A Phase 2, Randomized, Modified Double-Blind, Active Controlled Study to Characterize the Safety and Immunogenicity of IVX-A12 in Adults 60 Years of Age and Older
Phase: PHASE2
Conditions: Healthy Participants
Sponsor: Icosavax, Inc.

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Clinical Study Protocol  
 
Study 
Intervention 
IVX-A12 
 
Study Code 
ICVX-12-202 
 
Version 
3.0 
 
Date 
06 June 2024  
 
 
 
 
 
 
 
 
 
 
 
A Phase 2, Randomized, Modified Double-Blind, Active Controlled 
Study to Characterize the Safety and Immunogenicity of IVX-A12 
in Adults 60 Years of Age and Older 
 
 
Sponsor Name: Icosavax, a member of the AstraZeneca Group 
Legal Registered Address: 1930 Boren Ave suite 1000, Seattle, WA 98101, USA 
Regulatory Agency Identifier Number(s): IND 28672 
This protocol has been subject to a peer review according to AstraZeneca standard procedures. 
The protocol is publicly registered and the results are disclosed and/or published according to 
the AstraZeneca Global Standard - Bioethics and in compliance with prevailing laws and 
regulations. 

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Version Scope: Global 
Brief Title: A study to characterize the safety and immunogenicity of IVX-A12 in adult 
participants 60 years of age and older 
Study Phase: II 
Study Clinical Lead Name and Contact Information will be provided separately. 
Study Clinical Lead is responsible for the clinical integrity of the study. 
 
 

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SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
CSP Version 3 
06 June 2024 
CSP Version 2 
11 April 2024 
CSP Version 1 
25 March 2024 
 
CSP Version 3.0, 06 June 2024 
Overall Rationale for the Modification: 
The purpose of this protocol modification is the addition of safety rules for halting enrollment 
of the study.  
Summary of Changes: 
List of Substantial Modifications 
Section Number and Name  
Description of Change  
Brief Rationale  
Section 5.5 
Addition of safety rules for halting 
enrollment of the study  
To provide safety rules for halting 
enrollment in the study as per FDA 
request 
 
 

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TABLE OF CONTENTS 
SUMMARY OF CHANGES TABLE ....................................................................................... 3 
TABLE OF CONTENTS ........................................................................................................... 4 
LIST OF ABBREVIATIONS .................................................................................................... 8 
1 
PROTOCOL SUMMARY .................................................................................... 10 
1.1 
Synopsis ................................................................................................................ 10 
1.2 
Schema .................................................................................................................. 12 
1.3 
Schedule of Activities ........................................................................................... 13 
2 
INTRODUCTION ................................................................................................ 14 
2.1 
Study Rationale ..................................................................................................... 14 
2.2 
Background ........................................................................................................... 14 
2.2.1 
Respiratory syncytial virus and human metapneumovirus ................................... 14 
2.2.2 
IVX-A12 ............................................................................................................... 15 
2.3 
Benefit/Risk Assessment ...................................................................................... 15 
2.3.1 
Risk Assessment ................................................................................................... 15 
2.3.1.1 
Study Procedures .................................................................................................. 16 
2.3.2 
Benefit Assessment ............................................................................................... 16 
2.3.3 
Overall Benefit/Risk Conclusion .......................................................................... 17 
3 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS ............................................ 18 
4 
STUDY DESIGN ................................................................................................. 19 
4.1 
Overall Design ...................................................................................................... 19 
4.2 
Scientific Rationale for Study Design .................................................................. 19 
4.2.1 
Rationale for Study Population ............................................................................. 19 
4.3 
Justification for Dose of IVX-A12 ....................................................................... 19 
4.4 
End-of-study Definition ........................................................................................ 20 
5 
STUDY POPULATION ....................................................................................... 20 
5.1 
Inclusion Criteria .................................................................................................. 20 
5.2 
Exclusion Criteria ................................................................................................. 21 
5.3 
Lifestyle Considerations ....................................................................................... 22 
5.4 
Screen Failures ..................................................................................................... 22 
5.5 
Criteria 
for 
Temporarily 
Delaying 
Enrollment, 
Randomization, 
or 
Administration of Study Intervention ................................................................... 23 
6 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ................... 23 
6.1 
Study Intervention(s) Administered ...................................................................... 23 
6.2 
Preparation, Handling, Storage, and Accountability ............................................ 24 
6.2.1 
Dose Preparation ................................................................................................... 25 
6.2.2 
Dose Administration ............................................................................................. 25 
6.3 
Assignment to Study Intervention ........................................................................ 25 

