Safety and Pharmacokinetic Evaluation of Zika Virus Immune Globulin in Healthy Volunteers
Phase: PHASE1
Conditions: Zika Virus Infection, Zika Virus Disease
Sponsor: Emergent BioSolutions

Protocol ZK-001 
Version 3.1, June 5, 2018 
 
Emergent BioSolutions Canada Inc. 
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Clinical Trial Protocol 
Safety and Pharmacokinetic Evaluation of Zika Virus Immune Globulin in 
Healthy Volunteers 
ZK-001 
Version 3.1 
June 5, 2018 
 
 
 
Emergent BioSolutions Canada Inc. 
 
 
CONFIDENTIAL 
This document is a confidential communication of the Sponsor.  Acceptance of this 
document constitutes an agreement by the recipient that no unpublished information 
contained within will be published or disclosed without prior written approval, except that 
this document may be disclosed to the appropriate Ethics Committee and Regulatory 
Authority under the condition that they keep it confidential. 

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Safety and Pharmacokinetic Evaluation of Zika Virus Immune Globulin in 
Healthy Volunteers 
Protocol ZK-001 
Version 3.1  
June 5, 2018 
 
Trial Sponsor: 
Emergent BioSolutions Canada Inc.  
 
 
 
Contract Research Organization (CRO): 
 
INC Research 
 
 
 
 
CRO Reference Laboratory:  
Dynacare 
 
 
 
 
Clinical Trial Scientist: 
 
 
 
 
 
 
 
 
 

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Sponsor’s Study Medical Monitor: 
 
 
 
 
 
 

Protocol ZK-001 
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ZK-001 Protocol Synopsis 
 
Title 
Safety and Pharmacokinetic Evaluation of Zika Virus Immune 
Globulin in Healthy Volunteers 
Sponsor 
Emergent BioSolutions Canada Inc. 
 
 
 
Trial Start 
Q2-Q3 2018 
Objectives 
Primary Objective: 
• To assess safety of ZIKV-IG in healthy volunteers.  
Secondary Objective: 
• To determine pharmacokinetics (PK) of ZIKV-IG in healthy 
volunteers. 
Subject 
Population 
Healthy male and non-pregnant female volunteers 
Sample Size 
30 subjects 
Number of Trial 
Sites 
The clinical trial will be conducted at a single trial site. 
Test Product 
Zika Virus Immune Globulin (Human) (ZIKV-IG) (code name: 
NP-024), a purified human immunoglobulin preparation 
containing neutralizing antibodies to Zika virus. ZIKV-IG is 
supplied as a sterile liquid suitable for intravenous administration 
to individuals with blood type O+ or O-. 
Reference 
Product 
Placebo (saline solution), supplied as a sterile liquid suitable for 
intravenous administration. 
Protocol Design 
Phase 1, single-center, randomized, double blind, placebo-
controlled trial design. 
Dosage 
One dose level of ZIKV-IG will be evaluated, along with placebo. 
Thirty subjects will be randomized to intravenously receive either 
ZIKV-IG dose (50.0 mL undiluted; n=19) or placebo (50.0 mL; 
n=11).   
Dosing of the first six subjects (group 1) will be staggered over 
three days, wherein two subjects per day will be randomized 1:1 

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and dosed at least 3 hours apart (subgroups 1A, 1B, 1C; each 
subgroup to be dosed at least one day apart). If in the opinion of 
the principal investigator there are no identified safety concerns 
after the first six dosed subjects, a group of six subjects (group 2) 
will be randomized 2:1 and dosed (at least 30 minutes apart) over 
the course of one day. A safety monitoring committee will be held 
to evaluate safety (collected up to 72 hours post-dosing) of the 
first 12 dosed subjects. If there are no safety signals identified, 
then the remaining 18 subjects will be randomized 2:1 and dosed 
(at least 30 minutes apart) in three separate groups of six subjects 
(groups 3, 4, 5) over a period of three days; each group of six 
subjects will be dosed over the course of one day.  
Each subject will be followed-up for 85 calendar days post-study 
treatment administration. 
Inclusion Criteria 
1. Informed consent voluntarily signed by subject. 
2. Age: 18–55 years of age.  
3. Blood type O+ or O-. 
4. Body mass index (BMI) of 18–30. 
• Note: minimum body weight of 50 kg. 
5. For female subjects (with male partners) that are not surgically 
sterilized (e.g., did not undergo hysterectomy, bilateral 
oophorectomy or tubal ligation), use of an effective method of 
contraception throughout the trial including: 
• Using hormonal contraception (oral, injectable or implant) 
continuously for 3 months prior to screening and willing to 
continue to use hormonal contraception throughout the 
entire trial. 
• Intrauterine device (IUD) inserted at least 1 month prior to 
screening. 
• Double barrier type of birth control measure (e.g., 
condoms, diaphragms, cervical sponge with spermicide). 
• True abstinence.  
• For female subjects who are post-menopausal, documented 
follicle-stimulating hormone (FSH) ≥40 mIU/mL must be 
obtained. If the FSH is <40 mIU/mL, the subject must 
agree to use an acceptable form of contraception (see 
above).  
• Females of childbearing potential without male sexual 
partners must be willing to maintain their sexual status as it 
is throughout the study. 

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6. For male subjects that have not had a vasectomy, use of a 
condom with spermicide or true abstinence for the duration of 
the study. Note: female partners (that are of childbearing 
potential) of male study subjects (that have not had a 
vasectomy) should use one of the effective contraception 
methods (eg, hormonal contraception, IUD or barrier type). 
Also, male subjects must not donate sperm for the duration of 
the study. 
• Males without female sexual partners must be willing to 
maintain their sexual status as it is throughout the study. 
7. Healthy as determined by principal investigator or a qualified 
designate based on medical history, physical exam, vital signs, 
urinalysis, blood chemistry and hematology test results at 
screening. 
Exclusion 
Criteria 
1. Use of any investigational product within the past 30 days.  
2. Use of any investigational product during the study. 
3. Individuals with blood type A, B or AB.  
4. Recipient of any blood product within the past 12 months. 
5. Plasma donation within 7 days or significant blood loss or 
blood donation within 56 days of baseline.  
6. Blood donation at any time during the study. 
7. Females with a hemoglobin level ≤120 g/L. 
8. Males with a hemoglobin level <130 g/L. 
9. History of hypersensitivity to blood or plasma products. 
10. History of allergy to latex or rubber. 
11. History of IgA deficiency.  
12. History of hypercoagulable conditions (e.g., deep vein 
thrombosis or pulmonary embolism). 
13. History of myocardial infarction.   
14. History of stroke. 
15. History of renal impairment/failure.  
16. Currently pregnant or lactating or planning to become pregnant 
during the study. 
17. History of flavivirus infection [ZIKV, dengue virus (DENV), 
West Nile virus (WNV), Japanese encephalitis virus (JEV), 

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yellow fever virus (YFV)] or vaccination with licensed or 
investigational flavivirus vaccine. 
18. Plans to travel to an area with active flavivirus (e.g., ZIKV 
and/or DENV) transmission during the study (and up to 10 
months after the study drug administration) or has returned 
from an endemic area with these diseases within 30 days of 
screening. 
19. Positive nucleic acid test (NAT) or serology for ZIKV or 
positive serology for WNV or DENV. 
20. Positive serology test (at screening) for human 
immunodeficiency virus 1 and 2 (HIV), hepatitis C virus 
(HCV); positive test for hepatitis B virus (HBV) as determined 
by HBsAg. 
21. History of chronic or acute severe neurologic condition (e.g., 
diagnosis of Guillain-Barre syndrome, epilepsy, Bell's palsy, 
meningitis or disease with any focal neurologic deficits). 
22. Heavy smokers (≥15cigarettes a day) or electronic cigarette 
use. 
23. History of, or suspected substance abuse problem (including 
alcohol). 
24. Failure of drug (urine) test at screening or baseline. 
25. Failure of alcohol (breath) test at screening or baseline. 
26. Receipt of a live vaccine within 28 days prior to screening or 
anticipated receipt of a live vaccine during the study period. 
27. Individuals with planned surgical procedures that will occur 
during the study. 
28. An opinion of the investigator that it would be unwise to allow 
participation of the subject in the study.  
Assessments 
Screening (within 35 days prior to Baseline): 
• Informed consent. 
• Review of study criteria. 
• Medical history, complete physical exam, vital signs 
(temperature, sitting blood pressure, respiratory rate, pulse 
oximetry and pulse rate), concomitant medications, body 
weight and height.  
• Blood type test. 

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• Electrocardiogram (ECG) assessment.  
• Hematology, blood chemistry and urinalysis (see Appendix I). 
• Viral marker testing: serology for HIV, HBV, HCV; ZIKV 
NAT (serum, urine) and serology for ZIKV, and serology for 
WNV and DENV. 
Note: ZIKV IgM serology will be performed by the site’s 
reference laboratory, while ZIKV IgG serology will be 
performed by the sponsor-developed non-diagnostic assay.  
• Serum pregnancy test for all female subjects of child bearing 
potential and FSH assessment for female subjects who are 
post-menopausal (defined as being amenorrheic for at least 1 
year). 
• Drug (urine) test. 
• Alcohol (breath) test. 
Baseline (Day -1; within 24 hours prior to Day 1): 
• Review of study criteria. 
• Complete physical exam, vital signs, body weight.  
• Hematology, blood chemistry (see Appendix I).   
• Medical history and concomitant medications. 
• Viral marker testing: ZIKV NAT (serum, urine) and serology 
for ZIKV. 
Note: ZIKV IgM serology will be performed by the site’s 
reference laboratory, while ZIKV IgG serology will be 
performed by the sponsor-developed non-diagnostic assay. 
• Serum pregnancy test for female subjects of child-bearing 
potential. 
• Alcohol (breath) and drug (urine) assessments. 
• Subjects will be required to stay overnight following their 
baseline assessment. 
Day 1 – Study Treatment Administration:  
Pre-study Treatment Administration Assessments: 
• 2 hours (±15 min) prior to study-treatment administration, vital 
signs will be assessed (to confirm screening eligibility for vital 
signs). 

