A Randomized, Double-Blind, Placebo-Controlled Dose Ranging Study Evaluating Safety, Pharmacokinetics and Clinical Benefit of FLU-IGIV in Hospitalized Patients With Serious Influenza A Infection
Phase: PHASE2
Conditions: Influenza A H3N2, Influenza A H1N1
Sponsor: Emergent BioSolutions



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FLU-IGIV, and placebo will be administered by intravenous 
infusion as follows: 
• Starting infusion rate of 1.0 mL/min for first 30 minutes;  
• Incremental infusion rate if tolerated (every 15-30 minutes) 
of 1.0 mL/min;  
• Maximum Infusion Rate of 4.0 mL/min. 
The duration of infusion for 500 mL will be approximately 3 
hours. 
Protocol Design 
A multi-center, double-blind, randomized, placebo-controlled, 3 
arm design. For participants in all three assigned treatment 
groups, the randomized treatment will be administered in 
addition to Standard of Care (SOC). Based on current CDC 
guidance on Treatment Considerations for Patients Hospitalized 
with Suspected or Confirmed influenza (or equivalent), SOC 
will include a minimum 5 day course of oseltamivir 75 
mg/twice a day (1), (2). Eligible patients will be randomized in 
a 1:1:1 ratio to receive either a low dose (5 vials) FLU-IGIV or 
high dose (10 vials) FLU-IGIV or placebo. 
Inclusion Criteria 
• Provision of voluntary informed consent in writing by 
patient, or legally authorized representative. 
• Age ≥ 18 years old. 
• Locally determined positive influenza A infection (Rapid 
Antigen (Ag) Test or PCR) from a specimen obtained 
within 2 days prior to randomization. 
• Onset of symptoms ≤ 6 days before randomization, defined 
as when the patient first experienced at least one respiratory 
symptom or fever. 
• Hospitalized (or in observation unit) with influenza, with 
anticipated hospitalization for more than 24 hours and will 
be/already are receiving CDC recommended antiviral SOC 
(oseltamivir 75 mg/twice a day x 5 days; Section 4.1.1). 
• Experiencing ≥ 1 respiratory symptom (ex. cough, sore 
throat, nasal congestion) and ≥ 1 constitutional symptom 
(ex. headache, myalgia, feverishness or fatigue). 
• For women of child-bearing potential: Through Day 60 of 
the study, willingness to use of at least 1 form of hormonal 
or barrier contraception or willingness to abstain from 
sexual intercourse [abstinence is not applicable to Spain]. 

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• Willingness to have blood and respiratory samples obtained 
and stored. 
• National Early Warning Score (NEW score) ≥ 3 at 
screening. 
Exclusion Criteria 
• Use of any investigational product within the past 30 days 
prior to screening. 
• History of hypersensitivity to blood or plasma products (as 
judged by the site investigator) or hypersensitivity to  
FLU-IGIV excipients (maltose, polysorbate 80). 
• History of allergy to latex or rubber. 
• Known medical history of IgA deficiency. 
• Pregnancy or lactation. 
• Medical conditions for which receipt of a 500 mL volume 
of intravenous fluid may be dangerous to the patient (e.g. 
decompensated congestive heart failure), based on 
investigator’s medical opinion with careful consideration of 
lab results. 
• Liver function LFT > 2.5 times ULN. 
• Renal Function GFR < 60 mL/min/1.73 m2 (age and sex 
adjusted). 
• A pre-existing condition or use of a medication that, in the 
opinion of the site investigator, may place the individual at 
a substantially increased risk of thrombosis (e.g. 
cryoglobulinemia, severe refractory hypertriglyceridemia, 
or clinically significant monoclonal gammopathy). 
• An opinion of the investigator that it would be unwise to 
allow participation of the patient in the study (the reason for 
exclusion of the patient must be documented). 
• Receiving extracorporeal membrane oxygenation (ECMO). 
• Anticipated life expectancy of < 90 days. 
• Confirmed bacterial pneumonia or any concurrent 
respiratory viral infection that is not influenza A (ex. 
respiratory syncytial virus (RSV) infection). 
Site Enrollment 
Duration 
18-19 months 
Participant Duration 
2 months 

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Study Procedures and 
Assessments 
Screening (within 48 hours of Baseline) 
• Informed consent. 
• Eligibility assessment. 
• Demographic assessment. 
• Medical history. 
• Including confirmation of influenza A infection (see 
local labs markers of viral infection below). 
• Physical examination. 
• Vital signs (including flu symptoms). 
• NEW score assessment. 
• Concomitant medications. 
• Local lab: 
• Markers of Viral Infection: Nasopharyngeal (NP) 
swab sample collection for local influenza A test 
(Rapid Ag Test or PCR) if not already completed as 
part of SOC assessment. 
• Hematology: CBC with differential white cell count, 
hemoglobin, hematocrit, platelets. 
• Blood chemistry: sodium, potassium, serum 
bicarbonate, BUN, creatinine, glucose, albumin, 
ALT, AST, total bilirubin, PTT, PT. 
• Central lab:  
• Markers of Viral Infection/Viral Load sample 
collection: NP swab for laboratory confirmation of 
influenza A infection followed by viral load 
assessment by both RT-qPCR and viral culture, and 
additional testing to identify strain. 
• For women of child-bearing potential, a serum 
pregnancy test. 
Day 1/Baseline (Pre-Infusion) 
Prior to randomization, the following assessments must be 
completed: 
• Medical history (update as required from screening). 
• Physical examination (if screening and baseline do not 
occur on the same day). 
• Vital signs (including flu symptoms; if screening and 
baseline do not occur on the same day). 

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• Hospital admission status. 
• Ordinal Scale assessment. 
• NEW score assessment.  
• Concomitant medications.  
• Local lab (if screening and baseline do not occur on the 
same day): 
• Hematology: CBC with differential white cell count, 
hemoglobin, hematocrit, platelets. 
• Blood Chemistry: sodium, potassium, serum 
bicarbonate, BUN, creatinine, glucose, albumin, 
ALT, AST, total bilirubin, PTT, PT. 
• Central lab (if screening and baseline do not occur on 
the same day): 
• Markers of Viral Infection/Viral Load sample 
collection: NP swab for RT-qPCR and viral culture. 
• Pre-infusion PK sample collection: serum sample for 
pre-infusion hemagglutination inhibition (HAI) and 
micro-neutralization (MN) analysis. 
Randomization 
Randomization occurs as soon as possible (within 48 hours) 
after screening and Day 1 Baseline Pre-Infusion assessments 
are complete. Randomization should be performed as close as 
possible to the time of infusion. Whether or not the subject is 
dosed, he/she will be followed as part of the Intent to Treat 
(ITT) population through Day 60, see Section 9.1.3. 
Treatment Infusion 
Refer to above section on Dosage for the study treatment. 
 
Day 1 (Post-Infusion)  
After administration of study treatment the following 
assessments must be performed (within 4 hours from the end of 
study treatment infusion): 
• Vital signs (including flu symptoms). 
• Adverse events (AEs) & unanticipated problems. 
• Concomitant medications. 
• NEW score assessment. 
• Central Lab: 

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• Post-infusion PK sample collection: within 90 
minutes after completion of study treatment 
infusion, serum sample for HAI and MN analysis.  
 
Patients will be followed through Day 60 after 
randomization. Study visits and related procedures are to 
be done at the same point in time in which the study 
treatment infusion was completed, within the window 
specified for each particular visit as follows: 
 
Day 2 (+/- 4 hours; if hospitalized) 
• Ordinal Scale assessment. 
• Vital signs (including flu symptoms). 
• NEW score assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
• Local lab: 
• Hematology: CBC with differential white cell count, 
hemoglobin, hematocrit, platelets. 
• Blood Chemistry: sodium, potassium, serum 
bicarbonate, BUN, creatinine, glucose, albumin, 
ALT, AST, total bilirubin, PTT, PT. 
• Central lab: 
• Markers of Viral Infection/Viral Load sample 
collection: NP swab for RT-qPCR and viral culture. 
• PK sample collection: serum sample for HAI and 
MN analysis. 
Day 3 (+/- 4 hours; if hospitalized) 
• Ordinal Scale assessment. 
• Vital signs (including flu symptoms). 
• NEW score assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
• Central lab: 
• Markers of Viral Infection/Viral Load sample 
collection: NP swab for RT-qPCR and viral culture. 

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• PK sample collection: serum sample for HAI and 
MN analysis. 
Day 4 (+/- 4 hours; telephonic if discharged) 
The Day 4 visit needs to be performed for all subjects. If the 
subject has already been discharged, perform the subset of 
assessments by telephone that do not need to be done in person.  
In Hospital Assessments: 
• Ordinal Scale assessment. 
• Vital signs (including flu symptoms). 
• NEW score assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
• Local lab: 
• Hematology: CBC with differential white cell count, 
hemoglobin, hematocrit, platelets. 
• Blood Chemistry: sodium, potassium, serum 
bicarbonate, BUN, creatinine, glucose, albumin, 
ALT, AST, total bilirubin, PTT, PT. 
Telephonic Assessments (if discharged): 
• Ordinal Scale assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
 
Day 6 (+/- 4 hours; if hospitalized) 
• Ordinal Scale Assessment. 
• Vital signs (including flu symptoms).  
• NEW score assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
Day 8 (+/- 1 day)  
If the subject has been discharged prior to Day 8, the study 
requires the subject to return to the site for Day 8 assessments. 
The last NP swab sample is collected at Day 8 or Hospital 
Discharge, whichever occurs first. 

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• Ordinal Scale Assessment. 
• Vital signs (including flu symptoms).  
• Physical examination. 
• NEW score assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
• Central Lab: 
• PK sample collection: serum sample for HAI and 
MN analysis. 
• Markers of Viral Infection/Viral Load sample 
collection: NP swab for RT-qPCR and viral culture. 
The last NP swab collected at Day 8 or Hospital 
Discharge, whichever occurs first. 
 
48 hourly (+/- 4 hours; if hospitalized) 
If the subject remains hospitalized past Day 8, continue to 
perform these assessments up until Day 30 every 48 hours as 
follows: 
• Ordinal Scale Assessment. 
• Vital signs (including flu symptoms).  
• Physical examination. 
• NEW score assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
 
Day 15 (+/- 2 days) 
If the subject has been discharged prior to Day 15, the study 
requires the subject return to the site for Day 15 assessments as 
follows: 
• Ordinal Scale assessment. 
• Vital signs (including flu symptoms). 
• Physical examination. 
• NEW score assessment. 
• Local lab: 

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• Hematology: CBC with differential white cell count, 
hemoglobin, hematocrit, platelets. 
• Blood Chemistry: sodium, potassium, serum 
bicarbonate, BUN, creatinine, glucose, albumin, 
ALT, AST, total bilirubin, PTT, PT. 
• AEs & unanticipated problems. 
• Concomitant medications. 
Hospital Discharge (if prior to Day 60) 
If discharge occurs on a regularly scheduled visit (Day 2, 3, 4, 
etc.), complete the Hospital Discharge assessments instead but 
include the PK sample collection, as applicable. The last NP 
swab sample is collected at Day 8 or Hospital Discharge, 
whichever occurs first.  
• Ordinal Scale assessment. 
• Vital signs (including flu symptoms). 
• Physical examination.  
• NEW score assessment.  
• AEs & unanticipated problems. 
• Concomitant medications. 
• Local lab: 
• Hematology: CBC with differential white cell count, 
hemoglobin, hematocrit, platelets. 
• Blood Chemistry: sodium, potassium, serum 
bicarbonate, BUN, creatinine, glucose, albumin, 
ALT, AST, total bilirubin, PTT, PT. 
• Central lab: 
• Markers of Viral Infection/Viral Load sample 
collection: NP swab for RT-qPCR and viral culture. 
The last NP swab sample is collected at Day 8 or 
Hospital Discharge, whichever occurs first. 
If hospital discharge occurs on Day 2, 3 or 8 also 
collect the PK sample: 
• PK sample collection: serum sample for HAI and 
MN analysis. 
Day 30 (+/- 2 days)  
The Day 30 assessments must be done in person:  

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• Ordinal Scale assessment.  
• AEs & unanticipated problems. 
• Concomitant medications. 
 
Day 60 End of Study and/or Early Withdrawal (+/- 2 days)  
The Day 60 assessments must be done in person:  
• Ordinal Scale assessment.  
• AEs & unanticipated problems. 
• Concomitant medications. 
Pharmacokinetic 
Parameters 
From the HAI and MN assays, the following pharmacokinetic 
parameters will be calculated using the non-compartmental 
approach: 
• AUC0-t: The area under the concentration-time curve from 
time 0 to the last quantifiable concentration, as calculated 
by the linear trapezoidal method. 
• AUC0-day 7: AUC from time 0 to day 7. 
• AUC0-inf: AUC0-t plus the additional area extrapolated to 
infinity, calculated using the terminal elimination rate 
constant. 
• AUC0-t/AUC0-inf: Ratio of AUC0-t to AUC0-inf. 
• Cmax: Maximum observed concentration. 
• Tmax: Sampling time at which Cmax occurs. Where the 
maximum value occurs at more than one time point, Tmax 
will be the first time point with this value. 
• Kel: Apparent first order terminal elimination rate constant 
calculated by linear least square regression analysis using 
the maximum number of points in the terminal log-linear 
phase. 
• t½: Apparent first order terminal elimination half-life. 
• Cl: Plasma clearance. 
• Vss: Total volume of distribution. 
Primary Endpoints 
• AEs. 
• FLU-IGIV PK parameters. 

