A Prospective, Open-Label, Single-Arm Clinical Trial to Assess the Anti-Hepatitis A Virus (HAV) Antibody Levels, Pharmacokinetics, and Safety of a Single Intramuscular Dose of a Polyvalent Human Immune Globulin in HAV Seronegative Healthy Subjects
Phase: PHASE4
Conditions: Anti-Hepatitis A Antibody Levels in Heathy Subjects
Sponsor: Grifols Therapeutics LLC

Protocol GC 1703 - Amendment 4 
Protocol Title: 
Investigational Product: 
22 Jan 2018 
Clinical Study Protocol 
A Prospective, Open-Label, Single-Arm Clinic'al 
Trial to Assess the Anti-Hepatitis A Virus (HA V) 
Antibody Levels, Pharmacokinetics, and Safety of a 
Single Intramuscular Dose of a Polyvalent Human 
Immune Globulin in HA V-Seronegative Healthy 
Subjects 
GamaST AN® [Immune Globulin (Human)] 
Sponsor's Name and Address: 
Grifols Therapeutics LLC 
79 TW Alexander Drive 
Sponsor's Telephone Number: 
Research Triangle Park, NC 27709 USA 
 
Study Numbe.r/Protocol 
Version Number/Date: 
Additional Identifier: 
Development Phase: 
 
GC1703/Protocol Version 5.0/22 Jan 2018 includes 
GC 1703/Protocol Version 4.0/30 Nov 2017, 
GC1703/Protocol Version 3.0/02 Nov 2017, 
GC 1703/Protocol Version 2.0/20 Oct 2017, and 
GC 1703/Protocol Version 1.0/21 Aug 2017 
GamaST AN PK Study 
Phase IV 
The undersigned confirm that they agree to conduct the study under the conditions 
described in this protocol: 
Clinical Assessment M 
Signature: 
Confidentiality Statement: 
CONFIDENTIAL 
 
Date: 
The.following confidential information is the property of Grifols. As long as 
the information contained in this protocol has not been published, it may 
only be used after permission has been obtainedfrom Grifols. it is not 
possible to make reproductions of all or sections of this protocol. 
Commercial use qf the information is only possible with the permission of 
the proprietor and is subject to a license fee. 
Page 1 of57 

Protocol GC1703 - Amendment 4
22 Jan 2018
CONFIDENTIAL
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Summary of Changes for Amendment 4
Protocol Version
Date of Approval
5.0
Amendment 4 + Integrated Protocol
22 Jan 2018
4.0
Amendment 3 + Integrated Protocol
30 Nov 2017
3.0
Amendment 2 + Integrated Protocol
02 Nov 2017
2.0
Amendment 1 + Integrated Protocol
20 Oct 2017
1.0
Original
21 Aug 2017
Amendment 4
The protocol for GC1703 (Version 4.0, dated 30 Nov 2017) has been amended and reissued 
as Protocol Amendment 4, Version 5.0, dated 22 Jan 2018.

Protocol GC1703 - Amendment 4
22 Jan 2018
CONFIDENTIAL
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Summary of Changes for Amendment 4
(Note: Administrative changes including minor administrative corrections and the changes in the protocol synopsis are not included in Protocol Summary of Changes.)
Sections
Change From:
(Version 4.0, dated 30 Nov 2017)
Change To:
(Version 5.0, dated 22 Jan 2018)
Rationale:
Global
Grifols Therapeutics Inc
Grifols Therapeutics LLC
Company name change
Synopsis,  5.1
Inclusion Criteria:
2. Subjects with a body mass index (BMI) of 
18.5 to 25.0 kg/m2
Inclusion Criteria:
2.Subjects with a body mass index (BMI) of 18.5 to 
29.9 kg/m2
To allow enrollment of 
subjects with a larger body 
mass index
4.3.1
Subject Numbering
Subjects in the study will receive a consecutive 
subject number. Subject numbers are generated 
beginning with the study center number (3 digits,
assigned by the sponsor) followed consecutively 
with a unique number for each subject (4 digits, 
including leading zeros). For example, if the 
Investigator's center number is 301, subject 
number will be 3010001, 3010002, 3010003, 
etc., in consecutive order. Subject numbers, once 
assigned, will not be reused. 
Subject Numbering
Subjects in the study will receive a consecutive subject 
number. Subject numbers are generated beginning 
with the study center number (3 digits, assigned by 
the sponsor) followed consecutively with a unique 
number for each subject (4 digits, including leading 
zeros). For example, if the Investigator's center 
number is 301, subject number will be 3010001, 
3010002, 3010003, etc., in consecutive order. 
Subject numbers, once assigned, will not be reused.
If a subject is re-screened, a different subject number 
will be assigned to this subject.
To provide the procedure for 
assigning subject numbers to 
rescreened subjects.
5.3.1
Screen Failures
Screening evaluations will be used to determine 
the eligibility of each subject for enrollment.  
Subjects who fail to meet eligibility criteria 
during screening evaluations will be considered 
screen failures and will not participate in the 
study. 
Screen Failures
Screening evaluations will be used to determine the 
eligibility of each subject for enrollment.  Subjects who 
fail to meet eligibility criteria during screening 
evaluations will be considered screen failures and will 
not participate in the study. However, subjects who fail 
the first screening evaluation are allowed to be re-
screened once.
To allow rescreening of 
subjects who previously fail 
the first screening evaluation.

Protocol GC 1703 - Amendment 4 
22 Jan 2018 
Investigator Signature Page 
The undersigned confirms that he/she agrees to conduct the study under the conditions 
described in this protocol and comply with the International Council/or Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (/CH) Good Clinical 
Practice (GCP) and all applicable regulatory requirements: 
 
USA 
INVESTIGATOR NAME (Please Print) 
LOCATION 
INVESTIGATOR SIGNATURE 
DATE 
Title of the Investigator: 
Principal Investigator 
Address of the Site: 
 
Telephone Number: 
 
CONFIDENTIAL 
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Protocol GC1703 - Amendment 4
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PROTOCOL SYNOPSIS
Title of Study:
A Prospective, Open-Label, Single-Arm Clinical Trial to Assess the Anti-Hepatitis A Virus 
(HAV) Antibody Levels, Pharmacokinetics, and Safety of a Single Intramuscular Dose of a 
Polyvalent Human Immune Globulin in HAV-Seronegative Healthy Subjects
Short Title:
GamaSTAN PK Study
Study Number:
GC1703
Phase:
Phase IV
Study Objectives:
Primary Efficacy Objective:
To evaluate whether a single 0.2 mL/kg intramuscular (IM) dose of the study treatment will 
provide protective levels of antibodies to HAV (anti-HAV) in HAV-seronegative healthy 
subjects for up to 60 days.
Pharmacokinetic (PK) Objectives:
To evaluate the PK parameters of anti-HAV antibodies following a single 0.2 mL/kg IM dose 
of the study treatment in HAV-seronegative healthy subjects.
The PK parameters of interest are:

Area under the plasma and/or serum concentration time curve extrapolated to infinity 
(AUC0-∞)

Cumulative area under the plasma and/or serum concentration time curve calculated 
from 0 to time of last observed quantifiable plasma and/or serum concentration 
(AUC0-T)

Maximum observed plasma and/or serum concentration (Cmax)

Time of maximum observed plasma and/or serum concentration (Tmax)

Apparent elimination rate constant (λz)

Terminal elimination half-life (Thalf)

Apparent total plasma and/or serum clearance (ClTOT/F)

Apparent volume of distribution (VD/F)
Safety Objective:
To evaluate the safety and tolerability of a single 0.2 mL/kg IM dose of the study treatment 
in HAV-seronegative healthy subjects.

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Overall Study Design and Description:
This is a single center, open-label, single-arm study. Approximately 28 HAV-seronegative 
healthy subjects will be enrolled in this study after obtaining their written informed consents. 
There will be a screening period of up to 28 days during which subjects will be screened for 
enrollment in the study.
The healthy subjects will receive a single IM dose of GamaSTAN (0.2 mL/kg), which is 
followed by a PK sampling period of 150 days (approximately 5 half-lives). The protective 
levels of anti-HAV antibodies will be assessed up to 60 days after the administration of 
GamaSTAN. A PK curve will be obtained during the PK sampling period.
Number of Subjects Planned:
Approximately 28 HAV-seronegative healthy subjects will be enrolled in the study which 
will provide about 20 evaluable subjects based on approximately 30% dropout rate.
Diagnosis and Main Criteria for Inclusion:
Only HAV-seronegative healthy adult subjects will be enrolled in this study.
Inclusion Criteria:
A subject must meet all the following inclusion criteria to be eligible for participation in this 
study.
1. Male subjects from 18 to 55 years of age, inclusive, or female subjects from 18 to 
65 years of age, inclusive
2. Subjects with a body mass index (BMI) of 18.5 to 29.9 kg/m2
3. Body weight greater than or equal to 50 kg at screening
4. Subjects willing and able to provide written informed consent
5. Subjects in good health in the judgment of the Investigator, as determined by medical 
history, physical examination, vital signs, ECG and laboratory assessments
6. A female study subject must meet one of the following criteria:
a.
If a female of childbearing potential – agrees to use one of the accepted 
contraceptive regimens from at least 30 days prior to study treatment 
administration and during the entire study duration. An acceptable method of 
contraception includes one of the following:

Abstinence from heterosexual intercourse (i.e. when abstinence is the 
preferred and usual lifestyle of the subject; periodic abstinence is not 
acceptable)

Non-estrogen containing hormonal contraceptives (birth control pills, 
injectable/implant/insertable hormonal birth control products, transdermal 
patch)

Intrauterine device without hormones

Condom with spermicide

Diaphragm or cervical cap with spermicide

Vasectomized partner (minimum 6 months since vasectomy prior to study 
treatment administration)

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b. If a female of non-childbearing potential – should be surgically sterile (i.e. has 
undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in 
a menopausal state (at least 1 year without menses prior to study treatment 
administration)
7. A male study subject must agree to use one of the accepted contraceptive regimens 
during the entire study duration;

Abstinence from heterosexual intercourse

Female partner with condom with spermicide used by male study subject

Female partner of non-childbearing potential

Male sterilization (if proof of sterilization is not provided, the subject must 
agree to use one of the above accepted contraceptive methods)
8. A male study subject must agree not to impregnate a female or donate sperm during the 
entire study duration
Exclusion Criteria:
A subject meeting any of the following exclusion criteria is NOT eligible for participation in 
the study.
1. Subject vaccinated against HAV, as documented the in medical history at the screening 
visit
2. Subject positive for anti-HAV antibodies in blood sample at the screening visit
3. Subject who previously received any type of immune globulin (IG), including HAV IG
within the past 12 months prior to study treatment administration
4. Subject with prolonged International Normalized Ratio (INR) or activated partial 
thromboplastin time (aPTT) at the screening visit
5. Subject with a platelet count below 100×109/L at the screening visit
6. Subject suffering from some acute or chronic medical, surgical or psychiatric significant 
condition or laboratory abnormality at the screening visit or prior to study treatment 
administration that, according to Investigator judgement, may increase the risk associated 
with study participation or study treatment administration, or may interfere with the 
successful completion or interpretation of the study results
7. Subject with a history of the following: angioedema, cardiac arrhythmia, angina pectoris, 
myocardial infarction, cerebrovascular accident, cardiac failure, thrombotic events, 
embolism, coagulopathy, diabetes mellitus, hyperlipidaemia, nephrotic syndrome, acute 
renal injury, chronic obstructive pulmonary disease, asthma, hepatic disease, 
reticuloendothelial system dysfunction, or nervous system disorder
8. Subject with known personal or family history of abnormal bleeding episodes
9. Subject not willing to receive study treatment via IM route of administration or unable to 
receive study treatment via IM route of administration
10. Subject with cardiovascular risk factors based on medical history: active tobacco 
smoking and/or ongoing diabetes mellitus at the screening visit
11. Subject with thrombosis risk factors: prolonged immobilization within 2 months prior to
the screening visit, history of venous or arterial thrombosis, use of estrogens (30 days 
prior to the study drug administration), indwelling central vascular catheters and 

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hyperviscosity or hypercoagulable states
12. Subject with known history of hypersensitivity/allergic reaction to blood/plasma products
13. Subject with known selective Immunoglobulin A (IgA) deficiency (with or without 
antibodies to IgA)
14. Subject who received any plasma-derived product infusion within 12 months prior to 
study treatment administration
15. Subject who received a blood or plasma transfusion within 12 months prior to study 
treatment administration
16. Subject with systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg 
at the screening visit and prior to treatment administration
17. Subject with anemia (hemoglobin <12 g/dL in women and 13 g/dL in men) at the 
screening visit
18. Subjects with proteinuria (>1+ on urine dipstick), blood urea nitrogen (BUN) or 
creatinine greater than the upper limit of normal at the screening visit
19. Subject with liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase 
[ALT] and gamma-glutamyl transferase [GGT]) levels greater than the upper limit of 
normal at screening visit
20. Subject who received any dose of parenteral, oral, or inhaled corticosteroids, 
immunosuppressants, or immunomodulators within 6 weeks prior to the screening visit
21. Subject who received any live virus vaccine within five months prior to the screening 
visit
22. Subject not willing to postpone receiving any live virus vaccines until 6 months after 
receiving study treatment
23. Currently receiving any anti-viral treatment, regardless of the route of administration
24. Subject with virus safety laboratory results (serology and/or nucleic acid amplification 
technology [NAT]) indicative of a current infection with HAV, hepatitis B virus (HBV), 
hepatitis C virus (HCV), human immunodeficiency virus (HIV) or parvovirus B19 
(B19V) at the screening visit
25. Participated in another clinical trial within 30 days prior to the screening visit or has
received any investigational products within 3 months prior to the screening visit
26. Positive urine drug panel testing at the screening visit or prior to study treatment 
administration
27. Known or suspected abuse of alcohol, opiates, psychotropic agents or other drugs or 
chemical substances; or has done so in the 12 months prior to the screening visit
28. In the opinion of the Investigator, the subject may have compliance problems with the 
protocol and the procedures of the protocol
29. Subject who has already been included in a previous group for this clinical study
Investigational Product, Dose and Mode of Administration:
Investigational Product:
GamaSTAN [Immune Globulin (Human)]
Dose and Mode of Administration:
Single 0.2 mL/kg IM dose in the anterolateral aspects of the upper thigh or the deltoid muscle 
of the upper arm.