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6.4 
Blinding ................................................................................................................ 26 
6.5 
Study Intervention Compliance ............................................................................ 27 
6.6 
Dose Modification ................................................................................................ 27 
6.7 
Continued Access to Study Intervention After the End of the Study ................... 27 
6.8 
Treatment of Overdose ......................................................................................... 27 
6.9 
Prior and Concomitant Therapy ............................................................................ 27 
6.9.1 
Permitted Concomitant Medications .................................................................... 28 
6.9.2 
Prohibited Concomitant Medications ................................................................... 28 
7 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................. 29 
7.1 
Discontinuation of Study Intervention ................................................................. 29 
7.2 
Participant Discontinuation/Withdrawal From the Study ..................................... 30 
7.3 
Lost to Follow-up ................................................................................................. 30 
8 
STUDY ASSESSMENTS AND PROCEDURES ................................................ 31 
8.1 
Administrative and General/Baseline Procedures ................................................ 32 
8.2 
Efficacy Assessments ............................................................................................ 32 
8.3 
Safety Assessments ............................................................................................... 32 
8.3.1 
Physical Examinations .......................................................................................... 32 
8.3.2 
Vital Signs ............................................................................................................. 32 
8.3.3 
Electrocardiograms ............................................................................................... 32 
8.3.4 
Clinical Safety Laboratory Tests........................................................................... 32 
8.3.5 
Other Safety Assessments ..................................................................................... 32 
8.3.5.1 
Immediate Post-vaccination Observation ............................................................. 32 
8.4 
AEs, SAEs, and Other Safety Reporting .............................................................. 33 
8.4.1 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information ................................................................................................. 34 
8.4.2 
Follow-up of Adverse Events and Serious Adverse Events ................................. 34 
8.4.3 
Causality Collection ............................................................................................. 34 
8.4.4 
Adverse Events Based on Examinations and Tests .............................................. 35 
8.4.5 
Adverse Events Based on Signs and Symptoms .................................................. 35 
8.4.6 
Solicited Adverse Reactions (Reactogenicity) ..................................................... 35 
8.4.7 
Adverse Events of Special Interest ....................................................................... 36 
8.4.8 
Medically-attended Adverse Events ..................................................................... 36 
8.4.9 
Hy’s Law ............................................................................................................... 37 
8.4.10 
Reporting of Serious Adverse Events ................................................................... 37 
8.4.11 
Pregnancy ............................................................................................................. 38 
8.4.12 
Medication Error and Study Intervention Misuse ................................................ 38 
8.4.12.1 
Timelines .............................................................................................................. 38 
8.4.12.2 
Medication Error ................................................................................................... 38 
8.4.12.3 
Study Intervention Misuse .................................................................................... 38 
8.4.13 
Reporting of Overdose .......................................................................................... 38 
8.5 
Pharmacokinetics .................................................................................................. 39 
8.6 
Pharmacodynamics ............................................................................................... 39 

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8.7 
Optional Genomics Initiative ................................................................................ 39 
8.8 
Biomarkers ............................................................................................................ 39 
8.9 
Immunogenicity Assessments ............................................................................... 39 
8.9.1 
Neutralizing Antibody Responses ........................................................................ 39 
8.9.2 
Cellular Mediated Immune Responses and Exploratory Analyses ....................... 39 
8.10 
Health Economics OR Medical Resource Utilization and Health Economics ..... 40 
8.11 
Study Participant Feedback Questionnaire ........................................................... 40 
9 
STATISTICAL CONSIDERATIONS ................................................................... 40 
9.1 
Statistical Hypotheses ........................................................................................... 40 
9.2 
Sample Size Determination .................................................................................. 40 
9.3 
Populations for Analyses ...................................................................................... 40 
9.4 
Statistical Analyses ............................................................................................... 41 
9.4.1 
General Considerations ......................................................................................... 41 
9.4.2 
Immunogenicity .................................................................................................... 41 
9.4.2.1 
Primary and Secondary Endpoint(s) ..................................................................... 41 
9.4.2.2 
Exploratory Endpoint(s) ....................................................................................... 42 
9.4.3 
Safety .................................................................................................................... 42 
9.4.4 
Other Analyses ...................................................................................................... 43 
9.5 
Planned Analyses .................................................................................................. 43 
9.6 
Data Monitoring Committee ................................................................................. 43 
10 
SUPPORTING 
DOCUMENTATION 
AND 
OPERATIONAL 
CONSIDERATIONS ............................................................................................ 43 
REFERENCES ........................................................................................................................ 62 
 
LIST OF FIGURES 
Figure 1 
Study Design ............................................................................................... 12 
 
LIST OF TABLES 
Table 1 
Schedule of Activities ................................................................................. 13 
Table 2 
Objectives and Endpoints ............................................................................ 18 
Table 3 
Study Interventions ..................................................................................... 24 
Table 4 
Predefined Solicited Adverse Reactions for Reactogenicity Assessment ... 36 
Table 5 
Populations for Analysis ............................................................................. 41 
Table 6 
Severity Grading for Solicited Injection Site Adverse Reactions ............... 55 
Table 7 
Severity Grading for Solicited Systemic Adverse Reactions ...................... 55 
 

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LIST OF APPENDICES 
Appendix A 
Regulatory, Ethical, and Study Oversight Considerations .......................... 44 
Appendix B 
AEs: Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting .............................................................................................. 52 
Appendix C 
Handling of Human Biological Samples ..................................................... 58 
Appendix D 
Protocol Version History ............................................................................. 61 
 

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LIST OF ABBREVIATIONS  
Abbreviation or special term 
Explanation 
AE 
Adverse event 
AESI 
Adverse event of special interest  
ANCOVA 
Analysis of covariance 
AR 
Adverse reaction 
ARI 
Acute respiratory illness 
CFR 
Code of Federal Regulations 
CHO 
Chinese Hamster Ovary 
CI 
Confidence interval 
CMI 
Cell-mediated immunity 
CRO 
Contract Research Organization 
CSR 
Clinical Study Report 
CTIS 
Clinical Trials Information System 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture 
EU 
European Union 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GFP 
Green fluorescence protein 
GMFR 
Geometric mean fold rise 
GMT 
Geometric mean titer 
GSK 
GlaxoSmithKline 
HBS 
Human Biological Sample(s) 
hMPV 
Human metapneumovirus 
IATA 
International Air Transport Association 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IM 
Intramuscular 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
LRTD 
Lower respiratory tract disease 
MAAE 
Medically-attended adverse event 

