A Phase 1, Single-Center, Partial Double-Blind, Randomized, Controlled (Versus Fresh Frozen Plasma [FFP] in Cohort 3 Only) Clinical Study of the Safety of Ascending Doses of Autologous Freeze Dried Plasma (FDP) in Healthy Volunteers
Phase: PHASE1
Conditions: Freeze Dried Plasma in Healthy Volunteers
Sponsor: U.S. Army Medical Research and Development Command

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A PHASE 1, SINGLE-CENTER, PARTIAL 
DOUBLEBLIND, RANDOMIZED, CONTROLLED 
(VERSUS FRESH FROZEN PLASMA [FFP] IN COHORT 3 
ONLY) CLINICAL STUDY OF THE SAFETY OF 
ASCENDING DOSES OF AUTOLOGOUS FREEZE DRIED 
PLASMA (FDP) IN HEALTHY VOLUNTEERS 
 
 
NCT02930226 
 
 
IND17154; S-14-12 Study 
 
 
Protocol version 6.0 dated 19Apr2018 
 
 
 

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A PHASE 1, SINGLE-CENTER, PARTIAL DOUBLE- 
BLIND, RANDOMIZED, CONTROLLED (VERSUS 
FRESH FROZEN PLASMA [FFP] IN COHORT 3 ONLY) 
CLINICAL STUDY OF THE SAFETY OF ASCENDING 
DOSES OF AUTOLOGOUS FREEZE DRIED PLASMA 
(FDP) IN HEALTHY VOLUNTEERS 
Sponsor 
The Surgeon General, Department of  the Army 
Falls Church, VA 22041-3258 
Sponsor’s Representative (Acting) 
Robert E. Miller, PhD, RAC 
Office of Regulated Activities  (ORA) 
US Army Medical Research and Materiel Command (USAMRMC) 
1430 Veterans Drive, Fort Detrick, MD  21702-9232 
Telephone: 301-619-0317 
Fax: 301-619-0197 
E-mail: usarmy.detrick.medcom-usammda.mbx.usamrmc-regulatory- 
affairs@mail.mil 
Research Monitor 
Matthew Montgomery, MD 
Hoxworth Blood Center 
University of Cincinnati 
3130 Highland Avenue, Cincinnati, OH  45267 
Telephone: 513-558-1339 
Fax: 513-558-1341 
Email:  montgmw@ucmail.uc.edu 
Principal Investigator 
Jose A. Cancelas, MD, PhD 
Hoxworth Blood Center 
University of Cincinnati 
3130 Highland Avenue, Cincinnati, OH  45267 
Telephone: 513-558-1324 
Fax: 513-558-1522 
Email:  Jose.Cancelas@cchmc.org 
 
Clinical Trial Site 
Hoxworth Blood Center 
University of Cincinnati 
3130 Highland Avenue, Cincinnati, OH  45267 
Telephone: 513-558-1324 
Fax: 513-558-1522 
Email:  Jose.Cancelas@cchmc.org 

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Clinical Laboratories and Other Departments/Institutions Involved in the   Trial 
 
Contract Manufacturer 
Steve Penegor, Vice President Biological  Development 
Vascular Solutions, Inc. (a wholly owned subsidiary of Teleflex) 
6464 Sycamore Court North, Minneapolis, MN 55369  
Telephone: 763-656-4365 
Fax: 763-656-4250 
Email:  Steve.Penegor@teleflex.com 
Clinical Research Organization 
(CRO) Principal  Investigator 
Margot Krauss, MD, MPH, FACPM 
Westat 
1600 Research Boulevard, WB 270, Rockville, MD  20850 
Telephone: 301-279-4513 
Fax: 301-294-4494 
Email:  MargotKrauss@westat.com 
Statistician 
Brandy Rutledge, PhD 
Westat 
1600 Research Boulevard, WB 460, Rockville, MD  20850 
Telephone: 240-314-2330 
Fax: 301-738-8379 
Email:  BrandyRutledge@westat.com 
Data Management 
Whitney Smith 
Westat 
5615 Kirby Drive, Suite 710, Houston, TX  77005 
Telephone: 713-353-7948 
Fax: 713-529-4924 
Email:  whitneysmith@westat.com 
Institutional Review Board 
(IRB) 
 
 
 
 
USAMRMC Office of Research 
Protections 
Michael Link, PhD 
University of Cincinnati 
University Hall, Suite 300 
51 Goodman Drive, PO Box 210567, Cincinnati, OH   45221-0567 
Telephone: 513-558-5259 
Email: irb@ucmail.uc.edu 
Human Research Protection Office 
USAMRMC 
ATTN: MCMR-RPH 
504 Scott Street, Fort Detrick, MD 21702-5012 
Telephone: 301-619-2165 
Fax: 301-619-7803 
Email:  usarmy.detrick.medcom-usamrmc.other.hrpo@mail.mil 
 
 
 
 
FOR OFFICIAL USE  ONLY 
Information and data included in this document contain privileged and/or proprietary information, which is the 
property of the United States Army. No person is authorized to make it public without express written permission of 
the United States Army. These restrictions on disclosure will apply equally to all future information, which is 
indicated as privileged or  proprietary. 

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INVESTIGATOR’S AGREEMENT 
 
A PHASE 1, SINGLE-CENTER, PARTIAL DOUBLE- 
BLIND, RANDOMIZED, CONTROLLED (VERSUS 
FRESH FROZEN PLASMA [FFP] IN COHORT 3 ONLY) 
CLINICAL STUDY OF THE SAFETY OF ASCENDING 
DOSES OF AUTOLOGOUS FREEZE DRIED PLASMA 
(FDP) IN HEALTHY VOLUNTEERS 
 
“I have read this protocol and agree to conduct the study as outlined herein in accordance with 
International Conference on Harmonisation Good Clinical Practice Guidelines and Food and Drug 
Administration (FDA), Department of Defense, and United States Army   Regulations.” 
 
 
 
Jose A. Cancelas, MD, PhD 
Date 
Principal Investigator 
Hoxworth Blood Center/University of  Cincinnati 

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EMERGENCY CONTACT INFORMATION 
Table 1: 
Emergency Contact Information 
 
Role in Study 
Name 
Address and Telephone 
Number 
Principal Investigator 
Jose A. Cancelas, MD, PhD 
Hoxworth Blood Center 
University of Cincinnati 
3130 Highland Avenue 
Cincinnati, OH 45267 
Telephone: 513-558-1324 
Email: 
Jose.Cancelas@cchmc.org 
Clinical Research Coordinator 
Neeta Rugg 
Hoxworth Blood Center 
University of Cincinnati 
3130 Highland Avenue 
Cincinnati, OH 45267 
Telephone: 513-558-1525 
Email: ruggn@ucmail.uc.edu 
Research Monitor 
Matthew Montgomery, MD 
Hoxworth Blood Center 
University of Cincinnati 
3130 Highland Avenue, 
Cincinnati, OH 45267 
Telephone: 513-558-1339 
Fax: 513-558-1341 
Email: 
montgmw@ucmail.uc.edu 
Sponsor’s Representative (Acting) 
Robert E. Miller, PhD, RAC 
Office of Regulated Activities 
USAMRMC 
1430 Veterans Drive 
Fort Detrick, MD 21702-5009 
Telephone: 301-619-0317 
Email: usarmy.detrick.medcom- 
usammda.mbx.usamrmc- 
regulatory-affairs@mail.mil 
IRB 
Michael Link, PhD 
University of Cincinnati 
University Hall, Suite 300 
51 Goodman Drive 
PO Box 210567 
Cincinnati, OH 45221-0567 
Telephone: 513-558-5259 
Email: irb@ucmail.uc.edu 

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2. 
SYNOPSIS 
 
Name of Sponsor: 
The Surgeon General, Department of the  Army 
Name of Investigational  Product: 
RePlas™ 
Name of Active Ingredient: 
Human Plasma, Freeze Dried 
Title of Study: 
A Phase 1, Single-Center, Partial Double-Blind, Randomized, Controlled (versus Fresh Frozen 
Plasma [FFP] in Cohort 3 only) Clinical Study of the Safety of Ascending Doses of Autologous 
Freeze Dried Plasma (FDP) in Healthy  Volunteers 
Study Center(s): 
Hoxworth Blood Center/University of  Cincinnati 
Principal Investigator: 
Jose A. Cancelas, MD, PhD 
Study Period (years): 
Estimated date first subject enrolled: February 2017 
Estimated date last subject completed: July  2018 
Phase of Development: 1 
Objectives: 
Primary: The primary objective of this study is to assess the safety of single infusions with the 
RePlas™ FDP product at increasing fixed doses of either 1 unit (approximately 270 mL), 2 units 
(approximately 540 mL), or 3 units (approximately 810 mL) in normal healthy subjects. In the 2   
lower dose cohorts, safety will also be assessed in terms of the type of autologous plasma used as the 
starting material in the manufacture of the investigational  product: 
 
RePlas™ FDP product manufactured from autologous FFP derived from whole blood (WB) 
donations where Citrate Phosphate Dextrose (CPD) is the anticoagulant, or   RePlas™
FDP-CPD; and 
 
RePlas™ FDP product manufactured from autologous FFP collected during plasmapheresis 
where Acid Citrate Dextrose (ACD) is the anticoagulant, or RePlas™   FDP-ACD.
The highest dose cohort will receive FDP manufactured only from FFP collected by plasmapheresis 
(FDP-ACD). Conclusions on whether the study meets its safety objectives will be based only on 
treatment emergent adverse events (TEAEs). TEAEs are adverse events (AEs) that occur after 
administration of the study treatment, plasma infusion, has begun. AEs occurring prior to treatment 
(e.g., AEs that occur during autologous plasma collection) will not be considered relevant to the 
study’s objectives. 
Secondary: The secondary objectives are  to: 
 Assess the safety of a fixed-dose infusion of 3 FDP units (approximately 810 mL) in 
comparison to infusion with the same dose of autologous FFP collected during 
plasmapheresis; and
 Determine if the changes in specific coagulation factors, hematology, and chemistry values 
are similar within clinically meaningful levels after infusion of either 3 units of autologous 
FDP or FFP.

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Methodology: 
Overview. This single-site, partial double-blind study in healthy volunteers is designed to assess the 
safety of infusing ascending doses of reconstituted autologous FDP in 3 fixed-dose cohorts. Subjects   
in Cohort 1 will receive 1 unit of FDP, which is approximately 270 mL. Subjects in Cohort 2 will 
receive 2 units of FDP, which is approximately 540 mL. Subjects will be enrolled for a specific dose 
cohort beginning with the lowest dose in Cohort 1. In the absence of TEAEs or implementation of 
protocol stopping rules (SR), subjects will be enrolled in Cohort 2. In both Cohorts 1 and 2, subjects 
will be methodically assigned to 1 of 2 single infusion treatment arms where they will receive the 
corresponding dose of either FDP-CPD or FDP-ACD, products manufactured with autologous plasma 
derived from WB or autologous plasma collected by  plasmapheresis. 
In the absence of TEAEs or implementation of protocol stopping rules (SR) in Cohort 2 subjects, 
infusions in Cohort 3 subjects may proceed. These subjects will receive 3 autologous FDP-ACD units 
(approximately 810 mL), which is the highest trial dose of the experimental product and undergo an 
additional separate infusion where they will receive the same dose of autologous FFP. Subjects 
participating in this randomized, controlled, crossover infusion treatment cohort will be randomized    
to a specific infusion schedule where they will first be infused with either 3 units of FDP or 3 units of 
FFP at the first infusion visit, followed by infusion with the alternate product at the second infusion 
visit. Crossover treatment of FDP and FFP enables comparison of infusion safety parameters and   
select coagulation factor recoveries between FDP and FFP within the same subject at this higher dose. 
Unlike Cohorts 1 and 2, the FDP and FFP infusion products in Cohort 3 will be sourced only from 
autologous plasmapheresis donations. A 2-week period between infusion visits is required for all  
Cohort 3 subjects regardless of the infusion  schedule. 
Collection of Autologous Plasma. Use of autologous plasma in the trial assists in the elimination of 
potential AEs related to allogeneic plasma infusion, but it also adds additional burden to participating 
subjects who, upon consent and enrollment, need to donate sufficient volume of plasma to provide the 
autologous plasma needed for the trial infusions (eg, manufacture of autologous FDP units in all 
cohorts; in Cohort 3, the additional need for FFP in addition to FDP). Blood donation standards 
typically require a 56-day interval between WB donations; however, an abbreviated donation period    
of 28 days will be in use for the duration of this study. Without the loss of red blood cells (RBCs) in 
plasmapheresis, these types of donations can be made more frequently, with an approximate 7 to 10  
day interval between donations. Also, depending on the donor’s size, plasmapheresis donations yield 
greater plasma volume per collection. Summarily, compared to WB collection, the use of 
plasmapheresis to net the per subject plasma volume required presents practical advantages to    
subjects (eg, requires fewer collection visits) while minimizing increased risk for Cohort 3   subjects. 
FDA’s volume limits for automated collection of plasma are summarized and presented in the 
Collection Volume Limits via Plasmapheresis Collection table below   (FDA-1992). 
Collection Volume Limits via Plasmapheresis  Collection 
*includes anticoagulant volume 
As shown in the Cohort and Treatment Arm Details table below, subjects’ assigned cohorts and 
treatment arms indicate the type, frequency, and total volume of blood/plasma donations required. 
Subjects in Cohorts 1 and 2 are to provide sufficient plasma volume for a single infusion with either 1 
or 2 units, respectively, and based on assigned treatment arm, they are to provide plasma through   WB 
Donor Weight 
Plasma Volume or Weight 
Collection Volume* 
10 – 149 lbs 
625 mL (640 g) 
690 mL (705 g) 
150-174 lbs 
750 mL (770 g) 
825 mL (845 g) 
≥175 lbs 
800 mL (820 g) 
880 mL (900 g) 

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or plasmapheresis collection for manufacture of autologous FDP-CPD or FDP-ACD. Cohort 2 
subjects in the FDP-CPD treatment arm are required to successfully make 2 WB donations within a 
relatively short period of time to provide adequate volume for their use in the trial. Because of the 
extraordinarily long time required to accrue sufficient WB-derived plasma for the high dose cohort 
(approximately 11 months), the FDP-CPD treatment arm is not included in Cohort 3. The total 
starting volume of plasma needed from each Cohort 3 subject is approximately 1,620 mL; triple that 
of Cohort 2 and thus inclusion of this treatment arm in Cohort 3 would require 6 WB donations, 
increasing subject risk for significant iron store depletion and  anemia. 
Cohort and Treatment Arm  Details 
1 Assumes an average range of 600 to 800 mL donation volume. 
Pharmacovigilance. 
The study will be paused to assess the safety of study continuation using the following SRs that will 
be applied to all study subjects throughout the  trial: 
1. An SAE that is determined to be possibly, probably, or definitely related to the study   product; 
2. An AE related to the study product that the PI, RM, and/or the sponsor’s PVG MD agree 
jeopardizes the subject’s health or safety; 
3. An AE related to the study product that requires medical or surgical intervention to prevent 
occurrence of an SAE; 
4. A post-infusion, coagulation function assay result that is abnormal and also greater than a  
20% change from the baseline value recorded for prothrombin time and international 
normalized ratio (PT/INR) and/or activated partial thromboplastin time (aPTT) (eg, a subject 
who has a baseline INR of 1.0 with a post-infusion INR of 1.3 will activate an SR, because 
this is an abnormal coagulation function assay result that is also a greater than 20% change 
from the pre-infusion assay result);  and/or 
5. Post-infusion development of deep vein thrombosis (DVT), cardiac ischemia, pulmonary 
embolism (PE), or hemolysis. 
Dose Cohorts and Treatment 
Arms 
Number 
of   
Subjects 
Donation 
Type 
Approximate 
Volume 
Autologous 
Plasma Required 
Number of 
Donations 
Cohort 1: One unit single infusion [approximately 270  mL] 
Arm 1: FDP-CPD 
4 
WB 
270 
1 
Arm 2: FDP-ACD 
4 
Plasmapheresis 
270 
1 
Cohort 2: Two units single infusion [approximately 540  mL] 
Arm 3: FDP-CPD 
4 
WB 
540 
2 
Arm 4: FDP-ACD 
4 
Plasmapheresis 
540 
1 
Cohort 3: Three units crossover infusion [approximately 810 mL,  each] 
Arm 5: FDP-ACD x FFP 
4 
Plasmapheresis 
1,620 
3-41 
Arm 6: FFP x FDP-ACD 
4 
Plasmapheresis 
1,620 
3-41 

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Data and Safety Monitoring Board (DSMB). A designated DSMB will formally review subjects’  
data following the completion of infusions in each cohort for the purpose of assessing safety. DSMB 
meetings will be scheduled to maximize the amount of subject data reported to the DSMB through the 
28-day follow-up visit. The DSMB will have at a minimum all data through the 7-Day Follow Up  
Visit. Following each meeting, the DSMB will provide the sponsor with a recommendation about 
proceeding with infusions in the subsequent cohort. Following the meeting to review Cohort 3 data,   
the DSMB will provide a recommendation about proceeding with the next planned FDP trial. After    
the receipt and consideration of each DSMB recommendation, the sponsor will make a final 
determination about proceeding to the next cohort or the next FDP  trial. 
Estimated Number of Subjects to Screen:  48 
Maximum Number of Subjects to Enroll:  24 
Cohort 1, Arm 1: (n=4) subjects are to be infused with 1 autologous FDP unit (FDP-CPD) 
manufactured from WB-derived FFP. 
Cohort 1, Arm 2: (n=4) subjects are to be infused with 1 autologous FDP unit (FDP-ACD) 
manufactured from FFP collected via  plasmapheresis. 
Cohort 2, Arm 3: (n=4) subjects are to be infused with 2 autologous FDP (FDP-CPD) units 
manufactured from WB-derived FFP. 
Cohort 2, Arm 4: (n=4) subjects are to be infused with 2 autologous FDP units (FDP-ACD) 
manufactured from FFP collected via  plasmapheresis. 
Both arms of Cohort 3 are to be infused with 3 units of autologous plasma product at each of 2 
infusion visits. Infusion visits are to be scheduled such that there is a period of no less than 2 weeks 
between infusions. 
Cohort 3, Arm 5: (n=4) subjects will receive 3 autologous FDP units (FDP-ACD) manufactured 
from FFP collected via plasmapheresis at their first infusion visit followed by infusion with 3 
autologous FFP units, collected via plasmapheresis, at their second  visit. 
Cohort 3, Arm 6: (n=4) subjects will be infused with these products in the opposite order as Arm  
5 (eg, autologous FFP at first infusion and autologous FDP-ACD at the   second). 
Eligibility and Main Criteria for Inclusion/Exclusion: 
Inclusion Criteria: 
1. Males and non-pregnant/non-breastfeeding  females; 
2. For females, a minimum weight of 140 pounds and a maximum weight of 220 pounds; for 
males a minimum weight of 140 pounds and a maximum weight of 250   pounds; 
3. 18-55 years of age; 
4. Self-reports that he or she feels well and  healthy; 
5. Scores ≥ 35 on the Duke Activity Status  Index; 
6. Able to donate a unit of WB or plasma by plasmapheresis based on the AABB donor history 
questionnaire with modifications indicated. Subjects with history of travel which puts them at 
risk for Creutzfeldt-Jakob Disease, malaria, or Zika will be eligible to   participate; 
7. Has read the educational materials on donating blood and has had his or her questions 
answered; 
8. Able and willing to provide written informed  consent; 
9. Available and able to come to the treatment clinic for scheduled study visits for the duration 
of the trial, which is approximately 12 weeks for subjects in Cohort 1 and Cohort 2, Arm   4 

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and approximately 16 weeks for Cohort 2, Arm 3 and Cohort 3 (includes time for collections, 
product manufacture, and  infusions); 
10. Females of childbearing potential should either be surgically sterile (hysterectomy or tubal 
ligation), or should use a highly effective, medically accepted contraceptive regimen. Highly 
effective methods of birth control are 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, sexual abstinence, 
condoms with spermicide, or vasectomized  partner; 
11. All females must have a negative urine pregnancy test prior to enrollment;   and 
12. Understands the English language. 
Exclusion Criteria: 
1. Known liver, kidney, cardiovascular, neurologic, gastrointestinal, blood, endocrine/metabolic, 
autoimmune or pulmonary disease, or treated or untreated  hypertension; 
2. Cancer of any kind, under treatment or  resolved; 
3. Known or past coagulopathy  conditions; 
4. Any conditions, medications, etc. on the AABB medical deferral  list; 
5. Past history of asthma (defined as use of a prescribed daily asthma controller medication or 
required asthma medication in the past 2  weeks); 
6. Past diagnosis of stroke, deep vein thrombosis, venous or arterial thrombosis, blood clots, or 
transient ischemic attack; 
7. Family history of venous or arterial thrombosis before the age of 50 in first-degree relatives 
(i.e., biological parents, full siblings, or  children); 
8. D-dimer result ≥0.5 FEU/mL; 
9. History of abnormal electrocardiogram  (EKG); 
10. Current smoker (defined as having smoked within the last 6  months); 
11. Known Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome 
(AIDS)-related illness or received a positive test result for HIV  infection; 
12. Positive test for Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) or Human T-cell 
Lymphotropic Virus (HTLV); 
13. History or significant treated or untreated mental health  issues; 
14. Female subject who is pregnant, lactating, or with a positive pregnancy   test; 
15. Currently taking an antibiotic or another medication for an  infection; 
16. Treatment or use of aspirin (or other platelet inhibiting agents) within 14 days of study 
donation and infusion visits; 
17. Currently using any medications for anticoagulant  therapy; 
18. Previous use of clotting factor  concentrate(s); 
19. Receipt of blood or blood products within the past 12  months; 
20. In the past week, has had a headache and fever at the same  time; 
21. Known intolerance to any excipients (citrate) in the study drug  formulation; 
22. Systolic blood pressure greater than 140  mmHg; 
23. Diastolic blood pressure greater than 90  mmHg; 
24. Temperature greater than 100°F; 
25. Known hematocrit less than 38% for both male and female  donors; 

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26. Positive direct antiglobulin test  (DAT); 
27. Treatment with any investigational agent within 1 month before treatment infusion for this 
trial; 
28. Participation in any phase of any other investigational trials while participating in this   trial; 
29. 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 subject’s return for 
follow-up visits on schedule; 
30. Other unspecified reasons that, in the opinion of the PI, make the subject unsuitable for 
enrollment; or 
31. Institutionalized because of legal or regulatory  order. 
Investigational Product Dosage, Schedule, and Mode of  Administration: 
Cohort 1, Arm 1: Subjects will be infused with 1 unit (approximately 270 mL) of autologous 
FDP-CPD. 
Cohort 1, Arm 2: Subjects will be infused with 1 unit (approximately 270 mL) of autologous 
FDP-ACD. 
Cohort 2, Arm 3: Subjects will be infused with 2 units (approximately 540 mL) of autologous 
FDP-CPD. Cohort 2, Arm 4: Subjects will be infused with 2 units (approximately 540 mL) of 
autologous FDP-ACD. 
Cohort 3, Arms 5 & 6: Subjects will be infused with 3 units (approximately 810 mL) of  
autologous FDP-ACD and 3 units (approximately 810 mL) of autologous control FFP following a   
2 week cross-over period. Subjects will receive in total 6 units (approximately 1,620 mL) over the 
course of 2 infusion visits. Subjects are to be randomized to treatment schedule arms that dictate  
the sequence for infusing FDP-ACD and FFP across the 2 infusion visits (eg, FDP-ACD at the   
first infusion followed by FFP or vice  versa). 
Duration of Treatment: Cohort  dependent 
Duration of Subject Participation, by Cohort and Treatment Arm   Assignment 
The timeline for screening, autologous plasma collection(s), and FDP manufacturing are estimated.  
The time to complete WB/Plasma collection may be extended if needed to obtain the required amount 
of study plasma and will be assessed on a per-subject basis. The manufacturing time has been set at 5 
weeks to allow time for shipping, manufacture, and testing of the FDP  product. 
Cohort, 
Screening 
WB/Plasma 
FDP 
Planned 
Total 
Treatment Arm 
Period 
Collection 
Manufacturing 
Study 
Expected 
Time 
Time 
Follow-up 
Duration 
Period 
Cohort 1, Arm 1 
~2 Weeks 
1 Week 
~5 Weeks 
4 Weeks 
~12 Weeks 
Cohort 1, Arm 2 
~2 Weeks 
1 Week 
~5 Weeks 
4 Weeks 
~12 Weeks 
Cohort 2, Arm 3 
~2 Weeks 
~5 Weeks 
~5 Weeks 
4 Weeks 
~16 Weeks 
Cohort 2, Arm 4 
~2 Weeks 
1 Week 
~5 Weeks 
4 Weeks 
~12 Weeks 
Cohort 3, Arm 5 
~2 Weeks 
~3 Weeks 
~5 Weeks 
6 Weeks 
~16 Weeks 
Cohort 3, Arm 6 
~2 Weeks 
~3 Weeks 
~5 Weeks 
6 Weeks 
~16 Weeks 

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The longest expected duration of subject participation is approximately 16 weeks for subjects in 
Cohort 2, Arm 3 and Cohort 3, Arms 5 and  6. 
Reference Therapy, Dosage, Schedule, and Mode of  Administration: 
The reference therapy for this study is autologous FFP. Subjects in Cohort 3 are treated in a crossover 
design randomizing product infusion order across the two infusion visits. The initial infusion will be 
either 3 units of autologous FDP-ACD or 3 units of autologous control plasma (FFP). Subjects in 
Cohort 3 will receive a second infusion of reference product or investigational product, depending on 
their initial treatment. Subjects in Cohort 3 are to receive a total of 6 units of autologous   plasma. 
Criteria for Evaluation: 
Primary Endpoints. The primary endpoints to be assessed are AEs, specifically TEAEs; SAEs; 
Suspected, Unexpected, Serious Adverse Reactions (SUSARs); and  death. 
Secondary Endpoints. In Cohort 3, the change in pre- and post-infusion measurement of the 
endpoints listed below will be  compared: 
 
PT, INR, aPTT, Factors I, II, V, VII, VIII, IX, X, XI, D-Dimer, von Willebrand factor 
activity, Protein S activity, Protein C activity, PF 1+2, TAT, Antithrombin III, Alpha-2 
Antiplasmin, and C3a des Arg compared to pre-infusion values after 3 unit infusion of 
FDP compared to 3 unit infusion of FFP;  and 
 
Hematology, urinalysis, vital signs, DAT and chemistry values compared to pre-infusion 
values after 3 unit infusion of FDP compared to 3 unit infusion of  FFP. 
Statistical Methods: 
Descriptive statistics will be used to present the study data. Categorical variables will be presented as 
number and percent of subjects for each outcome. For quantitative variables, summaries will include  
the sample size, mean, median, standard deviation, minimum, and maximum and 25th and 75th 
percentile. All data will be presented either as listings, summary tables, figures, or all 3. For summary 
descriptive statistics, missing data will be represented by counts; no adjustments will be made. For the 
crossover study (Cohort 3), descriptive statistics will be provided for each treatment, treatment by 
period (first or second administration), treatment by sequence (FDP then FFP [Sequence 1] or FFP   
then FDP [Sequence 2]) by period, and will include the sample size, mean, median, standard    
deviation, minimum, and maximum and 25th and 75th percentile.. All statistical analyses will be 
performed using SAS version 9.3 or higher (SAS Institute Inc., Cary,  NC). 