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• 1 hour (±15 min) prior to study-treatment administration, vital 
signs will be assessed (to establish baseline vital signs).   
• Within 2 hours prior to study-treatment administration, blood 
sample for baseline anti-ZIKV antibody assessment (pre-dose 
PK sample) will be collected.  
After the above assessments have been completed, ZIKV-IG or 
placebo will be administered intravenously. 
Assessments during IV Administration of Study Treatment:  
15 minutes (±5 min) into the IV infusion and at the end of IV 
infusion (+5 min): 
• Assessment of vital signs.  
• Adverse events. 
• Concomitant medications (if applicable).  
Day 1: 1 Hour (±5 min), 3 Hours (±30 min), 8 Hours (±1 hr) 
and 24 Hours (±3 hrs) after End of Study Treatment 
Administration 
• Blood sample collection for anti-ZIKV antibody assessment 
(PK sample). 
• Assessment of vital signs, adverse events and concomitant 
medications. 
Subjects will stay in the clinic until 24-hour time-point post-study 
treatment assessments are completed. 
Day 2 (Discharge Day): 24 Hours (±3 hrs after End of Study 
Treatment Administration 
• Blood sample collection for anti-ZIKV antibody assessment 
(PK sample). 
• Assessment of vital signs, adverse events and concomitant 
medications.  
• Blood chemistry and hematology; note: if ≥2 g/dL (i.e., ≥20 
g/L) hemoglobin drop from baseline (Day -1) is observed, 
hemolysis tests will be performed (see Appendix I). 
Day 3 (48±3 hrs), Day 4 (72±3 hrs), Day 6 (120±6 hrs), Day 8 
(168±6 hrs), Day 10 (216±12 hrs), Day 12 (264±12 hrs), Day 15 
(336±12 hrs), Day 22 (504±24 hrs), Day 29 (672±24 hrs), Day 
43 (1008±48 hrs) and Day 57 (1344±48 hrs) after Study 
Treatment Administration*:  

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* Note: study visits are indicated as calendar days, while time-
points in relation to end of study treatment administration are 
indicated in the brackets. 
• Blood sample collection for anti-ZIKV antibody assessment 
(PK sample). 
• Assessment of vital signs, adverse events and concomitant 
medications. 
• Blood chemistry and hematology assessments; note: if ≥2 g/dL 
(i.e., ≥20 g/L) hemoglobin drop from baseline (Day -1) is 
observed [ONLY up to Day 15 visit (336±12 hrs post-study 
treatment administration), hemolysis tests will be performed 
(see Appendix I)].  
Day 85 (2016±72 hrs after end of study treatment 
administration) or Early Withdrawal: 
• Blood sample collection for anti-ZIKV antibody assessment 
(PK sample). 
• Assessment of vital signs, adverse events and concomitant 
medications. 
• Assessment of blood chemistry and hematology (see Appendix 
I). 
• Serum pregnancy test for female subjects of child-bearing 
potential.  
• Viral marker testing: serology for HIV, HBV, HCV and ZIKV 
NAT (serum, urine) and serology for ZIKV. 
Note: ZIKV IgM serology will be performed by the site’s 
reference laboratory, while ZIKV IgG serology will be 
performed by the sponsor-developed non-diagnostic assay. 
• Complete physical exam.  
Primary 
Endpoint(s) 
The primary endpoint is the number and severity of adverse 
events. 
Secondary 
Endpoints 
The secondary endpoints are ZIKV-IG pharmacokinetic 
parameters (see below). 
Safety 
Parameters 
Safety will be evaluated based on the following parameters: 
• Adverse events  
• Laboratory test results (hematology, blood chemistry, viral 
marker testing)  

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• Physical exams 
• Vital signs 
Pharmacokinetic 
Parameters 
Based on serum concentrations of ZIKV antibodies, the following 
PK parameters will be calculated using non-compartmental 
analysis: 
• AUC0-t: area under the concentration-time curve from time 0 
to the last quantifiable concentration. 
• AUC0-day 7. 
• AUC0-inf: AUC0-t plus the additional area extrapolated to 
infinity. 
• Cmax: maximum observed concentration. 
• Tmax: time at which Cmax occurs. 
• λz: terminal elimination rate constant. 
• t1/2: apparent first order terminal elimination half-life.  
• CL: total body clearance following IV administration. 
• VZ: volume of distribution following IV administration. 

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Schedule of Events for ZK-001  
 
 
Screening  
(within 35 
days of 
Baseline) 
Baseline  
(Day -1; 
within 24 
hrs of 
Day 1) 
Post Study Treatment Administration Visits* 
Day 1 
(Dosing 
Day) 
Day 2 
(Discharge 
Day) 
Day 3  
 
Day 4 
 
Day 6 
 
Day 8 
 
Day 10  
 
Day 12 
 
Day 15 
 
Day 22 
 
Day 29 
 
Day 43 
 
Day 57 
 
Day 85  
or  
Early 
Withdrawal 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
X1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete 
physical exam 
X2 
X2 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Study treatment 
administration 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs3 
X 
X 
X4a 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
X 
X 
 
X5  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood chemistry 
X 
X 
 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Drug (urine) test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alcohol (breath) 
test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test 
X6 
X6 
 
 
 
 
 
 
 
 
 
 
 
 
 
X6 

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Screening  
(within 35 
days of 
Baseline) 
Baseline  
(Day -1; 
within 24 
hrs of 
Day 1) 
Post Study Treatment Administration Visits* 
Day 1 
(Dosing 
Day) 
Day 2 
(Discharge 
Day) 
Day 3  
 
Day 4 
 
Day 6 
 
Day 8 
 
Day 10  
 
Day 12 
 
Day 15 
 
Day 22 
 
Day 29 
 
Day 43 
 
Day 57 
 
Day 85  
or  
Early 
Withdrawal 
Viral markers 
X7 
X8 
 
 
 
 
 
 
 
 
 
 
 
 
 
X9 
PK sample 
collection 
 
 
X4b 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
 
 
X4b 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications 
X 
X 
X4b 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1 Update of medical history (if necessary).  
2 Including assessment of BMI; height and body weight will be measured at Screening and only body weight again at Baseline.  
3 Vital signs include temperature, sitting blood pressure, respiratory rate, pulse oximetry and pulse. 
4a Vital signs to be performed 2 hours (±15 min) and 1 hour (±15 min) prior to dosing, during the IV infusion at 15 minutes (±5 min) and at the end of the IV infusion (+5 min)], 
and post-dosing at 1 hour (±5 min), 3 hours (±30 min) and 8 hours (±1 hr). 
4b PK sample collection, adverse events and concomitant medications assessments at 1 hour (±5 min), 3 hours (±30 min) and 8 hours (±1 hr) post-dosing. Pre-dose (i.e., baseline) 
PK sample to be collected within 2 hours prior to dosing.  
5 To be performed 24 hours (±3 hours) post-dosing.  
6 At screening serum pregnancy test for female subjects of child-bearing potential and FSH assessment for post-menopausal female subjects. The serum pregnancy test is required 
only for women of childbearing potential for Baseline (Day -1) and Day 85 study visits.  
7 Serology testing for HIV, HBV, HCV, DENV, WNV; ZIKV NAT (serum, urine) and ZIKV serology. 
8 ZIKV NAT (serum, urine) and ZIKV serology testing.  
9 Serology testing for HIV, HBV, HCV; ZIKV NAT (serum, urine) and ZIKV serology. 
 
* Day 1 includes 1 hour (±5 min), 3 hours (±30 min) and 8 hours (±1 hr) time-points post-dosing, Day 2 is 24 hours (±3 hrs),  Day 3 is 48 hours (±3 hrs), Day 4 is 72 hours (±3 
hrs), Day 6 is 120 hours (±6 hrs), Day 8 is 168 hours (±6 hrs),  Day 10 is 216 hours (±12 hrs), Day 12 is 264 hours (±12 hrs), Day 15 is 336 hours (±12 hrs), Day 22 is 504 hours 
(±24 hrs), Day 29 is 672 hours (±24 hrs), Day 43 is 1008 hours (±48 hrs), Day 57 is 1344 hours (±48 hrs) and Day 85 is 2016 hours (±72 hrs) post-dosing.  
 
NOTE: all study laboratory assessments (for a list of all laboratory tests see Appendix I) will be performed by the Phase 1 clinic’s reference laboratory, except for ZIKV IgG serology 
(screening, baseline and Day 85 samples) which will be performed by the sponsor-developed non-diagnostic assay. In addition, the subjects’ PK samples will be tested with two types of 
assays (a binding ZIKV antibody assay and a neutralizing ZIKV antibody assay). 

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Table of Contents 
1 
BACKGROUND INFORMATION ............................................................................21 
1.1 
Zika Virus .............................................................................................................21 
1.2 
Trial Drug .............................................................................................................21 
1.3 
Clinical Trial Rationale .......................................................................................22 
2 
TRIAL OBJECTIVES..................................................................................................23 
2.1 
Primary Objective ................................................................................................23 
2.2 
Secondary Objective ............................................................................................23 
3 
TRIAL DESIGN............................................................................................................23 
3.1 
Trial Design ..........................................................................................................23 
3.2 
Anticipated Centers .............................................................................................23 
3.3 
Sample Size ...........................................................................................................23 
3.4 
Randomization .....................................................................................................24 
3.5 
Blinding .................................................................................................................24 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS .............................................25 
4.1 
Subject Inclusion Criteria ...................................................................................25 
4.2 
Subject Exclusion Criteria ..................................................................................26 
4.3 
Subject Withdrawal .............................................................................................27 
4.3.1 
Subject Withdrawal Criteria ...............................................................................27 
4.3.2 
Subject Replacement ...........................................................................................28 
4.3.3 
Follow-up for Withdrawn Subjects .....................................................................28 

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5 
TRIAL MEDICATION ................................................................................................28 
5.1 
Packaging and Formulation ................................................................................28 
5.2 
Labeling ................................................................................................................29 
5.3 
Storage Conditions ...............................................................................................29 
5.4 
Preparation ...........................................................................................................29 
5.5 
Administration .....................................................................................................30 
5.6 
Medication Shipment ...........................................................................................31 
5.7 
Drug Accountability.............................................................................................31 
6 
TRIAL PROCEDURES ...............................................................................................32 
6.1 
Screening (within 35 days prior to Baseline) .....................................................32 
6.2 
Randomization .....................................................................................................33 
6.3 
Baseline Assessments (Day -1; within 24 hours prior to Day 1) ......................33 
6.4 
Study Treatment Administration (Day 1) .........................................................34 
6.5 
Trial Assessments during/following Study Treatment Administration ..........35 
6.6 
Handling of Samples for PK Analysis ................................................................36 
6.7 
Shipment of Samples for PK Analysis ...............................................................37 
6.8 
Pharmacokinetic Sample Analysis .....................................................................37 
6.9 
Concomitant Medications ...................................................................................38 
7 
ASSESSMENT OF PHARMACOKINETICS ...........................................................38 
7.1 
PK Parameters .....................................................................................................38 
7.2 
Assessment of PK Parameters ............................................................................38 
8 
ASSESSMENT OF SAFETY .......................................................................................39 
8.1 
Adverse Event/Serious Adverse Event Definition .............................................39 
8.2 
Definitions .............................................................................................................39 

