A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Immunogenicity of AV-1959R in Healthy Participants
Phase: PHASE1
Conditions: Alzheimer Disease, Alzheimer Disease (AD), Alzheimers Disease Prevention
Sponsor: Nuravax, Inc.

Protocol No. AU-AV1959R-101 
 
 
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CLINICAL STUDY PROTOCOL 
 
A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Safety, Tolerability and Immunogenicity of AV-1959R in 
Healthy Participants 
 
PROTOCOL NO. AU-AV1959R-101 
 
Version No:  
4.0  
Protocol Date: 
25 June 2024 
Product: 
AV-1959R 
Phase: 
Phase I 
Sponsor: 
Arvax Pty Ltd 
Level 5 
63 Pirie Street 
Adelaide SA 5000 
 
 
This document contains confidential information proprietary to Arvax Pty Ltd. Except as otherwise 
agreed to in writing, by accepting and reviewing this document, you agree to hold this formation in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes. In the event of any actual or suspected breach of this obligation, Arvax Pty Ltd 
must be promptly notified. 
 

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Sponsor Signature Page 
PROTOCOL NUMBER: 
AU-AV1959R-101 
PROTOCOL VERSION: 
4.0 
PROTOCOL DATE:  
25 June 2024 
PROTOCOL TITLE:   
A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Safety, Tolerability and Immunogenicity of AV-1959R in 
Healthy Participants 
 
I, on behalf of Arvax Pty Ltd, approve this protocol and agree to comply with all requirements regarding the 
obligations of Sponsor and all other pertinent requirements of Good Clinical Practice (ICH E6, R2), the 
Declaration of Helsinki, and applicable regulatory requirements. 
 
 
_______________________________ 
 
 
_________________________ 
Sponsor’s authorized signatory 
 
 
 
Date 
Name and Title 
 
 

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Investigator Signature Page 
PROTOCOL NUMBER: 
AU-AV1959R-101 
PROTOCOL VERSION: 
4.0 
PROTOCOL DATE:  
25 June 2024 
PROTOCOL TITLE:   
A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Safety, Tolerability and Immunogenicity of AV-1959R in 
Healthy Participants. 
 
By my signature below, I certify that I have read and understand the foregoing protocol and I agree to 
personally conduct or supervise the described investigation. I agree to conduct the study in accordance with 
the current protocol and in compliance with the Guidance on Good Clinical Practice (ICH, E6, R2), the 
Declaration of Helsinki, and applicable regulatory requirements. 
I agree to the content of this protocol and the confidential nature of the documentation made a part of this 
study. I also acknowledge that Arvax Pty Ltd has the right to discontinue this study at any time. 
 
 
 
Signature of Investigator 
 
 
 
Date 
Printed Name 
 
 

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Table of Contents 
Sponsor Signature Page ................................................................................................................. 2 
Investigator Signature Page ........................................................................................................... 3 
Table of Contents ........................................................................................................................... 4 
Protocol Synopsis........................................................................................................................... 8 
List of Abbreviations ................................................................................................................... 16 
1. 
Introduction .......................................................................................................................... 19 
1.1 
Background............................................................................................................... 19 
1.2 
Investigational Product: adjuvanted recombinant protein vaccine, AV-1959R ....... 19 
1.3 
Study Rationale ........................................................................................................ 21 
1.4 
Target population and participants selection strategy .............................................. 22 
1.5 
Mechanism of Action ............................................................................................... 22 
1.6 
Proposed doses and immunization schedule ............................................................ 24 
2. 
Study Objectives .................................................................................................................. 25 
2.1 
Primary Objective ..................................................................................................... 25 
2.2 
Secondary Objectives ............................................................................................... 25 
3. 
Investigational Plan .............................................................................................................. 26 
3.1 
Study Design ............................................................................................................ 26 
4. 
Study Population .................................................................................................................. 29 
4.1 
Number of Subjects .................................................................................................. 29 
4.2 
Selection of Study Population .................................................................................. 29 
4.2.1 
Inclusion Criteria .................................................................................. 29 
4.2.2 
Exclusion Criteria ................................................................................. 30 
4.3 
Subject Disposition and Discontinuation ................................................................. 32 
4.3.1 
Duration of Study Participation ............................................................ 32 
4.3.2 
Subjects Withdrawal and Discontinuation ............................................ 32 
4.3.3 
Handling of Withdrawals ...................................................................... 34 
4.3.4 
Replacement of Subjects ....................................................................... 34 
4.3.5 
Screen Failures ...................................................................................... 34 
4.4 
Safety Review / Dose Escalation Committee ........................................................... 34 
4.5 
Dose Escalation Rules .............................................................................................. 35 
4.6 
Stopping Rules.......................................................................................................... 35 
5. 
Study Treatments ................................................................................................................. 37 
5.1 
Investigational Product ............................................................................................. 37 
5.1.1 
Identity of Study Drugs Used in the Study ........................................... 37 
5.1.2 
Formulation, Packaging, and Labeling ................................................. 37 
5.1.3 
Storage and Handling of Investigational Product ................................. 37 
5.1.4 
Investigational Product Accountability ................................................ 38 

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5.1.5 
Disposal and Destruction ...................................................................... 38 
5.1.6 
Method of Assigning Subjects to Treatment Groups ........................... 39 
5.2 
Treatment Administered ........................................................................................... 39 
5.3 
Treatment Compliance ............................................................................................. 40 
5.4 
Subject Numbering ................................................................................................... 40 
5.5 
Blinding 40 
5.5.1 
Breaking the Blind ................................................................................ 40 
6. 
Study Procedures and Evaluations ....................................................................................... 42 
6.1 
Study Visits .............................................................................................................. 42 
6.1.1 
Screening Period (Days -28 to -1) ........................................................ 42 
6.1.2 
Day -1  Visit .......................................................................................... 43 
6.1.3 
Day 1 - Immunization #1 ...................................................................... 43 
6.1.4 
Day 15 (±2) ........................................................................................... 44 
6.1.5 
Day 28 (±2) – Immunization #2 ........................................................... 44 
6.1.6 
Day 42 (±3) ........................................................................................... 45 
6.1.7 
Day 98 (±5) – Immunization #3 ........................................................... 45 
6.1.8 
Day 112 (±5) ......................................................................................... 46 
6.1.9 
Day 140 (±5) ......................................................................................... 46 
6.1.10 
Day 154 (±7) – End of Study / Early Termination (EOS/ET) .............. 46 
6.1.11 
Unscheduled Visits ............................................................................... 47 
6.1.12 
Phone Follow-Up Days 2, 29 (±2) and 99 (±5) .................................... 47 
6.2 
Study Procedures ...................................................................................................... 48 
6.2.1 
Demographics, Medical/Surgical and Prior/Concomitant Medication History
 .............................................................................................................. 48 
6.2.2 
Body Height and Weight ...................................................................... 48 
6.2.3 
Physical Examinations .......................................................................... 48 
6.2.4 
Vital Sign Measurements ...................................................................... 48 
6.2.5 
12-Lead Electrocardiograms ................................................................. 49 
6.2.6 
Clinical Laboratory Tests...................................................................... 49 
6.2.7 
MRI Examination ................................................................................. 51 
6.2.8 
Local Tolerability Assessment.............................................................. 51 
6.2.9 
Documentation of Concomitant Medications ....................................... 51 
6.2.10 
Prohibited Medications ......................................................................... 51 
6.2.11 
Restricted Treatments and Medications ................................................ 52 
7. 
Assessment and Management of Adverse Events ............................................................... 54 
7.1 
Adverse Events ......................................................................................................... 54 
7.2 
Serious Adverse Events ............................................................................................ 58 
7.3 
Additional Points to Consider for Adverse Events ................................................... 58 
7.4 
Local Tolerability Assessment ................................................................................. 59 

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7.5 
Reporting of Serious Adverse Events....................................................................... 60 
7.6 
Follow-up of Serious Adverse Events ...................................................................... 60 
7.7 
Subject Deaths .......................................................................................................... 61 
8. 
Data Analysis and Statistical Methods................................................................................. 63 
8.1 
Study outcome measures .......................................................................................... 63 
8.2 
Adverse Events ......................................................................................................... 63 
8.3 
Clinical Laboratory Tests ......................................................................................... 64 
8.4 
Vital Sign Measurements ......................................................................................... 64 
8.5 
Safety 12-Lead Electrocardiograms ......................................................................... 64 
8.6 
Other Safety Data ..................................................................................................... 64 
8.7 
Sample Size .............................................................................................................. 64 
9. 
Study Compliance ................................................................................................................ 65 
9.1 
Modification to Protocol........................................................................................... 65 
9.2 
Protocol Deviations .................................................................................................. 65 
10. Data Handling, Management and Records Keeping ............................................................ 66 
10.1 
Data Management ..................................................................................................... 66 
10.2 
Case Report Forms ................................................................................................... 66 
10.2.1 
Query Process ....................................................................................... 67 
10.2.2 
Source Documents ................................................................................ 67 
10.2.3 
User ID .................................................................................................. 67 
10.2.4 
Audit trail .............................................................................................. 68 
10.2.5 
Management of Investigator Site File ................................................... 68 
10.2.6 
Records Retention at the Study Site ..................................................... 68 
11. Quality Control and Quality Assurance ............................................................................... 69 
11.1 
Good Clinical Practice .............................................................................................. 69 
11.2 
Study Monitoring...................................................................................................... 69 
11.3 
Inspection of Records ............................................................................................... 69 
11.4 
Quality Control ......................................................................................................... 70 
11.5 
Quality Assurance .................................................................................................... 70 
12. Human Research Ethics Committee Review ....................................................................... 71 
12.1 
Regulatory Approvals/Notifications ......................................................................... 71 
12.2 
Informed Consent ..................................................................................................... 72 
12.3 
Confidentiality of Subject Records .......................................................................... 72 
12.4 
Delegation of Investigator Duties ............................................................................. 73 
12.5 
Study Termination .................................................................................................... 73 
12.6 
Financing, Insurance and Indemnification ............................................................... 73 
13. Ownership of Data and Publication Policy .......................................................................... 74 
14. Appendices ........................................................................................................................... 75 

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14.1 
Appendix A: List of Immunomodulatory or Growth Stimulating Factors ............... 75 
15. Revision History .................................................................................................................. 77 
16. References ............................................................................................................................ 79 

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Protocol Synopsis 
Protocol Number: 
AU-AV1959R-101 
Title: 
A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, 
Tolerability and Immunogenicity of AV-1959R in Healthy Participants.  
Study Phase: 
1 
Rationale: 
Alzheimer’s disease (AD) is a neurodegenerative condition, clinically characterized by 
progressive impairment of memory and cognitive functions. The amyloid cascade 
hypothesis proposes that Aβ oligomer formation is a critical feature for the initiation of 
downstream pathological processes that include tau pathology, which is directly associated 
with neurodegeneration (inflammation, oxidative stress, and synaptic, neuronal loss) and 
cognitive decline. Immunotherapy is one of the most promising therapeutic strategies for 
AD prevention. 
AV-1959R is a cGMP-grade recombinant protein composed of three copies of the N-
terminal region of human Aβ spanning amino acids 1-11 (Aβ1-11) and an immunogenic 
vaccine platform composed of 12 foreign promiscuous T helper (Th) cell epitopes [one 
synthetic epitope and 11 epitopes from several microorganisms (tetanus; hepatitis B and 
influenza)] collectively designated as the MultiTEP vaccine platform.  
Advax-CpG55.2 is an adjuvant based on a combination of delta inulin and CpG55.2, that 
has been tested in combination with different vaccines in 10 human clinical trials, 
conducted in USA, Australia and Iran, involving >26,000 administrations to >13,000 
individual subjects across the Phase 1, 2, 3 and booster study trials.  
Adjuvanted AV-1959R was extensively studied in multiple pre-clinical safety and efficacy 
studies in mice, rabbits, non-human primates (NHP). Delivered intramuscularly (IM) this 
vaccine generates robust cellular immune responses to foreign epitopes avoiding 
activation of potentially harmful autoreactive T cells and induces high titers of 
therapeutically potent anti-Aβ antibodies in mice, rabbits and NHP (1, 2). In safety 
toxicology studies, there were no adverse findings in health observations, food intake, 
body weights, gross necropsy, absolute organ weights or weigh ratios, clinical pathology 
or the histopathology data attributed to IM administration of a mouse model of AD. In 
initial Phase I trial, Sponsor will seek to determine the safety and immunogenicity of the 
adjuvanted vaccine in healthy participants.  
The proposed Phase I study is a single-center, double-blind, randomized, placebo-
controlled trial to determine the safety and tolerability of AV-1959R at 100 µg and 300 
µg doses or placebo (formulation without active ingredient) both formulated with Advax-
CpG55.2 via IM administration in healthy participants. Each participant will be 
immunized at Weeks 0, 4 and 14 and undergo follow-up period of 8-weeks post last 
immunization. 
Objectives: 
Primary objective:  
• 
To determine the safety and tolerability of adjuvanted AV-1959R vaccine 
compared to placebo in healthy participants. 
Secondary objective:  
• 
To evaluate the immunogenicity of the adjuvanted AV- 1959R vaccine by 
assessing the level of humoral immune responses (anti-Aβ antibody levels: IgM 
and IgG isotypes and IgG1, IgG2, IgG3, and IgG4 subclasses) in plasma. 
Subject Population: 
This study will enroll up to 16 healthy volunteers. 

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Study Duration: 
Approximately up to 26 weeks (4 weeks [Screening period] + 14 weeks [Treatment 
period] + 8 weeks [Follow-up, i.e., 56±7 days after the last dose of IP])  
Study Design: 
This is a Phase 1, randomized, double-blind, placebo-controlled, multiple dose-escalating 
trial consisting of 2 ascending dose cohorts in healthy male and female participants, 40-
60 years of age.  
Subjects will undergo Screening visits within 4 weeks (up to 28 days) prior to the 
administration of the investigational product (IP) as per Table 1 to identify eligible 
participants. Screening procedures may be performed in two or more screening visits. MRI 
examination for determination of subject eligibility will be performed at the later stage of 
screening.  
A total of sixteen (16) subjects will be enrolled into the study in one of two dose cohorts. 
Eligible participants will be randomly assigned in a 3:1 ratio to receive 3 intramuscular 
injections of either AV-1959R or placebo both formulated with Advax-CpG55.2 adjuvant 
at baseline (Week 0), Weeks 4 and 14 and undergo follow-up visit at Week 22 (Table 1). 
Each cohort will contain up to 8 subjects; six (6) will be randomly assigned to receive AV-
1959R and two (2) participants to receive a placebo. The following doses will be 
administered at each immunization time point: 
• 
Cohort 1: 100 µg of AV-1959R or placebo  
• 
Cohort 2: 300 µg of AV-1959R or placebo  
 
A Safety Review Committee (SRC) will be established to review the study progress, 
provide oversight for the determination of the safety of dose escalation, and determine if 
it is appropriate to continue the study or modify the protocol. Should the SRC choose not 
to escalate to the next dose level, previous dose level may be repeated if deemed necessary. 
Dose-limiting toxicity (DLT) will be monitored during the entire study. DLT is defined as 
a serious or severe clinically significant AE (CTCAE Grade 3 or higher) not resolving 
within 14 days after each immunization in the dosing cohort that may be considered by 
the Investigator to be related to the study drug. 
For each dose level, dosing will be staggered such that 2 subjects will be dosed prior to 
the rest of the group. Initially, 2 subjects (one active and one placebo) in each Cohort will 
be dosed (Immunization #1, Day 0) prior to the rest of the cohort. General tolerability to 
treatment will be monitored over 14 days following each immunization of AV-1959R or 
placebo by the Investigator. If the safety assessments (AEs, clinical laboratory test results, 
vital sign measurements, 12 lead ECG results, and physical examination) are acceptable 
based on the judgement of the Investigator on Day 15±2 and Day 42±3, individual 
participants will receive Immunization # 2 (Day 28±2) and Immunization # 3 (Day 98±5), 
respectively as planned.  
Investigator will also determine whether the remaining 6 subjects (five active and one 
placebo) in the Cohort will be dosed after review of a minimum of 14 days safety 
assessments (AEs, clinical laboratory test results, vital sign measurements, ECG results, 
and physical examination) following first immunization of AV-1959R or placebo in 
sentinel group. 
Dose escalation decision will be made by SRC based upon review of adverse events (AEs) 
and all safety data from 14 days after the first immunization of all 8 participants in first 
cohort before escalation to the second dose cohort.  

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Dose escalation will be determined by the number of subjects experiencing DLT not 
resolving within 14 days after first immunization: 
• 
If ≤1 participant experienced a DLT two weeks after the first immunization, then 
initiation of the second dose (300µg) cohort may proceed.                       
• 
If ≥ 2 participants experience DLT in two weeks after the first immunization, then 
no further dose increase will occur.  
 
Dose escalation will be suspended or stopped if any of the following occurs: 
• 
Death from any cause other than events clearly unrelated to the study drug;  
• 
Any CTCAE Grade 3 or higher adverse event that certainly, probably/likely or 
possibly related to the study drug and persists for more than two weeks; 
• 
Any serious or severe clinically significant AE (CTCAE Grade 3 or higher) that 
certainly, probably/likely or possibly related to the study drug and occurs within 
4 weeks after product administration; 
• 
Any other event(s) that in the opinion of the Investigator should invoke suspension 
of further enrollment. 
 