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Secondary Endpoints 
The secondary endpoint is an outcome based on the ordinal 
scale at Day 8 that has 6 mutually exclusive categories:  
• Death;  
• Hospitalization in the intensive care unit (ICU);  
• Non-ICU hospitalization, requiring supplemental oxygen;  
• Non-ICU hospitalization, not requiring supplemental 
oxygen;  
• No longer hospitalized, but unable to resume normal 
activities; or  
• No longer hospitalized with full resumption of normal 
activities. 
Exploratory 
Endpoints 
The exploratory endpoints are:  
• Ordinal scale assessment at Day 4 (72 hours post dose). 
• Change from baseline to Day 4 in NEW score. 
• Number of days hospitalized. 
• Pharmacodynamic (PD) assessment of the relationship 
between PK and viral load. 
Safety Parameters 
AEs related to the study treatment, lab results and concomitant 
medications will be collected throughout the study. 

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Table of Contents 
1 
BACKGROUND INFORMATION ............................................................................22 
1.1 
Trial Drug .............................................................................................................22 
1.2 
Clinical Trial Rationale .......................................................................................24 
2 
TRIAL OBJECTIVES AND PURPOSE ....................................................................25 
2.1 
Hypothesis .............................................................................................................25 
2.2 
Primary Objective ................................................................................................25 
2.3 
Secondary Objective ............................................................................................25 
3 
TRIAL DESIGN............................................................................................................25 
3.1 
Trial Design ..........................................................................................................25 
3.2 
Anticipated Centers .............................................................................................26 
3.3 
Sample Size ...........................................................................................................26 
3.4 
Randomization .....................................................................................................26 
3.5 
Blinding .................................................................................................................26 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS .............................................27 
4.1 
Subject Inclusion Criteria ...................................................................................27 
4.1.1 
Required Standard of Care (SOC) ......................................................................27 
4.2 
Subject Exclusion Criteria ..................................................................................28 
4.2.1 
Subject Withdrawal .............................................................................................29 
4.2.2 
Subject Withdrawal Criteria ...............................................................................29 
4.2.3 
Subject Replacement ...........................................................................................30 
4.2.4 
Follow-up for Withdrawn Subjects .....................................................................30 
5 
TRIAL MEDICATION ................................................................................................30 
5.1 
Packaging and Formulation ................................................................................30 
5.2 
Labeling ................................................................................................................30 
5.3 
Storage Conditions ...............................................................................................30 
5.4 
Preparation ...........................................................................................................31 
5.5 
Medication Shipment ...........................................................................................31 
5.6 
Drug Accountability.............................................................................................32 
6 
TRIAL PROCEDURES ...............................................................................................32 
6.1 
Screening Assessments (within 48 hours of Baseline) .......................................32 
6.2 
Day 1 Assessments: Baseline (Pre-Infusion of Study Treatment) ...................33 
6.3 
Randomization .....................................................................................................34 
6.4 
Study Treatment Administration (Day 1) .........................................................34 
6.5 
Day 1 (Post-Infusion of Study Treatment).........................................................35 
6.6 
Additional Assessments .......................................................................................35 
6.6.1 
Day 2 Assessments (+/- 4 hours; if hospitalized) ...............................................35 

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6.6.2 
Day 3 Assessments (+/- 4 hours; if hospitalized) ...............................................36 
6.6.3 
Day 4 Assessments (+/- 4 hours; telephonic if discharged) ................................36 
6.6.4 
Day 6 (+/- 4 hours; if hospitalized) .....................................................................37 
6.6.5 
Day 8 (+/- 1 day) .................................................................................................37 
6.6.6 
48 hourly (+/- 4 hours; if hospitalized) ...............................................................37 
6.6.7 
Day 15 Assessments (+/- 2 days) ........................................................................38 
6.6.8 
Hospital Discharge (if prior to Day 60) ..............................................................38 
6.6.9 
Day 30 (+/- 2 days) .............................................................................................39 
6.6.10 Day 60 End of Study and/or Early Withdrawal (+/- 2 days) ..............................39 
6.7 
Trial Assessment Details......................................................................................39 
6.7.1 
Informed Consent................................................................................................39 
6.7.2 
Eligibility ............................................................................................................39 
6.7.3 
Demography ........................................................................................................40 
6.7.4 
Medical History ..................................................................................................40 
6.7.5 
Hospital Admission Status ..................................................................................40 
6.7.6 
Physical Exam .....................................................................................................40 
6.7.7 
Vital Signs/Flu Symptoms ..................................................................................40 
6.7.8 
Ordinal Scale .......................................................................................................40 
6.7.9 
National Early Warning (NEW) Score ...............................................................41 
6.7.10 Markers of Viral Infection/Viral Load Sample Collection .................................41 
6.7.11 Pharmacokinetic (PK) Sample Collection ..........................................................41 
6.7.12 Adverse Events (AE) and Unanticipated Problems ............................................41 
6.7.13 Concomitant Medications ...................................................................................41 
6.7.14 Blood Chemistry .................................................................................................42 
6.7.15 Hematology .........................................................................................................42 
6.7.16 Pregnancy Test ....................................................................................................42 
6.8 
Handling of Samples ............................................................................................42 
6.8.1 
Pharmacokinetic (PK) Samples ..........................................................................42 
6.8.2 
Markers of Viral Infection/Viral Load Samples .................................................43 
6.9 
Concomitant Medications ...................................................................................43 
6.10 
Excluded Concomitant Medications ..................................................................44 
7 
ASSESSMENT OF PK .................................................................................................44 
7.1 
PK Parameters .....................................................................................................44 
7.2 
Assessment of PK Parameters ............................................................................44 
8 
ASSESSMENT OF SAFETY .......................................................................................45 
8.1 
Adverse Event/Serious Adverse Event Definition .............................................45 
8.1.1 
Definitions...........................................................................................................45 
8.1.2 
Assessment of Severity (Intensity) .....................................................................46 
8.1.3 
Assessment of Causality (ICH Classification) ....................................................46 
8.2 
Description of Known AE Profile for FLU-IGIV .............................................47 
8.3 
Adverse Event Reporting ....................................................................................47 
8.4 
Reporting of SAEs................................................................................................48 
8.5 
Safety Data Monitoring .......................................................................................48 

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9 
STATISTICAL ISSUES IN TRIAL DESIGN AND PK ASSESSMENT ................48 
9.1 
Sample Size Calculation ......................................................................................48 
9.1.1 
Safety Population ................................................................................................49 
9.1.2 
PK Population .....................................................................................................49 
9.1.3 
Intent to Treat Population (ITT) .........................................................................49 
9.1.4 
Clinically Evaluable Population (CE) .................................................................49 
9.2 
Trial Endpoints ....................................................................................................49 
9.2.1 
Primary Endpoint ................................................................................................49 
9.2.2 
Secondary Endpoints ..........................................................................................50 
9.2.3 
Exploratory Endpoints ........................................................................................50 
9.2.4 
Safety Endpoints .................................................................................................50 
9.2.5 
Criteria for Early Termination of the Trial .........................................................50 
9.3 
Interim Analyses ..................................................................................................51 
9.4 
Planned Method of Analyses ...............................................................................51 
10 
REGULATORY AND ETHICAL ISSUES ................................................................53 
10.1 
Declaration of Helsinki ........................................................................................53 
10.2 
Informed Consent ................................................................................................53 
10.3 
Institutional Review Board (IRB)/Ethics Committee (EC) ..............................55 
10.4 
Documentation Required Prior to Trial Initiation ...........................................55 
10.5 
Subject Confidentiality ........................................................................................56 
11 
ADMINISTRATIVE AND LEGAL REQUIREMENTS ..........................................56 
11.1 
Sponsorship ..........................................................................................................56 
11.2 
Protocol Amendments .........................................................................................56 
11.3 
Deviations from the Protocol ..............................................................................57 
11.4 
Source Documentation and Storage ...................................................................57 
11.5 
Electronic Data .....................................................................................................58 
11.6 
Monitoring ............................................................................................................58 
11.6.1 Medical Monitoring ............................................................................................59 
11.7 
Quality Control and Quality Assurance ............................................................59 
11.8 
Quality Management ...........................................................................................59 
11.9 
Publication Policy.................................................................................................59 
12 
REFERENCES ..............................................................................................................60 
  

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List of Abbreviations and Definition of Terms 
AE 
Adverse event 
Ag 
Antigen 
ALT 
Alanine transaminase 
AST 
Aspartate transaminase 
AUC0-day 7 
Area under the serum concentration curve from time 0 to day 7 
AUC0-inf 
Area under the serum concentration curve from time 0 to infinity 
AUC0-t 
Area under the serum concentration curve from time 0 to the last measurable 
concentration 
BUN 
Blood urea nitrogen 
CDC 
Centers for Disease Control and Prevention 
CE 
Clinically evaluable population 
Cl 
Drug clearance rate 
Cmax 
Maximum serum concentration 
DSMB 
Data and Safety Monitoring Board 
CBC 
Complete blood count 
CRF 
Case report form 
CRO 
Contract research organization 
EC 
Ethics Committee 
ECMO 
Extracorporeal membrane oxygenation 
eCRF 
Electronic case report form 
FLU-IGIV 
Anti-Influenza Immunoglobulin Intravenous (Human) 
GCP 
Good clinical practices 
HAI 
Hemagglutination inhibition 
ICF 
Informed consent form 
ICH 
International conference on harmonization 
ICU 
Intensive care unit 
IND 
Investigational New Drug Application 
IRB 
Institutional review board 

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ITT 
Intent to treat population 
IV 
Intravenous 
mITT 
Modified intent to treat population 
mL 
Milliliter 
mg 
Milligram 
min 
Minute 
MN 
Microneutralization 
NEW 
National Early Warning 
NIAID 
National Institute of Allergy and Infectious Diseases 
NP 
Nasopharyngeal 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PPT 
Partial thromboplastin time 
PT 
Prothrombin time 
RSV 
Respiratory syncytial virus 
RT-qPCR 
Quantitative reverse transcription 
SAE 
Serious adverse event 
SOC 
Standard of care 
vITT 
Virologically confirmed modified intent to treat population 
Vss 
Volume of distribution at steady state 
WHO 
World Health Organization 
 

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1 
BACKGROUND INFORMATION 
1.1 
Trial Drug 
Emergent BioSolutions Canada Inc. is an innovative biopharmaceutical company with a long 
history of developing, manufacturing and marketing a variety of fractionated plasma products 
for international markets. The Sponsor will refer to Emergent BioSolutions Canada Inc. 
throughout this protocol.  
The Sponsor is developing an Anti-Influenza Immunoglobulin Intravenous (FLU-IGIV) 
human product for the treatment of serious influenza infection in hospitalized patients. The 
FLU-IGIV product will be manufactured using the same hyperimmune manufacturing 
platform process as the FDA and Health Canada licensed products: CNJ-016® [Vaccinia 
Immune Globulin Intravenous (Human), VIGIV], ANTHRASIL® [Anthrax Immune 
Globulin Intravenous (Human), AIGIV], WinRho® SDF [Rho(D) Immune Globulin 
Intravenous (Human)], HepaGam B® [Hepatitis B Immune Globulin (Human) Injection], and 
VARIZIG® [Varicella Zoster Immune Globulin Intravenous (Human)]†. 
Proprietary Name: To be determined (TBD) 
Proper / Common Name: Anti-Influenza Immunoglobulin Intravenous (Human) 
Abbreviated Name: FLU-IGIV 
Code Name: NP-025 
Anti-Influenza Immunoglobulin Intravenous will be formulated in multiple single-use vial(s) 
as a sterile liquid stabilized with 10% maltose and 0.03% polysorbate 80 (pH between 5.0 
and 6.5) and free of any preservatives. 
Anti-Influenza Immunoglobulin is produced from source plasma collected from Food and 
Drug Administration (FDA) licensed plasma collection establishments in the United States 
(US) and Health Canada/US FDA licensed plasma collection establishments in Canada from 
healthy donors who have recovered from influenza (convalescent) and/or were vaccinated 
against seasonal influenza strains. The plasma contains a relatively high concentration of 
antibodies directed against seasonal influenza strains, specifically influenza A strains H1N1 
and H3N2. Influenza antibodies have been correlated with vaccine efficacy and the passive 
                                                 
 
 
 
† CNJ-016® and ANTHRASIL® and all Emergent BioSolutions Inc. brand, product, service and feature 
names, logos and slogans are trademarks or registered trademarks of Emergent BioSolutions Inc. in the United 
States or other countries. All rights reserved. 
 
WinRho® SDF, HepaGam B® and VARIZIG® are trademarks of their respective owners. Emergent 
BioSolutions Canada Inc. manufactures these products under a contract manufacturing agreement. All other 
brand, product, service and feature names or trademarks are the property of their respective owners. 