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8.3 
Assessment of Severity (Intensity) ......................................................................40 
8.3.1 
Assessment of Causality (ICH Classification) ....................................................41 
8.4 
Description of Known Adverse Event Profile for ZIKV-IG ............................41 
8.5 
Adverse Event Reporting ....................................................................................42 
8.6 
Reporting of SAEs................................................................................................43 
8.7 
Safety Monitoring Committee ............................................................................43 
9 
STATISTICAL ISSUES IN TRIAL DESIGN AND PK ASSESSMENT ................44 
9.1 
Sample Size Calculation ......................................................................................44 
9.1.1 
Safety Population ................................................................................................45 
9.1.2 
PK Population .....................................................................................................45 
9.2 
Trial Endpoints ....................................................................................................45 
9.2.1 
Primary Endpoint ................................................................................................45 
9.2.2 
Secondary Endpoints ..........................................................................................45 
9.2.3 
Safety Endpoints .................................................................................................45 
9.2.4 
Criteria for Early Termination of the Trial .........................................................46 
9.3 
Interim Analyses ..................................................................................................47 
9.4 
Planned Method of Analyses ...............................................................................47 
10 
REGULATORY AND ETHICAL ISSUES ................................................................48 
10.1 
Declaration of Helsinki ........................................................................................48 
10.2 
Informed Consent ................................................................................................48 
10.3 
Institutional Review Board (IRB).......................................................................50 
10.4 
Documentation Required Prior to Trial Initiation ...........................................50 
10.5 
Subject Confidentiality ........................................................................................51 
11 
ADMINISTRATIVE AND LEGAL REQUIREMENTS ..........................................51 

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11.1 
Sponsorship ..........................................................................................................51 
11.2 
Protocol Amendments .........................................................................................51 
11.3 
Deviations from the Protocol ..............................................................................51 
11.4 
Source Documentation and Storage ...................................................................52 
11.5 
Electronic Data Forms .........................................................................................53 
11.6 
Monitoring ............................................................................................................53 
11.7 
Quality Control and Quality Assurance ............................................................54 
11.7.1 Quality Management ...........................................................................................54 
11.8 
Publication Policy.................................................................................................54 
12 
REFERENCES ..............................................................................................................55 
13 
APPENDIX I .................................................................................................................57 

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List of Abbreviations and Definition of Terms 
ADE 
Antibody-dependent enhancement  
AE 
Adverse event 
AIGIV 
Anthrax Immune Globulin Intravenous (Human)  
ANTHRASIL® 
Anthrax Immune Globulin Intravenous (Human)  
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 
BMI 
Body mass index 
CL/F 
Apparent clearance  
Cmax 
Maximum serum concentration 
CNJ-16® 
Vaccinia Immune Globulin Intravenous (Human) 
CRO 
Contract research organization 
CS 
Clinically significant  
CSR 
Clinical study report  
CZS 
Congenital Zika syndrome  
DENV 
Dengue virus 
EC 
Ethics committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone  
GBS 
Guillain–Barré syndrome  
GCP 
Good Clinical Practices 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 

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HepaGam B® 
Hepatitis B Immune Globulin (Human)  
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
ICH 
International conference on harmonization 
IRB 
Institutional review board 
IUD 
Intrauterine device  
IV 
Intravenous 
JEV 
Japanese encephalitis virus  
kDa 
kilodalton 
MedDRA 
Medical Dictionary for Regulatory Activities  
NAT 
Nucleic acid testing 
NCS 
Not clinically significant  
NP-024 
Anti-Zika Virus Immune Globulin (Human) 
SAE 
Serious adverse event 
SMC 
Safety monitoring committee  
US(A) 
Unites States (of America) 
VARIZIG® 
Varicella Zoster Immune Globulin Intravenous (Human) 
VIGIV 
Vaccinia Immune Globulin Intravenous (Human) 
VZ/F 
Apparent volume of distribution  
WinRho® SDF 
Rho(D) Immune Globulin Intravenous (Human)  
WNV 
West Nile virus 
YFV 
Yellow fever virus 
ZIKV 
Zika virus 
ZIKV-IG 
Anti-Zika Virus Immune Globulin (Human)  
 
 
 

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1 
BACKGROUND INFORMATION 
1.1 
Zika Virus 
Zika virus (ZIKV) is an RNA flavivirus closely related to other flaviviruses such as dengue 
virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV) and West Nile 
virus (WNV). ZIKV is primarily transmitted through the bite of an infected Aedes species 
mosquito (Ae. aegypti and Ae. albopictus); however, sexual transmission has been frequently 
reported (1, 2). Most individuals infected by ZIKV are asymptomatic, while symptomatic 
individuals typically present with acute onset of fever, maculopapular rash, arthralgia, 
headache or nonpurulent conjunctivitis that usually last from several days to one week (1). 
However, ZIKV infection has been linked to Guillain–Barré syndrome (GBS) (3, 4) and 
other neurological impairments (5), albeit infrequently. ZIKV infection during pregnancy has 
been linked to adverse fetal/infant outcomes including fetal/infant microcephaly (6, 7), 
serious brain anomalies (8), ocular disorders (9), intrauterine growth restriction, and other 
congenital malformations resulting in congenital Zika syndrome (CZS) (10, 11). The 
percentage of fetuses/infants with possible ZIKV-associated birth defects ranges from 4-8%, 
depending on maternal time of ZIKV exposure during pregnancy (12). The ability of ZIKV 
to infect and damage developing fetuses implies that the virus can cross and/or bypass the 
placental barrier, but the mechanism remains unclear (13). Other flaviviruses, including 
DENV, are not associated with vertical transmission or congenital disorders, which suggest 
that this mechanism may be specific to ZIKV (14). Currently, there are no licensed or 
available products for prevention or treatment of ZIKV infection. Therefore, there is an 
unmet medical need to develop interventions against ZIKV. To that end Emergent 
BioSolutions Inc. is developing an Anti-Zika Virus Immune Globulin (Human) product (see 
Section 1.2).   
1.2 
Trial Drug  
Emergent BioSolutions Inc. (referred to as the sponsor throughout the protocol) is developing 
an Anti-Zika Virus Immune Globulin (Human) (ZIKV-IG) (code name: NP-024) product as 
an intervention for ZIKV. The ZIKV-IG product will be manufactured using the same 
hyperimmune manufacturing platform process as the one used to manufacture United States 
(US) Food and Drug Administration (FDA)-licensed products that include CNJ-016® 
[Vaccinia Immune Globulin Intravenous (Human), VIGIV], ANTHRASIL® [Anthrax 
Immune Globulin Intravenous (Human)], WinRho® SDF [Rho(D) Immune Globulin 
Intravenous (Human)], HepaGam B® [Hepatitis B Immune Globulin (Human)], and 
VARIZIG® [Varicella Zoster Immune Globulin Intravenous (Human)]1. ZIKV-IG is 
                                                          
1 CNJ-016® (VIGIV) and ANTHRASIL® (AIGIV) 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. All brand, product, 
service and feature names or trademarks of these products are the property of their respective owners.   

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produced with plasma collected from the FDA-licensed plasma collection centers from 
healthy donors with elevated levels of antibodies reactive to ZIKV antigens.  
ZIKV-IG is a purified human immune globulin preparation containing neutralizing 
antibodies to ZIKV. It is a glycoprotein of approximately 160 kilodaltons (kDa). The final 
ZIKV-IG product will be formulated in multiple single-use vials 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.  
Due to the limited number of plasma donors used to generate the plasma pool for 
manufacture of the ZIKV-IG clinical lot, donor plasma with high isoagglutinin titers (e.g. 
anti-A antibodies) were not excluded from plasma pools used for the manufacture of ZIKV-
IG. Therefore, ZIKV-IG is intended for intravenous (IV) administration only to individuals 
with blood type O+ or O-.  
The safety profile for immune globulin products is well-established due to a long history of 
their use in the clinical practice for a range of medical conditions (for more details refer to 
ZIKV-IG Investigator’s Brochure). Immune globulins are normal constituents of the human 
body fluid, and they are used at physiological levels without creating pharmacologic and 
toxicologic active metabolites (15). The planned ZIKV-IG dose for this clinical trial falls into 
the range of doses used for products manufactured with Emergent’s hyperimmune platform; 
hence, ZIKV-IG is expected to have a similar safety and pharmacokinetic (PK) profile to 
these hyperimmune products.  
1.3 
Clinical Trial Rationale 
ZK-001 clinical trial is designed to evaluate safety and PK of ZIKV-IG in healthy volunteer 
subjects. The trial will be conducted in compliance with this protocol, GCP and the 
applicable regulatory requirement(s). 
ZIKV-IG is an immune globulin (human IgG) product enriched with ZIKV antibodies. The 
general safety profile for immune globulin products is well-established in the clinic due to 
extensive use of these products for various types of medical conditions and infections (16). 
Furthermore, the sponsor has a long history of developing immune globulin based therapies, 
including the licensed products outlined in Section 1.2. Like other human immune globulins, 
the sponsor’s products manufactured on the hyperimmune platform have been studied in 
several healthy volunteer and patient clinical trials; the safety profile of these immune 
globulin products is consistent with other commercial immune globulin products and the PK 
profile is similar among the sponsor’s licensed immune globulin products with a half-life of 
approximately 24 to 30 days after IV administration. The proposed dose for this clinical trial 
[50 mL undiluted, total of 4.65 g of protein; administered as an IV infusion) is within the 
dose levels tested in clinical trials of the sponsor’s other licensed immune globulin products 
(outlined in Section 1.2) and is expected to display similar safety and PK profile to those 
products.  

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Based on non-clinical studies with ZIKV-IG, a single dose of ZIKV-IG [50 mL dose (total of 
4.65 g of protein), to be administered as an IV infusion] was selected for evaluation in ZK-
001; the clinical ZIKV-IG dose is in the range of efficacious doses evaluated in lethal mouse 
model of ZIKV infection [refer to Investigator’s Brochure for ZIKV-IG (NP-024)]. In 
addition, the levels of excipients in the selected ZIKV-IG dose for ZK-001 are well below the 
animal maximum tolerated doses, hence these substances are not expected to pose any health 
risks to humans [refer to Investigator’s Brochure for ZIKV-IG (NP-024)].  
Results from ZK-001 clinical trial will provide safety information on the intravenously 
administered ZIKV-IG dose, as well as PK parameters such as peak ZIKV-IG plasma levels, 
trough titers of ZIKV antibodies and ZIKV-IG half-life; these PK parameters will be used for 
dose selection in subsequent clinical trials with ZIKV-IG.    
2 
TRIAL OBJECTIVES  
2.1 
Primary Objective 
The primary objective of ZK-001 is to assess safety of ZIKV-IG in healthy volunteers. 
2.2 
Secondary Objective 
The secondary objective of ZK-001 is to determine pharmacokinetics (PK) of ZIKV-IG in 
healthy volunteers. 
3 
TRIAL DESIGN 
3.1 
Trial Design 
ZK-001 is designed as a Phase 1, single-center, double-blind, randomized, placebo-controlled 
clinical trial to evaluate safety and PK of ZIKV-IG in healthy volunteer subjects.  
3.2 
Anticipated Centers 
ZK-001 clinical trial will be conducted at a single Phase 1 clinical site, located in 
 
. 
3.3 
Sample Size 
Sample size for ZK-001 will be 30 healthy volunteers who will be randomized to receive 
either one dose level of ZIKV-IG (n=19) or placebo (n=11). While there was no formal 
sample size calculation as this is a Phase 1 clinical trial evaluating safety and PK of only one 
dose level of ZIKV-IG, up to 19 subjects treated with ZIKV-IG will allow for safety 
evaluation and calculation of PK parameters.  

