 
measures. 
1.10 Study Population 
1.10.1 Patient Numbers 
Approximate number of patients screened:  120 

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Approximate number of patients consented:  60 
Approximate number of patients enrolled:  30 
Maximum Number of Patients Completed:  24 (8 patients in Cohorts 1-3) 
Evaluable patients:  24 
A patient is evaluable if they have completed their Day 6 follow up for Cohorts 1- 3. 
 
1.10.2 Target Population 
Patients will be screened as they are identified by the clinical trial site.  Patients will be selected 
and approved for inclusion by the Principal Investigator based on inclusion/exclusion criteria as 
specified in 1.11 
Inclusion /Exclusion Criteria of the study protocol, without any limitations 
to gender or ethnicity. 
1.11 Inclusion /Exclusion Criteria 
1.11.1 Inclusion Criteria 
1. Males and non-pregnant/non-breastfeeding females at least 18 - 74 years of age. 
2. Ability to comprehend the study procedures and signed informed consent. 
3. Diagnosed with any the following: acute leukemia (ALL or AML), myelodysplasia, aplasia, 
and/or therapy (chemotherapy or radiation) induced bone marrow aplasia or hypoplasia with 
thrombocytopenia (see #6 below) for a minimum of 2 days. Patients who have received 
either autologous or allogeneic bone marrow transplant, peripheral, or cord blood stem cells 
may be enrolled if they do not have chronic or acute graft-versus-host disease (GVHD). 
4. WHO Grade 1 (subset) or 2 bleeding or at risk for same within 4 weeks of screening. Subset 
of patients with Grade 1 bleeding are those who have either epistaxis, hematuria, oral 
petechiae, oropharyngeal bleeding, or bleeding at invasive or other wound sites. WHO 
Grades 0, 3 or 4 are not inclusion criteria for eligibility.  
5. If not hospitalized, willing to be observed in a clinic up to the 6-hour post-infusion time 
point. Patients may be admitted and observed in the hospital overnight at the discretion of the 
PI. 
6. Thrombocytopenia with platelet count ≥ 5,000/ µL and ≤ 70,000/µL. 
7. Has permanent address and phone/email for contact and notifications, and available for the 
duration of the trial, which is expected to be a maximum of 8 weeks. 
8. Agrees to not take any nonsteroidal inflammatory drugs within 5 days prior to infusion and 
during the 6 Day study follow-up period. 
9. Agrees to not take any aspirin or aspirin containing drugs within 5 days prior to infusion and 
during the 6 Day study follow-up period. 

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10. Agrees to not take any COX-2 inhibitor drugs within 5 days prior to infusion and during the 
6 Day study follow-up period. 
11. Female patients must have a negative pregnancy test prior to enrollment and during study.  
Women who are postmenopausal for at least 1 year (>12 months since last menses) or are 
surgically sterilized do not require this test. 
12. Females of childbearing potential should either be surgically sterile (hysterectomy or tubal 
ligation) or should use an effective, medically accepted contraceptive regimen.  An effective 
method of birth control is defined as those which result in a lower failure rate (i.e., less than 
1% per year) when used consistently and correctly such as implants, injectables, combined 
oral contraceptives, some intrauterine devices (IUDs), abstinence, or vasectomized partner. 
1.11.2 Exclusion Criteria 
1. Medical diagnosis of acute or chronic DIC (not based on fibrin degradation products alone).  
2. PT or aPTT > 1.3 times the upper limit of normal for the laboratory. 
3. Past diagnosis of stroke or thromboembolic events including deep vein thrombosis (DVT), 
pulmonary embolism, venous or arterial thrombosis, blood clots, or transient ischemic attack 
(TIA), not to include central or peripheral line-related thrombosis. 
4. History of major operative procedures that required general anesthesia in the past 2 weeks. 
5. A history or diagnosis of immune thrombocytopenia, thrombotic thrombocytopenic purpura, 
or hemolytic uremic syndrome. 
6. Known inherited disorder of coagulation or platelet function (by history).  
7. Receiving active treatment with Plavix (clopidrogel bisulfate) or Ticlid (ticlopidine 
hydrochloride), or other platelet inhibiting therapy. 
8. Receiving tranexamic acid or other antifibrinolytics within 48 hours prior to infusion. 
9. Receiving active, inpatient treatment full anticoagulation therapy. Note: a heparin flush may 
be given daily and before and after blood draws to patients with a central line to keep the line 
patent. Prophylactic anticoagulation is not a contraindication. 
10. History of persistent headaches or migraines. Persistent headaches are defined as the 
headache frequency is 15 or more days a month for longer than 3 months in the absence of 
organic pathology.2  
11. History of an MI, stent placement, had valve replacement and/or repair. 
12. For patients with an active acute infection, suspected infection, or a single oral temperature 
of greater than equal to 101°F or a temperature greater than equal to 100.4° F sustained over 
a one hour period 3 in the past 24 hours. Fever related either to the patient’s underlying 
diagnosis (cancer or other neoplastic process) or to the treatment of that disease process is 
 
2 Silberstein SD, et al. Classification of daily and near-daily headaches: field trial of revised IHS 
criteria. Neurology. 1996;47(4):871. 
3 Freifeld et al. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic 
Patients with Cancer: 2010 Update by the Infectious Diseases Society of America. Clinical 
Infectious Diseases. 2011;52(4):e56-e93. 

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not an exclusion to study participation. Subjects receiving antibiotics either to treat an 
infection or as expectant treatment of a clinically-suspected infection are excluded from 
study enrollment until the infection is resolved or ruled out. Subjects receiving prophylactic 
antibiotics to prevent an infection are not excluded from study. 
13. Systolic blood pressure greater than 160 mmHg or lower than 90 mmHg; or diastolic 
pressure higher than 100 mmHg. 
14. Treatment with any investigational agent within one month before treatment infusion for this 
trial, other than for treatment of their underlying disease. 
15. Unwilling or unable to comply with the requirements of this protocol, including the presence 
of any condition (physical, mental, or social) that is likely to affect the patient’s return for 
follow-up visits on schedule as determined by the investigator. 
16. Other unspecified reasons that, in the opinion of the Investigator or Medical Monitor, make 
the patient unsuitable for enrollment.  
17. Patient is institutionalized because of legal or regulatory order. 
1.11.3 Inclusion of Women and Minorities 
The NIH Revitalization Act of 1993, PL 103-43, signed into law on June 10, 1993, directed the 
NIH to establish guidelines for inclusion of women and minorities in clinical research.  It is 
believed that gender or racial differences will not have an effect on study outcomes, and 
therefore, the inclusion of women and minorities for this proposed clinical trial is not limited. 
1.12 Recruitment Process 
Patients will be recruited consecutively as they volunteer and as they meet the eligibility criteria 
and study timelines. 
1.13 Sample Size Justification 
For this Phase 1 dose escalation study (Cohorts 1 through 3), there is no statistical basis for the 
selection of the sample size.  The sample size, 8 patients per cohort, was selected to provide a 
reasonable balance in order to assess safety while minimizing the number of patients potentially 
at risk.  Further details will be given in 1.16 Data Analysis. 
1.14 Informed Consent Process 
Per 21 CFR Part 50 and 45 CFR Part 46, this clinical trial will require Informed Consent of each 
patient prior to participation.  The informed consent form (original and any amended forms) will 
be reviewed and approved by IRBs.  If acceptable, a central IRB will be designated for use by 
all participating sites, involved in the conduct of this clinical trial.  Additionally, HIPAA 
Authorizations will be obtained as required. 
The informed consenting interview process will be conducted during Visit 1 prior to patient 
screening activities.  Potential patients are provided consent material ahead of time for their 
review.  A member of the research team will review the informed consent form, in a factual 

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manner, with the individual, in a private area of the study site.  The potential patient is allowed 
time to read the informed consent and then given an opportunity to ask questions.  They are 
given ample time and left alone for as long as is needed before signing the informed consent.  A 
research team member is in the area close-by and the Principal Investigator (PI) (or sub-
investigator) is available via phone to answer any questions.  
After the potential patients have read the consent, a member of the research team asks the 
individual whether they have any other questions.  It is reiterated during the consent process that 
they can withdraw from the study at any time.  The PI’s phone is included in the Informed 
Consent Form in case they have any questions after signing the informed consent.  
The research team member will note any lack of mental capability during the review of the 
consent with the patient and/or during the question and answer section of the process.  If there 
are any concerns noted by the research team member, they will contact the PI (or sub-
investigator) and discuss.  The final decision regarding this requirement will be made by the PI 
(or sub-investigator), after the PI (or sub-investigator) has either: 
• Heard clear and convincing information from the research team member that the patient does 
not meet an entry criterion, or  
• Directly interviewed the patient to determine whether entry criteria are met. 
As described in additional sections of this Study Protocol, as informed consent is an ongoing 
process, the interview process at the beginning of each study visit will re-address the information 
presented during the Informed Consent interview with the intention to confirm the volunteer’s 
acceptance of continued participation.  Verbal consent to continue study participation will be 
obtained prior to additional study procedures performed at that particular study visit. 
Ample time and opportunity will be provided for a question and answer session to ensure that the 
patient can make an informed decision as to whether the research project is of interest.  The 
patient will be encouraged to consult with family, friends or other counsel prior to choosing to 
participate in the study. 
The Informed Consent Form will be initialed (as required by the IRB), signed and dated by the 
patient and witnessed and dated by the person conducting the consent interview.  A signed copy 
of the consent form will be offered to the patient with the original form kept in study records. 