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Doses over 5 mL are to be divided and injected into several muscle sites to reduce local pain 
and discomfort.
The gluteal region should not be used as an injection site due to the risk of injury to the 
sciatic nerve. The investigational product (IP) is not to be administered subcutaneously or 
intravenously.
Reference Therapy, Dose and Mode of Administration:
There is no reference therapy in this study.
Duration of Treatment:
After a screening period of up to 28 days, subjects will receive a single dose of the study 
treatment, which will be followed by a PK sampling period of 150 days. The total duration of 
participation for each subject in this study will be up to approximately 178 days.
Key Study Variables:
Primary Efficacy Variable:

Proportion of subjects maintaining protective anti- HAV antibody levels (defined as anti-
HAV antibody titer ≥10 mIU/mL in plasma and/or serum) up to 60 days after study 
treatment administration
PK Variables for anti-HAV antibodies in plasma and/or serum:

AUC0-∞: Area under the plasma and/or serum concentration time curve extrapolated to 
infinity

AUC0-T: Cumulative area under the plasma and/or serum concentration time curve 
calculated from 0 to time of last observed quantifiable plasma and/or serum concentration

Cmax: Maximum observed plasma and/or serum concentration

Tmax: Time of maximum observed plasma and/or serum concentration

λz: Apparent elimination rate constant

Thalf: Terminal elimination half-life

ClTOT/F: Apparent total plasma and/or serum clearance

VD/F: Apparent volume of distribution
Safety Variables:

Adverse events (AEs) including serious adverse events (SAEs), suspected adverse drug 
reactions (ADRs), and adverse reactions (ARs)

Clinical laboratory parameters including chemistry, hematology, and urinalysis

Physical examination

Vital signs (heart rate (HR), blood pressure (BP), respiratory rate (RR), and body
temperature)
Study Assessments and Procedures:
Screening Visit (Day -28 to Day -2):
Subjects will be screened for enrollment in this study. The following procedures will be 

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done:
•
Obtain informed consent
•
Review of inclusion and exclusion criteria for determination of subject’s study eligibility
•
Documentation of medical history
•
Documentation of demographics
•
Height and weight measurement and determination of BMI
•
Full physical examination (excluding breast and genitourinary examination)
•
ECG
•
Vital signs measurement (HR, BP, RR, and body temperature)
•
Clinical laboratory assessments (chemistry, hematology, urinalysis) (see Table 7-1 for 
details)
•
Virus safety testing (see Table 7-1 for details)
•
Coagulation tests (INR, aPTT)
•
Immunoglobulin A (IgA) testing (see Table 7-1 for details)
•
Urine alcohol and drug panel testing (see Table 7-1 for details)
•
Urine pregnancy test for females
•
Record prior (30 days prior to screening visit) and concomitant medications
•
Record AEs
Treatment Period:
Day -1:
Subjects will be admitted to the clinical research unit on the day prior to study drug injection.
The following procedures will be done upon admission:
•
Review of subject eligibility (review of inclusion/exclusion criteria)
•
Record concomitant medications
•
Record AEs
•
Vital signs measurement (HR, BP, RR, and body temperature)
•
Symptom-directed physical examination
•
ECG
•
Clinical laboratory assessments (chemistry, hematology, urinalysis) (see Table 7-1 for 
details)
•
Urine alcohol and drug panel testing (see Table 7-1 for details)
•
Urine pregnancy test for females
Day 1:
The following procedures will be done (all pre-dose procedures are to be performed within 
1 hour prior to dosing):
•
Collection of virus safety retain samples prior to study drug injection
•
Vital signs measurement (HR, BP, RR, and body temperature) prior to study drug 
injection, 60 minutes post study drug injection (a window of ±10 minutes is permitted) 
and 12 hours post study drug injection (a window of ±10 minutes is permitted)

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•
Record AEs and concomitant medications prior to and post study drug injection
•
Study drug injection
•
PK blood sampling prior to study drug injection, 60 minutes post study drug injection (a 
window of ±10 minutes is permitted) and 12 hours post study drug injection (a window 
of ±1 hour is permitted)
•
Injection site evaluation 60 minutes (±10 minutes) post study drug injection (Note: any 
reactions will be recorded as AEs)
Day 2:
•
Record concomitant medications
•
Record AEs
•
PK blood sample will be collected approximately 24 hours following study treatment 
administration (a window of ±1 hour is permitted)
•
Injection site evaluation approximately 24 hours post study drug injection (prior to 
discharge) (Note: any reactions will be recorded as AEs)
•
Symptom-directed physical examination approximately 24 hours post study drug 
injection (prior to discharge)
•
Subjects will be discharged from the clinical research unit on Day 2, following clinical 
assessments and procedures, and will return for each of the remaining scheduled 
ambulatory visits (from Days 3 to 150).
Day 3 to Day 115:
A PK blood sample will be collected on each of the following days:
•
Days 3, 4 and 5 (a window of ±4 hours is permitted)
•
Days 7, 10, and 14 (a window of ±1 day is permitted)
•
Days 21 and 28 (a window of ±2 days is permitted)
•
Days 60, 79, and 115 (a window of ±4 days is permitted)
Procedures performed on Days 3, 4, 5, 7, 10, 14, 21, 28, 60, 79 and 115 (the window for 
these procedures is the same as that for the PK sample to be collected on the same study 
Day):
•
Record concomitant medications
•
Record AEs
•
Vital signs measurement (HR, BP, RR, and body temperature) (Day 5, 28, and 60 visits 
only)
•
Symptom-directed physical examination (Day 5, 28, and 60 visits only)
•
Clinical laboratory assessments (chemistry, hematology, urinalysis) (Day 5, 28, and 
60 visits only) (see Table 7-1 for details)
Final Visit (Day 150 ±7 days)/Early Discontinuation Visit:
•
Record concomitant medications
•
Record AEs

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•
A PK blood sample will be collected
•
Full physical examination (excluding breast and genitourinary examination)
•
Vital signs measurement (HR, BP, RR, and body temperature)
•
Clinical laboratory assessments (chemistry, hematology, urinalysis) (see Table 7-1 for 
details)
•
Collection of virus safety retain samples (see Table 7-1 for details)
Statistical Methods:
Efficacy analysis:
The percentage of subjects maintaining anti-HAV antibody levels ≥10 mIU/mL up to Day 60 
following study treatment administration will be summarized. The anti-HAV antibody levels 
during the PK sampling period (up to Day 150 following study treatment administration) will 
be summarized. The efficacy analyses will be performed on the evaluable and safety 
populations.
PK Analysis:
PK analyses will be performed on the PK population. All PK parameters (AUC0-∞, AUC0-T, 
Cmax, Tmax, λz, Thalf, ClTOT/F and VD/F) will be listed and summarized using arithmetic as 
well as geometric means and standard deviation (SD), percent coefficient of variation (CV), 
median, and minimum/maximum, as appropriate. PK parameters will be estimated using both 
anti-HAV antibody baseline uncorrected and baseline corrected levels.
Safety Analysis:
Safety analyses will be performed on the safety population. Safety data will be summarized 
with descriptive statistics and frequency tables and will include clinical laboratory values, 
vital signs and physical examination findings. The incidence of AEs, suspected ADRs, ARs, 
and AEs by severity and causality will be summarized. Deaths, subjects with SAEs and AEs 
leading to premature discontinuation from the study will be listed and presented in narrative 
form.
Determination of Sample Size:
Approximately 28 healthy subjects will be enrolled and treated in this study which will 
provide about 20 evaluable subjects based on approximately 30% dropout rate. The sample 
size is chosen based on clinical considerations but not on a formal sample size calculation.

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TABLE OF CONTENTS
PROTOCOL SYNOPSIS ..........................................................................................................5
TABLE OF CONTENTS.........................................................................................................13
GLOSSARY AND ABBREVIATIONS..................................................................................17
1
GENERAL INFORMATION..........................................................................................20
2
BACKGROUND INFORMATION ................................................................................20
2.1
Name and Description of the Investigational Product(s).......................................20
2.2
Relevant Findings from Nonclinical and Clinical Trials.......................................20
2.2.1
Pre-exposure Prophylaxis for Hepatitis A Infection....................................20
2.2.2
Rationale for Clinical Investigation of GamaSTAN....................................21
2.3
Known and Potential Risks and Benefits to Human Subjects ...............................21
2.4
Description of and Justification for the Route of Administration, Dosage, 
Dosage Regimen, and Treatment Period(s) ...........................................................22
2.4.1
Administration of Investigational Products .................................................22
2.4.2
Justification for Selection of Doses/Timing of Investigational Products ....22
2.5
Compliance Statement ...........................................................................................23
2.6
Study Population....................................................................................................23
3
STUDY OBJECTIVES AND PURPOSE .......................................................................23
3.1
Efficacy Objectives................................................................................................23
3.2
Pharmacokinetic Objectives...................................................................................23
3.3
Safety Objectives ...................................................................................................23
4
STUDY DESIGN.............................................................................................................23
4.1
Primary Endpoint and Secondary Endpoints .........................................................23
4.2
Study Design and Plan...........................................................................................24
4.3
Measures Taken to Minimize/Avoid Bias .............................................................25
4.3.1
Subject Numbering ......................................................................................25
4.3.2
Randomization.............................................................................................25
4.3.3
Blinding........................................................................................................25
4.4
Study Treatments ...................................................................................................25
4.4.1
Treatments to Be Administered ...................................................................25
4.4.1.1
GamaSTAN........................................................................................25
4.4.2
Labeling of Investigational Product.............................................................25
4.4.3
Packaging of Investigational Product ..........................................................26
4.4.4
Storage of Investigational Product...............................................................26
4.5
Expected Duration of Subject Participation in the Study ......................................26
4.6
Discontinuation Criteria for Individual Subjects and Study..................................26
4.6.1
Discontinuation Criteria for Individual Subjects.........................................26
4.6.2
Premature Termination of Study..................................................................26

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4.7
Accountability Procedures for Investigational Product(s).....................................27
4.8
Maintenance of Treatment Randomization Codes.................................................27
4.9
Data to Be Recorded Directly on the eCRFs .........................................................27
5
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................27
5.1
Inclusion Criteria ...................................................................................................27
5.2
Exclusion Criteria ..................................................................................................28
5.3
Subject Withdrawal Criteria ..................................................................................30
5.3.1
Screen Failures.............................................................................................30
5.3.2
Removal of Subjects ....................................................................................30
5.3.3
Subject Replacement....................................................................................31
5.3.4
Follow-up of Subjects Withdrawn from Study............................................31
6
TREATMENT OF SUBJECTS.......................................................................................31
6.1
Administration and Timing of Investigational Products for Each Subject............31
6.2
Prior and Concomitant Therapy.............................................................................32
6.2.1
Prohibited Medications Prior to Study Participation ...................................32
6.2.2
Prohibited Concomitant Medications during the Study...............................32
6.2.3
Restricted Concomitant Medications during the Study ...............................32
6.3
Treatment Compliance...........................................................................................32
7
ASSESSMENT OF EFFICACY AND PHARMACOKINETICS..................................33
7.1
Efficacy Variables..................................................................................................33
7.1.1
Primary Efficacy Variable ...........................................................................33
7.2
Pharmacokinetic Variables ....................................................................................33
7.3
Methods and Timing for Assessing, Recording, and Analyzing Efficacy 
Parameters..............................................................................................................33
7.3.1
Observations and Measurements .................................................................33
7.3.2
Description of Laboratory Tests and Procedures.........................................36
7.3.3
Drug Concentration Measurements .............................................................37
8
ASSESSMENT OF SAFETY..........................................................................................37
8.1
Safety Parameters...................................................................................................37
8.2
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters..............................................................................................................38
8.2.1
Adverse Events ............................................................................................38
8.2.2
Clinical Laboratory Evaluations ..................................................................38
8.2.3
Virus Safety Testing ....................................................................................38
8.2.4
Vital Signs....................................................................................................38
8.2.5
Physical Examinations.................................................................................39
8.3
Procedures for Eliciting Reports of and for Recording and Reporting Adverse 
Event and Intercurrent Illnesses.............................................................................39
8.3.1
Warnings/Precautions ..................................................................................39