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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................. 1 
EMERGENCY CONTACT INFORMATION.................................................................................. 4 
2. 
SYNOPSIS ..................................................................................................................... 5 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ................ 12 
TABLE OF CONTENTS ................................................................................................................ 12 
LIST OF TABLES ........................................................................................................................... 17 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................. 18 
5. 
INTRODUCTION ........................................................................................................ 21 
5.1. 
Limitations of Fresh Frozen Plasma Products ............................................................. 21 
5.2. 
Military Relevance ....................................................................................................... 21 
5.3. 
Rationale for Study ...................................................................................................... 22 
5.4. 
Name and Description of the Investigational Product ................................................. 23 
5.5. 
Summary of Nonclinical and Clinical Trials ............................................................... 24 
5.5.1. 
Nonclinical Studies ...................................................................................................... 24 
5.5.1.1. 
Toxicology Testing ...................................................................................................... 24 
5.5.1.2. 
Pharmacology ............................................................................................................... 24 
5.5.2. 
Clinical Studies ............................................................................................................ 24 
5.5.2.1. 
Toxicology in Humans ................................................................................................. 25 
5.5.2.2. 
Pharmacokinetics and Biological Disposition ............................................................. 25 
5.6. 
Known and Potential Risks and Benefits to Human Subjects ..................................... 25 
5.6.1. 
Risks/Discomfort to Subjects and Precautions to Minimize Risk ............................... 25 
5.6.1.1. 
Venipuncture ................................................................................................................ 25 
5.6.1.2. 
Whole Blood Collection Reactions .............................................................................. 25 
5.6.1.3. 
Plasmapheresis Reactions ............................................................................................ 25 
5.6.1.4. 
Local Reactions and Systemic Infusion Reactions ...................................................... 26 
5.6.1.5. 
Pregnancy ..................................................................................................................... 27 
5.6.1.6. 
Lactation ....................................................................................................................... 27 
5.6.1.7. 
Allergic Reaction ......................................................................................................... 27 
5.6.1.8. 
Unknown Risks ............................................................................................................ 27 

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5.6.2. 
Alternatives to this Investigational New Drug Product or Study................................. 27 
5.6.3. 
Intended Benefit for Subjects ....................................................................................... 27 
5.6.4. 
Risks to the Study Personnel and the Environment ..................................................... 27 
5.7. 
Route   of   Administration,   Dosage   Regimen,   Treatment   Period,   and 
Justification .................................................................................................................. 28 
5.8. 
Compliance Statement ................................................................................................. 29 
5.9. 
Study Population .......................................................................................................... 29 
5.10. 
Study Site ..................................................................................................................... 29 
6. 
TRIAL OBJECTIVES AND PURPOSE ..................................................................... 31 
6.1. 
Primary Objective ........................................................................................................ 31 
6.2. 
Secondary Objectives ................................................................................................... 31 
6.3. 
Trial Design .................................................................................................................. 31 
6.4. 
Study Endpoints ........................................................................................................... 31 
6.4.1. 
Primary Endpoints ........................................................................................................ 31 
6.4.2. 
Secondary Endpoints .................................................................................................... 31 
6.5. 
Overall Study Design ................................................................................................... 32 
6.6. 
Measures Taken to Minimize/Avoid Bias .................................................................... 49 
6.6.1. 
Randomization ............................................................................................................. 49 
6.6.2. 
Blinding ........................................................................................................................ 49 
6.6.3. 
Unblinding.................................................................................................................... 50 
6.7. 
Investigational Product................................................................................................. 51 
6.7.1. 
Investigational Product Packaging and Labeling ......................................................... 52 
6.7.2. 
Investigational Product Storage and Preparation ......................................................... 52 
6.7.3. 
Investigational Product Accountability ........................................................................ 53 
6.8. 
Duration of Subject Participation ................................................................................. 54 
6.9. 
Dose-Adjustment Criteria ............................................................................................ 54 
6.9.1. 
Safety Criteria for Dose Adjustment or Stopping Doses ............................................. 54 
6.10. 
Trial Treatment Randomization Codes ........................................................................ 55 
6.11. 
Identification of Data to be Recorded on the Case Report Forms ............................... 55 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS ............................................... 55 
7.1. 
Recruitment of Subjects ............................................................................................... 55 
7.2. 
Eligibility Screening ..................................................................................................... 56 
7.3. 
Re-Screening Visits ...................................................................................................... 56 

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7.4. 
Subject Inclusion Criteria ............................................................................................. 56 
7.5. 
Subject Exclusion Criteria ............................................................................................ 57 
7.6. 
Subject Withdrawal Criteria ......................................................................................... 58 
7.6.1. 
When and How to Withdraw Subjects ......................................................................... 59 
7.6.2. 
Data Collected for Withdrawn Subjects....................................................................... 59 
7.6.3. 
Replacement of Subjects .............................................................................................. 59 
7.6.4. 
Follow-Up for Withdrawn Subjects ............................................................................. 60 
8. 
TREATMENT OF SUBJECTS ................................................................................... 60 
8.1. 
Whole Blood and Plasma Collection ........................................................................... 60 
8.1.1. 
Cohort 1 Blood and Plasma Collection ........................................................................ 60 
8.1.2. 
Cohort 2 Blood and Plasma Collection ........................................................................ 61 
8.1.3. 
Cohort 3 Plasma Collection ......................................................................................... 62 
8.2. 
Plasma Infusion ............................................................................................................ 63 
8.2.1. 
Cohorts 1 and 2 Plasma Infusion ................................................................................. 63 
8.2.2. 
Cohort 3 Plasma Infusion ............................................................................................. 65 
8.3. 
Follow-Up Visits .......................................................................................................... 66 
8.3.1. 
24-Hour Follow-Up Visit ............................................................................................. 66 
8.3.2. 
Telephone Follow-Up .................................................................................................. 67 
8.3.3. 
7-Day Follow-Up Visit ................................................................................................ 67 
8.3.4. 
28-Day Follow-Up Visit .............................................................................................. 67 
8.3.5. 
Biological Samples ....................................................................................................... 68 
8.4. 
Early Withdrawal Procedures ...................................................................................... 68 
8.5. 
Unscheduled Visits ....................................................................................................... 69 
8.6. 
Concomitant Medications ............................................................................................ 69 
8.7. 
Procedures for Monitoring Subject Compliance .......................................................... 69 
9. 
PHARMACOKINETIC ASSESSMENTS .................................................................. 70 
10. 
SAFETY ASSESSMENT ............................................................................................ 70 
10.1. 
Specification of Safety Endpoints ................................................................................ 71 
10.1.1. 
Vital Signs .................................................................................................................... 71 
10.1.2. 
Laboratory Assessments ............................................................................................... 72 
10.1.2.1. 
Hematology and Clinical Chemistry ............................................................................ 72 
10.1.2.2. 
Urinalysis ..................................................................................................................... 74 
10.1.2.3. 
Coagulation Markers .................................................................................................... 74 

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10.1.2.4. 
Drug Screen .................................................................................................................. 76 
10.1.2.5. 
Pregnancy Screen ......................................................................................................... 76 
10.2. 
Investigational New Drug Safety Reporting ................................................................ 76 
10.2.1. 
Adverse Event or Suspected Adverse Reaction ........................................................... 76 
10.2.2. 
Serious Adverse Event or Serious Suspected Adverse Reaction ................................. 76 
10.2.3. 
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction ................... 77 
10.2.4. 
Expected Adverse Events ............................................................................................. 77 
10.2.5. 
Unanticipated Problems Involving Risks to Subjects or Others .................................. 78 
10.3. 
Relationship to Investigational Product ....................................................................... 78 
10.4. 
Severity Assessment ..................................................................................................... 79 
10.5. 
Recording and Reporting Adverse Events ................................................................... 79 
10.5.1. 
Methods and Timing for Assessing, Recording, and Analyzing  Adverse 
Events ........................................................................................................................... 80 
10.5.2. 
Duration of Follow-Up of Subjects after an Adverse Event ........................................ 81 
10.6. 
Reporting Adverse Events ............................................................................................ 81 
10.6.1. 
Reporting Serious Adverse Events ............................................................................... 81 
10.6.2. 
Reporting to the IRB .................................................................................................... 83 
10.6.3. 
Reporting Additional Immediately Reportable Events to the  Sponsor’s 
Safety Office ................................................................................................................ 83 
10.6.3.1. 
Pregnancy ..................................................................................................................... 83 
10.6.3.2. 
AE-Related Withdrawal of Consent ............................................................................ 84 
10.6.4. 
Pending Inspections/Issuance of Reports ..................................................................... 84 
10.6.5. 
IND Annual Report to the FDA ................................................................................... 84 
10.6.6. 
Final Report .................................................................................................................. 84 
11. 
STATISTICS................................................................................................................ 85 
11.1. 
Description of Statistical Methods and Analysis ......................................................... 85 
11.1.1. 
Endpoints for Primary Study Objective Analyses ........................................................ 85 
11.1.2. 
Endpoints for Secondary Study Objectives Analyses .................................................. 86 
11.1.2.1. 
Safety Analyses Comparing FDP to FFP (Secondary Objective #1)........................... 86 
11.1.2.2. 
Exploratory Analyses Comparing FDP to FFP (Secondary Objective 2).................... 89 
11.1.3. 
Safety Analyses ............................................................................................................ 89 
11.2. 
Planned Enrollment and Reason for Sample Size ........................................................ 89 
11.3. 
Level of Significance ................................................................................................... 90 
11.4. 
Interim Analysis and Stopping Rules ........................................................................... 90 

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11.5. 
Accounting for Missing, Unused, and Spurious Data .................................................. 90 
11.6. 
Procedures for Reporting Deviations from the Original Statistical Plan ..................... 90 
11.7. 
Selection of Subjects to be Included in Analyses ........................................................ 90 
12. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .......................................... 91 
12.1. 
Study Monitoring ......................................................................................................... 91 
12.2. 
Audits and Inspections ................................................................................................. 92 
12.3. 
Institutional Review Board .......................................................................................... 92 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE ........................................... 92 
14. 
ETHICS ........................................................................................................................ 93 
14.1. 
Ethics Review ............................................................................................................... 93 
14.1.1. 
Review/Approval of Study Protocol ............................................................................ 93 
14.1.2. 
Protocol Modifications ................................................................................................. 93 
14.1.3. 
Protocol Deviation Procedures ..................................................................................... 93 
14.2. 
Ethical Conduct of the Study ....................................................................................... 94 
14.2.1. 
Confidentiality .............................................................................................................. 94 
14.2.2. 
Compensation for Participation .................................................................................... 94 
14.2.3. 
Medical Care for Research-Related Injury .................................................................. 95 
14.3. 
Written Informed Consent............................................................................................ 95 
15. 
DATA HANDLING AND RECORDKEEPING ......................................................... 96 
15.1. 
Inspection of Records ................................................................................................... 96 
15.2. 
Retention of Records .................................................................................................... 97 
16. 
PUBLICATION POLICY ............................................................................................ 97 
17. 
LIST OF REFERENCES ............................................................................................. 98 
18. 
APPENDICES ............................................................................................................ 100 
APPENDIX A. STUDY PERSONNEL ROLES AND RESPONSIBILITIES .......................... 101 
APPENDIX B. AABB FULL-LENGTH DONOR HISTORY QUESTIONNAIRE ................ 103 
APPENDIX C. SAFETY REVIEW MEMO .............................................................................. 106 
APPENDIX D. TELEPHONE RECRUITMENT ...................................................................... 107 
APPENDIX E. RECRUITMENT FLYER ................................................................................. 110 
APPENDIX F. DUKE ACTIVITY STATUS INDEX (DASI) .................................................. 111 
APPENDIX G. IRON SUPPLEMENTATION FLYER ............................................................ 112 
APPENDIX H. TELEPHONE FOLLOW-UP SCRIPT ............................................................. 113 
APPENDIX I. HEMOVIGILENCE FORM ............................................................................... 115 

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APPENDIX J. SAE FORM ........................................................................................................ 119 
APPENDIX K. PREGNANCY FORM ...................................................................................... 124 
 
LIST OF TABLES 
TABLE 1:   EMERGENCY CONTACT INFORMATION .............................................................. 4 
TABLE 2:  ABBREVIATIONS ..................................................................................................... 18 
TABLE 3:  COHORT AND TREATMENT ARM DETAILS ....................................................... 33 
TABLE 4:  STUDY EVENTS SCHEDULE FOR COHORT 1, ARMS 1 AND 2 ........................ 35 
TABLE 5:  STUDY EVENTS SCHEDULE FOR COHORT 2, ARM 3 ....................................... 38 
TABLE 6:  STUDY EVENTS SCHEDULE FOR COHORT 2, ARM 4 ....................................... 40 
TABLE 7:   LABORATORY TESTING SCHEDULE AND VOLUMES FOR 
COHORTS 1 AND 2 ................................................................................................... 42 
TABLE 8:  STUDY EVENTS SCHEDULE FOR COHORT 3 ..................................................... 43 
TABLE 9:   LABORATORY TESTING SCHEDULE AND VOLUMES FOR  COHORT 
3    ..................................................................................................................................47 
TABLE 10:INVESTIGATIONAL PRODUCT .............................................................................. 51 
TABLE 11:HEMATOLOGY AND CLINICAL CHEMISTRY TESTS ........................................ 73 
TABLE 12:COAGULATION TESTS ............................................................................................ 75 
TABLE 13:STUDY CONTACTS FOR REPORTING SAES INVOLVING RISK TO   
SUBJECTS OR OTHERS ............................................................................................ 82 
TABLE 14:SAE INFORMATION TO BE REPORTED TO THE  SPONSOR’S 
SAFETY OFFICE ........................................................................................................ 83 
TABLE   15:SECONDARY   SAFETY   ENDPOINTS   AND   SCHEDULED 
MEASUREMENTS ..................................................................................................... 87 
TABLE 16:PRECISION ESTIMATES BASED ON SAFETY  OUTCOME 
INCIDENCE RATES AND SAMPLE SIZE ............................................................... 90 

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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations are used in this study  protocol. 
Table 2: 
Abbreviations 
Abbreviation 
Explanation 
 
ACD 
Acid Citrate Dextrose 
AE 
Adverse Event, Adverse Experience 
AIDS 
Acquired  Immunodeficiency Syndrome 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
aPTT 
Activated Partial Thromboplastin  Time 
AR 
Adverse Reaction 
AST 
Aspartate Aminotransferase 
AT-III 
Antithrombin III 
BUN 
Blood Urea Nitrogen 
C3 
Complement Factor 3 
CAP 
College of American Pathologists 
CBC 
Complete Blood Count 
CFR 
Code of Federal Regulations 
CO2 
Carbon Dioxide 
CPD 
Citrate Phosphate Dextrose 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse  Events 
DAT 
Direct Antiglobulin Test 
DCR 
Damage-Control Resuscitation 
DIC 
Disseminated  Intravascular Coagulation 
DIN 
Donation Identification Number 
DoD 
Department of Defense 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
eIT 
Enterprise Information Technology 
EKG 
Electrocardiogram 
FDA 
Food and Drug Administration 
FDP 
Freeze Dried Plasma 

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Abbreviation 
Explanation 
FDP-ACD 
Freeze Dried Plasma collected by plasmapheresis where Acid  Citrate Dextrose 
was used as the anticoagulant 
FDP-CPD 
Freeze Dried Plasma derived from whole blood where  Citrate Phosphate 
Dextrose was used as the anticoagulant 
FFP 
Fresh Frozen Plasma 
GCP 
Good Clinical Practice 
HBC 
Hoxworth Blood Center 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HHS 
US Department of Health and Human  Services 
HIPAA 
Health Insurance Portability and Accountability  Act 
HIV 
Human Immunodeficiency Virus (Types 1 and  2) 
HRPO 
Human Research Protections  Office 
HTLV 
Human T-cell Lymphotropic Virus (Types 1 and  2) 
ICF 
Informed Consent Form 
ICH 
International Conference on  Harmonisation 
ICSI 
Institute for Clinical Systems Improvement 
IgG 
Immunoglobulin G 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IV 
Intravenous 
K 
Potassium 
Kg 
Kilogram 
LyP 
Lyophilized Plasma 
Mg 
Milligram(s) 
mL 
Milliliter(s) 
mmHg 
Millimeter of Mercury 
NBCUS 
National Blood Collection and Utilization Survey  Report 
ORA 
Office of Regulated Activities [formerly Division of Regulated  Activities and 
Compliance (DRAC) and Clinical Services Support Division  (CSSD)] 
ORP 
Office of Research Protections 
PF 1+2 
Prothrombin Fragment 1+2 
PF24 
Plasma frozen 24-hours after  phlebotomy 
Plasma is refrigerated within 8 hours of  phlebotomy. 

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Abbreviation 
Explanation 
PF24RT24 
Plasma frozen 24- hours after  phlebotomy 
Plasma is held at room temperature from the time of phlebotomy to freezer 
storage 
pH 
Logarithmic measure of hydrogen ion  concentration 
PI 
Principal Investigator 
PLTs 
Platelets 
pRBCs 
Packed Red Blood Cells 
PSSB 
Product Safety Surveillance Branch, ORA,  USAMMDA 
PT 
Prothrombin Time 
PT/INR 
Prothrombin Time and International Normalized  Ratio 
PVG MD 
Pharmacovigilance Physician 
RBC 
Red Blood Cell 
RM 
Research Monitor 
SAE 
Serious Adverse Event 
SOC 
System, Organ, Class Designation 
SOCOM 
United States Special Operations  Command 
SOP 
Standard Operating Procedure 
SR 
Stopping Rule 
SUSAR 
Suspected, Unexpected, Serious Adverse  Reaction 
SWFI 
Sterile Water for Injection 
TAT 
Thrombin-Antithrombin Complex 
TEAE 
Treatment Emergent Adverse Event 
TSG 
The Surgeon General 
TTP 
Thrombocytopenic Purpura 
UAE 
Unexpected Adverse Event 
ULN 
Upper Limit of Normal 
USAMMDA 
United States Army Medical Materiel  Development Activity 
USAMRMC 
United States Army Medical Research and  Materiel Command 
US 
United States 
USP 
US Pharmacopeia 
VSI 
Vascular Solutions, Inc. (a wholly owned subsidiary of  Teleflex) 
vWF 
von Willebrand Factor 
WB 
Whole Blood 
WBC 
White Blood Cell 

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5. 
INTRODUCTION 
Recent studies have shown that early attention to coagulopathy in severely injured patients, and 
an earlier use of blood products (including plasma and platelets), may improve patient outcome 
(Borgman et al-2007, Holcomb et al-2007, Murad et  al-2010). 
FFP is plasma that is separated from a unit of whole blood (WB) and frozen within 8 hours of 
collection. FFP can also be manufactured from plasma collected during plasmapheresis;   
however, freezing must occur within 6 hours after collection. The anticoagulant used for 
collection of WB-derived FFP is Citrate Phosphate Dextrose (CPD), and for plasmapheresis- 
derived FFP, it is Acid Citrate Dextrose (ACD). Thawed plasma is FFP that has been thawed and 
stored at 4°C for as long as 5 days after thawing (AABB-2013). To treat hemorrhaging patients 
more quickly, many emergency rooms maintain thawed group AB plasma alongside “emergency 
release” group O packed red blood cells (pRBCs), which allows both the pRBCs and plasma to   
be used immediately (without the need to determine the blood type of the patient or crossmatch  
the red cells). The use of these “emergency release” blood products along with techniques such   
as implementation of a massive transfusion protocol, where blood products are transfused in a  
ratio of plasma:platelets:red cells of 1:1:1, result in reduced exsanguination rates in the first 24 
hours and better hemostasis than a ratio of 1:1:2 in patients who are massively bleeding  
(Holcomb et al-2015, Novak et al-2015). 
 
5.1. 
Limitations of Fresh Frozen Plasma Products 
Currently, the only licensed plasma products with consistently high levels of clotting factors in  
the United States must be stored in the frozen state (FFP, plasma frozen 24 hours after collection 
and refrigerated within 8 hours (PF24), or plasma frozen 24 hours after collection and held at  
room temperature (20°C-24°C) until freezing (PF24RT24)). These plasma products can be made 
available in civilian trauma centers, emergency rooms, and surgery suites, but have several 
limitations that make it difficult for their use. First, they must be stored and transported frozen 
because they have a short shelf life once thawed. Second, it can take 20-40 minutes for frozen 
plasma to reach the hemorrhaging patient due to the preparation, thawing, and delivery time that  
is required. Although thawed plasma can be immediately available for use, it does not avoid the 
shipping and storage problems associated with a frozen plasma product. Thawed plasma by the 
third day of storage has significantly reduced capacity to generate thrombin compared to 
immediately thawed plasma. This reduced ability to generate thrombin may reduce its efficacy, 
although clinical relevance of this reduced thrombin generation capacity is unknown (Spinella et 
al-2015). Third, there is considerable waste with use of frozen plasma products. The 2011 
National Blood Collection and Utilization Survey Report (NBCUS) distributed by the US 
Department of Health and Human Services (HHS) documented 128,759 outdated or 
processed/unused FFP units and 108,316 total plasma units wasted (HHS-2011). Although this 
reflects 2.2% of the plasma units processed for transfusion, this translates to approximately $13.4 
million, utilizing an average price of FFP reported by hospitals as  $58/unit. 
 
5.2. 
Military Relevance 
The deficiencies of the currently licensed frozen plasma products are of particular importance to 
the military because of their need for a readily available plasma product to treat acutely bleeding 
patients. A 10-year review of the US Military’s Joint Theater Trauma Registry demonstrated  the 

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implementation of damage-control resuscitation (DCR) in the treatment of combat wounded.   
This strategy focused on providing hemostasis balance to severely injured coagulopathic patients 
through transfusion with component blood products in a 1:1:1 ratio of FFP to platelets to red  
blood cells (RBCs) (Pidcoke et al-2012). 
In addition to the increased use of FFP as a result of DCR, the military’s interest in plasma 
products, particularly those that can be used in place of FFP, is based upon the costs associated 
with waste. The uncertainties of combat necessitate the distribution of many more blood products 
than are actually transfused to ensure adequate supply is available when needed. In comparison    
to HHS’s 2011 NBCUS report based on the civilian population, estimates of military product  
waste are significantly greater. For example, in support of Operation Iraqi Freedom/Operation  
New Dawn, of the 141,563 FFP units that were shipped over the decade of 2001-2011, only 64% 
were ultimately used in transfusion; bag breakage and thawed plasma unit expiration accounted  
for a large proportion of product waste (Rentas-2012). 
The specific problems that the military must address with use of the currently licensed, frozen 
plasma products include: 
 Critical time delays for treatment of an acutely bleeding patient (if thawed plasma is  
not available) from the time of the start of the patient’s resuscitation to the availability 
of the thawed plasma for infusion due to the time required to thaw the  product; 
 Problems with shipping a frozen plasma product to remote locations (such as military 
hospitals) with frequent breakage of the bag (container). The current estimate of the 
bag breakage rate is approximately 15% of all units shipped, which is much higher 
than what is reported in the literature for civilian shipments (approximately 3% of 
shipments) (Gorlin-1995, Hmel et al-2002). This increase is believed to be partly due 
to the increased number of receiving points in the multi-layered, spoke and hub 
shipping system that the military must use for  distribution; 
 Complexities in maintaining freezers and adequate power supply to support a frozen 
plasma inventory in settings which can be austere; 
 Complexities in maintaining licensed plasma thawing devices in settings which can 
be austere; and 
 Increased costs associated with out-dating of frozen or thawed plasma  products. 
5.3. 
Rationale for Study 
During World War II, freeze dried human plasma was used as an alternative to FFP. It required  
no refrigeration, was easy to reconstitute, and there were no known reports of lack of efficacy 
(Kendrick et al-1964). However, the safety of this product was not acceptable due to pathogen 
transmission. The product was found to transmit Hepatitis B Virus (HBV) because it was 
manufactured from large (hundreds of donors) plasma pools that were not pathogen inactivated 
(HHS-2005). The product was withdrawn from use. No supplies of FDP have been available  
since that time in the United States. Lyophilized plasma (LyP) has been available only through  
the German Red Cross and French Military on a limited, local basis. Clinical studies on LyP use 
in Germany and France have not been conducted. A recent Phase 1 clinical study was performed 
using autologous, reconstituted, LyP in 16 normal, healthy subjects, with evaluation of  global 

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measures of clotting, individual coagulation factor assays, and assessment of adverse events 
(AEs) (Cancelas et al-2011). There were no SAEs related to product infusion and no occurrence 
of predetermined AEs including thromboembolic events, infections, evidence of unusual 
bleeding/bruising, or relevant changes in international normalized ratio or activated partial 
thromboplastin time (aPTT) during the study. The results indicated no relevant clinical  
difference between large volumes of FFP and LyP  infusions. 
Because of the above-listed difficulties with currently licensed plasma products, the US Army 
Medical Research and Materiel Command (USAMRMC) and Vascular Solutions, Inc. (a wholly 
owned subsidiary of Teleflex) (VSI) entered into a cooperative research and development 
agreement to develop a single donor, FDP product that is durably packaged, can be easily stored 
and transported, is readily reconstituted, and made available for rapid transfusion for military  
use. In addition, FDP has the potential for much longer storage stability than frozen plasma 
products. An FDP product that can be reconstituted and used immediately with a long-term shelf-
life would virtually eliminate the costs associated with processed but unused or outdated frozen 
plasma. 
Because of these important advantages over currently licensed frozen plasma products, FDP is  
the highest priority blood-related product in development by the US Military. To improve safety 
from previous dried plasma products, FDP will be derived from screened, individual blood  
donors in order to significantly reduce the risk of bloodborne disease transmission and undesired 
transfusion-associated reaction. Each single-donor unit is tested (per requirements of the blood 
supply) to reduce the risk of transmission of infectious agents and, hence, will maximize patient 
safety. 
This “first-in-human” Phase 1 study is proposed to assess the safety of infusing reconstituted 
FDP manufactured for the USAMRMC. The study design incorporates autologous infusions (of 
both WB and plasmapheresis-derived plasma) and a crossover design to eliminate variables and 
events known to be related to allogeneic FFP transfusion. The dose of plasma will be increased  
in each of 3 cohorts for this study to evaluate the safety of escalating doses. The maximum 
dosage within this study will provide assessment of the safety of infusing large doses of FDP in 
comparison to FFP. Additionally, this study will evaluate the preservation of key coagulation 
proteins and factor activities post-infusion, and the effect of different anticoagulants (ACD or 
CPD) from the use of different starting materials. 
5.4. 
Name and Description of the Investigational Product 
RePlas™ FDP is a lyophilized unit of plasmapheresis or WB-derived human plasma product 
designed for rapid reconstitution. RePlas™ FDP is manufactured from FFP that is frozen at a 
temperature of -18°C or less within 8 hours of initial collection. To produce RePlas™ FDP, each 
FFP unit is thawed at a controlled temperature and time. Once thawed, a controlled volume,   
based on mass, is transferred aseptically into the customized lyophilization bag using a Food and 
Drug Administration (FDA)-approved tubing welder. The plasma-filled lyophilization bag is 
frozen at -40°C or less for a minimum of 1 hour and then lyophilized using an established freeze 
drying cycle. At the end of the drying cycle, the chamber vacuum is broken with a plasma grade 
carbon dioxide (CO2) gas to correct for loss of dissolved CO2 from the starting plasma material 
during the freeze drying process. In addition, RePlas™ FDP is packaged with an outer foil pouch 
that is flushed with a fixed amount of CO2 gas, which results in a near neutral pH in the 
reconstituted RePlas™ FDP product. 

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The resulting FDP product is a straw-colored cake that upon reconstitution looks similar in color 
and consistency to the thawed FFP. FDP is reconstituted prior to use with a commercially 
available Sterile Water for Injection (SWFI) US Pharmacopeia Convention (USP) that is FDA 
approved for use as a diluent or solvent in the aseptic preparation of parenteral solutions or as a 
vehicle for drug administration. 
 
5.5. 
Summary of Nonclinical and Clinical Trials 
5.5.1. 
Nonclinical Studies 
 
5.5.1.1. 
Toxicology Testing 
FDP is assumed to be active on a species-species basis. Human plasma may cause severe toxicity 
reactions in animals and is not tolerated at dosages approaching those generally used in humans. 
Routine toxicology testing in laboratory animals is not considered to contribute any relevant 
information for the safety and efficacy of FDP in clinical  use. 
 
5.5.1.2. 
Pharmacology 
HemCon Medical Technologies, Inc. developed lyophilized swine plasma which was compared 
with swine FFP in a coagulopathic, multi-trauma swine model (Spoerke et  al-2009). 
Anesthetized, instrumented female pigs (n=32) were studied under conditions of femur fracture, 
60% hemorrhage, 30-minute shock period, hypothermia, and Grade 5 liver injury. Clotting factor 
activity was decreased by an average of 14% in lyophilized swine plasma as determined by pre- 
and post-lyophilization measurements. Acute blood loss, survival, and heart rate were similar 
among all groups. Swine resuscitated with lyophilized swine plasma had equivalent or higher 
mean arterial pressure than those treated with FFP. Both lyophilized swine plasma and FFP,  
either in combination with RBCs (1:1) or alone, were similar in restoring standard coagulation 
function: prothrombin time (PT), aPTT, fibrinogen, and thromboelastogram tracings, to baseline 
values in this dilutional, coagulopathic, poly-trauma swine model. In conclusion, lyophilized 
swine plasma demonstrated equivalent efficacy to FFP in this swine resuscitation  model. 
 
5.5.2. 
Clinical Studies 
Lyophilized, pooled human plasma was used extensively in World War II for resuscitation, but   
its use was discontinued during the 1950s due to transmission of HBV. In the mid-1980s, the  
Thai Red Cross undertook a large-scale effort to produce LyP from single units of plasma for use 
in rural hospitals to meet the need for availability of blood products (Isarangkura et  al-1987). 
Since that time, only the German Red Cross and French Military have developed LyP products, 
and the use has been limited to the European Union and in theater in places such as Iraq or 
Afghanistan. Information about the current use of the French LyP product in Iraq and 
Afghanistan by U.S. Forces is largely anecdotal and clinical studies on the product were not 
conducted prior to introduction in those settings. Currently, United States Special Operations 
Command (SOCOM) is working under a special Expanded Access Investigational New Drug 
(IND) application that approves a joint venture between SOCOM and the French Military at the 
Centre de Transfusion Sanguine des Armées. This Expanded Access IND allows for the use of a 
French-developed FDP product in theater in Iraq and Afghanistan. The French-developed FDP 
has been approved by the French Ministry of Health, but has not been approved by the FDA 
(Enterprise Information Technology (eIT)-2014). 

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5.5.2.1. 
Toxicology in Humans 
Based on dried plasma use in World War II and the recent human clinical studies of FDP 
performed by HemCon Medical Technologies, Inc., there is evidence to suggest that the 
toxicology of FDP when infused into humans is similar to that of  FFP. 
It is important to note that RePlas™ FDP has similar levels of citrate compared to FFP.  
Although, this FDP product, RePlas™ has never been infused into humans, there is considerable 
information in the literature on the effects of citrate after transfusion of blood products. The 
additional citric acid in FFP has the potential to slightly increase the risk for citrate toxicity, a  
risk that is already present and well described in the literature for infusion of large volumes of 
blood products (Klein and Anstee-2005, Silberman et al-2009). 
Harmful effects of citrate infusion may occur if the dosage exceeds 250 mg/kg/hour. Citrate 
anticoagulant is present in blood or plasma collected and stored for transfusion, and rapid rate of 
infusion of blood (30 mL/kg/hour) can lead to a decrease in ionized calcium, known as citrate 
intoxication (Dart-2004). Uncorrected citrate intoxication and the insufficient ionized calcium  
that ensues can lead to cardiac dysrhythmia, cardiac arrest, tetany, or  seizures. 
 
5.5.2.2. 
Pharmacokinetics and Biological Disposition 
The pharmacokinetics and biological disposition of FDP are expected to be the same as  FFP. 
 
5.6. 
Known and Potential Risks and Benefits to Human Subjects 
5.6.1. 
Risks/Discomfort to Subjects and Precautions to Minimize  Risk 
Outlined below are anticipated and unexpected adverse reactions (ARs), and a brief description  
of procedures to ameliorate risks and symptoms. All known risks and precautions described here 
are explained in detail in the informed consent. 
 
5.6.1.1. 
Venipuncture 
Donation of blood and blood products and the collection of blood samples for laboratory testing 
carries minimal risk of minor discomfort and the possibility of pain/soreness, minor bruising, 
discoloration, swelling, at the site of the needle puncture and, rarely, the possibility of infection  
at the needle puncture site. 
 