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transfer of anti-influenza antibodies are effective in animal models of severe influenza (2), 
(4), (5), (6). Clinical proof of concept from treatment with convalescent plasma and purified 
intravenous immunoglobulin (IGIV) suggest that FLU-IGIV can raise antibodies levels and 
impact the course of serious illness caused by influenza A (7), (8), (9).  
FLU-IGIV is a purified immunoglobulin preparation containing antibodies to seasonal 
influenza A virus strains. It is a glycoprotein of 150–160 kilodaltons. 
FLU-IGIV will be used in conjunction with SOC, including supportive measures, ventilator 
and fluid management and the prevention and treatment of secondary bacterial pneumonia, 
which will be captured in the case report form (CRF). Based on current CDC guidance on 
Treatment Considerations for Patients Hospitalized with Suspected or Confirmed influenza  
(or equivalent) (1), (2) it is recommended that SOC include a minimum 5 day course of 
oseltamivir (75 mg/twice a day). All antiviral treatments post-symptom development and 
during the study will be recorded in the CRF. 
Immunoglobulin G molecules are glycoproteins composed of one or more units, each 
containing four polypeptide chains: two identical heavy chains (H) and two identical light 
chains (L). The amino terminal ends of each polypeptide show considerable variation in 
amino acid composition and are referred to as the variable (V) regions to distinguish them 
from the relatively constant (C) regions. The L chain consists of one variable domain VL and 
one constant domain CL. The H chain consists of a variable domain VH, and three constant 
domains (CH1, CH2, and CH3). The number of amino acids, along with the molecular weight 
of each heavy chain is approximately twice that of each light chain. 
Influenza therapies target prevention and treatment of influenza illness. Currently, seasonal 
influenza vaccines against circulating viral strains are available for active immunization to 
influenza A and B. In addition, antiviral therapies, including neuraminidase inhibitors, can 
prevent and treat acute uncomplicated influenza by inhibiting viral replication. Yet seasonal 
influenza remains a significant annual disease burden in the United States and worldwide. 
The current vaccines and therapeutics have not proven to be adequate to prevent serious 
influenza illness, including the significant number of annual medical visits, hospitalizations 
and deaths attributed to influenza (10). While vaccination reduces influenza incidence and 
severity, vaccine effectiveness is dependent on vaccine coverage, individual response rates 
and the match between the vaccine and circulating influenza strains. While neuraminidase 
inhibitors are potent at inhibiting virus replication, they have limited effectiveness when used 
beyond 48 hours after infection and antiviral resistant strains have emerged (11). Currently 
there are no approved therapies for serious influenza in hospitalized patients, creating an 
unmet need to treat and improve outcomes in this population. The use of convalescent 
plasma and fractionated immunoglobulins has been suggested as a complementary strategy to 
treat influenza virus infection, modify the outcomes of severe disease and provide additional 
benefit to the standard of care (12), (13). 
The safety profile for immunoglobulin products is well-established in the clinic. 
Immunoglobulins are normal constituents of the human body fluid, and they are used at 
physiological levels without creating pharmacologic/toxicologic active metabolites (14). The 

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planned clinical doses for FLU-IGIV fall into the range of doses used for VIGIV and 
ANTHRASIL, and are expected to have a similar safety and pharmacokinetic profile. 
1.2 
Clinical Trial Rationale 
There is an unmet medical need for the treatment of serious influenza in hospitalized 
patients. While neuraminidase inhibitors are utilized as part of the standard of care in 
hospitalized influenza they are most effective when used within 48 hours of symptoms (15), 
however, they are not approved for use in this indication. The Sponsor is developing FLU-
IGIV; an anti-influenza immunoglobulin product from high titer plasma to treat serious 
illness caused by influenza A in hospitalized patients. 
The safety profile for immunoglobulin products is well-established in the clinic. 
Immunoglobulins are normal constituents of the human body fluid, and they are used at 
physiological levels without creating pharmacologic/toxicologic active metabolites (14). 
Furthermore, The Sponsor has a long history of developing immunoglobulin-based therapies, 
including the licensed products outlined above. Like other human immunoglobulins, The 
Sponsor’s hyperimmune products have been studied in several healthy volunteer and patient 
trials; the safety profile is consistent with other immunoglobulin products and the 
pharmacokinetic profile is similar for each product with a half-life of approximately 24 to 28 
days after intravenous administration. Taking these data and the following factors into 
consideration, a Phase I safety and pharmacokinetic trial in healthy volunteers is not planned 
for FLU-IGIV. Baseline anti-influenza titers in healthy volunteers are expected to complicate 
the pharmacokinetic analysis, or if a threshold of acceptable baseline anti-influenza titers is 
set it would significantly restrict enrolment into a Phase I study. Furthermore, determining 
the anti-influenza titers and pharmacokinetic profile in severe patients is expected to be more 
informative and may be predictive of patient outcomes rather than a Phase I study in healthy 
volunteers. In addition, The Sponsor is currently manufacturing an anti-influenza 
hyperimmune for the US National Institute of Allergy and Infectious Diseases (NIAID) using 
the same standardized and validated hyperimmune manufacturing process and product 
formulation. The NIAID anti-influenza hyperimmune has been evaluated in a pilot study in 
influenza patients and is currently being studied in a Phase 3 trial in hospitalized influenza 
patients (16, 17, 18). While a Phase 1 safety and pharmacokinetic trial in healthy volunteers 
is not planned for FLU-IGIV, the doses planned for FLU-IGIV are bracketed by licensed 
products VIGIV and ANTHRASIL that were administered in healthy volunteer studies (VA-
003b, AX-001), and are expected to have a similar safety and pharmacokinetic profile. 
The Sponsor’s clinical development plan consists of a Phase 2 randomized, double-blind, 
placebo-controlled dose ranging study evaluating the safety, pharmacokinetics and clinical 
benefit of FLU-IGIV in hospitalized patients with serious illness caused by influenza A 
infection. The primary objective of this study, which initiated in the 2017–2018 flu season, is 
to determine the optimal dose of FLU-IGIV based upon safety and pharmacokinetics in 
hospitalized patients with serious illness caused by laboratory-confirmed influenza A 
infection. The secondary objective is to evaluate the clinical benefit of FLU-IGIV in the 
same population, and to examine exploratory efficacy endpoints to be used in further 
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A second study, a Phase 3 randomized, double-blind, placebo-controlled study evaluating the 
efficacy, safety, and pharmacokinetics of FLU-IGIV in hospitalized patients with serious 
influenza A infection is also planned. The primary objective of this study, which will be 
initiated following completion of the Phase 2 study, will be to evaluate the efficacy and 
clinical benefit of FLU-IGIV use in hospitalized patients with serious illness caused by 
laboratory-confirmed influenza A infection. 
In the clinical trials, the eligible serious hospitalized population will be defined by in-patient 
or intensive care unit status and the severity of illness using the National Early Warning 
(NEW) score (19), as discussed further in section 6.7.9 National Early Warning (NEW) 
Score below. The NEW score will capture key symptoms and signs of respiratory tract 
infection including oxygen saturation, requirement for supplemental oxygen, respiration rate, 
as well as body temperature, blood pressure, and level of consciousness. The serious 
hospitalized population will include patients with risk factors for influenza and influenza-
related complications. The ordinal scale will be used to evaluate the clinical status of patients 
based on activity levels, hospitalization status and requirements. 
2 
TRIAL OBJECTIVES AND PURPOSE 
2.1 
Hypothesis 
This protocol will allow for the safe use of FLU-IGIV in hospitalized patients with serious 
illness caused by laboratory-confirmed influenza A infection.  
2.2 
Primary Objective 
The primary objective is to determine the optimal dose of FLU-IGIV based upon evaluation 
of safety and pharmacokinetics (PK) in hospitalized patients with serious illness caused by 
laboratory-confirmed influenza A infection. 
2.3 
Secondary Objective 
The secondary objective is to evaluate the clinical benefit of FLU-IGIV in hospitalized 
patients with serious illness caused by laboratory-confirmed influenza A infection. 
3 
TRIAL DESIGN 
3.1 
Trial Design 
This trial is designed as a multi-center, double-blind, randomized, placebo-controlled, 3 arm 
study. For participants in all three assigned treatment groups, the randomized treatment will 
be administered in addition to Standard of Care (SOC) including antiviral treatment (see 
section 4.1.1).  

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3.2 
Anticipated Centers 
This is a multi-center trial utilizing up to 60 clinical trial sites globally. 
3.3 
Sample Size 
The sample size will be 75 hospitalized patients with serious illness caused by laboratory-
confirmed influenza A infection. While no formal sample size calculation was performed, 75 
patients are adequate for determination of optimal dose based on AE and PK data, with 
consideration of other safety data and clinical benefit data. Sample size was not inflated to 
compensate for losses to follow-up.  
3.4 
Randomization 
Patients will be randomized 1:1:1 into the study in a double-blind fashion to receive (in 
addition to antiviral SOC) either a low dose (5 vials) FLU-IGIV or high dose (10 vials) FLU-
IGIV or placebo. 
Randomization schedule generation and logistics will be handled by a DM vendor. A dummy 
randomization schedule will be created by the vendor and approved by The Sponsor. 
Subsequently, the production unblinded randomization schedule, differing only in random 
number-generating seed value, will be generated by the vendor and uploaded to the IXRS 
system for patient assignments. The randomization schedule will be stored electronically by 
the IXRS system on a protected server inaccessible to blinded study team members. 
Randomization will not be stratified, except by site. 
3.5 
Blinding 
The local site pharmacist will be unblinded in order to access the randomization assignment 
and prepare the study medication. There will be designated unblinded monitors, and an 
unblinded medical monitor. Other personnel involved in conduct of the study will remain 
blinded through database lock. There will be blinding covers for the IV bags as described in 
section 5.4 Preparation. 
EDC data will be blinded using role-based permissions. Randomization group and study 
medication dispensing data will be integrated with the clinical database prior to database 
lock, but unblinding data will be removed from blinded data extracts by the DM vendor until 
after database lock to ensure maintenance of the blind. Study medication dosing data will be 
reconciled with the randomized treatment group for each patient by the unblinded monitor, 
and any deviations will be reported in the Clinical Study Report. The trial will be unblinded 
once the clinical database is locked. 
While this is a double-blind trial, the blind may be broken if a patient’s health or safety is at 
risk and knowledge of the study arm may be beneficial to the medical management of the 
patient. In the event that unblinding is required, the IXRS will be contacted or the pharmacist 
or other authorized individual may disclose the patient’s treatment group allocation to the 

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Investigator or treating health care provider. In such an event, The Sponsor must be notified, 
and appropriate documentation completed. 
A Data and Safety Monitoring Board (DSMB) will provide another layer of patient safety 
assurance. The DSMB conducted a data review meeting following enrollment and data entry 
for the first 20 patients, and will conduct yearly reviews, as applicable. They will have access 
to unblinded data including at least demographics, medical history, study medication (FLU-
IGIV or placebo) dosing, AEs and SAEs. The DSMB may make a nonbinding 
recommendation that The Sponsor stop the study based on pre-specified stopping rules or 
based on their clinical judgment of patient safety (Further details will be outlined in the 
DSMB Charter). 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
Subject Inclusion Criteria 
Patients must meet the inclusion criteria to participate in this study. 
• Provision of voluntary informed consent in writing by patient, or legally authorized 
representative. 
• Age ≥ 18 years old. 
• Locally determined positive influenza A infection (Rapid Ag Test or PCR) from a 
specimen obtained within 2 days prior to randomization. 
• Onset of symptoms ≤ 6 days before randomization, defined as when the patient first 
experienced at least one respiratory symptom or fever. Earlier symptom onset is 
preferable.  
• Hospitalized (or in observation unit) with influenza, with anticipated hospitalization for 
more than 24 hours and will be/already are receiving CDC recommended antiviral SOC 
(oseltamivir 75 mg/twice a day x 5 days; section 4.1.1). 
• Experiencing ≥ 1 respiratory symptom (ex. cough, sore throat, nasal congestion) and ≥ 1 
constitutional symptom (ex. headache, myalgia, feverishness or fatigue). 
• For women of child-bearing potential: through Day 60 of the study, willingness to use at 
least 1 form of hormonal or barrier contraception or willingness to abstain from sexual 
intercourse [abstinence is not applicable in Spain]. 
• Willingness to have blood and respiratory samples obtained and stored. 
• National Early Warning Score (NEW score) ≥ 3 at screening. 
4.1.1 Required Standard of Care (SOC) 
FLU-IGIV will be used in conjunction with SOC, including supportive measures, ventilator 
and fluid management and the prevention and treatment of secondary bacterial pneumonia, 
which will be captured in the case report form (CRF). Based on current CDC guidance on 

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Treatment Considerations for Patients Hospitalized with Suspected or Confirmed influenza 
(or equivalent) (1), (2), it is recommended that SOC include a minimum 5 day course of 
oseltamivir (75 mg/twice a day). All antiviral treatments post-symptom development and 
during the study will be recorded in the CRF. This also applies to the assigned placebo study 
treatment group. 
It is up to the treating physician to follow SOC measures based upon their professional 
medical opinion. However, if patients hospitalized with serious illness caused by influenza A 
do not receive the antiviral SOC oseltamivir, they will not be eligible for our study.  
4.2 
Subject Exclusion Criteria 
Patients who have any of the exclusion criteria at screening and/or baseline will be excluded 
from participation in this study. 
• Use of any investigational product within the past 30 days prior to screening. 
• History of hypersensitivity to blood or plasma products (as judged by the site 
investigator) or hypersensitivity to FLU-IGIV excipients (maltose, polysorbate 80). 
• History of allergy to latex or rubber. 
• Known medical history of IgA deficiency.  
• Pregnancy or lactation. 
• Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be 
dangerous to the patient (e.g. decompensated congestive heart failure). 
• Liver function defined by a liver function test (LFT) > 2.5 times the upper limit of 
normal (ULN). 
• Renal function defined by a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 
(age and sex adjusted). 
• A pre-existing condition or use of a medication that, in the opinion of the site 
investigator, may place the individual at a substantially increased risk of thrombosis (e.g. 
cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant 
monoclonal gammopathy). 
• An opinion of the investigator that it would be unwise to allow participation of the patient 
in the study (the reason for exclusion of the subject must be documented). 
• Receiving extracorporeal membrane oxygenation (ECMO). 
• Anticipated life expectancy of < 90 days. 
• Confirmed bacterial pneumonia or any concurrent respiratory viral infection that is not 
influenza A (ex. respiratory syncytial virus (RSV) infection). 
Other infections are not explicitly exclusionary, but the Investigators shall use their best 
judgement to determine if the type of infection is a risk factor which makes study 

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participation potentially unsafe for the patient or would compromise interpretation of flu 
symptom improvement. 
4.2.1 Subject Withdrawal 
The subjects must be available, without coercion, for all required parts of the trial, including 
the follow-up visits post-discharge. 
At any point in the study, if continued participation jeopardizes the subject’s health, the 
subject should be withdrawn from the trial.  The investigator is encouraged to consult The 
Sponsor prior to the withdrawal of any subject, except in the event of a medical emergency.  
The reason for withdrawal of any subject must be clearly documented on the trial source 
documents and the appropriate Case Report Form (CRF). 
4.2.2 Subject Withdrawal Criteria 
All subjects are free to withdraw from participation in this trial at any time, for any reason, 
specified or unspecified, and without penalty or loss of benefits to which the subject is 
otherwise entitled.  
In addition, subjects may be withdrawn from the trial for any of, but not limited to, the 
following reasons: 
• The subject develops a concurrent illness that prevents completion of the trial. 
• The subject develops severe or serious adverse events.  
• It is the opinion of the Principal Investigator that it is unwise for the subject to 
continue in the study. 
• The subject is not compliant with the requirements of the trial to the satisfaction of 
the investigator and/or sponsor (e.g. non-cooperative, misses appointments, 
unreported use of concomitant medications). 
• The subject is lost to follow-up. 
• The subject does not meet the entry criteria for the trial but was erroneously entered 
into the trial. 
• If an anaphylactic reaction occurs during infusion, the infusion should be stopped 
immediately. 
• If any complication arises that requires stopping the infusion, e.g. myocardial 
infarction. 
• If a subject is withdrawn from the trial, they will not be re-entered into the trial for 
any reason. 
Subjects withdrawn from the trial with AEs will still require follow-up until the AE(s) are 
resolved. 