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8.3.2
Adverse Event Monitoring...........................................................................39
8.3.3
Adverse Event Definitions...........................................................................40
8.3.3.1
Adverse Events ..................................................................................40
8.3.3.2
Suspected Adverse Drug Reactions/Adverse Reactions....................40
8.3.4
Assessment of Causality of Adverse Event .................................................40
8.3.5
Severity of Adverse Event or Suspected Adverse Drug Reaction...............41
8.3.6
Expectedness of Adverse Event or Suspected Adverse Drug Reaction ......41
8.3.7
Seriousness of Adverse Event or Suspected Adverse Drug Reaction .........41
8.3.8
Adverse Event Documentation ....................................................................42
8.3.9
Reporting of Serious Adverse Events..........................................................43
8.3.9.1
Reporting of Serious Adverse Events................................................43
8.3.9.2
Reporting Pregnancy..........................................................................44
8.4
Type and Duration of the Follow-Up of Subjects after Adverse Events...............44
9
STATISTICS ...................................................................................................................45
9.1
Statistical Methods.................................................................................................45
9.1.1
Demographic and Baseline Characteristics .................................................45
9.1.2
Efficacy Analysis.........................................................................................45
9.1.3
Safety Analysis ............................................................................................45
9.1.3.1
Adverse Events ..................................................................................45
9.1.3.2
Clinical Laboratory Values................................................................46
9.1.3.3
Vital Signs..........................................................................................46
9.1.3.4
Physical Assessment ..........................................................................46
9.1.4
PK Analysis .................................................................................................47
9.2
Determination of Sample Size ...............................................................................48
9.3
Level of Significance to Be Used ..........................................................................48
9.4
Criteria for Termination of the Study ....................................................................48
9.5
Procedure for Accounting for Missing, Unused, and Spurious Data (if 
applicable)..............................................................................................................49
9.6
Reporting Deviation(s) from the Statistical Analysis Plan....................................49
9.7
Subject Population(s) for Analysis ........................................................................49
9.7.1
Safety Population:........................................................................................49
9.7.2
Evaluable Population:..................................................................................49
9.7.3
PK population: .............................................................................................49
10
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS..............................................49
11
QUALITY CONTROL AND QUALITY ASSURANCE...............................................50
12
ETHICS............................................................................................................................50
12.1
Institutional Review Board/Ethics Committee ......................................................50
12.2
Ethical Conduct of the Study.................................................................................50
12.3
Regulatory Authority Approvals/Authorizations...................................................51
12.4
Subject Information and Consent...........................................................................51

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12.5
Confidentiality .......................................................................................................51
13
DATA HANDLING AND RECORD KEEPING ...........................................................52
13.1
Data Handling........................................................................................................52
13.2
Record Retention ...................................................................................................52
14
FINANCING AND INSURANCE..................................................................................52
15
PUBLICATION POLICY ...............................................................................................53
16
REFERENCES ................................................................................................................53
17
APPENDICES .................................................................................................................55
LIST OF IN-TEXT TABLES
Table 7-1 Name, Description, and Location of Laboratory Tests and Procedures............36
Table 7-2 PK Blood Sampling Schedule ...........................................................................37
Table 9-1 Pharmacokinetic Parameters .............................................................................47
LIST OF APPENDICES
Appendix 1
Schedule of Study Procedures and Events.........................................56

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GLOSSARY AND ABBREVIATIONS
ADR
Adverse drug reaction
AE
Adverse event
ALP
Alkaline phosphatase
ALT
Alanine aminotransferase
aPTT
Activated partial thromboplastin time
AR
Adverse reaction
AST
Aspartate aminotransferase
AUC
Area under the concentration time curve
AUC0-T
Cumulative area under the plasma and/or serum concentration time curve 
calculated from 0 to time of last observed quantifiable plasma and/or 
serum concentration
AUC0-∞
Area under the plasma and/or serum concentration time curve 
extrapolated to infinity
B19V
Parvovirus B19
BMI
Body mass index
BUN
Blood urea nitrogen
CI
Confidence interval
CJD
Creutzfeldt-Jakob disease
ClTOT
Apparent total plasma and/or serum clearance
Cmax
Maximum observed plasma and/or serum concentration
eCRF
Case report form/electronic case report form
CRO
Contract research organization
CV
Coefficient of variation
DBP
Diastolic blood pressure
DNA
Deoxyribonucleic acid
F
Bioavailability
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GGT
Gamma-glutamyl transferase
HAV
Hepatitis A virus
HBV
Hepatitis B virus

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HCG
Human chorionic gonadotropin
HCV
Hepatitis C virus
HIV
Human immunodeficiency virus
HR
Heart rate
IB
Investigator’s brochure
ICF
Informed consent form
ICH
The International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use
IG
Immune globulin 
IgA
Immunoglobulin A
IgG
Immunoglobulin G
IgM
Immunoglobulin M
IM
Intramuscular
INR
International Normalized Ratio
IP
Investigational product
IRB/EC
Institutional Review Board/Ethics Committee
kg
Kilogram
LDH
Lactate dehydrogenase
MedDRA
Medical Dictionary for Regulatory Activities
NAT
Nucleic acid amplification technology
PK
Pharmacokinetic
PT
Prothrombin time
RR
Respiratory rate
RNA
Ribonucleic acid
SAE
Serious adverse event
SAP
Statistical analysis plan
SBP
Systolic blood pressure
SD
Standard deviation
S/D
Solvent/Detergent
TEAE
Treatment-emergent adverse event
Thalf
Terminal elimination half-life
Tmax
Time of maximum observed plasma and/or serum concentration

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US
United States
VD
Apparent volume of distribution
λz
Apparent elimination rate constant

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1
GENERAL INFORMATION
Protocol title and other key study information are provided on the title page. Information 
regarding additional key personnel and organizations involved in the conduct of the study, 
including names and contact details of participating investigators, monitors, clinical 
laboratories, technical departments and/or institutions, as well as information on members of 
additional study committees, will be found in the study files of the sponsor and at the 
Investigator sites within the study reference manual/file.
Investigators and staff will receive training either via an Investigators meeting or other 
appropriate individual site training session(s).
2
BACKGROUND INFORMATION
In addition to the information provided below, please also refer to the Investigator's Brochure
(IB) and any additional data supplied by the sponsor.
2.1
Name and Description of the Investigational Product(s)
See Section 4.4 Study Treatments for detail.
The following treatment will be used:

GamaSTAN (Immune Globulin ([Human]): a 15 to 18% protein solution of human 
Immunoglobulin G (IgG) for intramuscular (IM) injection
2.2
Relevant Findings from Nonclinical and Clinical Trials
2.2.1
Pre-exposure Prophylaxis for Hepatitis A Infection
The World Health Organization estimates an annual total of 1.5 million clinical cases of 
hepatitis A infection worldwide, but seroprevalence data indicate that tens of millions of 
hepatitis A virus (HAV) infections occur each year (1). Since the recommendation of HAV 
vaccination in 2006, vaccination rates and evidence of vaccine-induced immunity in young 
persons have increased in the past decade (2, 3). Yet hepatitis A vaccination coverage levels 
remain lower than those for other routinely recommended vaccines (4). Additionally, many 
older adults remain unvaccinated and susceptible to infection. International travel is the most 
commonly reported risk for HAV infection (5). After adjusting for under-ascertainment and 
under-reporting (6), the estimated number of new HAV infections in the US in 2015 was 
2,800 (95% confidence interval [CI] =1,900–3,100) (7).
Immune globulin (IG) provides protection against HAV infection through passive transfer of 
antibody. Efficacy is greatest when IG is administered early in the incubation period; when 
administered later, IG often only attenuates the clinical expression of hepatitis A infection (8).

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It has been shown that prophylactic IM injection of IgG with anti-HAV activities provides 
protection against HAV infection. GamaSTAN S/D is one such licensed product that is 
commonly administered to provide pre-exposure prophylaxis for persons travelling to areas 
with endemic hepatitis A (9). GamaSTAN S/D and GamaSTAN are both purified using a 
procedure based on the Cohn-Oncley process (10, 11), but GamaSTAN uses a 
caprylate/chromatography purification step.
2.2.2
Rationale for Clinical Investigation of GamaSTAN
GamaSTAN is manufactured from human plasma employing caprylate/chromatography steps 
in the purification scheme. This production process yields a final IgG product that is purer 
and more closely reflects the IgG subclass distribution found in plasma than earlier IgG 
products (12, 13). GamaSTAN is being developed for the same indications as those of 
GamaSTAN S/D including pre-exposure prophylaxis for persons travelling to areas with 
endemic HAV.
2.3
Known and Potential Risks and Benefits to Human Subjects
Because GamaSTAN is made from human plasma and is therefore a biological product, it 
may carry a risk of transmitting infectious agents (e.g., viruses and, theoretically, the 
Creutzfeldt-Jakob disease (CJD) agent). No cases of transmission of viral diseases or CJD 
have ever been identified for other products manufactured with the same 
caprylate/chromatography purification process. The risk that GamaSTAN can transmit an 
infectious agent has been reduced by screening plasma donors for prior exposure, testing 
donated plasma, and by the inclusion of steps in the manufacturing process with the 
demonstrated capacity to inactivate and/or remove pathogenic agents. Despite these 
measures, it may carry a risk of transmitting infectious agents. (9)
There is clinical evidence of an association between the administration of all 
immunoglobulins and thromboembolic events such as myocardial infarction, stroke, 
pulmonary embolism and deep vein thrombosis. Therefore, caution should be exercised when 
prescribing and administering immunoglobulins. Thrombosis may occur even in the absence 
of known risk factors.
GamaSTAN should be given with caution to subjects with a history of prior systemic allergic 
reactions following the administration of human IG preparations (14). GamaSTAN should not 
be given to subjects with isolated immunoglobulin A (IgA) deficiency. Such persons have the 
potential for developing antibodies to IgA and could have anaphylactic reactions to 
subsequent administration of blood products that contain IgA.Other antibodies in the 
GamaSTAN preparation may interfere with the response to live virus vaccines such as 
measles, mumps, polio, or rubella, and varicella. Therefore, use of such vaccines should be 
deferred until approximately 5 to 6 months after GamaSTAN administration. When 
administering GamaSTAN as prophylaxis for measles, wait 5 months before giving measles 
vaccine to a non-immunocompromised subject and wait 6 months for an 
immunocompromised subject (15).

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Local pain and tenderness at the injection site, urticaria, and angioedema may occur. 
Anaphylactic reactions, although rare, have been reported following the injection of human 
IG preparations. Anaphylaxis is more likely to occur if GamaSTAN is given intravenously; 
therefore, GamaSTAN must be administered only intramuscularly.
As with all preparations administered by the IM route, bleeding complications may be 
encountered in subjects with thrombocytopenia or other bleeding disorders.
Grifols' licensed Immune Globulin (Human) product, GamaSTAN S/D, is commonly 
administered as prophylaxis to provide active immunization following exposure to HAV, to 
provide pre-exposure prophylaxis for persons travelling to areas with endemic hepatitis A. 
GamaSTAN S/D is also indicated to prevent or modify measles, passive immunization 
against varicella, and prophylaxis in pregnant females exposed to rubella. The immediate 
administration of an IG product is intended to provide immediate passive virus neutralizing 
antibody coverage (2).
Since the study treatment is not being given to subjects to treat any symptoms or illness, 
there will be no direct medical benefit from participation in this trial.
2.4
Description of and Justification for the Route of Administration, 
Dosage, Dosage Regimen, and Treatment Period(s)
2.4.1
Administration of Investigational Products
A single 0.2 mL/kg dose of the investigational product (IP) will be injected intramuscularly 
in the anterolateral aspects of the upper thigh or the deltoid muscle of the upper arm.
Doses over 5 mL are to be divided and injected into several muscle sites to reduce local pain 
and discomfort.
The gluteal region should not be used as an injection site due to the risk of injury to the 
sciatic nerve. The IP is not to be administered subcutaneously or intravenously.
2.4.2
Justification for Selection of Doses/Timing of Investigational Products
Recently the Food and Drug Administration (FDA) approved and instituted an anti-HAV titer 
specification (Not Less Than >20 IU/mL) and revised dosing for GamaSTAN S/D. Due to 
the recently instituted titer specifications and revised dosing, Grifols committed to the FDA 
to evaluate anti-HAV titers following IM administration at the recommended dose of 
0.2 mL/kg in non-HAV (seronegative) healthy volunteers. An IM dose of 0.2 mL/kg was 
chosen, as it is the recommended dose for prophylaxis prior to exposure to hepatitis A for 
persons traveling to areas endemic with the virus.
Peak levels of IgG are obtained approximately 2 days after IM injection of immunoglobulins 
(12). The half-life of IgG in the circulation of individuals with normal IgG levels is 23 days (9). 
In this study, a 150-day follow-up period is chosen as it represents approximately 
5 half-lives.