5.6.1.2. 
Whole Blood Collection Reactions 
Side effects of WB collection include: 
 Complications such as a hematoma, redness, nerve damage, arterial puncture, or 
localized infection at the venipuncture site; and 
 Nausea, unpleasant taste, vomiting, light-headedness, fainting, malaise, or  seizures. 
5.6.1.3. 
Plasmapheresis Reactions 
Side effects of plasmapheresis include: 
 Blood loss from the inability to return RBCs during automated plasmapheresis, which 
may result in: 

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 Termination of the procedure; and 
 Deferral from donation for 8 weeks (21 Code of Federal Regulations (CFR) 
640.63(e)). 
 Complications such as a hematoma or localized infection at the venipuncture  site; 
 Tingling of lips or fingers or muscle cramping, spasms seizures, tetany, cardiac 
arrhythmia due to the citrate anticoagulant used in an automated plasmapheresis 
procedure; 
 Allergic reactions such as flushing, itching, hives, abdominal cramps, difficulty 
breathing, chest pain, or bronchospasm, which may vary in severity from mild to life- 
threatening; 
 Nausea, unpleasant taste, vomiting, light-headedness, fainting, malaise, or seizures; 
and 
 Any other adverse reaction specified by the manufacturer of the automated collection 
device in its operator's manual or instructions for use. 
5.6.1.4. 
Local Reactions and Systemic Infusion Reactions 
Known potential risks associated with allogeneic FFP infusion are well described in the   
literature. The known risks of FDP infusion are unknown but they are expected to be similar to 
those associated with the use of FFP. Some of these risks are mitigated by the use of autologous 
plasma in this study. Subjects receiving FDP are to be monitored during administration and up to  
7 days post-infusion for AEs. The expected risks of FDP infusion  include: 
 Pain at venipuncture site and other venipuncture related  ARs; 
 Tingling of lips or fingers, muscle cramping, spasms, seizures, or cardiac arrhythmia 
due to the citrate anticoagulant used during plasma collection; 
 Allergic reactions such as flushing, itching, hives, abdominal cramps, difficulty 
breathing, chest pain, or bronchospasm, which may vary in severity from mild to life- 
threatening; 
 Nausea, unpleasant taste, vomiting, light-headedness, fainting, malaise, or  seizures; 
 Non-immunologic complications such as the transmission of infectious agents, 
bacterial sepsis, transfusion-associated circulatory overload, hypothermia-cardiac 
arrhythmias; 
 Metabolic complications such as citrate toxicity-hypocalcemia, acidosis, alkalosis, 
hyper- or-hypokalemia, and coagulopathies; and 
 Hyperventilation. 
Other rare side effects that have occurred in patients receiving (1) non-autologous plasma 
therapy or (2) excess fluid, including their own plasma  include: 
 Lowered immunity; 
 Heart failure; 

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 Fluid in the lungs causing breathing difficulty; 
 Stroke or death; 
 Swelling of feet or hands; 
 Increase in blood pressure; 
 Fever; 
 Back pain; 
 Redness of urine; and 
 Kidney failure. 
5.6.1.5. 
Pregnancy 
Risks to unborn babies are unknown at this time; pregnant females will be excluded from this 
study. Study subjects should not become pregnant for at least 3 months after the last infusion of 
FDP. 
5.6.1.6. 
Lactation 
Risks to nursing infants are unknown at this time; breastfeeding and lactating females will be 
excluded from this study. 
 
5.6.1.7. 
Allergic Reaction 
As with any IND product administration and no matter what precautions are taken, there is  
always the risk of a serious, or even life-threatening, allergic reaction. Medical emergency 
equipment is at the site to handle emergencies, such as anaphylaxis, angioedema, bronchospasm, 
and laryngospasm. 
 
5.6.1.8. 
Unknown Risks 
Furthermore, as with all research there is the remote possibility of risks that are unknown or that 
cannot be foreseen based on information that is currently  available. 
 
5.6.2. 
Alternatives to this Investigational New Drug Product or  Study 
An alternative is to not participate in this study. 
 
5.6.3. 
Intended Benefit for Subjects 
There is no guaranteed benefit for study subjects other than any sense of satisfaction accruing 
from their contribution to medical science. 
 
5.6.4. 
Risks to the Study Personnel and the Environment 
The principal risks to study personnel involved in this trial are the same as those found in a day- 
to-day clinical setting (i.e., handling of needles that may be contaminated and the attendant risks 
including hepatitis, HIV, and other human pathogens). Adherence to standard operating 
procedures (SOPs) for working with infectious agents and universal precautions will reduce the 
risk of exposure. 

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There are no known risks to the environment other than those associated with the generation of 
biohazardous waste attendant to infusion of humans. All biohazardous waste will be disposed of 
as stipulated by local, state, and Federal regulations and in accordance with study site  SOPs. 
 
5.7. 
Route of Administration, Dosage Regimen, Treatment Period, and 
Justification 
In this safety study, 3 cohorts of healthy subjects will receive an intravenous (IV) infusion of 
FDP and/or FFP as follows: 
 Cohort 1: Eight enrolled subjects will each receive a 1 unit (approximately 270 mL) 
dose of FDP: 
 Arm 1 subjects will receive 1 unit (approximately 270 mL) of autologous FDP 
manufactured from WB. These subjects are expected to make one WB donation. 
Subjects with a low-volume donation (< 450 mL) may be withdrawn from the 
study. The site will discard the low-volume donation per their SOP for handling 
blood and blood products. 
 Arm 2 subjects will receive 1 unit (approximately 270 mL) of autologous FDP 
manufactured from plasmapheresis collected FFP. These subjects are expected to 
undergo one plasmapheresis session. Subjects with a low volume  donation 
(< 500 mL) may be withdrawn from the study. The site will discard the low- 
volume donation per their SOP for handling blood and blood  products. 
 Cohort 2: Eight enrolled subjects will each receive 2 units (approximately 540 mL) 
of FDP: 
 Arm 3 subjects will receive 2 units (approximately 540 mL) of autologous FDP 
manufactured from WB. These subjects are expected to make two WB donations 
that are scheduled a minimum of 28-days apart. Subjects with a low-volume 
donation (< 450 mL) may be withdrawn from the study. The site will discard the 
low-volume donation per their SOP for handling blood and blood  products. 
 Arm 4 subjects will receive 2 units (approximately 540 mL) of autologous FDP 
manufactured from plasmapheresis collected FFP. These subjects are expected to 
undergo one plasmapheresis session. Subjects with a low-volume  donation 
(< 500 mL) may be withdrawn from the study. The site will discard the low- 
volume donation per their SOP for handling blood and blood  products. 
Should an Arm 4 subject require a second plasmapheresis collection attempt, to 
ensure subject safety, serum protein electrophoresis (SPEP) and STAT total 
protein will be performed just prior to the subsequent plasmapheresis. If any 
abnormalities are detected, the subject will be referred to a physician, scheduled 
for early withdrawal, and replaced with another  subject. 
 Cohort 3: Eight subjects will each receive 2 separate infusion treatments, each dosed 
at approximately 810 mL. One 810 mL infusion will be with 3 units of autologous  
FDP and the other approximately 810 mL infusion will be with 3 units of autologous 
control plasma (FFP). Cohort 3 subjects will be randomized to a product treatment 
sequence indicating whether their first infusion will be FDP (Arm 5) or FFP (Arm  6). 

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The starting material for the manufacture of all Cohort 3 FDP units and FFP units will 
be from autologous plasmapheresis. 
 Arm 5 subjects will receive FDP at their first infusion and FFP at their second 
infusion; infusion treatments will be separated by a 2-week interval;  and 
 Arm 6 subjects will receive FFP at their first infusion and FDP at their second 
infusion; infusion treatments will be separated by a 2-week  interval. 
All subjects in Cohort 3 are expected to undergo 3 to 4 plasmapheresis sessions that 
are each separated by a minimum of 1 week. Subjects who do not meet the minimum 
volume requirement during plasmapheresis (≥500 mL) may be withdrawn from the 
study. Low volume collections (< 500 mL) will be discarded per the clinical site’s 
SOP for handling blood and blood products. 
As a measure of donor safety, SPEP will be performed on all subjects undergoing the procedure, 
regardless of assigned cohort/treatment arm. If any abnormalities are detected, the subject will be 
referred to a physician, scheduled for early withdrawal, and replaced with another  subject. 
For subjects undergoing multiple plasmapheresis collections, total protein measured by a 
Beckman Coulter AU analyzer will be performed STAT or up to 24 hours prior to initiating the 
plasmapheresis. Total protein will only be performed at subsequent plasmapheresis sessions, not 
during the first collection. 
5.8. 
Compliance Statement 
The study will be conducted according to the protocol and in compliance with FDA International 
Conference on Harmonization (ICH) Good Clinical Practice (GCP), Belmont Principles, and  
other applicable regulatory and Department of Defense (DoD) requirements. All identified study 
personnel will be trained to perform their roles and will carry out their responsibilities in 
accordance with FDA, ICH GCP guidelines, and study site’s SOPs. Roles and responsibilities of 
study staff are presented in Appendix A. 
 
5.9. 
Study Population 
Male and female healthy volunteers who are eligible for WB donation or plasmapheresis 
donation based on FDA regulations and the AABB donor history questionnaire will be included 
in this study. Subjects whose only reason for exclusion according to the AABB donor history 
questionnaire is travel deferral will be accepted. A sample of the complete AABB donor history 
questionnaire is presented in Appendix B. In addition to the eligibility criteria indicated by the 
questionnaire, potential subjects must also meet the Inclusion/Exclusion criteria as previously 
mentioned and later referred to in section 7.4 and section  7.5. 
Refer to section 11.2 for a statistical justification of the sample  size. 
 
5.10. 
Study Site 
The Hoxworth Blood Center (HBC) is an academic blood center that provides daily blood and 
cell therapy product needs to the whole community of the Greater Cincinnati area which is 
populated by approximately 1.9 million inhabitants. Cincinnati is located in Southwestern Ohio 
and is highly diverse with a population mostly composed of European (German, Irish,  Italian, 

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and Jewish) and African background inhabitants. HBC processes approximately 80,000 blood  
units a year and approximately 10,000 platelets apheresis a year. It routinely produces plasma 
products from WB and plasmapheresis procedures for the community and provides 
immunohematology reference laboratory services and transplantation immunology services for  
the Greater Cincinnati area hospitals. The HBC/University of Cincinnati research program is 
extremely active in the development and validation of innovative products in transfusion  
medicine and cell therapies. The center is located central to the University Medical campus, at a 1 
to 5 minute walking distance to the major hospitals and facilities of the University. The HBC has 
the personnel, expertise, and equipment necessary to perform this study, including blood   
donation staff, plasmapheresis devices, expert nurses in the field of plasmapheresis, and on-call 
doctor. The work is supervised and directed by Dr. Jose A. Cancelas, MD, PhD, who is Professor 
of Pediatrics and Deputy Director of the Blood Center, and who will be in charge of the medical 
aspects of the study. The HBC is uniquely qualified given its long-term experience in the 
development of clinical research trials in blood banking involving healthy volunteers and 
collection/infusion of large amounts of blood derived cell/plasma  products. 

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6. 
TRIAL OBJECTIVES AND PURPOSE 
6.1. 
Primary Objective 
The primary objective of this study is to assess the safety of single infusions with the RePlas™ 
FDP product at increasing fixed doses of either 1 unit (approximately 270 mL), 2 units 
(approximately 540 mL), or 3 units (approximately 810 mL) in normal healthy subjects. In the 2 
lower dose cohorts, safety will also be assessed in terms of the type of autologous plasma used as 
the starting material in the manufacture of the investigational  product: 
 FDP derived from WB where CPD was used as the anticoagulant, or FDP-CPD;  and 
 FDP collected by plasmapheresis where ACD was used as the anticoagulant, or FDP- 
ACD. 
The highest dose cohort will receive FDP manufactured only from FFP collected by 
plasmapheresis (FDP-ACD). Conclusions on whether the study meets its safety objectives will 
be based only on treatment emergent adverse events (TEAEs). These are adverse events (AEs) 
that occur after treatment (plasma infusion) has begun and throughout the study’s post-infusion 
follow-up period. 
6.2. 
Secondary Objectives 
The secondary objectives are to: 
 Assess the safety of a fixed-dose infusion of 3 FDP units (approximately 810 mL) in 
comparison to infusion with the same dose of autologous FFP collected during 
plasmapheresis; and 
 Determine if the changes in specific coagulation factors, hematology, and chemistry 
values are similar within clinically meaningful levels after infusion of either 3 units of 
autologous FDP or FFP. 
6.3. 
Trial Design 
The following sections describe information and procedures involving study subjects. 
Additional, detailed information will be explained in the study's Manual of Procedures  (MOP). 
6.4. 
Study Endpoints 
6.4.1. 
Primary Endpoints 
The primary endpoints to assess safety are TEAEs; SAEs; Suspected, Unexpected, Serious 
Adverse Reactions (SUSARs); and death. 
 
6.4.2. 
Secondary Endpoints 
The following secondary endpoints will only be evaluated in Cohort 3  subjects: 
 Change in pre- and post-infusion values for Prothrombin Time and International 
Normalized Ratio (PT/INR), aPTT, Factors I, II, V, VII, VIII, IX, X, XI, D-DIMER, 
von Willebrand Factor activity, Protein S activity, Protein C activity,  Prothrombin 

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Fragments 1+2 (PF 1+2), Thrombin/Antithrombin (TAT), Antithrombin III (AT-III), 
Alpha-2 antiplasmin, and C3a des Arg activity compared to pre-infusion values after 
infusion of 3 units of FDP compared to 3 units of FFP; and 
 Determine if the changes in specific hematology, urinalysis, vital signs, DAT, and 
chemistry values are similar within clinically meaningful levels after infusion of 
either 3 units of autologous FDP or FFP. 
6.5. 
Overall Study Design 
This single-site, partial double-blind study in healthy volunteers is designed to assess the safety  
of infusing ascending doses of reconstituted autologous FDP in 3 fixed-dose cohorts. Subjects in 
Cohort 1 will receive 1 unit of FDP, which is approximately 270 mL. Subjects in Cohort 2 will 
receive 2 FDP units, which total approximately 540 mL. Cohorts 1 and 2 are the lower-dose 
cohorts. Subjects will be assigned to these beginning with the lowest dose, Cohort 1. In the 
absence of TEAEs, SAEs or the implementation of protocol stopping rules (SRs), and with Data 
and Safety Monitoring Board (DSMB) recommendation and Sponsor approval subjects assigned 
to Cohort 2 will be infused with an increased dose of 2 units. For both of these cohorts subjects 
will also be assigned to 1 of 2 single infusion treatment  arms: 
1. Infusion of FDP manufactured with autologous plasma derived from WB (FDP-CPD), at 
the corresponding dose; or 
2. Infusion of FDP manufactured with autologous plasma collected by plasmapheresis 
(FDP-ACD), at the corresponding dose. 
In the absence of TEAEs, SAEs, or the implementation of protocol stopping rules (SRs) in  
Cohort 2 subjects, infusions in Cohort 3 subjects may be implemented. Cohort 3 is designed as a 
randomized, controlled, crossover infusion of 3 units of FDP (approximately 810 mL)  and 
3 units of FFP (approximately 810 mL) at separate visits. Subjects are randomized to a specific 
infusion schedule of either 3 units of FDP or 3 units of FFP at the first infusion visit, followed by 
infusion with the alternate product at the second infusion visit. Crossover of FDP and FFP  
enables comparison of infusion safety and select coagulation factor recoveries within the same 
subjects between FDP and FFP at this higher dose. Unlike Cohorts 1 and 2, the FDP and FFP 
infusion products in Cohort 3 are sourced solely from autologous plasmapheresis donations (FDP-
ACD). A 2-week period between infusion visits is required for all Cohort 3 subjects regardless of 
infusion schedule. 
Use of autologous plasma in the trial assists in the elimination of potential AEs related to 
allogeneic plasma infusion, but it also adds additional burden to participating subjects who, upon 
consent and enrollment, need to donate sufficient volume of plasma to provide the autologous 
plasma needed for the trial infusions (eg, manufacture of autologous FDP units in all cohorts; in 
Cohort 3, the additional need for FFP in addition to FDP). Blood donation standards typically 
require a 56-day interval between WB donations; however, a shortened study donation period of  
a minimum of 28 days between WB donations will be used for study subjects. Without the loss   
of RBCs in plasmapheresis, these types of donations can be made more frequently, with a 
minimum of 7 days between donations. Plasmapheresis donations yield up to 800 mL plasma 
depending on donor size. Thus, the trial’s overall design and use of plasmapheresis alone in 
Cohort 3 reduces the frequency in which subjects will need to donate due to significantly larger 
estimated plasma volumes per donation. Plasmapheresis offers practical advantages and  using 

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FDA’s guidance regarding automated plasma collection volumes, reduces potential safety 
implications (FDA-1992). 
Subjects in Cohorts 1 and 2 will provide sufficient plasma volume for a single infusion with  
either 1 or 2 units, respectively. Based on assigned treatment arm, subjects will provide plasma 
through either WB or plasmapheresis collection for manufacture of autologous FDP-CPD or FDP-
ACD. Cohort 2 subjects in the FDP-CPD treatment arm are required to successfully make 2 WB 
donations within a relatively short period of time to provide adequate volume for their use in the 
trial. Because of the extraordinarily long time required to accrue sufficient WB-derived  plasma 
for the high dose cohort (approximately 11 months), the FDP-CPD treatment arm is not included 
in Cohort 3. The total starting volume of plasma needed from each Cohort 3 subject is 
approximately 1620 mL; triple that of Cohort 2 and thus inclusion of this treatment arm in   
Cohort 3 would require 6 WB donations, increasing subject risk for significant iron store  
depletion and anemia. Table 3 provides details on assigned cohorts and treatment arms as well as 
indicates the type, frequency, and total volume of blood/plasma donations  required. 
Table 3: 
Cohort and Treatment Arm Details 
 
Dose Cohorts and Treatment 
Arms 
Number of 
Subjects 
Donation 
Type 
Approximate 
Volume 
Autologous 
Plasma Required 
Number of 
Donations 
Cohort 1: One unit single infusion [approximately 270  mL] 
Arm 1: FDP-CPD 
4 
WB 
270 
1 
Arm 2: FDP-ACD 
4 
Plasmapheresis 
270 
1 
Cohort 2: Two units single infusion [approximately 540  mL] 
Arm 3: FDP-CPD 
4 
WB 
540 
2 
Arm 4: FDP-ACD 
4 
Plasmapheresis 
540 
1 
Cohort 3: Three units crossover infusion [approximately 810 mL,   each] 
Arm 5: FDP ACD x FFP 
4 
Plasmapheresis 
1,620 
3-41 
Arm 6: FFP x FDP ACD 
4 
Plasmapheresis 
1,620 
3-41 
The following SRs will be applied to all study subjects throughout the  trial: 
1. An SAE that is determined to be possibly, probably, or definitely related to the study 
product; 
2. An AE related to the study product that the PI, RM, and/or sponsor’s PVG MD agree 
jeopardizes the subject’s health or safety; 
3. An AE related to the study product that requires medical or surgical intervention to 
prevent occurrence of an SAE; 
4. A post-infusion, abnormal coagulation function assay which is also a greater than 20% 
change from baseline for PT/INR and/or aPTT values (eg, a subject who has a baseline 
INR of 1.0 with a post-infusion INR of 1.3 will activate an SR, because this is  an 

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abnormal coagulation function assay result that is also a greater than 20% change from 
the pre-infusion assay result); and/or 
5. Post-infusion development of hemolysis or deep vein thrombosis (DVT), cardiac 
ischemia, or pulmonary embolism (PE). DVT will be determined following the Institute 
for Clinical Systems Improvement (ICSI) Health Care Guideline: Venous 
Thromboembolism Diagnosis and Treatment (includes assessment of D-Dimer results 
and Wells criteria ≥ 2) (Dupras et al-2013). 
If any of the above conditions occur, the study will be paused to assess continuation of the  study. 
The DSMB will convene after completion of each cohort. DSMB meetings will be scheduled to 
maximize the amount of subject data reported to the DSMB through the 28-day follow-up visit. 
The DSMB will have at a minimum all data through the 7-Day Follow-Up Visit. Following each 
meeting, the DSMB will provide the sponsor with a recommendation about proceeding with 
infusions in the subsequent cohort. Following the review of Cohort 3 data, the DSMB will  
provide a recommendation about proceeding with the next planned FDP trial. After the receipt  
and consideration of a DSMB recommendation, the sponsor will make a final determination  
about proceeding to the next cohort or the next FDP trial. It is up to the sponsor to make a final 
determination on how to proceed. 

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Table 4: 
Study Events Schedule for Cohort 1, Arms 1 and 2 
 
Visit Activities: 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Phone 
CallsL 
Visit 5 
Phone 
CallL 
Visit 6 
Screening 
WB/Plasmapheresis 
Collection 
Infusion 
24-Hour 
Follow-Up 
48 & 72 
hrs 
7-Day 
Follow-Up 
14-Day 
28-Day 
Follow-Up 
Study Day*: 
-56 to -49 
-35 
1 
2 
3 & 4 
8 
15 
29 
Visit Window: 
± 3 hrs 
± 2 hrs 
± 1 day 
± 2 hrs 
± 1 day 
General Procedures 
Informed Consent 
X 
Inclusion/Exclusion Criteria 
X 
Demographic Questionnaire 
X 
AABB Donor History 
QuestionnaireA 
X 
X 
Duke Activity Status Index 
X 
Subject Medical Health 
Standardized  QuestionnaireB 
X 
X 
X 
X 
X 
X 
Complete Physical ExamC 
X 
X 
X 
Abbreviated Physical  ExamD 
X 
X 
X 
Wells ScaleH 
X 
X 
X 
Vital SignsE 
X 
X 
XH 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
AEs 
X 
X 
X 
X 
X 
X 
X 
Blood/Plasma CollectionF 
X 
FDP Infusion 
X 
Visual Inspection of Blood 
Components 
X 
X 
Exit InterviewG 
X 
Laboratory Tests 
Urine Drug Screening 
X 
Urine Pregnancy Test (females 
only) 
X 
XK 
Urinalysis 
X 
XK 
X 
Chemistry PanelI 
X 
XK 
X 
X 
Complete Blood Count  (CBC)J 
X 
XK 
X 
X 
X 
Hematocrit 
X 
PT/INR, aPTT 
X 
XK 
X 
X 

Version 6.0 (19Apr2018) 
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Table 4: 
Study Events Schedule for Cohort 1, Arms 1 and 2  (continued) 
Visit Activities: 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Phone 
CallsL 
Visit 5 
Phone CallL 
Visit 6 
Screening 
WB/Plasmaph 
eresis 
Collections 
Infusion 
24-Hour 
Follow- 
Up 
48 & 72 
hrs 
7-Day 
Follow-Up 
14-Day 
28-Day Follow-Up 
Study Day*: 
-56 to -49 
-35 
1 
2 
3 & 4 
8 
15 
29 
Visit Window: 
± 3 hrs 
± 2 hrs 
± 1 day 
± 2 hrs 
± 1 day 
Direct Antiglobulin Test 
(DAT) (Immunoglobulin 
G (IgG) and  
Complement Factor 3 
(C3)) 
X 
XK 
X 
X 
D-Dimer Test 
X 
XK 
X 
Blood Type for ABO 
and Rh 
X 
XK 
Red-Cell Antibody 
Screen 
X 
Syphilis Screen 
X 
HTLV Antibody 
Screening Test 
X 
HIV-1/2, HBV, HCV, 
and West Nile Virus 
Nucleic Acid Tests 
X 
Cross-match RBC vs 
FDP 
XK 
Reverse Type of FDP 
XK 
SPEPM 
X 
*The estimated manufacturing time is 5  weeks. 
A The AABB donor history questionnaire is administered at all donation   visits. 
B Confirm data are accurate; subject is healthy with no significant medical    history change. 
C Complete physical exams to include height (screening only), weight, vital signsE, and a targeted assessment of health as described in section 7.2 and section 8.2. 
D Abbreviated physical exam to include vital signsE  and a general assessment of   health. 
E Vital signs monitored include blood pressure, heart rate, respiration rate, and temperature. These will be measured every 15 minutes (± 5 minutes) during the 
infusion, every 30 minutes (± 5 minutes) between 0 and 4 hours post-infusion, and then every 4 hours (±40 minutes) until the subject is released from the clinic.       
F Blood and plasma collection will generally be done approximately 5 weeks before the study infusion in order to allow sufficient time for product preparation, 
testing, release, and shipment back to the  site. 
G Exit interview may take place at any point during the study and is dependent upon subject’s continued enrollment status. 

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H Monitor vital signs every 15 minutes during infusion; every 30 minutes for up to 4 hours post-infusion; and after 6 hours, vital signs should be measured every      
4 hours until the subject is released. Subjects assessed for DVT, PE, and cardiac ischemia using the Wells Scale prior to infusion, at 30 minutes, 4 hours, and 24 
hours post-infusion before the subject can be released from the   clinic. 
I Chemistry panel includes Calcium, Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Bicarbonate, Chloride, 
Glucose, Potassium, Sodium, Total Bilirubin, Total Protein, Blood Urea Nitrogen (BUN), Lactate, and Creatinine. The chemistry panel also includes pH,    
Ionized Calcium, and Total Magnesium, which will only be measured at pre-infusion and 0.5 hour post-infusion. 
J CBC comprises Hematocrit, Hemoglobin, Platelet Count, RBC Count, and White Blood Cell (WBC) Count.    
K See Table 7 – Laboratory Testing Schedule and Volumes for Cohorts 1 and 2 for laboratory testing details. L  
Follow-up phone calls to the subject will be made 48 hours, 72 hours, and 14    days post infusion. 
M  SPEP performed for subjects undergoing plasmapheresis  only. 

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Table 5: 
Study Events Schedule for Cohort 2, Arm 3 
 
Visit Activities: 
Visit 1 
Visits 2a/2b 
Visit 3 
Visit 4 
Phone 
CallsL 
Visit 5 
Phone 
CallL 
Visit 6 
Screening 
WB 
Collections 
Infusion 
24-Hour 
Follow-Up 
48 & 72 hrs 
7-Day 
Follow-Up 
14-Day 
28-Day 
Follow-Up 
Study Day*: 
-84 to -77 
-63 to -35 
1 
2 
3 & 4 
8 
15 
29 
Visit Window: 
± 3 hrs 
± 2 hrs 
± 1 day 
± 2 hrs 
± 1 day 
General Procedures 
Informed Consent 
X 
Inclusion/Exclusion Criteria 
X 
Demographic Questionnaire 
X 
AABB Donor History Questionnaire A 
X 
X 
Duke Activity Status Index 
X 
Subject Medical Health Standardized 
Questionnaire B 
X 
X 
X 
X 
X 
X 
Complete Physical Exam C 
X 
X 
X 
Abbreviated Physical Exam D 
X 
X 
X 
Wells ScaleH 
X 
X 
X 
Vital Signs E 
X 
X 
XH 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
AEs 
X 
X 
X 
X 
X 
X 
X 
Blood CollectionF 
X 
SPEPF 
X 
FDP Infusion 
X 
Visual Inspection of Blood  Components 
X 
X 
Exit InterviewG 
X 
Laboratory Tests 
Urine Drug Screening 
X 
Urine Pregnancy Test (females  only) 
X 
XK 
Urinalysis 
X 
XK 
X 
Chemistry PanelI 
X 
XK 
X 
X 
CBCJ 
X 
XK 
X 
X 
X 
Hematocrit 
X 
PT/INR, aPTT 
X 
XK 
X 
X 
DAT (IgG and C3) 
X 
XK 
X 
X 
D-Dimer Test 
X 
XK 
X 
Blood Type for ABO and Rh 
X 
XK 

Version 6.0 (19Apr2018) 
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US Government Proprietary 
FDP-1 
IND 17154; S-14-12 
The Surgeon General 
Department of the Army 
 
 
 
Table 5:Study Events Schedule for Cohort 2, Arm 3   (continued) 
 
Visit Activities: 
Visit 1 
Visits 
2a/2b 
Visit 3 
Visit 4 
Phone 
CallsL 
Visit 5 
Phone 
CallL 
Visit 6 
Screening 
WB 
Collections 
Infusion 
24-Hour 
Follow-Up 
48 & 72 hrs 
7-Day 
Follow-Up 
14-Day 
28-Day 
Follow-Up 
Study Day*: 
-84 to -77 
-63 to -35 
1 
2 
3 & 4 
8 
15 
29 
Visit Window: 
± 3 hrs 
± 2 hrs 
± 1 day 
± 2 hrs 
± 1 day 
Red-Cell  Antibody Screen 
X 
Syphilis Screen 
X 
HTLV Antibody Screening  Test 
X 
HIV-1/2, HBV, HCV, and West Nile 
Virus Nucleic Acid Tests 
X 
Cross-match RBC vs FDP 
XK 
Reverse Type of FDP 
XK 
*The estimated manufacturing time is 5  weeks. 
AThe AABB donor history questionnaire is administered at all donation   visits. 
BConfirm data are accurate; subject is healthy with no significant medical    history change. 
CComplete physical exams to include height (screening only), weight, vital signsE, and a targeted assessment of health as described in section 7.2 and section 8.2 
DAbbreviated physical exam to include vital signsE  and a general assessment of   health. 
EVital signs monitored include blood pressure, heart rate, respiration rate, and temperature. These will be measured every 15 minutes (± 5 minutes) during the 
infusion, every 30 minutes ( ± 5 minutes) between 0 and 4 hours post-infusion, and then every 4 hours ( ± 40 minutes) until the subject is released from the 
clinic. 
FBlood and plasma collections will generally be done approximately 5 weeks before the study infusion in order to allow sufficient time for product preparation, 
testing, release, and shipment back to the clinical site. Arm 3 requires 2 WB donations. SPEP only performed for subjects undergoing plasmapheresis. 
GExit interview may take place at any point during the study and is dependent upon subject’s continued enrollment status. 
HMonitor vital signs every 15 minutes during infusion; every 30 minutes for up to 4 hours post-infusion; and after 6 hours, vital signs should be measured every      
4 hours until the subject is released. Subjects assessed for DVT, PE, and cardiac ischemia using the Wells Scale prior to infusion, at 30 minutes, 4 hours, and      
24 hours post-infusion before the subject can be released from the   clinic. 
IChemistry panel includes Calcium, ALP, ALT, AST, Bicarbonate, Chloride, Glucose, Potassium, Sodium, Total Bilirubin, Total Protein, BUN, Lactate, and 
Creatinine. pH, Ionized Calcium and Total Magnesium will only be measured at pre-infusion and 0.5 hour post-infusion. 
JCBC comprises Hematocrit, Hemoglobin, Platelet Count, RBC Count, and WBC    Count. 
KSee Table 7 - Laboratory Testing Schedule and    Volumes for Cohorts 1 and 2 for laboratory testing details. 
L  Follow-up phone calls to the subject will be made 48 hours, 72 hours, and 14 days   post infusion. 