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3.4 
Randomization 
Dosing of the first six subjects will be staggered over three days, wherein two subjects per 
day will be randomized 1:1 and dosed to receive either ZIKV-IG or placebo, while the 
remaining 24 subjects will be randomized 2:1 (four groups with six subjects in each group) in 
a double-blind fashion to receive either ZIKV-IG or placebo as described in Section 6.2.   
Randomization schedule generation and logistics will be handled by a designated individual 
(an unblinded statistician) at the Phase 1 CRO who will not be involved in study treatment 
administration or subject assessments. A dummy randomization schedule will be created by 
the CRO for review and approval by the sponsor. Subsequently, the production of unblinded 
randomization schedule will be generated by the CRO’s unblinded statistician for subject 
assignments. The randomization schedule will be stored in a locked room in a locked vault 
inaccessible to blinded personnel. 
3.5 
Blinding 
The pharmacy staff assigned to ZK-001 clinical trial at the CRO’s Phase 1 clinical site will 
be unblinded to access the randomization assignment and prepare the study treatment. There 
will be designated (subcontracted) unblinded clinical trial monitors, a segregated unblinded 
medical monitor and an independent unblinded Quality Assurance (QA) representative.  In 
addition, designated personnel at the sponsor’s bioanalytical laboratory who will be assigned 
to perform PK sample testing will indirectly become unblinded due to nature of test results, 
but measures will be implemented not to disseminate this information until database lock 
(see Section 6.8). Other personnel involved in the conduct of ZK-001 trial will remain 
blinded until database lock.   
Access to information in electronic data capture (EDC) system will be blinded using role-
based permissions. Randomization group and study treatment 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 CRO until after database lock to ensure 
maintenance of the blind. Study treatment dosing data will be reconciled with the randomized 
treatment group for each subject by the unblinded monitor, and any deviations will be 
reported in the Clinical Study Report (CSR). The ZK-001 trial will be unblinded once the 
clinical database is locked. 
While this is a double-blind trial, the blind may be broken if a subject’s health or safety is at 
risk and knowledge of the study treatment administered may be beneficial to the medical 
management of the subject. The pharmacist or other authorized individual may disclose the 
allocation of an individual subject’s study treatment if unblinding is required.  In such an 
event, the sponsor must be notified and appropriate documentation completed.  
A Safety Monitoring Committee (SMC) will be implemented to assure subject safety (for 
details on SMC see Section 0). The SMC will at a minimum consist of two blinded medical 
reviewers (Phase 1 clinic’s medical monitor and sponsor’s medical monitor) and one 
segregated unblinded medical monitor. 

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4 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
Subject Inclusion Criteria 
Subjects must meet the inclusion criteria to participate in ZK-001 trial. The inclusion criteria 
include the following: 
1. Informed consent voluntarily signed by subject. 
2. Age: 18–55 years of age. 
3. Blood type O+ or O-. 
4. Body mass index (BMI) of 18–30. 
• Note: minimum body weight of 50 kg. 
5. For female subjects (with male partners) that are not surgically sterilized (e.g., did not 
undergo hysterectomy, bilateral oophorectomy or tubal ligation), use of an effective 
method of contraception throughout the trial including: 
• Using hormonal contraception (oral, injectable or implant) continuously for 3 months 
prior to screening and willing to continue to use hormonal contraception throughout 
the entire trial. 
• Intrauterine device (IUD) at least 1 month prior to screening. 
• Double barrier type of birth control measure (e.g., condoms, diaphragms, cervical 
sponge with spermicide). 
• True abstinence.  
• For female subjects who are post-menopausal, documented follicle-stimulating 
hormone (FSH) ≥40 mIU/mL must be obtained. If the FSH is <40 mIU/mL, the 
subject must agree to use an acceptable form of contraception (see above).  
• Females of childbearing potential without male sexual partners must be willing to 
maintain their sexual status as it is throughout the study. 
6. For male subjects with female partners that have not had a vasectomy, use of a condom 
with spermicide or true abstinence for the duration of the study. Note: female partners 
(that are of childbearing potential) of male study subjects (that have not had a vasectomy) 
should use one of the effective contraception methods (e.g., hormonal contraception, IUD 
or barrier type). Also, male subjects must not donate sperm for the duration of the study. 
• Males without female sexual partners must be willing to maintain their sexual status 
as it is throughout the study.  
7. Healthy as determined by the principal investigator or a qualified designate based on 
medical history, physical exam, vital signs, urinalysis, blood chemistry and hematology 
test results at screening. 

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Note: for a list of specific laboratory tests (e.g., blood chemistry, hematology), refer to 
Appendix I. 
4.2 
Subject Exclusion Criteria 
Subjects who have any of the following exclusion criteria at screening and/or baseline will be 
excluded from participation in ZK-001 trial: 
1. Use of any investigational product within the past 30 days.  
2. Use of any investigational product during the study. 
3. Individuals with blood type A, B or AB. 
4. Recipient of any blood product within the past 12 months. 
5. Plasma donation within 7 days or significant blood loss or blood donation within 56 days 
of baseline. 
6. Blood donation at any time during the study. 
7. Females with a hemoglobin level ≤120 g/L. 
8. Males with a hemoglobin level <130 g/L. 
9. History of hypersensitivity to blood or plasma products. 
10. History of allergy to latex or rubber. 
11. History of IgA deficiency. 
12. History of hypercoagulable conditions (e.g., deep vein thrombosis or pulmonary 
embolism). 
13. History of myocardial infarction.  
14. History of stroke. 
15. History of renal impairment/failure.  
16. Currently pregnant or lactating or planning to become pregnant during the study. 
17. History of flavivirus infection [ZIKV, dengue virus (DENV), West Nile virus (WNV), 
Japanese encephalitis virus (JEV), yellow fever virus (YFV)] or vaccination with licensed 
or investigational flavivirus vaccine. 
18. Plans to travel to an area with active flavivirus (e.g., ZIKV and/or DENV) transmission 
during the study (and up to 10 months after study drug administration) or has returned 
from an endemic area with these diseases within 30 days of screening. 
19. Positive nucleic acid test (NAT) or serology for ZIKV (at screening) or positive serology 
for WNV or DENV (at screening). 

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20. Positive serology test (at screening) for human immunodeficiency virus 1 and 2 (HIV), 
hepatitis C virus (HCV); positive test for hepatitis B virus (HBV) as determined by 
HBsAg. 
21. History of chronic or acute severe neurologic condition (e.g., diagnosis of Guillain-Barre 
syndrome, epilepsy, Bell's palsy, meningitis or disease with any focal neurologic 
deficits). 
22. Heavy smokers (≥15cigarettes a day) or electronic cigarette use. 
23. History of, or suspected substance abuse problem (including alcohol). 
24. Failure of drug (urine) test at screening or baseline. 
25. Failure of alcohol (breath) test at screening or baseline. 
26. Receipt of a live vaccine within 28 days prior to screening or anticipated receipt of a live 
vaccine during the study period. 
27. Individuals with planned surgical procedures that will occur during the study. 
28. An opinion of the investigator that it would be unwise to allow participation of the 
subject in the study. 
Note 1: with respect to exclusion criterion no. 18, subjects will recommend to their partner(s) 
(if applicable) not to travel to flavivirus (e.g., ZIKV and/or DENV) endemic regions for the 
duration of the study and up to 10 months after the study drug administration. 
Note 2: for a list of specific laboratory tests (e.g., blood chemistry, hematology), refer to 
Appendix I. 
4.3 
Subject Withdrawal 
The subjects must be available, without coercion, for all parts of the trial. 
If continued participation jeopardizes the subject’s health at any point in the study, 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). 
4.3.1 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 an intercurrent illness that prevents completion of the trial. 

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• 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, subject misses study 
visits/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 
in the trial. 
Subjects withdrawn from the trial due to AEs will require follow-up until the AE(s) are 
resolved or stabilized (as per the investigator’s discretion). 
4.3.2 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. 
4.3.3 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 study period, will complete at a 
minimum all safety assessments for the early withdrawal visit as outlined in this protocol (see 
Section 6.5).  The investigator should inform the subjects that these assessments are for their 
own safety. 
5 
TRIAL MEDICATION 
5.1 
Packaging and Formulation  
ZIKV-IG (NP-024) is supplied in 3 cc (3 mL) glass vials with 2 mm siliconized bromobutyl 
rubber stoppers, aluminum seals and plastic flip-off caps. The extractable volume per vial is 
2 mL. Each vial is intended for single use. 
ZIKV-IG should be stored at 2–8ºC until required use (do not freeze ZIKV-IG).  
ZIKV-IG is provided 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 for IV administration. The final 
product is a clear to slightly opalescent and colorless liquid essentially free of particles. 
ZIKV-IG contains 30–130 mg/mL human plasma proteins (clinical lot for this trial contains 
93 mg/mL), of which at least 96% is human immune globulin G enriched with antibodies to 
ZIKV.  

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ZIKV-IG activity against ZIKV (product potency) is determined by a cell-based ZIKV 
microneutralization assay (potency release assay) that measures neutralization titer of ZIKV 
cytopathic effects.  
For more information, refer to the Investigator’s Brochure for ZIKV-IG. 
5.2 
Labeling 
ZIKV-IG vial labels will include information to comply with local regulations for the country 
in which the trial is conducted (Canada), in the appropriate language(s). 
Vial labels for Canada will include the following information in English and French: 
• “Investigational Drug to Be Used by Qualified Investigator Only” or similar wording 
• “For use in blood type O subjects only” 
• The name, number or identifying mark of the drug 
• The product’s protein concentration 
• The lot number 
• The expiration date 
• The protocol code or identification 
• The recommended storage conditions 
• The name and address of the sponsor 
Labeling for the shelf cartons will also bear this information. 
For dispensing labels for secondary receptacles, see Section 5.4 below.  
5.3 
Storage Conditions 
ZIKV-IG must be stored refrigerated at 2–8ºC 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 must be 
reported to the sponsor or designate. 
For further information, refer to the Investigator’s Brochure for ZIKV-IG. 
5.4 
Preparation 
The site will maintain documentation of a clear written formalized pharmacy study-specific 
procedure for study treatment preparation and blinding activities (including any sample 
labels and documentation to be completed), and documented training and delegation of the 
activity to appropriate trial staff. 