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1.15  Study Procedure 
Patient case report form information will be prepared and provided to the investigational site, outlining the inclusion/exclusion criteria, 
physical exams, sample collections, and other interventions for each visit.  Table 4 on the following pages provides the schedule of the 
evaluations for each patient. 
Table 4.  Schedule of Events 
Evaluation 
Initial 
Screen 
Rescreen (if 
applicable1) 
Day 12 
Base 
Line 
-2 hr 
pre- 
infusion 
1 hr 
post 
infusion 
± 15min 
6 hr post 
-1 or +2 
hr 
Day 2 
24 hr post 
± 3 hr 
If hospitalized  
Day 6 
(+ 4 
days) 
Day 30 
(+2 days) 
(by 
phone)  
Day 3 
Day 4 
Day 5 
Visit # 
1 
1A 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Sign ICF 
X 
 
 
 
 
 
 
 
 
 
 
Verbal 
reconfirmation of 
informed consent 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
History and 
complete physical 
exam4 
X 
 
 
 
 
 
 
 
 
 
 
WHO assessment 
X 
X 
X 
X 
X 
X 
 
 
 
X 
 
Abbreviated 
physical exam5 
 
X 
X 
X 
X 
X 
 
 
 
X 
 
Pregnancy test 
(serum or urine)-
applicable females 
only 
X 
X 
 
 
 
 
 
 
 
 
 
Concomitant 
medications 
(Medications, OTC 
Remedies, Herbal 
Preparations, 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

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Evaluation 
Initial 
Screen 
Rescreen (if 
applicable1) 
Day 12 
Base 
Line 
-2 hr 
pre- 
infusion 
1 hr 
post 
infusion 
± 15min 
6 hr post 
-1 or +2 
hr 
Day 2 
24 hr post 
± 3 hr 
If hospitalized  
Day 6 
(+ 4 
days) 
Day 30 
(+2 days) 
(by 
phone)  
Day 3 
Day 4 
Day 5 
Vitamins, 
Supplements and IV 
fluids) 
Record transfused 
blood products6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Infusion 
 
 
X 
 
 
 
 
 
 
 
 
Vital signs (pulse, 
BP, RR, temp) 
X 
X 
X 
Prior to infusion and then every 15 
min ±5 min after the start of infusion 
until 2 hrs; continue every hour ±5 
min until 4 hrs, then at 6 hrs, and 24 
hrs post infusion. 
 
 
 
X 
 
Pulse-Ox 
 
 
X 
Continuously monitor while 
monitoring for vital signs; record at 
same time points as for vital signs 
above. 
 
 
 
 
 
Monitor for AE 
 
 
X 
Prior to infusion and then every 15 
min ±5 min after the start of infusion 
until 2 hrs; continue every hour ±5 
min until 4 hrs, then at 6 hrs, and 24 
hrs post infusion, ±10 mins for all 
other time points.  Daily until 
discharged or Day 6. 
X 
X 
X 
X 
X3 
12-Lead EKG 
X 
 
X9 
 
X 
 
 
 
 
 
 

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Evaluation 
Initial 
Screen 
Rescreen (if 
applicable1) 
Day 12 
Base 
Line 
-2 hr 
pre- 
infusion 
1 hr 
post 
infusion 
± 15min 
6 hr post 
-1 or +2 
hr 
Day 2 
24 hr post 
± 3 hr 
If hospitalized  
Day 6 
(+ 4 
days) 
Day 30 
(+2 days) 
(by 
phone)  
Day 3 
Day 4 
Day 5 
Hematology 
CBC6,7 
(if blood products 
are transfused, 
then CBC pre and 
post transfusion) 
X 
X 
X 
X 
X 
X 
Minimum is daily CBC 
X 
 
ABO group, Rh 
type 
X 
 
 
 
 
 
 
 
 
 
 
Coagulation 
Tests8: 
PT/INR, aPTT, D-
dimer, Fibrinogen, 
TAT, PF 1+2, 
TEG or ROTEM, 
TGA 
Only 
PT/INR, 
aPTT, 
D-dimer, 
Fibrinogen 
Only 
PT/INR, 
aPTT, 
D-dimer, 
Fibrinogen 
X 
X 
X 
X 
 
 
 
 
 
Routine 
Chemistry: 
Na, K, Cl, CO2, 
Glucose, BUN, 
Creatinine, 
Albumin, 
Total Bili, Ca, 
AST, Alkaline 
Phosphatase, 
ALT, GGT, LDH, 
Total Cholesterol, 
Total Protein 
 
 
X 
 
X 
X 
 
 
 
 
 
Special Chemistry 
hsTroponin I or T 
Assay 
 
 
X 
 
X 
X 
 
 
 
 
 
Draw archive 
sample10 
X 
 
 
 
 
 
 
 
 
X 
 

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Evaluation 
Initial 
Screen 
Rescreen (if 
applicable1) 
Day 12 
Base 
Line 
-2 hr 
pre- 
infusion 
1 hr 
post 
infusion 
± 15min 
6 hr post 
-1 or +2 
hr 
Day 2 
24 hr post 
± 3 hr 
If hospitalized  
Day 6 
(+ 4 
days) 
Day 30 
(+2 days) 
(by 
phone)  
Day 3 
Day 4 
Day 5 
1 Rescreening performed on those patients who passed eligibility criteria, were not actively bleeding at time of initial screen, and started bleeding within 4 weeks. 
Patients who were initially screened within 4 days (+6 hrs) do not need to be re-screened except for WHO bleeding assessment and CBC.  
2 Baseline may occur on the same day (within 24 hours) as either Initial Screen or Rescreen. The WHO assessment, CBC and coagulation must be collected at baseline, 
not more than 2 hours prior to infusion.  Red cell transfusion must be specifically related to treatment of bleeding within 24 hours of onset of bleeding. 
3 Chart review for SAEs (only) needs to include data from day 1 though Day 30 (+2 days). Phone call with patient is to confirm if the patient had an SAE or required 
emergency medical care at an outside facility. 
4 Complete physical exam to include height, weight, general assessment of health by history and medical exam including neurological exam. History to include previous 
transfusion with red blood cells, plasma and/or platelets. 
5 Abbreviated Physical Exam to include general appearance, cardiovascular, respiratory, extremities, abdomen and head and neck. 
6 In the event of the transfusion of a blood component after infusion of Thrombosomes on Days 1-6, CBC results are required from a sample collected within 8 hours or 
less prior to the transfusion and within 1-hour (+30 min) post transfusion. 
7 Daily CBC required, but ALL CBC data for each patient during the hospitalization phase through Day 6 must be collected and entered into the database. 
8 If TEG or ROTEM testing is available, include samples for the record. 
9 Repeat EKG if performed more than 4 days before infusion. 
10 For each of the time points that require archive samples, two 10 ml samples will be drawn; one for plasma (EDTA) and one for serum. 
 