Version 6.0 (19Apr2018) 
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US Government Proprietary 
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The Surgeon General 
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Table 6: 
Study Events Schedule for Cohort 2, Arm 4 
 
Visit Activities: 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Phone 
CallsL 
Visit 5 
Phone 
CallL 
Visit 6 
Screening 
Plasmapheresis 
Collection 
Infusion 
24-Hour 
Follow-Up 
48 & 72 
hrs 
7-Day 
Follow-Up 
14-Day 
28-Day 
Follow-Up 
Study Day*: 
-56 to -49 
-45 to -35 
1 
2 
3 & 4 
8 
15 
29 
Visit Window: 
± 3 hrs 
± 2 hrs 
± 1 day 
± 2 hrs 
± 1 day 
General Procedures 
Informed Consent 
X 
Inclusion/Exclusion Criteria 
X 
Demographic Questionnaire 
X 
AABB Donor  History QuestionnaireA 
X 
X 
Duke Activity Status Index 
X 
Subject Medical Health Standardized 
QuestionnaireB 
X 
X 
X 
X 
X 
X 
Complete Physical ExamC 
X 
X 
X 
Abbreviated Physical  ExamD 
X 
X 
X 
Wells ScaleH 
X 
X 
X 
Vital SignsE 
X 
X 
XH 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
AEs 
X 
X 
X 
X 
X 
X 
X 
Plasma CollectionF 
X 
FDP Infusion 
X 
Visual Inspection of Blood  Components 
X 
X 
Exit InterviewG 
X 
Laboratory Tests 
Urine Drug Screening 
X 
Urine Pregnancy Test (females  only) 
X 
XK 
Urinalysis 
X 
XK 
X 
Chemistry PanelI 
X 
XK 
X 
X 
CBCJ 
X 
XK 
X 
X 
X 
Hematocrit 
X 
PT/INR, aPTT 
X 
XK 
X 
X 
DAT (IgG and C3) 
X 
XK 
X 
X 
D-Dimer Test 
X 
XK 
X 
Blood Type for ABO and Rh 
X 
XK 

Version 6.0 (19Apr2018) 
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US Government Proprietary 
FDP-1 
IND 17154; S-14-12 
The Surgeon General 
Department of the Army 
 
 
Table 6: Study Events Schedule for Cohort 2, Arm 4  (continued) 
 
Visit Activities: 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Phone 
CallsL 
Visit 5 
Phone 
CallL 
Visit 6 
Screening 
Plasmapheresis 
Collection 
Infusion 
24-Hour 
Follow-Up 
48 & 72 
hours 
7-Day 
Follow-Up 
14-Day 
28-Day 
Follow-Up 
Study Day*: 
-56 to -49 
-45 to -35 
1 
2 
3 & 4 
8 
15 
29 
Visit Window: 
± 3 hrs 
± 2 hrs 
± 1 day 
± 2 hrs 
± 1 day 
Red-Cell  Antibody Screen 
X 
Syphilis Screen 
X 
Screening Test for HTLV  Antibody 
X 
Nucleic Acid Tests for HIV-1/2, 
HBV, HCV, and West Nile  Virus 
X 
Cross-match RBC vs.  FDP/FFP 
XK 
Reverse Type of FDP/FFP 
XK 
SPEPM 
X 
*The estimated manufacturing time is 5  weeks. 
AThe AABB donor history questionnaire is administered at all donation   visits. 
BConfirm data are accurate; subject is healthy with no significant medical    history change. 
C Complete physical exams to include height (screening only), weight, vital signsE, and a targeted assessment of health as described in section 7.2 and section 8.2. 
DAbbreviated physical exam to include vital signsE  and a general assessment of   health. 
EVital signs monitored include blood pressure, heart rate, respiration rate, and temperature. These will be measured every 15 minutes (± 5 minutes) during the 
infusion, every 30 minutes (± 5 minutes) between 0 and 4 hours post-infusion, and then every 4 hours (± 40 minutes) until the subject is released from the 
clinic. 
FBlood and plasma collections will generally be done approximately 5 weeks before the study infusion in order to allow sufficient time for product preparation, 
testing, release, and shipment back to the clinical site. Cohort 2, Arm 4 subjects are expected to undergo 1 plasmapheresis procedure. 
GExit interview may take place at any point during the study and is dependent upon subject’s continued enrollment status. 
HMonitor vital signs every 15 minutes during infusion; every 30 minutes for up to 4 hours post-infusion; and after 6 hours, vital signs should be measured every 4 
hours until the subject is released.       Subjects assessed for DVT, PE, and cardiac ischemia using the Wells Scale prior to infusion, at 30 minutes, 4 hours, and 
24 hours post-infusion before the subject can be released from the   clinic. 
IChemistry panel includes Calcium, ALP, ALT, AST, Bicarbonate, Chloride, Glucose, Potassium, Sodium, Total Bilirubin, Total Protein, BUN, Lactate, and 
Creatinine. pH, Ionized Calcium and Total Magnesium will only be measured at pre-infusion and 0.5 hour post-infusion. 
JCBC comprises Hematocrit, Hemoglobin, Platelet Count, RBC Count, and WBC   Count. 
KSee Table 7 - Laboratory Testing Schedule and Volumes for Cohorts 1 and 2 for laboratory testing    details. 
L  Follow-up phone calls to the subject will be made 48 hours, 72 hours, and 14 days   post infusion. 
M SPEP performed for subjects undergoing plasmapheresis. Total Protein will be performed STAT or up to 24 hours prior to plasmapheresis if a subject requires 
multiple collections. 

Version 6.0 (19Apr2018) 
42 
US Government Proprietary 
FDP-1 
IND 17154; S-14-12 
The Surgeon General 
Department of the Army 
 
 
Table 7: 
Laboratory Testing Schedule and Volumes for Cohorts 1 and  2 
 
Laboratory Testing 
Screening 
Donation 
Visits 
Infusion Visit – Cohorts 1 and  2 
24-Hour 
Follow-Up 
Day 7 
Follow-Up 
Day 28 
Follow-Up 
Pre-Infusion 
Post-Infusion 
0.5 hr 
4 hrs 
Urine Pregnancy Test (females  only) 
X 
X 
Urine Drug Screening 
X 
Urinalysis 
X 
X 
X 
X 
X 
Chemistry PanelA 
X 
X 
X 
X 
X 
X 
CBCB 
X 
X 
X 
X 
X 
X 
X 
Hematocrit 
X 
PT/INR 
X 
X 
X 
X 
X 
X 
aPTT 
X 
X 
X 
X 
X 
X 
DAT (IgG and C3) 
X 
X 
X 
X 
D-Dimer 
X 
X 
XE 
XE 
X 
Blood Type for ABO and Rh 
X 
XC 
Red-Cell  Antibody Screen 
X 
Syphilis Screen 
X 
Screening Test for HTLV  Antibody 
X 
Nucleic Acid Tests for HIV-1/2, 
HBV, HCV, and West Nile  Virus 
X 
Cross-match RBC 
X 
Reverse Type FDP 
X 
WB/Plasma Collection 
X 
SPEP 
XF 
Total Blood Volume  Collected 
~51mL 
500 mL- 
607 mLD 
~36mL 
~36mL 
~30 mL 
~34mL 
~21mL 
~20 mL 
AChemistry panel includes Calcium, ALP, ALT, AST, Bicarbonate, Chloride, Glucose, Potassium, Sodium, Total Bilirubin, Total Protein, BUN, Lactate, and 
Creatinine. pH, Ionized Calcium and Total Magnesium will only be measured at pre-infusion and 0.5 hour post-infusion. 
BCBC comprises Hematocrit, Hemoglobin, Platelet Count, RBC Count, and WBC    Count. 
CABO only at the pre-infusion sampling  time. 
DCollection volume range for this visit includes the WB (approximately 500 mL) or plasma donation volume (approximately 600 mL) collected at each visit. ED-
Dimer collection at 30 minutes and 4 hours post-infusion must be done STAT. Results must be received and reviewed by the PI prior to the subject’s release from 
the clinic. 
FSPEP is performed for Cohort 2, Arm 4 subjects at each plasmapheresis session. Total Protein will be performed STAT or up to 24 hours prior to 
plasmapheresis if a subject requires multiple  collections. 

Version 6.0 (19Apr2018) 
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FDP-1 
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The Surgeon General 
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Table 8: 
Study Events Schedule for Cohort 3 
 
Visit Activities: 
Visit 1 
Visits 2a-2dP 
Visit 3 
Visit 4 
Phone 
Calls N 
Visit 5 
Visit 6 
Visit 7 
Phone 
Calls N 
Visit 8 
Phone 
Call N 
Visit 9 
Screening 
Plasmapheresis 
Collections 
Infusion 
#1 
24-Hour 
Follow- 
Up 
48 & 72 
hrs 
7-Day 
Follow- 
Up 
Infusion 
#2 
24- 
Hour 
Follow- 
Up 
48 & 72 
hrs 
7-Day 
Follow- 
Up 
14-Day 
28-Day 
Follow- 
Up 
Study Day*: 
-56 to -49 
-55 to -35 
1 
2 
3 & 4 
8 
15 
16 
17 & 18 
22 
29 
43 
Visit Window: 
± 3 hrs 
± 2 hrs 
± 1 
day 
± 3 days 
± 3 hrs 
± 2 hrs 
± 1 day 
± 2 hrs 
± 1 day 
General Procedures 
Informed Consent 
X 
Inclusion/Exclusio 
n Criteria 
X 
Demographic 
Questionnaire 
X 
AABB Donor 
History 
QuestionnaireA 
X 
X 
Duke Activity 
Status Index 
X 
Subject Medical 
Health 
Standardized 
QuestionnaireB 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete Physical 
ExamC 
X 
X 
X 
Randomization 
X 
Abbreviated 
Physical ExamD 
X 
X 
X 
X 
X 
X 
Wells ScaleH 
X 
X 
X 
X 
X 
Vital SignsE 
X 
X 
XH 
X 
X 
XH 
X 
X 
X 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma CollectionF 
X 

Version 6.0 (19Apr2018) 
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US Government Proprietary 
FDP-1 
IND 17154; S-14-12 
Table 8: Study Events Schedule for Cohort 3 (continued) 
The Surgeon General 
Department of the Army 
 
 
 
Visit Activities: 
Visit 1 
Visits 2a-2dP 
Visit 3 
Visit 4 
Phone 
Calls N 
Visit 5 
Visit 6 
Visit 7 
Phone 
Calls N 
Visit 8 
Phone 
Call N 
Visit 9 
Screening 
Plasmapheresis 
Collections 
Infusion 
#1 
24-Hour 
Follow-Up 
48 & 72 
hrs 
7-Day 
Follow- 
Up 
Infusion 
#2 
24- 
Hour 
Follow- 
Up 
48 & 72 
hrs 
7-Day 
Follow- 
Up 
14-Day 
28-Day 
Follow- 
Up 
Study Day*: 
-56 to -49 
-55 to -35 
1 
2 
3 & 4 
8 
15 
16 
17 & 18 
22 
29 
43 
Visit Window: 
± 3 hrs 
± 2 hrs 
± 1 
day 
± 3 days 
± 3 hrs 
± 2 hrs 
± 1 day 
± 2 hrs 
± 1 day 
Visual Inspection 
of Blood 
Components 
X 
X 
X 
FDP/FFP Infusion 
X 
X 
Exit InterviewG 
X 
Laboratory Tests 
Urine Drug 
Screening 
X 
Urine Pregnancy 
Test (females only) 
X 
XJ 
XJ 
Urinalysis 
X 
XJ 
X 
XJ 
X 
Chemistry PanelI 
X 
XJ 
X 
X 
XJ 
X 
X 
CBCK 
X 
XJ 
X 
X 
XJ 
X 
X 
X 
Hematocrit 
X 
PT/INR, aPTT 
X 
XJ 
X 
XJ 
X 
X 
DAT (IgG and C3) 
X 
XJ 
X 
XJ 
X 
X 
SPEP 
XL 
Blood Type for 
ABO and Rh 
X 
XJ 
XJ 
Red-Cell Antibody 
Screen 
X 
Syphilis Screen 
X 
HTLV Antibody 
Screening Test 
X 

Version 6.0 (19Apr2018) 
45 
US Government Proprietary 
FDP-1 
IND 17154; S-14-12 
Table 8: Study Events Schedule for Cohort 3 (continued) 
The Surgeon General 
Department of the Army 
 
 
 
Visit Activities: 
Visit 1 
Visits 2a-2dP 
Visit 3 
Visit 4 
Phone 
Calls N 
Visit 5 
Visit 6 
Visit 7 
Phone 
Calls N 
Visit 8 
Phone 
Call N 
Visit 9 
Screening 
Plasmapheresis 
Collections 
Infusion 
#1 
24-Hour 
Follow- 
Up 
48 & 72 
hrs 
7-Day 
Follow- 
Up 
Infusion 
#2 
24- 
Hour 
Follow- 
Up 
48 & 72 
hrs 
7-Day 
Follow- 
Up 
14-Day 
28-Day 
Follow- 
Up 
Study Day*: 
-56 to -49 
-55 to -35 
1 
2 
3 & 4 
8 
15 
16 
17 & 18 
22 
29 
43 
Visit Window: 
± 3 hrs 
± 2 hrs 
± 1 
day 
± 3 days 
± 3 hrs 
± 2 hrs 
± 1 day 
± 2 hrs 
± 1 
day 
HIV-1/2, HBV, 
HCV, & West Nile 
Virus Nucleic Acid 
Tests 
X 
Cross-match RBC 
vs. FDP/FFP 
X 
X 
Reverse Type of 
FDP/FFP 
X 
X 
Coagulation Factor 
TestsM 
XJ 
XJ 
D-Dimer Test 
X 
XJ 
X 
XJ 
X 
Total Protein O 
X 
XJ 
PF 1+2, TAT, AT- 
III, Alpha-2 
Antiplasmin, and 
C3a des ArgQ 
XJ 
XJ 
*The estimated manufacturing time is 5  weeks. 
AThe AABB donor history questionnaire is administered at all donation   visits. 
BConfirm data are accurate; subject is healthy with no significant medical    history change. 
C Complete physical exams to include height (screening only), weight, vital signsE, and a targeted assessment of health as described in section 7.2 and section 8.2. 
DAbbreviated physical exam to include vital signs E  and a general assessment of   health. 
EVital signs monitored are blood pressure, heart rate, respiration rate, and temperature. These will be measured every 15 minutes (± 5 minutes) during the 
infusion, every 30 minutes (± 5 minutes) between 0 and 4 hours post-infusion, and then every 4 hours (± 40 minutes) until the subject is released from the 
clinic. 
FEach plasmapheresis session is to be scheduled approximately 7-10 days apart. Cohort 3 will require 3 to 4 plasma donation sessions. 
GExit interview may take place at any point during the study and is dependent upon subject’s continued enrollment status. 

Version 6.0 (19Apr2018) 
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HMonitor vital signs every 15 minutes during infusion; every 30 minutes for up to 4 hours post-infusion; and after 6 hours, vital signs should be measured every 4 
hours until the subject is released. Subjects assessed for DVT, PE, and cardiac ischemia using the Wells Scale prior to infusion, at 30 minutes, 4 hours, and 
24 hours post-infusion before the subject can be released from the   clinic. 
IChemistry panel includes Calcium, ALP, ALT, AST, Bicarbonate, Chloride, Glucose, Potassium, Sodium, Total Bilirubin, Total Protein, BUN, Lactate, and 
Creatinine. pH, Ionized Calcium and Total Magnesium will only be measured at pre-infusion and 0.5 hour post-infusion. 
JSee Table 9 - Laboratory Testing Schedule and Volumes for Cohort    3 for sampling time points. 
KCBC comprises Hematocrit, Hemoglobin, Platelet Count, RBC Count, and WBC    Count. 
LSPEP is performed on the donated plasma at each plasmapheresis   visit. 
MCoagulation testing for Factors I, II, V, VII, VIII, IX, X, XI von Willebrand Factor activity, and Total Protein C and S activity. 
N Follow-up phone calls to the subject will be made 48 hours and 72 hours following both Infusion Visits. The 14-day follow-up phone call will only occur after 
Infusion Visit #2. 
O Total Protein can be performed up to 24 hours prior to each subsequent    plasmapheresis session. 
P Additional collection visits may be required in the event that a plasma unit experiences an issue during preparation (eg, leakage during transfer to lyophilization 
bag) or during lyophilization (eg, bag breakage during   freeze-drying). 
Q These tests are for research purposes only and will not be used to manage the safety of study participants. 

Version 6.0 (19Apr2018) 
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US Government Proprietary 
FDP-1 
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The Surgeon General 
Department of the Army 
 
 
Table 9: 
Laboratory Testing Schedule and Volumes for Cohort  3 
 
Laboratory and Coagulation Factor 
Testing 
Screening 
Collection 
Visits 
Infusion Visits 
#1 and #2 
24-Hour 
Follow-Up 
Visits 
7-Day 
Follow-Up 
Visits 
28-Day 
Follow-Up 
Visit 
Pre- 
Infusion 
Post-Infusion 
0.5 hr 
4 hrs 
Pregnancy Test (females only) 
X 
X 
Urine Drug Screening 
X 
Urinalysis 
X 
X 
X 
X 
X 
Chemistry PanelA 
X 
X 
X 
X 
X 
X 
CBCB 
X 
X 
X 
X 
X 
X 
X 
Hematocrit 
X 
PT/INR 
X 
X 
X 
X 
X 
X 
aPTT 
X 
X 
X 
X 
X 
X 
DAT (IgG and C3) 
X 
X 
X 
X 
Blood Type for ABO and Rh 
X 
XC 
Red-Cell  Antibody Screen 
X 
Syphilis Screen 
X 
HTLV Antibody Screening  Test 
X 
HIV-1/2, HBV, HCV, and West Nile 
Virus Nucleic Acid Tests 
X 
Cross-match RBC 
X 
Reverse Type FDP/FFP 
X 
Coagulation Factor TestsD 
X 
X 
X 
D-Dimer Test 
X 
X 
XF 
XF 
X 
Total Protein G 
X 
PF 1+2, TAT, AT-III, Alpha-2 
Antiplasmin, and C3a des  Arg 
X 
X 
Plasma Collection 
X 
SPEPG 
X 
Total Blood Volume  Collected 
~51mL 
~607mLE 
~68mL 
~64mL 
~58mL 
~34mL 
~21mL 
~20 mL 
AChemistry panel includes Calcium, ALP, ALT, AST, Bicarbonate, Chloride, Glucose, Potassium, Sodium, Total Bilirubin, Total Protein, BUN, Lactate, and 
Creatinine. pH, Ionized Calcium and Total Magnesium will only be measured at pre-infusion and 0.5 hour post-infusion. 
BCBC comprises Hematocrit, Hemoglobin, Platelet Count, RBC Count, and WBC    Count. 
CABO only at this time point. 
DCoagulation testing for Factors I, II, V, VII, VIII, IX, X, XI, von Willebrand factor activity, and Protein C and S activity. 
ECollection volume for this visit includes the plasma donation volume (approximately 600 mL plasma collected at each visit). 
FD-Dimer collection at 30 minutes and 4 hours post-infusion must be done STAT. Results must be received and reviewed by the PI prior to the subject’s release 
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GSPEP is performed for subjects at each plasmapheresis session. Total Protein will be performed STAT or up to 24 hours prior to plasmapheresis at each 
subsequent  plasmapheresis session. 

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6.6. 
Measures Taken to Minimize/Avoid Bias 
6.6.1. 
Randomization 
Subjects in Cohorts 1 and 2 will not be randomized. The list of WB and plasmapheresis donors 
who have previously indicated an interest in participating in research will be sorted by donation 
type. The center will work through the list using a systematic scheme that represents a diverse 
subset of the population without bias based on race, ethnicity, gender, or age (as determined by  
the protocol) until target numbers have been reached. Research recruitment flyers are also posted 
at the blood center. These flyers include a telephone number for donors to call if they are 
interested in learning about research participation. 
Subjects who are recruited and eligible for WB donations in Cohort 1 will be automatically 
assigned to the FDP-CPD study arm. Similarly, plasmapheresis donors who are enrolled will 
automatically be assigned to the FDP-ACD study arm of Cohort 1. The same process for 
assigning subjects to the FDP-CPD and FDP-ACD arms in Cohort 2 will be  applied. 
For Cohort 3, which includes product crossover of FDP-ACD and FFP, only plasmapheresis 
donors who consent to the study are potentially eligible for study enrollment. Cohort 3 subjects  
are randomized no more than 48 hours prior to their first infusion in a 1:1 ratio to one of two 
treatment arms that will determine the order in which the two plasma treatment products, FFP   
and FDP-ACD, are to be infused across the two study infusion visits. Based on this, some  
subjects will receive FDP-ACD at the first infusion visit while others will receive FFP at the first 
infusion visit. Cohort 3 subjects who leave the study without completing both infusion visits will 
be replaced; the replacement subject, assigned a unique SID, will be assigned to the same 
treatment arm as the discontinued subject. The randomization list allows for over-enrollments   
and additional randomization slots to compensate for subjects who discontinue early. The Westat 
Statistician is responsible for the randomization assignments performed via the study website 
[https://www.fdpcollaboration.org]. Fifth floor HBC FDP research staff who randomize and 
prepare plasma products will complete the FDP-1 Randomization Worksheet, which contains a 
series of questions to verify subject eligibility. HBC FDP research staff will log on to the website 
and submit the worksheet information to request randomization. Shortly after the request is 
submitted, they will receive a confirmation email of the unmasked study arm assignment 
(including the randomization number). Fifth floor HBC FDP research staff will maintain records 
and prepare the appropriate plasma product according to the clinical site’s SOPs and the study’s 
MOP. 
 
6.6.2. 
Blinding 
This is a partial double-blind study. Blinding is not necessary for Cohorts 1 and 2 because they 
will only receive a single infusion of FDP. Cohort 3 subjects are to receive FDP at one infusion 
and the control product, FFP, at another. Cohort 3 subjects randomized to a treatment sequence  
are to remain blinded to the product they receive at each visit. Additionally, the PI, the RM, the 
PVG MD, and third floor HBC FDP research staff are blinded to the randomly assigned   
treatment sequence throughout the trial. FDP research staff, assigned to the fifth floor at HBC  
will be responsible for randomization, product preparation, and blinding. To ensure the product 
being used during infusion remains unknown to subjects, fifth floor HBC FDP research staff  will 

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place a blinding bag over the infusion bag that will remain in place throughout the subjects’ 
infusions. 
Further efforts to achieve blinding will include the use of a limited list of clinical site personnel 
authorized to receive the unmasked randomization confirmation (only those who require this 
information to perform their duties). 
6.6.3. 
Unblinding 
Unblinding is not to occur until all study data are entered into the database, the data is cleaned,  
and the database is locked. Otherwise, unblinding of a subject’s individual randomization code is 
only to be performed in the case of a medical emergency, or in the event of a serious medical 
condition, when knowledge of the investigational study product is essential for the clinical 
management or welfare of the subject. The reason for unblinding is to be clearly specified in the 
source documentation. 
In the event of a medical emergency or serious medical condition, the PI should attempt to notify 
the sponsor prior to the request for emergency unblinding through 5th floor HBC FDP research 
staff. However, if the subject must be unblinded immediately, the PI will contact the study  
sponsor as soon as possible to report the unblinding. 
Authority to request emergency unblinding is limited to the PI, RM, and the PVG MD. The PI  
will notify the Office of Regulated Activities, USAMMDA, Product Safety Surveillance Branch 
(PSSB) of the emergency unblinding as soon as possible. If an emergency unblinding occurs, the 
PSSB will immediately notify the DSMB Chair. The DSMB Chair will determine whether the 
DSMB members need to be involved immediately versus during the next DSMB  meeting. 
For the clinical site or the DSMB to request unblinding for a non-emergency situation, the 
following procedure must be followed for the site to receive approval to unblind the subject’s 
treatment order assignment: 
1. The PI will send the request to the US Army Medical Materiel Development Activity 
(USAMMDA), ORA, PSSB (usarmy.detrick.medcom-usammda.mbx.sae- 
reporting@mail.mil). The PSSB will notify the PVG MD and the un-blinded Westat 
Statistician of the request to un-blind. The request must include the subject’s 
identification number, last completed study visit, date of last plasma infusion (or date of 
last donation visit if no infusion visit has taken place), and an explanation of why un- 
blinding information is requested (eg, subject has experienced a Grade 3 clinical toxicity 
that is related to the infusion); 
2. If the PVG MD approves the request to un-blind, authorization will be sent to the un- 
blinded Westat statistician via email; 
3. If the DSMB requires un-blinded data for Cohort 3, the DSMB Chair will send the 
request to the PSSB (usarmy.detrick.medcom-usammda.mbx.sae-reporting@mail.mil). 
PSSB will notify the Westat un-blinded biostatistician who will provide the un-blinded 
data directly to the DSMB for review. 

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6.7. 
Investigational Product 
The investigational product, FDP, is manufactured at VSI, Minneapolis, MN, stored at 1°C -6°C 
prior to reconstitution, and shipped to the clinical site on an as-needed basis during the trial. One 
unit of FDP contains approximately 21.5 g of solids that consist of human plasma proteins and 
lipids. FDP will be reconstituted with 250 mL SWFI,  USP. 
Table 10 presents a summary description of the investigational product and comparator  product. 
Table 10: 
Investigational Product 
Product Name 
FDP 
FFP 
Dosage Form 
Freeze dried human plasma 
prepared from FFP in a 
customized lyophilization bag and 
reconstituted with 250 mL SWFI, 
USP. 
Plasma from WB or plasmapheresis 
collection, separated by centrifugation 
and frozen within 8 hours of 
collection. 
Unit Dose 
~270 mL 
~270 mL 
Route of 
Administration 
IV infusion 
IV infusion 
Physical Description 
Straw-colored cake that, upon 
reconstitution, looks similar in 
color and consistency to thawed 
FFP. 
Liquid plasma separated from RBCs 
and frozen. 
Manufacturer 
VSI 
Hoxworth Blood Center (FFP 
manufactured on site) 
Lot Number 
Donation Identification Number 
(DIN). 
Product Indication 
  Management of preoperative or 
bleeding patients who require 
replacement of multiple plasma 
coagulation factors (eg, liver 
disease, disseminated 
intravascular coagulation 
(DIC)); 
 Patients undergoing massive 
transfusion who have clinically 
significant coagulation 
deficiencies; 
 Patients taking warfarin who are 
bleeding or need to undergo an 
invasive procedure before 
Vitamin K could reverse the 
warfarin effect or who need  
only transient reversal of 
warfarin effect; and 
Same as the DIN; however, the suffix 
may change. 
 Management of preoperative or 
bleeding patients who require 
replacement of multiple plasma 
coagulation factors (eg, liver 
disease, DIC); 
 Patients undergoing massive 
transfusion who have clinically 
significant coagulation deficiencies; 
 Patients taking warfarin who are 
bleeding, or need to undergo an 
invasive procedure before Vitamin 
K could reverse the warfarin effect 
or who need only transient reversal 
of warfarin effect; 
 Management of patients with 
selected coagulation factor 
deficiencies, congenital or acquired, 
for which no specific coagulation 

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concentrates are available; 
 
 

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 Management of patients with 
selected coagulation factor 
deficiencies, congenital or 
acquired, for which no specific 
coagulation concentrates are 
available. 
 
 
 
Contraindications 
  To correct for coagulopathy in 
cases where a specific therapy 
would be more effective, such as 
Vitamin K, Cryoprecipitated 
Antihemophilic Factor (AHF), 
prothrombin complex 
concentrates used to reverse 
warfarin, or specific coagulation 
factor concentrates. 
 When blood volume can be 
safely and adequately replaced 
with other volume expanders. 
 Transfusion or plasma exchange in 
patients with thrombotic 
thrombocytopenic purpura (TTP); 
and 
 Management of patients with rare 
specific plasma protein deficiencies, 
such as C1 inhibitor, when 
recombinant products are 
unavailable. 
 To correct for coagulopathy in  
cases where a specific therapy 
would be more effective, such as 
Vitamin K, Cryoprecipitated 
Antihemophilic Factor (AHF), 
prothrombin complex concentrates 
used to reverse warfarin, or specific 
coagulation factor concentrates. 
 When blood volume can be safely 
and adequately replaced with other 
volume expanders. 
 
 
 
6.7.1. 
Investigational Product Packaging and Labeling 
The RePlas™ FDP system consists of: 
 One container of RePlas™ (~270 mL plasma equivalent), separately packaged within a 
foil pouch; 
 One container of SWFI USP that contains 250 mL (B. Braun, NDA#  N019633); 
 A commercially available Fluid Transfer Set (B. Braun) for transfer of the SWFI fluid 
into the RePlas™ container; and 
 A commercially available Blood Set (B. Braun), for infusion of the FDP to the  subject. 
The investigational product, RePlas™ FDP, is covered under an IND application. Each container 
will be labeled for human administration and will include the following statement: “Caution:  
New Drug  Limited by Federal (or United States) Law to Investigational  Use.” 
Each unit of manufactured FDP will be labeled with a unique DIN that is directly traceable to the 
original donor. The DIN will be carried throughout the study and recorded on the study case  
report forms (CRFs). 
6.7.2. 
Investigational Product Storage and Preparation 
FDP units will be shipped to the clinical site using the guidelines specified in the study-specific 
SOPs developed by VSI. The clinical site has developed a study-specific SOP to detail the 
process used for receiving and tracking FDP units from  VSI. 
Prior to reconstitution, FDP should be stored at 1°C to 6°C and the reconstitution fluid should be 
stored at room temperature (20°C to 24°C). Storage refrigerators and cabinets used  for 

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investigational product should be in secure areas with controlled and limited access and clearly 
labelled as ‘Active Product.’ Temperatures should be monitored with a certified National   
Institute of Standards and Technology (NIST) thermometer or validated environmental  
monitoring system. Any temperature excursions must be reported to the sponsor’s representative 
within 24 hours of knowledge of the excursion. Prior to infusion, FDP product must be 
reconstituted according to the procedures provided by the product manufacturer. Reconstituted 
FDP should not be frozen and should remain at room temperature until administration. Once 
reconstituted, transfusion with the FDP should begin within 4 hours. If transfusion has not started 
within 4 hours of reconstitution or the product is not used for other purposes, the unit cannot be 
used and must be identified as a quarantined unit, moved to quarantine, and then  discarded. 
FDP products that are damaged, experience temperatures outside of the defined parameters for 
product storage, and those that are unused are not to be infused unless written approval has been 
given by the sponsor’s representative. Unused study product must be stored under appropriate 
conditions in a specified quarantine area separate from active product storage. At the direction of 
the sponsor’s representative, FDP product units such as these must be discarded by the study site 
using their SOP, Discard of Blood Components  (#CP-057-SOP). 
6.7.3. 
Investigational Product Accountability 
The sponsor’s representative is responsible for distributing the investigational product to the 
study site. The sponsor’s representative has delegated drug accountability responsibility for this 
product to the PI; however, the sponsor’s representative has ultimate responsibility for product 
accountability. After the investigational product is distributed, the PI is responsible for and will 
maintain records of investigational product receipt, storage, reconstitution, accountability by 
subject, and investigational product remaining before final disposition. The PI may delegate, in 
writing, this responsibility to another individual, but the PI is ultimately responsible for the 
investigational product and its proper storage upon receipt at the study site until it is destroyed, 
as directed by the sponsor’s representative. 
The PI or designee must assure that the donor identity of the plasmapheresis products, and later 
downstream units of FFP or FDP manufactured from those products, is identical to the recipient  
of those products. Before infusion, the identity of the donor/recipient must be confirmed to agree 
with identity of the product label and ABO compatibility confirmed by testing using a minor 
cross-match and repeat typing of samples from the product. 
All unused or partially used investigational product will be destroyed by the PI or designee by 
being incinerated and disposed of as biohazardous waste according to local SOPs, as directed by 
the sponsor’s representative and as stipulated by local, state, and Federal regulations. Unused or 
partially used investigational product may only be destroyed or transferred after authorization  
has been received from the sponsor’s representative. 
Clinical monitors will confirm that procedures for the storage, dispensation, and 
return/destruction of investigational product are safe, adequate, and properly documented in 
accordance with the study protocol. 