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Subject identifier (subject randomization number) must be recorded on the labels of the 
vial(s) used to prepare the study treatment.  Empty vials must be maintained for drug 
accountability. The study pharmacy staff will be only persons on-site who are unblinded to 
the study treatment assignment for each subject. 
To maintain the blind, all study treatments [ZIKV-IG or placebo (normal saline)] will be 
dispensed in a comparable manner. Both, the trial drug and placebo have the same 
administration volume and the site’s pharmacy staff who will prepare the study treatments 
will ensure that they are indistinguishable to maintain the blinding (details on preparation and 
maintaining the blind will be outlined in the site’s study-specific pharmacy procedure).   
The study treatments will be prepared for IV administration in secondary receptacles 
(syringes); hence, the dispensing label affixed to the syringes will capture the subject 
identifier (subject randomization number), visit number, expiry date of the prepared dose, 
principal investigator’s name, and protocol code (ZK-001).  
The trial drug (ZIKV-IG) will be prepared for administration at the appropriate dosage (total 
volume of 50 mL undiluted, prepared into a syringe) for an IV infusion; visual check to be 
completed to ensure total volume of 50 mL. The placebo (normal saline) will be prepared in 
the same manner for an IV infusion.  
The site pharmacy will be responsible for ensuring that the following supplies are available: 
• 
Normal saline 
• 
Syringes for study treatment dose preparation/administration 
For further information on ZIKV-IG dose preparation, refer to the Investigator’s Brochure 
for ZIKV-IG. In addition, details on study treatment preparation and handling will be 
outlined in the site’s study-specific pharmacy procedure. 
5.5 
Administration 
Administer ZIKV-IG within 3 hours of preparation into a syringe.  
Administer ZIKV-IG only under the supervision of the investigator and/or qualified 
designate(s).   
Once the ZIKV-IG dose is prepared into the syringe (50 mL total volume), connect it to an 
IV line and secure it on the infusion pump apparatus.  
Set the starting infusion rate at 1 mL/min for the first 15 minutes. If there are no adverse 
events (AEs), increase the rate to 2 mL/min for the remainder of the IV infusion (ie, at the 
recommended infusion rates and if no interruptions/reduction of the infusion rates, the IV 
infusion of 50 mL ZIKV-IG should be completed within 33 minutes). 
Note: the same administration procedure applies to IV infusion of the placebo. 
Monitor subjects closely during the IV infusion and for at least 1 hour after the study 
treatment administration. 

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If AEs occur during the IV infusion, such as flushing, headache, nausea, changes in pulse 
rate or blood pressure, the rate of infusion may be slowed or temporarily stopped until 
symptoms subside, at discretion of the investigator. The infusion rate may be resumed at a 
rate that is comfortable to the subject at discretion of the investigator [ie, if deemed 
necessary, infusion rate of less than 1 mL/min (eg, 0.5 mL/min) is permissible].  
Details on administration of study treatment (ZIKV-IG or placebo) will be outlined in the 
site’s study-specific procedure. 
The study subjects will be housed in the Phase 1 clinic for 24 hours after study treatment 
administration and will be regularly monitored throughout that period. 
5.6 
Medication Shipment 
ZIKV-IG will be shipped to the site at a temperature of 2–8ºC. 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. 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 designate.  
Trial drug 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. 
5.7 
Drug Accountability 
The principal investigator is responsible for maintaining accurate inventory records of ZIKV-
IG. 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. 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 will maintain a current inventory and ongoing record of 
test material supplies using the Drug Accountability Form(s) approved by the sponsor. This 
inventory record for ZIKV-IG 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 

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• 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. 
The inventory record will be stored in a locked pharmacy room at the site. 
These records will be reviewed by representatives of the sponsor, and may be reviewed by 
regulatory agencies. 
6 
TRIAL PROCEDURES 
6.1 
Screening (within 35 days prior to Baseline) 
Eligible subjects will first undergo informed consent counselling. Once informed consent has 
been obtained, subjects will undergo a screening visit to ascertain their eligibility in this trial.  
The screening visit assessments will include: 
• Written informed consent 
• Review of inclusion/exclusion criteria 
• Medical history  
• Complete physical exam, vital signs (temperature, pulse rate, pulse oximetry, respiration 
rate, sitting blood pressure), height and body weight (for BMI calculation) 
• ECG assessment. 
• Laboratory assessments:  
• Blood type test. 
• Blood chemistry, hematology and urinalysis (see Appendix I) 
• Serum pregnancy test for female subjects of child-bearing potential; FSH assessment 
for post-menopausal female subjects 
• Viral marker testing: serology for HIV, HBV, HCV; ZIKV NAT (serum, urine) and 
serology for ZIKV, serology for WNV and DENV 
Note: serology for ZIKV IgM testing will be performed by the site’s reference 
laboratory, while ZIKV IgG testing will be performed by the sponsor-developed non-
diagnostic assay. 
• Drug (urine) test.  
• Alcohol (breath) test. 
• Review of concomitant medications 

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Note: for a list of specific laboratory tests (e.g., blood chemistry, hematology), refer to 
Appendix I.  
6.2 
Randomization 
Following written informed consent, successful completion of the screening assessments and 
attendance at baseline study visit, 30 subjects will be randomized to receive an   IV infusion 
of either ZIKV-IG or placebo (normal saline).  
The subjects will be randomized and dosed in the following manner: the first six subjects 
(group 1) will be randomized 1:1 and dosed over three days (two subjects per day, dosed at 
least 3 hours apart; subgroups 1A, 1B and 1C; each subgroup to be dosed at least one day 
apart); the principal investigator will review the available safety information (adverse events, 
vital signs, concomitant medications) between each subject’s dosing interval. If in the 
opinion of the principal investigator there are no identified safety concerns after the first six 
dosed subjects, a group of six subjects (group 2) will be randomized 2:1 and dosed (at least 
30 minutes apart) over the course of one day. After review of safety data collected up to 72 
hours post study treatment administration for the first 12 dosed subjects by the Safety 
Monitoring Committee (SMC) and confirmation of no safety signals by the SMC (see 
Section 8.7 for details), the remaining 18 subjects will be randomized 2:1 and dosed (at least 
30 minutes apart) in three separate groups of six subjects (groups 3, 4 and 5) over a period of 
three days; each group of six subjects will be dosed over the course of one day. 
Randomization should occur after screening and as close as possible to study treatment 
administration on Day 1. 
6.3 
Baseline Assessments (Day -1; within 24 hours prior to Day 1) 
• Review of inclusion/exclusion criteria 
• Medical history [including updates (if applicable)] and concomitant medications. 
• Complete physical exam, vital signs (temperature, pulse, pulse oximetry, respiration rate, 
sitting blood pressure) and body weight  
• Laboratory assessments:  
• Blood chemistry and hematology 
• Serum pregnancy test for female subjects of child-bearing potential  
• Drug (urine) test and alcohol (breath) test  
• Viral marker testing: ZIKV NAT (serum, urine) and serology (IgM and IgG) for ZIKV 
Note: ZIKV NAT testing and IgM serology for ZIKV will be performed by the site’s 
reference laboratory, while ZIKV IgG testing will be performed by the sponsor-developed 
non-diagnostic assay.  

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• Collection of a blood sample for baseline (pre-dose) anti-ZIKV antibody assessment (PK 
sample); see Section 6.4 on timing for this pre-dose PK sample collection. 
The results of the baseline laboratory assessments for ZIKV viral marker testing 
(NAT/serology) will not be known prior to dosing of the subjects; however, this will not 
preclude the dosing of the subjects as study eligibility is determined by the screening 
assessments. The trial site must inform the sponsor of any aberrant baseline ZIKV 
NAT/serology assessments once the results are received. If the results of the baseline ZIKV 
(NAT and/or serology) laboratory tests confirm that the subject does not meet the clinical 
trial criteria for PK analysis (i.e., defined as ZIKV negative by NAT and serology test results 
and suitable level of baseline antibodies that bind ZIKV antigens), the subject(s) will be 
excluded from the PK analysis (also, the collection of PK samples will not take place at the 
remaining follow-up study visits). These subjects will continue to be followed for safety 
reasons and will be included in the safety analyses (i.e., all scheduled assessments and 
laboratory tests will be performed for these subjects in the follow-up visits, except for 
collection of PK samples). 
Since all subjects in group 1 may be admitted at the same time to the Phase 1 clinic 
(approximately 24 hours prior to Day 1), the group 1 subjects may have their baseline 
assessments performed on the admission day. For subgroup 1A, baseline assessments will be 
done approximately 24 hours prior to Day 1. However, for subjects who are not randomized 
into group 1A and who remain eligible for the study may remain in the Phase 1 clinic to 
await possible randomization into subgroups 1B or 1C, for which randomization may occur 
approximately 24 and 48 hours later, respectively. The baseline assessments for these 
subjects may not be repeated (eg, blood chemistry, hematology), at the discretion of the 
investigator, since they will be housed in a controlled environment and it is expected their 
baseline assessments will not significantly change over the course of one to two days.  
For subjects who are not randomized into subgroup 1A and who are randomized into 
subgroups 1B or 1C, pre-dose assessments on Day 1 may be performed more than once, at 
the discretion of the investigator (see Section 6.4 below).  
Note 1: laboratory assessments and related activities will be described in the site’s study-
specific laboratory procedure. 
Note 2: for a list of specific laboratory tests (e.g., blood chemistry, hematology), refer to 
Appendix I. 
6.4 
Study Treatment Administration (Day 1) 
The study treatment is to be administered only under the supervision of the principal 
investigator or a qualified sub-investigator(s) identified on the 1572 FDA form and/or Health 
Canada qualified investigator undertaking form (as applicable) or a designate listed on 
Delegation of Authority form (signed by the principal investigator). Under no circumstances 
will the investigator allow ZIKV-IG to be used other than as specified in the protocol. 
Prior to study-treatment administration, the following will be performed: 

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• 2 hours (±15 min) prior to study-treatment administration, vital signs will be assessed (to 
confirm screening eligibility for vital signs). 
• 1 hour (±15 min) prior to study-treatment administration, vital signs will be assessed (to 
establish baseline vital signs).   
• Within 2 hours prior to study-treatment administration, blood sample for baseline anti-
ZIKV antibody assessment (pre-dose PK sample) will be collected. 
After the above assessments have been completed, ZIKV-IG or placebo will be administered 
intravenously. 
Subjects will be assigned (randomized) to receive either 50 mL of undiluted ZIKV-IG or 50 
mL of placebo, administered by an IV infusion. For details on study treatment administration 
refer to Section 5.5 of the protocol and the Investigator’s Brochure for ZIKV-IG. 
Physical activity will be maintained at a minimal level during the first 24 hours following 
study treatment administration. Note: study treatment preparation (including measures to 
prevent unblinding), administration and other activities related to study treatment handling 
will be described in the site’s study-specific procedure. 
Subjects will stay in the Phase 1 clinic until assessments within the first 24 hours post-study 
treatment are completed (ie, subjects will be discharged on Day 2). Each subject will be 
followed up to Day 85 after study treatment administration (see Section 6.5). 
6.5 
Trial Assessments during/following Study Treatment Administration 
Day 1: 15 minutes (±5 min) into the IV infusion and at the end of the IV infusion (+5 
min): 
• Assessment of vital signs.  
• Adverse events. 
• Concomitant medications (if applicable). 
Day 1: 1 Hour (±5 min), 3 Hours (±30 min), 8 Hours (±1 hr) and 24 Hours (±3 hrs) after 
End of Study Treatment Administration 
• Blood sample collection for anti-ZIKV antibody assessment (PK sample). 
• 
Assessment of vital signs, adverse events and concomitant medications. 
Day 2 – Discharge Day (24±3 hrs after end of study treatment administration)  
• Blood sample collection for anti-ZIKV antibody assessment (PK sample). 
• Assessment of vital signs, adverse events and concomitant medications.  
• Blood chemistry and hematology. 