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Abbreviation or special term 
Explanation 
μg 
microgram 
mL 
milliliter 
MMRM 
Mixed model for repeated measures 
N/A 
Not applicable 
nAb 
Neutralizing antibody 
NIMP 
Non-investigational Medicinal Product  
PBMC 
Peripheral blood mononuclear cells 
preF 
Prefusion F 
RTSM 
Randomization and Trial Supply Management 
RSV 
Respiratory syncytial virus 
SAE 
Serious Adverse Event  
SAP 
Statistical Analysis Plan 
SoA 
Schedule of Activities 
SUSAR 
Suspected unexpected serious adverse reactions 
US 
United States 
USPI 
United States Prescribing Information 
VLP 
Virus-like Particle 
 

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Disclosure Statement:  
This is a parallel group, single-dose, modified double-blind, safety and immunogenicity study. 
Number of Participants: 
Approximately 140 participants ≥60 years of age will be randomized 1:1 in the study to 
receive IVX-A12 or licensed RSV vaccine, AREXVY® (GSK Biologicals, Rixensart, 
Belgium).  
Intervention groups and Duration: 
One dose of IVX-A12 300 µg IM injection or one dose of AREXVY IM injection.  
The study duration for each participant will be approximately 6 months following 
administration of the study intervention. 
Data Monitoring / Other Committee: 
Not Applicable. 
Statistical Methods: 
Only descriptive statistics will be used to summarize the immunogenicity and safety 
endpoints. There will be no formal hypothesis testing.  
The immunogenicity analysis set will include all randomized and dosed participants in the 
safety analysis set who had no protocol deviations judged to potentially interfere with the 
generation or interpretation of an immune response. The safety analysis set will include all 
randomized and dosed participants. Analyses conducted using these analysis sets will be based 
on the actual study intervention received. 
The sample size of 140 participants is based on having sufficient precision for a descriptive 
assessment of immunogenicity and safety.  
The Day 29 primary analysis will be conducted when all participants have completed their 
Day 29 visit. Subsequently, the final analysis will be performed when all participants complete 
the study. For the Day 29 primary analysis, adjusted GMTs and GMT ratios, along with their 
corresponding 95% CIs, will be estimated using an ANCOVA model that includes a dependent 
variable of log titers, study arm as a fixed effect, and log baseline titer and age group as 
covariates. For the final analysis, model-adjusted GMTs and GMT ratios at Days 29 and 181, 
along with their corresponding 95% CIs, will be estimated using an MMRM that includes a 
dependent variable of log titers, study arm as a fixed effect, log baseline titer, age group (60 to 
69, 70 to 79, and ≥80 years of age), visit indicators (Days 29 and 181) as covariates, and a 
study arm by visit interaction term.  

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Model-adjusted GMT and GMT ratios will be used for analyses of the nAb response 
endpoints. Geometric mean fold rises and seroresponse (defined as a GMFR ≥4) will be 
unadjusted.  
Model-adjusted GMT and GMT ratios, along with their corresponding 95% CIs, will be 
calculated for each study arm and will be summarized by visit based on the immunogenicity 
analysis set. Unadjusted GMFR and seroresponse, along with their corresponding 95% CIs 
will be calculated for each study arm and summarized by visit. 
1.2 
Schema 
The study groups and overall study design are described in Figure 1. 
Figure 1 
Study Design 
 
 
 

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1.3 
Schedule of Activities 
Table 1 
Schedule of Activities 
Procedure 
Vaccination and Follow-up Period 
Details in Protocol Section or Appendix 
Visit number 
1 
2 
3 
4 
 
Visit Day (window) days 
1 (N/A) 
8 (+2) 
29 (+3) 
181 (±14) 
 
Visit type  
Clinic 
Clinic  
Clinic 
Clinic 
 
Informed consent a 
X (pre-dose) 
 
 
 
Section 5.1 
Demography and Medical history 
X (pre-dose) 
 
 
 
Sections 5.1 and 5.2 
Targeted physical examination based on medical history 
X (pre-dose) 
 
 
 
Section 8.3.1 
Height, Weight 
X (pre-dose) 
 
 
 
Section 8.3.2 
Body temperature, Blood pressure 
X (pre-dose) 
 
 
 
Section 8.3.2 
Verify eligibility criteria 
X (pre-dose) 
 
 
 
Sections 5.1 and 5.2 
Randomization 
X (pre-dose) 
 
 
 
Section 6.3 
Immunogenicity serum sample 
X (pre-dose) 
 
X 
X 
Section 8.9.1 
Blood sample for cell-mediated immune responses  
X (pre-dose) 
X 
X 
X 
Section 8.9.2 
Vaccine administration 
X 
 
 
 
Sections 6.1 and 6.2 
Immediate post-vaccination assessment b 
X 
 
 
 
Section 8.3.5.1 
eDiary distribution and training for solicited ARs 
X 
 
 
 
Section 8.4.6 
Solicited ARs c 
X (ongoing through Day 8) 
 
 
Section 8.4.6 
eDiary collection 
 
X 
 
 
Section 8.4.6 
Unsolicited AEs 
X 
 
Section 8.4.1 and 8.4.2 
SAEs/AESIs/MAAEs 
X 
Section 8.4.1, 8.4.2, 8.4.7, 8.4.8, and 8.4.10 
Concomitant medications d 
X 
Section 6.9 
a 
Confirm consent form signed prior to any procedures. 
b 
Immediate unsolicited AEs to be collected during the 30-minute observation period following vaccination. 
c 
Predefined solicited ARs recorded by participant in eDiary to assess reactogenicity. Investigators are to follow-up on any solicited ARs that are ongoing at Day 8 through to their resolution (see 
Sections 8.4.6 and 9.4.3). 
d 
All concomitant medications will be recorded in the source documents. Prohibited medications and any medications used to treat SAEs or AESIs will also be recorded in the eCRF.  