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2.5
Compliance Statement
This study will be conducted under the conditions described in this protocol and in 
compliance with The International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH), Good Clinical Practice (GCP) and all applicable 
regulatory requirements.
2.6
Study Population
The study population will consist of HAV-seronegative healthy male and female subjects.
Subjects must meet all the inclusion criteria and none of the exclusion criteria at the 
screening visit to be eligible for participation in this study. Continued eligibility will be 
assessed upon admission to the clinical site, prior to study treatment administration.
3
STUDY OBJECTIVES AND PURPOSE
3.1
Efficacy Objectives
The primary efficacy objective is to evaluate whether a single 0.2 mL/kg IM dose of the 
study treatment will provide protective levels of anti-HAV antibodies in HAV-seronegative 
healthy subjects for up to 60 days.
3.2
Pharmacokinetic Objectives
The pharmacokinetic (PK) objective is to evaluate the PK parameters of anti-HAV antibodies 
following a single 0.2 mL/kg IM dose of the study treatment in HAV-seronegative healthy 
subjects.
3.3
Safety Objectives
The safety objective is to evaluate the safety and tolerability of a single 0.2 mL/kg IM dose 
of the study treatment in HAV-seronegative healthy subjects.
4
STUDY DESIGN
4.1
Primary Endpoint and Secondary Endpoints
The primary efficacy endpoint is the proportion of subjects maintaining protective anti-HAV 
antibody levels (defined as anti-HAV antibody titer ≥10 mIU/mL in plasma and/or serum) up 
to 60 days after study treatment administration.
With respect to the PK endpoint, the parameters of interest for this study are: AUC0-∞, 
AUC0-T, Cmax, Tmax, λz, Thalf, ClTOT/F and VD/F.
The safety endpoints will include a summary of the incidence of AEs, SAEs, suspected 
ADRs and ARs, as well as descriptive summary and statistics of the safety parameters 
(clinical laboratory values, vital signs and physical examination findings).

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4.2
Study Design and Plan
This is a single center, open-label, single-arm study design, in which approximately 
28 subjects will receive the same study treatment (0.2 mL/kg dose via IM injection). There is 
no reference therapy in this study.
The study will be explained to each subject prior to the subject providing written informed 
consent. All subjects will be screened to ensure that all the inclusion criteria and none of the 
exclusion criteria are met.
A sufficient number of subjects will be qualified by screening assessments and procedures
for reporting to the clinical site on Day -1. Subjects will be discharged from the clinic on Day 
2, following the scheduled assessments and procedures, and will return to the clinical site for 
the remaining ambulatory PK samples and safety monitoring, and again for the final visit 
(Day 150).
The total duration of study participation for subjects who complete the study will be 
approximately 178 days.
The Schedule of Study Procedures and Events is provided in Appendix 1.  The study consists 
of a Screening Visit, Treatment and Follow-up Visits, and Final Visit / Early Discontinuation 
Visit.  The overall study schema is presented in Figure 4-1.
Figure 4-1 Overall Study Diagram

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4.3
Measures Taken to Minimize/Avoid Bias
4.3.1
Subject Numbering
Subjects in the study will receive a consecutive subject number. Subject numbers are 
generated beginning with the study center number (3 digits, assigned by the sponsor) 
followed consecutively with a unique number for each subject (4 digits, including leading 
zeros). For example, if the Investigator's center number is 301, subject number will be 
3010001, 3010002, 3010003, etc., in consecutive order. Subject numbers, once assigned, will 
not be reused. If a subject is re-screened, a different subject number will be assigned to this
subject.
4.3.2
Randomization
As this is an open-label, single-arm study design, no randomization code will be provided.
4.3.3
Blinding
Not applicable as this is an open-label study.
4.4
Study Treatments
4.4.1
Treatments to Be Administered
A single 0.2 mL/kg IM injection of GamaSTAN, administered in the anterolateral aspects of 
the upper thigh or the deltoid muscle of the upper arm.
Doses over 5 mL are to be divided and injected into several muscle sites to reduce local pain 
and discomfort.
The gluteal region should not be used as an injection site due to the risk of injury to the 
sciatic nerve. The IP is not to be administered subcutaneously or intravenously.
4.4.1.1       GamaSTAN
GamaSTAN (Immune Globulin ([Human]) is a 15 to 18% protein solution of human IgG for 
IM injection solution of human IgG for IM injection. GamaSTAN contains a minimum of 
20 IU/mL of anti-HAV antibodies. GamaSTAN is a clear to opalescent, colorless to pale 
yellow sterile solution of polyvalent human IgG that contains no preservative.
GamaSTAN is provided in vials for single use. The batch number(s) of the study formulation 
will be indicated in the study files.
4.4.2
 
Labeling of Investigational Product
IP will be labeled according to the requirements of local law and legislation. Label text will 
be approved according to agreed Grifols procedures, and a copy of the labels will be made 
available to the study site.

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4.4.3
Packaging of Investigational Product
The sponsor will be responsible for ensuring that the IP is manufactured in accordance with 
applicable Good Manufacturing Practice regulations and requirements.
4.4.4
Storage of Investigational Product
GamaSTAN must be stored in a secure location accessible only to study personnel authorized 
by the Investigator, such as the pharmacy staff responsible for the preparation and dispensing 
of IP.
GamaSTAN must be stored at 2 to 8°C (36 to 46°F). Do not freeze.
Investigators or designees are responsible for maintaining storage temperature records and 
for immediately reporting deviations in temperature to the study monitor. Continuous 
24 hour, 7 days a week temperature monitoring is preferred.  IP storage monitoring should be 
recorded and maintained by pharmacy staff. Copies of the storage temperature monitoring 
records will be made available for review by the Site Monitor, if applicable, during the 
course of the study and will be provided to the Sponsor at completion of the study. Details of 
receipt, storage, dispensing, and destruction will be recorded and maintained in the pharmacy 
log book by pharmacy staff.
Unused IP will either be destroyed according to local or institutional disposal regulations and 
regulatory requirement or shipped return to the Sponsor at the end of the study. The Sponsor 
will provide written instructions regarding final disposition of the unused IP. Copies of the IP 
storage and destruction records will be provided to the Sponsor at completion of the study.
4.5
Expected Duration of Subject Participation in the Study
After a screening period of up to 28 days, subjects will receive a single dose of the study 
treatment, which will be followed by a PK sampling period of 150 days. The total duration of 
participation for each subject in this study will be up to approximately 178 days.
4.6
Discontinuation Criteria for Individual Subjects and Study
4.6.1
Discontinuation Criteria for Individual Subjects
See Section 5.3 Subject Withdrawal Criteria.
4.6.2
Premature Termination of Study
The sponsor, Institutional Review Board/Ethics Committee (IRB/EC), and/or regulatory 
authorities have the right to close this study or the study center, and an Investigator /sponsor 
has the right to close the study center, at any time, although this should occur only after 
consultation between involved parties. The IRB/EC must be informed. Should the 
study/center be closed prematurely, all study materials (except documentation that has to 
remain stored at site) must be returned to the sponsor. An Investigator will retain all other 
documents until notification given by the sponsor for destruction.

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The study center can be closed for the following reasons:
•
Lack of enrollment 
•
Non-compliance with the requirements of the study protocol
•
Non-compliance with ICH, GCP
4.7
Accountability Procedures for Investigational Product(s)
IP is to be used only for the study in accordance with the directions given in this protocol. An
Investigator, or designee such as the study pharmacist, is responsible for the distribution of 
the IP in accordance with directions given in the protocol.
An Investigator is responsible for maintaining accurate records of the IP for his/her site. IP 
inventory/dispensing documentation verifying the receipt, dispensing, damaged state or 
return must be maintained and kept current by an Investigator, or designee. The inventory 
must be made available for inspection by the monitor. IP supplies must be accounted for by 
the monitor and inventory/dispensing logs must be verified by the monitor prior to IP return 
or destruction. Written documentation of any used and unused inventory is required. At the 
end of the study, a copy of the inventory/dispensing log(s) will be retrieved by the monitor 
and returned to Grifols.
4.8
Maintenance of Treatment Randomization Codes
As this is an open-label, single-arm study design, no randomization code will be provided.
4.9
Data to Be Recorded Directly on the eCRFs
Source documents will be used to record all study-related data. Designated staff will enter the 
data required by the protocol into the Electronic Case Report Forms (eCRF).
5
SELECTION AND WITHDRAWAL OF SUBJECTS
This study will include HAV-seronegative healthy adult subjects.
5.1
Inclusion Criteria
A subject must meet all the following inclusion criteria to be eligible for participation in this 
study:
1. Male subjects from 18 to 55 years of age, inclusive, or female subjects from 18 to 
65 years of age, inclusive
2. Subjects with a body mass index (BMI) of 18.5 to 29.9 kg/m2
3. Body weight greater than or equal to 50 kg at screening
4. Subjects willing and able to provide written informed consent

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5. Subjects in good health in the judgment of the Investigator, as determined by medical 
history, physical examination, vital signs, ECG and laboratory assessments
6. A female study subject must meet one of the following criteria:
a.
If a female of childbearing potential – agrees to use one of the accepted 
contraceptive regimens from at least 30 days prior to study treatment 
administration and during the entire study duration. An acceptable method of 
contraception includes one of the following:

Abstinence from heterosexual intercourse (i.e. when abstinence is the 
preferred and usual lifestyle of the subject; periodic abstinence is not 
acceptable)

Non-estrogen containing hormonal contraceptives (birth control pills, 
injectable/implant/insertable hormonal birth control products, transdermal 
patch)

Intrauterine device without hormones

Condom with spermicide

Diaphragm or cervical cap with spermicide

Vasectomized partner (minimum 6 months since vasectomy prior to study 
treatment administration)
b. If a female of non-childbearing potential – should be surgically sterile (i.e. has 
undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in 
a menopausal state (at least 1 year without menses prior to study treatment 
administration)
7. A male study subject must agree to use one of the accepted contraceptive regimens 
during the entire study duration;

Abstinence from heterosexual intercourse

Female partner with condom with spermicide used by male study subject

Female partner of non-childbearing potential

Male sterilization (if proof of sterilization is not provided, the subject must 
agree to use one of the above accepted contraceptive methods)
8. A male study subject must agree not to impregnate a female or donate sperm during the 
entire study duration
5.2
Exclusion Criteria
A subject meeting any of the following exclusion criteria is NOT eligible for participation in 
the study:
1. Subject vaccinated against HAV, as documented the in medical history at the screening 
visit
2. Subject with positive anti-HAV antibodies in blood sample at the screening visit
3. Subject who previously received any type of IG, including HAV IG within the past 
12 months prior to study treatment administration

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4. Subject with prolonged International Normalized Ratio (INR) or activated partial 
thromboplastin time (aPTT) at the screening visit
5. Subject with a platelet count below 100×109/L at the screening visit
6. Subject suffering from some acute or chronic medical, surgical or psychiatric significant 
condition or laboratory abnormality at the screening visit or prior to study treatment 
administration that, according to Investigator judgement, may increase the risk associated 
with study participation or study treatment administration, or may interfere with the 
successful completion or interpretation of the study results
7. Subject with a history of the following: angioedema, cardiac arrhythmia, angina pectoris, 
myocardial infarction, cerebrovascular accident, cardiac failure, thrombotic events, 
embolism, coagulopathy, diabetes mellitus, hyperlipidaemia, nephrotic syndrome, acute 
renal injury, chronic obstructive pulmonary disease, asthma, hepatic disease, 
reticuloendothelial system dysfunction, or nervous system disorder
8. Subject with known personal or family history of abnormal bleeding episodes
9. Subject not willing to receive study treatment via IM route of administration or unable to 
receive study treatment via IM route of administration
10. Subject with cardiovascular risk factors based on medical history: active tobacco 
smoking and/or ongoing diabetes mellitus at the screening visit
11. Subject with thrombosis risk factors: prolonged immobilization within 2 months prior to 
the screening visit, history of venous or arterial thrombosis, use of estrogens (30 days 
prior to the study drug administration), indwelling central vascular catheters and 
hyperviscosity or hypercoagulable states
12. Subject with known history of hypersensitivity/allergic reaction to blood/plasma products
13. Subject with known selective IgA deficiency (with or without antibodies to IgA)
14. Subject who received any plasma-derived product infusion within 12 months prior to 
study treatment administration
15. Subject who received a blood or plasma transfusion within 12 months prior to study 
treatment administration
16. Subject with systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg 
at the screening visit and prior to treatment administration
17. Subject with anemia (hemoglobin <12 g/dL in women and 13 g/dL in men) at the 
screening visit
18. Subjects with proteinuria (>1+ on urine dipstick), blood urea nitrogen (BUN) or 
creatinine greater than the upper limit of normal at the screening visit
19. Subject with liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase 
[ALT] and gamma-glutamyl transferase [GGT]) levels greater than the upper limit of 
normal at screening visit
20. Subject who received any dose of parenteral, oral, or inhaled corticosteroids, 
immunosuppressants, or immunomodulators within 6 weeks prior to the screening visit