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Note: if ≥2 g/dL (i.e., ≥20 g/L) hemoglobin drop from baseline (Day -1) is observed, 
hemolysis tests (see Appendix I) will be performed. 
Day 3 (48±3 hrs), Day 4 (72±3 hrs), Day 6 (120±6 hrs), Day 8 (168±6 hrs), Day 10 
(216±12 hrs), Day 12 (264±12 hrs), Day 15 (336±12 hrs), Day 22 (504±24 hrs), Day 29 
(672±24 hrs), Day 43 (1008±48 hrs) and Day 57 (1344±48 hrs):   
Note: study visits are indicated as calendar days, while time-points in relation to end of study 
treatment administration are indicated in the brackets. 
• Blood sample collection for anti-ZIKV antibody assessment (PK sample). 
• Assessment of vital signs, adverse events and concomitant medications. 
• Blood chemistry and hematology. 
Note: if ≥2 g/dL (i.e., ≥20 g/L) hemoglobin drop from baseline (Day -1) is observed 
(ONLY up to Day 15 visit (336±12 hrs post-study treatment administration), 
hemolysis tests (see Appendix I) will be performed.  
Day 85 (2016±72 hrs after end of study treatment administration) or Early Withdrawal: 
• Blood sample collection for anti-ZIKV antibody assessment (PK sample). 
• Assessment of vital signs, adverse events and concomitant medications. 
• Blood chemistry and hematology. 
• Serum pregnancy test for female subjects of child-bearing potential  
• Viral marker testing: serology for HIV, HBV, HCV; ZIKV NAT (serum, urine) and 
serology for ZIKV.   
Note: serology for ZIKV IgM testing will be performed by the site’s reference 
laboratory, while ZIKV IgG testing will be performed by the sponsor-developed non-
diagnostic assay. 
• Complete physical exam. 
Note: for a list of specific laboratory tests (e.g., blood chemistry, hematology), refer to 
Appendix I.  
6.6 
Handling of Samples for PK Analysis  
To obtain samples for PK analysis of ZIKV-IG, 12 mL blood sample at Baseline (pre-dose) 
and 6 mL blood samples for subsequent PK time-points will be drawn into serum collection 
containing tubes. 
The blood will be allowed to clot for 15–30 minutes at room temperature and the clotted cells 
will be removed by centrifugation at room temperature for 15 minutes at 1,500 x g.  The 
serum will be transferred (as 3 approximately equal aliquots) into 3 sterile screw-cap 
cryotubes.  Each tube should be labelled with the following information:   

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6.9 
Concomitant Medications 
Subjects should not take prescription medications (except for hormonal contraceptives for 
females), over-the-counter drugs, vitamins and herbal preparations for at least 7 days before 
baseline and during the trial.   
The use of concomitant medication that the investigator considers unnecessary will be 
discouraged. No premedication will be permitted. Medications to treat minor ailments (e.g., 
headache, nausea, etc.) after the study treatment has been administered will be allowed at the 
discretion of the investigator. Trial subjects will be questioned about all concomitant 
medications including all herbal preparations and non-prescription medications that they are 
receiving. This information will be recorded by the investigator (or designate) in the eCRF.  
Concomitant medications taken in relation to adverse events will be denoted.  
Blood- or plasma-derived products/plasma exchange procedures during the study are allowed 
only for emergency reasons; the use of these types of products/procedures and the reason for 
such use will be recorded by the investigator (or designate) in the eCRF. 
7 
ASSESSMENT OF PHARMACOKINETICS 
7.1 
PK Parameters 
Based on serum concentrations of ZIKV antibodies, the following PK parameters will be 
calculated using non-compartmental analysis: 
• AUC0-t: area under the concentration-time curve from time 0 to the last quantifiable 
concentration. 
• AUC0-day 7. 
• AUC0-inf: AUC0-t plus the additional area extrapolated to infinity. 
• Cmax: maximum observed concentration. 
• Tmax: time at which Cmax occurs. 
• λz: terminal elimination rate constant. 
• t1/2: apparent first order terminal elimination half-life.  
• CL: total body clearance following IV administration. 
• VZ: volume of distribution following IV administration. 
7.2 
Assessment of PK Parameters 
Analysis of pre-dose (baseline) and post-dose samples at 1 hour, 3 hours, 8 hours (all part of 
Day 1 visit), 24 hours (Day 2 visit), Day 3, Day 4, Day 6, Day 8, Day 10, Day 12, Day 15, 
Day 22, Day 29, Day 43, Day 57 and Day 85 with anti-ZIKV antibody assays will determine 
serum concentrations of ZIKV antibodies over time, which will be used for calculation of PK 

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parameters (ie, PK analysis will be based on binding PK assay test results; however, PK 
analysis based on neutralizing PK assay test results will also be explored to the extent that the 
data permit). The full PK analysis will be performed for subjects that received ZIKV-IG and 
may be performed for placebo subjects (if needed). 
8 
ASSESSMENT OF SAFETY 
The safety of the trial drug will be assessed by monitoring adverse events (AE), laboratory 
results for blood chemistry, hematology and concomitant medications collected throughout 
the study. 
Note: for a list of specific laboratory tests (e.g., blood chemistry, hematology), refer to 
Appendix I.  
8.1 
Adverse Event/Serious Adverse Event Definition 
The capture of AEs will begin during and after dosing, and any medical history changes that 
occur after baseline assessments during randomization and before dosing should be updated 
as medical history. 
Adverse events are spontaneously reported by the subject and/or elicited by the investigator 
(or designate) by asking the subject non-leading questions. The association of the AE to 
ZIKV-IG is to be judged by the investigator as related or not-related/no relationship. 
8.2 
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 and/or sub-investigator(s) 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 AE’s.  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 
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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. 
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 eCRF.   
8.3 
Assessment of Severity (Intensity) 
All adverse events will be examined by a principal investigator or sub-investigator for 
assessment of severity using the following criteria:  
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. 

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8.3.1 Assessment of Causality (ICH Classification) 
All adverse events will be examined by a principal investigator or sub-investigator for 
assessment of causality (relatedness) using the criteria below. 
In accordance with ICH E2A and 21.CFR.312, the following definitions are used to assess 
causality (relatedness) of the adverse events: 
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. 
8.4 
Description of Known Adverse Event Profile for ZIKV-IG 
Although no clinical studies have been performed to date using ZIKV-IG, extensive clinical 
experience is available with immune globulin products (16). The safety profile of ZIKV-IG is 
expected to be comparable to other commercially available immune globulin products, 
including those manufactured at Emergent by the same manufacturing platform process and 
with IV route of administration (17, 18, 19).  
A potential risk of antibody-dependent enhancement (ADE) of ZIKV and/or DENV infection 
may exist in those individuals with pre-existing levels of flavivirus antibodies (such as 
antibodies to ZIKV, DENV or WNV), but this risk is undefined for products such as ZIKV-
IG. The sponsor has conducted preliminary in vivo ADE experiments in a mouse model of 
ZIKV infection and has not observed evidence of in vivo ZIKV ADE [refer to Investigator’s 
Brochure for ZIKV-IG (NP-024)]. Currently, there is no clinical evidence to suggest that pre-
existing flavivirus (DENV) antibodies enhance ZIKV infection (20-22) or that ZIKV 
antibodies clinically enhance other flavivirus infections such as DENV or WNV (23, 24). 
Nevertheless, to mitigate the potential risk of ADE for study subjects that will receive ZIKV-
IG, this clinical trial was designed to reduce exposure of subjects to ZIKV and/or DENV or 
other flaviviruses after administration of ZIKV-IG by conducting the study in ZIKV/DENV 
non-endemic region where the mosquito viral transmission vector is not present (in Canada), 
by requiring the subjects not to travel to ZIKV and/or DENV regions for the duration of the 
study (from screening until end of study) and by requiring subjects to use highly effective 
contraceptive methods throughout the study period. Also, subjects will recommend to their 
partner(s) (if applicable) not to travel to these endemic regions for the duration of the study. 
Collectively, these measures during the study period will mitigate the potential risk of ZIKV 
and DENV ADE for the study subjects who receive ZIKV-IG. In addition, the clinical dose 
intended for the Phase 1 study is expected to maintain ZIKV-IG levels well above the levels 

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that elicited in vitro ZIKV/DENV ADE effect (and presumably for WNV, which circulates in 
Canada during summer months); refer to Investigator’s Brochure for ZIKV-IG.  
The general safety profile of human immune globulins is well established and the most 
common types of adverse reaction (related AEs) to immune globulin intravenous products 
(IGIVs) are non-anaphylactic infusion reactions, such as back or abdominal pain, nausea and 
vomiting within the first 30 minutes of the infusion. Fever, headache, chills, rash, fatigue 
may begin at the end of the IV infusion and continue for several hours. More severe reactions 
of this type may require treatment with corticosteroids or acetaminophen. The incidence of 
adverse reactions associated with IV administration of immune globulin products is typically 
in the range of 1-15%(17-19, 25-27). Infrequent events associated with IV immune globulin 
administration (ie, product class-specific) have also been reported, typically in individuals 
who have significant, underlying risk factors for the development of the following: 
hypersensitivity reactions, renal failure, aseptic meningitis syndrome (AMS), hemolysis, 
transfusion-related acute lung injury (TRALI) and thrombotic events, (28).  
8.5 
Adverse Event Reporting 
Occurrence of AEs will be monitored throughout the trial and will cover all participating 
subjects. Trial subjects will be provided with a telephone number to contact trial personnel in 
case of an untoward reaction.  
All AEs must be followed to resolution, or up to 30 days after the subject has completed the 
trial, whichever occurs first. The investigator will follow SAEs to resolution, or in the case of 
disability or incapacity, until the condition has stabilized. If a patient does not complete the 
trial, efforts must be made to obtain information regarding all AEs, with a minimum follow-
up of 30 days post-dosing. 
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study will be reported as AEs. These tests will be repeated until the 
values return to normal or baseline or are no longer considered clinically significant by the 
investigator or medical monitor. If such values do not return to normal/baseline within a 
period of time judged reasonable by the investigator, the etiology should be identified and the 
sponsor notified. If laboratory values from non-protocol specified laboratory assessments 
performed at the institution’s reference laboratory require a change in participant 
management or are considered clinically significant by the investigator, then the results must 
be recorded in the eCRF as AEs. 
If a subject becomes pregnant or if a subject’s partner becomes pregnant during the clinical 
trial, this should be reported by the subject to the site within 24 hours of the subject 
becoming aware of their pregnancy/their partner’s pregnancy. The pregnancies will be 
recorded as AEs and will be followed until termination of pregnancy or birth (as per 
sponsor’s follow-up procedure): a separate pregnancy follow-up consent form for subject’s 
partner will be required. If a pregnancy results in an abnormal outcome that the reporting 
health care professional considers might be due to the trial drug, then the guidelines for 