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1.15.1 Measures to Protect Study Patients 
• An emergency study contact number will be provided to all patients. If not hospitalized, 
patients will be advised to go to an emergency room if immediate attention is needed. They 
will be advised to tell the emergency room staff that they are in a clinical study. 
• Each patient will be monitored for 30 (+2) days after infusion. 
• Patients in Cohorts 2-3 will not receive infusion of study material until all eight patients in 
the previous cohort have received infusion of study material and been observed through the 
completion of visit Day 6, and the study data has been reviewed by one of the study 
investigators, the medical monitor, and the DMC.  
• Stopping rules and DMC review processes have been established. See 1.9.8 
Stopping 
Rules and Procedures for Study 
• Adverse events, including clinical signs and symptoms, abnormal laboratory test results 
post-infusion, and events reported directly by patients will be documented on AE case 
report forms and reported by the PI to the sponsor as they are identified (see 1.22.6
 
Adverse Events and Unanticipated Problems). 
• Because in vitro evaluation of Thrombosomes indicates some properties common to partially 
activated platelets, the PI is requested to be alert for signs/symptoms of vascular 
occlusions/thrombosis, including stroke, heart attack, peripheral vascular occlusion, 
anaphylaxis, and acute lung injury.  Definitions for an MI, ALI and Anaphylaxis are 
presented in Appendix C- Definition of Myocardial Infarction, Appendix D- Definition of 
ALI, and Appendix G – Modified Definition of Anaphylaxis respectively.  Algorithms from 
an ICSI guideline on the Diagnosis and Treatment of Venous Thromboembolism and 
Pulmonary Embolism are in Appendix E- DVT and PE Algorithm Pages from ICSI 
Guideline of this protocol and the complete guidance will be provided to the PI.4 
1.15.2 Receipt and Storage of Thrombosomes 
Thrombosomes will be shipped to the study site by Cellphire, Inc.  Procedures will be established 
by which: 
1. Thrombosomes are checked upon receipt to assure the packaging is intact, no seals are 
broken and the temperature range recorded on the internal monitoring device has not 
exceeded 40ºC. 
2. Vial(s) of Thrombosomes will be stored at ambient temperature (not to exceed 40oC) in a 
secure area for clinical supplies. The amount of product received, accepted into inventory and 
returned to the Sponsor will be entered into study records. 
3. All reconstituted Thrombosomes will be retained at 4°C on site for at least 7 days after the 
infusion and be destroyed at the site as a biological material.   
4. Unused, unopened vial(s) of Thrombosomes will be returned to Cellphire. 
 
4 https://www.icsi.org/_asset/5ldx9k/VTE0113.pdf 
 

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1.15.3 Drawing Blood Samples from Patients 
The samples to be collected from the patient for this study are listed below.  Blood will be 
collected according to policies at each site or central laboratory, in tubes and volumes per site 
specifications, and will be listed in the informed consent form for that site. For each of the 
timepoints that require archive samples, two 10 ml samples will be drawn; one for plasma 
(EDTA) and one for serum.  
Blood Sample Requrements for All Cohorts Test(s) performed: 
• Coagulation Panel  
• Archive Sample 
• Hematology: CBC 
• Pregnancy (serum) 
• Special Chemistry 
• hs Troponin I or T 
• Routine Chemistry 
Note:  A frozen archive sample will be retained at the site.  Upon request by the Sponsor, archive 
samples will be shipped to the Sponsor. Archived samples will be destroyed by the Sponsor 
within 180 days after FDA review of the final study report.  Archived samples will be used to 
repeat any one of the tests described in the protocol.  
1.15.4 Instructions for Reconstitution and Administration of Thrombosomes  
See Appendix F –  Instructions for Reconstitution and Preparation of Thrombosomes – for 
instructions for reconstituting the vial(s) of Thrombosomes and preparing Thrombosomes doses 
for use. Study sites receiving, storing, preparing and administering Thrombosomes should be 
operating under BSL-2 workplace biosafety measures as applied in the blood establishment 
setting (AABB Technical Manual, 19th edition, 2017, Chapter 2, Facilities, Work Environment 
and Safety). Thrombosomes should be kept at room temperature and infused by IV within one 
hour of reconstitution. Use a Hemo-Nate® filter supplied by the Sponsor, in the administration 
of the product (see Appendix F –  Instructions for Reconstitution and Preparation of 
Thrombosomes for Administration).5   
To administer the study material in patients, the investigator may use the central or existing IV 
line if available.  If not, obtain IV access in patient. Begin the administration of normal saline 
using an infusion administration set with a standard medication injection site.  Check the identity 
 
5 Although preclinical, laboratory, and clinical testing to date do not suggest that Thrombosomes® 
need to be filtered during administration, the FDA has recommended the use of a blood filter for 
this study as a precautionary measure.  Cellphire conducted studies of several FDA cleared blood 
filters with pore sizes from 18 to 150 microns. None of the filters tested affected the biologic or 
physical characteristics of Thrombosomes. The Hemo-Nate® Filter #4020009 (Utah Medical 
Products, Midvale, UT) has been selected for use in this clinical trial and will be supplied to sites by 
the sponsor. Selection was based on the material (stainless steel), low priming volume (0.7 ml), 18 
micron size, and ease of use. 

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of the patient with the prepared label. Stop the normal saline infusion and begin administration of 
the predetermined dose of study material at the rate of 1ml/min through the medication injection 
site using a syringe infusion device capable of delivery at the required rate.  After the infusion, 
begin administration of the normal saline and use approximately 25 ml to flush the line.  
1.15.5 Blinding of Study Patients  
This is an open label study and no blinding is required. 
1.15.6 Unscheduled/ Emergency Follow-up Visits 
Patients will be provided with a study number to call, in the event of emergency, but will be 
advised to go to an emergency room if immediate attention is needed.  If a patient calls to request 
a physician follow-up for any health problem possibly related to the study at any time after 
infusion of Thrombosomes, the following procedure should be followed: 
1.15.6.1 
Non-emergent Unscheduled Patient Evaluation (minimum) 
A. Perform a complete physical exam to include vitals (BP, pulse, RR and temperature) and 
general assessment of health and medications, and if an AE occurs, document on CRF.  
Assess patient for acute reactions to include coagulopathies, thromboses and delayed 
hemolytic transfusion reactions.  Treat clinical symptoms and presentation according to 
standard of care.  In addition, refer to the guidance provided on definitions for MI, 
Pulmonary Embolism, Anaphylaxis, ALI, and Venous Thromboembolism in Appendix 
C- Definition of Myocardial Infarction, Appendix D- Definition of ALI Adapted from 
NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4, 
Appendix E- DVT and PE Algorithm Pages from ICSI Guideline, and Appendix G – 
Modified Definition of Anaphylaxis if suspected. 
B. Conduct patient interview to assess health and self-declared AE by the patient. 
C. Obtain complete information on any adverse events and any medications used. 
D. Perform appropriate testing (as determined by the PI) to determine the cause of the 
adverse event. 
E. If hospitalization is required or extended, report to Cellphire as soon as possible, and 
complete the medical evaluation as needed. 
1.15.6.2 
Blood Sampling/Testing 
A. Additional tests for evaluation and/or treatment of safety and/or laboratory events may 
occur.  The additional tests will be determined by the patient’s signs, symptoms or review 
of laboratory data, and will not be dictated by the protocol.  A recommendation for the 
need for additional testing will be made by the patient’s treating physician.  The patient 
must agree to the additional tests before these tests can be performed. 
B. Label all blood tubes following sites standard operating procedures (SOP) and patient 
study ID number, date, time and visit number. 
C. Send samples for testing following site’s SOP. 

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D. Complete Adverse Event Form that includes description of the event, relatedness, start 
date, stop date, medications used to treat and results of laboratory testing. 
1.15.6.3 
AE Evaluation 
A. If necessary, consult with emergency physicians and obtain emergency medical 
treatment. 
B. Schedule follow-up visits; frequency of these visits at the discretion of the Investigator. 
C. Contact the Medical Monitor to assist with a full evaluation of any AE.  See Section 1.22
 
Study Organization and Management Plan of this clinical protocol for AE and 
Serious Adverse Event (SAE) reporting information, if needed. 
1.16 Data Analysis  
Separate data summaries will be prepared for each cohort: 
• Demographic and medical history data will be summarized.  For quantitative variables, 
summaries will include the sample size, mean, median, standard deviation, minimum, and 
maximum.  For qualitative variables summaries include the number and percent of patients 
for each outcome. 
• Exploratory analyses will include the observed response and the change from baseline to 
each of the post-infusion time points for each of the laboratory tests (hematology, 
coagulation, platelet and chemistry).  Additionally, summaries of the number and percent 
of patients with both a change of >5% from baseline and whose results are outside of 
reference ranges will be displayed.  For quantitative variables summaries of the observed 
response and the change from baseline to each of the post-baseline time points will include 
the sample size, mean, median, standard deviation, minimum, and maximum.  Additionally, 
for the change from baseline summaries, the statistical significance will be determined using 
either a t-test or the Wilcoxon Signed Rank test, as appropriate.  Summaries for qualitative 
variables will include the number and percent of patients for each outcome.  
• Incidence of AEs and SAEs per patient and by body system will be summarized showing the 
number and percent of patients for each outcome.  Summaries will also be prepared by 
severity and relationship to treatment. 
• Summaries of vital signs and clinical data including WHO bleeding scores will include the 
observed response and the change from baseline to each of the post-infusion time points for 
each of the variables.  For quantitative variables summaries of the observed response and the 
change from baseline to each of the post-baseline time points will include the sample size, 
mean, median, standard deviation, minimum, and maximum.  Additionally, for the change 
from baseline summaries, the statistical significance will be determined using either a t-test 
or the Wilcoxon Signed Rank test, as appropriate.  Summaries for qualitative variables will 
include the number and percent of patients for each outcome. 
A statistical analysis plan will be developed as part of the data analysis plan. 
1.17 Data Management 