Based on information of occurred DLT events, the SRC may at any time decide to 
terminate the study and the sponsor will submit appropriate reports to HREC and TGA. 
A local screening MRI will be performed at screening and then at Week 22 as safety 
measure. The MRI scans will be reviewed by the Investigator or qualified designee for 
immediate participant management. 
Inclusion Criteria: 
A subject must meet all of the following inclusion criteria to participate in this study: 
1. Healthy, adult, male or female of non-childbearing potential, 40 to 60 years of age, 
inclusive, at Screening visit. 
2. Body mass index (BMI) ≥18.0 and ≤32.0 kg/m2 at Screening visit 
3. Medically healthy with no clinically significant medical history, abnormalities in 
physical examination, laboratory variables, vital signs, ECG or MRI at the time of 
Screening and Baseline (if applicable), as deemed by the Investigator or designee. 
4. Signed informed consent form by the participant prior to initiation of any study-related 
procedures. 
5. If female of non-childbearing potential, must meet at least one of the following 
criteria: 
a. post-menopausal status defined as amenorrhea for at least 12 months prior to 
study drug dosing in absence of any exogenous hormonal treatments and 
follicle stimulating hormone (FSH) levels in the laboratory defined post-
menopausal range. 
b. subject report of surgical sterilization (i.e., hysterectomy, bilateral tubal 
ligation, bilateral oophorectomy/ salpingectomy) at least 6 weeks prior to 
Day 1. Documented evidence of surgical sterilization is required.   
6. If male, must have had a vasectomy 90 days prior to the Screening visit with a follow 
up negative sperm count, or agree to not donate sperm for 90 days after the last dose 
of study drug and, if engaging in vaginal sexual intercourse with a female partner of 
childbearing potential, agree to use a condom in addition to the female partner must 
use a highly effective method of birth control (e.g. intrauterine device, diaphragm, 
hormonal contraceptives) throughout the duration of the study treatment period and 
for 90 days after the last dose of study drug. Abstinence from heterosexual intercourse 
is an acceptable method of contraception. Subjects with same-sex partners (abstinence 

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from penile-vaginal intercourse) are eligible without needing contraception when this 
is their usual form of sexual relations. 
7. Ability, in the opinion of the investigator, to understand the nature of the trial and 
comply with protocol requirements, including the prescribed dosage regimens, 
scheduled visits, laboratory tests, and other trial procedures. 
Exclusion Criteria: 
A subject will be excluded from participation in this study if he or she meets any of the 
following criteria: 
1. Any clinically significant medical history or observations at the time of Screening visit 
not specifically excluded in other criteria that, in the opinion of the Investigator or 
designee, may confound the results of the study, compromise the safety of the subject 
or otherwise render the subject unsuitable for participation. 
2. Magnetic resonance imaging (MRI) showing evidence of any of the following at the 
Screening:  
o 1 or more small non-cortical lacunar infarct greater than 1.0 cm 
o Any territorial infarct including acute or chronic  
o Subjects who have microbleeds and areas of leptomeningeal hemosiderosis  
o Subjects who have a presence of any other significant cerebral abnormalities, 
including ARIA-E, as assessed in the screening MRI scan. 
3. Contraindications for MRI scanning, including implanted metallic devices (e.g., non-
MRI-safe cardiac pacemaker or neurostimulator; some artificial joints metal pins; 
surgical clips; or other implanted metal parts), or claustrophobia or discomfort in 
confined spaces. 
4. Any serious illness requiring systemic treatment and/or hospitalization within 4 weeks 
prior to study entry. 
5. History/evidence of clinically relevant pathology related to the cardiovascular system, 
respiratory tract, gastrointestinal tract, endocrinology, immunology, hematology, or 
any other systemic disorder/major surgeries that, in the opinion of the Investigator, 
would confound participation and follow-up. 
6. History or presence of any of the following: 
o clinically significant acute illness or surgery within the previous 3 months of 
Day 1. 
o hypersensitivity reaction or anaphylaxis to any medication to be of clinical 
significance to the current study or compromise the safety of the subject in 
the opinion of the Investigator 
o history or suspicion of routine or chronic drug or alcohol abuse or 
dependence within 1 year prior to Day 1 based on subject report; excessive 
alcohol intake (defined as routine weekly intake of greater than 21 
glasses/units per week, with one unit=150 mL of wine or 360 mL of beer or 
45 mL of 45% alcohol. 
7. Clinically significant laboratory abnormalities at Screening visit, including (but not 
limited to): 
o hemoglobin, hematocrit, total white blood count (WBC) or platelet count 
below the lower limit of the normal range  
o alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >1.5 
times the upper limit of the normal range  
o serum creatinine above the upper limit of the normal range or estimated 
creatinine clearance <90 mL/minute as calculated by the Cockcroft-Gault 
equation 

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o positive testing for human immunodeficiency virus (HIV-1 or -2), hepatitis 
B surface antigen (HBsAg), or positive testing for hepatitis C (HCV)  
Clinical laboratory tests may be repeated as per Investigator’s discretion. 
8. Systolic blood pressure (BP) >160 millimeters of mercury (mmHg), or <90 mmHg; 
diastolic BP >95 mmHg or <50 mmHg blood at Screening visit or Day 1. Vital signs 
may be repeated as per Investigator’s judgement. 
9. Supine heart rate less than 45 beats per minute (bpm) or higher than 100 bpm at the 
Screening visit or Day 1. Vital signs may be repeated as per Investigator’s judgement. 
10. ECG with QTcF interval duration equal or greater than 450 msec for males and 470 
msec for females obtained after at least 5 minutes in a supine or semi-recumbent 
position at quiet rest at Screening visit or Day 1. 
11. Any other medical, psychological, or social condition that, in the opinion of the 
Investigator, would prevent the participant from fully participating in the study would 
represent a concern for study compliance or would constitute a safety concern to the 
participant. 
12. Participation in another investigational drug study or treatment with an investigational 
drug within 30 days or 5 half-lives, whichever is longer, before dosing. 
13. Prior administration of any tau or amyloid-beta immunotherapy (vaccine, antibody) 
within 1 year prior to Screening. 
14. The use of immunomodulatory or growth-stimulating factors such as systemic 
corticosteroids, cyclosporine, methotrexate, azathioprine, anti-CD25 antibody, GM-
CSF, C-CSF, interferon (IFN), or interleukin-2 (IL-2) within 30 days prior to study 
entry.  
15. Chronic use (>3 months) of warfarin, other coumarin derivatives, anticoagulants, or 
an anti-platelet agent (e.g., clopidogrel). 
16. Parenteral use of immunoglobulin preparations, blood products, and plasma 
derivatives. 
17. History/evidence of severe local or systemic reactions to vaccination or significant 
allergic reactions. 
18. Female of childbearing potential. 
19. Any skin condition and/or tattoo that may interfere with the evaluation of safety at 
the injection site. 
20. Donation of blood or significant blood loss greater than 400 ml within the last 30 
days prior to dosing. 
Investigational 
Product, Reference 
Therapy, Dose, 
Mode of 
Administration, and 
Dose Regimen: 
Active: AV-1959R, 100 µg, 300 µg plus adjuvant per immunization 
Placebo: Normal saline solution  (without active compound) plus adjuvant 
Adjuvant: Advax-CpG55.2 [Advax-15mg, and CpG-0.15mg] combination adjuvant 
comprising delta inulin and CpG55.2 (Vaxine Pty. Ltd)  
Dosing regimen: Three immunizations will be administrated at Weeks 0, 4 and 14. 
Mode of administration: Intramuscular (IM) injection. 
Study Outcomes 
Measures: 
Primary Outcome 
● The number of participants with Treatment-Emergent Adverse Events 
(TEAEs) or Serious Adverse Events (SAEs). 
 
Secondary Outcomes 
● Number of participants with clinically significant changes in vital signs. 
● Number of participants with clinically significant changes in ECG results. 
● Number of participants with clinically significant changes in laboratory 
tests. 

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● Number of participants with clinically significant changes in physical 
examinations. 
● Immunological Outcomes: 
o Serum anti- Aβ and anti-MultiTEP antibodies concentrations, i.e., IgM, 
total IgG and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) 
Statistical 
Considerations: 
Up to 16 subjects will be enrolled in this study. The sample size was chosen pragmatically 
based on clinical considerations and considered sufficient for the safety objectives of this 
study, in which subjects will receive the investigational product in sequential ascending 
doses.  
Descriptive statistical analyses, including graphs, will be based on the different dosing 
cohorts. Each participant will be coded as valid or not valid for safety and immunogenicity 
evaluation before unblinding the results. Categorical variables will be summarized in 
frequency tables (n, %), by treatment group and dose. Continuous variables will be 
summarized using descriptive statistics. Demographic and baseline characteristics will be 
summarized overall for all participants. The number who enrolled in the study, who 
discontinued, and reasons for discontinuation will be presented. Data will also be presented 
in individual listings. 
Safety Analysis: 
Safety will be evaluated in terms of reported AEs and other clinical observations, clinical 
laboratory test results (hematology, serum chemistry, coagulation, and urinalysis), vital sign 
measurements (blood pressure, heart rate, respiratory rate, and body temperature), 12-lead 
safety ECG results, neurological and physical examination findings, MRI results.  
Treatment-emergent AEs will be coded using the latest version of MedDRA by System 
Organ Class (SOC) and Preferred Term (PT), classified from verbatim terms. The duration 
of TEAEs will be determined and included in listings, along with the action taken and 
outcome. ECG, vital signs and safety laboratory parameters will be summarized at each 
scheduled time point using descriptive statistics. Post-dose assessments will be compared 
with baseline measurements. The incidence of laboratory abnormalities will be 
summarized. Physical examination findings will be presented in listings. 
Immunological 
Analysis: 
The immunogenicity variables (antibody titers) will be summarized in listings and tables 
as absolute values and changes from baseline and graphically presented by time profiles. 
For each treatment group, geometric mean titers (GMTs) of the serum anti- Aβ antibodies 
along with their associated 95% confidence intervals (CIs) will be calculated. In addition, 
median, minimum, and maximum values will be calculated for each vaccine group at each 
time point.  
 
 
 
 

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Table 1.  Schedule of Assessments 
Study Period ►  Screening 
Period a 
Check-
In 
Treatment Period  
Follow-up Period 
Assessment▼ Study 
Day► 
Days -28 
to -2 
D -1 
D1 
D2 
D15 
±2 
D28 
±2 
D29  
±2 
D42 
±3 
D98 
±5 
D99  
±5 
D112 
±5 
D140
±5 
D154 ±7 or 56 
±7 days after 
the last dose   
 
Baseline 
Phone    
Call b
 
 
Phone  
Call b 
 
EOT 
Phone    
Call b 
 
 
EOS / ET 
    Study 
Week► 
Weeks -4 
to 0    
0 
0 
2 
4 
6 
14 
16 
20 
22 
Informed Consent 
x  
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
x 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility  
x 
x c 
x c, p 
 
 
 
 
 
 
 
 
 
 
Medical History, and 
update d 
x 
 
x p 
 
 
 
 
 
 
 
 
 
 
Height/Weight/BMI e 
x 
 
 
 
 
 
 
 
 
 
 
 
x 
Physical Examination f 
x 
 
 
 
x 
x 
 
x 
x 
 
 
 
x 
12-Lead ECG g 
x 
 
x 
 
x 
x 
 
x 
x 
 
x 
x 
x 
Vital Signs i 
x 
 
x 
 
x 
x 
 
x 
x 
 
x 
x 
x 
Viral Serology 
x 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test (females) 
x 
x 
 
 
 
x p 
 
 
x p 
 
 
 
x 
Specimen collection 
(Chemistry, 
Hematology, 
Coagulation and 
Urinalysis)  
x 
x 
 
 
x 
x p 
 
x 
x p 
 
x 
 
x 
Alcohol and drug testing 
x 
 
x p 
 
 
x p 
 
 
x p 
 
 
 
 
MRI Examination j 
x 
 
 
 
 
 
 
 
 
 
 
 
x 
Randomization 
 
 
x p 
 
 
 
 
 
 
 
 
 
 
IP Administration - 
immunization number k 
 
 
x(1) 
 
 
x(2) 
 
 
x(3) 
 
 
 
 
Local Tolerability l 
 
 
x 
 
 
x 
 
 
x 
 
 
 
 
Blood collection for 
anti- Aβ and anti-
MultiTEP antibodies m 
 
 
x p 
 
 
 
 
x 
x p 
 
x 
x 
x 
Prior and Concomitant 
Treatments n 
 
Adverse Events o 
 
 
Abbreviations: Aβ=amyloid-beta protein; BMI=body mass index; D=day; ECG=electrocardiogram; EOT=end of treatment; 
EOS=end of study; ET=early termination; MRI=magnetic resonance imaging. 
a Screening period will occur within 28 days prior to participant randomization on Day 1. Screening procedures may be 
performed in two or more screening visits. Extension of screening period beyond the 28 days window to allow completion 
of screening procedures may be permitted after discussion between the Investigator and the Medical Monitor on a case-by-
case basis. 
b Subjects will be contacted via phone call, internet/web, or other acceptable means of communication and will be 
questioned for assessment of adverse events the next day after each IP dosing in the trial. 
c Inclusion/exclusion criteria will be reassessed on Day -1 and Day 1 (pre-dose) to ensure ongoing participant 
eligibility.  

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d Medical occurrences that begin before the start of IP dosing but after obtaining informed consent will be recorded as 
medical history.  
e Height measurement and BMI calculation are required only at Screening. Body weight will be obtained with the participant's 
shoes off, jacket or coat removed. 
f Complete physical and neurological examinations should be completed at Screening, Days 42 and 154 (or EOS/ET). A 
symptom-directed examination) should be completed at Days 15, 28 and 98. Additional physical and/or neurological 
examinations may be done at any time point during the trial at the investigator’s discretion. 
g 12-Lead ECG assessments will be performed after the participant has been supine and at rest for approximately 5 
minutes. 12-lead ECGs on Immunization Days will be obtained within 30 minutes before and 4 hours post-immunization. 
Additional ECGs can be performed at the investigator’s discretion (eg, if abnormalities are noted). 
i Vital signs will be measured after the participant has been supine and at rest for approximately 5 minutes.  Vital signs 
on Immunization Days will be measured within 15 minutes before and at 15 min, 1 hour, 2 hours and 4 hours post-
immunization. Additional vitals can be performed at the investigator’s discretion (eg, if abnormalities are noted). 
j MRI examination will be performed for the detection of vasogenic edema, superficial siderosis, microhemorrhages, and 
macrohemorrhages, lacunar and cortical infarcts and other imaging abnormalities. MRI examination at Screening should 
be performed at the latest stage of the screening.  
k Subject will be randomized to the treatment on Day 1 upon eligibility confirmation prior to 1st immunization. 
l Assessments of injection site reactions on Immunization Days will be performed at 30 min, 1 hour, 2 hours and 4 hours 
post-dose (±15 minutes), and more frequently, if deemed necessary by the investigator. Assessments of injection site on 
other days will be performed in subjects who have unresolved injection site AEs.  
m Blood will be collected for immunological assessment (detection of antibodies specific to Aβ) and stored at the clinical 
site.  
n Concomitant medications should be recorded from Screening through the participant’s last visit/contact. 
o Adverse events (serious and nonserious) will be recorded from the informed consent through the participant’s last 
visit/contact. 
p Procedure will be performed prior to immunization. 
 