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2 
INTRODUCTION 
2.1 
Study Rationale 
The candidate vaccine, IVX-A12, is a single-dose liquid formulation for intramuscular (IM) 
injection (0.5 mL dose) in adults ≥60 years of age to prevent lower respiratory tract disease 
(LRTD) caused by respiratory syncytial virus (RSV) and human metapneumovirus (hMPV). 
In IVX-12-202, the vaccine candidate will be evaluated at a dosage level of 150 µg RSV / 
150 µg hMPV and will be mixed with an aqueous diluent. This Phase 2 clinical study, 
IVX-12-202, will expand the safety and immunogenicity database of the candidate vaccine, 
IVX-A12, in relation to a United States (US)-licensed RSV vaccine. The primary purpose of 
this trial will be to assess the immunogenicity and safety of IVX-A12 compared with a 
licensed RSV vaccine, AREXVY (GlaxoSmithKline [GSK] Biologicals, Rixensart, Belgium) 
in adults ≥60 years of age.  
2.2 
Background 
2.2.1 
Respiratory syncytial virus and human metapneumovirus 
RSV and hMPV are two highly contagious and common causes of respiratory infection across 
all age groups. In older adults and other high-risk groups, such as infants and the 
immunocompromised, RSV and hMPV are a significant cause of morbidity and mortality.  
In one study evaluating the infectious causes of hospitalized community-acquired pneumonia 
in adults in the US, hMPV and RSV were the third and fourth most common viral pathogens 
identified, respectively (Jain et al 2015). Globally in developed countries in 2019, there was 
an estimated 5.2 million RSV related acute respiratory illnesses (ARIs) in adults 65 years and 
older, with 9.67% hospitalized (Savic et al 2023). In the US, RSV infects approximately 3 to 
7% of adults 65 years and older each year (Falsey et al 2005). The burden of disease for RSV 
among US adults 65 years of age and older has been estimated to be 60,000 to 160,000 
hospitalizations (Branche et al 2022, McLaughlin et al 2022, Zheng et al 2022, US CDC 
2023) and 6,000 to 10,000 deaths (Thompson et al 2003, Matias et al 2014) each year. RSV 
has been identified as the cause of medically-attended ARI in up to 12% of adults 50 years or 
age and older with a mortality rate of 6 to 8% in those hospitalized (Colosia et al 2017).  
While the burden of disease for hMPV has been less studied, hMPV infections can similarly 
lead to severe disease in at-risk populations as shown recently in 2023 when hMPV infections 
in the US peaked in mid-March with 1 in 10 patients in intensive care beds testing positive for 
hMPV (Wise 2023). Furthermore, the average annual rates of hospitalization associated with 
RSV and hMPV in adults 65 years of age and older in the US have been reported to be similar 
to influenza (Widmer et al 2012).  
In May 2023, two vaccines indicated for the prevention of LRTD caused by RSV in adults 
60 years of age and older obtained approval in the US and other countries: AREXVY (GSK) 

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and ABRYSVO® (Pfizer). Both RSV vaccines are given intramuscularly in a 0.5 mL dose, 
manufactured in Chinese Hamster Ovary (CHO) cell lines, and contain 120 µg of recombinant 
RSV prefusion F (preF). AREXVY is adjuvanted (AS01E) while ABRYSVO does not contain 
an adjuvant. However, no vaccines against hMPV or a combination RSV and hMPV vaccine 
are currently licensed. 
2.2.2 
IVX-A12 
Icosavax (a member of the AstraZeneca group of companies) is developing IVX-A12, an 
RSV/hMPV combination vaccine, to protect adults 60 years of age and older against RSV- and 
hMPV-associated respiratory disease. IVX-A12 utilizes a novel virus-like particle (VLP) 
vaccine platform, which presents a high-density, multivalent display of the respective viral 
antigen. The multi-antigen structural display is similar to F-protein arrangement presented to 
the immune system during viral infection and is hypothesized to elicit a stronger, more 
durable, and broader antibody response (Mohsen and Bachmann, 2022).  
The VLP platform technology is composed of two components: Component A (a trimeric 
protein genetically fused to the target infectious disease antigen of interest and produced in 
CHO cells) and Component B (a common, computationally-designed, homopentamer 
component used across multiple vaccine candidates and produced in E. coli). When the two 
components are mixed, self-assembly of a VLP occurs with icosahedral symmetry and particle 
size to mimic a virion (each VLP has 12 copies of the Component B pentamer). The VLP 
Component A antigen for the RSV vaccine candidate (IVX-121) is using a similar RSV A 
preF antigen as in GSK’s licensed RSV vaccine (DS-Cav1, licensed from the National 
Institutes of Health) (Ruckwardt et al 2021) and presents 60 copies of the RSV preF protein 
on the VLP surface. The VLP Component A antigen for the hMPV vaccine candidate 
(IVX-241) uses the hMPV A preF protein and presents 60 copies of the hMPV preF protein on 
the VLP surface. 
Further description of the chemistry, pharmacology, efficacy, and safety of IVX-A12 is 
provided in the Investigator’s Brochure (IB). 
2.3 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of IVX-A12 can be found in the IB and Development Safety Update Report. 
2.3.1 
Risk Assessment 
The safety precautions, eligibility, and study design are based on other RSV vaccines and 
emerging clinical data for IVX-A12. Anaphylaxis and other serious hypersensitivity reactions 
are important potential risks associated with administration of any vaccine. Hypersensitivity 
reactions, including anaphylaxis, are acute serious allergic reactions with multi-organ-system 
involvement that can present as, or rapidly progress to a severe life-threatening reaction 