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Data will be gathered and managed by a fully qualified CRO.  Electronic case report forms will 
be completed at the site and sent to the CRO where the data will be screened for typographical 
errors and then validated to check for logical errors.  Errors found will be reviewed to determine 
if there is an error in the data or clarification from the site is required.  Records will be retained 
by the CRO as required by CFR and guidance documents. 
1.18 Risk Assessment 
1.18.1 Foreseeable or Potential Risks 
The following risks to participation of this clinical trial are outlined in the Table 5 below: 
Table 5. Potential Study Risks 
Trial Stage 
Risks Identified 
AEs Possibly Related 
or Related to 
Thrombosomes 
Infusion during Phase 
1 Study No. 2011-1 
• 
Prothrombin Level Increased (Elevated Prothrombin Fragment 1+2) 
• 
White Blood Cell Count Increased 
• 
Fibrin D-dimer Increased 
• 
Electrocardiogram T-wave Abnormal 
• 
Autoantibody Positive (Platelet Autoantibody) 
AEs Associated with 
Blood Product 
Infusion including 
Platelet Infusion 
which may also be 
associated with 
Thrombosomes 
 
• 
Hematoma or localized infection at the venipuncture site 
• 
Nausea/vomiting, dizziness/ fainting, seizures 
• 
Allergic reaction (flushing, itching, hives, abdominal cramps, difficulty 
breathing, chest pain, or bronchospasm, which may vary in severity from 
mild to life-threatening) 
• 
Difficulty breathing, chest pain, or bronchospasm, which may vary in 
severity from mild to life-threatening) 
• 
A minimal risk of cancer cannot be completely and definitely ruled out 
• 
Immune suppression 
• 
Infectious disease transmission 
• 
Cardiac failure 
• 
Noncardiac pulmonary edema 
• 
Stroke 
• 
Thrombocytopenia 
• 
Formation of platelet antibodies 
• 
Thrombosis – arterial or venous 
• 
Pulmonary Embolism 
• 
Heart attack 
• 
Death 
Miscellaneous 
• 
Breach of patient confidentiality 
 
 
 
1.18.2 Potential Patient Risks for Special Vigilance by Investigator 
See 1.15.1 
Measures to Protect Study Patients. 

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1.18.3 Potential Risks to Study Personnel 
Risks associated with the handling of blood and blood products are expected for this clinical 
trial.  All study personnel will be trained in good clinical practices, including Universal 
Precautions, in the sampling and handling of blood and body fluids that are collected, processed 
or tested during the course of this clinical trial.  The Investigator will be responsible for ensuring 
that staff who will handle blood or body fluids be trained in Bloodborne Pathogens, Infection 
Control and Universal Precautions. 
1.18.4 Risk Management and Emergency Response 
1.18.4.1 
Pregnancy 
Risks associated with use of this investigational product are unknown.  Therefore, the 
inclusion/exclusion criteria require that women of childbearing potential must have a negative 
pregnancy test and must agree to practice a medically acceptable contraception regimen 
throughout the participation in the clinical trial, (which can be up to 8 weeks).  An effective 
method of birth control is defined as those which result in a lower failure rate (i.e., less than 1% 
per year) when used consistently and correctly such as implants, injectables, combined oral 
contraceptives, some intrauterine devices (IUDs), abstinence or vasectomized partner. Women 
who are postmenopausal for at least 1 year (> 12 months since last menses) or are surgically 
sterilized also meet the inclusion criteria. 
Should the patient become pregnant during the course of the study, she will be withdrawn from 
the study.  The PI should have a discussion with the patient on whether the patient wishes to 
provide continued follow-up and further data collection subsequent to their withdrawal from the 
interventional portion of the study.  The PI must distinguish between study-related interventions 
and continued follow-up of associated clinical outcome information, such as medical course or 
laboratory results obtained through non-invasive chart review, and address the maintenance of 
privacy and confidentiality of the patient’s information.  If a patient withdraws from the 
interventional portion of the study, but agrees to continued follow-up of associated clinical 
outcome information as described above, the investigator must obtain the patient’s informed 
consent for this limited participation in the study.6 
1.18.4.2 
Risk Management 
As this is a dose escalation study design, infusions must take place according to cohort 
assignment.  Patients in Cohorts 2 and 3 will not receive infusion of study material until all 
eight patients in the previous cohort have received infusion of study material and been observed 
through the completion of visit Day 6 and the study data has been reviewed by one of the study 
investigators, the medical monitor, and the DMC.  Stopping rules for select safety events are also 
part of the study protocol.  See 1.9.8 Stopping Rules and Procedures for Study. 
 
6 From the FDA Guidance, “Guidance for Sponsors, Clinical Investigators, and IRBs” Data Retention When Subjects 
Withdraw from FDA-Regulated Clinical Trials (2008) 

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Research staff must be trained in the venipuncture, sample collection and infusion procedures 
described in this protocol and in the recognition and treatment of known potential side effects of 
these procedures. 
1.18.4.3 
Emergency Care and Treatment 
Medical oversight must be available to the patient as required.  Follow-up blood sample draws 
will be conducted at site. 
1.18.5 Stopping Criteria and DMC Review 
See 1.9.8 
Stopping Rules and Procedures for Study.  
1.18.6 Potential Benefits 
There are no definitive benefits to study patients participating in the study.  Thrombosomes may 
have efficacy to reduce bleeding; however, it is not now known whether this potential benefit is 
better than, equal or less than the efficacy of apheresis platelets. 
1.19 Study Personnel 
1.19.1 Key Study Personnel 
The roles and responsibilities of key study personnel will be assigned and documented using a 
local form for “Authorized Signatures and Delegation of Responsibilities Log” prior to the trial 
initiation. 
1.19.2 Conflict of Interest 
The Principal Investigator and key staff will provide in writing and retain records of all financial 
information and all other records required under applicable FDA regulations and IRB 
requirements, including but not limited to 21 CFR Part 54.6.  The Investigator and key staff will 
be required to authorize the Sponsor, the FDA, and other government agencies to have access to, 
copy and verify these records.  The Sponsor will be notified immediately in writing if any of the 
information disclosed changes during such time period.  Investigator Financial Disclosure Form 
will be used to facilitate disclosure. 
If conflicts of interest do exist and are disclosed, efforts to mitigate the impact of conflicts of 
interest will be undertaken.  Information regarding conflicts of interest will be disclosed to 
volunteers as part of the consent form for the study. 
1.20 Medical Monitoring 
Qualified medical monitoring will be performed by Joan C. Pehta, MD.  The Medical Monitor 
will review all adverse events, unanticipated problems involving risk to patients or others 
(unexpected serious adverse drug reactions), serious adverse events and all deaths associated 
with the protocol and provide an unbiased written report of the event to Cellphire.  At a 
minimum, the Medical Monitor will comment on the outcomes of the event or problem and, in 