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List of Abbreviations 
Abbreviation 
Definition 
3xTg-AD 
Triple transgenic mice, expressing human APP, PSEN1, MAPT 
Aβ 
Amyloid-beta, peptide derived from APP 
Aβ11 
Peptide spanning 1-11 amino acids of APP 
Aβ42 
Amyloid-beta 1-42 peptide derived from APP (spanning 671-713 amino 
acids) cleaved with β and γ secretases 
AD 
Alzheimer’s disease 
ADL 
Activities of daily living 
AE 
Adverse event 
APC 
Antigen presenting cells 
APP 
Amyloid Precursor Protein 
APP/Tg 
Transgenic mice, expressing human APP 
ARIA 
Amyloid-related imaging abnormalities 
APS 
Amyloid probability score 
BMI 
Body mass index 
CAA 
Cerebral amyloid angiopathy 
CDR 
Clinical dementia rating 
CFR 
Code of Federal Regulations 
cGMP 
Current good manufacturing practice 
CNS 
Central nervous system 
CRA 
Clinical research associate 
CSF 
Cerebrospinal fluid 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CTCAE 
CTN 
Common Terminology Criteria for Adverse Events 
Clinical Trial Notification 
CV 
Coefficient of variation 
DNA 
Deoxyribonucleic acid 
DLT 
Dose Limiting Toxicity 
ECG 
EDC 
Electrocardiogram 
Electronic Data Capture 
EOT 
End of treatment 
EOS 
End of study 
ET 
Early termination 
eCRF 
Electronic case report form 
FAT 
Fast axonal transport 

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FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GFAP 
Glial fibrillary acidic protein 
GM-CSF 
Granulocyte macrophage colony-stimulating factor 
GMT 
Geometrical mean titers 
HIPAA 
Health Insurance Portability and Accountability Act 
HREC 
Human Research Ethical Committee 
HLA-DR 
MHC class II cell surface receptor 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
ID 
Intradermal 
IgG 
Immunoglobulin G 
IM 
Intramuscular 
INR 
International normalized ratio 
IP 
Investigational product 
ISF 
Investigator’s site file 
IV 
Intravenous 
kg 
Kilogram 
MCI 
Mild cognitive impairment 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHC 
Major Histocompatibility Complex 
MMSE 
Mini Mental State Examination 
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose 
NCS 
Not clinically significant 
NfL 
Neurofilament light chain 
NIA 
National Institute on Aging 
NIH 
National Institute of Health 
NMDA 
N-methil-D-aspartate 
PCS 
Potentially clinically significant 
PAD 
Phosphatase activating domain 
PBMC 
Peripheral blood mononuclear cells 
PET 
Positron emission tomography 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SOP 
Standard operating procedure 

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SRC 
Safety Review Committee 
SSRIs 
Selective serotonin reuptake inhibitors 
SNRIs 
serotonin norepinephrine re-uptake inhibitors 
TEAE 
TGA 
Treatment-emergent adverse event 
Therapeutic Goods Administration 
US 
United States 
WMS-R LM-II 
Wechsler Memory Scale-Revised Logical Memory subscale II 

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1. 
Introduction 
1.1 
Background 
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized clinically by 
deterioration of memory and cognition, progressive impairment of activities of daily living (ADL) and 
a variety of behavioral disturbances. According to the World Health Organization (WHO), there are an 
estimated 47 million people with dementia worldwide, and there are 10 million new cases every year. 
AD is the most common cause of dementia and may contribute to 60-70% of all dementia cases. (3, 4, 
5) This enormous and increasing worldwide healthcare burden due to AD, combined with a lack of 
effective treatments, indicate that new prophylactic and/or therapeutic approaches for treating AD are 
essential. In some patients with early or mid-stage AD, cholinesterase inhibitors, such as donepezil 
hydrochloride, may slow the progressive decline of memory and cognitive function. Another class of 
drugs that block NMDA glutamate receptors (e.g., memantine) has shown some improvement in patients 
with moderate to severe symptoms of confusion and memory loss. Additionally, there are drugs 
available that help to control some of the behavioral symptoms of AD such as sleeplessness, anxiety, 
and depression. However, currently there are no effective disease- modifying drugs that halt or reverse 
AD. The key neuropathological findings of AD are the accumulation of diffuse and neuritic plaques, 
mainly comprised of amyloid beta 40-43 amino acid peptides (Aβ), which are cleaved from amyloid 
precursor protein (APP) by β- and γ-secretases (6, 7, 8) and neurofibrillary tangles, consisting of 
hyperphosphorylated cytoskeletal microtubule (MT) associated protein, (9, 10, 11) Profound loss of 
neuronal synapses and cells, particularly of cholinergic neurons, gliosis, and inflammation are also 
apparent (12).  
In AD, it has become increasingly recognized that amyloid accumulation in the brain occurs decades 
before such symptoms as memory loss and personality change begin. Current data suggest that Aβ 
pathology emerges prior to Tau pathology and may accelerate toxic oligomers and neurofibrillary tangle 
formation (aggregates) (13, 14, 15, 16).    
1.2 
Investigational Product: adjuvanted recombinant protein vaccine, AV-1959R 
AV-1959R is a cGMP-grade recombinant protein composed of three copies of the N-terminal region of 
human Aβ and an immunogenic vaccine platform composed of 12 foreign promiscuous T helper (Th) 
cell epitopes [one synthetic epitope and 11 epitopes from several microorganisms (tetanus toxin; 
hepatitis B and influenza viruses)] collectively designated as the MultiTEP vaccine platform (Figure 1).   

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Figure 1.  Schematic representations of AV-1959R vaccine construct. 
AV-1959R encodes 3 copies of Aβ1-11 fused to MultiTEP, one universal synthetic Th epitope, PADRE 
and eleven foreign promiscuous Th epitopes from infectious agents. 
The MultiTEP is a string of twelve foreign T helper (Th) epitopes composed of one promiscuous 
synthetic (PADRE) peptide and eleven peptides from microorganisms (Tetanus, HBV, Flu) that most 
adults would have either been exposed to or vaccinated against. (1, 2, 17, 18, 19, 20, 21, 22, 23, 24, 25, 
26, 27, 28) These Th cell epitopes bind to various human MHC class II molecules (aka “immune 
response genes” termed HLA-DR/DQ/DP). AV-1959R formulated with Advax-CpG55.2 adjuvant (aka 
AdvaxCpG) generated strong anti-Aβ1-11 antibody responses in wildtype mice and AD mouse models 
and reduced Aβ pathology in the bigenic mouse model of AD without any adverse findings attributed 
to the adjuvanted AV-1959R. (1, 2).    
To enhance the immunogenicity of AV-1959R the Advax-CpG55.2 (Vaxine Pty. Ltd) adjuvant is 
planned to be used in this trial. Advax-CpG55.2 is manufactured from plant derived delta inulin plus 
synthetic CpG55.2 oligonucleotide. Vaccines containing Advax-CpG55.2 adjuvant have been tested in 
10 human clinical trials, conducted in USA, Australia and Iran. Advax-CpG-55.2 adjuvant has been 
safely administered to human subjects, involving >26,000 administrations to >13,000 individual 
subjects across the Phase 1 (30 subjects received active vaccine), Phase 2 (300 subjects received active 
vaccine) Phase 3 (12,757 subjects received active vaccine) and Booster study (250 subjects received 
active vaccine) trials. Symptoms reported by study subjects receiving vaccines containing Advax-
CpG55.2 adjuvant are consistent with those reported following administration of other licensed 
adjuvants, with injection site tenderness, redness and swelling being the most common local adverse 
events and headache, fatigue and myalgia being the most common systemic adverse events. These and 
other solicited reactions were predominantly mild and self-limited. No pattern of clinically significant 
changes in any hematological or biochemical parameters has been observed in subjects immunized with 
vaccines containing Advax-CpG55.2 adjuvant. (29, 30, 31, 32, 33, 34, 35)  AV- 1959R at 100 µg/animal 
dose formulated in Advax-CpG-55.2 adjuvant, induced production of high titers of anti-Aβ antibodies 
in non-human primates (36). 

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No pattern of clinically significant changes in any hematological or biochemical parameters has been 
observed in subjects immunized with vaccines containing Advax-CpG55.2 adjuvant. These trials have 
provided collective data to support the safety, tolerability, and potency of Advax- CpG55.2 adjuvant.   
1.3 
Study Rationale  
AD is a complex and multifactorial disease involving various genetic and environmental risk factors 
that lead to the development of two hallmark pathologies: Aβ soluble oligomers/fibrils/ plaques and 
soluble tau aggregates and neurofibrillary tangles (NFT) followed by inflammation and severe 
neurodegeneration. Findings that mutations in APP and PS1/PS2 that alter Aβ metabolism are tightly 
linked to inherited forms of AD and that up to 75% of adults with Down syndrome develop AD-like 
dementia strongly support the "amyloid cascade" hypothesis. (37, 38, 39) Genetic and postmortem data 
and neuroimaging studies in preclinical AD people and patients with MCI/AD indicate that Aβ 
deposition precedes cortical tau accumulation and drives tau-mediated neurodegeneration in AD. (40, 
41). Not surprisingly, the development of potential therapies for AD has been focused largely on 
reducing pathological Aβ or tau and, more recently, on associated inflammation in the brain. Various 
groups tested Aβ/tau immunotherapeutics in clinical settings with mixed results, indicating that there is 
not much clinical benefit, likely because it is initiated in people with already developed AD. (42, 43, 
44, 45, 46, 47) Although the development of AD therapeutics has still focused on targeting Aβ/tau 
pathology, a fair number of preclinical research suggest other important targets (e.g., pathological 
effects of cholesterol metabolism, ApoE, the endocytic system, microglial activation, etc.). Accordingly, 
various groups are working on the development of novel therapeutics associated with or not linked to 
pathological Aβ/tau accumulation in the brain. (48) Nevertheless, the mountains of pathophysiological 
and genetic data indicate that Aβ/tau are the best targets for the preventive treatment of AD, defined as 
delaying the onset of the disease. (2, 17, 23, 28, 49, 50, 51, 52)  
As it was reported previously, antibodies against Aβ delayed Aβ42 oligomerization/fibrillization but did 
not prevent oligomer formation. Importantly, the same antibodies disaggregate preformed fibrils into 
small aggregates that are even more toxic than fibrils/plaques. (50) Later it was demonstrated that only 
preventive vaccinations reduced AD-like pathology and behavioral deficits in immunized mouse models 
of AD. (49) These data have been supported by preclinical data published by other groups (53, 54, 55, 
56)and results from active and passive immunotherapy trials. (44, 45, 57, 58, 59, 60) 
In this Phase I trial, Sponsor will seek to determine the safety, tolerability, and immunogenicity of an 
active preventive vaccine, AV-1959R, targeting N-terminus of amyloid beta in healthy participants. 

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1.4 
Target population and participants selection strategy  
Hallmarks of AD are the amyloid plaques consisting of early accumulation of oligomeric and fibrillar 
Aβ and, later in this disease, neurofibrillary Tau tangles. Importantly, AD is a progressive disease and, 
in regard to clinical scores, a highly variable disease. Nevertheless, data from the A4 prevention trial of 
late-onset AD (preclinical stage) showed that even before an amyloid scan turns positive, subthreshold 
accumulation of Aβ correlates with subtle memory deficits and presages future decline (61). Published 
data and current results from pre-clinical studies (49, 50),  and clinical trials (62, 63, 64) indicate that 
AD vaccine targeting pathological Aβ may not be therapeutic if vaccination is initiated in patients with 
advanced pathologic stage of AD with neurodegeneration, particularly synapse loss, (65)Importantly, 
recent results of an Aβ immunotherapy clinical trial demonstrated that monoclonal antibodies are 
effective if they are administered in early AD patients (66, 67, 68, 69), and two amyloid beta-directed 
antibodies, aducanumab and lecanemab-irmb (BAN2401), have shown promising results and have got 
the FDA approval under the Accelerated Approval Pathway. 
Not surprisingly, the development of potential therapies for AD has been focused largely on reducing 
pathological Aβ or tau and, more recently, on inflammation. However, various groups tested Aβ 
immunotherapeutics in clinical settings with mixed results, indicating that the clinical benefit is less 
likely if the treatment was initiated as a therapeutic measure in diseased people. (42, 43, 44, 45, 46, 47, 
60, 70, 71, 72). Therefore, AD immunotherapeutic development has shifted from treatment to 
prevention, consistent with our long-standing theory, (2, 49, 50, 52) that safe and immunogenic 
preventive vaccine should be initiated in unimpaired people at risk of AD with biomarker evidence of 
Alzheimer's pathology. (64) 
Therefore, the primary indication for the envisioned vaccine is for prevention or delay of onset of AD, 
postpone cognitive impairment. In this protocol, we suggest evaluating the safety and tolerability of the 
first-in-human adjuvanted Aβ vaccine, AV-1959R in healthy volunteers.   
1.5 
Mechanism of Action 
Data demonstrated that the AV-1959R formulated with AdvaxCpG adjuvant, which has been shown to 
be safe and effective in human trials, (73, 74, 75, 76) is highly immunogenic not only in wildtype mice 
but also in bigenic mouse model of AD exhibiting both Aβ and tau pathologies as well as rabbits and 
non-human primates. AV-1959R vaccine was safe and generated high titers of antibodies against Aβ as 

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evidence by the reduction of Aβ pathology in the brains of vaccinated mouse models of disease. (2) 
Delivered intramuscularly this adjuvanted vaccine generated robust cellular immune responses to 
foreign T helper epitopes avoiding activation of potentially harmful autoreactive T cells and induced 
high titers of a therapeutically potent antibody specific to pathological Aβ in all animal models. 
Immunogenicity and overall safety profile of cGMP AV-1959R vaccine were evaluated in rabbits and 
monkeys. These studies demonstrated that adjuvanted AV-1959R vaccine generates robust anti-Aβ 
antibodies without inducing potentially harmful Th cell responses specific to self-Aβ peptide (i.e., 
autoreactive T cells). 
Thus, data generated with MultiTEP-based vaccines for neurodegenerative diseases in mouse models 
of AD/PD, rabbits, and monkeys. (1, 2, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 28) suggest that in 
vaccinated participants AV-1959R  can potentially overcome high polymorphism of MHC class II genes 
by activating a broad repertoire of naïve and memory Th cells specific to carrier (MultiTEP): 
i. 
Could induce high titers of antibodies against the self B cell epitope, Aβ1-11, and only low 
titers of antibodies specific to the vaccine platform itself. 
ii. 
Could generate therapeutic anti-Aβ antibodies in the vast majority of immunized people. 
iii. 
Could not induce vasogenic edema nor increase microhemorrhage, T- and B-cell infiltration, 
glial activation, and neuronal degeneration.  
AV-1959R vaccine, along with other vaccines based on MultiTEP, stimulates adaptive immunity, 
providing broad coverage of human MHC polymorphisms and activating both naive Th cells and pre-
existing memory Th cells (49, 52)generated in response to conventional vaccines and/or infections with 
various pathogens during one’s lifespan. These “non-self” anti-MultiTEP Th cells activate B cells 
specific to disease associated Aβ epitope and induce the production of therapeutically potent antibodies 
specific to Aβ protein in humans similar to that observed in animal models. Our published data and data 
presented in the Investigator Brochure (36) supported this mechanism of action and demonstrated that 
the AV-1959R vaccine based on this platform is highly immunogenic in mice (1, 2), in rabbits, and 
macaques. 

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1.6 
Proposed doses and immunization schedule 
This protocol proposes a Phase 1 study design consisting of 2 sequential cohorts administrated with 
ascending doses of adjuvanted AV-1959R/A of 100 µg and 300 µg.  
The 16 participants enrolled at a single site will be randomly assigned in 3:1 allocation to receive either 
active (AV- 1959R) or placebo (normal saline solution), both formulated with Advax-CpG55.2 [Advax-
15 mg and CpG-0.15 mg] via IM injections on Week 0 (Day 1), Week 4 (Day 28 ± 2d) and Week 14 
(Day 98 ± 5d) and will be followed up for up to 8 weeks after last dose of IP.  
Importantly, safety data generated with AV-1959R vaccine in 5XFAD transgenic mice mouse models, 
rabbits, and monkeys indicated that 100µg (mice, ~2500 µg/kg) and 50, 100, and 300µg (rabbits, ~15-
100 µg/kg) and 100µg (monkeys, ~15µg/kg) delivered IM had been safe and immunogenic after 5 
immunizations. These doses are ~3-500 times higher than the highest dose of AV-1959R (300µg per 
immunization, on average 5 µg/kg) proposed in the Phase I study calculated on per kg basis. Two 
immunizations (within two-week interval) with an immunogenic dose of AV-1959R followed by 1-2 
booster injections with the same dose have been shown to be sufficient for the generation of robust 
cellular immune responses in all vaccinated animals, such as transgenic mouse model, rabbits, and 
monkeys. The strongest Th cell immune responses specific to the MultiTEP vaccine platform are 
detected 7-10 days after three immunizations in peripheral blood mononuclear cells (PBMC) isolated 
from monkeys and splenocytes obtained from mice. These Th cells synthesize and secrete cytokines to 
stimulate activated anti-Aβ specific B cells, producing therapeutically potent antibodies on days 14-21 
after the third/fourth vaccinations. These dynamic data of immune responses support the schedule of 
immunizations and blood collection to detect antibodies in the proposed study. At the same time, it is 
well known that the half- life of human IgG antibodies is about 15-30 days, depending on concentration. 
(77, 78, 79) Therefore, antibody titers will be monitored in vaccinated subjects during the entire study 
in order to better understanding of the boosting regimen for future trials. 
In human clinical trials, a dose of up to 15 mg of Advax and up to 0.15 mg of CpG55.2 given twice 3 
weeks apart in adult human subjects was found to be safe and well tolerated.(29, 30, 31, 80) 
(ClinicalTrials.gov: NCT04453852; NCT04944368; NCT05005559; NCT05175625; NCT05231590; 
NCT05285384; NCT05148871; NCT05542862; NCT05279456; NCT03945825; NCT03038776; 
NCT01951677).  
 
 

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2. 
Study Objectives 
2.1 
Primary Objective 
The primary objective of this study is to determine the safety and tolerability of adjuvanted AV-1959R 
vaccine compared to placebo in healthy participants. 
2.2 
Secondary Objectives 
The secondary objective is to evaluate the immunogenicity of the adjuvanted AV- 1959R vaccine by 
assessing the level of humoral immune responses (anti-Aβ antibody levels: IgM and IgG isotypes and 
IgG1, IgG2, IgG3, and IgG4 subclasses) in plasma.   
 