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requiring immediate medical attention. Strategies used to mitigate the important potential risk 
of anaphylaxis and other serious hypersensitivity reactions are provided in the study exclusion 
criteria (Section 5.2).  
Another risk very rarely observed with licensed RSV and influenza vaccines is Guillain-Barré 
Syndrome, which typically occurs within the first 3 weeks after vaccination. Monitoring will 
be conducted for Guillain-Barré Syndrome and other immune-mediated neurologic diseases, 
and atrial fibrillation, as they are considered adverse events of special interest (AESIs). 
The safety database supporting IVX-A12 (all dosages evaluated with or without adjuvant 
(MF59®: oil-in-water emulsion) includes over 300 adults 60 years of age and older from two 
studies: the Phase 1 Study ICVX-12-101 (NCT05664334) and Phase 2a Study ICVX-12-201 
(NCT05903183).  
Available safety data from the Phase 1 and 2a studies show that, to date, IVX-A12 is well 
tolerated up to the maximum dose level tested of 300 µg. Reactogenicity events were 
monitored as solicited adverse reactions (ARs) and were consistent with reactions frequently 
observed following any vaccination. Solicited ARs were mostly mild or moderate in intensity 
and lasting less than 3 days post-vaccination. Across IVX-A12 groups, the most commonly 
reported solicited injection site ARs were tenderness and pain. The most commonly reported 
solicited systemic ARs were headache and myalgia in the Phase 1 Study ICVX-12-101, and 
myalgia and fatigue in the Phase 2a Study ICVX-12-201. There were no vaccine-related 
serious adverse events (SAEs), deaths, adverse events (AEs) leading to discontinuation, or 
vaccine-related medically-attended adverse events (MAAEs) reported up to Day 28 
post-vaccination. 
AEs, SAEs, MAAEs, and AESIs will be collected in this study (see Section 8.4.1). 
Participants will be provided an eDiary, which allows the investigator to review local 
reactions and systemic reactions post-vaccination.  
For risks associated with AREXVY, please refer to the US Prescribing Information (USPI). 
2.3.1.1 
Study Procedures 
Venipuncture will be performed during this study. Therefore, at the venipuncture site, there is 
a risk of bleeding, bruising, formation of a hematoma, and infection. In order to mitigate this, 
the blood draws in this study will only be conducted by appropriate site personnel. 
2.3.2 Benefit Assessment 
IVX-A12 is an investigational RSV/hMPV combination vaccine with the anticipated benefit 
to prevent LRTD caused by RSV and hMPV in adults 60 years of age and older.  
Assessment of IVX-A12’s clinical benefit is currently based on analysis of nAb levels 

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observed in the Phase 1 and 2a clinical studies assessing immunogenicity of IVX-A12. In the 
Phase 1 Study ICVX-12-101 and the Phase 2a Study ICVX-12-201, a rise in nAb titers for 
RSV and hMPV was observed in older adults ≥60 years and older up to 28 days following 
vaccination across all IVX-A12 dosage levels of up to 300 µg. 
This study provides an opportunity for participants to receive either IVX-A12 or a licensed 
RSV vaccine. Furthermore, participants will also be contributing to the development of a 
vaccine which may have prophylactic benefits in an area of unmet medical need as there 
currently are no licensed hMPV vaccines. Additionally, combining RSV/hMPV into one 
vaccine could decrease morbidity and mortality of respiratory disease in the older adult 
population, while also improving vaccination coverage, and save preparation/administration 
time for providers. 
Recipients of IVX-A12 do not have any guaranteed benefit. The information gained from this 
study will inform future decisions for the development of a safe and effective vaccine for the 
prevention of RSV and hMPV.  
2.3.3 
Overall Benefit/Risk Conclusion 
For the safety of participants, this protocol has incorporated various risk mitigation measures 
including appropriate inclusion and exclusion criteria (see Sections 5.1 and 5.2) and close 
monitoring of participants to minimize known and potential risks.  
Taking into account the measures to minimize risks to study participants, the known and 
potential risks identified in association with IVX-A12 are justified by the anticipated benefits 
of protection from RSV/hMPV for participants who receive IVX-A12.  

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4 
STUDY DESIGN 
4.1 
Overall Design 
This Phase 2 clinical study is a randomized, modified double-blind, active controlled study to 
characterize the safety and immunogenicity of IVX-A12. 
Approximately 140 participants will be randomized in a 1:1 ratio to receive IVX-A12 
(approximately N=70) or licensed RSV vaccine, AREXVY (approximately N=70). 
Randomization will be centrally stratified by age (60 to 69, 70 to 79, and ≥80 years of age). 
The Schedule of Activities (SoA) is presented in Section 1.3. Blood will be taken for 
immunological assessments as per the SoA. All participants will be given a thermometer, 
ruler, and a proprietary eDiary application designed for use with the participant’s smart device 
or a provisioned eDiary device with instructions for use. Participants will be asked to report 
on solicited ARs in the eDiary beginning on the day of vaccination (Day 1) and for 7 days 
following the day of vaccination (up to Day 8). Unsolicited AEs will be collected by 
participants through Visit 3. SAEs, MAAEs, and AESIs will be recorded throughout the study.  
The duration of each participant’s involvement in the study will be approximately 6 months 
following administration of study vaccination. 
The study is planned to be conducted at approximately 4-5 sites in the US. 
4.2 
Scientific Rationale for Study Design 
The overall study design is similar to other vaccine studies evaluating immunogenicity and 
safety of an investigational product to a licensed vaccine (NCT06147063, NCT04583618, 
NCT03698279, NCT05245838). The primary endpoints are standard immunogenicity and 
safety assessments. The study will assess immunogenicity descriptively to help refine 
assumptions for potential Phase 3 endpoints. 
4.2.1 Rationale for Study Population 
This study will be conducted in the intended initial target population for IVX-A12, adults 
60 years and older, who are the recommended population for receiving a licensed RSV 
vaccine ahead of the winter season. 
4.3 
Justification for Dose of IVX-A12 
The dose of IVX-A12 for this protocol is 300 μg (150 μg RSV and 150 μg hMPV), as a 
non-adjuvanted dose. This dose was selected based on pre-clinical data of IVX-A12 and 
clinical data generated from the Phase 1 (ICVX-12-101) and Phase 2a (ICVX-12-201) studies. 