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21. Subject who received any live virus vaccine within five months prior to the screening 
visit
22. Subject not willing to postpone receiving any live virus vaccines until 6 months after 
receiving IP
23. Currently receiving any anti-viral treatment, regardless of the route of administration
24. Subject with virus safety laboratory results (serology and/or nucleic acid amplification 
technology [NAT]) indicative of a current infection with hepatitis A virus (HAV), 
hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) 
or parvovirus B19 (B19V) at the screening visit
25. Participated in another clinical trial within 30 days prior to the screening visit or has 
received any IPs within 3 months prior to the screening visit
26. Positive urine drug panel testing at the screening visit or prior to study treatment 
administration
27. Known or suspected abuse of alcohol, opiates, psychotropic agents or other drugs or 
chemical substances; or has done so in the 12 months prior to the screening visit
28. In the opinion of the Investigator, the subject may have compliance problems with the 
protocol and the procedures of the protocol
29. Subject who has already been included in a previous group for this clinical study
5.3
Subject Withdrawal Criteria
5.3.1
Screen Failures
Screening evaluations will be used to determine the eligibility of each subject for enrollment.  
Subjects who fail to meet eligibility criteria during screening evaluations will be considered 
screen failures and will not participate in the study. However, subjects who fail the first 
screening evaluation are allowed to be re-screened once.
5.3.2
Removal of Subjects
Subjects may voluntarily withdraw from the study, or be removed from the study at the 
discretion of an Investigator or Sponsor at any time. An Investigator may withdraw a subject 
at any time if it is determined that continuing the study would result in a significant safety 
risk to the subject.
If such withdrawal occurs, or if the subject fails to return for visits, an Investigator should 
determine the primary reason for a subject's premature withdrawal from the study and record 
the reason in the respective subject's study documents.
Subjects may withdraw or be withdrawn from the study for the following reasons:
1. At their own request or at the request of their legally acceptable representative

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2. If, in an Investigator's opinion, continuation in the study would be detrimental to the 
subject's well-being
3. At the specific request of the sponsor
Also subjects may be withdrawn for the following reasons:
•
Noncompliance with the protocol requirements
•
Difficulties with blood collection
•
Pregnancy
•
AE
•
Unanticipated event that could result in an inadequately characterized PK profile (such as 
missed PK blood samples, for example)
•
Other
In all cases, the reason for withdrawal must be recorded in the eCRF and in the subject's 
records.
5.3.3
Subject Replacement
Subjects who are withdrawn from the study will not be replaced.
5.3.4
Follow-up of Subjects Withdrawn from Study
Subjects who receive any amount of IP and discontinue early from the study will be 
requested to return for the early discontinuation visit procedures within approximately 7 days 
following discontinuation.
6
TREATMENT OF SUBJECTS
See Section 4.4 for the treatment to be administered, including the name of the IP, the dose, 
the dosing schedule and the route/mode of administration.
6.1
Administration and Timing of Investigational Products for Each 
Subject
Administration of the IP will be staggered between subjects for the purpose of accurate 
sampling time.
A single 0.2 mL/kg dose of the IP will be injected intramuscularly in the anterolateral aspects 
of the upper thigh or the deltoid muscle of the upper arm.
Doses over 5 mL are to be divided and injected into several muscle sites to reduce local pain 
and discomfort.
The gluteal region should not be used as an injection site due to the risk of injury to the 
sciatic nerve. The IP is not to be administered subcutaneously or intravenously.

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The subjects will be discharged from the clinic on Day 2, following the scheduled 
assessments and clinical procedures. Subjects will be asked to return to the clinic for the 
remaining PK blood samples and clinical assessments, and for the final visit.
6.2
Prior and Concomitant Therapy
Concomitant medications must be recorded in the eCRF, including the trade and generic 
names of the medication, the dose, the route of administration, and the duration of the 
medication (frequency).
6.2.1
Prohibited Medications Prior to Study Participation
As per the exclusion criteria (see section 5.2), subjects are prohibited from taking any of the 
following prior to study participation:
1. Any type of IG, including HAV IG
2. Estrogens (for at least 30 days prior to the study drug administration and during the entire 
study duration)
3. Any plasma-derived product infusion
4. Any blood or plasma transfusion
5. Any live virus vaccine
6. Any anti-viral treatment, regardless of the route of administration
7. Any dose of parenteral, oral, or inhaled corticosteroids, immunosuppressants, or 
immunomodulators
6.2.2
Prohibited Concomitant Medications during the Study
In addition to the medications listed in section 6.2.1, subjects are prohibited from taking any 
IPs that are not for this study.
6.2.3
Restricted Concomitant Medications during the Study
No concomitant medications will be restricted during the study with the exception of any 
medication described in section 6.2.1.
6.3
Treatment Compliance
Reasons for any deviation from the administration of less than 100% of the IP dose, as 
prepared by the pharmacist or designee, must be recorded in the eCRF and in the subject’s 
medical records.
To ensure treatment compliance, study treatment administrations will be observed and 
verified by a site staff member.

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7
ASSESSMENT OF EFFICACY AND PHARMACOKINETICS
7.1
Efficacy Variables
7.1.1
Primary Efficacy Variable
The primary efficacy variable in this study is the proportion of subjects maintaining 
protective anti- HAV antibody levels (defined as anti-HAV antibody titer ≥10 mIU/mL in 
plasma and/or serum) up to 60 days after study treatment administration.
7.2
Pharmacokinetic Variables
The PK Variables for anti-HAV antibody in plasma and/or serum are:
•
AUC0-∞: AUC from time zero to time infinity
•
AUC0-T: AUC from time zero to time of last measured concentration
•
Cmax: maximum concentration
•
Tmax: time to Cmax
•
λz: terminal elimination rate
•
Thalf: estimated elimination half-life
•
ClTOT/F: apparent total plasma and/or serum clearance
•
VD/F: apparent volume of distribution
PK parameters will be estimated using both anti-HAV antibody baseline uncorrected and 
baseline corrected levels.
7.3
Methods and Timing for Assessing, Recording, and Analyzing 
Efficacy Parameters
7.3.1
Observations and Measurements
The following is a description of the procedures/assessments to take place at each study visit. 
See the Schedule of Study Procedures and Events in Appendix 1.
Screening Visit (Day -28 to Day -2):
Subjects will be screened for enrollment in this study. The following procedures will be 
done:
•
Obtain informed consent
•
Review of inclusion and exclusion criteria for determination of subject’s study eligibility
•
Documentation of medical history
•
Documentation of demographics
•
Height and weight measurement and determination of BMI
•
Full physical examination (excluding breast and genitourinary examination)
•
ECG

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•
Vital signs measurement (heart rate [HR], blood pressure [BP], respiratory rate [RR], and 
body temperature)
•
Clinical laboratory assessments (chemistry, hematology, urinalysis) (see Table 7-1 for 
details)
•
Virus safety testing (see Table 7-1 for details). Note: the viral safety test results for HAV 
serology (HAV antibody differential (Immunoglobulin M [IgM]/IgG)) will be used to 
determine subject eligibility
•
Coagulation tests (INR, aPTT)
•
Immunoglobulin A (IgA) testing (see Table 7-1 for details)
•
Urine alcohol and drug panel testing (see Table 7-1 for details)
•
Urine pregnancy test for females
•
Record prior (30 days prior to screening visit) and concomitant medications
•
Record AEs
Treatment Period:
Day -1:
Subjects will be admitted to the clinical research unit on the day prior to study drug injection. 
The following procedures will be done upon admission:
•
Review of subject eligibility (review of inclusion/exclusion criteria)
•
Record concomitant medications
•
Record AEs
•
Vital signs measurement (HR, BP, RR, and body temperature)
•
Symptom-directed physical examination
•
ECG
•
Clinical laboratory assessments (chemistry, hematology, urinalysis) (see Table 7-1 for 
details)
•
Urine alcohol and drug panel testing (see Table 7-1 for details)
•
Urine pregnancy test for females
Day 1:
The following procedures will be done (all pre-dose procedures are to be performed within 
1 hour prior to dosing):
•
Collection of virus safety retain samples prior to study drug injection
•
Vital signs measurement (HR, BP, RR, and body temperature) prior to study drug 
injection, 60 minutes post study drug injection (a window of ±10 minutes is permitted) 
and 12 hours post study drug injection (a window of ±10 minutes is permitted)
•
Record AEs and concomitant medications prior to and post study drug injection
•
Study drug injection

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•
PK blood sampling prior to study drug injection, 60 minutes post study drug injection 
(a window of ±10 minutes is permitted) and 12 hours post study drug injection (a window 
of ±1 hour is permitted)
•
Injection site evaluation 60 minutes (±10 minutes) post study drug injection (Note: any 
reactions will be recorded as AEs)
Day 2:
•
Record concomitant medications
•
Record AEs
•
PK blood sample will be collected approximately 24 hours following study treatment 
administration (a window of ±1 hour is permitted)
•
Injection site evaluation approximately 24 hours post study drug injection (prior to 
discharge) (Note: any reactions will be recorded as AEs)
•
Symptom-directed physical examination approximately 24 hours post study drug 
injection (prior to discharge)
•
Subjects will be discharged from the clinical research unit on Day 2, following clinical 
assessments and procedures, and will return for each of the remaining scheduled 
ambulatory visits (from Days 3 to 150).
Day 3 to Day 115:
A PK blood sample will be collected on each of the following days:
•
Days 3, 4 and 5 (a window of ±4 hours is permitted)
•
Days 7, 10, and 14 (a window of ±1 day is permitted)
•
Days 21 and 28 (a window of ±2 days is permitted)
•
Days 60, 79, and 115 (a window of ±4 days is permitted)
Procedures performed on Days 3, 4, 5, 7, 10, 14, 21, 28, 60, 79 and 115 (the window for 
these procedures is the same as that for the PK sample to be collected on the same study 
Day):
•
Record concomitant medications
•
Record AEs
•
Vital signs measurement (HR, BP, RR, and body temperature) (Day 5, 28, and 60 visits 
only)
•
Symptom-directed physical examination (Day 5, 28, and 60 visits only)
•
Clinical laboratory assessments (chemistry, hematology, urinalysis) (Day 5, 28, and 
60 visits only) (see Table 7-1 for details)
Final Visit (Day 150 ±7 days)/Early Discontinuation Visit:
•
Record concomitant medications
•
Record AEs

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•
A PK blood sample will be collected
•
Full physical examination (excluding breast and genitourinary examination)
•
Vital signs measurement (HR, BP, RR, and body temperature)
•
Clinical laboratory assessments (chemistry, hematology, urinalysis) (see Table 7-1 for 
details)
•
Collection of virus safety retain samples (see Table 7-1 for details)
7.3.2
Description of Laboratory Tests and Procedures
Detailed descriptions of laboratory test procedures are located in the study Laboratory 
Manual. Table 7-1 provides a summary of the laboratory tests to be conducted for this study.
Table 7-1 Name, Description, and Location of Laboratory Tests and Procedures
Test Panel
Description
Location
Hematology
Hemoglobin, hematocrit, platelets, red blood cell count, white blood 
cell count (absolute and % with differential)
Central
Chemistry
Sodium, potassium, creatinine, calcium, BUN, LDH, AST, ALT, GGT, 
ALP, glucose, total bilirubin, direct and indirect bilirubin
Central
Coagulation 1
INR and aPTT
Central
Immunoglobulin A (IgA)1
Quantitative
Central
Urine pregnancy test 2
Qualitative urine β-HCG for female subjects
Local
Urine test for alcohol and
drugs of abuse
Alcohol, marijuana, opiates, cocaine, amphetamines, 
methamphetamines, and benzodiazepines
Central
Urinalysis
Microscopic evaluation is done only with cause.
pH, protein, glucose and blood
Central
Virus safety (NAT) testing
Screening:
HAV ribonucleic acid (RNA), HBV DNA, HCV RNA, HIV-1 RNA, 
and B19V DNA testing
Central
Virus safety (serology) 
testing
Screening:
hepatitis A antibody differential (IgM/IgG), hepatitis B core antibody 
differential (IgM/IgG), hepatitis C antibody, HIV-1/-2 + Group O 
antibody, and B19V antibody differential (IgM/IgG) testing
Central
Virus safety (NAT and 
serology) retain samples 3
Day 1 prior to study drug injection and final visit
1.
Screening visit only.
2.
Screening and on Day -1, prior to study treatment administration.
3.
Virus safety (NAT and serology) retain samples collected during the study will only be tested if subject 
exhibits clinical signs and symptoms consistent with HAV, HBV, HCV, HIV or B19V infection while 
participating in the study.  Virus safety retain samples will be retained until all analyses in support of the 
study are complete.
If samples collected for laboratory analyses are non-analyzable due to various factors 
(i.e., lost, quantity not sufficient/useful, laboratory error), they will need to be recollected by 
contacting the subject and arranging for re-sampling.