 

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3. 
Investigational Plan 
3.1 
Study Design 
This is a Phase 1, randomized, double-blind, placebo-controlled, multiple dose-escalating trial 
consisting of 2 ascending dose cohorts in healthy male and female participants, 40-60 years of age.  
Subjects will undergo Screening visits within 4 weeks (up to 28 days) prior to the administration of the 
investigational product (IP) as per Table 1 to identify eligible participants. Screening procedures may 
be performed in two or more screening visits. MRI examination for determination of subject eligibility 
will be performed at the later stage of screening.  
A total of sixteen (16) subjects will be enrolled into the study in one of two dose cohorts. Eligible 
participants will be randomly assigned in a 3:1 ratio to receive 3 IM injections of either AV-1959R or 
placebo both formulated with Advax-CpG55.2 adjuvant at baseline (Week 0), Weeks 4 and 14 and 
undergo follow-up visit at Week 22 (Table 1). Each cohort will contain up to 8 subjects; six (6) will be 
randomly assigned to receive AV-1959R and two (2) participants to receive a placebo. 
The following doses will be administered at each immunization time point: 
Cohort 
Study Drug (Dose) 
Number of subjects 
Cohort 1: 
AV-1959R (100 µg) 
 6 
Placebo 
 2 
Cohort 2: 
AV-1959R (300 µg) 
 6 
Placebo 
 2 
 
A Safety Review Committee (SRC) will be established to review the study progress, provide oversight 
for the determination of the safety of dose escalation, and determine if it is appropriate to continue the 
study or modify the protocol. Should the SRC choose not to escalate to the next dose level, previous 
dose level may be repeated if deemed necessary.  
DLT will be monitored during the entire study. The DLT is defined as a serious or severe clinically 
significant AE (CTCAE Grade 3 or higher) not resolving within 14 days after each immunization in the 
dosing cohort that may be considered by the Investigator to be related to the study drug. 
For each dose level, dosing will be staggered such that 2 subjects will be dosed prior to the rest of the 
group. Initially, 2 subjects (one active and one placebo) in each Cohort will be dosed (Immunization #1, 
Day 0) in a randomization ratio of 3:1 (active to placebo) prior to the rest of the cohort. General 
tolerability to treatment will be monitored over 14 days following each immunization of AV-1959R or 
placebo by the Investigator. If the safety assessments (AEs, clinical laboratory test results, vital sign 
measurements, 12 lead ECG results, and physical examination) are acceptable based on the judgement 

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of the Investigator on Day 15±2 and Day 42±3, individual participants will receive Immunization # 2 
(Day 28±2) and Immunization # 3 (Day 98±5), respectively as planned.  
Investigator will determine whether the remaining 6 subjects (five active and one placebo) in the Cohort 
will be dosed after review of a minimum of 14 days safety assessments (AEs, clinical laboratory test 
results, vital sign measurements, 12 lead ECG results, and physical examination) following first 
immunization of AV-1959R or placebo in sentinel group. 
Dose escalation decision will be made by SRC based upon review of adverse events (AEs), and all 
safety data from 14 days after the first immunization of all 8 participants in first cohort before escalation 
to the second dose cohort.  
Dose escalation will be determined by the number of subjects experiencing DLT not resolving within 
14 days after the first immunization per dosing cohort: 
• If ≤1 participant experienced a DLT two weeks after the first immunization, then initiation of 
the second dose (300µg) cohort may proceed.                       
• If ≥ 2 participants experience DLT two weeks after the first immunization, then no further dose 
increase will occur.  
Dose escalation will be suspended or stopped if any of the following occurs: 
• Death from any cause other than events clearly unrelated to the study drug;  
• Any CTCAE Grade 3 or higher adverse event that certainly, probably/likely or possibly related 
to the study drug and persists for more than two weeks; 
• Any serious or severe clinically significant AE (CTCAE Grade 3 or higher) that certainly, 
probably/likely or possibly related to the study drug and occurs within 4 weeks after product 
administration; 
• Any other event(s) that in the opinion of the Investigator should invoke suspension of further 
enrollment. 
Based on safety information  and number of DLT events, the SRC may decide to terminate the study at 
any time and the sponsor will submit appropriate reports to HREC and/or TGA. 
Screening of new subjects may continue during SRC review meetings period between dose escalations. 
Safety and tolerability are assessed through AEs, physical examinations, vital signs, ECGs, laboratory 
assessments, and MRI examinations. A local screening MRI will be performed at screening as part of 
the study eligibility criteria and then at Week 22 for safety assessment. The MRI scans will be reviewed 
by the Investigator or qualified designee for immediate participant management.  

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Blood will be collected to measure anti-Aβ and anti-MultiTEP antibody titers prior to initiation of 
immunization (prior to 1st immunization) and at Weeks 6, 14 (prior to last immunization), 16, 20, and 
22.  
The overall study schematic is presented in Figure 2 below: 
 
Figure 2.  Study design scheme.  
 
 
 

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4. 
Study Population 
4.1 
Number of Subjects 
Up to 16 eligible healthy male or female of 40 to 60 years of age will be enrolled in this study.  
4.2 
Selection of Study Population 
The Investigator will be responsible for confirming subject eligibility by documenting in the electronic 
case report form (eCRF) that each subject meets all of the inclusion criteria in Section 4.2.1 and does 
not meet any of the exclusion criteria in Section 4.2.2.  
Prior to any study-related activities, an ICF approved by the HREC must be signed and personally dated 
by the subject. The subject’s original signed and dated ICF (together with any subsequent amended 
versions approved by the HREC) must be retained by the investigator in the subject’s file. A copy of 
the original signed and dated ICF must be given to the subject.  
4.2.1 Inclusion Criteria 
A subject must meet all of the following inclusion criteria to participate in this study: 
1. Healthy, adult, male or female of non-childbearing potential, 40 to 60 years of age, inclusive, at 
Screening visit. 
2. Body mass index (BMI) ≥18.0 and ≤32.0 kg/m2 at Screening visit 
3. Medically healthy with no clinically significant medical history, abnormalities in physical 
examination, laboratory variables, vital signs, ECG or MRI at the time of Screening and Baseline 
(if applicable), as deemed by the Investigator or designee. 
4. Signed informed consent form by the participant prior to initiation of any study-related 
procedures. 
5. If female of non-childbearing potential, must meet at least one of the following criteria: 
a. post-menopausal status defined as amenorrhea for at least 12 months prior to study 
drug dosing in absence of any exogenous hormonal treatments and follicle stimulating 
hormone (FSH) levels in the laboratory defined post-menopausal range. 
b. subject report of surgical sterilization (i.e., hysterectomy, bilateral tubal ligation, 
bilateral oophorectomy/ salpingectomy) at least 6 weeks prior to Day 1.  Documented 
evidence of surgical sterilization is required.  

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6. If male, must have had a vasectomy 90 days prior to the Screening visit with a follow up negative 
sperm count, or agree to not donate sperm for 90 days after the last dose of study drug and, if 
engaging in vaginal sexual intercourse with a female partner of childbearing potential, agree to 
use a condom in addition to the female partner must use a highly effective method of birth control 
(e.g. intrauterine device, diaphragm, hormonal contraceptives) throughout the duration of the 
study treatment period and for 90 days after the last dose of study drug. Abstinence from 
heterosexual intercourse is an acceptable method of contraception. Subjects with same-sex 
partners (abstinence from penile-vaginal intercourse) are eligible without needing contraception 
when this is their usual form of sexual relations. 
7. Ability, in the opinion of the investigator, to understand the nature of the trial and comply with 
protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory 
tests, and other trial procedures. 
4.2.2 Exclusion Criteria 
A subject will be excluded from participation in this study if he or she meets any of the following 
criteria: 
1. Any clinically significant medical history or observations at the time of Screening visit not 
specifically excluded in other criteria that, in the opinion of the Investigator or designee, may 
confound the results of the study, compromise the safety of the subject or otherwise render the 
subject unsuitable for participation. 
2. Magnetic resonance imaging (MRI) showing evidence of any of the following at the Screening:  
o 1 or more small non-cortical lacunar infarct greater than 1.0 cm 
o Any territorial infarct including acute or chronic  
o Subjects who have microbleeds and areas of leptomeningeal hemosiderosis  
o Subjects who have a presence of any other significant cerebral abnormalities, including 
ARIA-E, as assessed in the screening MRI scan. 
3. Contraindications for MRI scanning, including implanted metallic devices (e.g., non-MRI-safe 
cardiac pacemaker or neurostimulator; some artificial joints metal pins; surgical clips; or other 
implanted metal parts), or claustrophobia or discomfort in confined spaces. 
4. Any serious illness requiring systemic treatment and/or hospitalization within 4 weeks prior to 
study entry. 

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5. History/evidence of clinically relevant pathology related to the cardiovascular system, 
respiratory tract, gastrointestinal tract, endocrinology, immunology, hematology, or any other 
systemic disorder/major surgeries that, in the opinion of the Investigator, would confound 
participation and follow-up. 
6. History or presence of any of the following: 
o clinically significant acute illness or surgery within the previous 3 months of Day 1. 
o hypersensitivity reaction or anaphylaxis to any medication to be of clinical significance 
to the current study or compromise the safety of the subject in the opinion of the 
Investigator 
o history or suspicion of routine or chronic drug or alcohol abuse or dependence within 1 
year prior to Day 1 based on subject report; excessive alcohol intake (defined as routine 
weekly intake of greater than 21 glasses/units per week, with one unit=150 mL of wine 
or 360 mL of beer or 45 mL of 45% alcohol. 
7. Clinically significant laboratory abnormalities at Screening visit, including (but not limited to): 
o hemoglobin, hematocrit, total white blood count (WBC) or platelet count below the 
lower limit of the normal range  
o alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >1.5 times the 
upper limit of the normal range  
o serum creatinine above the upper limit of the normal range or estimated creatinine 
clearance <90 mL/minute as calculated by the Cockcroft-Gault equation 
o positive testing for human immunodeficiency virus (HIV-1 or -2), hepatitis B surface 
antigen (HBsAg), or positive testing for hepatitis C (HCV)  
Clinical laboratory tests may be repeated as per Investigator’s discretion. 
8. Systolic blood pressure (BP) >160 millimeters of mercury (mmHg), or <90 mmHg; diastolic BP 
>95 mmHg or <50 mmHg blood at Screening visit or Day 1. Vital signs may be repeated as per 
Investigator’s judgement. 
9. Supine heart rate less than 45 beats per minute (bpm) or higher than 100 bpm at the Screening 
visit or Day 1. Vital signs may be repeated as per Investigator’s judgement. 
10. ECG with QTcF interval duration equal or greater than 450 msec for males and 470 msec for 
females obtained after at least 5 minutes in a supine or semi-recumbent position at quiet rest at 
Screening visit or Day 1. 

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11. Any other medical, psychological, or social condition that, in the opinion of the Investigator, 
would prevent the participant from fully participating in the study would represent a concern for 
study compliance or would constitute a safety concern to the participant. 
12. Participation in another investigational drug study or treatment with an investigational drug 
within 30 days or 5 half-lives, whichever is longer, before dosing. 
13. Prior administration of any tau or amyloid-beta immunotherapy (vaccine, antibody) within 1 
year prior to Screening. 
14. The use of immunomodulatory or growth-stimulating factors such as systemic corticosteroids, 
cyclosporine, methotrexate, azathioprine, anti-CD25 antibody, GM-CSF, C-CSF, interferon 
(IFN), or interleukin-2 (IL-2) within 30 days prior to study entry.  
15. Chronic use (>3 months) of warfarin, other coumarin derivatives, anticoagulants, or an anti-
platelet agent (e.g., clopidogrel). 
16. Parenteral use of immunoglobulin preparations, blood products, and plasma derivatives. 
17. History/evidence of severe local or systemic reactions to vaccination or significant allergic 
reactions. 
18. Female of childbearing potential. 
19. Any skin condition and/or tattoo that may interfere with the evaluation of safety at the injection site. 
20. Donation of blood or significant blood loss greater than 400 ml within the last 30 days prior to 
dosing. 
4.3 
Subject Disposition and Discontinuation 
4.3.1 Duration of Study Participation 
The maximum duration of participation for each subject will be approximately 26 weeks, including up 
to 4 weeks for screening, 14 weeks for treatment, and 8 weeks follow up period after the last dose of 
IP. The duration of study participation is defined for each subject as the date written informed consent 
is provided through the end of study (EOS) visit, which is up to 56±7 days post last dose or the date of 
early termination (ET) for subjects who are withdrawn prior to the end of study assessment. 
4.3.2 Subjects Withdrawal and Discontinuation 
Subjects will be informed that they are free to withdraw from the study at any time. The Investigator 
may exercise his or her medical judgment to terminate a subject’s participation in the study due to 

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clinically significant changes in any clinical or laboratory parameters, or non-compliance with study 
procedures.  
Sponsor also reserves the right to terminate the study at any time for any reason. All data normally 
collected at completion of the study will be collected either at the time of the subject’s early termination, 
or on or before the scheduled study visit. 
Study drug administration or a subject’s participation in this trial may be discontinued for any of the 
following reasons at the discretion of the Investigator: 
• If the subject withdraws his/her consent for any reason. 
• If the subject’s condition has worsened to the degree that the Investigator feels it is unsafe for the 
subject to continue in the study. 
• If the subject has poor venous access making it difficult/impossible to obtain laboratory samples. 
• If an adverse event (AE) occurs for which the subject desires to discontinue treatment or the 
Investigator determines that it is in the subject’s best interest to be discontinued. 
• If there is a major protocol deviation or a trend in major deviations. 
• If a concomitant therapy is reported or required which is likely to interfere with the results of the 
study or compromise subject safety. 
• If the subject is lost to follow-up. The Investigator will document efforts to reach the subject at 
least twice by telephone and by a certified follow-up letter before determining that the subject is 
lost to follow-up. 
• If a subject becomes pregnant. If a subject pregnancy is reported during study participation, the 
pregnancy will be followed until the outcome of the pregnancy and the resulting child will be 
followed for 1 year post birth. 
• Administrative reasons. 
• Other. Note: This category includes withdrawals caused by an accidental or a medical emergency, 
unblinding, or other rare cases. This also includes withdrawal due to medical, psychological, or 
social condition which, in the opinion of the Investigator would prevent the subject from fully 
participating in the study, would represent a concern for study compliance, or would constitute a 
safety concern to the subject. The specific reasons will be recorded on the eCRF. 
The clinical report will include reason(s) for subject withdrawals as well as details relevant to the subject 
withdrawal. 

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4.3.3 Handling of Withdrawals 
The Investigator may terminate a subject’s study participation at any time during the study if the subject 
meets the withdrawal criteria described in Section 4.3.2. In addition, a subject may discontinue his or 
her participation without giving a reason at any time during the study. Should a subject’s participation 
be discontinued, the primary reason for termination must be recorded. If a subject is discontinued from 
the study for any reason, efforts should be made to perform final assessments outlined for the Day 154 
(± 7d) follow up visit if deemed safe by the Investigator.  
In the event that a subject discontinues from the study at any time due to an AE, the reason for 
discontinuation, the nature of the event and its clinical course must be fully documented. In this case, 
the Investigator must follow the subject until the AE has resolved, becomes clinically insignificant, or 
is stabilized, unless the subject is lost to follow-up. 
4.3.4 Replacement of Subjects 
Subjects who withdraw or are withdrawn for non-safety reasons during the study drug treatment may 
be replaced on a case-by-case basis per Sponsor’s discretion. 
4.3.5 Screen Failures 
Any subject who sign the ICF and is deemed ineligible to participate in the study or eligible subjects 
who are not randomized (due to completion of enrollment or backup subjects) will be considered as 
screen failure. Subjects who do not qualify based on a reversible condition or mild intercurrent illness, 
in the opinion of the Investigator, may be rescreened after the underlying condition is resolved. 
4.4 
Safety Review / Dose Escalation Committee 
A Safety Review Committee (SRC) will provide study oversight for the determination of the safety of 
dose escalation. The SRC will include the sponsor’s medical monitor, independent medical monitor and 
the PI, additional experts may be included in the SRC but will not be voting members. Details of SRC 
responsibilities, membership, procedures, and documentation will be specified in SRC charter. 
The SRC will be informed of all deaths, serious unexpected adverse events, and all serious adverse 
events immediately after the Sponsor has been notified. The chair of the SRC will receive a report of an 
event as soon as the Sponsor receives the report from the Investigator. The report will then be reviewed 
by the full SRC. 