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4.4 
End-of-study Definition 
For the purpose of Clinical Trial Transparency the definition of the end of the study differs 
under Food and Drug Administration (FDA) and European Union (EU) regulatory 
requirements: 
EU requirements define study completion as the last visit of the last participant for any 
protocol- related activity. 
FDA requirements defines two completion dates: 
Primary Completion Date – the date that the final participant is examined or receives an 
intervention for the purposes of final collection of data for the primary outcome measure, 
whether the clinical study concluded according to the pre-specified protocol or was 
terminated. In the case of clinical studies with more than one primary outcome measure with 
different completion dates, this term refers to the date on which data collection is completed 
for all of the primary outcomes. 
Study Completion Date – the date the final participant is examined or receives an intervention 
for purposes of final collection of data for the primary and secondary outcome measures and 
AEs (for example, last participant’s last visit), whether the clinical study concludes according 
to the pre-specified protocol or is terminated. 
A participant is considered to have completed the study if they have completed all phases of 
the study including the last scheduled procedure shown in the SoA. 
5 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Adults ≥60 years of age at the time of signing informed consent. 
Type of Participant and Disease Characteristics 
2. Participants who are medically stable such that, according to the judgment of the 
Investigator, hospitalization within the study period is not anticipated and the 
participant appears likely to be able to remain on study through the end of 
protocol-specified follow-up. 

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A stable medical condition is defined as disease not requiring significant change in 
therapy or hospitalization for worsening disease during the 3 months prior to 
enrollment. 
3. Able to understand and comply with study requirements/procedures including 
attending all scheduled study visits (if applicable, with assistance by caregiver, 
surrogate, or legally authorized representative or equivalent representative as locally 
defined) based on the assessment of the Investigator. 
Informed Consent 
Capable of giving signed informed consent as described in Appendix A. Consenting to study 
participation includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol and also agreeing to any locally required authorization 
(eg, Health Insurance Portability and Accountability Act in the US). Consent must be obtained 
from the participant prior to performing any protocol -related procedures, including screening 
evaluations. 
5.2 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Acute (time-limited) or febrile (temperature ≥38.0 °C [100.4 ºF]) illness/infection 
within 3 days of planned dosing; participants excluded for transient acute illness may 
be dosed if illness resolves. 
2. History of a clinically significant bleeding disorder (eg, factor deficiency, 
coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising 
following IM injections or venipuncture. 
3. History of hypersensitivity to any component of the study vaccination. 
4. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis). 
5. Known or suspected congenital or acquired immunodeficiency. 
6. Known or suspected autoimmune condition as determined by history and/or physical 
examination. 
7. History of Guillain-Barré syndrome or any other demyelinating condition. 
8. History of malignancy other than treated non-melanoma skin cancers or locally-treated 
cervical cancer in previous 5 years. 
9. Any condition that may significantly increase the risk to the participant because of 
participation in the study, impact the participant’s ability to participate in the study, or 
impair the interpretation of the study data. 

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Prior/Concomitant Therapy 
10. Receipt of any licensed or investigational RSV and/or hMPV vaccine any time prior to 
administration of study intervention.  
11. Receipt of any licensed vaccine (other than licensed influenza or COVID-19 vaccines) 
within 28 days prior to or expected receipt within 28 days after administration of study 
intervention. Licensed influenza or COVID-19 vaccines are permitted beginning 
>14 days prior to and >14 days after administration of study intervention 
12. Receipt of immunoglobulin or blood products within 3 months prior to administration 
of study intervention or expected receipt during the study. 
13. Receipt of immune-modifying drugs or immunosuppressive therapy, such as 
anti-cancer chemotherapy or radiation therapy within 6 months prior to enrollment (or 
expected receipt during study), or long-term systemic corticosteroid therapy 
(prednisolone or equivalent at a dose of ≥20 mg daily or every other day for more than 
2 consecutive weeks) within 6 months prior to study intervention or anticipated receipt 
during study. Topical/inhaled steroids or short-term oral steroids are permitted. 
Prior/Concurrent Clinical Study Experience 
14. Participation in another study or receiving interventional study investigational 
medicinal product (IMP), in the preceding 28 days or expected receipt of another study 
intervention (or participation in another study) during the period of study follow-up.  
Other Exclusions 
15. Employees of the Sponsor involved in planning, executing, supervising, or reviewing 
the IVX-A12 program, clinical study site staff, or any other individuals involved with 
the conduct of the study, or immediate family members of such individuals. 
16. Alcohol or substance abuse that, in the opinion of the Investigator, might interfere with 
the study conduct or completion. 
17. Deprived of freedom by an administrative or court order, or in emergency setting, or 
hospitalized involuntarily.  
18. Judgment by the Investigator that the participant should not participate in the study if 
the participant is unlikely to comply with study procedures, restrictions, and 
requirements. 
5.3 Lifestyle Considerations 
Restrictions relating to concomitant medications are described in Section 6.9. 
5.4 
Screen Failures 
A screen failure occurs when a participant who has consented to participate in the clinical 
study is not subsequently assigned to study intervention. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet 
the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 

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respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Only a single rescreening is allowed in the study. Rescreened participants should 
be assigned the same participant number as for the initial screening.  
5.5 
Criteria for Temporarily Delaying Enrollment, Randomization, or 
Administration of Study Intervention  
The clinical trial enrollment will be halted if there is clear evidence of potential harm or 
harmful effects. Vaccine administration will be paused for further review and assessment if 
any of the following events occur:  
 
Any SAE (including death and serious allergic or hypersensitivity reaction) or AESI (see 
Section 8.4.7) that could be related to vaccine as per the Investigator or Sponsor.  
 