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the case of an unexpected serious adverse drug reaction or death, comment on the relationship to 
participating in the study and study products.  The Medical Monitor will also indicate whether 
he/she concurs with the details of the report provided by the study Investigator.  Reports for 
serious, unexpected adverse events determined by the Medical Monitor to be possibly, probably 
or definitely related to study drug including reports of events resulting in death will be promptly 
forwarded to the FDA and the IRB of record. 
Safety reports (as defined by 21 CRF 312.32) will additionally be provided to the FDA as part of 
study records. 
1.21 Study Monitoring and Auditing 
Cellphire, Inc. or its designee, is responsible for the monitoring and auditing of the clinical study 
conducted at investigator sites according to Good Clinical Practices and FDA regulations. 
Additionally, employees of FDA, BARDA, the IRB of record or other regulatory authorities may 
audit or observe an audit of the study during a visit at the Investigator’s site. 
For all monitoring or auditing visits, it is expected that the Investigator facilitate the processes by 
providing time, adequate facilities, study and patient records, and personnel necessary to support 
the monitoring or auditing process. 
1.22 Study Organization and Management Plan 
1.22.1 Study Management 
Training at the clinical site will be provided by the study Sponsor and designees prior to 
commencement of the clinical trial.  Training activities will include:  informed consenting 
procedures specific to the study; enrollment procedures; randomization of patients; modified 
WHO bleeding assessments; investigational product labeling, storage requirements, 
reconstitution, use and accountability; data collection (CRF form), data query procedures and 
data corrections; reporting of adverse events; and study monitoring requirements.  All training 
elements will be covered with respect to observation of Good Clinical Practices. 
1.22.2 Study Timeline 
The estimated timeline for conducting this Phase I IND study is approximately 12 months from 
first patient enrollment. 
1.22.3 Patient Withdrawal 
Patients may discontinue participation in the study at any time without penalty or loss of benefits 
to which the patient is otherwise entitled.  If the patient indicates a desire to withdraw from the 
study, consideration must be made as to the timing of the patient’s decision versus the study 
procedures performed to date.  Table 6 indicates the appropriate planned follow-up given each 
stage of the study.

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Table 6. Requirements Following Patient Withdrawal 
Visit 
Number 
Procedures 
Follow-up Required 
1or 1A 
Initial 
screening or 
Rescreening 
None 
2 through final 
visit 
Infusion 
• 
If patient was not infused prior to withdrawing, complete the 
withdrawal form.   
• 
If infusion was initiated before withdrawal, discontinue the 
infusion, and complete the final exam and blood draws to assess 
for safety.  Request that patient return for follow-up visits as 
scheduled to ensure safety.  Minimally, obtain patient contact 
information and perform follow-up phone calls if the patient 
doesn’t come for visits.  Provide clinic contact information for 
procedure-related concerns or patient-initiated follow-up. 
• 
If infusion was completed before withdrawal, complete the final 
exam and blood draws to assess for safety.  Request that patient 
return for follow-up visits as scheduled to ensure safety.  
Minimally, obtain patient contact information and perform follow-
up phone calls if the patient doesn’t come for visits.  Provide clinic 
contact information for procedure-related concerns or patient-
initiated follow-up. 
 
Patient interview will be documented by a written record of the interview and patient responses, 
signed and witnessed by the participant and staff conducting the exit interview at the time of 
withdrawal. 
The anticipated circumstances under which the patient’s participation may be terminated by the 
Investigator are indicated as follows: 
• Non-compliance (e.g., no-show for scheduled visit, impairment due to drugs/alcohol, 
agitation or disruption during visit, inability to follow clinic-established rules concerning 
conduct) 
• Safety issues (e.g., patient does not meet inclusion criteria for ongoing stages of the study, 
clinic safety due to unacceptable conduct, study cancelled due to product safety) 
• Sponsor-initiated study termination 
• Investigator-initiated study termination 
• IRB of record or FDA study termination 
 
1.22.4 Protocol Modifications 
Modifications to the research protocol (other than purely administrative changes) including any 
modifications that could potentially increase risk to patients must be submitted to the IRB, for 

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approval prior to implementation and submitted to FDA.  Some examples of major modifications 
include a change in Investigator, addition of a research site, changes in study design and addition 
or widening of a study population. 
Protocol modification other than administrative (changes in phone, addresses, spelling errors, 
etc.) will be submitted to the central or institutional IRB for review as well as to the FDA. 
1.22.5 Protocol Deviations 
1.22.5.1 
Anticipated Deviations 
Anticipated deviations are events that the Investigator anticipates or would like to be aware of 
prior to when they occur.  See Table 7. An anticipated deviation must be reported using the EDC 
and discussed with the Sponsor prior to its occurrence.  The Sponsor will assess the requested 
deviation for a possible effect on safety or rights of the patient or on the impact to study data or 
quality.  The Medical Monitor will be consulted for opinion regarding anticipated deviations. 
Table 7.  Protocol Deviations (Anticipated) 
Anticipated Deviations 
Action Required 
Patient does not return for scheduled visit 
post-infusion follow-up 
Attempt to call at least two times.  Document 
call times on phone log. Contact by registered letter if still 
unresponsive. 
Visit dates outside of range specified in 
protocol 
Note correct time/day on CRF and keep a log of same for 
entire study 
 
1.22.5.2 
Unanticipated Deviations 
Unanticipated deviations are events not foreseen by the Investigator, and typically reflect 
reactions or judgment calls by the Investigator.  Unanticipated deviations can also result from 
Investigator or staff error.  An unanticipated deviation must be reported to the Sponsor using the 
EDC as soon as it is recognized.  Report can primarily be verbal; however, it must be followed 
with written documentation.  The written report must explain the reason and rationale for the 
deviation, if the deviation affects the safety or rights of the patient or additional patients and 
recommended corrective actions.  The Sponsor will formulate an appropriate follow-up plan (e.g., 
additional site training).  The Medical Monitor may be consulted for opinion regarding 
unanticipated deviations.  Any deviation to the protocol will be documented in study records.  
Deviations that may have an effect on the safety or rights of the patient or the integrity of the 
study must be promptly reported to the IRB of record.  Documentation of any actions taken by the 
IRB of record related to the deviation report will be provided to the study Sponsor. 
1.22.6 Adverse Events and Unanticipated Problems 
1.22.6.1 
Definition of Terms 
A. Adverse Event (or Adverse Experience): 
Any untoward medical occurrence in a patient administered a pharmaceutical product and 
which does not necessarily have to have a causal relationship with this treatment.  An 

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adverse event (AE) can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding, for example), symptom or disease temporally associated with 
the use of a medicinal product, whether or not considered related to the medicinal product. 
An abnormal laboratory finding that requires medical or surgical intervention or leads to 
study treatment interruption or discontinuation must be recorded as an AE (or SAE, if 
applicable).  If the changes from baseline are mild and in the opinion of the investigator not 
clinically significant, the event is not considered an AE, however, the investigator should 
continue to carefully monitor the values.  Laboratory tests may be repeated, as clinically 
indicated, without prior approval by Sponsor or Medical Monitor.  Special attention must be 
paid to the results of coagulation parameter results not within reference ranges. 
B. Adverse Drug Reaction (ADR): 
In the clinical experience with a new medicinal product or its new usages, particularly as the 
therapeutic dose(s) may not be established all noxious and unintended responses to a 
medicinal product related to any dose should be considered adverse drug reactions.  The 
phrase "responses to a medicinal product" means that a causal relationship between a 
medicinal product and an adverse event is at least a reasonable possibility, i.e., the 
relationship cannot be ruled out. 
C. Unexpected ADR: 
An adverse reaction, the nature or severity of which is not consistent with the applicable 
product information (e.g., Investigator's Brochure for an unapproved investigational 
medicinal product). 
D. SAE or ADR: 
An adverse event that occurs during a clinical investigation and if suspected to be medicinal 
product-related (adverse drug reactions), and might be significant enough to lead to 
important changes in the way the medicinal product is developed (e.g., change in dose, 
population, needed monitoring, consent forms.  These events result in: 
• Death. 
• Life-threatening situation (patient is at immediate risk of death). 
• In-patient hospitalization (excluding those for study therapy or placement of an 
indwelling catheter, unless associated with other SAEs). 
• Prolongation of existing hospitalization. 
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions. 
• Congenital anomaly/birth defect in the offspring of a patient who received study drug. 
• Other:  important medical events that may not be immediately life- threatening or result 
in death or hospitalization, but based upon appropriate medical and scientific judgment, 
may jeopardize the patient or may require medical or surgical intervention to prevent one 
of the outcomes listed above. 
Examples of such events are as follows: 

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• Intensive treatment in an emergency room or at home for allergic bronchospasm. 
• Blood dyscrasias or convulsions that do not result in hospitalization. 
• Development of drug dependency or drug abuse. 
E. Clarification of SAE 
 