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4.5 
Dose Escalation Rules 
Dose-limiting toxicity (DLT) will be monitored during the entire study. The DLT is defined as a serious 
or severe clinically significant AE (CTCAE Grade 3 or higher) not resolving within 14 days after each 
immunization in the dosing cohort that may be considered by the Investigator to be related to the study 
drug. 
For each dose level, dosing will be staggered such that 2 subjects will be dosed prior to the rest of the 
group. Initially, 2 subjects (one active and one placebo) in each Cohort will be dosed (Immunization #1, 
Day 0) prior to the rest of the cohort. General tolerability to treatment will be monitored over 14 days 
following each immunization of AV-1959R or placebo by the Investigator. If the safety assessments 
(AEs, clinical laboratory test results, vital sign measurements, 12 lead ECG results, and physical 
examination) are acceptable based on the judgement of the Investigator on Day 15±1 and Day 42±3, 
individual participants will receive Immunization # 2 (Day 28±2) and Immunization # 3 (Day 98±5), 
respectively as planned.  
Investigator will also determine whether the remaining 6 subjects (five active and one placebo) in the 
Cohort will be dosed after review of a minimum of 14 days safety assessments (AEs, clinical laboratory 
test results, vital sign measurements, 12 lead ECG results, and physical examination) following first 
immunization of AV-1959R or placebo in sentinel group. 
Dose escalation decision will be made by SRC based upon review of AEs, and all safety data from 14 
days after the first immunization of all 8 participants in first cohort before escalation to the second dose 
cohort.  
Dose escalation will be determined by the number of subjects experiencing DLT not resolving within 
14 days after first immunization: 
• If ≤1 participant experienced a DLT two weeks after the first immunization, then initiation of the 
second dose (300µg) cohort may proceed.                       
• If ≥ 2 participants experience DLT in two weeks after the first immunization, then no further dose 
increase will occur. 
4.6 
Stopping Rules 
When an investigator identifies an event potentially associated with a stopping rule noted below, the 
Investigator must notify Sponsor Medical Monitor (MM) immediately. MM will then notify the SRC. 
The SRC will determine if any of the following stopping rules shall be invoked: 

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• Death from any cause other than events clearly unrelated to the study drug;  
• Any CTCAE Grade 3 or higher adverse event that certainly, probably/likely or possibly related 
to the study drug and persists for more than two weeks; 
• Any serious or severe clinically significant AE (CTCAE Grade 3 or higher) that certainly, 
probably/likely or possibly related to the study drug and occurs within 4 weeks after product 
administration; 
• Any other event(s) that in the opinion of the Investigator should invoke suspension of further 
enrollment. 
The Sponsor has the right to terminate the study at any time in case of safety concerns or it becomes 
unjustifiable for medical or ethical reasons to continue the study. In addition, termination or 
modification may be recommended for any other perceived safety concern based on clinical judgment, 
including but not limited to a higher than anticipated rate for any component of the primary endpoint, 
device failures resulting in adverse events, or unexpected SAEs. 

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5. 
Study Treatments 
5.1 
Investigational Product  
5.1.1 Identity of Study Drugs Used in the Study 
The AV-1959R drug product is clear to slightly opalescent, colorless to slightly yellow solution. AV-
1959R will be supplied in vials containing a drug product formulated to the final protein concentration 
of 1.1mg/mL. The fill volume target is about 0.7mL. 
Placebo will be prepared by the pharmacy by mixing Advax, CpG and normal saline solution, and 
will not contain a drug product. 
AV-1959R and Placebo formulations are manufactured, tested, and released according to Good 
Manufacturing Practices. 
Advax and CpG55.2 are supplied separately as preservative-free suspensions in phosphate buffered 
saline in glass vials that contain: 
- 
Advax vial - 0.5 mL at 50mg/mL, total content 25 mg 
- 
CpG55.2 vial - 0.5 mL at 2 mg/ml, total content 1 mg 
5.1.2 Formulation, Packaging, and Labeling 
AV-1959R and Placebo will be packaged by Sponsor or sponsor-approved vendor and supplied in 
single-dose vials. All labeling and packaging will be the responsibility of the Sponsor and will be 
performed according to GMP and the local regulatory requirements. 
The Advax and CpG55.2 adjuvant is presented as two separate vials, one containing delta inulin and 
the other containing CpG55.2 which need to be mixed together before use. 
The AV-1959R and adjuvant component(s) are diluted with natural saline solution, drawn up into 
separate syringes, via Fluid Dispensing Connector mixed in the new  syringe for injection. 
Further details of study drug preparation will be provided in the Pharmacy Manual for the study. 
5.1.3 Storage and Handling of Investigational Product 
Drug product AV-1959R and Placebo must be kept in a freezer at ≤ - 60oC, while Advax and CpG55.2 
adjuvants must be kept at 2-8oC (Do not freeze) in a secure cabinet or room with access restricted to 
necessary study site personnel. Prior to using the AV-1959R vials should be thawed at 4-8oC. When 
completely thawed, the vials should be gently mixed, and formulation with Advax and CpG55.2 
should be prepared and administered as described in a Pharmacy Manual.  

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The study drugs must be stored as labeled in a secure area with access limited to the authorized staff. 
The study drugs will be stored securely under the appropriate conditions according to local standard 
operating procedures. The Investigator has overall responsibility for ensuring that study drugs are 
stored in a secure, limited-access location. Limited responsibility may be delegated to the pharmacist 
or member of the study team, but this delegation must be documented. 
The Sponsor will provide a sufficient quantity of study drugs supplies to the site. Upon receipt of the 
study medication, the Investigator or the responsible pharmacist will inspect the study drugs. All study 
drugs will be handled, reconstituted, prepared, labeled, dispensed, and accounted for according to the 
Pharmacy Manual.  
The study medication will be kept in the pharmacy or in a locked and secured storage room at the site 
accessible only to those authorized by the Investigator to dispense the study medication. The 
personnel responsible for study drug will keep an inventory of unused and used vials. This will include 
a description of the formulation and the quantity of investigational materials received for the study 
and a record of the materials that are dispensed.  
5.1.4 Investigational Product Accountability 
In accordance with the Code of Federal Regulations (21 CFR 312.62), the Investigator is required to 
keep accurate records showing the final disposition of all study drugs. 
The Investigator and/or delegated pharmacist will maintain records of the product delivery at the site, 
the inventory at the site, the use by each subject, the return to the Sponsor or alternative disposition 
of unused products. These records will include dates, quantities, batch numbers, expiry date, and the 
unique code numbers assigned to the IP and study subject. 
The Investigator must not use material provided for this particular study in another study without prior 
written approval from the Sponsor. 
Adequate records of the receipt and disposition of all received IP are to be maintained at the site. 
5.1.5 Disposal and Destruction 
At the end of the study and once IP inventory accountability is completed, the Sponsor may authorize 
destruction of all used, partially used, and unused vials. If the site is capable of destroying designated 
study materials, it may do so only upon authorization by the Sponsor. Used vials of drug product, 
placebo, and Advax-CpG55.2 admixtures may be destroyed in accordance with site- specific SOPs 

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following each monitoring visit where study product accountability is monitored, and resolution of 
any discrepancies. 
5.1.6 Method of Assigning Subjects to Treatment Groups 
A statistician who will not be involved in the ongoing study will generate the randomization schedule. 
The randomization treatment assignment information will be secured and housed kept in a locked 
storage area, accessible only by the assigned unblinded pharmacist and his or her verifier.  
Approximately 16 subjects will be randomly assigned to receive either AV-1959R or placebo treatment 
in a 3:1 ratio.  Randomization is to occur on Day 1 before study drug administration. 
Blinding information is provided in Section 5.5. 
5.2 
Treatment Administered 
The following treatments will be administered in each cohort:  
 
Cohort 
Study Drug (Dose) 
Adjuvant 
Number 
of 
subjects 
Cohort 1: 
AV-1959R (100 µg) 
Advax-CpG55.2 [Advax-15mg, and CpG-0.15mg] 
6 
Placebo 
Advax-CpG55.2 [Advax-15mg, and CpG-0.15mg] 
2 
Cohort 2: 
AV-1959R (300 µg) 
Advax-CpG55.2 [Advax-15mg, and CpG-0.15mg] 
6 
Placebo 
Advax-CpG55.2 [Advax-15mg, and CpG-0.15mg] 
2 
 
Preparation of AV-1959R or Placebo with adjuvant: Vaccine formulation (AV-1959R or Placebo) 
should contain an appropriate dose of the AV-1959R (100 µg or 300 µg) or Placebo with adjuvant 
Advax-CpG55.2. Study vaccine preparation will be performed by the site’s pharmacist or designee 
on the day of administration. Admixture of vaccine and adjuvants by the unblinded research 
pharmacist or designee must be performed under a laminar flow hood using an aseptic technique 
according to USP 797 guidelines and local institutional guidelines. Detailed instructions for vaccine 
preparation will be described in the Pharmacy Manual. 
Treatment administration: AV-1959R vaccine or Placebo administration to the subject will be 
performed by a blinded study personnel member. Each dose of the study drug will be administered to 
the subject via a single IM injection into the deltoid muscle of the subject’s preferred arm. The site of 
injection (right and left arms sequentially when possible) and time of study vaccine administration to 
the subject will be recorded on the appropriate source document. An aseptic technique will be used 
for the withdrawal and administration of each dose of the study vaccine using a disposable, sterile 

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needle appropriate in length for each subject. Details of dosing procedures will be provided in the 
Pharmacy Manual. 
5.3 
Treatment Compliance 
All doses of the study drug will be administered at the site under direct observation of study personnel 
and recorded in the eCRF. Clinic personnel will confirm that the subject has received the entire dose 
of study drug. 
5.4 
Subject Numbering 
Randomized subjects will be assigned unique subject numbers in sequential order based on their order 
of qualification. 
5.5 
Blinding 
The study will be double-blind and a randomization schedule will be prepared by unblinded 
statistician. The randomization schedule will be secured within the pharmacy and only the unblinded 
pharmacist will have access to the randomization schedule.  
Neither the subjects nor clinical staff administering or dispensing the study drug will know whether 
the subject is receiving active treatment or placebo. To maintain the blind, ready to be administered 
syringes with adjuvanted active AV-1959R and adjuvanted placebo normal saline solution without 
the active AV-1959R) will be prepared by the Pharmacy and delivered to the trial clinical site on the 
day of immunization.  
5.5.1 Breaking the Blind 
The investigator and site study personnel must remain blinded to the participant’s treatment 
assignment. The blind should be broken only if the participant experiences a medical emergency and 
knowledge of the blinded treatment assignment is deemed necessary for further management of the 
participant. An emergency code break in a sealed envelope will be available to the PI and/or 
pharmacist.  
If unblinding is deemed necessary for the safety of the participant, before breaking the blind, the 
investigator will attempt to contact the medical monitor to discuss the need for the unblinding. The 
investigator may break the blind independent of the medical monitor if the event is considered an 
emergency by the investigator and the code break is necessary for the management of the participant. 
The investigator must inform the medical monitor as soon as possible. 

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Individual code breaks by the investigator will result in withdrawal of the participant from the study. 
The date and reason for the code break must be documented in the source documents and on the 
appropriate electronic case report form (eCRF). The sponsor must be informed as soon as possible. 

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6. 
Study Procedures and Evaluations 
6.1 
Study Visits 
Refer to the schedule of assessments (Table 1) for a summary of the schedule of study procedures. 
The duration of study participation for each subject is approximately up to 26 weeks. 
6.1.1 Screening Period (Days -28 to -1) 
The prospective subjects will visit the study center and be assessed by qualified properly educated, 
and instructed study staff. 
Written information on the study and the associated risks will be provided to the subjects at the initial 
screening visit. Subjects must be allowed to read and understand the information provided and to 
prepare questions prior to being asked for consent. Subject must personally date and sign a written 
informed consent that has been approved by an HREC. No study-related procedures or activities will 
be performed until the subject is fully informed about the study and the consent form is properly 
signed and dated. The Investigator, or a qualified person designated by the Investigator, will explain 
the purpose and procedures of the study as well as potential benefits and risks and respond to any 
questions raised by the subject. Each subject will be given a copy of the fully signed and dated consent 
form. 
The screening period will occur within 28 days prior to participant randomization on Day 1. Subjects 
will be instructed to return to the study site for additional visits as appropriate within the Screening 
period for completion of the required screening assessments. Extension of the Screening period 
beyond the 28-day window to allow completion of screening procedures may be permitted after 
discussion between the Investigator and the Medical Monitor on a case-by-case basis. 
Screening procedures may be performed in two or more screening visits. MRI examination for 
determination of subject eligibility will be performed at the later stage of screening. 
Other safety assessments may be repeated at each screening visit at the discretion of the Investigator 
or when indicated. 
The following assessments/procedures will be performed during screening period: 
● Informed consent; 
● Demographics; 
● Medical history; 

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● Collection of prior/concomitant medication information; 
● Height, body weight measurement and BMI calculation; 
● Physical examination; 
● Recording of vital signs (heart rate, blood pressure, respiratory rate and body 
temperature); 
● 12-lead ECG; 
● Collection of blood and urine samples for clinical laboratory tests, including hematology, 
serum chemistry, coagulation, urinalysis, serology, pregnancy (all females), and FSH 
(postmenopausal females) tests. 
● Alcohol and drug tests 
● MRI Examination 
 
Subjects who meet all eligibility criteria will be  scheduled for Day -1 check-in visit. 
6.1.2 Day -1  Visit 
The following assessments/procedures will be performed on Day -1: 
● Review of concomitant medications 
● Clinical laboratory tests (biochemistry, hematology, coagulation and urinalysis) and 
pregnancy test (females) 
Subject eligibility will be reassessed, and eligible subjects will remain confined to the study site from 
Day -1 till the completion of the scheduled study procedures on Day 1.  
6.1.3 Day 1 - Immunization #1 
Subjects who meet the eligibility criteria will be randomized into one of the treatment groups. Study 
medication will not be dispensed until all screening procedures have been completed, eligibility has 
been verified and the subject has been randomized. 
The following assessments/procedures will be performed on Day 1: 
Pre-dose: 
● Subject eligibility will be reviewed to ensure the subject remains eligible for the study 
since screening. 
● Update medical history as applicable since screening. 
● Review of concomitant medications 

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● Symptom-driven physical examination 
● Vital signs within 15 minutes before the immunization (pre-dose) 
● 12-lead ECG within 30 minutes before the immunization (pre-dose) 
● Alcohol and drug tests 
● Blood collection for anti-Aβ and anti-MultiTEP antibodies 
Study drug (Active or Placebo) will be administered – Immunization #1. 
Post-dose: 
● 12-lead ECG at 4 hours post-dose 
● Recording of vital signs at 15 min, 1 hour, 2 hours and 4 hours post-dose 
● Assessment of AEs. 
● Injection site reaction assessment at 30 min, 1 hour, 2 hours and 4 hours post-dose 
Subjects will be instructed to return to the study site on Day 15 (±2d). 
6.1.4 Day 15 (±2) 
The following assessments/procedures will be performed on Day 15 (±2d): 
● Symptom-driven physical examination 
● 12-lead ECG 
● Vital signs 
● Clinical laboratory tests (biochemistry, hematology, coagulation and urinalysis) 
● Review of concomitant medications 
● Assessment of AEs. 
Subjects will be instructed to return to the study site on Day 28 (±2d). 
6.1.5 Day 28 (±2) – Immunization #2 
The following assessments/procedures will be performed on Day 28 (±2d): 
Pre-dose: 
● Review of concomitant medications 
● Symptom-driven physical examination 
● Vital signs within 15 minutes before the immunization (pre-dose) 
● 12-lead ECG within 30 minutes before the immunization (pre-dose) 
● Clinical laboratory tests (biochemistry, hematology, coagulation and urinalysis) and 
pregnancy test (females) 

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● Alcohol and drug tests 
Study drug (Active or Placebo) will be administered – Immunization #2.  
Post-dose: 
● 12-lead ECG at 4 hours post-dose 
● Recording of vital signs at 15 min, 1 hour, 2 hours and 4 hours post-dose 
● Assessment of AEs. 
● Injection site reaction assessment at 30 min, 1 hour, 2 hours and 4 hours post-dose 
Subjects will be instructed to return to the study site on Day 42 (±3d). 
6.1.6 Day 42 (±3) 
The following assessments/procedures will be performed on Day 42 (±3d): 
● Complete physical examination 
● 12-lead ECG 
● Vital signs 
● Clinical laboratory tests (biochemistry, hematology, coagulation and urinalysis) 
● Blood collection for anti- Aβ and anti-MultiTEP antibodies  
● Review of concomitant medications 
● Assessment of AEs. 
Subjects will be instructed to return to the study site on Day 98 (±5d). 
6.1.7 Day 98 (±5) – Immunization #3 
The following assessments/procedures will be performed on Day 98 (±5d): 
Pre-dose: 
● Review of concomitant medications 
● Symptom-directed physical examination 
● Vital signs within 15 minutes before the immunization (pre-dose) 
● 12-lead ECG within 30 minutes before the immunization (pre-dose) 
● Clinical laboratory tests (biochemistry, hematology, coagulation and urinalysis) and 
pregnancy test (females) 
● Alcohol and drug tests 
● Blood collection for anti-Aβ and anti-MultiTEP antibodies 

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Study drug (Active or Placebo) will be administered – Immunization #3. 
Post-dose: 
● 12-lead ECG at 4 hours post-dose 
● Recording of vital signs at 15 min, 1 hour, 2 hours and 4 hours post-dose 
● Assessment of AEs. 
● Injection site reaction assessment at 30 min, 1 hour, 2 hours and 4 hours post-dose 
Subjects will be instructed to return to the study site on Day 112 (±5d). 
6.1.8 Day 112 (±5) 
The following assessments/procedures will be performed on Day 112 (±5d): 
● 12-lead ECG 
● Vital signs 
● Clinical laboratory tests (biochemistry, hematology, coagulation and urinalysis) 
● Blood collection for anti- Aβ and anti-MultiTEP antibodies  
● Review of concomitant medications 
● Assessment of AEs. 
Subjects will be instructed to return to the study site on Day 140 (±5d). 
6.1.9 Day 140 (±5) 
The following assessments/procedures will be performed on Day 140 (±5d): 
● 12-lead ECG 
● Vital signs 
● Blood collection for anti-Aβ and anti-MultiTEP antibodies  
● Review of concomitant medications 
● Assessment of AEs. 
Subjects will be instructed to return to the study site on Day 154 (±7d). 
6.1.10 Day 154 (±7) – End of Study / Early Termination (EOS/ET) 
The following assessments/procedures will be performed on Day 154 (±7d): 
● Weight 
● Complete physical examination 
● 12-lead ECG 
● Vital signs 

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● Clinical laboratory tests (biochemistry, hematology, coagulation and urinalysis) and 
pregnancy test (females) 
● Blood collection for anti-Aβ and anti-MultiTEP antibodies  
● MRI examination 
● Review of concomitant medications 
● Assessment of AEs. 
Should any subject withdraw or be withdrawn from the study, all the end-of-study evaluations 
scheduled for Day 154 (±7d) should be performed at the time of discontinuation, if deemed safe by the 
Investigator. 
6.1.11 Unscheduled Visits 
Unscheduled visits are allowed by investigator discretion for safety reasons, administrative reasons 
(e.g., re-supply of study medication or diaries), or to address subject concerns or questions about the 
study. The following procedures and evaluations may be conducted at this visit as per investigator 
discretion if needed: 
● Collection of concomitant medication information since the last visit 
● Physical examination 
● Weight 
● Recording of vital signs 
● 12-lead ECG 
● Clinical laboratory tests (biochemistry, hematology, coagulation and urinalysis) and 
pregnancy test (females) 
● Blood collection for anti-Aβ and anti-MultiTEP antibodies  
● MRI examination 
● Assessment of AEs. 
6.1.12 Phone Follow-Up Days 2, 29 (±2) and 99 (±5)  
Subjects will be contacted via phone call, internet/web, or other acceptable means of communication 
and will be questioned for assessment of adverse events the next day after each IP dosing in the trial. 