≥ 3 participants per group experiencing ≥ Grade 3 unsolicited non-serious reaction of the 
same or similar type (not explained by any other possible etiology) assessed as related to 
study vaccine. 
 
If any of the above criteria are met, a decision will be made as to whether dosing in the study 
will be allowed to resume. 
6 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
Study interventions are all pre-specified, IMPs and non-investigational medicinal product 
(NIMPs), medical devices and other interventions (eg, surgical and behavioral) intended to be 
administered to the study participants during the study conduct. 
6.1 
Study Intervention(s) Administered 
Participants will be randomized in a 1:1 ratio to receive either IVX-A12 or AREXVY on 
Visit 1. Details of these study interventions are presented in Table 3. 
It is recommended that the study interventions be administered as an IM injection into the 
deltoid of the non-dominant arm. 
All study participants will be observed in the clinic for at least 30 minutes after administration 
of study intervention (see Section 8.3.5.1). Allergic reactions to vaccines are possible. 
Therefore, appropriate drugs and medical equipment to treat acute anaphylactic reactions must 
be immediately available, and study personnel must be trained to recognize and treat 
anaphylaxis. 

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Table 3 
Study Interventions 
Intervention 
name  
IVX-A12 
AREXVY 
Type  
Vaccine 
Vaccine 
Dose formulation 
0.6 mg/mL IVX-121 and 0.6 mg/mL of 
IVX-241 in aqueous buffer (20 mM Tris, 
100 mM NaCl, 4% (w/v) Trehalose, 0.05% 
(v/v) PS-20, pH 7.4). 
Solid concentrate for suspension for 
injection supplied as a single-dose vial of 
lyophilized antigen component to be 
reconstituted with the accompanying vial 
of adjuvant suspension component 
Unit dose 
strength(s) 
0.5 mL 
0.5 mL 
Dosage level(s) 
Single IM dose of 300 μg (150 μg RSV / 
150 μg hMPV) 
Single IM dose of 120 μg RSVPreF3 
antigen 
Route of 
administration 
IM injection 
IM injection 
Use 
Investigational 
Active Comparator 
IMP or 
NIMP/AxMP 
IMP  
IMP 
Sourcing 
Icosavax 
Icosavax 
Packaging and 
labelling 
Study intervention will be provided in a 
glass vial. Each glass vial will be labelled 
as required per country requirement. 
AREXVY will be packaged and labelled as 
required per country requirement. 
6.2 
Preparation, Handling, Storage, and Accountability 
 
The Investigator or designee (eg, unblinded pharmacist) must confirm appropriate 
conditions (eg, temperature) have been maintained during transit for all study intervention 
received at the site and throughout the entire study until authorization is provided for on-site 
destruction or removal of the IMP, reflecting completion of the study. In the event of a 
temperature excursion detected at any time during the study, sites will follow the reporting 
procedures for notifying the Sponsor (or designated party); release of IMP for clinical use can 
only occur once the event has been reviewed and approval is provided by the Sponsor (or 
designated party). 
 
Only participants enrolled in the study may receive study intervention, and only 
authorized site staff may supply, prepare, or administer study intervention. All study 
intervention must be stored in a secure, environmentally-controlled, and monitored (manual or 
automated) area in accordance with the labelled storage conditions with access limited to the 
Investigator and authorized site staff. 

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 
The Investigator, institution, and the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record maintenance (ie, 
receipt, reconciliation, and final disposition records). 
 
Further guidance and information for the final disposition of unused study 
interventions are provided in the Pharmacy Manual or specific handling instructions. 
6.2.1 
Dose Preparation 
The dose of IVX-A12 and AREXVY for administration must be prepared by the unblinded 
pharmacy staff members (or an appropriate designee trained in study drug preparation), using 
aseptic technique in compliance with local regulations and site requirements.   
Doses of AREXVY vaccine administered as part of this study will be prepared in accordance 
with current local pharmacy or clinic guidelines per the USPI. 
Refer to the Pharmacy Manual for detailed information on dose preparation and handling 
procedures for IVX-A12 and AREXVY. 
6.2.2 
Dose Administration 
IVX-A12 must reach room temperature prior to administration. Once the IVX-A12 vial is 
punctured to perform dilution and drawn into a syringe for administration, the dose must be 
administered within 4 hours of vial puncture. The study intervention will be administered as a 
single IM injection, according to standard procedures for IM injections.  
Doses of AREXVY vaccine administered as part of this study will be administered in 
accordance with current local pharmacy or clinic guidelines per the USPI. 
The dose of IVX-A12 and AREXVY may be administered by an unblinded pharmacy staff 
member (or an appropriate designee in accordance with local and institutional regulations) 
who is independent of safety and other trial evaluations. 
Once the IMP administration is completed, the syringe must be discarded with the blinding 
cover in place to ensure that the blind is maintained. 
Refer to the Pharmacy Manual for detailed information on dose administration for IVX-A12 
and AREXVY. 
6.3 
Assignment to Study Intervention 
All participants will be centrally assigned to randomized study intervention using an 
Interactive Response Technology (IRT)/ Randomization and Trial Supply Management 
(RTSM). Randomization will be centrally stratified by age (60 to 69, 70 to 79, and ≥80 years 