• Death is an outcome of an AE, and not an AE in itself.  In reports of death due to 
“Disease Progression,” where no other information is provided, the death will be assumed 
to have resulted from progression of the disease being treated with the study treatment(s). 
• All deaths, regardless of cause or relationship, must be reported for patients on study and 
for deaths occurring within 30 (+2) days of last study treatment or within 30 (+2) days of 
last study evaluation, whichever is longer. 
• “Occurring at any dose” does not imply that the patient is receiving study treatment at the 
time of the event.  Dosing may have been given as treatment cycles or interrupted 
temporarily before the onset of the SAE, but may have contributed to the event. 
• “Life-threatening” means that the patient was at immediate risk of death from the event 
as it occurred.  This does not include an event that might have led to death if it had 
occurred with greater severity. 
• Complications that occur during hospitalizations are AEs.  If a complication prolongs the 
hospitalization, it is a SAE. 
• “In-patient hospitalization” means the patient has been formally admitted to a hospital for 
medical reasons, for any length of time.  This may or may not be overnight.  It does not 
include presentation and care within an emergency department. 
• The Investigator should attempt to establish a diagnosis of the event on the basis of signs, 
symptoms, and/or other clinical information.  In such cases, the diagnosis should be 
documented as the AE and/or SAE and not the individual signs/symptoms. 
A distinction should be drawn between seriousness and severity of AEs.  An AE that is 
assessed as severe should not be confused with a SAE.  Severity is a category utilized for 
rating the intensity of an event, and both AEs and SAEs can be assessed as severe.  An event 
is defined as "serious" when it meets one of the predefined outcomes described above. 
1.22.6.2 
Relationship to Investigational Product 
The site PI must assign a relationship of each AE to the receipt of the investigational product.  
The PI will use clinical judgment in conjunction with the assessment of a plausible biologic 
mechanism, a temporal relationship between the onset of the event in relation to receipt of the 
investigational product, and identification of possible alternate etiologies including underlying 
disease, concurrent illness, or concomitant medications.  The following guidelines should be 
used to assess the relationship of an AE to study product administration and ONLY THE 
INVESTIGATOR (QUALIFIED MD/DO) CAN MAKE THIS DETERMINATION: 
• Not related: No relationship to investigational product.  Applies to those events for which 
evidence exists that there is an alternate etiology.  

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• Unlikely: Likely unrelated to the investigational product.  Likely to be related to factors other 
than investigational product, but cannot be ruled out with certainty.  
• Possibly: An association between the event and the administration of investigational product 
cannot be ruled out.  There is a reasonable temporal association, but there may also be an 
alternative etiology such as the patient’s clinical status or underlying factors including other 
therapy.  
• Probably: There is a high degree of certainty that a relationship to the investigational product 
exists.  There is a reasonable temporal association, and the event cannot be explained by 
known characteristics of the patient’s clinical state or factors including other therapy. 
• Definite: An association exists between the receipt of an investigational product and the 
event.  Any association to other factors has been ruled out. 
1.22.6.3 
Severity Assessment 
All AEs will be assessed for severity by the PI.  Inherent in this assessment is the medical and 
clinical consideration of all information surrounding the event including any medical 
intervention required.  The CDC National Healthcare Safety Network Hemovigilance Module 
criteria will be used to help define transfusion-related events.  The NCI Common Terminology 
Criteria (CTCAE version 4.0, June 14, 2010) for toxicity grade will be used to assign the severity 
for all AEs (transfusion and non-transfusion related) (HHS-2010).  The criteria below may be 
used for any symptom not included in the grading scale.  Any Grade 4 (life-threatening) or Grade 
5 (fatal) AE must be reported as an SAE. 
• Mild Grade 1 Does not interfere with routine activities Minimal level of discomfort  
• Moderate Grade 2 Interferes with routine activities Moderate level of discomfort  
• Severe Grade 3 Unable to perform routine activities Significant level of discomfort  
• Life-threatening Grade 4 Hospitalization or emergency room visit for potentially life-
threatening event  
• Fatal Grade 5 Results in Death  
1.22.6.4 
Adverse Event Reporting 
The PI is responsible for reporting all adverse events or unanticipated events to the local IRB, as 
required, and to Cellphire on a schedule related to the seriousness of the event.  A case report 
form will be provided for these reports.  Events that meet the definition of “serious,” including 
unexpected adverse reactions (SUSARs), thrombotic adverse events, and deaths as described 
above, must be entered into the electronic data capture (EDC).   
All SAEs must be reported to Cellphire and or Sponsor’s designee, the Contract Research 
Organization (CRO), in the EDC within 24 hours of the Investigator becoming aware of the 
SAE. If the site is unable to enter the event information into EDC for any reason the site can 
alternatively complete the paper SAE Form, which should be faxed/emailed within 24 hours 
from the point in time when the investigator becomes aware of the SAE. In addition, all SAEs 
that occur up to and including 30 days after administration of Thrombosomes must be reported to 

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the Sponsor or Sponsor’s designee within 24 hours from when the investigator becomes aware of 
the SAE.  
To report an SAE, sites will enter the SAE information into the EDC or complete an SAE Report 
and send the SAE report to the CRO, Clinipace Worldwide, Inc.  
 
The investigator must report new significant follow-up information for these events to the 
Sponsor’s designee immediately (i.e., no more than 24 hours after becoming aware of the 
information). 
Cellphire is responsible for reporting to the DMC and the FDA according to the charter, policies 
and applicable guidance or regulations. 
 
Adverse Event Reporting Contacts 
• Medical Monitor Contact: Joan C. Pehta, MD 
Office: 203 972 0481 
Cell: 203 536 7604 
Fax: 203 972 6705 
Email: JCPehta@aol.com 
 
• Safety Reporting Contact:  Clinipace Worldwide 
Fax: 919 573 0332 
Email: safetygroup@clinipace.com 
 
• Cellphire Contact: G. Michael Fitzpatrick, PhD 
Office: 240 268 2470 
Cell: 301 525 6885 
Fax: 240 268 1145 
Email: mfitzpatrick@cellphire.com 
 
1.22.7 Study Forms and Recording of Information 
It is the Investigator's obligation to ensure that all Case Report Forms and data collection 
instruments are accurate and complete.  All study forms must be signed and dated by the 
Principal Investigator or designee, to attest that they are an accurate and complete record.  A 
Signature and Delegation log will be completed and signed by the Principal Investigator during 
the training/initiation visit and kept as a part of the study records. 
1.22.8 Continuing Review and Reporting 
The IRB of record requires approval of all protocol amendments, acceptance of continuing 
review reports, reporting of protocol deviations and unexpected serious adverse drug reactions.  
A copy of the approved continuing review report and the local IRB approval notification may be 
submitted by Cellphire to the responsible Biomedical Advanced research and Development 
Authority (BARDA) representative or the Contracting Officer’s Representative (COR) as 

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appropriate.  A copy of the final report and local IRB approval notification may be submitted to 
BARDA as soon as these documents become available. 
Additionally, BARDA requires reporting of any pending compliance inspection/visit by the 
FDA, OHRP or other government agency concerning the research, the issuance of Inspection 
Reports, FDA Form 483, warning letters or actions taken by any Regulatory Agencies including 
legal or medical actions and any instances of serious or continuing noncompliance with the 
regulations or requirements must be reported immediately to the responsible BARDA 
representative or the COR as appropriate. 
1.22.9 Applicable Regulatory Requirements 
The conduct of this clinical trial will adhere to the following regulations: 
• 21 CFR Parts 11, 50, 54, 56, 312  
• 21 CFR 600-640 subparts A, D, G 
• 45 CFR 46, Protection of Human Subjects 
• 32 CFR 219.103, Assurance of Compliance for the Protection of Human Research Subjects 
• Health Insurance Portability and Accountability Act of 1996 (HIPAA) 
• FDA guideline “Good Clinical Practice: Consolidated Guideline” (ICH E6) 
1.22.10 Confidentiality and Disposition of Records 
1.22.10.1 Confidentiality of Study Information 
This collaborative clinical investigation is a CONFIDENTIAL study performed by the 
Investigator and Cellphire, Inc.  No information concerning the nature and performance of this 
study, the results of this study, or the evaluation of those results is to be disclosed without the 
written approval of Cellphire, Inc.  It is expected that any proprietary information provided by 
Cellphire, Inc will be maintained by the Principal Investigator in a secure fashion to restrict 
access only to authorized personnel. 
The primary source document for the study will be the study participant’s research records.  The 
research records will be considered the source documents for the purposes of auditing the study.  
Any information that would identify the patient will be kept in a secure location at the clinical 
site.  Secure is defined as access only to members of the research team by method of a locked 
location with key access only available to limited research team members.  Applicable source 
data will be entered to approved CRFs.  All data will be de-identified and a copy of each 
completed CRF will be retained at the Sponsor according to 21CFR 312.57(c), record retention.  
At, the study site the data will be kept in secure storage for the required length of time as 
indicated in 21CFR 312.62(c), record retention. 