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4.2.3 Subject Replacement 
Subjects withdrawn from the trial or who withdraw consent prior to randomization will be 
replaced.  Subjects withdrawn from the trial or who withdraw consent after randomization 
will not be replaced. 
4.2.4 Follow-up for Withdrawn Subjects 
Every attempt will be made to ensure that subjects who are withdrawn, or who withdraw 
from the trial during the active treatment or follow-up period, will complete all safety 
assessments for the early withdrawal visit as outlined in this protocol.  The investigator 
should inform the subjects that these assessments are for their own safety. 
5 
TRIAL MEDICATION 
5.1 
Packaging and Formulation 
FLU-IGIV is supplied in 50 mL Type 1 glass vials sealed with 20 mm siliconized 
bromobutyl rubber stoppers, aluminum seals, and plastic flip-off caps. The extractable 
volume per vial is 45 mL. Each vial is intended for single use only by the IV route. 
FLU-IGIV should be stored at 2-8°C (35-46°F) until required for use. 
FLU-IGIV is provided as a sterile liquid for IV administration.  The product is a clear to 
slightly opalescent and colorless or pale yellow liquid essentially free of foreign particles. 
FLU-IGIV contains a target of 60 mg/mL human plasma protein, of which at least 96% is 
human immunoglobulin G (IgG) containing a portion of specific antibodies against seasonal 
influenza A (H1N1, H3N2). 
For more information, please refer to the Investigator’s Brochure for FLU-IGIV. 
5.2 
Labeling 
FLU-IGIV vial and shelf carton labels will include information to comply with local 
regulations for the country in which the trial is conducted, in the appropriate language(s). 
Labeling for the shelf cartons will also include a space for patient ID (which includes the site 
number) to be noted by the site. 
For dispensing labels for secondary receptacles, see section 5.4 Preparation.  
5.3 
Storage Conditions 
FLU-IGIV must be stored refrigerated at 2-8°C (35-46°F) in a secured area until prepared by 
the pharmacist for use.  The temperature in the storage area should be monitored with 
properly calibrated instruments and recorded on a temperature log. Temperature excursions 

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must be reported to The Sponsor or designate as per instructions provided in the Pharmacy 
Manual. 
For further information, refer to the Investigator’s Brochure and the Pharmacy Manual for 
FLU-IGIV. 
5.4 
Preparation 
The site must maintain documentation of a clear written formalized procedure for trial drug 
preparation activities (including any sample labels and documentation to be completed), and 
documented training and delegation of the activity to appropriate trial staff. 
Patient identifier (patient ID number) must be recorded on the labels of the carton used to 
prepare the dose.  Empty vials must be maintained for drug accountability. The study 
pharmacists will be only persons on-site who are unblinded to the treatment assignment for 
each patient.  
To maintain the blind, all study treatments (low dose of FLU-IGIV in normal saline, high 
dose of FLU-IGIV in normal saline or placebo (normal saline only)) are to be dispensed in a 
comparable manner.    
The trial drug will be prepared for administration at the appropriate dosage and transferred 
into IV bags before administration. The IV bag for both FLU-IGIV doses and placebo 
requires the dispensing label affixed to the secondary receptacle IV bag. The IV bag label 
will capture at a minimum the following study information: patient ID, expiry date of the 
prepared dose, investigator name, protocol code or identification (Protocol IA-001: FLU-
IGIV Study) and caution statement “For investigational use only”. The IV bag requires a 
cover to maintain blinding. Protective covering for the IV bags will be provided by the CRO 
on behalf of The Sponsor as part of the study material.   
The site pharmacy will be responsible for ensuring that the following supplies are available:  
• Normal saline – in 500 mL IV bags or in bulk  
• Empty IV bags (if bulk saline is used)  
For further information, refer to the Investigator’s Brochure and the Pharmacy Manual for 
FLU-IGIV. 
5.5 
Medication Shipment 
FLU-IGIV will be shipped to the site at a temperature of 2-8°C (35-46°F). During shipment, 
the temperature of the drug will be monitored to ensure the required temperature conditions 
are maintained. The site pharmacist or designate will be responsible for checking the number 
of vials and the condition of the vials received and entering this information into the drug 
accountability records, reporting the condition to The Sponsor or designate. The site 
pharmacist or designate will be responsible for assessment of the shipping temperature 
including upload of temperature data from the electronic temperature monitoring device, as 
well as returning of the shipping container and all required documentation to The Sponsor or 

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designate. Study treatment will be released for use by the site only after the data logger 
results are reviewed and written authorization has been issued to the Investigator/designate 
by The Sponsor or designate. At the end of the trial, or upon request of The Sponsor, all 
unused, partially used or empty vials will be returned to The Sponsor or destroyed at the site 
as directed by The Sponsor. 
5.6 
Drug Accountability 
The investigator is responsible for maintaining accurate inventory records of FLU-IGIV.  
The investigator or designate will inventory all Investigational Product shipments upon 
receipt; acknowledge possession by signing all required documentation, and returning these 
to The Sponsor or designate.  The investigator must ensure that all drug supplies are kept in a 
secure location in the site pharmacy in accordance with recommended storage conditions.  
For blinded trials, a research pharmacist or a designated individual not involved in FLU-
IGIV administration will maintain a current inventory and ongoing record of test material 
supplies using the Drug Accountability Form provided by The Sponsor.  This inventory 
record for the FLU-IGIV will include: 
• Protocol name, number and sponsor. 
• Product name and description. 
• Trial site and investigator name. 
• Product lot number and date of manufacture and/or Use-by/Expiry/Re-test date. 
• Number of vials dispensed, date and time of dispensing and study subject for whom 
product was dispensed. 
• Product balance. 
• Name and title of qualified individual dispensing product. 
These records will be reviewed by representatives of The Sponsor and may be reviewed by 
regulatory agencies. 
6 
TRIAL PROCEDURES 
6.1 
Screening Assessments (within 48 hours of Baseline) 
Eligible patients will first undergo informed consent counselling. Once written informed 
consent has been obtained, patients will undergo screening to ascertain their eligibility in this 
trial.  The screening assessments will include: 
• Informed consent. 
• Eligibility assessment. 
• Demographic assessment. 
• Medical history. 

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• Including confirmation of influenza A infection (see Local Labs: Markers of Viral 
Infection below). 
• Physical examination. 
• Vital signs (including flu symptoms). 
• NEW score assessment. 
• Concomitant medications. 
• Local lab: 
• Markers of Viral Infection sample collection: Nasopharyngeal (NP) swab for local 
influenza A test (Rapid Ag Test or PCR) if not already completed as part of SOC 
assessment. 
• Hematology: complete blood count (CBC) with differential white cell count, 
hemoglobin, hematocrit, platelets. 
• Blood chemistry: sodium, potassium, serum bicarbonate, BUN, creatinine, glucose, 
albumin, ALT, AST, total bilirubin, PTT, PT. 
• Central lab: 
• Markers of Viral Infection/Viral Load sample collection: NP swab for laboratory 
confirmation of influenza A infection followed by viral load assessment by both RT-
qPCR and viral culture, and additional testing to identify strain. 
• For women of child-bearing potential, a serum pregnancy test. 
6.2 
Day 1 Assessments: Baseline (Pre-Infusion of Study Treatment) 
Prior to randomization, the following assessments must occur.  
• Medical history (update as required from screening). 
• Physical examination (if screening and baseline do not occur on the same day). 
• Vital signs (including flu symptoms, if screening and baseline do not occur on the same 
day). 
• Hospital admission status. 
• Ordinal Scale assessment. 
• NEW score assessment.  
• Concomitant medications.  
• Local lab (if screening and baseline do not occur on the same day): 
• Hematology: CBC with differential white cell count, hemoglobin, hematocrit, 
platelets. 
• Blood Chemistry: sodium, potassium, serum bicarbonate, BUN, creatinine, glucose, 
albumin, ALT, AST, total bilirubin, PTT, PT. 

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• Central lab (if screening and baseline do not occur on the same day): 
• Markers of Viral Infection/Viral Load sample collection: NP swab for RT-qPCR and 
viral culture. 
• Pre-infusion PK sample collection: serum sample for pre-infusion HAI and MN 
analysis. 
6.3 
Randomization 
Randomization occurs as soon as possible (within 48 hours) after screening and Day 1 
Baseline Pre-Infusion assessments are complete. Randomization should be performed as 
close as possible to the time of infusion. Study treatment administration was staggered by 3 
days (72 hours) between patients for the first 9 patients.  
6.4 
Study Treatment Administration (Day 1) 
The study treatment is to be administered for the first 30 minutes under the direct supervision 
of the investigator or a qualified sub-investigator or designate. Under no circumstances will 
the investigator allow FLU-IGIV to be used other than as specified in the protocol. For full 
details on FLU-IGIV preparation, storage, and administration refer to the Investigator’s 
Brochure. 
Patients will be assigned into one of the three arms based on their randomization to study 
treatment as follows: 
Arm 1: 5 vials (225 mL diluted to 500 mL with saline) FLU-IGIV; 
Arm 2: 10 vials (450 mL diluted to 500 mL with saline) FLU-IGIV; or 
Arm 3: Placebo: 500 mL normal saline. 
Taking into consideration the maximum protein concentration (refer to IB), the high dose 
group would receive a maximum IgG protein dose of 31.5 g.  Assuming a patient weight 
range of 60 kg to 100 kg, patients will receive approximately 0.32 – 0.53 g/kg of IgG protein 
for the high dose and approximately 0.16 – 0.26 g/kg for the low dose, in a single infusion. 
For participants in all three assigned treatment groups, the randomized treatment will be 
administered in addition to SOC as defined above in section 4.1.1 Required Standard of Care 
(SOC). Eligible patients will be randomized in a 1:1:1 ratio to receive either a low dose (5 
vials) FLU-IGIV or high dose (10 vials) FLU-IGIV or placebo. 
Both FLU-IGIV doses must be diluted with saline solution to a final volume of 500 mL to 
match the placebo volume administered in order to maintain blinding.  
All IV bags must be covered with a sleeve to maintain blinding.  
FLU-IGIV and placebo will be administered by intravenous infusion as follows: 
• Starting infusion rate of 1.0 mL/min for first 30 minutes.  
• Incremental infusion rate if tolerated (every 15-30 minutes) of 1.0 mL/min.  

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• Maximum Infusion Rate of 4.0 mL/min. 
• The duration of infusion for 500 mL will be approximately 3 hours.  
A lower maximum infusion rate of 2 mL/min should be used for patients with increased risk 
of acute renal dysfunction or thrombotic events, based on investigator’s medical opinion with 
careful consideration of lab results. If there is a tolerance issue during infusion, the rate can 
be scaled back. 
If adverse events occur, such as flushing, headache, nausea, changes in pulse rate or blood 
pressure, the rate of infusion should be slowed or temporarily stopped. When events resolve, 
the infusion rate may be resumed at a rate that is comfortable to the subject (start at half of 
the last tolerated rate and increase gradually). Refer to the IB (section 3.4.3 Administration) 
for more information.  
6.5 
Day 1 (Post-Infusion of Study Treatment) 
After administration of the study treatment, the following assessments must occur (within 4 
hours from when the infusion is complete).  
• Vital signs (including flu symptoms). 
• Adverse events (AEs) & unanticipated problems. 
• Concomitant medications. 
• NEW score assessment. 
• Central lab 
• Post-infusion PK sample collection: within 90 minutes after completion of study 
treatment infusion, serum sample (two 2 mL transport tubes per time point) will be 
collected for HAI and MN analysis.  
6.6 
Additional Assessments 
Patients will be followed through Day 60 after randomization. Study visits and related 
procedures are to be done at the same point in time in which the study treatment infusion was 
completed, within the window specified for each particular visit.  
6.6.1 Day 2 Assessments (+/- 4 hours; if hospitalized)  
• Ordinal Scale assessment. 
• Vital signs (including flu symptoms). 
• NEW score assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
• Local lab: 

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• Hematology: CBC with differential white cell count, hemoglobin, hematocrit, 
platelets. 
• Blood Chemistry: sodium, potassium, serum bicarbonate, BUN, creatinine, glucose, 
albumin, ALT, AST, total bilirubin, PTT, PT. 
• Central lab: 
• Markers of Viral Infection/Viral Load sample collection: NP swab for RT-qPCR and 
viral culture. 
• PK sample collection: serum sample for HAI and MN analysis. 
6.6.2 Day 3 Assessments (+/- 4 hours; if hospitalized) 
• Ordinal Scale assessment. 
• Vital signs (including flu symptoms). 
• NEW score assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
• Central lab: 
• Markers of Viral Infection/Viral Load sample collection: NP swab for RT-qPCR and 
viral culture. 
• PK sample collection: serum sample for HAI and MN analysis. 
6.6.3 Day 4 Assessments (+/- 4 hours; telephonic if discharged) 
The Day 4 visit needs to be performed for all subjects. If the subject has already been 
discharged, perform the subset of assessments by telephone that do not need to be done in 
person.  
 