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expedited reporting of serious, unexpected adverse drug reactions should be followed (see 
Section 8.6).  
8.6 
Reporting of SAEs 
The investigator will report all SAEs to the sponsor by telephone or e-mail (also informing 
the study medical monitor) 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.  
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 SAE reports should be made to:    
 
The sponsor will report every SAE to the regulatory agencies (FDA and Health Canada), 
while the investigator must report SAE(s) to the Institutional Review Board (IRB)/Ethics 
Committee (EC). 
8.7 
Safety Monitoring Committee 
A Safety Monitoring Committee (SMC) consisting at a minimum of two blinded medical 
reviewers (Phase 1 clinic’s medical monitor and sponsor’s medical monitor) and one 
unblinded segregated medical monitor will provide another layer of subject safety assurance.  
Dosing of the first six subjects (group 1) will be staggered over the period of three days, 
wherein two subjects per day will be randomized 1:1 and dosed at least 3 hours apart 
(subgroups 1A, 1B and 1C; each subgroup to be dosed at least one day apart). Based on the 
information available [i.e., reported adverse events within 3-hour period after study treatment 
administration, concomitant medications and vital signs 15 min into the IV infusion, at the 
end of the IV infusion, 1 hour and 3 hours after study treatment IV administration], the 
principal investigator will decide on subsequent dosing of each subject. If in the opinion of 
Sr. Specialist, Pharmacovigilance 
AND 
Medical Monitor  
  
 
 
 
 
 
 
 
 
 
 
 
  
 
Toll free phone: 
 
Toll free fax: 
 

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the principal investigator no safety concerns are identified after the first six subjects are 
dosed, a group of six subjects (group 2) will be randomized 2:1 and dosed (at least 30 
minutes apart) over the course of one day.    
The two blinded medical reviewers will then conduct a safety review following enrollment 
and data entry completion (up to 72 hours post-study treatment administration) of the first 12 
subjects dosed to monitor for any unexpected safety signals. The safety review will include 
blinded data on demographics, medical history and adverse events (AEs). A safety signal is 
defined as follows: 
• Two or more subjects report rare reactions for immune globulin intravenous products 
(such as hypersensitivity, hemolysis, thrombotic events). 
• Occurrence of two or more unexpected related AEs.  
• Two or more subjects report same related SAEs.  
• Two or more subjects experience a related moderate or higher severity AE associated 
with the same organ system. 
• Any other findings that, at the discretion of the medical monitor(s), that would 
indicate a safety signal. 
If there is no safety signal identified by the blinded safety data review, the remaining 18 
subjects will be randomized 2:1 and dosed (at least 30 minutes apart) in three separate groups 
over a period of three days (each group consisting of six subjects to be dosed over the course 
of one day). However, if there is a safety signal based on the blinded review of safety data 
from the first 12 dosed subjects, the safety review of the same data by the segregated 
unblinded medical monitor will be triggered (randomization scheme will be provided by the 
unblinded statistician at the CRO to the unblinded independent medical monitor to decode 
subject assignment) to determine if affected subject(s) received the trial drug (ZIKV-IG).   
The segregated medical monitor may recommend stopping the trial if the safety review 
identifies unforeseen adverse effects that impact subject safety (see Section 9.2.4). Only in 
the case where the independent medical monitor recommends stopping the trial (based on 
their safety review) would the other two medical monitors’ concurrence be required. 
The SMC process will be further outlined in the Medical Monitoring Plan for this study. 
9 
STATISTICAL ISSUES IN TRIAL DESIGN AND PK ASSESSMENT 
9.1 
Sample Size Calculation 
Sample size for ZK-001 will be 30 healthy volunteers; subjects will be randomized to receive 
either one dose level of ZIKV-IG (n=19) or placebo (n=11). While there was no formal 
sample size calculation as this is a Phase 1 clinical trial evaluating safety and PK of only one 
dose level of ZIKV-IG, up to 19 subjects treated with trial drug will allow for safety 
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9.1.1 Safety Population 
The safety population will include all subjects who received any amount of study treatment 
(ZIKV-IG or placebo). 
9.1.2 PK Population 
The PK population will include all subjects who received ZIKV-IG with adequate number of 
PK samples (a suitable pre-dose sample and at least one measurable post-dose sample). 
9.2 
Trial Endpoints 
9.2.1 Primary Endpoint 
The primary endpoint is the number and severity of adverse events. 
9.2.2 Secondary Endpoints 
Secondary endpoints are ZIKV-IG PK parameters, including: 
• AUC0-t: area under the concentration-time curve from time 0 to the last quantifiable 
concentration. 
• AUC0-day 7. 
• AUC0-inf: AUC0-t plus the additional area extrapolated to infinity. 
• Cmax: maximum observed concentration. 
• Tmax: time at which Cmax occurs. 
• λz: terminal elimination rate constant. 
• t1/2: apparent first order terminal elimination half-life.  
• CL: total body clearance following IV administration. 
• VZ: volume of distribution following IV administration. 
9.2.3 Safety Endpoints 
Safety will be evaluated based on the following endpoints: 
• Adverse events 
• Laboratory test results (hematology, blood chemistry, viral marker testing; refer to 
Appendix I for the list of specific laboratory tests)  
• Physical exams 
• Concomitant medications 
• Vital signs 

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9.2.4 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. This may be done at any time provided there is reasonable 
cause, and sufficient notice is given in advance of the intended termination. 
Meeting a safety stopping criterion will not automatically trigger study termination, but a 
hold on recruitment will be implemented until an ad hoc Safety Monitoring Committee 
(SMC) meeting is held. If any of the following safety criteria outlined below are fulfilled, the 
unblinded member of the SMC will review the unblinded safety data to assess the evidence 
for an excess of events in subjects who received ZIKV-IG relative to those subjects that 
received placebo. The SMC will determine whether trial termination is recommended. 
The safety criteria for early termination of the trial include: 
• Two or more subjects experience related rare reactions reported for immune globulin 
products such as thrombotic events or hypersensitivity. 
• Two or more subjects experience the same related SAE (per sponsor assessment). 
• Three or more subjects experience a related moderate or higher severity AE 
associated with the same organ system. 
• Any other findings that, at the discretion of the medical monitor(s), indicate that the 
study should be halted. 
Administrative issues affecting the Phase 1 clinical site may constitute grounds for stopping 
the trial. Examples include, but are not limited to, non-adherence to the trial protocol, 
sponsor’s procedures, GCP guidelines, requirements of IRB/EC/regulatory authorities, 
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 subject 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; recruitment 
is poor; research strategy or management priorities change; or a clinical hold is imposed by a 
regulatory authority. 
Any decision to voluntarily suspend or terminate a clinical trial will be carefully reviewed 
and fully justified. The sponsor will notify the FDA and Health Canada and the IRB/EC of 
any suspension or termination, along with justification for restarting or terminating the study 
as applicable. 

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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 safety monitoring committee will review blinded data for the first 12 dosed subjects.  
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 subjects, mean, standard deviation (SD), median, minimum and maximum. 
Categorical endpoints will be summarized by the total number of subjects, frequencies and 
percentages. 
Adverse events will be coded to system organ class and preferred term using the Medical 
Dictionary for Regulatory Activities (MedDRA), using the most current version at the time 
of coding. AEs will be defined as events beginning during and after study treatment 
administration that were not present prior to study treatment administration or those that were 
present prior to study treatment administration and subsequently worsened in severity. AE 
incidence for each system organ class and preferred term will be summarized for the safety 
population by study treatment overall and by gender, as well as separately by severity and for 
events related to study treatment (ZIKV-IG or placebo). SAEs will be summarized separately 
for the safety population overall and by study treatment.  
PK analysis for anti-ZIKV antibodies will be conducted for the PK population using the 
binding ZIKV antibody assay results; the PK analysis using neutralizing ZIKV antibody 
assay results will be performed to the extent that the data permit; hence this PK analysis will 
be exploratory. ZIKV-IG serum concentration versus time data will be analyzed by standard 
non-compartmental 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 
those listed in Section 9.2.2. The PK analysis will be performed for the PK population 
overall. Subjects with elevated baseline levels of ZIKV antibodies or subjects with 
inadequate number of PK time-points (e.g., no pre-dose sample, or no measurable post-dose 
samples) may be excluded from the PK analysis. Baseline correction will be implemented, if 
necessary. 
Subject disposition, including early termination reasons, will be summarized by study 
treatment for all subjects. Major and critical protocol deviations will be presented for the 
safety population. Subject demographics, medical history and study treatment (ZIKV-IG or 
placebo) dosing data will be tabulated for the safety population. 

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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. 
Laboratory test results will be summarized by time point and study treatment using 
descriptive statistics for the safety population. Changes in laboratory values and ‘clinically 
significant’ (as assessed by the investigator) abnormal values will be analyzed descriptively. 
Vital signs parameters will be presented in the same manner.  
The details of analyses will be further described in the study-specific Statistical Analysis 
Plan (SAP). 
10 REGULATORY AND ETHICAL ISSUES 
10.1 
Declaration of Helsinki 
The investigator shall ensure that this trial is conducted in accordance with the “Declaration 
of Helsinki.” 
10.2 
Informed Consent 
The investigator (or designates) will explain the nature of the study to the participant, answer 
all questions related to the study and 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. 
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 samples. 
• 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, if applicable. 
• 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 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.” 

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10.3 
Institutional Review Board (IRB) 
Before the start of the trial, the Investigator’s Brochure for ZIKV-IG, the ZK-001 protocol, 
proposed ICF, subject compensation (if any), sponsor-approved trial materials and 
advertisements, and any other written information to be provided to the subject will be 
submitted to a properly constituted IRB for review. The sponsor must receive a copy of the 
written approval from the IRB/EC for all of the above applicable documents prior to 
recruitment of subjects into the trial and shipment of ZIKV-IG. 
The IRB 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 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 and local regulatory 
requirements) 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 ICF and, where applicable, any other 
document listed above, have been approved by the IRB/EC. 
All correspondence between the investigator and the IRB/EC will be available for review by 
the sponsor (or designate), representatives of the sponsor (monitors) 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 an equivalent form 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 approval for the ZK-001 protocol, ZIKV-IG Investigator’s 
Brochure, ICF, subject compensation (if any), any trial materials and advertising, and any 
other written information to be provided to the subject. 
• Current Curriculum Vitae and a photocopy of medical license (if applicable) of the 
principal investigator, co/sub investigators and other site personnel as required. 
• Written statement that the IRB is properly constituted and operates according to 21 CFR 
part 56 regulations.  Investigators participating in this study, if IRB members, should 
state in writing that they have abstained from voting in regard to this protocol.  
• Laboratory normal ranges and documentation of laboratory certification. 