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1.22.10.2 Confidentiality of Patient Information 
Cellphire, Inc or its designees, employees of FDA or other regulatory authorities, the IRB of 
record, may consult source documents in order to verify data, and as such, confidentiality cannot 
be guaranteed.  The study records and laboratory specimens will be stored in a confidential 
manner and will be coded to protect the patient’s confidentiality. 
1.22.11 Security of Investigational Products 
Investigational products will be stored within a secure, limited access enclosure at each 
investigative site.  Access will be provided to only the Investigator and his designee(s) 
responsible for product storage, preparation, tracking and usage.  Investigational product 
accountability will be maintained. 
1.22.12 Shipping of Specimens 
It is the Investigator’s responsibility to ensure that there are trained personnel available to ship 
diagnostic specimens following DOT/IATA regulations and site’s Standard Operating 
Procedures. 
1.22.13 Clinical Trial Registration 
Information concerning this Phase I clinical trial will be registered on www.clinicaltrials.gov 
prior to study initiation pursuant to US Public Law 110-85, Title VIII, and Section 801. 

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1.22.14 Investigator Signature Page  
I have read the attached protocol entitled, “A Phase I, Multi-Center, Open-Label, Dose 
Escalation Study of Allogeneic Thrombosomes® in Bleeding Thrombocytopenic Patients in 
Three Cohorts” Version 2.0, dated 18 October 2018, and agree to conduct the study according 
to the provisions described therein. 
I agree to comply with the International Conference on Harmonization Guideline on Good 
Clinical Practice and applicable Food and Drug Administration (FDA) regulations set forth in 21 
CFR Parts 50, 54, and 312. 
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the evaluation or conduct of the clinical investigation without the prior 
consent of Cellphire, Inc. 
 
The signature below constitutes my agreement to conduct the study according to the 
provisions of this protocol the contents of this protocol. 
 
______________________________________________________ 
Principal Investigator 
Date 
 
___________________________________ 
Title 
___________________________________ 
Institution 
 
 
 

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Appendix A- Modified WHO Bleeding Score 
(Adapted from Supplement from Slichter SJ, Kaufman RM, Assmann SF, et al. Dose of 
prophylactic transfusions and prevention of hemorrhage. N Engl J Med 2010;362:600-13) 
 
Grade 1 
Grade 2 
Grade 3 
Oral and nasal 
• Oropharyngeal bleeding – 
total duration of all 
episodes in previous 24 
hours ≤ 30 minutes* 
• Petechiae of oral mucosa 
• Epistaxis – total duration 
of all episodes in previous 
24 hours ≤ 30 minutes* 
• Oropharyngeal bleeding – 
total duration of all episodes 
in previous 24 hours > 30 
minutes* 
• Epistaxis – total duration of 
all episodes in previous 24 
hours >30 minutes* 
• Any bleeding 
requiring RBC 
transfusion over 
routine transfusion 
needs** 
 
Skin, soft tissue, 
musculoskeletal 
• Petechiae of skin 
• Purpura ≤ 1 inch diameter 
• One or more spontaneous 
hematomas in the soft tissue 
or muscle > 1 inch 
• Purpura > 1 inch diameter 
• Spontaneous hematoma in 
deeper tissues 
• Joint bleeding (confirmed 
by aspiration, imaging study 
or other accepted technique) 
• Any bleeding 
requiring RBC 
transfusion over 
routine transfusion 
needs** 
 
Gastrointestinal 
• Positive stool occult blood 
test  
• Melanotic stool 
• Hematochezia – visible red 
blood mixed in stool, not 
requiring a transfusion 
• Hematemesis – Grossly 
visible blood in emesis or 
in nasogastric drainage tube 
(not related or secondary to 
swallowed blood) 
• Any bleeding 
requiring RBC 
transfusion over 
routine transfusion 
needs** 
Genitourinary 
• Any biochemical or 
microscopic Hb/RBCs 
without red urine  
• Abnormal vaginal bleeding 
(Unexpected bleeding out of 
normal cycle OR Bleeding 
heavier than normal OR 
Breakthrough bleeding 
(patient on hormonal therapy 
to prevent bleeding)) with 
spotting 
• Gross/visible hematuria 
without need for 
transfusion 
• Abnormal vaginal bleeding 
(Unexpected bleeding out 
of normal cycle OR 
Bleeding heavier than 
normal OR 
• Breakthrough bleeding 
(patient on hormonal 
therapy to prevent 
bleeding)) more than 
spotting 
• Any bleeding 
requiring RBC 
transfusion over 
routine transfusion 
needs** 
Pulmonary 
 
• Hemoptysis – Visible blood 
• Blood in broncho-
pulmonary lavage, or blood 
tinged sputum (excluding 
those with nose or 
oropharyngeal bleeding) 
• Any bleeding 
requiring RBC 
transfusion over 
routine transfusion 
needs** 
Body Cavity 
 
• Visible blood in body 
cavity fluid (e.g. red cells 
apparent in fluid aspirate) 
short of criteria for Grade 3 
or 4 
• Grossly bloody 
body cavity fluids 
and organ 
dysfunction with 
symptoms, and/or 
need to intervene 

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Grade 1 
Grade 2 
Grade 3 
(e.g. to aspirate), 
and/or need for 
transfusion 
Central Nervous 
System 
 
• Retinal bleeding without 
visual impairment 
• Lumbar puncture with blood 
(>5 RBC/μL in CSF on 
microscopic analysis and 
non-traumatic tap), no 
symptoms and no visible red 
color 
• Lumbar puncture 
with visible red 
color in absence of 
symptoms, and non-
traumatic tap 
Invasive Sites 
• Bleeding at invasive sites 
(venipuncture sites, 
intravenous lines or 
catheter exit sites): active 
oozing at site for a 
cumulative total of ≤ 1 
hour in the previous 24 
hours 
• Bleeding at invasive sites 
(venipuncture sites, 
intravenous lines or catheter 
exit sites): active oozing at 
site for a cumulative total of 
> 1 hour in the previous 24 
hours 
• Any bleeding 
requiring RBC 
transfusion over 
routine transfusion 
needs** 
Hemodynamic 
Instability 
 
 
• Any bleeding 
associated with 
moderate 
hemodynamic 
instability 
(hypotension; 
>30mmHg fall or 
>30% decrease in 
either systolic or 
diastolic blood 
pressure) and 
requiring RBC 
transfusion over 
routine transfusion 
needs** 
* Count actual bleeding (i.e. “running out” or need for basin, Kleenex, towel, etc.) not minor bleeding 
** Red cell transfusion must be specifically related to treatment of bleeding within 24 hours of onset of bleeding 
For inclusion, Grade 1 subset bleeding includes epistaxis, hematuria, oral petechiae, oropharyngeal bleeding, or 
bleeding at invasive or other wound sites. See bolded items above. 
 
Grade 4: 
• 
Any bleeding associated with severe hemodynamic instability (hypotension; >50mm/Hg fall or >50% 
decrease in either systolic or diastolic blood pressure, with associated tachycardia (heart rate increase 
of > 20% for 20 minutes) and requiring RBC transfusion over routine transfusion needs 
• 
Fatal bleeding from any source 
• 
Retinal bleeding with visual impairment (Visual impairment is defined as a field deficit, and patients 
with suspected visual impairment require an ophthalmologic consult for documentation) 
• 
CNS symptoms with non-traumatic bloody lumbar puncture 
• 
CNS bleeding on imaging study with or without dysfunction 

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Appendix B- Flow Diagram of Study Events  
(Each cohort = 8 patients)  
 
Recommend 
to proceed?
Yes
No
Stop infusions at all 
sites until resolved
DMC review
Yes
Cohort 1 or 2?
STOP
No
Recommend to 
proceed?
Begin next 
cohort (cohort 2 
or 3)
No
Pass 
Medical 
Monitor 
review?
Yes
No
Yes
No
Visit 1: Informed 
Consent & Initial 
Screening
Visit 2: Baseline/Infusion (Day 1)
Visit 3: 1 hr post infusion + 15 min
Visit 4: 6 hr post infusion - 1 hr, + 2 hr
Visit 5: 24 hr post infusion + 3 hr
Visit 6, 7, 8: Days 3, 4, 5 (if hospitalized)
Visit 9: Day 6 (+ 4 day) 
Visit 10: Day 30 (+2) - patient exit study
Results through 
Day 6 available on all 8 
patients in cohort?
Continue recruitment and 
treatment of remaining 
patients in the cohort
Final 
trial 
report 
to FDA
Any SAE?
Med. Monitor + 
DMC review 
current cohort 
and cumulative 
data
Does patient currently meet 
WHO  bleeding grade 1 
(subset) or 2?
Yes
Infuse patient
Rescreening if > 4days and < 4 weeks of 
initial screening:  Does patient meet WHO 
bleeding grade 1 (subset) or 2?
Yes
No
No
Do not infuse patient
Is this first patient in cohort or the 
previous patient reached Day 4 (Visit 
7)?
Yes
Yes
No
No
Yes
Withdraw patient 
from study.