In Hospital Assessments: 
• Ordinal Scale assessment. 
• Vital signs (including flu symptoms). 
• NEW score assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
• Local lab: 
• Hematology: CBC with differential white cell count, hemoglobin, hematocrit, 
platelets. 

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• Blood Chemistry: sodium, potassium, serum bicarbonate, BUN, creatinine, 
glucose, albumin, ALT, AST, total bilirubin, PTT, PT. 
Telephonic Assessments (if discharged): 
• Ordinal Scale assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
6.6.4 Day 6 (+/- 4 hours; if hospitalized) 
If the subject remains hospitalized at Day 6, complete assessments as follows: 
• Ordinal Scale Assessment. 
• Vital signs (including flu symptoms).  
• NEW score assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
6.6.5 Day 8 (+/- 1 day) 
If the subject has been discharged prior to Day 8, the study requires the subject to return to 
the site for the Day 8 assessments. The last NP swab sample is collected at Day 8 or Hospital 
Discharge, whichever occurs first. 
• Ordinal Scale Assessment. 
• Vital signs (including flu symptoms).  
• Physical examination. 
• NEW score assessment. 
• Adverse events & unanticipated problems. 
• Concomitant medications. 
• Central lab: 
• PK sample collection: serum sample for HAI and MN analysis. 
• Markers of Viral Infection/Viral Load sample collection: NP swab for RT-qPCR and 
viral culture. The final NP swab sample is collected at Day 8 or Hospital Discharge, 
whichever occurs first. 
6.6.6 48 hourly (+/- 4 hours; if hospitalized) 
If the subject remains hospitalized past Day 8, continue to perform these assessments up until 
Day 30 every 48 hours as follows: 

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• Ordinal Scale Assessment. 
• Vital signs (including flu symptoms).  
• Physical examination. 
• NEW score assessment. 
• AEs & unanticipated problems. 
• Concomitant medications. 
6.6.7 Day 15 Assessments (+/- 2 days) 
If the subject has been discharged prior to Day 15, the study requires the subject return to the 
site for Day 15 assessments as follows: 
• Ordinal Scale assessment. 
• Vital signs (including flu symptoms). 
• Physical examination. 
• NEW score assessment. 
• Local lab: 
• Hematology: CBC with differential white cell count, hemoglobin, hematocrit, 
platelets. 
• Blood Chemistry: sodium, potassium, serum bicarbonate, BUN, creatinine, glucose, 
albumin, ALT, AST, total bilirubin, PTT, PT. 
• AEs & unanticipated problems. 
• Concomitant medications. 
6.6.8 Hospital Discharge (if prior to Day 60) 
If discharge occurs on a regularly scheduled visit (Day 2, 3, 4, etc.), complete the Hospital 
Discharge assessments instead but include the PK sample collection, as applicable. The last 
NP swab sample is collected at Day 8 or Hospital Discharge, whichever occurs first.  
• Ordinal Scale assessment. 
• Vital signs (including flu symptoms). 
• Physical examination. 
• NEW score assessment.  
• AEs & unanticipated problems. 
• Concomitant medications. 
• Local lab: 
• Hematology: CBC with differential white cell count, hemoglobin, hematocrit, 
platelets. 

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• Blood Chemistry: sodium, potassium, serum bicarbonate, BUN, creatinine, glucose, 
albumin, ALT, AST, total bilirubin, PTT, PT. 
• Central lab: 
• Markers of Viral Infection/Viral Load sample collection: NP swab for RT-qPCR and 
viral culture. The last NP swab sample is collected at Day 8 or Hospital Discharge, 
whichever occurs first. 
If hospital discharge occurs on Day 2, 3 or 8 also collect the PK sample: 
• PK sample collection: serum sample for HAI and MN analysis. 
6.6.9 Day 30 (+/- 2 days) 
The Day 30 assessments must be done in person as follows:  
• Ordinal Scale assessment.  
• Adverse events & unanticipated problems. 
• Concomitant medications. 
6.6.10 Day 60 End of Study and/or Early Withdrawal (+/- 2 days) 
The Day 60 assessments must be done in person as follows:  
• Ordinal Scale assessment.  
• Adverse events & unanticipated problems. 
• Concomitant medications. 
6.7 
Trial Assessment Details 
The investigator should attempt to perform trial assessments, or if delegated, should ensure 
that the individual performing the task is qualified by education, training, and experience. 
Licensing requirements may vary by jurisdiction. Investigators should take such 
qualifications/licensing requirements into account when considering delegation of specific 
trial assessment tasks. In all cases, as a qualified physician, the Investigator should be 
responsible for all trial-related medical decisions and care. 
6.7.1 Informed Consent 
Details of informed consent are discussed in section 10.2 Informed Consent. 
6.7.2 Eligibility 
Eligibility will be assessed at screening by ensuring that the subject meets all inclusion 
criteria while not meeting any exclusion criteria (4.1 Subject Inclusion Criteria and 4.2 
Subject Exclusion Criteria). In order for the subject eligibility to be determined, all screening 

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assessments must be completed with the exception of those for PK/central lab that do not 
occur at the clinical trial site.  
6.7.3 Demography 
Demographic information will be obtained for each subject at screening and will include age/ 
date of birth, sex, race, and ethnicity. 
6.7.4 Medical History 
Medical history will be collected at screening and updated at Day 1 (Baseline). Collect if the 
subject has received the seasonal influenza vaccine for the present season. Ensure any 
medical history collected doesn’t affect the eligibility of the subject.  
6.7.5 Hospital Admission Status 
The hospital admission status (residing unit: general/ICU/other) will be obtained at baseline 
and throughout the study.  
6.7.6 Physical Exam 
A physical exam (including but not limited to eyes, ears, nose, throat, lymph nodes, heart, 
pulse, lungs, and abdomen assessments), will be performed throughout the study and the 
patient’s height, weight and body mass index (BMI) will be collected at screening.  
6.7.7 Vital Signs/Flu Symptoms 
Vital signs will be collected for subject including temperature, respiratory rate, blood 
pressure, pulse and solicitation of flu symptoms (fever, cough, sore throat, runny or stuffy 
nose, muscle or body aches, headaches, fatigue, vomiting or diarrhea). If a patient has 
required chest x-rays or other diagnostic methods during their hospitalization to determine 
the extent of infection in the respiratory tract (pneumonia), the available images should be 
redacted and the assessment details should be collected and input into the CRF for that 
subject at the next study visit. If a site is not able to provide redacted image files, clearly 
enter detailed assessment information (from the radiologist report) into the eCRF. At 
screening, baseline oxygen saturation on room air will be collected. 
6.7.8 Ordinal Scale 
The ordinal scale will be used to assess clinical improvement, which categorizes patients into 
one of six mutually-exclusive categories based on activity levels, hospitalization status and 
requirements as follows: 
• 
Death;  
• 
Hospitalization in the intensive care unit (ICU);  
• 
Non-ICU hospitalization, requiring supplemental oxygen;  

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• 
Non-ICU hospitalization, not requiring supplemental oxygen;  
• 
No longer hospitalized, but unable to resume normal activities; or  
• 
No longer hospitalized with full resumption of normal activities. 
The Hospital Discharge visit ordinal scale assessment should be one of the two “No longer 
hospitalized” options. 
6.7.9 National Early Warning (NEW) Score 
The NEW score will be collected for patients and will be defined by in-patient or intensive 
care unit status and the severity of illness. The NEW scoring system will capture key 
symptoms and signs of respiratory tract infection including oxygen saturation, requirement 
for supplemental oxygen, respiration rate, as well as body temperature, blood pressure, and 
level of consciousness. The NEW score parameters can be obtained from patient hospital 
medical records, nursing notes, etc. and will be recorded in the CRF. Screening NEW score 
can be calculated using values from hospital admission prior to medical intervention, as 
provided treatment (ex. Acetaminophen) may confound NEW scoring parameters (ex. fever). 
For more information on NEW score interpretation, please see Appendix I for the NEW 
Scoring Guide.  
6.7.10 Markers of Viral Infection/Viral Load Sample Collection 
To collect and ship samples for assessment for markers of viral infection and viral load for 
FLU-IGIV, collect nasopharyngeal (NP) swab samples according to the instructions provided 
in section 6.8.2 Markers of Viral Infection/Viral Load Samples and the Laboratory Manual. 
Nasal saline should not be administered prior to collecting the NP sample. 
6.7.11 Pharmacokinetic (PK) Sample Collection 
To collect and ship PK samples for assessment, follow instructions specified in section 6.8.1 
Pharmacokinetic (PK) Samples and in the Laboratory Manual.  
6.7.12 Adverse Events (AE) and Unanticipated Problems 
Collect any AE and unanticipated problem for patients as outlined in section 8 
ASSESSMENT OF SAFETY. 
6.7.13 Concomitant Medications 
Concomitant medications for patients will be collected from time of first symptom onset until 
end of study. The concomitant medications should be assessed and reported according to 
section 6.9 Concomitant Medications and 6.10 Excluded Concomitant Medications, and will 
include SOC antiviral treatment (section 4.1.1 Required Standard of Care (SOC)). 

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6.7.14 Blood Chemistry 
Clinical chemistry assessments for patients will include:  
• Serum sodium, potassium, bicarbonate, blood urea nitrogen (BUN), creatinine, glucose, 
albumin, alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin, 
partial thromboplastin time (PPT), prothrombin time (PT). 
6.7.15 Hematology 
Hematology assessments obtained for patients will include:  
• A complete blood count (CBC) with differential white cell count, hemoglobin, 
hematocrit, platelets. 
6.7.16 Pregnancy Test 
Pregnancy tests (serum) will be performed once at screening for all females of child bearing 
potential.  A woman is considered of child-bearing potential/age i.e. fertile, following 
menarche and until becoming post-menopausal unless permanently sterile. Permanent 
sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral 
oophorectomy. A pregnancy test is not required for female subjects who are postmenopausal 
> 2 years, or surgically sterilized. If a subject becomes pregnant prior to Day 60 this should 
be reported to the sponsor as a serious AE for appropriate follow-up. 
6.8 
Handling of Samples  
6.8.1 Pharmacokinetic (PK) Samples  
6.8.1.1 PK Sample Collection 
To obtain samples for analysis of PK for FLU-IGIV, refer to the provided Laboratory 
Manual.  
Briefly, sufficient blood will be drawn per time point to yield two 2 mL aliquots of serum. 
PK sampling kits will be provided for this purpose by the central laboratory. Each sample 
tube must be labelled as per instructions in the Laboratory Manual. Label information will be 
recorded in the CRF and into a logbook as described in the Laboratory Manual.   
Samples will be stored frozen at ≤ -15 °C until they are shipped to the designated central lab. 
The Sponsor or designate must be notified of any deviations in the storage temperature of the 
samples within 48 hours of occurrence. 
Samples collected for PK analysis will be retained according to The Sponsor’s standard 
procedures. 

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6.8.1.2 
PK Sample Shipment 
The trial central lab will initiate shipment of PK samples and arrange the date and method of 
shipment. 
Samples will be divided into two shipments. The second shipment (backup samples) will be 
initiated by the central laboratory once the first shipment has been received and inventory 
verified. Shipment must be arranged such that the central laboratory will have staff on duty to 
receive the samples. Refer to Laboratory Manual for details on PK sample shipment.  
6.8.1.3 
PK Sample Analysis 
The pharmacokinetic analysis will be performed using HAI and MN assays by The Sponsor’s 
bioanalytical laboratory. 
6.8.2 Markers of Viral Infection/Viral Load Samples 
6.8.2.1 
Viral Marker/Load Sample Collection 
To collect and ship samples for markers of viral infection and viral load assessments for 
FLU-IGIV, collect nasopharyngeal (NP) swab samples according to the Laboratory Manual. 
NP collection kits will be provided by the central lab.  
6.8.2.2 
Viral Marker/Load Shipment 
The trial central lab will initiate shipment of viral load/marker samples and arrange the date 
and method of shipment. Shipment must be arranged such that the central laboratory will 
have staff on duty to receive the samples. Refer to Laboratory Manual for details on sample 
shipment. 
6.8.2.3 
Viral Marker/Load Analysis 
The local lab will determine if there is influenza A infection at screening, by a Rapid Ag test 
or PCR, according to their procedures.  
The central lab will confirm if there is influenza A infection from the screening sample 
before performing any further testing. The central lab will perform viral load analysis by RT-
qPCR and viral culture and additional testing to identify the strain (ex. H1N1/H3N2) for all 
samples listed in the schedule of assessments and section 6 Trial Procedures and confirmed 
as influenza A positive.  
6.9 
Concomitant Medications 
The administration of concomitant medications is permitted during the trial period in keeping 
with the standard of care for subjects with serious illness due to influenza A infection.  Any 
medication taken by the subject, including transfusions, herbal preparations and non-
prescription medications within 6 days prior to treatment assignment and/or during the course 
of the trial and the reason for use will be recorded on the trial source documents and 
concomitant medications page of the CRF. 