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6.2 
Study Procedures 
6.2.1 Demographics, Medical/Surgical and Prior/Concomitant Medication History 
Demographics will include date of birth, sex, ethnicity, and race as described by the subject. The 
medical/surgical history of the subject will be obtained at the Screening visit(s). Specific information 
will be recorded on the CRF relating to any prior or existing medical conditions/surgical procedures 
involving the following: infectious diseases (including viral infections, such as hepatitis or HIV), 
allergies, metabolic/endocrine/nutritional, hematopoietic, musculoskeletal, dermatologic, head, ears, 
eyes, nose, and throat (HEENT), breasts, respirator cardiovascular, gastrointestinal /hepatic, 
genitourinary/renal, neurological and psychiatric/psychosocial.  
History of prior and concomitant medications will be recorded in the CRF at the Screening visit. 
6.2.2 Body Height and Weight 
Body height (centimeters) and weight (kilograms) will be measured. Height will be measured at the 
Screening only. The subject will wear lightweight clothing and no shoes during weighing. 
The subject’s BMI will be calculated at screening using metric units and rounded to one decimal place 
according to the following formula: BMI = weight (kg)/height (m)2 
6.2.3 Physical Examinations 
Physical examinations will be performed at the time points specified in the schedule of assessments 
(Table 1). 
Complete physical examination will include, at a minimum, examination of the following body 
systems: General Appearance, HEENT, Neck (incl Thyroid & Nodes), Cardiovascular, Respiratory, 
Gastrointestinal, Renal, Neurological, Musculoskeletal, Skin, Other and the neurological system 
examination (assessment of mental status, cranial nerves, visual fields, sensory, motor, gait, primitive 
reflexes and tendon reflexes). Symptom-driven physical and/or neurological examinations may be 
done at any time point during the trial at the investigator’s discretion. 
Any significant changes from baseline in physical examination findings will be recorded as AEs. 
6.2.4 Vital Sign Measurements 
Vital signs (blood pressure, heart rate, respiratory rate, and body temperature [°C]) will be measured at 
the time points specified in the schedule of assessments (Table 1). 

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Blood pressure and heart rate will be measured after the subject has been supine for at least 5 minutes. 
Pre-dose vitals will be performed within 15 minutes before dosing. Post dose vitals can be performed 
within ± 15 minutes from the scheduled time points. When vital signs are scheduled at the same time 
point as blood sample collection, vital signs will be measured first. Any significant deviations from 
Baseline vital signs, which are deemed CS in the opinion of the Investigator, will be recorded as an AE. 
6.2.5 12-Lead Electrocardiograms 
The ECG will be measured after the subject has rested in a supine position for at least 5 min at the time 
points specified in the schedule of assessments (Table 1). Pre-dose ECG will be performed within 30 
minutes before dosing. Post dose ECG can be performed within ± 30 minutes from the scheduled time 
points. Whether measurement is performed, date performed, results, and findings will be recorded in 
the eCRF. When a blood collection is scheduled concomitantly with an ECG, the ECG should be taken 
prior to the blood collection. 
Each 12-lead ECG will be evaluated by an appropriately qualified physician at the study site. ECG data 
will be evaluated using the following categories: 
• Normal 
• Abnormal, not clinically significant (NCS) 
• Abnormal, clinically significant (CS) 
Post-dosing (from first dose) abnormalities of clinical significance will be reported as AEs. Repeat 
measurements will be performed if needed. All ECG source documentation will be retained at the site. 
6.2.6 Clinical Laboratory Tests 
Subjects will be required to fast for at least 4 hours before the clinical laboratory tests. Blood for 
laboratory tests will be taken at specific timepoints detailed in the schedule of assessments (Table 1). 
The Investigator can order lab panels that contain additional laboratory tests beyond those listed below. 
The clinical laboratory tests listed below will be recorded in CRF. 
All clinical laboratory assays will be performed according to the laboratory’s normal procedures. 
Reference ranges supplied by the laboratory are used to assess the clinical laboratory data for clinical 
significance and out-of-range pathological changes. The following laboratory evaluations will be 
performed: 
• Hematology: Haematocrit, Haemoglobin, Mean Cell Haemoglobin (MCH), Mean Cell 
Volume (MCV), Mean Corpuscular Haemoglobin Concentration (MCHC), MPV, Platelets, 

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Red Cell Count, Red Cell Distrib. Width. White Cell Count, Basophils, Eosinophils, 
Lymphocytes, Monocytes and Neutrophils  
• Biochemistry: Albumin, ALP, ALT, Anion Gap, AST, Bicarbonate, Bilirubin (total, direct & 
indirect), Calcium (adjusted), Calcium, Chloride,  Creatinine, eGFR, GGT, Globulin, LD, 
Phosphorus, Potassium, Protein, Sodium, Urea and Uric Acid  
• Coagulation: Prothrombin time, activated partial thromboplastin time and International 
Normalized Ratio (INR). 
• Urinalysis: Bilirubin, Blood, Glucose, Ketones, Protein, Specific Gravity, leucocyte esterase, 
pH, nitrite and urobilinogen. Microscopy examination (identification of cells, casts and 
crystals) may be performed if the urinalysis is abnormal and /or at discretion of Investigator. 
• Serology:  
o Hepatitis Screen: HBsAg, and HCV Ab tests will be performed only at Screening.  
o HIV Screen: Subjects will have blood tested for HIV 1/ HIV 2 at Screening. Only those 
subjects negative for the presence of antibodies will be allowed to enroll in the study. 
The results of the HIV Ab testing will be retained by the study site in a confidential 
manner. 
• Pregnancy test will be performed for all females at timepoints detailed in the schedule of 
assessments (Table 1). Serum pregnancy test will be done at Screening, and urine tests at 
subsequent timepoints. 
• Follicle stimulating hormone (FSH) test will be performed on postmenopausal females. 
• Drugs of Abuse/Alcohol: Alcohol breath test (as per site procedures), Urine drug test 
including: Methamphetamine, Opiates, Cocaine, THC, Phencyclindine, Benzodiazepines, 
Barbiturates, Methadone, TCAs and Amphetamine 
The Investigator or medically qualified designee must interpret the laboratory findings (i.e., determine 
the clinical significance of any abnormal values indicated) and sign and date the laboratory report. 
Any clinically relevant changes requiring treatment during the study must be reported as an adverse 
event. 
Only authorized and qualified persons may collect biological samples from the subject. The date and 
time of sample collection is to be recorded. Sample collection and handling procedures for laboratory 
assessments will be performed according to the procedures designated by the clinical site or 
laboratory. 

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6.2.7 MRI Examination 
Magnetic resonance imaging (MRI) will be used to detect any evidence of brain impairment. The 
MRI Scan will be performed at the Screening visit and at EOS or ET (Table 1). Further details on the 
technique, procedures and analyses will be provided separately. 
6.2.8 Local Tolerability Assessment 
Assessment of injection site should be performed at 30 min, 1 hour, 2 hours and 4 hours post-dose 
with a window period of ±15 minutes, and more frequently, if deemed necessary by the investigator. 
Infusion site reactions will be recorded as AEs. If any visible adverse reaction is observed, a 
photograph of the same will be captured. Assessments of injection site on other days will be performed 
in subjects who have unresolved injection site AEs. 
6.2.9 Documentation of Concomitant Medications 
All medications and therapy will be recorded beginning from 28 days before administration of study 
drug through follow-up. Any therapy administered prior to informed consent will be recorded as prior 
medication and medication ongoing at the time of signing the ICF or administered after informed 
consent will be recorded as concomitant medication. Relevant information (i.e., name of medication, 
dose, unit, frequency of administration, dates, and reasons for use) will be recorded in the source 
documents and in the eCRF. All changes in medication will be noted. If the reason for medication use 
meets the definition of an AE, the AE will be recorded on the appropriate page of the eCRF and in 
the source documents for that subject. 
List of prohibited and restricted medications prior to/ during this study is provided below: 
6.2.10 Prohibited Medications 
• Concurrent use of warfarin or other coumarin derivatives or a combination of acetylsalicylic 
acid and an anti-platelet agent (e.g., clopidogrel) are prohibited. Low dose of acetylsalicylic 
acid (≤81 mg per day) is allowed. 
• The use of immunomodulatory or growth stimulating factors such as systemic corticosteroids, 
cyclosporine, methotrexate, azathioprine, anti-CD25 antibody, GM-CSF, C-CSF, interferon 
(IFN), or interleukin-2 (IL-2) within 30 days prior to study entry (Section 14.1). 
• CNS-active drugs are generally prohibited. 
• Parenteral immunoglobulin preparations, blood products, plasma derivatives are prohibited. 

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• Any tau or amyloid-beta immunotherapy (vaccine, antibody) is prohibited within 1 year prior 
to Screening. 
6.2.11 Restricted Treatments and Medications 
• Consumption of alcohol, nicotine, caffeine and xanthine containing products are restricted for 
24 hours prior to each dosing. 
• Participants are restricted from strenuous exercise for 24 hours prior to any blood collection for 
clinical laboratory testing. 
• Vaccination (e.g., flu shot or COVID-19). 
o Postpone the injection of IP to allow a 2-week lag after other vaccination, but no more 
than 4 weeks of the scheduled injection date.  
o Other anti-coagulants (non-coumarin related) are restricted for the duration of the 
study. 
o When appropriate, review the International normalized ratio (INR) level and adjust 
dosage according to the prescribing information. 
• Sedative hypnotics are restricted for the duration of the study. 
o Will be allowed if, in the opinion of the Investigator, use does not affect cognition AND 
participants are currently treated with a stable regimen (defined as no change to the 
participant’s medication intake pattern rather than adherence to the prescribed 
regimen) for at least 12 weeks prior to randomization. 
o If initiated during study, maintain a stable regimen (including in the 6 weeks prior to 
clinical evaluation). 
o If taken as needed, these must be held for 72 hours prior to cognitive assessments, MRI 
is performed (as applicable). 
• Selective serotonin re-uptake inhibitors (SSRIs, e.g., paroxetine, sertraline, citalopram, 
escitalopram), serotonin norepinephrine re- uptake inhibitors (SNRIs, e.g., venlafaxine, 
duloxetine), atypical antipsychotics, and low dose tricyclic antidepressants are restricted for 
the duration of the study.. 
o Will be allowed if, in the opinion of the Investigator, use does not represent an 
exclusionary condition AND provided participants are currently treated with a stable 

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regimen for at least 12 weeks prior to randomization. If initiated during study, 
maintain a stable regimen in the 6 weeks prior to clinical evaluation.

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7. 
Assessment and Management of Adverse Events 
7.1 
Adverse Events 
An AE is defined (per International Council for Harmonisation [ICH] of Technical Requirements for 
Registration of Pharmaceuticals for Human Use E2A, ICH, E2A) as any untoward medical occurrence 
in a patient or clinical investigation subject administered a pharmaceutical product and which does 
not necessarily have to have a causal relationship with this treatment. 
An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory 
finding, for example) symptom, or disease associated with the use of a medicinal (investigational) 
product, whether or not related to the medicinal (investigational) product. 
A TEAE is defined as an AE with an onset that occurred after receiving study drug through study 
discharge, or a continuing AE diagnosed before the date of first dose of study drug, which increased 
in severity after the start of dosing. 
An adverse reaction is any AE caused by a drug. Adverse reactions are a subset of all suspected 
adverse reactions for which there are reasons to conclude that the drug caused the event. 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the study drug 
caused the AE. For the purposes of investigational new drug safety reporting, “reasonable possibility” 
means that there is evidence to suggest a causal relationship between the study drug and the AE. A 
suspected adverse reaction implies a lesser degree of certainty about causality than adverse reaction, 
which means any AE caused by a study drug. 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the Investigator’s 
Brochure or at the specificity or severity that has been observed with the study drug being tested; or, 
if an Investigator’s Brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application. "Unexpected," 
as used in this definition, also refers to AEs or suspected adverse reactions that are mentioned in the 
Investigator’s Brochure as occurring with a class of drugs or as anticipated from the pharmacological 
properties of the drug but are not specifically mentioned as occurring with the particular drug under 
investigation. 
Any pre-existing conditions or signs and/or symptoms present in a participant prior to the start of the 
study (e.g., before informed consent) should be recorded as Medical/Surgical History. Any change in 
health status, which is reported after informed consent and up to the last study visit will be recorded 

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as an AE. At each study visit, the Investigator will assess whether any subjective AEs have occurred. 
A neutral question such as, “How have you been feeling since your last visit?” will be asked. Subjects 
may report AEs that occur at any other time during the study. 
All subjects experiencing AEs, whether considered associated with the use of the study drug or not, 
must be monitored until the symptoms subside and any clinically relevant changes in laboratory 
values have returned to Baseline or until there is a satisfactory explanation for the changes observed. 
All AEs will be documented on the AE page of the eCRF, whether or not the Investigator concludes 
the event to be related to the study drug. The event term, start and stop date, and severity will be 
documented, along with the Investigator’s opinion of the causal relationship between the event and 
study drug administration (certain, probable/likely, possible, unlikely, not related, unknown). All AEs 
will be followed until resolution or until the Investigator judges that further follow-up is not necessary. 
Each AE will be graded for severity by the Investigator using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (CTCAE) (Version 5.0). The severity of each AE and SAE 
recorded in the eCRF should be assigned to one the following criteria: 
• Mild: The experience does not cause substantial discomfort, symptoms are well tolerated, and 
do not interrupt or hinder the subject’s daily activities; the experience resolves spontaneously 
and no treatment is required beyond administration of nonprescription medication. 
• Moderate: The experience causes some discomfort, symptoms interfere with but do not 
interrupt the subject’s daily activities; the experience may require treatment with prescription 
medication. 
• Severe: The experience substantially hinders or interrupts the subject’s daily activities; the 
subject may be incapacitated and require prolonged treatment with prescription medication. 
• Life-Threatening or Disabling: An event that poses an immediate risk of death from the 
reaction as it occurred. 
• Death: The event resulted in death. 
It is the Investigator’s responsibility to assess the relationship between the study drug and the AE to 
determine if a reasonable causality exists. The degree of “relatedness” of the AE to the study drug 
will be described using the following scale: 
 

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Certain: 
● 
Event or laboratory test abnormality, with plausible time 
relationship to drug intake 
● 
Cannot be explained by disease or other drugs 
● 
Response to withdrawal plausible (pharmacologically, 
pathologically) 
● 
Event definitive pharmacologically or phenomenologically (i.e., an 
objective and specific medical disorder or a recognized 
pharmacological phenomenon) 
● 
Re-challenge satisfactory, if necessary 
Probable/Likely: 
● 
Event or laboratory test abnormality, with reasonable time 
relationship to drug intake 
● 
Unlikely to be attributed to disease or other drugs 
● 
Response to withdrawal clinically reasonable 
● 
Re-challenge not required 
Possible: 
● 
Event or laboratory test abnormality, with reasonable time 
relationship to drug intake 
● 
Could also be explained by disease or other drugs 
● 
Information on drug withdrawal may be lacking or unclear 
Unlikely: 
● 
Event or laboratory test abnormality, with a time to drug intake that 
makes a relationship improbable (but not impossible) 
● 
Disease or other drugs provide plausible explanations 
Not Related: 
● 
The event is either a predose event or is definitely due to causes 
separate from the administration of the study drug, i.e., 
− documented pre-existing condition 
− technical and manual procedural problems 
− concomitant medication 
− subject’s clinical state 
Unknown: 
● 
The event does not meet any of the above criteria, because of 
conflicting data and/or dubious or insufficient/poor evidence the 
event is not judged as related or not related 

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The type of follow-up (telephone or on-site visit) will depend on the severity of the event at study 
completion. 
Action Taken 
An AE might lead to treatment of the event or changes in regard to the study drug. The following 
actions might be taken: 
• None 
• Change in the study drug administration: 
o Drug withdrawn 
o Drug interrupted 
o Dose reduced 
o Dose increased 
• Drug treatment required (a medication was prescribed or changed; this will be recorded on the 
Concomitant Medication section of the eCRF) 
• Non-drug treatment required (a non-drug treatment was prescribed or changed) 
• Hospitalization/prolongation of hospitalization 
• Diagnostic or clinical test(s) conducted 
• Subject discontinued from the study 
Outcome Categories 
An AE can have one of the following outcomes: 
• Recovered without sequelae 
• Recovered with sequelae 
• Ongoing 
• Unknown 
• Fatal 
Severity of all adverse events will be evaluated by the Investigator based on the National Cancer 
Institute’s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 106 and will be 
coded to preferred term, higher level term, and system organ class using the Medical Dictionary for 
Regulatory Activities (MedDRA). 
 