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Blood and/or urine samples may be repeated at the discretion of the Principal Investigator 
and/or Sponsor.
7.3.3
Drug Concentration Measurements
Total anti-HAV antibody levels will be measured in the subjects throughout the study.
Table 7-2 PK Blood Sampling Schedule
Sample Number
Study Day
Time (Window)
01
1
Prior to treatment administration
02
1
60 minutes following treatment administration 
(±10 minutes)
03
1
12 hours following  treatment administration
(±1 hour)
04
2
24 hours following  treatment administration
(±1 hour)
05
3
48 hours following  treatment administration
(±4 hours)
06
4
72 hours following  treatment administration 
(±4 hours)
07
5
96 hours following  treatment administration 
(±4 hours)
08
7
(±1 day)
09
10
(±1 day)
10
14
(±1 day)
11
21
(±2 days)
12
28
(±2 days)
13
60
(±4 days)
14
79
(±4 days)
15
115
(±4 days)
16
150
(±7 days)
8
ASSESSMENT OF SAFETY
8.1
Safety Parameters
Safety of the IP will be evaluated in this study. Safety endpoints will include:

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•
AEs including SAEs, suspected ADRs, and ARs
•
Clinical laboratory parameters including chemistry, hematology, and urinalysis
•
Physical examination
•
Vital signs (HR, BP, RR, and body temperature)
8.2
Methods and Timing for Assessing, Recording, and Analyzing 
Safety Parameters
8.2.1
Adverse Events
Adverse events occurring at any time between signing of the subject’s informed consent form 
(ICF) and the last day of the subject's participation in the clinical trial will be reported and 
recorded on the appropriate subject's eCRF entry.
It is the Investigator’s responsibility to ensure that all AEs are appropriately recorded.
Adverse events will be elicited by spontaneous reporting by the study individual or by a 
non-leading inquiry or direct observation by the study staff.
8.2.2
Clinical Laboratory Evaluations
All clinical laboratory data will be listed for each subject (refer to Table 7-1).
An Investigator will be required to classify laboratory results out of the normal range 
reported by the laboratory as clinically significant or not according to his/her criteria. Clinical 
laboratory evaluations may be repeated at an Investigator’s discretion.
Laboratory results out of the normal range judged by an Investigator as clinically significant 
will be considered AEs.
8.2.3
Virus Safety Testing
Virus safety (NAT and serology) retain samples collected on Day 1 prior to IP administration 
and at the final visit or early discontinuation visit will be tested only if the subject exhibits 
clinical signs and symptoms consistent with hepatitis A, hepatitis B, hepatitis C, HIV, or 
B19V infection while participating in the study. Virus safety retain samples will be retained 
until all analyses in support of the study are complete. Additional samples for viral NAT and 
viral serology testing may be collected and tested during the study only if the subject exhibits 
clinical signs and symptoms consistent with hepatitis A, hepatitis B, hepatitis C, HIV, or 
B19V infection while participating in the study.
8.2.4
Vital Signs
Vital signs will be measured at the following visits: screening visit, study Days -1, 1, 5, 28 
and 60, and at final visit on Day 150 (or early discontinuation visit).

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The following vital signs will be assessed:
-
Temperature
-
Blood Pressure (systolic blood pressure [SBP]) and diastolic blood pressure [DBP]),
-
HR
-
RR
Vital signs will be routinely monitored by the study staff as detailed in Appendix 1. An
Investigator will be required to classify vital signs abnormalities as clinically significant or 
not according to his/her criteria. Results will be recorded in source documents and on the
subject eCRF. Vital signs abnormalities judged by an Investigator as clinically significant 
will be considered AEs.
8.2.5
Physical Examinations
A medically certified individual will conduct a physical examination, as necessary, at the 
following visits:
Screening visit, study Days -1, 2, 5, 28 and 60, and at final visit on Day 150 (or early 
discontinuation visit).
Physical examinations will be routinely monitored by the study staff as detailed in Appendix 
1. A complete physical examination will be performed by a medically qualified and licensed 
individual. The physical examination will include a review of the following: head and neck, 
heart, lungs, abdomen and general appearance. Any abnormalities judged by an Investigator 
as clinically significant will be considered AEs.
8.3
Procedures for Eliciting Reports of and for Recording and 
Reporting Adverse Event and Intercurrent Illnesses
8.3.1
Warnings/Precautions
For complete information on GamaSTAN, refer to the GamaSTAN IB and to protocol 
section 2.3.
8.3.2
Adverse Event Monitoring
Subjects must be carefully monitored for AEs. This monitoring includes clinical and 
laboratory tests and physical signs. AEs should be assessed in terms of their seriousness, 
severity, and causal relationship to the IP.
AEs will be elicited by spontaneous reporting by the study individual or by a non-leading 
inquiry or direct observation by the study staff.

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8.3.3
Adverse Event Definitions
8.3.3.1
Adverse Events 
An AE is defined as any untoward medical occurrence in a subject or clinical investigation 
subject administered a medicinal product or study treatment and which does not necessarily 
have a causal relationship with this administration. An AE can therefore be any unfavorable 
and unintended sign (including any abnormal laboratory finding, for example), symptom, or 
disease temporally associated with the use of a medicinal product, whether or not considered 
related to the medicinal product. In this study, all local site reactions are to be considered as 
AEs.
8.3.3.2
Suspected Adverse Drug Reactions/Adverse Reactions
All noxious and unintended responses to a medicinal product or study treatment related to 
any dose should be considered suspected ADRs. The phrase "responses to a medicinal 
product" means that a causal relationship between a medicinal product or study treatment and 
an AE is at least a reasonable possibility.
In the framework of this study, a suspected ADR for which there is a reason to conclude that 
the drug caused the event will be labeled as an adverse reaction (AR); thus, ARs are a subset 
of suspected ADRs.
An AE will be considered a Suspected ADR when either the sponsor or an Investigator 
considers that the drug might have caused the adverse event.
8.3.4
Assessment of Causality of Adverse Event
An Investigator is required to provide a causality assessment for each AE reported to the 
Sponsor. The Sponsor will consider an Investigator's causality assessment and also provide 
its own assessment.
Causal relationship to the study drug will be established according to medical judgment on 
whether there is a reasonable possibility of a causal relationship between the AE and the
IP administration:
An Investigator must determine and classify the AE causality according to the following 
categories:
Unrelated/Not related: there is not a reasonable possibility of causal relationship between 
the AE and the study drug.
Possibly related: there is evidence to suggest a causal relationship between the study drug 
and the AE.
Definitively related: there is a reason to conclude that the study drug caused the AE.

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Criteria to assess the causal relationship should take into account of the following conditions: 
1) a plausible temporal sequence from the study drug administration to the AE onset; 2) 
whether the event follows a known response pattern to the suspected treatment; 3) whether 
the AE could be reasonably explained by the subject's clinical state, comorbidities, or 
concomitant medications, as well as 4) the occurrence of improvement on stopping/reducing 
the treatment (positive dechallenge) and/or reappearance of the event on repeated exposure 
(positive rechallenge).
For expedited safety reporting purposes, AEs assessed as either "definitively related" or 
"possibly related" will be considered POTENTIALLY RELATED or just RELATED.
For any subject, all AEs that occur at any time from the beginning of IP administration until 
the final visit of the clinical trial will be considered treatment-emergent AEs (TEAEs).
8.3.5
Severity of Adverse Event or Suspected Adverse Drug Reaction
AEs and suspected ADRs will be classified depending on their severity according to the 
following definitions:
Mild: an AE which is well tolerated by the subject, causing minimum degree of malaise and 
without affecting normal activities.
Moderate: an AE that interferes with the subject’s normal activities.
Severe: an AE that prevents the subject from performing their normal activities.
AE and suspected ADR severity gradation must be distinguished from AE and suspected 
ADR seriousness gradation, which is defined according to event consequence. For example, 
headache can be mild, moderate or severe but not necessarily serious in all these cases.
An Investigator will be responsible for assessing the AE and suspected ADR intensity during 
the clinical trial, taking into account current criteria included in this section.
8.3.6
Expectedness of Adverse Event or Suspected Adverse Drug Reaction
An AE or suspected ADR is considered "unexpected" if the nature, seriousness, severity or 
outcome of the reaction(s) is not consistent with the reference information. The expectedness 
shall be determined by the Sponsor according to the reference document (i.e., IB) for any 
serious suspected ADRs (potentially related SAEs) for expedited safety reporting purposes.
8.3.7
Seriousness of Adverse Event or Suspected Adverse Drug Reaction
An AE or suspected ADR is considered "serious" if, in the view of either an Investigator or 
Sponsor, it results in any of the following outcomes:
•
Death

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•
Life-threatening AE (life-threatening in the definition of "serious" refers to an event in 
which the subject was at risk of death at the time of the event; it does not refer to an event 
which hypothetically might have caused death if it were more severe)
•
In-patient hospitalization or prolongation of existing hospitalization
•
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions
•
A congenital anomaly/birth defect
•
An important medical event (important medical event in the definition of "serious" refers 
to those events which may not be immediately life-threatening, or result in death, or 
hospitalization, but from medical and scientific judgment may jeopardize the subject 
or/and may require medical or surgical intervention to prevent one of the other outcomes 
listed above)
*Hospitalization is to be considered only hospital stay for equal or more than 24 hours. 
The following hospitalizations should not be reported as SAEs:
-
hospitalization or prolongation of hospitalization needed for procedures required by 
the clinical trial protocol
-
hospitalization or prolongation of hospitalization as part of a routine procedure 
followed by the center
-
hospitalization for a survey visit, annual physicals, or social reasons
-
elective or pre-planned hospitalizations for a pre-existing condition that had not 
worsened from Baseline (e.g. elective or scheduled surgery arranged prior to start of 
the study)
-
admissions not associated with an AE (e.g. social hospitalization for purposes of 
respite care)
This definition permits either the Sponsor or an Investigator to decide whether an event is 
"serious". If either the Sponsor or an Investigator believes that the event is serious, the event 
must be considered "serious" and evaluated by the Sponsor for expedited reporting.
8.3.8
Adverse Event Documentation
All AEs occurring after the subject has signed the ICF through the final visit (i.e., end of 
study) must be fully recorded in the subject's eCRF as well as in the medical record. If no 
AE has occurred during the study period, this should also be indicated in the eCRF. Each 
SAE must be fully recorded on the SAE Report Form as well as in the medical records and 
indicated as serious in the eCRF.
It is the responsibility of an Investigator to ensure that AEs including SAEs are appropriately 
recorded.
At each visit, AEs will be elicited by asking the individual a non-leading question such as 
"Do you feel different in any way since the last visit?"  Moreover, AEs will also be collected 
through directly observed events or spontaneously volunteered by the subject. Clearly related 

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signs, symptoms and abnormal diagnostic procedures should preferably be grouped together 
and recorded as a single diagnosis or syndrome wherever possible.
The following variables must be recorded in the AE eCRF:
•
The verbatim term (a diagnosis is preferred)
•
Date/time of onset
•
Date/time of resolution
•
Severity (mild, moderate, severe)
•
Causality (unrelated, possibly related, definitely related)*
•
Seriousness (yes, no)
•
Action taken (with regard to IP)
•
Other action (to treat the event)
•
Outcome and sequel (follow-up on AE)
*Causality assessment will be made only when the AE occurs after the subject has initiated at 
least one infusion of the IP. An AE occurring before subject's exposure to IP will be always 
labeled as "unrelated".
In addition to an Investigator’s own description of the AEs, each AE will be encoded 
according to the Medical Dictionary for Regulatory Activities (MedDRA®).
For example, a laboratory test abnormality considered clinically significant, e.g., causing the 
subject to withdraw from the study, requiring treatment or causing apparent clinical 
manifestations, or judged clinically significant in the context of the subject's medical history 
by an Investigator, should be reported as an AE. Each event must be described in detail along 
with start and stop dates, severity, relationship to IP, action taken and outcome. Each event 
must be adequately supported by documentation as it appears in the subject's medical or case 
file.
8.3.9
Reporting of Serious Adverse Events
8.3.9.1
Reporting of Serious Adverse Events
Any SAE (see section 8.3.7) that occurs after signing the study ICF through the final visit 
(i.e., end of study) must be expeditiously reported whether or not considered attributable to 
the study drug.
SAEs will be reported using the designated SAE Report Form. When an Investigator 
becomes aware of an SAE, she/he must submit a completed, signed and dated SAE Report 
Form (in English) within 24 hours to the Sponsor by email/fax. The date of this SAE 
discovery by the site staff should be documented in the source documents (i.e., medical 
records).

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Each SAE must be followed up until resolution or stabilization. After the initial report, all 
relevant information for SAE follow-up, and for the outcome, must also be supplied to the 
Sponsor in a timely manner (within 3 days from its identification or within 24 hours for 
relevant new information) by means of the SAE Report Form. In addition, the Sponsor or 
contract research organization (CRO) may request additional information and/or reports.
All SAE Report Forms must be reported by e-mail to:
Grifols Global Pharmacovigilance
When required, and according to local law and regulations, SAEs must be reported to the 
IRB/EC and regulatory authorities.
8.3.9.2
Reporting Pregnancy
While pregnancy itself is not a true "AE," pregnancy occurring in a clinical study must be 
followed, to collect information regarding the experiences of gestation and pregnancy with IP 
exposure. An Investigator must report any pregnancy that occurs in a female study subject / 
partner of a male study subject subsequent to first treatment exposure to the Final Study Visit 
(Day 150)/Early Discontinuation Visit. Any female subject who becomes pregnant during the 
study will be discontinued from IP treatment and will be followed for pregnancy outcome.
A pregnancy not verified prior to study treatment administration but occurring during the 
course of the study will be not considered an AE, unless a relation to the study drug is 
suspected. In any case, a Pregnancy Report Form must be completed and sent as soon as 
possible to the Sponsor. A copy of the form should be filed at the study site for follow-up 
until the end of the pregnancy. Any pregnancy must be followed by an Investigator until 
delivery or to the end of pregnancy. Any anomalies, complications, abnormal outcomes, or 
birth defect observed in the child must be reported as an SAE within 24 hours of Investigator 
or study personnel's first knowledge.
Please use the email address or fax numbers (back up only) in section 8.3.9.1 for reporting 
pregnancy.
8.4
Type and Duration of the Follow-Up of Subjects after Adverse 
Events
In so far as is possible, all individuals will be followed up until the AE or suspected ADR has 
been resolved. If an AE/suspected ADR/SAE is present when the subject has completed the 
study, the course of the event must be followed until the final outcome is known, or the event 
has been stabilized and no further change is expected and an Investigator decides that no 
further follow-up is necessary.