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FLU-IGIV will be used in conjunction with SOC, including supportive measures, ventilator 
and fluid management and the prevention and treatment of secondary bacterial pneumonia, 
which will be captured in the CRF. Based on current CDC guidance (or equivalent) on 
Treatment Considerations for Patients Hospitalized with Suspected or Confirmed Influenza 
(1), (2) it is recommended that SOC include a minimum 5 day course of oseltamivir (75 
mg/twice a day). All antiviral treatments post-symptom development and during the study 
will be recorded in the CRF. This also applies to the assigned placebo study treatment group. 
6.10 
Excluded Concomitant Medications 
There are no known excluded concomitant medications. Refer the Investigator’s Brochure for 
full details on potential impaired efficacy for vaccines. 
7 
ASSESSMENT OF PK 
7.1 
PK Parameters 
From the HAI and MN assays the following pharmacokinetic parameters will be calculated 
using the non-compartmental approach: 
• AUC0-t: The area under the concentration-time curve (AUC) from time 0 to the last 
quantifiable concentration, as calculated by the linear trapezoidal method. 
• AUC0-day 7: AUC from time 0 to day 7. 
• AUC0-inf: AUC0-t plus the additional area extrapolated to infinity, calculated using the 
terminal elimination rate constant. 
• AUC0-t/AUC0-inf: Ratio of AUC0-t to AUC0-inf. 
• Cmax: Maximum observed concentration. 
• Tmax: Sampling time at which Cmax occurs. Where the maximum value occurs at more 
than one time point, Tmax will be the first time point with this value. 
• Kel: Apparent first order terminal elimination rate constant calculated by linear least 
square regression analysis using the maximum number of points in the terminal log-linear 
phase. 
• t½: Apparent first order terminal elimination half-life. 
• Cl: Plasma clearance. 
• Vss: Total volume of distribution. 
7.2 
Assessment of PK Parameters 
PK will be assessed in all subjects, including those subjects assigned to the placebo group, 
who will have natural antibody production. Due to the buildup of anti-influenza antibodies 

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from subjects’ natural immunity, PK parameters will be estimates only and cannot quantify 
precisely the levels of FLU-IGIV in dosed subjects.  
8 
ASSESSMENT OF SAFETY 
The safety of the trial drug will be assessed by monitoring closely adverse events (AE) 
defined as related to study treatment, lab results for chemistry and hematology and 
concomitant medications collected throughout the study. Any lab results and concomitant 
medications will be monitored regularly.  
8.1 
Adverse Event/Serious Adverse Event Definition 
The occurrence of AEs will be monitored throughout all phases of the trial and will cover all 
participating subjects. AE capture will begin after randomization, and any medical history 
changes that occur after baseline assessments during randomization and before dosing should 
be updated as medical history. 
Adverse events are to be elicited by the investigator (or designate) by asking the subject non-
leading questions.  The association of the AE to the study treatment is to be judged by the 
investigator as related or not-related/no relationship. 
8.1.1 Definitions 
An Adverse Event (AE):  Any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and that does not 
necessarily have a causal relationship with this treatment.  An adverse event (AE) can 
therefore be any unfavourable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) 
product. 
NOTE: A diagnosis should be preferentially captured as an adverse event term and 
signs and symptoms should be captured only in the absence of a unifying diagnosis.  
In the event that there are multiple diagnoses, then all diagnoses should be captured.  
The worsening of an existing sign, symptom or disease is also considered to be an 
AE.  An abnormal laboratory finding deemed by the Principal Investigator as not 
clinically significant will not be captured as an AE, but an abnormal laboratory 
finding that worsens after dosing with the study drug, from not clinically significant 
to clinically significant, is considered an AE.  Surgical procedures are not AEs.  They 
are the action taken to treat a medical condition.  Interventions that were planned 
prior to study entry for medical conditions that started prior to study entry, but did 
not worsen during the clinical trial are not reported as AEs. 
A Serious Adverse Event (SAE):  Any untoward medical occurrence that at any 
dose: results in death, is life threatening, requires inpatient hospitalization or 
prolongation of existing hospitalization, results in persistent or significant 
disability/incapacity, or is a congenital anomaly/birth defect. 

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Important medical events which may not result in death, be life threatening, or require 
hospitalization may be considered a SAE when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. 
NOTE: Death is an outcome and not an event. The condition leading to death is the 
event. Death will be considered an event only when no other information regarding 
the cause of death is available. 
Hospitalization that is planned before inclusion into the study or outpatient treatment 
without overnight hospitalization is not considered a SAE.  Hospitalization that 
occurs during a trial for social reasons (e.g., transportation difficulties, respite care) 
is not considered to be a SAE. 
Adverse Drug Reaction:  Any noxious and unintended response to a medicinal 
product related to any dose. 
Expected Adverse Drug Reaction/Event:  An adverse reaction, the nature or 
severity of which is consistent with the applicable product information (e.g. 
Investigator’s Brochure for an unapproved investigational product or package 
insert/summary of product characteristics for an approved product). 
Unexpected Adverse Drug Reaction/Event:  An adverse reaction, the nature or 
severity of which is not consistent with the applicable product information (e.g. 
Investigator’s Brochure for an unapproved investigational product or package 
insert/summary of product characteristics for an approved product). 
All adverse events, including those that are not of a serious nature and those that are 
expected, will be documented by the investigators (or designates) in the source 
documents and appropriately transcribed into the CRF.  All adverse events will be 
examined by a physician investigator or sub-investigator for assessment of both 
severity and causality using the following criteria: 
8.1.2 Assessment of Severity (Intensity) 
The adverse event severity should be assessed based on the MedDRA Lowest Level Term 
(LLT) scale below. 
Mild: awareness of a sign or symptom but subject can tolerate. 
Moderate: discomfort enough to cause interference with normal daily activity. 
Severe: resulting in an inability to do work or do usual daily activity. 
8.1.3 Assessment of Causality (ICH Classification) 
In accordance with ICH E2A and 21.CFR.312, the following definitions are used to assess 
causality (relatedness) of the adverse events: 

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Related:  There is a reasonable possibility that the AE was caused by the product in 
question. The expression “reasonable possibility” is meant to convey in general that 
there are facts (evidence) or arguments to suggest a causal relationship. 
Not-related / No relationship:  The AE is clearly or most probably caused by other 
etiology such as the patient’s underlying condition, therapeutic intervention or 
concomitant therapy, or the delay between the administration of the product and the 
onset of the AE is incompatible with a causal relation, or the AE started before the 
administration of the product. 
8.2 
Description of Known AE Profile for FLU-IGIV 
The safety of human IV immunoglobulins is well established.  The incidence of AEs 
associated with administration of IV immunoglobulin products is reported by the 
manufacturers to be in the range of 1 to 15%, usually less than 5% (20, 21).  Non-
anaphylactic reactions are most common and the majority of AEs are mild and self-limiting 
in nature. 
A complete list of risks with details are outlined in the Investigator’s Brochure which 
includes: 
• Hypersensitivity 
• Renal dysfunction/failure 
• Aseptic Meningitis Syndrome (AMS) 
• Hemolysis 
• Thrombotic events 
• Transfusion-Related Acute Lung Injury (TRALI) 
• Infusion rate reactions 
• Interference with blood glucose testing 
8.3 
Adverse Event Reporting 
Occurrence of adverse events will be monitored throughout the trial and will cover all 
participating patients, including any randomized subject.  Trial subjects will be provided with 
a 24 hour telephone number to contact trial personnel in case of an untoward reaction after 
hospital discharge.  
All AEs must be followed to resolution, or up to 60 days after the patient has completed the 
trial, whichever occurs first.  The investigator will follow serious related adverse events to 
resolution, or in the case of disability or incapacity, until the condition has stabilized.  In the 
event that a patient does not complete the trial, efforts must be made to obtain information 
regarding all AEs, with a minimum follow-up of 60 days post-dosing. 
If a subject becomes pregnant during a clinical trial, these pregnancies will be considered as 
SAEs and will be followed until termination of pregnancy or birth.  If a pregnancy results in 

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an abnormal outcome that the reporting health care professional considers might be due to 
the trial drug, then the guidelines for expedited reporting of serious, unexpected adverse drug 
reactions should be followed. 
8.4 
Reporting of SAEs 
The investigator will report all serious adverse events to The Sponsor’s Pharmacovigilance 
Department by telephone or e-mail (with the Medical Monitor in copy) within 24 hours of 
the investigator’s knowledge of occurrence.  This will be followed by a fax or e-mail copy of 
the SAE Form, with the Medical Monitor in copy.  A written SAE report by the investigator 
to The Sponsor (including medical summary of the SAE) must follow within 3 days of the 
investigator’s knowledge of occurrence of the SAE. 
All reports should be made to:  
 
AND 
Medical Monitor  
 
 
Emergent BioSolutions Canada Inc. 
SGS North America Inc. 
 
  
 
 
 
 
 
 
 
  
Toll free phone: 
 
Toll free fax
 
8.5 
Safety Data Monitoring  
Study treatment administration was staggered by 3 days (72 hours) between patients for the 
first 9 patients. An independent Data Safety and Monitoring Board (DSMB) will provide on-
going review of safety data during the trial.  The DSMB will be responsible for assessing 
safety and monitoring overall conduct and integrity of the trial.  In fulfilling these 
responsibilities, the DSMB may make recommendations concerning continuation and/or 
stopping of the trial as it relates to safety and risk to the patient population as outlined in 
section 9.2.5 Criteria for Early Termination of the Trial. 
9 
STATISTICAL ISSUES IN TRIAL DESIGN AND PK ASSESSMENT 
9.1 
Sample Size Calculation 
The sample size will be 75 hospitalized patients with serious illness caused by laboratory-
confirmed influenza A infection. While no formal sample size calculation was performed, 75 
patients are adequate for determination of optimal dose based on AE and PK data, with 
consideration of other safety data and clinical benefit data. 

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9.1.1 Safety Population  
The safety population will include all patients who receive any amount of study 
medication (FLU-IGIV or placebo). 
9.1.2 PK Population  
The PK population will include all patients who have adequate PK data for analysis 
that includes day 1 pre-infusion/baseline, post-infusion plus at least one additional 
time point. 
9.1.3 Intent to Treat Population (ITT) 
The intent to treat population will include all randomized patients regardless of study 
medication treatment status, influenza type or protocol deviations. Patients will be 
analyzed according to the treatment to which they were randomized. 
9.1.3.1 Modified Intent to Treat Population (mITT) 
The mITT population will include those patients from the ITT population who met 
eligibility criteria, received study medication (FLU-IGIV or placebo) and have 
confirmed influenza A by the local lab Rapid Ag or PCR markers of viral infection 
test from the screening NP swab sample. Patients will be analyzed according to the 
treatment to which they were randomized. 
9.1.3.2 Virologically Confirmed Modified Intent to Treat Population (vITT) 
The vITT population will include any patients from the mITT population who met 
eligibility criteria, received study medication (FLU-IGIV or placebo) and have 
confirmed influenza A by the central lab RT-qPCR markers of viral infection test 
from the screening NP swab sample. Patients will be analyzed according to the 
treatment to which they were randomized. 
9.1.4 Clinically Evaluable Population (CE) 
The CE population will include all patients who met eligibility criteria, received ≥ 80% of 
study medication (FLU-IGIV or placebo) infusion matching their randomized treatment 
group, ≥ 80% of the oseltamivir and have a non-missing Day 8 ordinal scale assessment. 
9.2 
Trial Endpoints 
9.2.1 Primary Endpoint 
Primary endpoint analyses will include AE incidence and severity and PK parameters, 
upon which optimal dose determination will be based. 

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9.2.2 Secondary Endpoints 
The secondary endpoint is an outcome based on the ordinal scale at Day 8 that has six 
mutually exclusive categories:  
• Death;  
• Hospitalization in the intensive care unit (ICU);  
• Non-ICU hospitalization, requiring supplemental oxygen;  
• Non-ICU hospitalization, not requiring supplemental oxygen;  
• No longer hospitalized, but unable to resume normal activities; or  
• No longer hospitalized with full resumption of normal activities. 
9.2.3 Exploratory Endpoints 
The exploratory endpoints are:  
• Ordinal scale assessment at Day 4 (72 hours post dose). 
• Change from baseline to Day 4 in NEW score. 
• Number of days hospitalized. 
• Pharmacodynamic (PD) assessment of the relationship between PK and viral load. 
9.2.4 Safety Endpoints 
Adverse events related to the study treatment, lab results and concomitant medications will 
be collected throughout the study. 
9.2.5 Criteria for Early Termination of the Trial  
The Sponsor and/or the principal investigator may elect to terminate the trial early as defined 
by the clinical trial agreement. Meeting a safety stopping criterion will not automatically 
trigger study termination, but a hold on recruitment will be implemented until an ad hoc 
DSMB meeting is held. If any of the following criteria are fulfilled, the DSMB will review 
the unblinded safety data to assess the evidence for an excess of events in the FLU-IGIV 
treatment groups relative to the placebo group. The DSMB will determine whether trial 
termination is recommended, which would require a majority vote. 
• Two or more subjects experience related rare reactions reported for immunoglobulin 
intravenous (human) (IGIV), such as thrombotic events, hemolysis or transfusion 
related acute lung injury (TRALI). 
• Three or more subjects experience the same related SAE (per sponsor assessment). 
• Five or more subjects experience the same related severe AE. 
• Ten or more subjects experience a related moderate or higher AE associated with the 
same organ system. 