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6.8. 
Duration of Subject Participation 
Subjects in Cohort 1 will complete the study in approximately 3 months. Subjects in Cohort 2, 
Arm 3 will complete the study in approximately 4 months; subjects in Cohort 2, Arm 4 will  
require approximately 3 months. Subjects in Cohort 3 will complete the study in approximately 4 
months. The first infusion for all cohorts is defined as Study Day 1. Study Day 15 is the second 
infusion for Cohort 3. The manufacturing time is currently estimated to be 5 weeks and although 
accounted for in study participation time, no subject activities are planned during this  time. 
Screening and baseline assessment and informed consent visits will require approximately 2 
hours. Final eligibility assessments and WB collection or plasmapheresis will require 
approximately 4 hours. On the day of infusion, the infusion and post-infusion studies will require 
approximately 8 hours. 
For all cohorts, the on-site follow-up assessments will take 1 to 2 hours to complete, and the 
telephone assessments will take 15 to 20 minutes to complete. Cohorts 1 and 2 will have on-site 
follow-up assessments on Study Days 2, 8, and 29 and telephone follow-up assessments on  
Study Days 3, 4, and 15. Cohort 3 will have on-site follow-up assessments on Study Days 2,  8, 
16, 22, and 43 and telephone follow-up assessments on Study Days 3, 4, 17, 18, and  29. 
 
6.9. 
Dose-Adjustment Criteria 
6.9.1. 
Safety Criteria for Dose Adjustment or Stopping  Doses 
If any of the following events occur, administration of investigational product will be 
discontinued until a thorough review of the events is undertaken by the PI, local Institutional 
Review Board (IRB) and/or the USAMRMC Office of Research Protections (ORP) Human 
Research Protection Office (HRPO), RM, and/or sponsor’s safety office (USAMMDA, ORA, 
PSSB). The study may be resumed with the concurrence of the PVG MD, sponsor’s 
representative, PI, and the FDA. 
The following SRs will be applied to all study subjects throughout the  trial: 
1. An SAE that is determined to be possibly, probably, or definitely related to the study 
product; 
2. An AE related to the study product that the PI, RM, and/or the sponsor’s PVG MD agree 
jeopardizes the subject’s health or safety; 
3. An AE related to the study product that requires medical or surgical intervention to 
prevent occurrence of an SAE; 
4. A post-infusion, abnormal coagulation function assay which is also a greater than 20% 
change from baseline for PT/INR and/or aPTT values (eg, a subject who has a baseline 
INR of 1.0 with a post-infusion INR of 1.3 will activate an SR, because this is an 
abnormal coagulation function assay result that is also a greater than 20% change from 
the pre-infusion assay result); and/or 
5. Post-infusion development of hemolysis or DVT, cardiac ischemia, or PE. DVT will be 
determined following the ICSI Health Care Guideline: Venous Thromboembolism 
Diagnosis and Treatment (includes assessment of D-Dimer results and Wells criteria ≥ 2). 
(Dupras et al-2013) 

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If any of the above conditions occur, the study will be paused to assess continuation of the study. 
A form (Appendix C) will document the decisions made by the PI, RM, and/or PVG MD 
regarding the review of the data from the first 5 subjects in each cohort. The completed form will 
be emailed to the clinical site, Westat, and USAMRMC USAMMDA ORA and will be  
maintained as part of the study documentation. 
6.10. 
Trial Treatment Randomization Codes 
The data management center for the study will provide a list of the randomized order for 
administration of FDP and FFP for Cohort 3. Unblinding prior to the end of the study will occur 
only to protect subject safety. 
The codes will be maintained by the website randomization system. The system will only send 
out website randomization confirmation with unmasked treatment assignment to the personnel 
that have been designated in the randomization, masking, and unmasking plan. Unblinding will 
occur at the end of the study after all study data are entered in the database, cleaned, and the 
database is locked. Study arm assignment information will only be provided to 5th floor HBC 
FDP research staff. 
6.11. 
Identification of Data to be Recorded on the Case Report Forms 
The electronic case report form (eCRF) data will be transcribed from source documentation. No 
source data will be recorded directly on the eCRF (i.e., without prior written or electronic record 
of data). The transcribed data will be consistent with the source documents or the discrepancies 
will be explained. 
For more information on data handling, refer section  15. 
 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1. 
Recruitment of Subjects 
HBC maintains lists of potential study subjects who have previously donated WB or plasma at   
the site and have indicated an interest in participating in research studies. Site personnel will 
contact (Appendix D) those people who have indicated an interest in research participation to 
inform them about this study. If the potential subject expresses an interest in learning more about 
the study and/or participating, then a screening visit will be scheduled. In addition to this    
process, advertisements (Appendix E) for healthy volunteers may also be used to recruit subjects. 
The subjects are typically not socioeconomically  disadvantaged. 
Subjects will be screened for inclusion as they present to the clinical site with an interest in 
participating and provide written informed consent. Subjects will be selected based on 
inclusion/exclusion criteria and eligibility requirements as specified in the study protocol, 
without any limitations to gender or ethnicity. 
Recruitment of Cohort 2 subjects will begin following the infusion of the last subject in  Cohort 
1. Enrollment, screening, and collection visits will be completed but infusion visits will not occur 
until the DSMB recommends and the Sponsor provides their approval to proceed. The same 
process will also be applied to the recruitment for Cohort 3 subjects. Concurrent infusions  will 

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not take place across cohorts ensuring infusions at the next higher does do not begin until all 
subject infusions at the previous dose have been completed. 
Refer to section 5.9 for a detailed description of the subject  population. 
 
7.2. 
Eligibility Screening 
Subjects who meet all the inclusion criteria and sign the informed consent form (ICF), will be 
enrolled in the study via the Oracle© Clinical (OC) Remote Data Capture (RDC) database. Each 
subject will be identified by a sequential number starting with 1. Demographic data (age, gender, 
and race/ethnicity) will be collected. Each subject must meet all inclusion and no exclusion 
criteria. In addition to the inclusion/exclusion criteria, the subject must also be eligible for 
donation based on the AABB donor history questionnaire (with exceptions for travel  deferral). 
The PI or designee will make the final decision regarding eligibility. Only subjects deemed 
eligible based on all required screening activities will be enrolled. To determine and confirm 
subject eligibility for enrollment, subjects are required to: 
 Provide a complete medical history, including concomitant  medications; 
 Undergo a complete physical examination that includes measurement of height, body 
weight, and vital signs (blood pressure, heart rate, respiration rate, and temperature), and 
evaluation of cardiopulmonary systems, basic neurological function, and presence of   
DVT or PE. DVT will be assessed in conjunction with a subjects’ D-dimer test results   
and Wells scale score, similar to the ICSI DVT Diagnosis Algorithm (Dupras et  al-2013); 
 Provide a urine sample for a toxicology drug screen, urinalysis for occult organ 
dysfunction and measurement of specific gravity, pH, glucose, ketones, protein, blood, 
leukocyte esterase, nitrite, bilirubin, and urobilinogen. Pregnancy tests will be performed 
for all females; and 
 Provide blood samples for all tests as indicated in the Schedule of Events tables (Table 4, 
Table 5, Table 6, and Table 8). 
 
7.3. 
Re-Screening Visits 
To ensure ongoing subject eligibility, subjects will be rescreened if the interval between  
screening and infusion exceeds 12 weeks, providing adequate time to identify changes in clinical 
and laboratory values that would impact subjects' eligibility. The same tests and procedures 
described in section 7.2 will be repeated during this  visit. 
7.4. 
Subject Inclusion Criteria 
Subjects must meet all of the following criteria to be included in the  study: 
 Males and non-pregnant/non-breastfeeding females; 
 For females, a minimum weight of 140 pounds and maximum weight of 220 pounds; for 
males a minimum weight of 140 pounds and a maximum weight of 250  pounds; 
 Ages 18-55 years; 
 Subject self-reports that he or she feels well and healthy; 

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 Subject scores ≥ 35 on the Duke Activity Status Index (Appendix  F); 
 Subject is able to donate a unit of WB or plasma by plasmapheresis based on the AABB 
donor history questionnaire with modifications indicated: subjects with history of travel 
which puts them at risk for Creutzfeldt-Jakob Disease, malaria, or Zika will be eligible to 
participate; 
 Has read the educational materials on donating blood and has had his or her questions 
answered; 
 Able and willing to provide written informed consent; 
 Available for the duration of the trial, which is approximately 12 weeks for subjects in 
Cohort 1 and Cohort 2, Arm 4; approximately 16 weeks for Cohort 2, Arm 3 and Cohort  
3 (includes time for collections, product manufacture, and infusions), and able to come to 
the treatment clinic for scheduled study visits; 
 Females of childbearing potential should either be surgically sterile (hysterectomy or 
tubal ligation), or should use a highly effective medically accepted contraceptive 
regimen. Highly effective methods of birth control are 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, sexual 
abstinence, condoms with spermicide, or vasectomized  partner; 
 All females must have a negative urine pregnancy test prior to enrollment;  and 
 Understands the English language. 
7.5. 
Subject Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from the  study: 
 Known liver, kidney, cardiovascular, neurologic, gastrointestinal, blood, 
endocrine/metabolic, autoimmune or pulmonary disease, or treated or untreated 
hypertension; 
 Cancer of any kind, under treatment or resolved; 
 Known or past coagulopathy conditions; 
 Any conditions, medications, etc. on the AABB medical deferral  list; 
 Past history of asthma (defined as use of a prescribed daily asthma controller medication 
or required asthma medication in the past 2 weeks); 
 Past diagnosis of stroke, DVT, venous or arterial thrombosis, blood clots, or transient 
ischemic attack; 
 Family history of venous or arterial thrombosis before the age of 50 in first degree 
relatives (i.e., biological parents, full siblings, or children); 
 D-dimer test result ≥ 0.5 FEU/mL; 
 History of an abnormal Electrocardiogram (EKG); 

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 Current smoker (defined as having smoked within the last 6  months); 
 Known HIV or Acquired Immunodeficiency Syndrome (AIDS)-related illness or 
received a positive test result for HIV infection; 
 Positive test for HBV, HCV, or HTLV; 
 History of significant treated or untreated mental health  issues; 
 Female subject who is pregnant, lactating, or with a positive pregnancy  test; 
 Currently taking an antibiotic or another medication for an  infection; 
 Treatment or use of aspirin (or other platelet inhibiting agents) within 14 days of study 
donation and infusion visits; 
 Currently using any medications for anticoagulant therapy; 
 Previous use of clotting factor concentrate(s); 
 Receipt of blood or blood products within the past 12  months; 
 In the past week, has had a headache and fever at the same  time; 
 Known intolerance to any excipients (citrate) in the study drug  formulation; 
 Systolic blood pressure greater than 140  mmHg; 
 Diastolic blood pressure greater than 90 mmHg; 
 Temperature greater than 100°F; 
 Known hematocrit less than 38% for both male and female  donors; 
 Positive DAT; 
 Treatment with any investigational agent within 1 month before treatment infusion for 
this trial; 
 Participation in any phase of any other investigational trials while participating in this 
trial; 
 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 subject’s 
return for follow-up visits on schedule; 
 Other unspecified reasons that, in the opinion of the PI, make the subject unsuitable for 
enrollment; or 
 Institutionalized because of legal or regulatory order. 
7.6. 
Subject Withdrawal Criteria 
Each subject may withdraw consent at any time during the study without penalty. Counseling 
about the subject’s health will be provided if he or she decides to discontinue participation in the 
study. Medical advice regarding what is in the best interest of the subject will be  provided. 

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The PI may discontinue the subject’s activity without the subject’s consent if any of these criteria 
are met: 
 A subject fails to comply with study procedures; 
 A subject’s safety or health may be compromised by further participation;  or 
 A subject’s Primary Care Physician wishes to withdraw the  subject. 
7.6.1. 
When and How to Withdraw Subjects 
A subject may end his or her participation in the study at any time. If a subject withdraws, the PI 
will make a reasonable effort to determine the reason for the withdrawal from the study and to 
complete termination procedures as described in section 8.4. Telephone calls, registered letters, 
and email correspondence are considered reasonable effort. A minimum of 2 documented 
attempts to contact the subject should be made over the course of 1 week. If the site personnel 
receive no response, they should send a registered letter requesting that the subject contact the  
site regarding his or her status in the study. If the subject does not respond at this point, the date 
the certified letter was mailed will be considered the date of study withdrawal. For subjects 
leaving the study, a targeted examination may be performed, if medically indicated and if 
permitted by the subject. 
A subject may be withdrawn for an AE or SAE resulting in a safety concern or for  
noncompliance with protocol requirements. When a subject withdraws due to an AE or is 
withdrawn by the PI due to an AE, the PVG MD, the sponsor’s safety office (USAMRMC 
USAMMDA ORA) must be notified within 72 hours (usarmy.detrick.medcom- 
usammda.mbx.sae-reporting@mail.mil). The PI must follow specific policies regarding the  
timely reporting of AEs and SAEs to the local IRB (section 10.6.2). In all cases, the PI will make  
a reasonable effort to complete study termination  procedures. 
If a subject meets the withdrawal conditions for a concomitant medication violation or 
noncompliance, this should clearly be stated in the source document and the study termination 
eCRF. 
 
7.6.2. 
Data Collected for Withdrawn Subjects 
If a subject is withdrawn, all data collected up to the time of withdrawal will be reported.  
Ongoing AEs should be followed to resolution or stabilization, if the subject consents to passive 
review of his or her medical record. The study termination eCRF will be completed, with the 
reason for withdrawal specified. 
 
7.6.3. 
Replacement of Subjects 
A total of 24 subjects (8 in each cohort) are to fully complete the trial. Depending on the cohort, 
study completion is defined as: 
 Cohorts 1 and 2: infused with autologous FDP and completion of the 7-day post- 
infusion follow-up visit; and 
 Cohort 3: infused with both the autologous experimental and control products per the 
assigned treatment sequence and completion of the 7-day post-infusion follow-up  
visit subsequent to the second infusion. 

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In cases where subjects discontinue participation prior to study completion, a replacement  
subject will be enrolled in the study. The replacement, assigned a new and unique SID, will be 
assigned to the same treatment arm as the discontinued subject. This is necessary to maintain the 
1:1 subject ratio across study arms. 
7.6.4. 
Follow-Up for Withdrawn Subjects 
Subjects who are withdrawn from the study will be followed to satisfactory resolution of any 
ongoing AEs (or until the PI deems the event to be chronic/stable) at the time of withdrawal by 
passive observation and recording of the subject’s medical record, if the subject consents to this 
process. 
 
8. 
TREATMENT OF SUBJECTS 
8.1. 
Whole Blood and Plasma Collection 
The purposeful use of plasmapheresis in this study, particularly for Cohort 3 subjects, provides 
practical advantages to subjects (eg, fewer required collection visits) and minimizes potential 
issues related to subject safety. WB donations generally provide a net volume of approximately 
250 mL of derived plasma and typically require a 56-day interval between donations. In this  
study, subjects who are required to make more than one autologous WB donation (eg, subjects in 
Cohort 2, Arm 3), the donation interval will be abbreviated to 28 days. Plasmapheresis  
collections, in contrast, have a much shorter 7- to 10- day donation interval since there is    
minimal loss of red blood cells (RBCs) during the process. The volume that can be collected  
during single plasmapheresis is ≤ 800 mL, depending on the donor’s size, which is over twice the 
plasma volume derived from WB donation. Limiting enrollment of subjects to those who  weigh 
≥140 lbs and ≤ 220 lbs will help ensure each autologous plasmapheresis yields 600 mL to  
800 mL plasma based on established volume limits for automated plasma collection (FDA- 
1992). Regardless of cohort or treatment arm, all subjects will have SPEP performed at each 
plasmapheresis collection. If any abnormalities are detected, subjects will be referred to a 
physician, scheduled for early withdrawal, and replaced with another subject. For  subjects 
undergoing multiple plasmapheresis collections, total protein will be performed STAT or up to 
24 hours prior to initiating the plasmapheresis. Total protein will only be performed at 
subsequent plasmapheresis sessions, not during the first collection. All subjects regardless of 
cohort or treatment arm will be provided with information and instructions regarding the use of 
iron supplements (see Appendix G) during the donation  period. 
Following standard blood product SOPs, subjects’ plasma products collected, manufactured, and 
prepared for autologous infusion will be visually examined. The visual inspection of both FFP  
and reconstituted FDP will include observation for signs of lipemia, hemolysis, clotting, and 
macroscopic particulate matter. Plasma units that do not meet the visual examination criteria will 
be discarded per the site’s SOP for the destruction of blood and blood  products. 
8.1.1. 
Cohort 1 Blood and Plasma Collection 
WB donors who are enrolled in the study will automatically be assigned to the FDP-CPD study 
arm of Cohort 1. Similarly, plasmapheresis donors who are enrolled will automatically be 
assigned to the FDP-ACD study arm of Cohort 1. Subjects in Treatment Arm 1 will receive a  1 

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unit (approximately 270 mL) transfusion of FDP manufactured from WB-derived plasma. 
Subjects in Treatment Arm 2 will receive a 1 unit (approximately 270 mL) transfusion of FDP 
manufactured from plasmapheresis. During the collection visit all subjects in Cohort  1will: 
 Be asked to provide information about medical history, concomitant medications, and 
AEs since the screening visit; 
 Undergo an abbreviated physical exam which includes vital signs (blood pressure, heart 
rate, respiration rate, and temperature) and a general assessment of  health; 
 Complete the AABB Donor History Questionnaire; and 
 Provide a sample of blood for hematocrit testing prior to donation per the SOPs in place 
at the site. 
Treatment Arm 1 subjects will provide a single unit (approximately 500 mL) WB donation using 
the standard WB donation procedures in place at the site. Post-donation, subjects will be 
monitored for any adverse effects associated with WB donation (see section  5.6.1.2). 
Treatment Arm 2 subjects will provide a single unit plasmapheresis donation (approximately 
600 mL) using the standard plasmapheresis donation procedures in place at the site. Post- 
donation, subjects will be monitored for any adverse effects associated with plasmapheresis 
donation (see section 5.6.1.3). 
If a subject has low hematocrit on the day of donation, they may, at the discretion of the 
investigator, be rescheduled for a second attempt at blood/plasma  collection. 
Subjects who provide low volume donations, <450 mL for Treatment Arm 1 and <500 mL for 
Treatment Arm 2, may, at the discretion of the investigator, be withdrawn from the study or 
rescheduled for a second attempt at blood/plasma collection. If, for example, the low volume 
donation occurs in a subject who enrolled early enough for a second donation attempt to be made 
within the scheduled time frame for the cohort, the subject will remain in the study and be given 
the opportunity for a second donation. Those subjects in Treatment Arm 2 who provide a low 
volume donation and who are scheduled for another attempt at the plasmapheresis collection will 
have another SPEP performed in addition to STAT total protein. All low-volume collections will 
be discarded by the clinical site following their SOP for handling blood and blood  products. 
 
8.1.2. 
Cohort 2 Blood and Plasma Collection 
Cohort 2 subjects will be assigned to 1 of the 2 treatment arms as described in section 6.6.1. 
Subjects in Treatment Arm 3 will receive a 2 unit (approximately 540 mL) transfusion of FDP 
manufactured from WB-derived plasma. Subjects in Treatment Arm 4 will receive a 2 unit 
(approximately 540 mL) transfusion of FDP manufactured from plasmapheresis. During 
collection visits all Cohort 2 subjects will: 
 Be asked to provide information about medical history, concomitant medications, and 
AEs since the screening visit; 
 Undergo an abbreviated physical exam which includes vital signs (blood pressure, heart 
rate, respiration rate, and temperature) and a general assessment of  health; 
 Complete the AABB Donor History Questionnaire; and 

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 Provide a sample of blood for hematocrit testing prior to (each) donation per the SOPs in 
place at the site. 
Treatment Arm 3 subjects will provide a single unit (approximately 500 mL) WB donation using 
the standard WB donation procedures in place at the site. Post-donation, subjects will be 
monitored for any adverse effects associated with WB donation (see section 5.6.1.2). Due to the 
volume of plasma required to manufacture 2 units (approximately 540 mL, total) of FDP, 
Treatment Arm 3 subjects will be scheduled for a second WB donation session, no less  than 
28 days from the date of their first donation. Subjects in this arm who provide a low-volume 
donation (< 450 mL) may, at the discretion of the investigator, be withdrawn from the study or 
scheduled for a second donation attempt. The donation portion of each WB donation visit is 
expected to take no more than 1 hour. The procedures described above will be followed at both 
WB donation visits. 
Treatment Arm 4 subjects will provide a single unit plasmapheresis donation (up to 800 mL)  
using the standard procedures in place at the site. Subjects will undergo SPEP, which will be 
measured during their plasmapheresis donation. Post-donation, subjects will be monitored for  
any adverse effects associated with plasmapheresis donation (see section 5.6.1.3). A second 
plasmapheresis donation visit should not be required for Treatment Arm 4 subjects. Subjects 
providing a low volume plasmapheresis donation (< 500 mL) may, at the discretion of the 
investigator, be withdrawn from the study or scheduled for a second donation attempt. If a 
subsequent visit is scheduled to collect the volume of plasma required to manufacture the 2 units 
(approximately 540 mL, total) of FDP, an additional visit may be scheduled no less than 7 days 
from the date of the first donation. SPEP and STAT Total Protein will both be performed at any 
subsequent collection visits as a condition of initiating  plasmapheresis. 
Following standard blood collection SOPs, subjects who present to a collection visit with a low 
hematocrit may, at the discretion of the PI, be rescheduled for a later blood/plasma  collection. 
All low-volume collections will be discarded by the clinical site following their SOP for 
handling blood and blood products. 
8.1.3. 
Cohort 3 Plasma Collection 
WB-derived plasma will not be used in Cohort 3 due to safety concerns regarding the number of 
donations required to collect the volume of plasma needed to manufacture 3 units (approximately 
810 mL) of FDP and 3 units (approximately 810 mL) of FFP. All subjects in Cohort 3 will  
undergo plasmapheresis collection. Cohort 3 subjects will be randomized no more than 48 hours 
prior to the first infusion to 1 of 2 treatment arms that will be based on the order of the products 
received. Subjects in Treatment Arm 5 will receive a 3 unit (approximately 810 mL) transfusion  
of FDP followed by a 3 unit (approximately 810 mL) transfusion of FFP. Subjects in Treatment 
Arm 6 will receive a 3 unit (approximately 810 mL) transfusion of FFP followed by a 3 unit 
(approximately 810 mL) transfusion of FDP. Subjects will be blinded to their treatment order 
assignments. 
During the Collection Visits, all Cohort 3 subjects will: 
 Be asked to provide information about medical history, concomitant medications, and 
AEs since the screening visit; 

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 Undergo an abbreviated physical exam which includes vital signs (blood pressure, heart 
rate, respiration rate, and temperature) and a general assessment of  health; 
 Complete the AABB Donor History Questionnaire; 
 Provide a sample of blood for hematocrit testing prior to (each) donation per the SOPs in 
place at the site; and 
 Provide a plasma donation by plasmapheresis in compliance with the clinical site’s SOPs 
regarding plasmapheresis donation. 
Cohort 3 subjects will need to make 2 to 3 plasmapheresis donations (up to 800 mL per 
collection) that will be scheduled to take place, minimally, a week apart. Post-donation, subjects 
will be monitored for any adverse effects associated with plasmapheresis donation (see section 
5.6.1.3). The SPEP will be routinely performed at as part of all Cohort 3 collection visits. Should 
the SPEP results reveal the subject as ineligible for their current plasmapheresis, the subject may 
be rescheduled to return in no less than 7 days. Just prior to Cohort 3 subjects’ second or 
subsequent plasmapheresis donation at each plasmapheresis collection, a SPEP test will be 
performed. After the first plasmapheresis collection, a STAT Total Protein will be performed as   
a condition of initiating plasmapheresis at subsequent collection visits. Post-donation, all   
subjects will be monitored for any adverse effects associated with plasmapheresis donation (see 
section 5.6.1.3). 
Approximately 10% of plasma units that are supplied for manufacturing of FDP are damaged 
during the process. Those units must be discarded and cannot be infused. If that happens to a 
subject’s plasma unit, they will be asked to return to the clinic for additional plasmapheresis 
collections in order to meet the total required volume for the manufacturing of 1,620 mL of 
plasma. 
Subjects who do not meet the study’s minimum collection volume requirements of 500 mL 
during plasmapheresis may be withdrawn from the study. The low volume donation collections 
(< 500 mL) will be discarded per the clinical site’s SOP for handling blood and blood  products. 
8.2. 
Plasma Infusion 
8.2.1. 
Cohorts 1 and 2 Plasma Infusion 
Prior to plasma infusion of subjects’ in Cohorts 1 and 2, the following activities and procedures 
must be completed: 
 Review of medical history, concomitant medications, and AEs since the collection 
visit(s); 
 Conduct a complete physical examination that includes measurement of, body weight, 
and vital signs (blood pressure, heart rate, respiration rate, and temperature), and 
evaluation of cardiopulmonary systems, basic neurological function, and presence of 
DVT, cardiac ischemia, or PE. DVT will be assessed in conjunction with a subjects’ D- 
Dimer test results and Wells scale score.(Dupras et  al-2013); 
 Collect urine and blood samples as noted for all tests listed in the Schedule of Events 
tables (Table 4, Table 5, and Table 6); 

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 Cross-match subject’s RBCs to FDP; and 
 Reverse ABO type on FDP. 
At the discretion of the PI, a study plasma infusion may not be given if, in the PI’s opinion, the 
subject’s clinical status precludes a study plasma infusion and the planned protocol assessments. 
The reason for the PI’s decision to withhold a study plasma infusion will be documented in the 
source documents and eCRFs. This does not preclude a standard of care plasma  infusion. 
After reconstitution of the FDP, a visual examination for signs of lipemia, hemolysis, clotting, or 
other issues that impact the quality and acceptability of the plasma for re-infusion will be 
performed. This visual inspection of FDP also includes observation of macroscopic particulate 
matter. Reconstituted FDP that does not meet visual examination criteria will be discarded per  
the site’s SOP for the destruction of blood and blood products. 
The date, start, and stop times of each plasma infusion will be recorded in the source document 
and eCRF. The scheduled dose of FDP will be transfused into subjects using a standard plasma 
administration set according to the clinical site’s SOPs. The plasma product will be pumped into 
the vein at an initial rate of approximately 2-3 mL/minute for the first 10 minutes, and then the 
rate will be adjusted to not more than 10 mL/minute until completion of the plasma  infusion. 
During the course of the infusion, vital signs (blood pressure, heart rate, respiration rate, and 
temperature) for all subjects will be monitored every 15 minutes (± 5 minutes) until the 
transfusion is completed. 
Subjects will be observed during and after the study plasma infusion for evidence of acute 
transfusion reactions including: allergic reactions, bradycardia, tachycardia, or other cardiac 
dysrhythmia, hypertension, hypotension, dyspnea, hemolysis, fever, chills, thromboembolic 
events, bleeding, and infection. Subjects will remain at the study site under direct observation 
and actively monitored for a minimum of 5 to 6 hours  post-infusion. 
Vitals will be measured every 30 minutes (± 5 minutes) up to 4 hours post-infusion and then 
once every 4 hours (± 40 minutes) until the subject is released. The following laboratory tests 
will be performed at 30 minutes (± 5 minutes) and at 4 hours (± 40 minutes) post-infusion (see 
Table 7): 
 Urinalysis; 
 CBC (Hematocrit, Hemoglobin, Platelet Count, RBC Count, WBC  Count); 
 Chemistry panel (pH, Ionized Calcium and Total Magnesium [at 30 minutes post- 
infusion only], ALP, ALT, AST, Calcium, bicarbonate, lactate, Chloride, Glucose, 
Potassium, Sodium, Total Bilirubin, Total Protein, BUN, and  Creatinine); 
 PT/INR and aPTT; and 
 D-dimer testing. 
Prior to release, subjects will undergo an additional physical evaluation (eg, focus on 
cardiopulmonary systems, basic neurological function, and presence of DVT). The investigator 
will interpret exam findings in conjunction with the subjects’ 4-hour post-infusion D-dimer test 
results and Wells criteria to determine the medical suitability for  release. 