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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, 
enrollment) 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 ZK-001.  
Subjects must be informed that his/her records at the site may be reviewed by the sponsor, its 
designate(s), the IRB and the appropriate regulatory authority(ies) through direct access to 
the subject’s original medical records at the site. 
11 ADMINISTRATIVE AND LEGAL REQUIREMENTS 
11.1 
Sponsorship 
This clinical study is sponsored by Emergent BioSolutions Canada Inc., 
 
 who is the manufacturer of ZIKV-IG. 
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 (e.g., 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. 
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 

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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 eCRF 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. 
• 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 

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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 FDA, other 
government agencies as appropriate (Health Canada), 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 Forms 
The investigator (or designate) will record data collected in ZK-001 on electronic CRFs 
(eCRFs) [i.e., via electronic data capture (EDC) system]. The eCRFs are to be completed on 
a contemporaneous basis. Data reported on the CRF or entered in the eCRF that are 
transcribed from source documents must be consistent with the source documents or the 
discrepancies must be explained. 
The data are the property of the sponsor of the trial. Questions arising from eCRF data will 
resolved by the issuance of data queries within the EDC system by the sponsor’s Clinical 
Data and Statistics personnel (or designate) to the investigator. 
11.6 
Monitoring 
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 (or their representatives) 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 eCRFs of the subjects to ensure that 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, independent subcontracted unblinded monitors will be 
utilized for monitoring for verifying the unblinded drug accountability at the site pharmacy.  
The Phase 1 clinical site will be provided with the trial related training/ instructions at the 
initiation and throughout the conduct of the trial. 

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11.7 
Quality Control and Quality Assurance 
The sponsor’s Quality Assurance (QA) 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 to verify that the trial is being or has been conducted in accordance with protocol 
requirements, GCP, as well as the applicable regulatory requirements. 
11.7.1 Quality Management  
The sponsor maintains a quality management oversight through encompassing SOPs, risk 
assessment, risk management with defined data management plans, monitoring plans and 
audit plans to assure regulatory compliance, subject safety, robust data management and 
scientific integrity. 
11.8 
Publication Policy 
Data arising from this trial are the sole property of the sponsor of the trial.  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. Hennessey M, Fischer M, Staples JE. Zika Virus Spreads to New Areas - Region of the 
Americas, May 2015-January 2016. MMWR Morb Mortal Wkly Rep. 2016 Jan 
29;65(3):55-8.  
2. Coelho FC, Durovni B, Saraceni V, Lemos C, Codeco CT, Camargo S, et al. Higher 
incidence of Zika in adult women than adult men in Rio de Janeiro suggests a significant 
contribution of sexual transmission from men to women. Int J Infect Dis. 2016; 51:128-
32.  
3. Arias A, Torres-Tobar L, Hernández G, Paipilla D, Palacios E, Torres Y, et al. Guillain-
Barré syndrome in patients with a recent history of Zika in Cúcuta, Colombia: A 
descriptive case series of 19 patients from December 2015 to March 2016. J Crit Care. 
2016; 37:19-23. 
4. Dirlikov E, Major CG, Mayshack M, Medina N, Matos D, Ryff KR, et al. Guillain-Barré 
Syndrome during ongoing Zika Virus transmission - Puerto Rico, January 1-July 31, 
2016. MMWR Morb Mortal Wkly Rep. 2016; 65(34):910-4.  
5. Ritter JM, Martines RB, Zaki SR. Zika Virus: Pathology From the Pandemic. Arch 
Pathol Lab Med. 2017;141(1):49-59. 
6. Johansson MA, Mier-y-Teran-Romero L, Reefhuis J, Gilboa SM1, Hills SL. Zika and the 
Risk of Microcephaly. N Engl J Med. 2016; 7:375(1):1-4. 
7. Kleber de Oliveira W, Cortez-Escalante J, De Oliveira WT, do Carmo GM, Henriques 
CM, Coelho GE, et al. Increase in reported prevalence of microcephaly in infants born to 
women living in areas with confirmed Zika virus transmission during the first trimester of 
pregnancy - Brazil, 2015. MMWR Morb Mortal Wkly Rep. 2016; 65(9):242-7. 
8. Brasil P, Pereira JP, Gabaglia CR, Damasceno L, Wakimoto M, Nogueira RM, et al. Zika 
virus infection in pregnant women in Rio de Janeiro. N Engl J Med. 2016 Dec 
15;375(24):2321-2334. 
9. Ventura CV, Maia M, Travassos SB, Martins TT, Patriota F, Nunes ME, et al. Risk 
factors associated with the ophthalmoscopic findings identified in infants with presumed 
Zika Virus congenital infection. JAMA Ophthalmol. 2016; 134(8):912-8. 
10. Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika virus and birth defects-
reviewing the evidence for causality. N Engl J Med. 2016; 374(20):1981-7. 
11. Moore CA, Staples JE, Donyns WB, Pessoa A, Ventura CV, Borges da Fonseca E, et al. 
Characterizing the pattern of anomalies in congenital Zika Syndrome for pediatric 
clinicians. JAMA Pedriat. JAMA Pediatr. 2017;171(3):288-295. 
12. Shapiro-Mendoza CK, Rice ME, Galang RR, et al. Pregnancy Outcomes After Maternal 
Zika Virus Infection During Pregnancy - U.S. Territories, January 1, 2016–April 25, 
2017. MMWR Morb Mortal Wkly Rep 2017;66:615-621. 

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13. Tabata T, Petitt M, Puerta-Guardo H, Michlmayr D, Wang C, Fang-Hoover J, et al. Zika 
virus targets different primary human placental cells, suggesting two routes for vertical 
transmission. Cell Host Microbe. 2016; 20(2):155-66. 
14. Coyne CB, Lazear HM. Zika virus - reigniting the TORCH. Nat Rev Microbiol. 2016; 
14(11):707-15.  
15. Kurz M. Developing therapeutic immunoglobulins: European regulatory perspectives and 
implications. BioDrugs. 2008;22(3):145-60. 
16. Bozzo J, Jorquera JI. Use of human immunoglobulins as an anti-infective treatment: the 
experience so far and their possible re-emerging role. Expert Rev Anti Infect Ther. 
2017;15(6):585-604.  
17. VariZIG® Product Monograph. Aptevo BioTherapeutics LLC; 2016. 
18. ANTHRASIL® Package Insert. Cangene Corporation; 2015. 
19. CNJ-016™ (Vaccinia Immune Globulin Intravenous (Human) [VIGIV]). Emergent 
BioSolutions; 2017. 
20. Terzian ACB, Schanoski AS, Mota MTO, da Silva RA, Estofolete CF, Colombo TE, et 
al. Viral Load and Cytokine Response Profile Does Not Support Antibody-Dependent 
Enhancement in Dengue-Primed Zika Virus-Infected Patients. Clin Infect Dis. 
2017;65(8):1260-1265. 
21. Halai UA, Nielsen-Saines K, Moreira ML, de Sequeira PC, Junior JPP, de Araujo Zin A, 
et al. Maternal Zika Virus Disease Severity, Virus Load, Prior Dengue Antibodies, and 
Their Relationship to Birth Outcomes. Clin Infect Dis. 2017;65(6):877-883. 
22. Sariol CA, Nogueira ML, Vasilakis N. A Tale of Two Viruses: Does Heterologous 
Flavivirus Immunity Enhance Zika Disease? Trends Microbiol. 2018;26(3):186-190.  
23. Priyamvada L, Suthar MS, Ahmed R, Wrammert J. Humoral Immune Responses Against 
Zika Virus Infection and the Importance of Preexisting Flavivirus Immunity. J Infect Dis. 
2017;216(suppl. 10):S906-S911.  
24. Martín-Acebes MA, Saiz JC, Jiménez de Oya N. Antibody-Dependent Enhancement and 
Zika: Real Threat or Phantom Menace? Front Cell Infect Microbiol. 2018;8:44. 
25. BIVIGAM® Package Insert. Biotest Pharmaceuticals Corporation; 2013. 
26. GAMMAPLEX®  Package Insert. Bio Products Laboratory Limited; 2015.   
27. Privigen® Package Insert. CSL Behring LLC; 2017. 
28. Hamrock DJ. Adverse events associated with intravenous immunoglobulin therapy. Int 
Immunopharmacol. 2006;6(4):535-42.  
 
 

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13 APPENDIX I 
Below is the listing of laboratory tests for ZK-001 clinical trial. All laboratory tests will be 
performed/managed by the Phase 1 CRO’s reference laboratory (Dynacare), except where 
noted.  
Laboratory Assessment Category 
List of Specific Tests 
Blood type  
ABO/Rh blood typing 
Blood chemistry 
Glucose, urea, calcium, albumin, total bilirubin, sodium, potassium, 
chloride, alkaline phosphatase, lactate dehydrogenase (LD), gamma-
glutamyl transferase (CGT), aspartate aminotransferase (AST), 
alanine aminotransferase (ALT), thyroid stimulating hormone 
(TSH), creatinine. 
Hematology 
White blood count, neutrophils, lymphocytes, monocytes, 
eosinophils, basophils, neutrophils, blood smear (morphology: 
platelets, red blood cells, white blood cells), hemoglobin*, 
hematocrit, red blood cells, platelets. 
Pregnancy  
Chorionic gonadotropin (CG) for females of child bearing potential  
Follicle-stimulating hormone (FSH) for post-menopausal females 
Urinalysis 
Micro: red blood cells, squamous epithelial, white blood cells, 
bacteria. 
Chemical: glucose, bilirubin, ketones, specific gravity, blood, pH, 
protein, urobilinogen, nitrite, leukocytes. 
Viral marker serology 
HIV-1/HIV-2, Hep B Ag, Hep C, ZIKV (IgM, IgG**), DENV (IgM, 
IgG), WNV (IgM, IgG). 
Viral marker nucleic acid test (NAT) 
ZIKV (serum, urine). 
Urine drug test 
Amphetamine, benzodiazepine, cannabinoids, cocaine, opiates, 
oxycodone. 
* If hemoglobin drops ≥2 g/dL (i.e., 20 g/L) from baseline (up to Day 15 study visit), the following 
hemolysis tests will be performed: direct Coombs test, serum haptoglobin, plasma-free hemoglobin, and 
urinalysis testing including urine hemosiderin.  
** ZIKV IgG test will be performed by the sponsor-developed non-diagnostic assay.