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7.2 
Serious Adverse Events 
An SAE is defined as any untoward medical occurrence that at any dose: 
• Results in death; 
• Is life threatening (i.e., the subject was at risk of death from the event. “Life threatening” in the 
definition of “serious” refers to an event in which the subject was at immediate risk of death at 
the time of the event; it does not refer to an event that hypothetically might have caused death if 
it were more severe; 
• Requires inpatient hospitalization or prolongation of existing hospitalization; 
• Results in persistent or significant disability/incapacity; 
• Results in congenital anomaly/birth defect; 
• Important medical events that do not result in death, are not life threatening or do not require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, 
they may jeopardize the subject and may require medical or surgical intervention to prevent one 
of the outcomes listed in this definition. 
If an SAE occurs, based on the Investigator’s judgment, appropriate therapy will be administered. 
Subjects will then be monitored closely as appropriate. 
7.3 
Additional Points to Consider for Adverse Events 
Diagnoses versus signs and symptoms: 
• Each AE will be recorded to represent a single diagnosis. Accompanying signs (including 
abnormal laboratory values or ECG findings) or symptoms will NOT be recorded as additional 
AEs. If a diagnosis is unknown, sign(s) or symptom(s) will be recorded as an AE(s). 
Laboratory values and ECG findings: 
• Changes in laboratory values or ECG parameters are only considered to be AEs if they are judged 
to be clinically significant (i.e., if some action or intervention is required or if the Investigator 
judges the change to be beyond the range of normal physiological fluctuation). 
• If abnormal laboratory values or ECG findings are the result of pathology for which there is an 
overall diagnosis (e.g., increased creatinine in renal failure), only the diagnosis will be reported 
as an AE. 
 
 

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Pre-existing conditions: 
• Pre-existing conditions (present before the start of the AE collection period) are considered 
concurrent medical conditions and will NOT be recorded as AEs. However, if the subject 
experiences a worsening or complication of such a concurrent condition, the worsening or 
complication will be recorded as an AE. The Investigator will ensure that the AE term recorded 
captures the change in the condition (e.g., “worsening of…”). 
Preplanned surgeries or procedures: 
• Preplanned procedures (surgeries or therapies) that were scheduled prior to the start of AE 
collection are not considered AEs. However, if a preplanned procedure is performed early (e.g., 
as an emergency) due to a worsening of the pre-existing condition, the worsening of the 
condition will be captured as an AE. 
Elective surgeries or procedures: 
• Elective procedures preplanned or performed where there is no change in the subject’s medical 
condition will not be recorded as AEs but will be documented in the subject’s source documents. 
Overdose: If a subject has received more than the required amount of study medication inadvertently, 
this will be considered an overdose. 
• Cases of study drug overdose without manifested side effects are NOT considered AEs. 
• Any instance of symptomatic overdose (suspected or confirmed) must be considered as a SAE 
and reported accordingly. 
7.4 
Local Tolerability Assessment 
Injection site reactions will be recorded in the eCRF separately to AEs and assessed as per the FDA 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials (September 2007) 
 Table for Clinical Abnormalities 
 
Local Reaction to 
Injectable Product 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life 
Threatening (Grade 4) 
Pain 
Does not interfere 
with activity 
Repeated use of non- 
narcotic pain reliever 
> 24 hours or 
interferes with 
activity 
Any use of 
narcotic pain 
reliever or 
prevents daily 
activity 
Emergency room (ER) 
visit or hospitalization 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant 
discomfort at rest 
ER visit or 
hospitalization 

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Erythema/Redness * 
2.5 - 5 cm 
5.1 - 10 cm 
> 10 cm 
Necrosis or exfoliative 
dermatitis 
Induration/Swelling** 
2.5 - 5 cm and does 
not interfere with 
activity 
5.1 - 10 em or 
interferes with 
activity 
> 10 cm or 
prevents daily 
activity 
Necrosis 
* 
In addition to grading the measured local reaction at the greatest single diameter, the measurement 
should be recorded as a continuous variable. 
** 
Induration/Swelling should be evaluated and graded using the functional scale as well as the actual 
measurement. 
 
7.5 
Reporting of Serious Adverse Events 
Serious AEs require immediate reporting to the Sponsor (or delegate) and the Medical Monitor within 
24 hours of the Investigator’s knowledge of the event, whether or not the Investigator believes that the 
experience is related to study drug. 
An SAE Form must be completed, signed by the Investigator, and include at a minimum: the event 
term(s), a short description of the AE, the reason why the AE is categorized as serious, the 
Investigator’s current opinion of the relationship between the experience and the study drug (causality 
assessment), as well as the subject’s identification number, sex, age, and relevant medical history. 
Additional information, as appropriate, can be sent to the Sponsor and Medical Monitor when it 
becomes available (e.g., copies of relevant subject records, autopsy reports, and other documents). A 
corresponding AE eCRF must also be completed. 
The Sponsor is responsible for notifying the HREC in writing of any SAE. All SAEs are to be 
documented in the eCRF with the date of onset and resolution, frequency, determination of 
seriousness, severity, action taken, outcome, and relationship to study drug. 
Any SAE, including death, occurring while the subject is receiving study drug irrespective of the 
Investigator’s opinion regarding study drug relationship, will be reported. Within 24 hours, the 
Investigator must complete, sign, and date the SAE pages, verify the accuracy of the information 
recorded on the SAE pages with the corresponding source documents, and send a copy by fax or email 
to the Sponsor (or delegate) and Medical Monitor. 
Any SAEs that occur from the informed consent through the participant’s last visit/ contact that come 
to the attention of the Investigator, and are thought to be related to study drug, will be reported to the 
Sponsor (or delegate) and the Medical Monitor. 
7.6 
Follow-up of Serious Adverse Events 
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All follow-up information on SAEs is to be reported within 24 hours of receipt by the Investigator in 
the manner described previously. 
All fatal or life-threatening Suspected Unexpected Serious Adverse Reactions (SUSAR) will 
immediately be reported by the investigator to the sponsor, with a follow-up detailed report when this 
information is not contained in the initial report; the sponsor will report the event to the TGA 
immediately, but no later than seven calendar days after being made aware of the event, with any 
follow up information submitted to the TGA within a further eight calendar days.  
All other SUSARs should be reported by the sponsor to the TGA no later than 15 calendar days after 
being made aware of the event.  
All significant safety issues (SSIs) requiring implementation of urgent safety measures (USMs) 
should be reported by the investigator to the sponsor, and then the sponsor will be report to the TGA 
and HREC within 24 hours (where possible) and in any case, no later than 72 hours of the measure 
being taken. SSIs that arise from analysis of overseas reports (relating to a clinical trial in Australia) 
should be reported to the TGA under the same timeframe.  
Action with respect to safety that has been taken by an overseas regulatory authority (relevant to an 
ongoing clinical trial in Australia) must be reported to the TGA by the sponsor without undue delay 
and no later than 72 hours of the sponsor becoming aware of the action.  
All other SSIs (e.g., suspension of the trial, early termination of trial for safety reasons) must be 
reported by the sponsor to the TGA without undue delay and no later than 15 calendar days of the 
sponsor becoming aware of the issue or suspension or early termination.  
Sponsor will prepare an expedited report for the TGA based on information provided by Investigator, 
and copies will be distributed to the Investigator. 
A register of all event reports assessed and classified is to be retained by the Investigator and reported 
to the trial sponsor annually and the HREC.  
7.7 
Subject Deaths 
All deaths of subjects, regardless of cause, occurring within 30 days after subject termination from 
the study, and which are known to the Investigator will be reported on the appropriate page of the 
eCRF. Documentation of the subject’s cause of death and a copy of the autopsy report, if any, will 
also be provided. Pharmacovigilance (contact details provided in Section 7.4) must be notified 
immediately by telephone of all subject deaths. Fax/email modes of communication must be utilized 

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in case of any difficulty with telephone lines; written follow-up must be received within 3 working 
days of initial notification. 
Death will not be reported as an SAE, but as a clinical outcome. The cause of death on a source 
document, such as the death certificate or autopsy report, will be used as the event term for the SAE. 
For subjects in which concurrent AEs or SAEs are present at the time of death, such AEs or SAEs 
will be marked as resolved with the date of resolution entered as the date of death. 
Only the SAE that caused the subject’s death will be marked with an outcome of “Fatal.”

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8. 
Data Analysis and Statistical Methods 
All data collected will be presented in data listings. Data from subjects excluded from an analysis 
population will be presented in the data listings, but not included in the calculation of summary 
statistics. For categorical variables, frequencies and percentages will be presented. Continuous 
variables will be summarized using descriptive statistics (number of subjects, mean, median, standard 
deviation [SD], minimum, and maximum). Demographic and baseline characteristics will be 
summarized overall for all subjects. The number of subjects who enroll in the study and the number 
and percentage of subjects who discontinue and reasons for discontinuation will be presented. Details 
of all statistical analyses will be described in a separate statistical analysis plan (SAP). 
8.1 
Study outcome measures 
Primary Outcome Measures 
● Number of participants with Treatment-Emergent Adverse Events (TEAEs) or Serious 
Adverse Events (SAEs) [Time frame: Baseline up to Week 22]. 
Secondary Outcome Measures 
● Number 
of 
participants 
with 
clinically 
significant 
changes 
in 
vital 
signs 
[Time Frame: Baseline up to Week 22]. 
● Number of participants with clinically significant changes in ECG results 
[Time Frame: Baseline up to Week 22]. 
● Number of participants with clinically significant changes in laboratory test 
[Time Frame: Baseline up to Week 22]. 
● Number of participants with clinically significant changes in physical examinations 
[Time frame: Screening up to Week 22]. 
● Immunological Outcomes: 
- Serum anti-Aβ and anti-MultiTEP antibodies concentrations [Time Frame: Baseline up 
to Week 22]. 
8.2 
Adverse Events 
Adverse events will be summarized by system organ class (SOC) and preferred term. 
Summary tables for TEAEs will include numbers and percentages of subjects experiencing TEAEs 
by system organ class and preferred term. If a subject has more than 1 TEAE that codes to the same 
preferred term, the subject will be counted only once for that preferred term. Similarly, if a subject 

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has more than 1 TEAE within a system organ class category, the subject will be counted only once in 
that system organ class category. The following summary tables will be included for each treatment 
and overall: summary of TEAEs, relationship of TEAEs to study drug, severity of TEAEs, AEs 
leading to study drug discontinuation, and SAEs. Adverse events will be listed by subject and 
tabulated for each cohort as well as pooled across cohorts for each dose level of the components. 
Different pooled groups will be detailed in the study SAP. 
Data listings will be provided for all AEs, AEs leading to study drug discontinuation, and SAEs. 
8.3 
Clinical Laboratory Tests 
Clinical laboratory results and change from before dosing to the end of the study will be summarized 
for each treatment using descriptive statistics (sample size, mean, SD, minimum, median, and 
maximum) at each scheduled time point. Shift tables will be provided for hematology, serum chemistry, 
coagulation, and urinalysis values. Clinical laboratory values that are outside of the reference ranges 
will be flagged in the data listings as clinically significant (CS) or not clinically significant (NCS). All 
clinical laboratory data will be presented in data listings. 
8.4 
Vital Sign Measurements 
Descriptive statistics (number of subjects, mean, SD, CV, median, minimum, and maximum) of each 
vital sign measurement will be tabulated for each treatment. Abnormal results of vital sign 
measurements will be flagged in the data listings as CS or NCS. All vital sign data will be listed in the 
data listings. 
8.5 
Safety 12-Lead Electrocardiograms 
Descriptive statistics (number of subjects, mean, SD, CV, median, minimum, and maximum) of each 
safety 12-lead ECG measurement will be tabulated for each treatment. Abnormal results of 12-lead ECG 
measurements will be flagged in the data listings as CS or NCS. All safety 12-lead ECG data will be 
presented in the data listings. 
8.6 
Other Safety Data 
The physical examination findings and concomitant medications will be presented in the data listings. 
8.7 
Sample Size 
The sample size of 16 subjects has no formal statistical basis and was chosen pragmatically based on 
clinical considerations to provide sufficient data for the safety objectives of this study.

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9. 
Study Compliance 
The Investigator agrees that the study will be conducted according to the principles of the ICH E6 (R2) 
and this Clinical Protocol. The Investigator will conduct all aspects of this study in accordance with AU 
TGA regulations, the ICH E6 (R2) GCP, and applicable local, state, and federal laws. 
9.1 
Modification to Protocol 
The Sponsor will document all material changes to the protocol in the form of an amendment. Each 
amendment will be signed by the authorized Sponsor representative and the Investigator and approved 
by the HREC before implementation. 
9.2 
Protocol Deviations 
No deviations to the protocol are permitted, except in instances when an emergency occurs that requires 
a departure from the protocol for participant safety. The nature and reasons for all protocol deviations 
will be recorded and reported at the end of the study in the CSR. 
A minor protocol deviation is any protocol deviation that does not significantly impact on the 
participants’ safety or compromise the integrity of study data.  
A major protocol deviation is a protocol deviation that may significantly impact the completeness, 
accuracy, and/or reliability of the key study data or that may significantly affect a participant’s rights, 
safety, or wellbeing. Key study data is any data that relates to primary and key secondary endpoints or 
activities critical to ensure participant safety, privacy and rights. 
Should a major protocol deviation occur, the Sponsor must be informed as soon as possible. Reporting 
of major protocol deviations to the HREC and in accordance with applicable regulatory authority 
mandates is a PI responsibility.  
All protocol deviations and the reasons for the deviations will be documented by the PI or designated 
staff.  

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10. Data Handling, Management and Records Keeping 
10.1 
Data Management 
The full details of data management activities including procedures for handling of eCRF, database set-
up and management, data entry and verification, data validation, quality control of database, and 
documentation of the performed activities will be provided in the Data Management Plan. The database, 
data entry screens, and program will be designed in accordance with the clinical protocol. 
AEs, medical history, and concurrent conditions will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). Prior and concomitant medications will be classified according to the 
WHO Drug dictionary. 
10.2 
Case Report Forms 
Completed eCRFs are required for each subject enrolled in the study. The Investigator retains full 
responsibility for the accuracy and authenticity of all data entered into the eCRF. The completed dataset 
and their associated files are the sole property of the Sponsor and should not be made available in any 
form to third parties, except for authorized business representatives or appropriate governmental health 
or regulatory authorities, without written permission of the Sponsor.  
Clinical data will be entered into eCRFs directly from the source documents. All data must be entered 
in English. The eCRF will include password protection and internal quality checks, such as automatic 
range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Authorized trial site 
personnel designated by the Investigator will enter data into eCRF. Appropriate training and security 
measures will be completed with the Investigator and all authorized trial site personnel prior to the trial 
being initiated and any data being entered into the system for any study subject.  
The eCRFs should always reflect the latest observations on the subjects participating in the trial. 
Therefore, the eCRFs should be completed as soon as possible during or after the subject’s visit. To 
avoid inter-observer variability, every effort should be made to ensure that the same individual who 
made the initial baseline determinations completes all safety evaluations. The Investigator must attest 
that all data entries in the eCRFs are accurate and correct. If some assessments are not done, or if certain 
information is not available, not applicable or unknown, the Investigator should indicate this in the 
eCRF. The Investigator will be required to electronically sign off the clinical data. 
 