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8.2.2. 
Cohort 3 Plasma Infusion 
Cohort 3 subjects will be scheduled for 2 infusion visits to occur on Study Days 1 and 15.  
Because of the crossover, no more than 48 hours prior to administration of a subject’s first 
infusion, he or she will be randomly assigned to a study arm (Arm 5 or Arm 6) indicating the 
specific product to be administered. The alternate product of what is received at the first Infusion 
Visit, either FDP (Test) or FFP (Control), will be infused at the second Infusion  Visit. 
At the time of each scheduled Infusion Visit, the prior activities and procedures must be 
completed for each subject before infusion may begin: 
 Review of medical history, concomitant medications, and AEs since the collection 
visit(s); 
 Conduct a complete physical examination that includes measurement of weight, and vital 
signs (blood pressure, heart rate, respiration rate, and temperature), and evaluation of 
cardiopulmonary systems, basic neurological function, and presence of DVT, cardiac 
ischemia, or PE. DVT will be assessed in conjunction with a subjects’ D-dimer test  
results and Wells scale score (Dupras et al-2013). 
 Collect urine and blood samples as noted for all tests listed in the Schedule of Events 
table (Table 8); 
 Cross-match subject’s RBCs to FDP or FFP; and 
 Reverse ABO type on FDP or FFP. 
At the discretion of the PI, a study plasma infusion may not be given if, in the PI’s opinion, the 
subject’s clinical status precludes a study plasma infusion and the planned protocol assessments. 
The reason for the PI’s decision to withhold a study plasma infusion will be documented in the 
source documents and eCRFs. This does not preclude a standard of care plasma  infusion. 
After reconstitution of the FDP or FFP, a visual examination for signs of lipemia, hemolysis, 
clotting, or other issues that impact the quality and acceptability of the plasma for re-infusion   
will be performed. This visual inspection of reconstituted FDP also includes observation of 
macroscopic particulate matter. Reconstituted FDP or FFP that does not meet visual examination 
criteria will be discarded per the site’s SOP for the destruction of blood and blood  products. 
The date, start, and stop times of each plasma infusion will be recorded in the source document 
and eCRF. The scheduled dose of FDP or FFP will be transfused into subjects using a standard 
plasma administration set according to the clinical site’s SOPs. The plasma product will be 
pumped into the vein at an initial rate of approximately 2-3 mL/minute for the first 10 minutes, 
and then the rate will be adjusted to not more than 10 mL/minute until completion of the plasma 
infusion. During the course of the infusion, vital signs (blood pressure, heart rate, respiration  
rate, and temperature) for all subjects will be monitored every 15 minutes (± 5 minutes) until the 
infusion is completed. 
Subjects will remain at the study site and be actively monitored under direct observation for a 
minimum of 5 to 6 hours post-infusion. They will be asked about and observed during and after 
the study plasma infusion for evidence of acute transfusion reactions including: allergic 
reactions, bradycardia, tachycardia, or other cardiac dysrhythmia, hypertension, hypotension, 
dyspnea, hemolysis, fever, chills, thromboembolic events, bleeding, and  infection. 

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Vitals will be measured every 30 minutes (± 5 minutes) up to 4 hours post-infusion. 
Measurement of vitals will then be decreased to every 4 hours (± 40 minutes) until the subject is 
released. The following laboratory tests will be performed at 30 minutes (± 5 minutes) and  at 
4 hours (± 40 minutes) post-infusion (see Table 9): 
 Urinalysis; 
 CBC (Hematocrit, Hemoglobin, Platelet Count, RBC Count, WBC  Count); 
 Chemistry panel (pH, Ionized Calcium and Total Magnesium [at 30 minutest post- 
infusion only], ALP, ALT, AST, Calcium, Bicarbonate, lactate, Chloride, Glucose, 
Potassium, Sodium, Total Bilirubin, Total Protein, BUN, and  Creatinine); 
 PT/INR and aPTT; 
 DAT (IgG and C3); 
 Coagulation factor tests (Factors I, II, V, VII, VIII, IX, X, XI, D-Dimer, von Willebrand 
Factor activity, Protein C activity, and Protein S activity); and 
 PF 1+2, TAT, AT-III, Alpha-2 Antiplasmin, and C3a des Arg at 30 minutes post-infusion 
only. These tests are for research purposes only and will not be used to assess subject 
safety. 
Prior to release, subjects will undergo an additional physical evaluation (eg, focus on 
cardiopulmonary systems, basic neurological function, and presence of DVT). The investigator 
will interpret exam findings in conjunction with the subjects’ 4-hour post-infusion D-dimer test 
results and Wells criteria to determine the medical suitability for  release. 
8.3. 
Follow-Up Visits 
8.3.1. 
24-Hour Follow-Up Visit 
Subjects in all 3 cohorts should be scheduled for an on-site follow-up visit 24 hours (± 3 hours) 
after the completion of the plasma infusion. During this visit, the following procedures will be 
performed: 
 Review of medical history, concomitant medications, and AEs since the infusion  visit; 
 Conduct a complete physical examination that includes measurement of, body weight, 
and vital signs (blood pressure, heart rate, respiration rate, and temperature), and 
evaluation of cardiopulmonary systems, basic neurological function, and presence of 
DVT, cardiac ischemia, or PE. DVT will be assessed in conjunction with a subjects’ D- 
Dimer test results and Wells scale score; and 
 Collect urine and blood samples as noted for all tests listed in the Schedule of Events 
tables (Table 4, Table 5, Table 6, and Table 8). 
NOTE: Since subjects in Cohort 3 receive 2 separate infusions, a 24-hour post-infusion follow- 
up visit will be scheduled after each infusion. 

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8.3.2. 
Telephone Follow-Up 
In addition to scheduled on-site follow-up visits, subjects in all 3 cohorts will be contacted by 
phone at 48 hours (± 2 hours), 72 hours (± 2 hours), and 14 days (± 2 hours) (ie, Study Days 3, 4, 
and 15) after the completion of the plasma infusion. During the calls, subjects will be asked 
specific questions (Appendix H) regarding possible signs and symptoms of any AEs they may 
have experienced and any concomitant medications taken since the infusion visit. The date and 
time of the call, as well as the subject’s responses will be recorded in the source documents and  
the eCRF. 
Cohort 3 subjects’ will have no 14- day follow-up phone call after the first infusion since it 
would occur on the same day as the second infusion (Study Day 15). The 14-day follow-up 
phone call subsequent to the second infusion visit will occur on Study Day  29. 
8.3.3. 
7-Day Follow-Up Visit 
A post-infusion follow-up visit will be scheduled 7 days (± 1 day) post-infusion for subjects in 
all 3 cohorts. The following procedures will be performed at these  visits: 
 Review of medical history, concomitant medications, and AEs since the last telephone 
follow-up contact; 
 Abbreviated physical exam which includes vital signs (blood pressure, heart rate, 
respiration rate, and temperature) and a general assessment of health;  and 
 Collect blood samples as noted for all tests listed in the Schedule of Events tables 
(Table 4, Table 5, Table 6, and Table 8). 
NOTE: Since subjects in Cohort 3 receive 2 separate infusions, a 7-day post-infusion follow-up 
visit should also be scheduled after the second infusion. The second 7-day post-infusion follow- 
up visit will also follow the procedures described in this  section. 
8.3.4. 
28-Day Follow-Up Visit 
A post-infusion follow-up visit will be scheduled 28 days (± 1 day) post-infusion for subjects 
enrolled in Cohorts 1 and 2. For subjects enrolled in Cohort 3, a 28-day post-infusion follow-up 
visit will take place after the second plasma infusion, only, approximately 42 days after the first 
infusion visit. The following procedures will be performed at these follow-up  visits: 
 Review of medical history, concomitant medications, and AEs since the 14-day 
telephone follow-up contact; 
 Abbreviated physical exam which includes vital signs (blood pressure, heart rate, 
respiration rate, and temperature) and a general assessment of  health; 
 Collect blood samples as noted for all tests listed in the Schedule of Events tables 
(Table 4, Table 5, Table 6, and Table 8); and 
 Exit interview concluding the subject’s study participation. 

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8.3.5. 
Biological Samples 
Samples collected under this protocol will be used to conduct protocol-related safety and    
efficacy evaluations as noted in Table 4, Table 5, Table 6, and Table 8. No genetic testing will be 
performed on these samples. Total volumes, by visit, for laboratory tests performed during the 
course of the study are listed in Table 7 and Table 9. 
Samples will be stored in a quality-controlled environment. Transport and storage of these 
biological samples will be handled according to the clinical site’s SOP. Any study for the future 
use of these biological samples will have IRB approval. In addition, a subject may decide at any 
point to withdraw consent for the future use of his or her samples. Should a subject withdraw 
consent for the use of his or her samples, the samples will be destroyed according to the clinical 
site’s SOP. 
8.4. 
Early Withdrawal Procedures 
Subjects who withdraw from the study at any time before the Infusion Visit who have not 
experienced an AE will have the Exit Interview administered by telephone. Subjects who 
withdraw from the study any time after the infusion and before the 7-Day Post-Infusion Follow- 
Up Visit will be asked to complete all Early Discontinuation Visit procedures to ensure safety  
and to collect as much data as possible: 
 Review of medical history, concomitant medications, and AEs since the telephone 
follow-up contact; 
 Abbreviated physical exam which includes vital signs (blood pressure, heart rate, 
respiration rate, and temperature) and a general assessment of health;  and 
 Laboratory tests including: 
 Urinalysis; 
 Urine pregnancy test (females only); 
 CBC (Hematocrit, Hemoglobin, Platelet Count, RBC Count, WBC  Count); 
 Chemistry panel (ALP, ALT, AST, Calcium, Chloride, Potassium, Sodium, 
Lactate, Bicarbonate, Glucose, Total Bilirubin, Total Protein, BUN, and 
Creatinine); 
 PT/INR and aPTT; 
 DAT; 
 D-dimer; and 
 COHORT 3 ONLY – Coagulation factor tests (Factors I, II, V, VII, VIII, IX, X, 
XI, von Willebrand factor, Protein C activity, and Protein S activity), PF 1+2, 
TAT, AT-III, alpha-2 antiplasmin, and C3a des Arg. PF 1+2, TAT, AT-III, alpha- 
2 antiplasmin, and C3a des Arg are for research purposes only and will not be  
used to assess subject safety. 

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8.5. 
Unscheduled Visits 
Unscheduled visits are allowed for the following  reasons: 
 To perform confirmatory laboratory testing for clinically abnormal values;  and 
 If the PI feels that it is clinically required for safety reasons related to the subject’s 
participation in the study. 
Findings during these unscheduled visits must be reported on the eCRF in the Unscheduled Visit 
section. 
8.6. 
Concomitant Medications 
Subjects should not be taking prescription medications or over the counter drugs included in the 
list of exclusion criteria or on the eligibility assessment questionnaire while participating in this 
study. If the subject develops a medical condition between the time of plasmapheresis and re- 
infusion, the medication should be approved by the PI prior to the subject taking the medication. 
If a medication is taken that is contraindicated to the objectives of the study, the infusion will 
either be deferred or the subject will be taken off study. 
The AABB Medication Deferral List includes: 
 Proscar©  (finasteride); 
 Avodart©, Jalyn (dutasteride); 
 Propecia©  (finasteride); 
 Accutane©  (Amnesteem, Claravis, Sotret, isotretinoin); 
 Soriatane©  (acitretin); 
 Tegison©  (etretinate); 
 Growth hormone from human pituitary glands; 
 Insulin from cows (bovine, or beef insulin); 
 Hepatitis B immune globulin; 
 Plavix (clopidogrel) and Ticlid (ticlopidine); 
 Feldene; and 
 Experimental medication or unlicensed (experimental)  vaccine. 
8.7. 
Procedures for Monitoring Subject Compliance 
A record of each study plasma infusion will be documented in the clinical database via relevant 
eCRFs and additional source documentation. Only the individual product unit identifier will be 
stored in the clinical database. The clinical database will document that the infusion occurred. 
Additionally, for unit identifiers documented in the clinical database, final disposition will be 
reconciled by linking to a separate Plasma Unit Tracking Form that will be maintained by 5th 
floor HBC FDP research staff and VSI. 

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9. 
PHARMACOKINETIC ASSESSMENTS 
No pharmacokinetic assessments will be done in this  study. 
 
10. 
SAFETY ASSESSMENT 
Safety monitoring throughout the study will identify safety issues and concerns. The process of 
continual review of the data and the imperative to appropriately and promptly address identified 
safety concerns is a shared effort of the PI and clinic staff, the designated clinical and research 
monitors, USAMRMC USAMMDA ORA, and the PVG MD for the protocol. A DSMB will be 
convened for this protocol. The roles and responsibilities of the monitors and DSMB are outlined 
below. 
Clinical Site: Consists of the PI, RM, Clinical Research Coordinator, and other research staff.  
The clinical site is responsible for ensuring the safety of study subjects by managing, collecting, 
and recording AEs/SAEs, and reporting SAEs appropriately according to the requirements of the 
protocol and their local IRB. The PI will promptly forward all SAEs to the IRB and  HRPO. 
Research Monitor: The Department of Defense research monitor is responsible for overseeing 
the safety of the research and reporting observations/findings to the IRB or a designated 
institutional official. The research monitor will review all unanticipated problems involving risks 
to subjects or others associated with the protocol and provide independent reports of the events   
to the IRB. The research monitor may discuss the research protocol with the investigators; shall 
have authority to stop a research protocol in progress, remove individual human subjects from a 
research protocol, and take whatever steps are necessary to protect the safety and well-being of 
human subjects until the IRB can assess the monitor’s report; and shall have the responsibility to 
promptly report their observations and findings to the IRB or other designated official and the 
HRPO. 
In addition to the responsibilities above, the research monitor is required to review and provide 
unbiased written reports for all SAEs and subject deaths to the USAMMDDA PSSB (Safety 
Office) within 24 hours of becoming aware of the event. The report provided must include at a 
minimum, a brief summary of the research monitor's review of the event and event outcome, 
relationship of the event to the investigational product, and whether or not the research monitor 
concurs with the details of the study investigator's report. 
Clinical Monitor: The designated clinical monitor for the trial is  to: 
1. Conduct initial, periodic, and termination clinical site  visits; 
2. Check that the clinical site is adhering to the protocol in its conduct of the study 
and to information presented in the informed consent documents, SOPs, and 
applicable regulations; 
3. Oversee study file and regulatory documents, and cross check source documents 
and eCRFs; and 
4. Observe study procedures. 

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Pharmacovigilance Physician: 
The USAMMDA Safety PVG MD, as delegated by the sponsor, evaluates all safety cases and 
provides a final determination on relatedness to the product and whether expedited reporting is 
warranted per current FDA regulation and guidance. In coordination with USAMRMC 
USAMMDA ORA, each SAE report is reviewed for medical consistency, accuracy, and 
completeness and each event followed until it is satisfactorily resolved. In addition, the PVG MD 
will serve as an arbiter in cases where the PI and RM’s review of these data results in discordant 
determinations. 
The PVG MD is responsible for the review of SAE data and reports. In reviewing SAEs, the 
PVG MD will: 
1. Review SAE reports to ensure the content is medically consistent, accurate, and 
complete; 
2. Follow each SAE until it is satisfactorily resolved; and 
3. Perform an assessment of the reporting status to the  FDA/DSMB. 
Data and Safety Monitoring Board: An independent DSMB will be convened to review   
clinical trial safety data and provide recommendations to the USAMMDA ORA PSSB. The  
PSSB will deliver the DSMB recommendations to the Sponsor’s Representative for final  
decision. The USAMRMC USAMMDA ORA will communicate the final decision to the PI, who 
will notify the IRB. USAMRMC USAMMDA ORA will communicate the final decision to the 
FDA, as appropriate. A further description of the DSMB roles and responsibilities, functions,   
and reporting requirements is included in the DSMB  charter. 
10.1. 
Specification of Safety Endpoints 
The investigator will review subjects’ medical records and administer a focused review of 
systems and a physical examination to all subjects to determine the presence of symptoms or 
signs of coagulation abnormalities. 
Primary safety endpoints will include those related to vital signs, clinical laboratory parameters 
(chemistry, hematology, urine analysis, and coagulation), and  AEs. 
 
10.1.1. 
Vital Signs 
Vital signs to be measured include blood pressure, heart rate, respiration rate, and oral 
temperature. Vital sign measurements are collected at every on-site visit as part of the physical 
examination process. During and after the infusion process, vital sign measurements are used to 
observe for evidence of acute transfusion reactions (eg, bradycardia, tachycardia, cardiac 
dysrhythmia, hypertension, hypotension, fever, etc.) and are collected every 15  minutes 
(± 5 minutes) during the infusion, every 30 minutes (± 5 minutes) between 0 and 4 hours post- 
infusion, and then every 4 hours (± 40 minutes) until the subject is released from the  clinic. 
Temperature will be standardly evaluated following HBC’s SOP, Welch Allyn Spot Vital Sign 
Procedure (# WB-032-SOP). 

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10.1.2. 
Laboratory Assessments 
Laboratory assessments should be performed whenever possible in a College of American 
Pathologists (CAP)/Clinical Laboratory Improvement Act certified environment or at least, 
following SOP-driven, QC-reviewed procedures. 
The total amounts of blood drawn from a study subject who completes all study procedures are 
shown in Table 7 and Table 9. 
 
10.1.2.1. 
Hematology and Clinical Chemistry 
Table 11 summarizes the hematology and clinical chemistry markers that subjects will be tested 
for at the specified time points in the study. 

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Table 11: 
Hematology and Clinical Chemistry Tests 
 
HEMATOLOGY 
Pre-Infusion 
Post-Infusion 
Early 
Withdrawal 
Screening 
Collection 
Day 
Infusion 
Day 
0.5 
Hours 
4 
Hours 
24 
Hours 
7 
Days 
28 
Days 
CBC (Hematocrit, Hemoglobin, Platelet 
Count, RBC Count, WBC  Count) 
X 
X 
X 
X 
X 
X 
X 
X 
DAT (IgG and C3) 
X 
X 
X 
X 
X 
Hematocrit 
X 
Cross-match RBC 
X 
Reverse Type FDP/FFP 
X 
Blood Type (ABO and Rh) 
X 
X 
Red-Cell  Antibody Screen 
X 
Syphilis Screen 
X 
Screening Test for HTLV  Antibody 
X 
Nucleic Acid Tests for HIV-1/2, HBV, HCV, 
and West Nile Virus 
X 
CLINICAL CHEMISTRY 
ALP 
X 
X 
X 
X 
X 
X 
X 
ALT 
X 
X 
X 
X 
X 
X 
X 
AST 
X 
X 
X 
X 
X 
X 
X 
Ionized Calcium; Total  Magnesium 
X 
X 
Electrolytes (Calcium, Chloride, Potassium, 
Sodium, Lactate, Bicarbonate) 
X 
X 
X 
X 
X 
X 
X 
pH 
X 
X 
Glucose 
X 
X 
X 
X 
X 
X 
X 
Total Bilirubin 
X 
X 
X 
X 
X 
X 
X 
Total Protein 
X 
X 
X 
X 
X 
X 
X 
BUN 
X 
X 
X 
X 
X 
X 
X 
Creatinine 
X 
X 
X 
X 
X 
X 
X 
SPEP (All subjects undergoing 
plasmapheresis) 
X 
Total Protein (All subjects undergoing 
multiple  plasmapheresis sessions) 
X 
 
 
 
 
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10.1.2.2. 
Urinalysis 
A clean-catch urine sample will be collected from all subjects at the screening visit to confirm 
study eligibility prior to enrollment. Additional urine samples will be collected from enrolled 
subjects on the day(s) they are infused and at the 24-hour post-infusion follow-up visit(s). The 
urinalysis will include: 
 Visual exam – urine sample will be inspected for color and clarity;  and 
 Chemical exam – reagent test strips will be used to determine specific gravity, pH, as  
well as detect the presence of protein, glucose, ketones, blood, leukocyte esterase, nitrite, 
bilirubin, and urobilinogen. 
 
10.1.2.3. 
Coagulation Markers 
Table 12 summarizes the coagulation markers subjects will be tested for at the specified time 
points in the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 12: 
Coagulation Tests 
 
Coagulation Tests 
Screening 
Pre-Infusion 
Post-Infusion 
Early 
withdrawal 
Infusion Day 
0.5 Hours 
4 Hours 
24 Hours 
28 Days 
ALL SUBJECTS: 
PT/INR 
X 
X 
X 
X 
X 
X 
X 
aPTT 
X 
X 
X 
X 
X 
X 
X 
D-Dimer 
X 
X 
X 
X 
X 
X 
COHORT 3 SUBJECTS  ONLY: 
Factor I 
X 
X 
X 
X 
Factor II 
X 
X 
X 
X 
Factor V 
X 
X 
X 
X 
Factor VII 
X 
X 
X 
X 
Factor VIII 
X 
X 
X 
X 
Factor IX 
X 
X 
X 
X 
Factor X 
X 
X 
X 
X 
Factor XI 
X 
X 
X 
X 
von Willebrand Factor 
activity 
X 
X 
X 
X 
Protein C activity 
X 
X 
X 
X 
Protein S activity 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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10.1.2.4. 
Drug Screen 
A urine drug screening will be performed for Cannabinoids, cocaine, amphetamines, opiates and 
PCP (NIDA-5) at the screening visit only. Potential subjects with a positive urine drug screen  
will be ineligible for enrollment. 
10.1.2.5. 
Pregnancy Screen 
An FDA-cleared qualitative urine pregnancy test that evaluates human beta-chorionic 
gonadotropin will be used to test all females (at screening, pre-infusion, and early withdrawal 
ONLY). 
10.2. 
Investigational New Drug Safety Reporting 
The following terms, as defined by 21 CFR 312.32, apply to this  protocol. 
 
10.2.1. 
Adverse Event or Suspected Adverse Reaction 
An AE is defined as any untoward medical occurrence associated with the use of a drug/biologic 
in humans, whether or not it is considered to be related to the  drug/biologic. 
A suspected AR is any AE for which there is a reasonable possibility that the drug/biologic 
caused the AE. For the purposes of IND safety reporting, a “reasonable possibility” means there  
is evidence to suggest a causal relationship between the drug/biologic and the AE. Suspected AR 
implies a lesser degree of certainty about causality than AR, which means any AE caused by a 
drug/biologic. 
An AE or suspected AR is considered “life-threatening” if, in the view of either the investigator 
or sponsor, its occurrence places the patient or subject at immediate risk of death. It does not 
include an AE or suspected AR that, had it occurred in a more severe form, might have caused 
death. 
10.2.2. 
Serious Adverse Event or Serious Suspected Adverse  Reaction 
An AE is considered “serious” if, in the view of either the PI or sponsor, it results in any of the 
following outcomes: 
 Death; 
 A life-threatening AE; 
 Inpatient hospitalization or prolongation of existing  hospitalization; 
 Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions; or 
 Congenital anomaly/birth defect. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the patient or subject and may require medical or surgical intervention to prevent 
1 of the outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood  dyscrasias 

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or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
10.2.3. 
Unexpected Adverse Event or Unexpected Suspected Adverse  Reaction 
An unexpected adverse event (UAE) or unexpected suspected AR is an AE that is  not: 
 Listed in the Investigator’s Brochure (IB); 
 Listed at the specificity or severity that has been observed; or 
 Consistent with the risk information described elsewhere in the current application.   
For example, if the IB referred only to elevated hepatic enzymes or hepatitis as expected  AEs, 
under this definition, hepatic necrosis would be a UAE by virtue of the greater clinical severity. 
Similarly, if the IB only listed cerebral vascular accidents as an expected AE, the occurrence of 
cerebral thromboembolism and cerebral vasculitis would be a UAE by virtue of greater 
specificity. “Unexpected,” as used in this definition, also refers to AEs or suspected ARs that are 
mentioned in the IB as occurring with a class of drugs/biologics or as anticipated from the 
pharmacological properties of the drug/biologic, but are not specifically mentioned as occurring 
with the particular drug/biologic under investigation. 
10.2.4. 
Expected Adverse Events 
An expected AE is a predetermined event, identified in the IB. The following expected AEs for 
this study include: 
 Pain, bleeding, bruising, scarring, and local infection associated with fingerstick blood 
sampling procedures; 
 Pain/soreness, bruising, discoloration, swelling, blood clot or bleeding, nerve damage, 
arterial puncture, local infection, dizziness, light-headedness, syncope, fatigue, iron 
deficiency with or without anemia associated with  venipuncture; 
 Blood loss from the inability to return RBCs during automated plasmapheresis 
procedures; 
 Tingling of lips or fingers or muscle cramping, spasms, seizures, tetany, cardiac 
arrhythmia due to the citrate anticoagulant used in an automated plasmapheresis 
procedure; 
 Allergic reactions such as flushing, itching, hives, abdominal cramps, difficulty 
breathing, chest pain, or bronchospasm, which may vary in severity from mild to life- 
threatening associated with both plasmapheresis donation and plasma  infusion; 
 Nausea, unpleasant taste, vomiting, light-headedness, fainting, malaise, or seizures 
associated with both plasmapheresis donation and plasma  infusion; 
 Non-immunologic complications such as the transmission of infectious agents, bacterial 
sepsis, transfusion-associated circulatory overload, hypothermia-cardiac  arrhythmias; 
 Metabolic complications such as citrate toxicity-hypocalcemia, acidosis, alkalosis, hyper- 
or-hypokalemia, and coagulopathies; and 

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 Transfusion reactions. 
10.2.5. 
Unanticipated Problems Involving Risks to Subjects or  Others 
Federal regulations require that unanticipated problems involving risks to subjects or others be 
promptly reported to the IRB. These events encompass a broader category of events than SAEs, 
and may include issues such as problems with loss of control of subject data or the 
investigational product; adverse psychological reactions; or breach of confidentiality. Risks to 
others (eg, program personnel) must also be  reported. 
Unanticipated problems involving risks to subjects or others are any incident, experience, or 
outcome that meets all of the following criteria: 
 Unexpected (in terms of nature, severity, or frequency) given (a) the procedures that are 
described in the protocol, IB, or informed consent document; and (b) the characteristics of 
the subject population; 
 Related or possibly related to a subject’s participation in the study;  and 
 Suggests that the study places subjects or others at a greater risk of harm than was 
previously known or recognized. 
The clinical site’s IRB and the USAMRMC’s HRPO will evaluate the PI’s and RM’s reports to 
determine whether or not a given incident, experience, or outcome constitutes an unanticipated 
problem involving risk to subjects or others, and will ensure reporting of the unanticipated 
problems involving risk to subjects or others to the appropriate regulatory offices, as  applicable. 
 
10.3. 
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 A PHYSICIAN 
CAN MAKE THIS DETERMINATION: 
Not related: There is no reasonable causal relationship between the  investigational product 
administered and the SAE. Applies to those events for which an alternate etiology  exists. 
Unlikely: Likely unrelated to the investigational product. Likely to be related to factors 
other than investigational product, but cannot be ruled out with  certainty. 
Possible:   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 subject’s clinical status or underlying factors including 
other therapy. 
Probable: 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 subject’s clinical state or factors including other  therapy. 

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Definite: An association exists between the receipt of an investigational product and the 
event. An association to other factors has been ruled  out. 
10.4. 
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 PI will use the CDC National Healthcare Safety Network 
Hemovigilance Module criteria (Appendix I) to define transfusion-related AEs.. The NCI 
Common Terminology Criteria 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. 
The eCRF for AEs will reflect only the highest severity for continuous days an event  occurred. 
 
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 
Potentially life threatening or life-threatening and 
requires hospitalization, emergency room visit, or 
urgent intervention 
Fatal 
Grade 5 
Death 
The terms “serious” and “severe” are not synonymous. The term “severe” describes the intensity 
of a specific event (eg, mild, moderate, or severe headache), whereas the event itself may not  
meet the seriousness criteria. 
If a subject is evaluated in an emergency room for non-life-threatening illness or symptoms (i.e., 
visits emergency department on weekend for mild problems because the physician’s office is 
closed), the information from that visit will be reviewed and severity of the AE will be assessed 
according to the subject’s clinical signs and symptoms. 
As defined by the ICH guideline for GCP, the term “severe” is often used to describe intensity 
(severity) of a specific event (as in mild, moderate, or severe myocardial infarction); the event 
itself however, may be of relatively minor medical significance (such as severe headache). This 
is not the same as “serious,” which is based on subject/event outcome or action criteria usually 
associated with events that pose a threat to a subject’s life or functioning. Seriousness (not 
severity) serves as a guide for defining regulatory reporting  obligations. 
 
10.5. 
Recording and Reporting Adverse Events 
Section 6.6.3 presents procedures to request unblinding of a subject’s randomization code due to  
a medical emergency or serious medical condition. 

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10.5.1. 
Methods and Timing for Assessing, Recording, and Analyzing Adverse  Events 
All AEs will be assessed at all study visits, documented in the source records, and recorded on 
the eCRFs using accepted medical terms and/or the diagnoses that accurately characterize the 
event. When a diagnosis is known, the AE term recorded on the eCRF will be the diagnosis 
rather than a constellation of symptoms. The PI will assess and record for all AEs/SAEs: a 
description of the event (if the event consists of a cluster of signs and symptoms, a diagnosis 
should be recorded rather than each sign and symptom); onset date and time, and stop date and 
time; intensity (recorded as mild, moderate or severe); seriousness; causality (relationship to 
study drug); outcome (eg, resolved, resolved with sequelae, not resolved, fatal, or unknown if 
applicable); action taken with the study agent (eg, no action, study agent discontinued and other 
action taken). 
When an event is not resolved by study closure, it will be documented on the AE eCRF as “"not 
recovered/not resolved". 
AEs will be assessed using an open-ended question such as: “How have you been feeling since  
we last spoke?” If an AE that requires medical attention is reported to a nurse, it should be 
reported to a study physician immediately. The PI or study physician will assess subjects for any 
medical side effects, through a focused review of systems and physical exam. Specifically, they 
will be looking for evidence of coagulation disturbances. Subjects with suspected positive 
findings will be referred to their treating physicians for clinically indicated and appropriate 
evaluation and management. Acute plasma infusion reactions will also be specifically 
documented as follows: 
 Fever (by oral or axillary temperature); 
 Allergic reactions (i.e., skin rash; urticarial; pruritus; generalized flushing; localized 
angioedema; edema of the lips, tongue, or uvula; erythema of the periorbital area; 
conjunctival edema by physical exam); 
 Bronchospasm (by symptoms); 
 Chills (by subject report after specific query by clinical staff); 
 Tachycardia, bradycardia, other dysrhythmias, dyspnea, hypertension, hypotension (by 
vital sign measurements – heart rate, blood pressure, and respiration  rate); 
 Hemolysis or acute hemolytic transfusion reactions resulting in circulatory/cardiovascular 
dysfunction (by clinical laboratory result); and 
 Infection (by physical exam or clinical laboratory results). 
The timeframe for the collection of AEs will begin at plasma collection and will continue   
through 7 days after the last required sample collection (Day 29). Any AE, regardless of its 
relationship to study product, will be recorded in the AE section of the eCRF. However, any AE 
that occurs after the informed consent is signed, but before the first infusion visit, will be  
recorded as medical history, unless it is related to a study procedure. AEs associated with a study 
procedure (eg, blood or plasma donation) will be recorded in the AE section of the  eCRF. 