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9
STATISTICS
9.1
Statistical Methods
Unless otherwise specified, descriptive statistics will include the number of non-missing 
observations (n), mean, standard deviation (SD), median, minimum and maximum values for 
the continuous/quantitative data or absolute and relative frequency counts and percentages 
for categorical/qualitative data.
Data handling and evaluation procedures will be described in the Statistical Analysis Plan
(SAP).
9.1.1
Demographic and Baseline Characteristics
Demographic and baseline characteristics will be listed and summarized. For quantitative 
variables, mean, SD, median, and minimum/maximum will be provided. For qualitative 
variables, the frequency and percentage will be provided.
9.1.2
Efficacy Analysis
The percentage of subjects maintaining anti-HAV antibody levels ≥10 mIU/mL up to Day 
60 following study treatment administration will be listed and summarized. The anti-HAV 
antibody levels during the PK sampling period (up to Day 150 following study treatment 
administration) will be listed and summarized. N, mean (SD), 90% CI for mean, 
% coefficient of variation (CV), median, minimum, maximum, geometric mean will be 
provided. The individual plasma and/or serum concentration/time profiles will be presented 
using the actual sampling times whereas the mean plasma and/or serum concentration/time 
profiles will be presented using the nominal sampling times.
The efficacy analyses will be performed on the evaluable and safety populations (if 
different).
9.1.3
Safety Analysis
Safety analyses will be performed on the safety population. Adverse events, clinical 
laboratory values, vital signs and physical examination findings will be analyzed. Data will 
be described using descriptive analyses.
9.1.3.1
Adverse Events
Safety analysis will be primarily focused on a descriptive analysis of suspected ADRs. Safety 
assessment will be based on the prevalence of suspected ADRs that occurred during the 
clinical trial.
Suspected ADRs are the AEs with causality assessment of possibly or definitely related. 
Adverse reactions are the AEs with causality assessment of definitely related.

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Adverse events will be coded and classified using MedDRA® terms (system organ class and 
preferred terms).
Adverse events will be classified as TEAEs or non-TEAEs depending on the comparison of 
AE onset date/time with the start date/time of study treatment with the IP. A TEAE will be 
defined as an AE which occurs between the beginning of the study drug injection and the 
final visit of the clinical trial. A non-TEAE will be defined as an AE which occurs prior to 
the start of study treatment. Non-TEAEs and TEAEs will be summarized separately.
All AEs will be summarized by presenting subject incidences and percentages, and they will 
also be listed by body systems with subject number.
In addition, TEAEs, including suspected ADRs, will be summarized by system organ class, 
preferred term, causal-relationship, intensity (severity) and seriousness (serious vs 
non-serious) using descriptive statistics. For the summary by severity or causality at each 
level of summarization (number of subjects, System Organ Class, or Preferred Term), a 
subject will only be counted once per system organ class or preferred term using the most 
severe AE or the AE with the strongest causal relationship to the IP.
Subjects with an SAE or who withdraw from the study because of an AE will also be 
individually listed and summarized.
AEs for which an Investigator causality assessment is missing or is not determined will be 
individually listed.
9.1.3.2
Clinical Laboratory Values
All clinical laboratory data collected in this study will be listed for each subject.
An Investigator will be required to classify out of the normal range laboratory results 
reported by the laboratory as clinically significant or not according to his/her criteria.
Out of the normal range laboratory results judged by an Investigator as clinically significant 
in the context of the subject's medical history will be considered AEs.
9.1.3.3
Vital Signs
Vital signs [HR, BP (systolic and diastolic), RR, and body temperature] will be listed for 
each clinical trial subject.
Clinically significant vital signs abnormalities will be considered AEs. Clinical relevance 
will be based on an Investigator's criteria. For each subject, every vital sign will be 
considered.
9.1.3.4
Physical Assessment
Physical examination findings (normal and abnormal) will be listed for each clinical trial 
subject. Any clinically significant abnormality developed by individual during the clinical 
trial and not already present at screening and/or baseline will be reported as AE.

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9.1.4
PK Analysis
Anti-HAV antibody plasma and/or serum concentrations produced by the administration of 
the study treatment will be determined in order to establish the PK profile of the IP. The PK
parameters that will be derived from the plasma and/or serum concentrations versus time 
profiles are listed in Table 9-1. All reported sampling time deviations will be taken into 
consideration for evaluation of PK parameters. It is recognized that there may be 
circumstances where PK sampling may fall outside of the time windows. The actual times for 
collection of PK samples will be captured in the source data and eCRF for analysis.
In the case where concentrations of anti-HAV antibodies cannot be determined due to 
bioanalytical or clinical reasons, these values will be set to missing for the statistical and PK
analyses.
The main PK parameters of interest for this study will be AUC0-∞, AUC0-T, Cmax, Tmax, λz, 
Thalf, ClTOT/F and VD/F.
Table 9-1 Pharmacokinetic Parameters
PK Parameter
Definition
Cmax
Maximum observed plasma and/or serum concentration
Tmax
Time of maximum observed plasma and/or serum concentration; if it occurs at 
more than one time point, Tmax is defined as the first time point with this value
TLQC
Time of last observed quantifiable plasma and/or serum concentration
AUC0-T
Cumulative area under the plasma and/or serum concentration time curve 
calculated from 0 to TLQC using the linear trapezoidal method, where TLQC
represents time of last observed quantifiable plasma and/or serum 
concentration
AUC0-∞
Area under the plasma and/or serum concentration time curve extrapolated to 
infinity, calculated as AUCT + CLQC/λZ, where CLQC is the measured 
concentration at time TLQC
TLIN
Time point where the log-linear elimination phase begins
λZ
Apparent elimination rate constant, estimated by linear regression of the 
terminal linear portion of the log concentration versus time curve
Thalf
Terminal elimination half-life, calculated as ln(2)/λZ
VD/F
Apparent Volume of Distribution, calculated as follows:








AUC
K
Dose
F
V
el
D
*
/
ClTOT/F
Apparent Total plasma and/or serum Clearance, calculated as follows:








AUC
Dose
F
ClTOT /

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PK parameters will be estimated using both anti-HAV antibody baseline uncorrected and 
baseline corrected levels. The main absorption and disposition parameters will be estimated 
using a non-compartmental approach with a log-linear terminal phase assumption. The 
trapezoidal rule will be used to estimate the area under the curve (linear trapezoidal linear 
interpolation) and the terminal phase will be estimated by maximizing the coefficient of 
determination estimated from the log-linear regression model. However, AUC0-∞, λZ, Thalf, 
ClTOT/F and VD/F parameters will be estimated for individual concentration-time profiles 
only when the terminal log-linear phase can be reliably characterized using the following 
criteria:

Phoenix® WinNonlin® Best fit range selection

R2 of at least 80%
PK parameters will be listed and summarized using descriptive statistics for the PK 
population. N, mean (SD), 90% CI for mean, % CV, median, minimum, maximum, 
geometric mean (except Tmax), and 90% CI for geometric mean (except Tmax) will be 
provided.
The individual plasma and/or serum concentration/time profiles will be presented using the 
actual sampling times whereas the mean plasma and/or serum concentration/time profiles 
will be presented using the nominal sampling times.
PK analyses will be generated using validated PK software.
9.2
Determination of Sample Size
Approximately 28 healthy subjects will be enrolled and treated in this study which will 
provide about 20 evaluable subjects based on approximately 30% dropout rate. The sample 
size is chosen based on clinical considerations but not on a formal sample size calculation.
9.3
Level of Significance to Be Used
Not applicable since only descriptive statistics will be provided and there will be no 
statistical hypothesis testing.
9.4
Criteria for Termination of the Study
The sponsor or its representative may terminate the study at any time for scientific or 
corporate reasons.
If the trial is prematurely terminated or suspended for any reason, the Principal Investigator 
should promptly inform the trial subjects, should assure appropriate therapy and follow-up 
for the subjects and should inform the regulatory authority (ies) when required.

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9.5
Procedure for Accounting for Missing, Unused, and Spurious Data
(if applicable)
Handling of missing, unused and spurious data will be described in the SAP. All available 
safety, efficacy and PK data will be included in data listings.
9.6
Reporting Deviation(s) from the Statistical Analysis Plan
The detailed statistical analysis methodologies will be documented in the SAP. If there are 
any deviations from the originally planned analyses in the SAP, they will be fully described 
and justified in the protocol amendment(s) and/or final Clinical Study Report.
9.7
Subject Population(s) for Analysis
9.7.1
Safety Population:
The safety population consists of all subjects who received any amount of study drug.
9.7.2
Evaluable Population:
The evaluable population consists of all subjects who received the entire dose of IP and had 
no major protocol deviations that would impact the efficacy analysis up to Day 60. Any 
deviations from the protocol will be recorded in the protocol deviation list and evaluated 
before database lock.
9.7.3
PK population:
The PK population consists of all subjects who received the entire dose of the IP and who
provided sufficient plasma and/or serum concentration data to facilitate calculation of PK 
parameters. Subjects who do not complete the PK sampling schedule may be included in the 
PK analysis only for the PK parameters that are judged not to be affected by the missing 
sample(s). This decision is to be documented and approved by the sponsor before the start of 
the sample analysis by the bioanalytical facility.
10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTS
The data will be recorded and kept current in eCRFs by the study site personnel directly 
responsible for the information and reviewed for completeness by the monitor. Grifols 
personnel or designee can review the records.
In accordance with ICH GCP guidelines, the monitor must have direct access to the 
Investigator’s source documentation in order to verify the data recorded in the eCRFs for 
consistency and to verify adherence to the protocol, and the completeness, consistency, and 
accuracy of data entered. "Source documentation" includes individual subject files, separate 
from the eCRFs, which should be maintained and include visit dates, laboratory results, 
concomitant treatment, vital signs, ECGs, medical history, examinations, AEs, IP dispensing 
logs, and other notes as appropriate. An Investigator agrees to cooperate with the monitor to 
ensure that any problems noted during the course of these monitoring visits are resolved.

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11 QUALITY CONTROL AND QUALITY ASSURANCE
Monitoring and auditing procedures defined/agreed by the sponsor will be followed, in order 
to comply with ICH GCP guidelines. Each center will be visited at regular intervals by a 
monitor to ensure compliance with the study protocol, ICH GCP and legal aspects. The 
on-site verification of the eCRF for completeness and clarity will include cross checking with 
source documents, and clarification of administrative matters. Query verification of data will 
be described in the Data Management Plan.
Representatives of regulatory authorities or of Grifols may conduct audits or inspections or 
audits of the Investigator study site. If an Investigator is notified of an audit or inspection by 
a regulatory authority, the Investigator agrees to notify the Grifols Representative 
immediately. An Investigator agrees to provide to representatives of a Regulatory Agency or 
Grifols access to records, facilities, and personnel for the effective conduct of an audit or 
inspection.
12 ETHICS
12.1
Institutional Review Board/Ethics Committee
Documented approval from appropriate IRBs/ECs will be obtained for all participating 
centers/countries prior to study start, according to ICH GCP guidelines, local laws, 
regulations and organizations. When necessary, an extension, amendment or renewal of the 
IRBs/ECs approval must be obtained and also forwarded to the sponsor. The IRBs/ECs must 
supply to the sponsor, upon request, a list of the IRBs/ECs members involved in the vote and 
a statement to confirm that the IRBs/ECs is organized and operates according to ICH GCP 
guidelines and applicable laws and regulations.
12.2
Ethical Conduct of the Study
The procedures set out in this protocol, pertaining to the conduct, evaluation, and 
documentation of this study, are designed to ensure that the sponsor and Investigator abide 
by ICH GCP guidelines. The study will also be carried out in keeping with applicable local 
law(s) and regulation(s). This may include an audit by the sponsor representatives and/or an 
inspection by Regulatory Authority representatives at any time. An Investigator must agree 
to the audit or inspection of study-related records by the sponsor representatives and/or 
Regulatory Authority representatives, and must allow direct access to source documents to 
the sponsor and/or Regulatory Authority representatives.
Modifications to the study protocol will not be implemented by either the sponsor or an
Investigator without agreement by both parties. However, an Investigator may implement a 
deviation from, or a change to, the protocol to eliminate an immediate hazard(s) to the study 
subjects without prior IRB/EC/Sponsor approval/favorable opinion. As soon as possible, the 
implemented deviation or change, the reasons for it and if appropriate the proposed protocol 
amendment should be submitted to the IRB/EC/Sponsor. Any deviations from the protocol 
must be fully explained and documented by an Investigator.