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• Eight or more patients who were not able to tolerate the entire 500 mL IV infusion, 
but were administered a partial study medication infusion (FLU-IGIV or placebo). 
• Proportion of deaths due to complications from worsened primary conditions or co-
morbidities ≥ 10% higher than that reported for the influenza season by CDC  
FLUVIEW (https://www.cdc.gov/flu/weekly/fluviewinteractive.htm). 
• Any other findings that, at the discretion of the medical monitors, indicate that the 
study should be halted. 
Administrative issues affecting one or more sites may constitute grounds for stopping the 
trial at that site(s). Examples include, but are not limited to, non-adherence to the protocol, 
unavailability of the Principal Investigator or staff for The Sponsor’s (or their authorized 
representative) monitoring personnel, inadequate evidence of the Principal Investigator’s 
personal conduct or supervision of the trial, relocation of the investigator or reallocation of 
investigator’s responsibilities or disqualification of the investigator by the regulatory 
authority. 
The Sponsor and the site principal investigator(s) may elect to terminate the trial early for a 
variety of other reasons. A decision to terminate the trial early may be based on data 
suggesting that the trial treatment (or participation in the trial) may be unsafe; the protocol or 
conduct of the trial is flawed such that the safety or rights of the trial subjects may be 
adversely affected; the ethics committee withdraws the approval for the trial and denies 
reconsideration; the investigational treatment is found to be ineffective; recruitment is poor; 
research strategy or management priorities change; or a clinical hold is imposed by a 
regulatory authority, to name a few. 
Any decision to voluntarily suspend or terminate a clinical trial will be carefully reviewed 
and fully justified. The Sponsor will notify the regulatory authorities and the Institutional 
Review Boards (IRB)/Ethics Committees (EC) of any suspension or termination, along with 
justification for restarting or terminating the study as applicable. 
The principal investigator must notify the IRB/EC in writing of the trial’s completion or early 
termination. The Sponsor must receive a copy of the notification letter from the IRB/EC 
indicating receipt of the completion or early termination letter. 
9.3 
Interim Analyses 
A DSMB data review occurred in March 2018, after enrollment and data entry for 20 
subjects. Thereafter, the DSMB will conduct yearly reviews, as applicable. 
No formal interim analysis is planned. 
9.4 
Planned Method of Analyses 
In general, continuous endpoints will be summarized by descriptive statistics including 
number of patients, mean, standard deviation (SD), median, minimum and maximum. 
Categorical endpoints will be summarized by the total number of patients, frequencies and 
percentages. 

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AEs will be coded to system organ class and preferred term using the Medical Dictionary for 
Regulatory Activities (MedDRA), using the current version at the time of coding. AEs will 
be defined as events beginning after first study medication administration that were not 
present prior to first study medication administration or those that were present prior to first 
study medication administration and subsequently worsened in severity. AE incidence for 
each system organ class and preferred term will be summarized for the safety population by 
treatment group overall as well as separately by severity and for events related to study 
medication (FLU-IGIV or placebo). Serious AEs will be summarized separately for the same 
population, as will deaths.  Separate subgroup analyses of AE and SAE incidences by sex, 
race (Caucasians, African Americans, and others) and age (over 55 versus 18-54) will be 
performed by treatment group. 
PK analysis for anti-influenza antibodies will be conducted for the PK population using HAI 
and MN analysis. Serum concentration versus time data will be analyzed by standard 
noncompartmental methods (i.e., trapezoidal method). Actual times and not nominal times 
will be used in the analysis, and concentrations below the limit of quantitation (LOQ) and/or 
detection (LOD) will be imputed as half of this value. Calculated PK parameters will include 
maximum serum concentration (Cmax), time of maximum serum concentration (tmax), half-life 
(t1/2), area under the concentration-time curve (AUC) for 0-t (time 0 to the last 
concentration), AUC0-7 (time 0 to Day 7), AUC0-inf (time 0 to infinity), ratio of AUC0-t/AUC0-
inf, terminal elimination rate constant (Kel), clearance (Cl) and volume of distribution (Vss). 
PK parameters will be reported using descriptive statistics by treatment group for the PK 
population. Dose proportionality will be explored using log-transformed PK data. Serum 
concentration-time data will be plotted by treatment group. Relevant subset analyses may be 
performed. 
Patient disposition, including early termination reasons, will be summarized by treatment 
group for all patients. Major protocol deviations will be presented by treatment group for the 
safety population. Patient demographics, medical history and study medication (FLU-IGIV 
or placebo) dosing data will be tabulated by treatment group for the safety population. 
Important baseline values such as ordinal score assessment, NEW score and flu symptoms 
will be summarized by treatment group for the safety and ITT populations. Pre-infusion 
medications, concomitant medications and concomitant medical procedures will be coded 
using the WHO Drug Dictionary and displayed by treatment group for the safety population. 
Ordinal scale assessment will be analyzed at Days 4 and 8 for the ITT and CE populations 
using a proportional odds model investigating the effect of treatment group on ordinal 
outcome. An odds ratio will be computed for each study treatment group relative to placebo, 
interpretable as the mean location shift across the ordinal scale attributed to IVIG treatment. 
After verification of the proportional odds assumption for dose, a dose-response relationship 
will be tested using ordinal logistic regression with a cumulative logit link and an ordinal 
dose variable, adjusting for significant prognostic factors using stepwise selection. If the 
proportional odds assumption is significantly violated, then a partial proportional odds model 
for dose will be explored. Relevant subset analyses may be performed. 

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Change from baseline to Day 4 in NEW score will be compared between treatment groups 
for the ITT and CE populations using nonparametric rank analysis. Viral load data from 
central laboratory NP swabs will be summarized by time point for the ITT and CE 
populations by treatment group and tested for differences between treatment groups at key 
time points (e.g, Days 2 and 3). The relationship between PK and viral load will be 
investigated for patients belonging to both the PK and ITT populations. 
Central clinical laboratory test results will be summarized by time point and treatment group 
using descriptive statistics for the safety population. Vital signs parameters will be presented 
in the same manner. 
10 REGULATORY AND ETHICAL ISSUES 
10.1 
Declaration of Helsinki 
The investigator shall ensure that this trial is conducted in accordance with the ethical 
principles that have their origin in the “Declaration of Helsinki.” 
10.2 
Informed Consent 
The investigator (or his/her representative) will obtain written informed consent from 
prospective trial candidates before enrolment or the performance of any trial procedures.  The 
proper completion of consent forms will be monitored by sponsor personnel and the original 
signed informed consent form(s) (ICF) will be maintained in the Investigator site file.  If 
applicable, identify different consent forms that are needed for the study (e.g. future use of 
specimen, assent from minors, etc.). A copy of the signed ICF must be given to the subject.  
If the ICF is revised, all trial subjects who are ongoing in the trial must be re-consented to the 
current IRB/EC-approved version of the ICF at their next trial visit.  While obtaining 
informed consent from these subjects, the investigators (or designates) will inform the 
subject of the following: 
• That the trial involves research. 
• The purpose of the trial. 
• The trial treatment(s) and the probability for random assignment to each treatment. 
• The trial procedures to be followed, including all invasive procedures. 
• The type and amount of biological samples to be collected for PK analysis, and the 
retention period for these, and the fate of these samples whether analyzed or not 
(backup).  
• The subject's responsibilities. 
• Those aspects of the trial that are experimental. 
• The reasonably foreseeable risks or inconveniences to the subject and, when applicable, 
to an embryo, fetus, or nursing infant. 

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• The reasonably expected benefits.  When there is no intended clinical benefit to the 
subject, the subject should be made aware of this. 
• The alternative procedure(s) or course(s) of treatment that may be available to the 
subject, and their important potential benefits and risks. 
• The compensation and/or treatment available to the subject in the event of trial related 
injury. 
• The anticipated prorated payment, if any, to the subject for participating in the trial. 
• The anticipated expenses, if any, to the subject for participating in the trial. 
• That the subject's participation in the trial is voluntary and that the subject may refuse to 
participate or withdraw from the trial, at any time, without penalty or loss of benefits to 
which the subject is otherwise entitled. 
• The consequences of a subject’s decision to withdraw from the study and procedures for 
orderly termination of participation by the subject. 
• That the monitor(s), the auditor(s), the IRB/EC, and the regulatory authority(ies) will be 
granted direct access to the subject's original medical records for verification of clinical 
trial procedures and/or data, without violating the confidentiality of the subject, to the 
extent permitted by the applicable laws and regulations and that, by signing a written 
informed consent form, the subject or the subject's legally acceptable representative is 
authorizing such access. 
• That records identifying the subject will be kept confidential and, to the extent permitted 
by the applicable laws and/or regulations, will not be made publicly available.  If the 
results of the trial are published, the subject’s identity will remain confidential. 
• That the subject or the subject's legally authorized representative will be informed in a 
timely manner if information becomes available that may be relevant to the subject's 
willingness to continue participation in the trial. 
• The person(s) to contact for further information regarding the trial and the rights of trial 
subjects, and whom to contact in the event of trial related injury. 
• The foreseeable circumstances and/or reasons under which the subject's participation in 
the trial may be terminated. 
• The expected duration of the subject's participation in the trial. 
• The approximate number of subjects involved in the trial. 
• In FDA-regulated clinical trials, the following statement shall be provided to each clinical 
trial subject in informed consent documents and processes: “A description of this clinical 
trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This 
Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time.” 
• Considering other jurisdictions, the following statement shall be provided to each clinical 
trial subject in informed consent documents and processes: “This description will be 

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available on other Clinical Trial registration sites specific to the jurisdictions this study is 
being carried out in (ex. https://eudract.ema.europa.eu/ in Europe, https://health-
products.canada.ca in Canada, etc.), according to their respective laws. These Web sites 
will not include information that can identify you. At most, these Web sites will include a 
summary of the results. You can search this Web site at any time.” 
10.3 
Institutional Review Board (IRB)/Ethics Committee (EC) 
Before the start of the trial, the Investigator’s Brochure, the protocol, proposed informed 
consent form(s), subject compensation (if any), The Sponsor-approved trial materials and 
advertisements, and any other written information to be provided to the subject, will be 
submitted to a properly constituted Institutional Review Board (IRB) or Ethics Committee 
(EC) for review.  The Sponsor must receive a copy of the written approval from the IRB for 
all of the above applicable documents prior to recruitment of subjects into the trial and 
shipment of FLU-IGIV. 
The IRB/EC must provide written approval for all amendments to any of the above 
documents prior to implementation of these amendments at the investigational site.  The 
investigator is obliged to report SAEs, as well as any unanticipated problems, to the IRB/EC 
in addition to other information as required by the IRB/EC. 
The names (or title, if IRB/EC procedures prohibit publishing of names) and associated 
backgrounds of the members of IRB/EC (to assist in assuring that the board membership is 
properly constituted and operates according to 21 CFR part 56 (or equivalent local 
regulations) and ICH GCP guidelines will be given to The Sponsor prior to the start of the 
trial along with a signed and dated statement stating that the protocol and Informed Consent 
Form and, where applicable, any other document listed above, have been approved by them. 
All correspondence between the investigator and the IRB/EC will be available for review by 
The Sponsor (or designate), contract research organization (CRO) personnel, and the 
applicable regulatory authority(ies). 
10.4 
Documentation Required Prior to Trial Initiation  
The investigator (or designate) is responsible for forwarding the following documents to The 
Sponsor for review prior to trial initiation: 
• Signed protocol signature page, form FDA 1572 (or equivalent, depending on local 
regulatory requirements), financial disclosure form, debarment certification statement, 
Clinical Trial Agreement, and any other required regulatory documents. 
• Copy of IRB/EC-approved informed consent form. 
• Copy of the written IRB/EC approval for the protocol, Investigator’s Brochure, informed 
consent form(s), subject compensation (if any), any trial materials and advertising, and 
any other written information to be provided to the subject. 

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• Current Curriculum Vitae and a photocopy of medical license (if applicable) of the 
principal investigator, co/sub investigators and other site personnel as required by the 
Sponsor/CRO. 
• Written statement that the IRB/EC is properly constituted and operates according to 21 
CFR part 56 regulations and/or ICH GCP, as applicable.  Investigators participating in 
this study, if IRB members, should state in writing that they have abstained from voting 
in regards to this protocol.  
• Laboratory normal ranges and documentation of laboratory certification. 
10.5 
Subject Confidentiality 
The investigator must ensure the anonymity of each subject is maintained at all times.  
Subjects should only be identified by their initials and Subject Trial ID (randomization, 
enrolment) number on the CRF, or on any other trial documents provided to The Sponsor or 
their designate(s).  Any documents that identify the subject should be kept in strict 
confidence by the principal investigator.  
Based on ICH GCP guidelines and regulatory requirements, the investigator is required to 
allow authorized personnel of The Sponsor (or its designate), the IRB, and members of the 
appropriate regulatory authority(ies) to review subject’s files that are related to IA-001.  
Subjects must be informed that his/her records may be reviewed by The Sponsor, its 
designate(s), the IRB/EC and the appropriate regulatory authority(ies) through direct access 
to the subject’s original medical records. 
11 ADMINISTRATIVE AND LEGAL REQUIREMENTS 
11.1 
Sponsorship 
This clinical study is sponsored by Emergent BioSolutions Canada Inc., Winnipeg, MB, 
Canada, who is the manufacturer of FLU-IGIV. 
11.2 
Protocol Amendments 
Protocol amendments will only be made by The Sponsor.  Any change to the protocol must 
be made in the form of a formal amendment to the protocol and must be approved in writing 
by the principal investigator, The Sponsor, and the IRB/EC prior to implementation.  The 
investigator must receive written IRB/EC approval for all protocol amendments prior to 
implementing protocol amendments at the trial site, and the investigator must send a copy of 
any IRB/EC correspondence and all approval/disapproval letters from the IRB/EC to The 
Sponsor. Minor changes (ex. change of contact details or logistic arrangements) to the 
protocol will be submitted to the IRB/EC as a non-substantial amendment for information 
only. 