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10.5.2. 
Duration of Follow-Up of Subjects after an Adverse  Event 
PIs are required to follow SAEs to resolution, even if this extends beyond the prescribed 
reporting period or until study closure. Resolution is the return to baseline status or stabilization 
of the condition with the probability that it will become chronic. The SAE outcomes will be 
reported to the sponsor’s Representative using the Serious Adverse Event Report Form 
(Appendix J). 
Follow-up should be emailed to usarmy.detrick.medcom-usammda.mbx.sae-reporting@mail.mil 
or faxed using a new SAE Reporting Form. The follow-up form should state “this is a follow-up 
to the previously reported SAE” and provide the date of the original report. Each reoccurrence, 
complication, or progression of the original event should be reported as a follow-up to that event 
regardless of when it occurs. The follow-up information should describe whether the event has 
resolved or continues, if and how it was treated, and whether the participant continued or 
withdrew from study participation. 
PIs are not obligated to actively seek SAEs in former subjects; however, if an SAE, considered to 
be related to the investigational product is brought to the attention of the PI at any time following 
completion of the study, the event will be reported to the sponsor’s safety office as defined in 
section 10.6.1. 
10.6. 
Reporting Adverse Events 
The PI will report all AEs to the sponsor (USAMRMC ORA) and the local IRB in the   
appropriate safety, annual, and/or final reports. After appropriate data cleaning and query 
resolution between the clinical site, Clinical Monitor, and Clinical Data Manager, AEs marked as 
“serious” in the clinical database will be reconciled with the sponsor’s SAE database. SAEs and 
AEs for inclusion in annual and final reports to the FDA will be provided from the clinical 
database by the Clinical Data Manager. 
10.6.1. Reporting Serious Adverse Events 
All SAEs must be reported promptly (within 24 hours of discovery of the event) to the sponsor’s 
safety office as per 21 CFR 312.64 whether or not they are considered related to the study 
product. The completed SAE Reporting Form must be emailed to usarmy.detrick.medcom- 
usammda.mbx.sae-reporting@mail.mil or faxed within 24 hours of discovery of the  event. 
Further, the investigator will comply with relevant study site SOPs on reporting SAEs to the 
IRB. 

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Contact information for reporting SAEs is provided in Table  13. 
Table 13: 
Study Contacts for Reporting SAEs Involving Risk to Subjects or  Others 
Sponsor’s Safety Office 
USAMRMC ORA 
ATTN: MCMR-UMR 
1430 Veterans Drive 
Fort Detrick, MD 21702-5009 
Fax: 301-619-7790 
Telephone: 301-619-1106 
Email: usarmy.detrick.medcom-usammda.mbx.sae- 
reporting@mail.mil 
IRB 
University of Cincinnati 
University Hall, Suite 300 
51 Goodman Drive 
PO Box 210567 
Cincinnati, OH 45221-0567 
Telephone: 513-558-5259 
Email: irb@ucmail.uc.edu 
USAMRMC Office of Research 
Protections 
HRPO 
U.S. Army Medical Research and Materiel Command 
ATTN: MCMR-RPH 
504 Scott Street 
Fort Detrick, MD 21702-5012 
Fax: 301-619-7803 
Telephone: 301-619-2165 
Email:   usarmy.detrick.medcom-usamrmc.other.hrpo@mail.mil 
Research Monitor 
Matthew Montgomery, MD 
Hoxworth Blood Center 
University of Cincinnati 
3130 Highland Avenue, Cincinnati, OH  45267 
Telephone: 513-558-1339 
Fax: 513-558-1341 
Email: montgmw@ucmail.uc.edu 

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Table 14: 
SAE Information to be Reported to the Sponsor’s Safety  Office 
Notification Method 
Information to be Provided 
Email or Fax 
(within 72 hours) 
Cover sheet or letter containing: IND number, sponsor study number, name 
of the investigational product, investigator name, and contact  number 
Subject identification number 
Sponsor approved SAE Report Form documenting: SAE term and 
description, onset date, date(s) of investigational product administration, 
severity, relationship to study product, and subject’s current  status 
Concomitant medication CRF or a list of concomitant medications taken 
within 30 days of SAE onset 
Medical history Case Report Form 
Discharge summary and/or medical record progress notes, History and 
Physical, pertinent laboratory/diagnostic test  results 
 
 
NOTE: When submitting SAE reports via email, the subject line of each email notification will read as 
follows: 
SAFETY REPORT – IND #  
_, Sponsor Study #  
_, Subject #  
, Event term:   
 
To comply with regulations mandating sponsor notification of specified SAEs to the FDA within  7 
calendar days, the PI must submit additional information as soon as it is available. The sponsor or 
designee will report unexpected SAEs associated with the use of the study product to the FDA as 
specified at 21 CFR 312.32 (c). 
The PI must follow all relevant regulatory requirements as well as specific policy regarding the 
timely reporting of SAEs to the RM, the local IRB, and the USAMRMC  ORP. 
Reporting to the sponsor’s safety office does not fulfill the PI’s duty to report all unanticipated 
problems involving risk to human subjects or others to the IRB. The PI will notify the local IRB, 
the USAMRMC ORP, and the RM. 
 
10.6.2. 
Reporting to the IRB 
Unanticipated problems involving risk to subjects or others, SAEs related to participation in the 
study, and all subject deaths related to participation in the study should be promptly reported by 
the PI via telephone, email, or fax to the local IRB and/or USAMRMC HRPO. A complete 
written report should follow the initial notification. 
The PI is required to forward safety information provided by the sponsor or designee to the IRB, 
following the institutional policies. 
 
10.6.3. 
Reporting Additional Immediately Reportable Events to the Sponsor’s Safety 
Office 
 
10.6.3.1. 
Pregnancy 
Each pregnancy (for subjects and for female partners of participating male subjects) must be 
reported by the PI within 72 hours of identification by emailing the Pregnancy Report  Form 

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(FORM.5.2.4) (Appendix K) to the sponsor’s safety office (ORA). The incident must also be 
reported to the local IRB and/or the USAMRMC ORP in accordance with the IRB  policy. 
Subjects who become pregnant after receipt of investigational product will be withdrawn from  
the study and followed to term. The following information will be gathered, documented, and 
reported on the follow-up Pregnancy Report Form: outcome; date and type of delivery; APGAR 
scores; and health status of mother and child, including the child’s gender, height, and weight. 
Complications and/or abnormal outcomes should be reported including any premature 
terminations, and are to be followed as above under the AE section. A pregnancy is reported as  
an AE or SAE only when there is suspicion that the investigational product may have interfered 
with the effectiveness of contraception or there was a serious complication in the pregnancy, 
including a spontaneous abortion, an elective termination for medical rationale, or the infant has  
a congenital anomaly/birth defect. 
 
10.6.3.2. 
AE-Related Withdrawal of Consent 
Any AE-related withdrawal of consent during the study must be reported by the PI immediately 
(within 72 hours of identification) by email or fax to the sponsor’s representative, CRO’s PI. 
The incident must also be reported to the local IRB and/or the USAMRMC ORP in accordance 
with the IRB policy. 
 
10.6.4. 
Pending Inspections/Issuance of Reports 
The knowledge of any pending compliance inspection/visit by the FDA, Office for Human 
Research Protections, HHS, or other government agency concerning clinical investigation or 
research, the issuance of Inspection Reports, FDA Form 483, warning letters, or actions taken by 
any regulatory agency including legal or medical actions and any instances of serious or 
continuing noncompliance with the regulations or requirements will be reported immediately to 
the local IRB and/or the USAMRMC ORP. 
 
10.6.5. 
IND Annual Report to the FDA 
The sponsor or designee will be responsible for the preparation of a detailed annual synopsis of 
clinical activity, including AEs. The sponsor or designee will deliver the annual report to the 
FDA. Each annual report will summarize IND activity for 1 year beginning  approximately 
3 months before the IND FDA anniversary date. The report will include, but is not limited to, 
summaries of all reported SAEs, submitted IND safety reports, number of subject withdrawals 
with reasons, updates to the general investigation plan, updates to the IB, and any protocol 
updates. The sponsor’s representative or designee will notify the PI of the due date allowing 
sufficient time to assemble the required information. 
 
10.6.6. 
Final Report 
A final study report will be prepared by the sponsor’s representative or designee in accordance 
with “Guidance for Industry: Submission of Abbreviated Reports and Synopses in Support of 
Marketing Applications” and ICH E3 Guideline “Structure and Content of Clinical Study 
Reports.” 
The report will provide a description of the conduct of the study and will be accompanied by 
tables, listings, and figures (displaying all study data and  results). 

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This final report will be submitted to the FDA. 
The clinical site’s local IRB may request a summary of study activities on a regular basis. The 
sites should comply with their local IRB requirements for the submission of safety, annual, 
and/or final reports. 
 
11. 
STATISTICS 
Detailed statistical procedures, listings, table shells, and figures will be provided in a separate 
statistical analysis plan (SAP). The SAP will be finalized before study close-out and database 
lock. The following key statistical components will be considered and a detailed description will 
be documented in the SAP: 
 Primary and secondary endpoints and how they will be  measured; 
 Statistical methods and tests that will be used to analyze the endpoints;  and 
 Planned exploratory analyses and justification of their  importance. 
11.1. 
Description of Statistical Methods and Analysis 
The primary objective of this study is to assess the safety of single infusions with RePlas™ FDP 
product at increasing fixed doses of either 1 unit (approximately 270 mL), 2 units (approximately 
540 mL), or 3 units (approximately 810 mL) in normal healthy subjects. Safety will be assessed  
by evaluating vital signs, laboratory tests during and after infusion, FDP-related AEs. No formal 
statistical hypotheses will be tested. Demographics, medical history, and safety data will be 
summarized for each cohort using standard descriptive statistics. For quantitative variables, 
summaries will include the sample size, mean, median, standard deviation, minimum, maximum 
and 25th and 75th percentile. For categorical variables, summaries will include the frequency (eg, 
number and percent) of subjects for each outcome. Additional analytic data will be prepared and 
summarized using only Cohort 3 data to address the study’s secondary  objectives. 
The demographic and subject disposition tables will include all 5 populations per Section 11.7. If 
it is shown that both full populations include the same subjects, only one table will be produced 
with the title indicating that it represents both full populations. AE tables that display overall AE 
incidence will include all 5 populations. Tables that are restricted to TEAEs will include the  
safety populations only. Study drug exposure will be presented in the first safety population. All 
other analyses will be performed in the third safety population  only. 
After the completion of each cohort and at the conclusion of the study, the DSMB will review all 
subjects’ cumulative safety data and make a recommendation to the sponsor on whether or not to 
proceed to the next cohort and for cohort 3 to proceed with conducting the next planned FDP   
trial protocol. 
11.1.1. 
Endpoints for Primary Study Objective Analyses 
The primary endpoints for the study to be assessed are  specifically: 
 TEAEs; 
 SAEs; 

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 Suspected, unexpected, serious adverse reactions (SUSARs);  and 
 Deaths. 
Safety endpoints for subjects’ that will be assessed just prior to infusion and again after 
infusion include evaluations presented in sections 8.2 and  8.3. 
Descriptive statistics will be used to analyze the primary safety endpoints. Tables produced to 
exhibit the primary safety endpoint data will be presented by the specific type of plasma product 
infused. In Cohorts 1 and 2, this data will be presented by FDP product type, FDP-ACD and 
FDP-CPD; in Cohort 3 by experimental product and control product, FDP-ACD and FFP. The 
primary safety data reported to the DSMB for Cohort 3 will be masked. Unblinding during the 
study will only occur in accordance with section 6.6.3. 
In general, AEs that occur in Cohort 3 subjects within 14 days after infusion will be attributed to 
the most recently infused product. However, there may be exceptions to use of this temporal 
attribution rule to all transfusion-related AEs given the possibility that those AEs that occur after 
infusion with the second product may potentially be related to infusion with the first infusion 
product (e.g., an immunogenic response). 
The safety endpoints measured prior to the infusion will serve as the “baseline” to which all 
subsequent measurements will be compared. 
11.1.2. 
Endpoints for Secondary Study Objectives  Analyses 
 
11.1.2.1. 
Safety Analyses Comparing FDP to FFP (Secondary Objective  #1): 
Using Cohort 3 data, descriptive statistics similar to those described in section 11.1.1 will be 
presented for the change between baseline and each time point, where appropriate, of the safety 
endpoint measures shown in Table 15. Descriptive statistics will be provided for each type of 
plasma product treatment, treatment period, and treatment sequence arm (FDP-ACD then FFP 
[Sequence 1] or FFP then FDP-ACD [Sequence 2]). The mean and standard deviation at each 
time point for each treatment group, based on the original values, will be exhibited in  figures. 
Color-coded spaghetti plots will display by treatment group individual data for each subject over 
time. 
Definitions for Secondary Objectives: 
 Change from baseline: (Post-baseline value – baseline  value); 
 Body mass index (kg/m2): (weight (kg)/(height (cm) *100)2;  and 
 Total amount administered per kg of weight (ml/kg): total amount administered 
(ml)/weight (kg). 
The secondary endpoints for this study and associated time points for analysis are listed in 
Table 15. 

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Table 15: 
Secondary Safety Endpoints and Scheduled  Measurements 
Safety Endpoints 
 
 
Pre-Infusion 
 
 
0.5 
Post-Infusion 
4 Hours 
24 Hours 
28-Day 
Hours 
Vital Signs 
Blood Pressure 
X 
X 
X 
Heart Rate 
Respiration Rate 
X 
X 
X 
X 
X 
X 
Temperature 
X 
X 
X 
Urinalysis: 
Specific gravity 
X 
X 
X 
pH 
Glucose 
X 
X 
X 
X 
X 
X 
Ketones 
Protein 
X 
X 
X 
X 
X 
X 
Blood 
Leukocyte esterase 
X 
X 
X 
X 
X 
X 
Nitrite 
Bilirubin 
Urobilinogen 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CBC 
Hematocrit 
X 
X 
X 
X 
Hemoglobin 
X 
X 
X 
X 
Platelet Count 
X 
X 
X 
X 
RBC Count 
X 
X 
X 
X 
WBC Count 
DAT (IgG and C3) 
X 
X 
X 
X 
X 
X 
Clinical Chemistry 
ALP 
X 
X 
X 
ALT 
X 
X 
X 
AST 
Ionized Calcium 
Total Magnesium 
pH 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Safety Endpoints 
 
Pre-Infusion 
 
0.5 
Post-Infusion 
4 Hours 
24 Hours 
28-Day 
Hours 
Electrolytes (Calcium, Chloride, 
Potassium, Sodium, Lactate, and 
Bicarbonate) 
X 
X 
X 
Glucose 
X 
X 
X 
Total Bilirubin 
X 
X 
X 
Total Protein 
X 
X 
X 
BUN 
X 
X 
X 
Creatinine 
X 
X 
X 
Coagulation Tests 
PT 
X 
X 
X 
X 
X 
INR 
X 
X 
X 
X 
X 
aPTT 
X 
X 
X 
X 
X 
D-dimer 
X 
X 
X 
X 
Cohort 3 safety analyses will also include measurements taken at each Infusion Visit at 
the following post-infusion time points. 
Factor I 
X 
X 
X 
Factor II 
X 
X 
X 
Factor V 
X 
X 
X 
Factor VII 
X 
X 
X 
Factor VIII 
X 
X 
X 
Factor IX 
X 
X 
X 
Factor X 
X 
X 
X 
Factor XI 
X 
X 
X 
von Willebrand Factor activity 
X 
X 
X 
Protein C activity 
X 
X 
X 
Protein S activity 
X 
X 
X 
PF 1+2 
X 
X 
TAT 
X 
X 
Antithrombin III 
X 
X 
Alpha-2 Antiplasmin 
X 
X 
C3a des Arg 
X 
X 

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11.1.2.2. 
Exploratory Analyses Comparing FDP to FFP (Secondary Objective  2) 
The analyses conducted for secondary objective 1 will be used to meet secondary objective 2. In 
addition, descriptive statistics on a post-infusion, abnormal coagulation function assay that is 
greater than a 20% change in either direction from baseline for PT/INR and/or aPTT values will 
be presented using separate shift tables. Shift tables based on the upper limit of normal (ULN) 
will also be provided for D-dimer, PF 1+2, TAT, and C3a des  Arg. 
11.1.3. 
Safety Analyses 
AEs will be coded using the most recent version of the Medical Dictionary of Regulatory 
Activities preferred terms and will be grouped by system, organ, class designation  (SOC). 
AEs will be summarized using standard FDA-recommended templates distinguishing those 
defined as TEAEs. A TEAE will be defined as an AE that emerges during or following treatment 
(infusion), having been absent pretreatment. For all TEAEs, relatedness to infused product will   
be presented. TEAEs related to study treatment will be defined as definitely or probably related   
to study treatment. 
Use of the Centers for Disease Control National Healthcare Safety Network Hemovigilance 
Module criteria will ensure consistent definitions are applied when using transfusion-related   
event terms, such as transfusion related acute lung injury or transfusion associated circulatory 
overload. The National Cancer Institute Common Terminology Criteria will be used to assess all 
AEs for toxicity grade, or severity, regardless of whether the event is transfusion-related (HHS- 
2010). AEs will also be presented by maximum severity or maximum common terminology 
criteria for AE (CTCAE) grade (depending on collection). A summary of SAEs and a summary   
of AEs leading to treatment discontinuation will be presented. 
11.2. 
Planned Enrollment and Reason for Sample Size 
The sample size for this single-site study is set to 24. The primary objective of this study is to 
assess the safety of single infusions with the RePlas FDP product at increasing fixed doses of 
either 1 unit (approximately 270 mL), 2 units (approximately 540 mL), or 3 units (approximately 
810 mL) in normal healthy subjects. Safety will be measured using the following primary safety 
endpoints: AEs, TEAEs, SAEs, SUSARs, and deaths. The sample size was selected to reasonably 
balance the ability to address the study’s primary objective while minimizing the number of 
subjects potentially at risk. Precision estimates were calculated using different safety outcome 
incidence rates and different sample sizes as exhibited in Table 16. For example, in 24 subjects, a 
safety outcome with an incidence rate of 10% would have a 95% confidence interval of  1.6-
29.2% and a corresponding width=27.6 at a 2-sided alpha of 0.05. To account for subject attrition 
and for comparison purposes, a sample size of 20 and 28, are, respectively, included in Table 16. 
Concurrent infusions will not take place across cohorts ensuring infusions at the next higher dose 
do not begin until all subject infusions at the previous dose have been completed. The duration   
for which each cohort will remain active has been estimated based on the study schedule such   
that Cohorts 1 and 2 are expected to each be active for approximately 6 months and Cohort 3 will 
be active for approximately 7 months. 

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Sections 5.10 and 7.1 contain information on the capabilities of HBC to recruit the required 
number of subjects for this study. 
Table 16: 
Precision Estimates Based on Safety Outcome Incidence Rates  and Sample 
Size 
 
Sample Size 
Incidence 
10% 
25% 
50% 
20 
(1.2-31.7) 
δ=30.5 
(8.7-49.1) 
δ=40.4 
(27.2-72.8) 
δ=45.6 
24 
(1.6-29.2) 
δ=27.6 
(9.8-46.7) 
δ=36.9 
(29.1-70.9) 
δ=41.8 
28 
(2.0-27.3) 
δ=25.4 
(10.7-44.9) 
δ=34.2 
(30.6-69.4) 
δ=38.7 
11.3. 
Level of Significance 
The level of significance does not apply since no statistical testing will be done in this  study. 
 
11.4. 
Interim Analysis and Stopping Rules 
The SRs for the study are presented in section 6.5. No interim analysis is planned for this  study. 
At the conclusion of each cohort and after Cohort 3 study activities, the DSMB will review all 
patient safety data and make a recommendation to the sponsor on whether to proceed with dose 
escalation in the subsequent cohort and after cohort 3 with the next planned FDP trial protocol as 
mentioned in section 11.1. No adjustment for multiple testing is necessary since no statistical 
hypotheses are being tested. (The planned descriptive analyses are described in section  11.1.) 
11.5. 
Accounting for Missing, Unused, and Spurious Data 
Non-analyzable data will be documented in the deviations and reported in the final clinical study 
report. 
For summary descriptive statistics, missing data will be represented by  counts. 
 
11.6. 
Procedures for Reporting Deviations from the Original Statistical Plan 
Any deviation(s) from the original statistical plan as indicated in the protocol will be described in 
an amendment to the protocol and the SAP. Deviations from the SAP will be documented in 
accordance with the data management center’s SOPs. 
11.7. 
Selection of Subjects to be Included in Analyses 
Healthy male and female volunteers determined to be acceptable WB or plasmapheresis donors 
based on FDA regulations and responses to the AABB donor history questionnaire (Appendix B) 
of the protocol) are eligible to provide study consent. In addition, the study considers those 
deferred from donating due only to travel, as outlined by the AABB donor history  questionnaire, 

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as eligible to consent for potential study enrollment. All subjects subsequently enrolled must 
meet the study inclusion and exclusion criteria, detailed in sections 7.4 and 7.5 of the  protocol. 
There will be 5 analysis populations for this study, 2 full analysis populations, and 3 safety 
populations. 
The full analysis population encompasses all enrolled subjects, including those who  were: 
 Enrolled but withdrawn from the study prior to the Infusion Visit and were never 
infused; and 
 Enrolled and presented for treatment at the Infusion Visit (includes infused and not 
infused). 
The 3 subject populations for assessing safety are those  who: 
 Received any volume of infused product (ie, In Cohort 3 subjects this includes those 
who received a partial dose at either Infusion Visit); 
 Received the full infusion dose and had at least one outcome measure;  and 
 Received the full infusion dose and can be fully evaluated  because: 
 Cohort 1 and 2: the subjects completed, at a minimum, the 7-Day Follow-Up 
Visit; and 
 Cohort 3: the subjects had both complete infusion doses and completed, at a 
minimum, the 7-Day Follow-Up Visit after the second  infusion. 
 
12. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
Subjects will be identified on eCRFs by a unique subject identification number and on source 
documents by name and date of birth. No personal identifier will be used in any publication or 
communication used to support this research study. The subject identification number will be  
used if it becomes necessary to identify data specific to a single subject. Representatives of 
USAMRMC, the sponsor’s representative, the local IRB, the USAMRMC ORP, and the FDA   
are eligible to review medical and research records related to this study as a part of their 
responsibility to protect human subjects in clinical research. Personal identifiers will be removed 
from photocopied medical and research records. Study results will not be given to individual 
subjects, but will be published in the open literature and made available as a matter of public 
record. 
12.1. 
Study Monitoring 
Study monitoring will be the responsibility of the USAMRMC USAMMDA ORA designee, an 
independent contract research organization. Upon successful approval of the protocol and 
establishment of the regulatory file, the clinical monitor will establish a clinical monitoring plan. 
To ensure that the PI and the study staff understand and accept their defined responsibilities, the 
clinical monitor will maintain regular correspondence with the clinical site and may be present 
during the course of the study to verify the acceptability of the facilities, compliance with the 
investigational plan and relevant regulations, and the maintenance of complete  records. 

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Monitoring visits by a sponsor’s representative-designated clinical monitor will be scheduled to 
take place at the initiation of the study, during the study at appropriate intervals, and after the last 
subject has completed the study. A report of monitoring observations will be provided to the PI 
(for corrective actions), USAMRMC USAMMDA ORA, USAMMDA Office of Quality 
Management, and the Product Manager. 
12.2. 
Audits and Inspections 
Authorized representatives of the sponsor, the FDA, and the IRB may visit the clinical site to 
perform audits or inspections, including source data verification. The purpose of the audit or 
inspection is to systematically and independently examine all study-related activities and 
documents to determine whether or not these activities were conducted, and data were recorded, 
analyzed, and accurately reported according to the protocol, GCP guideline of the ICH, and any 
applicable regulatory requirements. 
The PI should contact the sponsor’s representative and ORP HRPO immediately if contacted by  
a regulatory agency about an inspection. 
12.3. 
Institutional Review Board 
The HBC IRB will serve as the responsible IRB and will review the protocol, informed consent, 
and progress reports on a continuing basis in accordance with all applicable regulations, 
including Title 21 CFR 50 and 56. 
The PI must obtain IRB approval for the study. Initial IRB approval, and all materials approved 
by the IRB for this study, including the subject consent form and recruitment materials, must be 
maintained by the PI and made available for inspection. 
The PI will be responsible for preparing and submitting continuing review reports per institution 
and IRB requirements. The PI or a designee will transmit the approved final study report to the 
IRB as soon as the documents are available. 
 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with GCP and all applicable regulatory requirements, the sponsor’s 
Representative may conduct quality assurance audits. Refer section 12.2 for more details 
regarding the audit process. 
Auditing of the clinical trial may be conducted at any time during the study to ensure continued 
compliance with regulations, policies, and procedures. Auditing will be undertaken, as needed,  
by independent personnel designated by the Office of Quality Management, USAMMDA. Audit 
findings will be documented in a formal audit report that will detail the conduct of the audit and 
summarize the observations noted. 

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14. 
ETHICS 
14.1. 
Ethics Review 
The study is based on adequately performed laboratory and animal experimentation and will be 
conducted under a protocol reviewed by the local IRB and ORP. The study is to be conducted by 
scientifically and medically qualified persons. The IRB will determine whether or not the   
benefits of the study are in proportion to the risks. The rights and welfare of the subjects will be 
respected; the physicians conducting the study will ensure that the hazards do not outweigh the 
potential benefits; the results to be reported will be accurate; subjects will give their informed 
consent and will be competent to do so and not under duress; and all study staff will comply with 
the ethical principles in 21 CFR Part 50 and the Belmont  Principles. 
14.1.1. 
Review/Approval of Study Protocol 
Before a clinical study can be initiated, the study protocol and other required documents will be 
submitted to the following departments in the order listed for review and/or approval, with the 
final review by the FDA: 
 Integrated Product Team; 
 Sponsor’s Representative Team (USAMRMC USAMMDA  ORA); 
 Local IRB and the ORP; 
 Sponsor’s Representative (acting for The Surgeon General [TSG] of the Army);  and 
 USAMRMC Commanding General, if applicable. 
Enrollment in this protocol may not begin until all approvals have been obtained and the formal 
authorization letter is received by the PI from the sponsor’s  representative. 
 
14.1.2. 
Protocol Modifications 
All modifications to the protocol and supporting documents (informed consent, study-specific 
procedures, SOPs, recruitment materials, etc.) must be reviewed and approved prior to 
implementation. Any protocol amendment will be agreed upon and approved by the sponsor’s 
representative prior to submission to the local IRB and prior to implementation of said change or 
modification. Any modification that could potentially increase risk to subjects must be submitted 
to USAMRMC ORP and the FDA prior to implementation. The ICF must be revised to concur 
with any amendment as appropriate and must be reviewed and approved with the  amendment. 
Any subject already enrolled in the program will be informed about the revision and asked to 
sign the revised informed consent document if the modification directly affects the individual’s 
participation in the program. A copy of the revised, signed, and dated informed consent 
document will be given to the subject. All original versions of the informed consent document 
will be retained in the protocol regulatory file, and a copy will be retained in the protocol 
regulatory file. 
14.1.3. 
Protocol Deviation Procedures 
All deviations from the protocol (eg, failure to return for follow-up visits or blood collection 
within the time indicated in the protocol) are to be documented. The PI or designee will  be 

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responsible for identifying and reporting all deviations, which are defined as isolated occurrences 
involving a procedure that did not follow the study protocol. Deviations will be reported    
annually in the continuing review report to the local IRB and the ORP and, if appropriate, in the 
final study report. Action taken in response to the deviation, and the impact of the deviation will  
be assessed by the PI and recorded as significant or  nonsignificant. 
Any protocol deviation that adversely affects the safety or rights of a subject or scientific   
integrity of the study will be reported immediately to the sponsor’s representative, local IRB, and 
the ORP. 
14.2. 
Ethical Conduct of the Study 
This study will be conducted in accordance with all applicable Federal and DoD human research 
protections requirements and the Belmont Principles of respect for persons, beneficence, and 
justice. 
The procedures set out in this study are designed to ensure that the sponsor’s representative and 
all study personnel abide by the principles of the ICH GCP guideline and the CFR. The PI 
confirms this by signing this study protocol and the Form FDA  1572. 
14.2.1. 
Confidentiality 
The Health Insurance Portability and Accountability Act (HIPAA) requires that researchers 
obtain the subject’s permission (HIPAA Authorization) to use and disclose health information 
about the subject that is either created by or used in connection with this research. The 
information includes the entire research record and supporting information from the subject’s 
medical records, results of laboratory tests, and both clinical and research observations made 
during the individual’s participation in the research. 
In this research, the subject’s health information will be collected and used to conduct the study;  
to monitor the subject’s health status; to measure effects of the investigational product; to 
determine research results; and possibly to develop new tests, procedures, and commercial 
products. Health information is used to report results of research to the sponsor’s representative 
and Federal regulators and may be reviewed during study audits for compliance with study plans, 
regulations, and research policies. After the study ends, each subject has the right to see and 
receive a copy of his or her information. 
Representatives of the TSG as the IND sponsor, the sponsor’s representative, the local IRB, the 
ORP, the DoD, and the FDA are eligible to photocopy and review records related to this protocol 
as a part of their responsibility to protect the subjects of this protocol. In addition, these 
representatives are eligible to witness the applicable study procedures to ensure the safety of 
subjects. 
No personal identifier will be used in any publication or communication used to support this 
research study. The subject’s identification number will be used in the event it becomes 
necessary to identify data specific to a single subject. 
14.2.2. 
Compensation for Participation 
Subjects will be compensated for time and travel expenses for participating in this study in 
accordance with local IRB policies and as described in the  ICF. 

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14.2.3. 
Medical Care for Research-Related Injury 
All non-exempt research involving human subjects shall, at a minimum, meet the requirement of 
32 CFR 219.116(a)(6). 
If a subject is injured because of participation in this research, emergency medical care will be 
provided. However, since there is no reimbursement available by the Department of Defense 
(DoD) or the non-DoD clinical site for medical expenses incurred to treat research-related 
injuries, subjects or their individual insurance companies may be responsible for these medical 
expenses. Subjects are waiving no legal rights by participation in the study and will only be 
treated for injuries directly caused by the research study. 
14.3. 
Written Informed Consent 
The informed consent process and document will be reviewed and approved by the local IRB 
and/or the ORP and sponsor’s representative prior to initiation of the study. The consent 
document contains a full explanation of the possible risks, advantages, and alternate treatment 
options, and availability of treatment in the case of injury, in accordance with 21 CFR 50. The 
consent document indicates that by signature, the subject, or where appropriate, legal guardian, 
permits witnessing of applicable study procedures by the sponsor’s representative, as well as 
access to relevant medical records by the sponsor’s representative and by representatives of the 
FDA. The sponsor’s representative will submit a copy of the initial IRB- and sponsor’s 
representative-approved consent form to the FDA and will maintain copies of revised consent 
documents that have been reviewed and approved by the local IRB and/or the  ORP. 
A written informed consent document, in compliance with 21 CFR Part 50, 32 CFR Part 219,    
and the Belmont Principles and HIPAA Authorization will be signed by the subject before any 
study-related procedures are initiated for that subject. This consent document must be retained by 
the PI as part of the study records. Each subject will receive a copy of the signed informed  
consent document. The PIs or their designees will present the protocol in lay terms to individual 
subjects. Questions on the purpose of the protocol, protocol procedures, and risks to the subjects 
will then be solicited. Any question that cannot be answered will be referred to the PI. No subject 
should grant consent until questions have been answered to his or her satisfaction. The subject 
should understand that the study product is an investigational drug and is not licensed by the    
FDA for commercial use, but is permitted to be used in this clinical research. Informed consent 
includes the principle that it is critical the subject be informed about the principal potential risks 
and benefits. This information will allow the subject to make a personal risk versus benefit 
decision and understand the following: 
 Participation is entirely voluntary; 
 Subjects may withdraw from participation at any time; 
 Refusal to participate involves no penalty; and 
 The individual is free to ask any questions that will allow him or her to understand the 
nature of the protocol. 
Should the protocol be modified, the subject consent document must be revised to reflect the 
changes to the protocol. If a previously enrolled subject is directly affected by the change,  the 

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subject will receive a copy of the revised informed consent document. The approved revision 
will be read, signed, and dated by the subject. 
The subject will be informed that a description of this clinical trial will be available on 
http://www.ClinicalTrials.gov, as required by US law. 
 