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No medical waivers for protocol inclusion/exclusion criteria will be allowed by the sponsor, 
and that in case the need for a change to the protocol is identified, it will be submitted as a 
protocol amendment to the competent regulatory authority and/or ethics committee as 
applicable per regulations.
12.3
Regulatory Authority Approvals/Authorizations
Regulatory Authority approvals/authorizations/notifications, where required, must be in place 
and fully documented prior to study start. Study information including contact information 
for Investigator sites responsible for conducting the study will be posted on a publicly 
accessible clinical registry(ies) as required by local law.
12.4
Subject Information and Consent
Subject information and ICF will be provided to Investigator sites. Prior to the beginning of 
the study, an Investigator must have the IRB/EC written approval/favorable opinion of the 
written ICF and any other written information to be provided to subjects. The written 
approval of the IRB/EC together with the approved subject information/ICF must be filed in 
the study files and a copy of the documents must also be provided to Sponsor by the 
Investigator site.
Written ICF must be obtained before any study specific procedure takes place. Participation 
in the study and date of ICF given by the subject should be documented appropriately in the 
subject's files. A signed copy of the subject ICF will be provided to the subject or subject's 
authorized representative.
12.5
Confidentiality
All 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.
Subject names will not be supplied to the sponsor. Only the subject code number and subject 
initials will be recorded in the eCRF, and if the subject's name appears on any other 
document (e.g., pathologist report), it must be retracted before a copy of the document is 
supplied to the sponsor. Study findings stored on a computer will be stored in accordance 
with local data protection laws. Subjects will be informed in writing that representatives of 
the sponsor, IRB/EC, or Regulatory Authorities may inspect their medical records and 
personal health information to verify the information collected, and that all personal 
information made available for an audit or inspection will be handled in strictest confidence 
and in accordance with local data protection laws.
If the results of the study are published, the subject's identity will remain confidential.
An Investigator will maintain a list to enable subjects' records to be identified.

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13 DATA HANDLING AND RECORD KEEPING
13.1
Data Handling
The study data will be recorded and kept current in the eCRF by the site study personnel 
directly responsible for the information. Entries made in the eCRF must be verifiable against 
source documents, or have been directly entered into the eCRF, in which case the entry in the 
eCRF will be considered the source data. The data in the eCRF will be monitored at the site 
by Grifols representatives at regular intervals and reviewed for completeness and compared 
with the source documents. Examples of acceptable source documents include individual 
subject medical records, prospective information gathered on source documentation 
worksheets, lab reports and other diagnostics pertinent to this study which are separate from 
the eCRFs. The listing of types of source documents which will be defined in the source data 
agreement will be filed in trial master file.
All adverse events and SAEs must be recorded. All SAEs must be recorded on the SAE form. 
The SAE form must be kept in site records with a copy provided to the designated person as 
detailed in the study file.
13.2
Record Retention
At study completion, all study data will be transferred to Grifols according to ICH GCP 
guidelines, local laws, regulations, and Grifols requirements. The study file and all source 
data should be retained until notification is given by the sponsor for destruction.
An Investigator is required by ICH GCP guidelines to retain the study files. If an Investigator
moves, withdraws from an investigation or retires, the responsibility for maintaining the 
records may be transferred to another person (e.g., other investigator). Grifols must be 
notified in writing of the person responsible for record retention and the notification will be 
retained in the sponsor study file and the Investigator site file.
14 FINANCING AND INSURANCE
In the event of subject injury as a direct result of either administration of IP or any 
non-standard of care study procedure, Sponsor will pay for the costs of treatment, provided 
the subject has followed the instructions given by a study Investigator and the illness or 
injury is not due to the natural progression of any conditions existing before the subject 
participated in the study. Financial compensation for such things as lost wages, disability, or 
discomfort due to any research-related injury is not available.
Sponsor shall maintain comprehensive general liability insurance or self-insurance in 
amounts adequate to cover any damage, demand, claim, loss or liability caused or incurred 
by Sponsor, or as otherwise required by applicable laws and/or regulations.

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15 PUBLICATION POLICY
Institution and the Investigator agree that the first publication shall be made in conjunction 
with the presentation of a joint publication of the study results. If such a publication is not 
submitted within twelve (12) months after conclusion of the study at the investigational site 
or after Grifols confirms there will be no joint publication, then institution and/or Investigator 
shall have the right, at their discretion, to publish, either in writing or orally, the results of the 
study performed under the protocol, subject to the conditions outlined below:
•
The results of the study will be reported in the publicly accessible registry(ies).
•
Institution and/or Investigator shall furnish Grifols with a copy of any proposed 
publication at least thirty (30) days in advance of the date of submission for publication.
•
Within said thirty (30) day period, Grifols shall:
-
Review such proposed publication for Confidential Information (other than Study 
results) and for subject information subject to the Health Insurance Portability and 
Accountability Act of 1996 ("HIPAA") and other applicable privacy laws;
-
Review such proposed publication for the unauthorized use of the name, symbols 
and/or trademarks of Grifols;
-
By written notice to the Investigator, identify with specificity the text or graphics in 
such proposed publication that Grifols contends contains Confidential Information, 
protected subject information, or the unauthorized use of Grifols' name, symbols 
and/or trademarks so that the proposed publication may be edited appropriately to 
remove such text or graphics before publication; and
-
By written request, Grifols may delay proposed publications up to sixty (60) days to 
allow Grifols to protect its interests in Grifols Inventions described in such 
publications.
•
Institution and/or Investigator shall give Grifols the option of receiving an 
acknowledgment for its sponsorship of the study in all such publications or presentation.
16 REFERENCES
1. Wasley A, Fiore A, Bell BP. Hepatitis A in the era of vaccination. Epidemiol Rev. 
2006;28:101-111.
2. Centers for Disease Control and Prevention. Prevention of hepatitis A through active or 
passive immunization: recommendations of the Advisory Committee on Immunization 
Practices. MMWR. 2006;55(RR-07):1-23.
3. Klevens RM, Kruszon-Moran D, Wasley AM, Gallagher K, McQuillan GM, Kuhnert 
WL, et al. Seroprevalence of hepatitis A antibodies in the United States: results from the 
National Health and Nutrition Examination Survey. Public Health Rep. 2011;126(4):522-
532.
4. Centers for Disease Control and Prevention. Vaccination coverage among children aged 
19-35 months – United States, 2015. MMWR. 2016 65(39):1065-1071.

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5. Klevens RM, Miller JT, Iqbal KI, Thomas A, Rizzo EM, Hanson H, et al. The evolving 
epidemiology of hepatitis A in the United States. Arch Intern Med 2010; 170(20):1811-
18.
6. Klevens RM, Liu SJ, Roberts H, Jiles RB, Holmberg SD. Estimating acute viral hepatitis 
infections from nationally reported cases. Am J Public Health. 2014;104(3):482-7.
7. Viral Hepatitis Surveillance, United States, 
2015.https://www.cdc.gov/hepatitis/statistics/2015surveillance/pdfs/2015HepSurveillanc
eRpt.pdf. Accessed on 27 July 2017.
8. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive 
immunization: recommendation of the Advisory Committee on Immunization Practices 
(ACIP). MMWR 1999; 48(RR12):1-37.
9. Product Information: GamaSTAN(R) S/D intramuscular injection solution, immune 
globulin (human) intramuscular injection solution. Grifols Therapeutics Inc., Research 
Triangle Park, NC. 2013
10. Cohn EJ, Strong LE, Hughes WL, Mulford DJ, Ashworth JN, Melin M, et al. Preparation 
and properties of serum and plasma proteins. IV. A system for the separation into 
fractions of the protein and lipoprotein components of biological tissues and fluids. J Am 
Chem Soc 1946 Mar;68(3):459-75.
11. Cohn EJ, Gurd FRN, Surgenor DM, Barnes BA, Brown RK, Derouaux G, et al. A system 
for the separation of the components of human blood: quantitative procedures for the 
separation of the protein components of human plasma. J Am Chem Soc. 1950 Jan;
72(1):465-74.
12. Barnette D, Roth NJ, Hotta J, Cai K, Gall M, Hartwell R, Kent JD, Willis T. Pathogen 
safety profile of a 10% IgG preparation manufactured using a depth filtration-modified 
process. Biologicals. 2012 Jul;40(4):247-253.
13. Lebing W, Remington KM, Schreiner C, Paul HI. Properties of a new intravenous 
immunoglobulin (IGIV-C, 10%) produced by virus inactivation with caprylate and 
column chromatography. Vox Sang. 2003 Apr;84(3):193-201.
14. Fudenberg HH. Sensitization to immunoglobulins and hazards of gamma globulin 
therapy. In: Merler E, editor. Immunoglobulins: biologic aspects and clinical uses. 
Washington DC: Nat Acad Sci; 1970. p. 211-220.
15. Kroger AT, Vázquez DJ. General recommendations on immunization. Best Practices 
Guidance of the Advisory Committee on Immunization Practices (ACIP). 
https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf
Accessed on 27 July 2017
16. Immune Globulin (Human) – GamaSTAN Investigator’s Brochure, Grifols Therapeutics 
Inc.

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17 APPENDICES

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Appendix 1
Schedule of Study Procedures and Events
Visits
Procedures and Evaluation
Screening 
Visit
Days -28 to -2
Day -1
Day 1a
Day 2
PK Sampling Visitsb
Days 3, 4, 5, 7, 10, 14, 21, 28, 60, 79, 115
Final Visit (Day 150)b/ 
Early Discontinuation Visit
Informed consent
X
Admission to clinical research 
unit
X
Inclusion/exclusion criteria
X
Continued eligibility 
verification
X
Medical history & 
demographics
X
Height and weight
X
ECG
X
X
Full physical exam c
X
X
Symptom-directed physical 
exam
X
X
X (Days 5, 28, and 60 visits only)
Vital signs d
X
X
X
X (Days 5, 28, and 60 visits only)
X
Clinical lab assessments e
X
X
X (Days 5, 28, and 60 visits only)
X
Coagulation tests (INR,
aPTT)
X
Immunoglobulin A (IgA)
X
Pregnancy test f
X
X
Urine alcohol and drug panel 
testing g
X
X
Virus safety testing h
X
Virus safety retain samples i
X
X
IP injection
X
Injection site evaluation
X
X

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Visits
Procedures and Evaluation
Screening 
Visit
Days -28 to -2
Day -1
Day 1a
Day 2
PK Sampling Visitsb
Days 3, 4, 5, 7, 10, 14, 21, 28, 60, 79, 115
Final Visit (Day 150)b/ 
Early Discontinuation Visit
PK sampling
(anti-HAV antibody level)
X
X
X
X
Concomitant medications
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
Discharge from clinical 
research unit
X
a
Collection of virus safety retain samples on Day 1 will be performed prior to study treatment administration. Vital signs will be measured prior to study drug 
injection, approximately 60 minutes (±10 minutes) and 12 hours (±10 minutes) after study treatment administration. Injection site evaluation will be 
performed approximately 60 minutes after study treatment administration. PK blood sampling on Day 1: prior to study drug injection, 60 minutes 
(±10 minutes) post study drug injection and 12 hours post study drug injection (a window of ±1 hour is permitted)
b
PK sampling visits will be conducted as close as possible to the exact time points. The PK sampling visits: Day 2 (window of ±1 hour); Days 3, 4 and 5 
(visits have a window of ±4 hours); Days 7, 10, and 14 (all 3 visits have a window of ±1 day); Days 21 and 28 (both visits have a window of ±2 days); Days 
60, 79 and 115 (all 3 visits have a window of ±4 days); Day 150 (a window of ±7 days)
c
Full physical examination (excluding breast and genitourinary examination)
d
Vital signs include systolic blood pressure, diastolic blood pressure, body temperature, heart rate, respiratory rate
e
Clinical laboratory assessments will include hematology, chemistry, and urinalysis. Hematology panel: hemoglobin, hematocrit, platelets, red blood cell 
count, and white blood cell count (absolute and % with differential). Chemistry panel: Sodium, potassium, creatinine, BUN, calcium, LDH, AST, ALT, 
GGT, ALP, glucose, total bilirubin, direct and indirect bilirubin. Urinalysis panel: Microscopic evaluation is done only with cause, pH, protein, glucose, and 
blood.
f
Dipstick urine pregnancy test at screening visit and on Day -1 administration.
g
Urine alcohol and drug panel testing (drug panel includes marijuana, opiates, cocaine, amphetamines, methamphetamines and benzodiazepines)
h
Virus safety testing: HAV RNA, HBV DNA, HCV RNA, HIV-1 RNA and B19V DNA by NAT methods as well as HAV antibody differential (IgM/IgG), 
hepatitis B core antibody differential (IgM/IgG), hepatitis C antibody, HIV-1/-2 + Group O antibody and B19V antibody differential (IgM/IgG) testing by 
serological methods.
i
Virus safety retain samples: serum and/or plasma samples for HAV RNA, HBV DNA, HCV RNA, HIV-1 RNA and B19V DNA testing by NAT methods as 
well as HAV antibody differential (IgM/IgG), hepatitis B core antibody differential (IgM/IgG), hepatitis C antibody, HIV-1/-2 + Group O antibody and 
B19V antibody differential (IgM/IgG) testing by serological methods will be collected on Day 1 prior to IP injection and at final visit (Day 150)/early 
discontinuation visit. These samples will be tested only if the subject exhibits clinical signs and symptoms consistent with HAV, HBV, HCV, HIV or B19V 
infection while participating in the study. Virus safety retain samples will be retained until all analyses in support of the study are complete.