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Appendix C- Definition of Myocardial Infarction 
Definition of Myocardial Infarction (two or more of the following): 
1. hs Troponin I or hs Troponin T level greater than the local lab reference range for normal. 
2. Electrocardiograms (EKGs; at least two) showing changes from baseline or serially in ST-T 
and/or Q-waves that were 0.03 seconds in width and/or greater than one-third of the total 
QRS complex in two or more contiguous leads. 
NOTE: Other EKG findings consistent with a diagnosis of myocardial infarction may also be 
considered a myocardial infarction. 
3. Clinical indications consistent with myocardial infarction as seen by prolonged (> 20 min) 
chest pain not relieved by rest and/or nitrates 
4. Radiologic evidence as seen by  
A. Angiographically documented coronary artery occlusion, or 
B. Imaging evidence of loss of viable myocardium 

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Appendix D- Definition of ALI Adapted from NHSN Biovigilance Component 
Hemovigilance Module Surveillance Protocol v2.4 
ALI is defined as the presence of the following: 
• NO evidence of acute lung injury (ALI) prior to infusion, and 
• Radiographic evidence of bilateral infiltrates, and 
• No left atrial hypertension (i.e., circulatory overload) as determined by clinical signs or left 
atrial pressure measurements, and 
• Hypoxemia defined by any one of these methods: 
- PaO2/FiO2 less than or equal to 300 mm Hg 
- Oxygen saturation less than 90% on room air 
- Other clinical evidence 

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Appendix E- DVT and PE Algorithm Pages from ICSI Guideline 

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Appendix F –  Instructions for Reconstitution and Preparation of Thrombosomes for 
Administration 
Study sites receiving, storing, preparing and administering Thrombosomes should be operating 
under BSL-2 workplace biosafety measures as applied in the blood establishment setting (AABB 
Technical Manual 19th edition chapter 2, Facilities, Work Environment and Safety).  These 
biosafety measures address agents of moderate potential hazard to personnel and the 
environment, usually from contact-associated exposure to certain infectious agents. Blood banks 
and laboratories typically operate under these measures, and pharmacies may also designate 
personnel, equipment, areas and procedures for the handling of such blood products. 
Appendix F.1 
Supplies and Equipment Required 
 
Investigational product is Thrombosomes.  Thrombosomes are prepared from pooled human 
blood product and  supplied for this trial as a lyophilized cake in a stoppered vial(s) for 
reconstitution with 10 ml sterile Water for Injection (WFI). 
Supplies and Equipment for Reconstitution of Thrombosomes and Preparation of Doses 
• Sterile Water for Injection, USP (may be used for multiple reconstitutions but discard at the 
end of the shift or day) 
• Sterile 10 and 20 ml syringes 
• Sterile Closed System Transfer Device (CSTD) (e.g. Chemotherapy Dispensing Pin, 
Universal Vial Spike with Clave or equivalent) 
• Alcohol wipes 
• Labels for syringe for final dose 
• Sterile syringe tip cap (dual function) 
• Hemo-Nate® Filter, 18 micron blood filter, (Product #402009, Utah Medical Products, 
Midvale, UT) 
Supplies and Equipment for Administration of Dose 
• IV administration set 
• Syringe pump capable of delivering a 10ml to 30ml dose at 1 ml/minute 
Appendix F.2 
Reconstitution of Thrombosomes 
Patients will require at least one vial of Thrombosomes to be reconstituted.  Aseptic technique 
must be used in the preparation of material. Thrombosomes should be infused within one hour of 
reconstitution 

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All reconstituted Thrombosomes vial(s) should be retained at 4°C on site for at least 7 days after 
infusion and be destroyed at the site as a biological material after completion of the study.  
Unused, unopened vial(s) of Thrombosomes will be returned to Cellphire. 
To rehydrate Thrombosomes: 
1. Remove vial(s) from room temperature storage and visually inspect for integrity.  If there are 
signs of breakage, damage to the seal or atypical appearance of the contents, do not use and 
contact Cellphire.  Record on the source document the vial(s) lot number, vial number, 
expiration date and other information as indicated on the form.  Record product information 
about the WFI and other supplies on the source document. 
2. Carefully remove any outer packaging from the vial(s).  Remove the tab of the protective cap 
of the vial(s) stopper, exposing the grey butyl stopper, but leaving the collar of the aluminum 
seal in place.  Swab with an alcohol wipe 
3. Swab the port on the WFI bag with an alcohol wipe [if exposed] and place a medication 
injection site in the port of the bag if needed.  Using this site and an appropriate sterile 
syringe, withdraw 10 ml WFI as indicated on the vial(s) label. 
4. Using a CSTD puncture the exposed stopper to allow venting of air.  Keep CSTD in place.  
5. Attach the syringe containing the WFI to the luerlock of the CSTD and slowly deliver the 
WFI to the vial(s) through the rubber stopper. Gently tip the CSTD/syringe, directing the 
stream against the inside side wall of the vial(s), not onto the cake. Keep CSTD and syringe 
in place. 
6. Record the start time/date of reconstitution on the vial(s) and on the source document. 
7 .  Gently swirl the vial(s) every few minutes until 10 minutes or the entire cake is resuspended. 
Rehydrated Thrombosomes should appear off-white and translucent in suspension. Note: If 
the product does not reconstitute within 10 minutes or demonstrates excessive clumping or 
discoloration upon visual inspection, do not use for transfusion and contact Cellphire.  In 
either case an alternate vial should be selected for rehydration. 
8. Thrombosomes should be transfused within one hour of the end time of reconstitution.   
Appendix F.3 
Preparation of Doses of Thrombosomes  
 
A dose table will be provided with each lot in the EDC. The method used to calculate dose is 
shown below. 
For example: Patient weight = 70 kg 
Label indicates a dosage of 0.1 ml/kg body weight 
70 x 0.1 =7.0 ml infusion dose. 
 
In this example, the 7.0 ml infusion dose requires reconstitution of one 10 ml vial of 
Thrombosomes.  If the volume calculated exceeds 10 ml, reconstitute additional number 
of vial(s) as required.   
Once reconstitution of the Thrombosomes is complete:  

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9. While the CSTD/syringe in place, withdraw the volume of Thrombosomes based on the 
calculated dose for the patient being treated.  Remove the syringe from the luerlock of 
CSTD. 
10. Attach the sterile filter to the syringe and cover filter end with a sterile tip cap. 
11. Attach syringe label with the designated recipient’s ID number, product lot number, vial 
number and expiration (date/time) of reconstituted material and other pertinent identification 
information required by local procedures.  
12. Provide to the responsible study personnel for infusion.   
13. After infusion, place reconstituted vial(s) in 4°C storage. 
 

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Appendix G – Modified Definition of Anaphylaxis 
(Supplement from Symposium on the Definition and Management of Anaphylaxis: Summary 
report Sampson, Hugh A. et al. Journal of Allergy and Clinical Immunology, Volume 115, Issue 
3, 584 – 591 and NHSN Hemovigilance Criteria.) 
Anaphylaxis is defined when any 1 of the 3 criteria are fulfilled:  
1. Acute onset of an illness (up to 4 hours post-infusion) with involvement of 
Skin/mucosal tissue (eg, hives, generalized itch/flush, swollen lips/tongue/uvula), and 
Airway compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced PEF), or 
Reduced Blood Pressure* or associated symptoms (eg, syncope) 
2. Two or more of the following after exposure to known allergen for that patient (up to 4 hours 
post-infusion) 
History of severe allergic reaction 
Skin/mucosal tissue (eg, hives, generalized itch/flush, swollen lips/tongue/uvula) 
Airway compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced PEF) 
Reduced BP* or associated symptoms (eg, syncope) 
3. Hypotension* after exposure to known allergen for that patient (up to 4 hours post-infusion) 
 *Systolic BP <100 mm Hg or >30% drop from their baseline 
BP: Blood pressure PEF: peak expiratory flow.