15. 
DATA HANDLING AND RECORDKEEPING 
The primary source document for this study will be the subject’s medical record. If separate 
research records are maintained by the PI(s), the medical record and the research records will be 
considered the source documents for the purposes of auditing the study. The source documents 
will be retained at the clinical site. Any paper records will be stored in a locked file cabinet with 
access limited to the PI. A subject identification list will be maintained in a separate, secure  file. 
For this study, an Electronic Data Capture (EDC) database system will be used for the collection 
of the study data in an electronic format. The EDC database system will be designed based on   
the protocol requirements, the approved eCRF layouts and specifications, and in accordance with 
21 CFR Part 11. The eCRF layouts and specifications define and identify the applicable source 
data that will be collected and captured into the EDC database system. The applicable source data 
will be electronically transcribed by the clinical site designee onto the eCRF (data entry screens) 
in the EDC database system. The PI is ultimately responsible for the accuracy of the data 
transcribed on the eCRF. Data monitoring and management will be performed in the EDC 
database system by the study clinical monitor and the designated data management  group. 
A detailed data management plan will be written and approved by the study team and the PI prior 
to study start, with approval by the sponsor’s data manager in the USAMRMC USAMMDA  
ORA. All updates to the data management plan must be approved before study close-out and 
database lock. 
15.1. 
Inspection of Records 
The sponsor’s representative or designee will be allowed to conduct site visits at the 
investigation facilities for the purpose of monitoring any aspect of the study. The PI agrees to 
allow the clinical monitor to inspect the drug storage area, investigational product stocks, drug 
accountability records, subject charts, study source documents, and other records relative to 
study conduct. 
Subjects’ health information is used to report results of research to the sponsor’s representative 
and Federal regulators, and may be reviewed during study audits for compliance with study 
plans, regulations, and research policies. The consent document indicates that by signature, the 
subject permits access to relevant medical records by the sponsor’s representative and by 
representatives of the FDA. 
Upon a subject’s termination from the trial, completed eCRFs will be ready and available for on- 
site review by the sponsor’s representative or the designated representative within 14 days after 
receipt of the subject’s data. 

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15.2. 
Retention of Records 
The PI must maintain all documentation relating to the study for a period of 2 years after the last 
marketing application approval, or if not approved, for 2 years following the discontinuance of  
the investigational product for investigation. If it becomes necessary for the sponsor’s 
representative or designee or the FDA to review any documentation relating to the study, the PI 
must permit access to such records. 
Completed, monitored eCRFs will be stored in a secure location by the sponsor’s representative 
or designee. A copy of each completed eCRF will be retained by the  PI. 
The PI will be responsible for retaining sufficient information about each subject, including the 
name, address, telephone number, Social Security Number, and subject identifier in the study, so 
that the sponsor’s representative, the local IRB, the FDA, employees of USAMRMC, or other 
regulatory authorities may have access to this information, should the need  arise. 
It is the policy of USAMRMC that data sheets are to be completed for all subjects participating   
in research (Form 60-R, Volunteer Registry Data Sheet). The data sheets will be entered into this 
Command’s Volunteer Registry Database. The information to be entered into this confidential 
database includes the subject’s name, address, and Social Security Number; study title; and dates 
of participation. The intent of this database is twofold: first, to readily answer questions 
concerning an individual’s participation in research sponsored by USAMRMC; and second, to 
ensure that USAMRMC can exercise its obligation to ensure research subjects are adequately 
warned (duty to warn) of risks and to provide new information as it becomes available. The 
information will be stored at USAMRMC for a minimum of 75 years. The Volunteer Registry 
Database is a separate entity and is not linked to the study  database. 
 
16. 
PUBLICATION POLICY 
All data collected during this study will be used to support this IND. All data may be published   
in the open medical or military literature with the identity of the subjects protected. Anyone 
desiring to publish or present data obtained during the conduct of the study will conform to the 
author’s local publication review authority’s policies and then forward the publication for review 
to the Commander, USAMMDA or designee and usarmy.detrick.medcom- 
usamrmc.list.clearances@mail.mil prior to submission. 

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17. 
LIST OF REFERENCES 
AABB. Circular of information for the use of human blood and blood components [Internet]. 
AABB, 2013 [cited 2015 Oct 09]. Available from: 
https://www.aabb.org/tm/coi/Documents/coi1113.pdf. 
Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, et al. The ratio 
of blood products transfused affects mortality in patients receiving massive transfusions at a 
combat support hospital. J Trauma. 2007; 63:805-13. 
Cancelas J, Rugg N, Pratt P, Worsham N, Hartman E, Dunn S. A safety clinical trial of dose- 
escalation of autologous lyophilized plasma versus fresh frozen plasma in normal healthy 
subjects. American Association of Blood Banks (AABB) Annual Meeting; 2011 Oct 22-25; San 
Diego, CA: Abstract. 
Dart RC editor. Medical toxicology. 3rd ed. Philadelphia: Lippincott, Williams, and Williams; 
2004. 
Dupras D, Bluhm J, Felty C, Hansen C, Johnson T, Lim K, Maddali S, Marshall P, Messner P, 
Skeik N. Institute for Clinical Systems Improvement. Venous Thromboembolism Diagnosis and 
Treatment.http://bit.ly/VTE0113. Updated January 2013. 
eIT Times. Enterprise Information Technology Project Management Office Quarterly 
Newsletter; 2014 January [Internet] [cited 2015 Sept 28]. Available from: 
http://eitpmo.amedd.army.mil/newsletters/EITPMONewsletter201401.pdf. 
Gorlin JB. Cold is cruel cryogenic bag failure: multi-center survey & rheologic testing. J 
Hematotherapy. 1995; 4:224. 
Hmel PJ, Kennedy A, Quiles JG, Gorogias M, Seelbaugh JP, Morrissette CR. Physical and 
thermal properties of blood storage bags: implications for shipping frozen components on dry 
ice. Transfusion. 2002; 42(7):836-46. 
Holcomb JB, Jenkins D, Rhee P, Johannigman J, Mahoney P, Mehta S, et al. Damage control 
resuscitation: directly addressing the early coagulopathy of trauma. J Trauma. 2007; 
62(2):307-10. 
Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, et al. Transfusion of 
plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with 
severe trauma: the PROPPR randomized clinical trial. JAMA. 2015;  315(5):471-82. 
Isarangkura PB, Pundhawong S, Pintadit P, Chantanakajornfung A, Sasanakul W, Chiewsilp P. 
Fresh dried plasma: a solution for the shortage of blood products in developing countries. Ric 
Clin Lab. 1987; 17(4):349-54. 
Kendrick DB, Heaton LD, Coates Jr JB, McFetridge EM. Blood program in World War II. 
Washington, D.C.: Office of the Surgeon General, Dept. of the Army; 1964;  265-323. 
Klein HG, Anstee DJ. Mollison’s blood transfusion in clinical medicine. 11th ed. Oxford, UK: 
Blackwell Publishing; 2005; 685-8. 
Murad MH, Stubbs JR, Gandhi MJ, Wang AT, Paul A, Erwin PJ, et al. The effect of plasma 
transfusion on morbidity and mortality: a systematic review and meta-analysis. Transfusion. 
2010; 50(6):1370-83. 

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NCI Common Terminology Criteria for Adverse  Events. 
Novak DJ, Bai Y, Cooke RK, Marques MB, Fontaine MJ, Gottschall J, et al. Making thawed 
universal donor plasma available rapidly for massively bleeding trauma patients: experience 
from the Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR)  trial. 
Transfusion. 2015; 55(6):1331-9. 
Pidcoke HF, Aden JK, Mora AG, Borgman MA, Spinella PC, Dubick MA, et al. Ten-year 
analysis of transfusion in Operation Iraqi Freedom and Operation Enduring Freedom: increased 
plasma and platelet use correlates with improved survival. J Trauma Acute Care Surg. 2012;  
73(6 Suppl 5):S445-52. 
Rentas F, Lincoln D, Harding A, Maas P, Giglio J, Fryar R, et al. The Armed Services Blood 
Program: blood support to combat casualty care 2001 to 2011. J Trauma Acute Care Surg. 2012; 
73(6 Suppl 5):S472-8. 
Silberman TL. Febrile, allergic, and nonimmune transfusion reactions. In: Simon TL, Snyder EL, 
Stowell CP, Strauss RG, Solheim BG, Petrides M, eds. Rossi’s principles of transfusion   
medicine. New Jersey: Wiley-Blackwell Publishing, Ltd; 2009;  842-5. 
Spinella PC, Frazier E, Pidcoke HF, Dietzen DJ, Shibani P, Gorkun O, et al. All plasma products 
are not created equal: characterizing differences between plasma products. J Trauma Acute Care 
Surg. 2015; 78(6 Suppl 1):S18-25. 
Spoerke N, Zink K, Cho D, Differding J, Muller P, Karahan A, et al. Lyophilized plasma for 
resuscitation in a swine model of severe injury. Arch Surg. 2009;  144(9):829-34. 
US Centers for Disease Control and Prevention (CDC). The National Healthcare Safety Network 
(NHSN) Manual: Biovigilance Component v2.2. Atlanta, GA: Division of Healthcare Quality 
Promotion, National Center for Emerging and Zoonotic Infectious Diseases. Available at: 
http://www.cdc.gov/nhsn/PDFs/Biovigilance/BV-HV-protocol-current.pdf. 
US Food and Drug Administration (FDA). Volume Limits - Automated Collection of Source 
Plasma [Internet]. Center for Biologics Evaluation and Research, 1992 [cited 1992 Nov 4]. 
Available from: 
http://www.fda.gov/downloads/Biolog...toBloodEstablishments/UCM062820.pdf 
US Department of Health and Human Services (HHS). The 2005 National Blood Collection and 
Utilization Survey Report [Internet]. U.S. Department of Health and Human Services, 2005 
[cited 2015 Sept 28]. Available from:  http://www.hhs.gov/ash/bloodsafety/nbcus 
US Department of Health and Human Services (HHS). Common Terminology Criteria for 
Adverse Events (CTCAE) v4.03 [Internet]. National Institutes of Health, National Cancer 
Institute 2010 [cited 2010 June 14]. Available from: 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference 
US Department of Health and Human Services (HHS). The 2011 National Blood Collection and 
Utilization Survey Report [Internet]. U.S. Department of Health and Human Services, 2011  
[cited 2015 Sept 28]. Available from:  http://www.hhs.gov/ash/bloodsafety/2011-nbcus.pdf 

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18. 
APPENDICES 

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APPENDIX A.   STUDY PERSONNEL ROLES AND RESPONSIBILITIES 
Principal Investigator: The PI will have overall responsibility for the study and for compliance 
with the GCP guideline. The PI will conduct the study according to the investigational plan, 
institutional policies, and all applicable regulations. The PI will comply with the PI’s agreement 
(Form FDA 1572), supervise the use of the test articles, and maintain accurate study records. The 
PI will permit and comply with audits and monitoring requirements. The PI will report all SAEs  
to appropriate regulatory bodies, including the local IRB, as required; the sponsor’s   
representative through the USAMRMC USAMMDA ORA; the RM, and the USAMRMC  ORP. 
Clinical Research Coordinator: The clinical site clinical research coordinator will be  
responsible for quality control on all aspects of the study, to include sample collection, volunteer 
records, source documents and eCRFs, regulatory binders, and data sheets. The clinical research 
coordinator will maintain regulatory files, host visits of auditors, monitor all inspections, 
coordinate routing of all protocol activity, and maintain and update files of study staff curriculum 
vitae and GCP training certificates. 
Research Staff: The research staff will assist in the preparation of the protocol, eCRFs, and other 
associated documents as needed, monitor various aspects of the study, review information on 
eCRFs to ensure data are complete and correct, and assist in rectifying discrepancies on eCRFs; 
maintain study records and logs; assist in evaluating study results and preparing reports; ensure 
that volunteers have read and understand the informed consent document and have had all 
questions appropriately answered; ensure that informed consent documents are properly signed  
and dated; collect pre-and post-infusion vital signs, conduct blood draws, and collect and ensure 
the integrity of blood samples; collect and record AEs and follow up and consult with PIs on all 
moderate and severe AEs; and assist the Protocol Administrator with maintenance of regulatory 
files and update all study staff curriculum vitae and GCP training  certificates. 
Clinical Monitor: Study clinical monitoring will be the responsibility of the USAMRMC 
USAMMDA ORA designated clinical monitor. The clinical monitor will conduct initial,  
periodic, and termination study site visits; check protocol adherence including adherence with 
information presented in the informed consent documents, SOPs, and applicable regulations; 
oversee study file and regulatory documents, cross check source documents and eCRFs; confirm 
procedures for the storage, dispensation, and destruction of investigational product are in 
compliance with the study protocol; and observe study  procedures. 
Research Monitor: The RM is affiliated with the clinical site where the trial is taking place but   
is not otherwise involved with this protocol. The RM is a safety advocate for study subjects and  
as such, will review all AEs, SAEs, treatment emergent adverse events (TEAEs), protocol 
violations, and annual reports. For the first 5 subjects in each cohort, the RM will individually 
review each subject’s data through the 24-hour post-infusion follow-up visit prior to the infusion 
of the subsequent subject. The RM will look for any signs of SAEs or AEs that meet SR criteria. 
The RM is required to review all unanticipated problems involving risk to study volunteers, other 
SAEs, and any volunteer deaths associated with the protocol and to provide an unbiased written 
report of the event. The RM may discuss the protocol with study investigators, interview subjects, 
and consult with others outside the study about the research and is authorized to stop  the  
protocol, remove subjects from the protocol, and take any necessary steps to protect the  safety  
and well-being of subjects until the IRB can assess the RM’s  report. 

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The RM’s report, at a minimum, is to provide comment on the outcomes of the event or problem 
and, in the case of an SAE or death, comment on the event’s relatedness to study participation. 
The RM should also indicate whether or not he or she concurs with the details of the report 
provided by the study PI. Reports of events determined by either the PI or the RM to be possibly 
or definitely related to participation, and reports of events resulting in death should be promptly 
forwarded to appropriate regulatory bodies, including the sponsor’s representative through 
USAMRMC USAMMDA ORA; Westat’s PI; and USAMRMC  ORP. 
Clinical Data Manager: The data management center will be responsible for the oversight of   
the development of the study eCRFs, database design and validation, data management plan, and 
for performing data quality/data cleaning activities. 
Biostatistician: Biostatisticians, employed by the data management center, will assist in the 
design and development of the protocol and the study database. The biostatisticians will prepare 
the study SAP, perform statistical analyses, and review the study final  report. 
Product Manager: The product manager will be responsible for the overall management of the 
product development effort. 
Regulatory Affairs Scientist: The regulatory affairs scientist conducts all regulatory reviews 
and obtains the IND sponsor representative’s approval and is responsible for all submissions to 
and all communications with the US FDA. 
Pharmacovigilance Physician: The USAMMDA PVG MD, part of the USAMRMC 
USAMMDA ORA staff, will serve as an arbiter in cases where the PI and RM’s review of these 
data results in discordant determinations. In addition, the PVG MD evaluates all SAEs and 
provides the final determination on relatedness to the product, and whether expedited reporting is 
warranted, per current FDA regulation and guidance. 
The PVG MD is responsible for integrating the review of safety data regarding SAEs and 
reviewing each SAE report. In reviewing SAEs, the PVG MD  will: 
1. Review submitted SAE safety reports to ensure the content is medically consistent, 
accurate, and complete; 
2. Follow each event until it is satisfactorily resolved; and 
3. Perform an assessment of the reporting status to the  FDA/DSMB. 
Quality Assurance Support: Quality Assurance support may be asked to perform audits to 
verify compliance to the protocol and other requirements of this  study. 
Clinical Trial Manager: The clinical trial manager coordinates development of the protocol and 
protocol amendments, coordinates review of the protocol and all protocol-related documents; and 
coordinates completion of the study start and study close out  checklists. 

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APPENDIX B. AABB FULL-LENGTH DONOR HISTORY 
QUESTIONNAIRE 
The questionnaire provided here is a sample and may have undergone revisions since the  
protocol was drafted. Only the most recent version in use at the clinical site will be administered 
to study subjects. 
 
Yes 
No 
Are you 
1.   Feeling healthy and well today? 
 
 
2.   Currently taking an antibiotic? 
 
 
3.   Currently taking any other medication for an  infection? 
 
 
Please read the Medication Deferral List. 
4. Are you now taking or have you ever taken any medications on 
the Medication Deferral List? 
 
 
5.   Have you read the educational materials? 
 
 
In the past 48 hours 
6.   Have you taken aspirin or anything that has aspirin in  it? 
 
 
In the past 6 weeks 
7. Female donors: Have you been pregnant or are you pregnant 
now? (Males: check “I am male.”) 
 
 
am 
male 
In the past 8 weeks have you 
8.   Donated blood, platelets, or plasma? 
 
 
9.   Had any vaccinations or other shots? 
 
 
10. Had contact with someone who had a smallpox  vaccination? 
 
 
In the past 16 weeks 
11. Have you donated a double unit of red cells using an apheresis 
machine? 
 
 
In the past 12 months have you 
12. Had a blood transfusion? 
 
 
13. Had a transplant such as organ, tissue, or bone marrow? 
 
 
14. Had a graft such as bone or skin? 
 
 
15. Come into contact with someone else’s blood? 
 
 
16. Had an accidental needlestick? 
 
 
17. Had sexual contact with anyone who has HIV/AE or has had a 
positive test for the HIV/AE virus? 
 
 
18. Had sexual contact with a prostitute or anyone else who takes 
money or drugs or other payment for sex? 
 
 

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19. Had sexual contact with anyone who has ever used needles to take 
drugs or steroids, or anything not prescribed by their doctor? 
 
 
20. Had sexual contact with anyone who has hemophilia or has used 
clotting factor concentrates? 
 
 
 
 
In the past 12 months have you (continued) 
Yes 
No 
21. Female donors: Had sexual contact with a male who has ever had 
sexual contact with another male? (Males: check “I am  male.”) 
 
 
am 
male 
22. Had sexual contact with a person who has hepatitis? 
 
 
23. Lived with a person who has hepatitis? 
 
 
24. Had a tattoo? 
 
 
25. Had ear or body piercing? 
 
 
26. Had or been treated for syphilis or gonorrhea? 
 
 
27. Been in juvenile detention, lockup, jail, or prison for more than 
72 hours? 
 
 
In the past three years have you 
28. Been outside the United States or Canada? 
 
 
From 1980 through 1996 
29. Did you spend time that adds up to three (3) months or more in 
the United Kingdom? (Review list of countries in the  UK.) 
 
 
30. Were you a member of the US Military, a civilian military 
employee, or a dependent of a member of the US  Military? 
 
 
From 1980 to the present, did you 
31. Spend time that adds up to five (5) years or more in Europe? 
(Review list of countries in Europe.) 
 
 
32. Receive a blood transfusion in the United Kingdom or France? 
(Review list of countries in the UK.) 
 
 
From 1977 to the present, have you 
33. Received money, drugs, or other payment for sex? 
 
 
34. Male donors: Had sexual contact with another male, even once? 
(Females: check “I am female.”) 
 
 
 
I am 
female 
Have you EVER 
35. Had a positive test for the HIV/AE virus? 
 
 
36. Used needles to take drugs, steroids, or anything not prescribed 
by your doctor? 
 
 
37. Used clotting factor concentrates? 
 
 
38. Had hepatitis? 
 
 

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39. Had malaria? 
 
 
40. Had Chagas’ disease? 
 
 
41. Had babesiosis? 
 
 
42. Received a dura mater (or brain covering) graft? 
 
 
 
 
Have you EVER (continued) 
Yes 
No 
43. Had any type of cancer, including leukemia? 
 
 
44. Had any problems with your heart or lungs? 
 
 
45. Had a bleeding condition or a blood disease? 
 
 
46. Had sexual contact with anyone who was born in or lived in 
Africa? 
 
 
47. Been in Africa? 
 
 
48. Have any of your relatives had Creutzfeldt-Jakob  disease? 
 
 

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APPENDIX C.   SAFETY REVIEW MEMO 
 
 

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APPENDIX D.   TELEPHONE RECRUITMENT 
Recruitment Telephone Call Script 
“Hello  
.  My name is  
and I am a staff member at Hoxworth Blood Center. 
I am reaching out to you regarding a research study that is looking for volunteers. You are being 
contacted because of your history of donating blood at our center and because you have  
expressed an interest in participating in research  studies. 
 
Would you be interested in learning more about our study  today?” 
 If No: 
o “Thank you for your time, we hope you continue to support Hoxworth Blood 
Center by donating blood in the future.” 
o End the call and record response in the research participant  database. 
 If Yes, but not a good time: 
o “Is there a better time to discuss the study with you? Would you like 
information about the study mailed to your house?” 
o Arrange for a follow-up call at a later date, AND/OR 
o Collect information for mailing consent to the potential  participant. 
 If Yes: 
o “Thank you for your interest! Our study is looking at the safety of a new, 
experimental plasma product called freeze-dried plasma or FDP. Currently 
hospitals rely on infusions of fresh frozen plasma as definitive care for patients 
who are bleeding after major surgery or have been in an accident to help control 
bleeding, fight infection, and restore fluid levels. However, that type of plasma  
can take a couple of hours to thaw which can be life-threatening for patients who 
immediately need plasma products. A new method has been developed in which 
the plasma is ‘freeze-dried’ instead of frozen. FDP, like fresh frozen plasma, is 
made from donor plasma, but instead of being frozen it is changed to a powder 
form for storage through freeze-drying and can be rapidly dissolved back into a 
liquid form within a few minutes. Because FDP is an experimental product it is  
not currently approved by the FDA.  Participants in the study will donate their  
own blood or plasma and will receive an infusion of their own reconstituted FDP. 
The amount of blood or plasma donated and infused depends on which study 
group you are assigned to.  There are a lot of blood tests and some follow-up  
visits required of people who participate in the study.” 

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I’d like to go over some pre-screening questions with you to see if you would be a good 
candidate for participation.  Is that OK? 
 If Yes: 
o “Great, let’s get started.” 
o Proceed to next question. 
 If No: 
o “Thank you for taking the time to speak with me today.” 
Do you have any questions about the study so far? 
 If Yes: 
o Answer all questions until the potential participant is  satisfied. 
o Proceed to next question. 
 If No: 
o Proceed to next question. 
Are you currently participating in any other research  studies? 
 If Yes: 
o Are you receiving an investigational product in the research study? When do 
you expect to complete that study? 
 Record answers supplied by the potential participant to discuss with Dr. 
Cancelas. The exclusion criterion states that participants cannot have 
received an investigational agent within 1 month of infusion; but does not 
preclude participation entirely. 
o “Thank you, I’m not sure if you’ll qualify for participation in this study but I’d 
like to go ahead and complete the rest of the pre-screening questions just in case 
you are eligible. I’ll talk to Dr. Cancelas, the investigator for this study, about 
your responses.” 
o Proceed to next question. 
 If No: 
o Proceed to next question. 
 
The expected duration of the study is approximately 4 months. Are you planning on 
remaining in the area (ex. Not moving out of state, etc.) during that time  period? 
 If Yes: 
o Proceed to next question. 
 If No: 
o “Thank you for your time. Since there are several times throughout the study 
where you will need to come to Hoxworth Blood Center for tests, we are looking 
for participants who will be local to Hoxworth Blood Center for the duration of 
their time in the study.” 
o End the call and record response in the research participant  database. 
Would you say your health is generally good? 
 If Yes: 
o Proceed to next question. 
 If No: 
o “Thank you for your time; unfortunately for the safety of the study participants 
we’re only enrolling people who believe they are in good health. We hope you 
continue to support Hoxworth Blood Center donating blood in the  future.” 

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[For Females Only] Are you pregnant, planning to get pregnant, or currently  breastfeeding? 
 If Yes: 
o “Thank you, unfortunately due to safety reasons we are only enrolling women 
who are not currently pregnant, planning on getting pregnant, or breastfeeding at 
this time. We hope you continue to support Hoxworth Blood Center donating 
blood in the future.” 
o End the call and record response in the research participant  database. 
 If No: 
o Proceed to next question. 
Are you interested in participating in this study? 
 If Yes: 
o “I would like to set up an initial visit to go over the study in more depth. 
Attending this initial visit does not commit you to participating in the study. If 
you consent to participate by signing the informed consent form, you will be 
screened for all exclusion and inclusion criteria and we will collect blood and 
urine samples to confirm you are healthy enough to participate. We anticipate 
this visit could take up to 3 hours.” 
o Schedule the consent and screening visit. 
o “Thank you for your interest in the study!  Your initial visit is scheduled  for 
  
.  Please feel free to contact us if you have any questions about 
the study in the meantime. If you change your mind about participating in the 
study, or need to reschedule the screening visit, please contact  us. 
o End the call and record response in the research participant  database. 
 If No: 
o “Thank you for taking the time to speak with me today.  I really appreciate  it.” 
 
 
If a printed copy of the Pre-Screening Telephone Call Script is used to document 
information collected during the call, then it must be maintained as part of the source 
documentation. If the subject signs a consent and is assigned a subject ID number (SID), 
then the paper copy of the Pre-Screening Telephone Call Script should be labeled with the 
SID. 

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APPENDIX E. RECRUITMENT FLYER 
 
 

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APPENDIX F. DUKE ACTIVITY STATUS INDEX (DASI) 
 
For each selection in the table, select either yes or no. If the answer is yes, the DSAI value corresponding to the question will be added 
to the total displayed at the bottom. 
 
Item 
Activity 
Please Circle One 
If Yes: DASI 
Value 
1 
Can you take care of yourself (eating, dressing, bathing, or using the   toilet)? 
No 
Yes 
2.75 
2 
Can you walk indoors such as around your  house? 
No 
Yes 
1.75 
3 
Can you walk a block or two on level  ground? 
No 
Yes 
2.75 
4 
Can you climb a flight of stairs or walk up a  hill? 
No 
Yes 
5.50 
5 
Can you run a short distance? 
No 
Yes 
8.00 
6 
Can you do light work around the house like dusting or washing   dishes? 
No 
Yes 
2.70 
7 
Can you do moderate work around the house like vacuuming, sweeping floors, or carrying in 
groceries? 
No 
Yes 
3.50 
8 
Can you do heavy work around the house like scrubbing floors or lifting and moving heavy 
furniture? 
No 
Yes 
8.00 
9 
Can you do yard work like raking leaves, weeding, or pushing a power   mower? 
No 
Yes 
4.50 
10 
Can you have sexual relations? 
No 
Yes 
5.25 
11 
Can you participate in moderate recreational activities like golf, bowling, dancing, doubles tennis, 
or throwing a baseball or  football? 
No 
Yes 
6.00 
12 
Can you participate in strenuous sports like swimming, singles tennis, football, basketball, or 
skiing? 
No 
Yes 
7.50 
Total DASI: 
Assessment Done By:  
 
Date:   
 
 
 
 
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APPENDIX G.IRON SUPPLEMENTATION FLYER 

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APPENDIX H.TELEPHONE FOLLOW-UP SCRIPT 
Telephone Follow-Up Script 
 
(Administered 48 and 72 hours and 14 days after each Infusion Visit, for subjects in all Cohorts.) 
SID:   
 
Introductory Telephone Script: 
 
Hello,  
. This is  
from Hoxworth Blood Center following up after 
your last study visit. I would like to ask you some questions about any medical problems 
including any medications that you may have started taking since your last visit to the blood 
center. 
 
A. 
Record the date, time, and visit information for the contact. This information will be 
recorded on the Telephone Follow-Up CRF. 
 
Contact: 
1st  48-Hour Call    2nd  48-Hour Call (Cohort 3) 1st 
72-Hour Call 2nd 72-Hour Call (Cohort 3) 14-Day 
Call* 
Date: 
Time: 
*For Cohort 3, the 14-Day Call only takes place after the second Infusion  Visit. 
 
B. 
Review the following with the subject and record the responses on the checklist 
provided below. 
 
1. During the last 24 hours have you 
had any of the following: 
Response 
Comment 
Headache or migraine? 
Yes 
No 
Any new vision or hearing 
defects? 
Yes 
No 
Loss of strength or sensitivity in 
any part of your body? 
Yes 
No 
Chest pain? 
Yes 
No 
Shortness of breath? 
Yes 
No 
Abdominal pain? 
Yes 
No 

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Swollen legs, ankles, or calf 
pain? 
Yes 
No 
Rash or unusual bruising on 
your skin? 
Yes 
No 
Blood in your urine or stool? 
Yes 
No 
If the response to any question above is ‘Yes’, notify the Principal Investigator (PI) 
immediately. Reported signs and symptoms are recorded on the Adverse Event  CRF. 
2. Are you currently taking any 
medications since the last visit? 
Yes 
No 
If yes, write down the name of each medication the subject is taking. Reported medications 
are recorded on the 
Prior and Concomitant Medications CRF. 
 
 
C. 
Confirm the subject’s availability for upcoming study  visit: 
- 72-hour telephone contact (if calling for the 48-hour telephone contact);  OR 
- 7-day on-site visit (if calling for the 72-hour telephone  contact). 
 
 
D. 
Complete the Visit Report CRF to indicate the telephone contact took place. The 
Visit Report CRF is completed after each contact or  visit. 

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APPENDIX I.  HEMOVIGILENCE FORM 

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APPENDIX J. SAE FORM 

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APPENDIX K.PREGNANCY FORM 

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