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11.3 
Deviations from the Protocol 
The investigator agrees to conduct the clinical trial in compliance with the protocol agreed to 
by The Sponsor and approved by the IRB/EC.  The investigator and The Sponsor shall sign 
the protocol to confirm this agreement. 
The investigator will not deviate from this protocol for any reason without prior approval of 
the sponsor and the IRB/EC, except in cases of medical emergencies.  The investigator may 
deviate from the protocol without the prior approval of the IRB/EC or The Sponsor only 
when the deviation is necessary to eliminate an apparent immediate hazard to the subjects.  In 
that event, the investigator must notify the IRB/EC and The Sponsor in writing as soon as 
possible and no more than 5 working days after the deviation is implemented.  The 
investigator shall document and explain any deviation from the approved protocol. 
11.4 
Source Documentation and Storage 
The source documentation requirements described below apply to all source documentation 
and trial records in any form, including those maintained in the institution’s Electronic 
Health Record system, if applicable. 
The investigator should maintain adequate and accurate source documents and trial records 
that include all pertinent observations on each of the site’s trial subjects. Source data should 
be attributable, legible, contemporaneous, original, accurate, and complete. Changes to 
source data should be traceable, should not obscure the original entry and should be 
explained if necessary (e.g., via an audit trail). 
The principal investigator will maintain the following information: 
• Medical history/physical condition of the trial subject before involvement in the trial 
sufficient to verify protocol entry criteria. 
• Dated and signed notes on the day of entry into the trial including the trial number, the 
drug being evaluated, subject trial ID number assigned, and a statement that informed 
consent was obtained, noting the time the consent was obtained. 
• Dated and signed notes from each trial subject visit that refer to the protocol or CRFs for 
further information, if appropriate (i.e., for specific procedures and exams). 
• The investigator will assess each abnormal lab result as clinically significant (CS) or not 
clinically significant (NCS).  For Clinically Significant results, a brief explanation will be 
written on the laboratory report.  These assessments will be noted on the laboratory report 
source document, and signed and dated on the date of the investigator’s review. 
• Notes regarding concomitant medications taken during the trial (including start and stop 
dates). 
• Source documents regarding adverse events occurring during the trial including date of 
onset and cessation, seriousness, severity, causality, action taken and related concomitant 
medications. 
• Trial subjects’ condition upon completion, or withdrawal from the trial. 

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• All communications with the IRB/EC responsible for the trial. 
• Drug accountability records. 
• Any other records as required by The Sponsor/designate, the IRB/EC or the regulatory 
authority(ies). 
The investigator must arrange for the retention of the subject identification codes for at least 
25 years after the completion or discontinuation of the trial (Revised Canadian CTA 
Regulations, September 2001).  Subject files and other source data must be securely stored 
and kept for the maximum time permitted by the hospital, institution or private practice but 
not less than 25 years after completion or termination of the trial.  Archival data may be held 
on microfiche or electronic record, provided that a backup exists and that hard copy can be 
obtained from it if required.  If source documents are to be destroyed as per hospital or local 
regulatory policy, the investigator is requested to contact The Sponsor. 
Records from the trial that identify the subject will be confidential except that they may be 
given to and inspected by The Sponsor of the trial (or designate(s)), the IRB/EC, the Food 
and Drug Administration, other relevant regulatory agencies as appropriate, and will not 
otherwise be released except as required by law.  All information provided to the investigator 
by The Sponsor is to be considered confidential unless otherwise stated. 
11.5 
Electronic Data  
The investigator (or designate) will record data collected in this clinical trial on electronic 
CRFs (eCRFs).  The electronic forms are to be completed on a contemporaneous basis. 
The data are the property of The Sponsor of the trial.  Questions arising from eCRF data will 
be dealt with by the issuance of Data Queries within the EDC environment by The Sponsor 
Clinical Data and Statistics (or designate) to the investigator. 
11.6 
Monitoring 
Safety will be monitored using a risk-based monitoring approach. At the time the trial is 
initiated, monitors from The Sponsor/CRO will thoroughly review the protocol and data 
forms with the investigators and their staff. During the trial, the monitors will be available to 
discuss by telephone, e-mail, or in person (during site visits), questions regarding adverse 
reactions, removal of subjects from the trial, conduct of the trial and other clinical trial 
matters. Monitors from The Sponsor/CRO will visit at the initiation of the trial, during the 
trial and at the completion of the trial. At the time of each monitoring visit, the monitors will 
check the case report forms of the subjects to ensure that all items have been completed, that 
the data are accurate and obtained in the manner specified in the protocol and that data 
recorded on the data forms for the trial agree with medical records at the site. The monitors 
will also check for general protocol and regulatory compliance by subjects and site 
personnel. 
To ensure maintenance of the blind, each clinical site will have two separate monitors 
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unblinded drug accountability at the site pharmacy. The clinical sites will be provided with 
the trial related training/ instructions at the initiation and throughout the conduct of the trial.   
11.6.1 Medical Monitoring 
Medical Monitor(s), appointed by the Sponsor, will be available during the trial to assist sites 
with study related questions such as medically relevant conduct issues, questions regarding 
inclusion/exclusion, safety trending analysis, safety reporting issues, and patient management 
questions. Medical Monitor(s) will collaborate with study project, medical, and 
pharmacovigilance teams, as well as data safety monitoring board with regard to all project-
specific medical and safety-related questions. An unblinded Medical Monitor will also be 
involved to provide consultation/ guidance to the unblinded study team. Roles and 
responsibilities for the Medical Monitoring team will be further defined in the Medical 
Monitoring Plan. 
11.7 
Quality Control and Quality Assurance 
The Sponsor Quality Assurance department (or authorized representatives) may conduct 
onsite audits of all aspects of the clinical trial prior to, during the trial, or after the trial has 
been completed.  The clinical trial may also be inspected by regulatory authorities or the 
IRB/EC to verify that the trial is being or has been conducted in accordance with protocol 
requirements, GCP, as well as the applicable regulatory requirements. 
11.8 
Quality Management  
The Sponsor maintains a Quality Management System encompassing SOPs, risk assessment, 
risk management with defined data management plans, monitoring plans and audit plans to 
assure regulatory compliance, patient safety, robust data management and scientific integrity. 
11.9 
Publication Policy 
Data arising from this trial are the sole property of The Sponsor of the trial, The Sponsor.  
The Sponsor must provide written, prior agreement to any publication based, in whole or in 
part, on data from this trial.  All proposed abstracts, manuscripts or presentations from the 
study must be provided to The Sponsor for review at least 60 days prior to submission for 
publication/presentation. Any information identified by The Sponsor as confidential must be 
deleted prior to submission. 
The Publication Policy applicable to this protocol is the one agreed upon and described in the 
Clinical Trial Agreement between The Sponsor and the principal investigator. 

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12 REFERENCES 
1. 
CDC. Influenza Antiviral Medications: Summary for Clinicians [Internet]. Atlanta (GA) 
[cited 2017 Feb 27]. Available from: 
https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm  
2. 
European Centre for Disease Prevention and Control. Expert opinion on neuraminidase 
inhibitors for the prevention and treatment of influenza – review of recent systematic 
reviews and meta-analyses. Stockholm: ECDC; 2017.  
3. 
Herbreteau CH, Jacquot F, Rith S, Vacher L, Nguyen L, Carbonnelle C, et al. Specific 
polyclonal F(ab')2 neutralize a large panel of highly pathogenic avian influenza A viruses 
(H5N1) and control infection in mice. Immunotherapy. 2014;6(6):699-708.  
4. 
Herbreteau CH, Denizot M, Lowther S, Riddell S, Frazer L, Haining J, et al. Efficacy of a 
specific polyclonal equine F(ab')2 against avian influenza (H5N1) in ferrets: synergy with 
oseltamivir. Immunotherapy. 2016 Sep;8(9):1021-32.  
5. 
Bal C, Herbreteau CH, Buchy P, Rith S, Zaid M, Kristanto W, et al. Safety, potential 
efficacy, and pharmacokinetics of specific polyclonal immunoglobulin F(ab')₂ fragments 
against avian influenza A (H5N1) in healthy volunteers: a single-centre, randomised, 
double-blind, placebo-controlled, phase 1 study. Lancet Infect Dis. 2015 Mar;15(3):285-
92. doi: 10.1016/S1473-3099(14)71072-2.  
6. 
Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood 
products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 
2006 Oct 17;145(8):599-609.  
7. 
Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) 
infection. N Engl J Med. 2007 Oct 4;357(14):1450-1.  
8. 
Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, et al. Convalescent plasma 
treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 
virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56.  
9. 
Hung IF, To KK, Lee CK, Lee KL, Yan WW, Chan K, et al. Hyperimmune IV 
immunoglobulin treatment: a multicenter double-blind randomized controlled trial for 
patients with severe 2009 influenza A(H1N1) infection. Chest. 2013 Aug;144(2):464-73.  
10. Rolfes MA, Foppa IM, Garg S, Flannery B, Brammer L, Singleton JA, et al. Estimated 
Influenza Illnesses, Medical Visits, Hospitalizations, and Deaths Averted by Vaccination 
in the United States. 2016 Dec 9 [2017 Feb 27]; Available from:  
https://www.cdc.gov/flu/about/disease/2015-16.htm  

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11. Hayden FG, de Jong MD. Emerging Influenza Antiviral Resistance Threats. The Journal 
of Infectious Diseases. 2011;203(1):6-10.  
12. Ye J, Shao H, Perez DR. Passive immune neutralization strategies for prevention and 
control of influenza A infections. Immunotherapy. 2012 Feb;4(2):175-86.  
13. Beigel JH, Luke TC. A Study in Scarlet - Convalescent Plasma for Severe Influenza. 
Critical Care Medicine. 2012;40(3):1027-1028.  
14. Kurz M. Developing therapeutic immunoglobulins: European regulatory perspectives and 
implications. BioDrugs. 2008;22(3):145-60.  
15. Moscona A. Neuraminidase inhibitors for influenza. N Engl J Med. 2005 Sep 
29;353(13):1363-73.  
16. Davey RT, Markowitz N, Beigel J, Wentwork D, Babiker A, Rehman T, et al. INSIGHT 
FLU005: An Anti-Influenza Virus Hyperimmune Intravenous Immunoglobulin Pilot 
Study. J Infect Dis. 2016 Feb 15;213(4):574-8. 
17. National Institute of Allergy and Infectious Diseases (NIAD). Anti-Influenza 
Hyperimmune Intravenous Immunoglobulin Pilot Study (INSIGHT 005: Flu-IVIG Pilot). 
In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 
2000- [2017 Feb 27]. Available from: https://clinicaltrials.gov/show/NCT02008578 NLM 
Identifier: NCT02008578. 
18. National Institute of Allergy and Infectious Diseases (NIAD). Evaluating the Safety and 
Efficacy of Anti-Influenza Intravenous Hyperimmune Immunoglobulin (IVIG) in Adults 
Hospitalized With Influenza. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National 
Library of Medicine (US). 2000- [2017 Feb 27]. Available from: 
https://clinicaltrials.gov/show/NCT02287467 NLM Identifier: NCT02287467. 
19. Royal College of Physicians. National Early Warning Score (NEWS): Standardising the 
assessment of acute illness severity in the NHS. Report of a working party. London: 
RCP, 2012. 
20. Dunhem C, Dicato MA, Ries F. Side-effects of intravenous immunoglobulins Clin Exp 
Immunol 1994;97 (Suppl 1):79-83.  
21. NIH Consensus conference on intravenous immunoglobulin: prevention and treatment of 
disease. JAMA 1990;24:3189-93.  

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APPENDIX I 
 

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APPENDIX I 
NCT03315104
A Randomized, Double-Blind, Placebo-Controlled Dose Ranging Study
Evaluating the Safety, Pharmacokinetics and Clinical Benefit of FLUIGIV
in Hospitalized Patients with Serious Influenza A Infection
Version 4.0
24 May 2018
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VERSION 2.0 10.MAY.2018 
NEW SCORING GUIDE
Protocol No. / Title 
IA-001 / A Randomized, Double-Blind, Placebo-Controlled Dose Ranging 
Study Evaluating the Safety, Pharmacokinetics and Clinical Benefit of FLU-
IGIV in Hospitalized Patients with Serious Influenza A Infection 
Category 
Score 
Value 
Category 
Score 
Value 
Respiratory 
Rate 
(breaths/min) 
3 
≤ 8 
SpO2 
(%) 
3 
≤ 91 
1 
9-11 
2 
92-93 
0 
12-20 
1 
94-95 
2 
21-24 
0 
≥ 96 
3 
≥ 25 
Inspired O2 
(%) 
2 
Yes: Any 
supplemental O2 
0 
Not receiving 
supplemental O2 
Temperature 
3 
≤ 35 °C 
Systolic Blood 
Pressure 
(mmHg) 
3 
≥ 220 
≤ 95 °F 
1 
35.1-36 °C 
0 
111-219 
95.1-96.8 °F 
0 
36.1-38 °C 
1 
101-110 
96.9-100.4 °F 
1 
38.1-39 °C 
2 
91-100 
100.5-102.2 °F 
2 
≥ 39.1 °C 
3 
≤ 90 
≥ 102.3 °F 
Heart Rate 
(BPM) 
3 
≥ 131 
Level of 
Consciousness 
0 
Alert 
2 
111-130 
3 
Voice (V) 
Pain (V) 
Unresponsive (U) 
1 
91-110 
0 
51-90 
TOTAL: 
_____________ 
Add up all assigned score 
values in each category* 
to obtain the total NEW 
score. 
1 
41-50 
3 
≤ 40