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10.2.1 Query Process 
The monitor will review the eCRFs and evaluate them for completeness and consistency. Each eCRF 
should be compared with the respective source documents to ensure that there are no discrepancies 
between all data. All entries, corrections, and alterations are to be made by the Investigator or designee. 
The monitor cannot enter data in the eCRFs. Once clinical data have been submitted to the central server 
via the eCRF, corrections to the data fields will be audit trailed, meaning that the reason for change, the 
name of the person who made the change, together with time and date will be logged. Roles and rights 
of the site personnel responsible for entering clinical data into the eCRF will be determined in advance. 
If additional corrections are needed, the responsible monitor or data manager will raise a query in the 
electronic data capture application.  
The appropriate investigational personnel will answer the queries in the eCRF. This will be audit trailed 
by the electronic data capture application meaning that the name of investigational personnel, time, and 
date is logged. 
10.2.2 Source Documents 
All information collected during the study will be recorded in source documents. Direct entries on the 
eCRFs are not allowed. The eCRF is essentially considered a data entry form and should not constitute 
the original (or source) medical records unless otherwise specified. Source documents are all documents 
used by the Investigator or clinical site that relate to the subject’s medical history, that verifies the 
existence of the subject, the inclusion and exclusion criteria, and all records covering the subject’s 
participation in the trial. They include, but are not limited to, laboratory notes, memoranda, material 
dispensing records, subject files, any electronic record etc. 
The Investigator must provide source documents for each subject who signed the Subject Informed 
Consent for inspection by the monitor at each monitoring visit. All supportive documentation, such as 
laboratory or medical site records, should be clearly identified with Subject Number. In case subject 
source document are to be shared with Sponsor or its designee, any personal information, including 
subject name, should be removed or rendered illegible to preserve individual confidentiality. 
10.2.3 User ID 
eCRF records will be automatically appended with the identification of the creator, by means of their 
unique User ID. Specified records will be electronically signed by the Investigator to document his/her 
review of the data and acknowledgement that the data are accurate. This will be facilitated by means of 

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the Investigator’s unique User ID and password; date and time stamps will be added automatically at 
time of electronic signature. If an entry in an eCRF requires change, the correction should be made in 
accordance with the relevant software procedures. 
10.2.4 Audit trail 
All changes will be fully recorded in a protected audit trail, and a reason for the change will be required. 
Once all data has been entered, verified, and validated, the database will be locked. 
10.2.5 Management of Investigator Site File 
Investigator Site File (ISF) will be managed and maintained by the Investigator. This will be the 
responsibility of the Investigator to keep the file updated and make the file available for review to study 
monitor, Sponsor designee, auditor or regulatory representative. 
10.2.6 Records Retention at the Study Site 
The Investigator agrees to keep the records and those documents that include (but are not limited to) the 
study-specific documents, identification log of all participating subjects, medical records, source 
worksheets, all original signed and dated ICFs, subject authorization forms regarding the use of personal 
health information (if separate from the ICFs), copies of all eCRFs, query responses, and detailed 
records of drug disposition, to enable evaluations or audits from regulatory authorities, the Sponsor or 
its designees. All study records will be stored by the Sponsor for 15 years after the end of the study.  
 
Refer to the Clinical Trials Research Agreement for the Sponsor’s requirements on record retention. 
The Investigator should contact and receive written approval from the Sponsor before disposing of any 
such documents. 
 
 
 

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11. Quality Control and Quality Assurance 
Sponsor or its designee will perform the quality assurance and quality control activities of this study; 
however, responsibility for the accuracy, completeness, and reliability of the study data presented to 
Sponsor lies with the Investigator generating the data. 
Before study initiation, Sponsor or designee will explain the protocol, IB, and eCRFs to the Investigator 
and study site personnel. In addition, the monitor will be available to explain applicable regulations and 
to answer any questions regarding the conduct of the study. 
11.1 
Good Clinical Practice 
This study will be carried out in accordance with Good Clinical Practice (GCP) as required by the 
following: 
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46; 21 CFR Parts 50, 54, 56, 312 and 320) 
• ICH E6 (R2) 
11.2 
Study Monitoring 
Monitoring visits to the study site will be made periodically during the study to ensure that all aspects 
of the protocol are followed. Source documents will be reviewed for verification of data recorded in the 
eCRFs. Source documents are defined as original documents, data, and records. The Investigator and 
clinical site guarantee access to source documents by the Sponsor or its designee and by the HREC. 
All aspects of the study and its documentation will be subject to review by the Sponsor or designee, 
including but not limited to the ISF, study drug, subject medical records, informed consent 
documentation, documentation of subject authorization to use personal health information (if separate 
from the ICFs), and review of eCRFs and associated source documents. It is important that the 
Investigator and other study personnel are available during the monitoring visits and that sufficient time 
is devoted to the process. 
The details of the scope and frequency of monitoring will be provided in the Monitoring Plan. 
11.3 
Inspection of Records 
The Investigator involved in the study will permit study-related monitoring, audits, HREC review, and 
regulatory inspection(s). In the event of an audit, the Investigator agrees to allow the Sponsor, 
representatives of the Sponsor, the competent authority, or other regulatory agency access to all study 

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records. The Investigator will promptly notify the Sponsor of any audits scheduled by any regulatory 
authorities and promptly forward copies of any audit reports received to the Sponsor. 
11.4 
Quality Control 
The clinical site shall implement and maintain quality control and quality assurance procedures with 
written SOPs to ensure that the trial is being conducted and data are being generated, documented and 
reported in compliance with the protocol, GCP and applicable regulations. The Investigator may not 
deviate from the protocol without a formal protocol amendment having been implemented and approved 
by an appropriate HREC, except when necessary to eliminate immediate hazards to the subject or when 
the change involves only logistical or administrative aspects of the study. 
The Investigator and Sponsor share the responsibility to ensure data quality and integrity. Training 
sessions, regular monitoring of investigation by Sponsor or designated personnel, instruction manuals, 
data verification, cross-checking and data audits will be performed to ensure quality of all study data. 
On-site site initiations will be performed to prepare Investigators and other study personnel for 
appropriate conduct of the study and collection of study data. 
The Investigator will personally ensure the quality of the data by overseeing all study activities, 
including the timely review of both source data and eCRF data as transferred from source. The 
Investigator will sign and date a declaration attesting to his/her responsibility for the quality of all data 
recorded and stating that the data represents a complete and accurate record of each subject’s 
participation in the study, and that it had been medically reviewed in a timely fashion throughout the 
data acquisition period. 
Logic and consistency checks are to be performed on all data entered into the eCRFs to ensure accuracy 
and completeness. 
11.5 
Quality Assurance 
At its discretion, Sponsor or Sponsor’s designee may conduct audits as part of the implementation of 
quality assurance to ensure that the study is being conducted in compliance with the ICH harmonized 
tripartite guideline E6 (R2): GCP, the protocol, SOPs, and all applicable regulatory requirements. Audits 
will be independent of and separate from the routine monitoring and quality control functions. The clinic 
site may also be compelled to undergo an inspection by a regulatory authority. 
 
 

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12. Human Research Ethics Committee Review 
The Protocol and written ICF will be reviewed and approved by an HREC prior to any involvement of 
potential subjects. The composition of the HREC will be in accordance with the recommendations of 
the World Health Organization, ICH guidelines, and TGA regulations. If any member of the HREC has 
direct participation in this study, written notification regarding his or her abstinence from voting must 
also be obtained. If the US center is unwilling to provide names and titles of all members due to privacy 
and conflict of interest concerns, the center should instead provide a Federal Wide Assurance Number 
or comparable number assigned by the Department of Health and Human Services. 
The Sponsor or designee will supply relevant documents for submission to HREC for the protocol’s 
review and approval. This protocol, the IB or package insert, a copy of the ICF, and, if applicable, 
subject recruitment materials and/or advertisements and other documents required by all applicable laws 
and regulations, must be submitted to HREC for approval. Written approval by HREC of the protocol 
and subject informed consent must be obtained and submitted to the Sponsor or designee before 
commencement of the study (i.e., before shipment of the study drug). The HREC approval must refer 
to the study by exact protocol title, number, and version date; identify versions of other documents (e.g., 
ICF) reviewed; and state the approval date. 
The Investigators will comply with all HREC reporting requirements. This may include notification to 
the HREC regarding: protocol amendments, updates to the ICF, recruitment materials intended for 
viewing by subjects, local safety reporting requirements, reports and updates regarding the ongoing 
review of the study at intervals specified by the respective HREC, and submission of the Investigator’s 
final status report to HREC. All changes in research activities and all unanticipated problems involving 
risks to subjects will be immediately reported. No changes will be made in the conduct of the study 
without HREC approval, except when required to eliminate apparent immediate hazards to subjects. 
The HREC approval and relevant documentation for these items must be provided to the Sponsor or its 
designee. 
12.1 
Regulatory Approvals/Notifications 
The study will be submitted by Sponsor or Sponsor designee to the TGA through CTN path. The study 
can be initiated at the site, once it has been approved by the responsible HREC. 
 
 

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12.2 
Informed Consent 
Written consent documents will embody the elements of informed consent as described in the 
Declaration of Helsinki, the ICH Guidelines for GCP, and in accordance with all applicable laws and 
regulations. The ICF describes the planned and permitted uses, transfers and disclosures of the subject’s 
personal and personal health information for purposes of conducting the study. The ICF further explains 
the nature of the study, its objectives, and potential risks and benefits as well as the date informed 
consent are given. The ICF will detail the requirements of the participant and the fact that he or she is 
free to withdraw at any time without giving a reason and without prejudice to his or her further medical 
care. 
The ICF must be written in a language fully comprehensible to the prospective subject. It is the 
responsibility of the Investigator to explain the detailed elements of the ICF to the subject. Information 
should be given in both oral and written form whenever possible and in the manner deemed appropriate 
by the HREC. In the event the subject is not capable of rendering adequate written informed consent, 
then the subject’s legally acceptable representative may provide such consent for the subject in 
accordance with applicable laws and regulations. 
The current version of the HREC-approved consent form will be reviewed with the prospective study 
subject or his/her legal representative, and the investigator or his/her designee will answer questions 
regarding procedures, risks, and alternatives. The Investigator or his/her entitled designee (as defined 
on the Delegation List) will obtain written informed consent from each subject or from the subject’s 
legal representative or designee. Written informed consent must be obtained before any study-specific 
procedure is performed. Documentation of the subject’s informed consent for and participation in this 
study will be noted in the subject’s medical record. 
Once signed, the original ICF will be stored in ISF. A copy of the signed ICF shall be given to the 
subject. 
All revised ICFs must be reviewed and signed in the same manner as the original informed consent. The 
date the revised consent was obtained should be recorded in the subject’s medical record and the subject 
should receive a copy of the revised ICF. 
 
12.3 
 Confidentiality of Subject Records 
With respect to subject information collected in this study, the Investigator shall comply with the Privacy 
Act 1988. To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the 

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Sponsor requires that the Investigator permit its monitor or designee’s monitor, representatives from 
any regulatory authority (e.g., TGA), the Sponsor’s designated auditors, and the appropriate HREC to 
review the subject’s original medical records (source data or documents), including, but not limited to 
laboratory test result reports, ECG reports, admission and discharge summaries for clinical site 
admissions occurring during a subject’s study participation, and autopsy reports. Access to a subject’s 
original medical records requires the specific authorization of the subject as part of the informed consent 
process. 
12.4 
Delegation of Investigator Duties 
The Investigator is responsible for personally conducting or supervising the study at the site. However, 
the Investigator is allowed to delegate certain study related tasks to sub-investigators and study staff. 
When tasks are delegated, the Investigator is responsible for providing adequate supervision and training 
of those to whom tasks are delegated. 
12.5 
Study Termination 
Stopping rules for the study are specified in Section 4.6. In addition, the study may be terminated if 
one of the following criteria is satisfied: 
• New information regarding the safety or efficacy of the study drug that indicates a change in the 
known risk/benefit profile for the investigational medicinal product, such that the risk/benefit is 
no longer acceptable for subjects participating in the study. 
• Significant violation of GCP that compromises the ability to achieve the primary study 
objectives or compromises subject safety. 
In general, the study may be discontinued for valid scientific or administrative reasons. 
12.6 
Financing, Insurance and Indemnification 
Financing, insurance and indemnification shall be of a separate agreement(s) between the Investigator 
and Sponsor or its designee. 
 
 
 

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13. Ownership of Data and Publication Policy 
Data derived from the trial are the exclusive property of Sponsor. 
All publications associated with this study will be coordinated through the publication committee. The 
publication committee will consist of the Investigators, pharmacokineticist and representatives of the 
Sponsor. No publications will go forward without permission from the Sponsor. The Sponsor will 
provide the major findings of the study to the Investigators. At the Sponsor’s request, the submission or 
other disclosure of a proposed publication will be delayed for up to 30 days to allow the Sponsor to seek 
patent or similar protection of any inventions, know- how or other intellectual or industrial property 
rights disclosed in the proposed publication. As a single center study, the first publication, or disclosure 
of study results shall be a complete report or disclosure coordinated by the Investigators and Sponsor. 
Thereafter, any secondary publications will reference the original publication(s). If a written contract 
for the conduct of the study, which includes publication provisions inconsistent with this statement is 
executed, that contract’s publication provisions shall apply rather than this statement.

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14. Appendices 
14.1 
Appendix A: List of Immunomodulatory or Growth Stimulating Factors 
The list below is not all-inclusive. The investigator must consult with Medical Monitor in case of other 
previous or concomitant immunomodulatory or growth stimulating factor medications. 
Immunosuppressive or Immunomodulatory Drugs (generic names) 
5-fluorouracil 
Abatacept 
Adalimumab 
Altretamine 
Anakinra 
Azathioprine 
Basiliximab 
Belatacept 
Bendamustine 
Budesonide ≥ 6 mg 
Busulfan 
Carmustine 
Certolizumab pegol 
Chlorambucil 
Cisplatin 
Cyclophosphamide 
Cyclosporine 
Cytarabine 
Daclizumab 
Darvadstrocel 
Diaziquone 
Dimethyl fumarate 
Etanercept 
Everolimus 
Fingolimod 
Glatiramer 
Golimumab 
Hydrocortisone ≥ 80 mg 
Hydroxychloroquine 
Interferon beta-1a 
Interferon beta-1b 
Ixekizumab 
Ifosfamide 
Infliximab 
Lomustine 
Mechlorethamine 

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Melphalan 
Mercaptopurine 
Methotrexate 
Methylprednisolon
e ≥ 16 mg 
Mycophenolate 
mofetil 
Natalizumab 
Ocrelizumab 
Ofatumumab 
Oxaliplatin 
Ozanimod 
Prednisolone ≥ 20 mg 
Prednisone ≥ 20 mg 
Procarbazine 
Rituximab 
Ponesimod 
Satralizumab 
Secukinumab 
Sirolimus 
Siponimod 
Streptozocin 
Tacrolimus 
Thalidomide 
Temozolomide 
Teriflunomide 
Thioguanine 
Thiotepa 
Tocilizumab 
Tofacitinib 
Vedolizumab 
Ustekinumab 
 
Growth Stimulating Factors 
Somatropin (Genotropin®, Humatrope®, Norditropin®, Saizen®, Serostim®, Flexpro® 
Nutropin®, Nutropin AQ®, Omnitrope®, Skytrofa®, Sogroya®, ZomactonTM, Zorbtive®) 
Epoetin (Epogen® or Procrit®) 
Darbepoetin alfa (Aranesp®) 
Luspatercept (Reblozyl®) 
Granulocyte colony stimulating factor (G-CSF, filgrastim, or Neupogen®) 
Granulocyte macrophage-colony stimulating factor (GM-CSF, sargramostim, or Leukine) 
Pegfilgrastim (Neulasta®) 
Romiplostim (Nplate®) 
Eltrombopag (Promacta®) 
Oprelvekin (interleukin-11, IL-11, or Neumega®)

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15. Revision History 
Date: 
Comment: 
27 November 2023 
Original Version 1.0 
15 January 2024 
Version 2.0 
Rationale for the amendment: 
The protocol amendment was required to: 
- Inclusion criterion #1 is amended to exclude female of 
childbearing potential and avoid potential risk for fetus 
and newborns.  
- Inclusion criterion #5 is removed in accordance with 
changes in criterion # 1 
- Exclusion criterion #18: “Female of childbearing potential” is 
added. 
- Exclusion criterion #19: “Any skin condition and/or tattoo 
that may interfere with the evaluation of safety at the injection 
site” is added. 
29 January 2024 
Version 3.0 
Rationale for the amendment: 
The broken link in the section 6.2.7 is restored.  
25 June 2024 
Version 4.0 
Rationale for the amendment - refer to Summary of changes from Protocol 
version 3.0  (January 29, 2024) to Protocol version 4.0 (June 25, 2024): 
The protocol amendment was required to: 
- To further clarify participants dosing rule after safety 
assessment at post dose review period. 
- To further clarify dose escalation suspension/stopping 
rules. 
- To clarify documentation of sterilization for females with 
non-childbearing potential. 
- To clarify contraception requirement for males. 
- To correct inconsistency regarding subject position during 
vital signs measurement 
- To add new Exclusion criteria # 20 
- To correct the placebo solution composition and the 
product preparation procedures. 
- To clarify alcohol and drug testing timepoint on Day 1 
prior to dosing. 

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- To clarify specimen collection (Chemistry, Hematology, 
Coagulation and Urinalysis) on Day 28 (±2) prior to 
dosing. 
- To correct inconsistencies regarding type and timing for 
conduct of physical examinations during the study. 
- To correct inconsistency regarding timing of adverse 
events recording during the study. 
- To correct discrepancies regarding allowable time window 
for the pre-dose vital measurements on Immunization 
Days. 
- To correct inconsistency regarding timing for weight 
measurement during the study. Weight measurement is not 
required on Day 1. 
- To correct inconsistency regarding timing for safety labs. 
Specimen collection (Chemistry, Hematology, 
Coagulation and Urinalysis) is not required on Day 140 
(±5). 
- To correct inconsistency regarding timing of serious 
adverse events recording during the study. 
- To correct typo regarding last measurable timepoint for 
the study outcome measures. 
- Other administrative changes and grammatical edits were 
made for consistency and accuracy throughout the 
protocol. 
 

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