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of age). Before the study is initiated, the telephone number and call-in directions for the IRT 
and/or the log in information and directions for the RTSM will be provided to each site. 
Study intervention will be dispensed at the study visits summarized in the SoA (Section 1.3). 
Returned study intervention should not be re-dispensed to the participants. 
The IRT/RTSM will provide to the Investigator(s) or pharmacists the kit identification number 
to be allocated to the participant at the dispensing visit. Routines for this will be described in 
the IRT/RTSM user manual that will be provided to each center. 
6.4 
Blinding 
Neither the participant nor any of the Investigators or Sponsor staff who are involved in the 
treatment or clinical evaluation and monitoring of the participants will be aware of the study 
intervention received. Since IVX-A12 and AREXVY are visually distinct prior to dose 
preparation (due to differences in packaging), the study intervention will be handled by an 
unblinded pharmacist and may be administered by an unblinded administrator (or designee, in 
accordance with local and institutional regulations) at the study site who will be independent 
of safety evaluations and other trial evaluations if another blinded study site member trained 
to give IMP injections is not available. Thus, personnel preparing and administering study 
intervention may be the same individual. Syringe masking will be required in order to 
maintain the blind. Refer to the Pharmacy Manual for detailed information on syringe 
masking procedures for IVX-A12 and AREXVY. 
The following personnel will have access to the randomization list during the study, prior to 
clinical database lock: 
 
Those generating the randomization list and IRT/RTSM system 
The randomization code should not be broken except in medical emergencies when the 
appropriate management of the participant requires knowledge of the treatment 
randomization. The Investigator documents and reports the action to the Sponsor, without 
revealing the treatment given to participant to the Sponsor staff. 
The Sponsor retains the right to break the code for SAEs that are unexpected and are 
suspected to be causally related to an IMP and that potentially require expedited reporting to 
regulatory authorities. Randomization codes will not be broken for the planned analyses of 
data until all decisions on the evaluability of the data from each individual participant have 
been made and documented. 
The IRT/RTSM will be programmed with blind-breaking instructions. Unblinding should only 
occur within the IRT/RTSM system. In case of an emergency, in which the knowledge of the 
specific blinded study intervention will affect the immediate management of the participant’s 
condition, the Investigator has the sole responsibility for determining if unblinding of a 
participants’ intervention assignment is warranted. Participant safety must always be the first 

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consideration in making such a determination. If a participant’s intervention assignment is 
unblinded, the Sponsor must be notified within 24 hours after breaking the blind. The 
Investigator documents and reports the action to the Sponsor, without revealing the treatment 
given to participant to the Sponsor staff. 
6.5 
Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention(s) directly from 
the Investigator or designee, under medical supervision. The date, and time if applicable, of 
dose administered in the clinic will be recorded in the source documents and recorded in the 
electronic case report form (eCRF). The dose of study intervention and study participant 
identification will be confirmed at the time of dosing by a member of the study site staff other 
than the person administering the study intervention.  
6.6 
Dose Modification 
Study intervention will be administered as described in Section 6.1 and Section 6.2 and per the 
schedule in the SoA (Section 1.3). Dose modification is not permitted. 
6.7 
Continued Access to Study Intervention After the End of the 
Study 
There is no intervention after the end of the study (see definition in Section 4.4). 
6.8 
Treatment of Overdose 
For this study, any dose of study intervention exceeding that specified in the protocol will be 
considered an overdose. 
There is no specific treatment for an overdose with vaccine study intervention. If overdose 
occurs, the participant should be treated supportively with appropriate monitoring as 
necessary. 
An overdose with associated AEs is recorded as the AE diagnosis/symptoms on the relevant 
AE modules in eCRF and on the Overdose CRF module. An overdose without associated 
symptoms is only reported on the Overdose CRF module. Refer to Section 8.4.13 for details 
of AE/SAE reporting related to overdose. 
6.9 
Prior and Concomitant Therapy 
All concomitant medications will be recorded in the source documents. Prohibited 
medications will additionally be recorded in the eCRF.  
For SAEs and AESIs, medications (over-the-counter and prescription) used to treat the SAE or 
AESI will also be recorded in the eCRF along with the information listed below. Vitamins 

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and/or herbal supplements should not be recorded. 
 
Reason for use 
 
Dates of administration including start and end dates 
 
Dosage information including dose, frequency, and route 
The Study Clinical Lead should be contacted if there are any questions regarding concomitant 
or prior therapy. 
6.9.1 
Permitted Concomitant Medications 
 Participants may take concomitant medications prescribed by their primary care provider 
for management of chronic medical conditions and/or for health maintenance.  
 Primary care providers or Investigators, where appropriate, should prescribe concomitant 
medications or treatments deemed necessary to provide full supportive care and comfort 
during the study. 
 Participants who develop adverse events after receiving study intervention should be 
treated with licensed medications and interventions according to standard of care. 
 The use of antipyretics and other pain medication to treat symptoms associated with study 
intervention administration or ongoing conditions is permitted.  
Note: Prophylactic use of these medications to prevent symptoms associated with study 
intervention administration are not permitted. However, if a participant is taking 
medication for another condition, even if it may have antipyretic or pain-relieving 
properties, it should not be withheld prior to study vaccination. 
 All routine vaccinations other than influenza or COVID-19 vaccines are permitted 
>28 days prior to and >28 days after the last dose of study intervention. Licensed 
influenza or COVID-19 vaccines are permitted beginning >14 days before and >14 days 
after administration of study intervention. 
6.9.2 
Prohibited Concomitant Medications 
The following are prohibited, and the Sponsor must be notified if a participant receives any of 
these prohibited medications. Any use of prohibited medications must be recorded in the 
eCRF and reported as a protocol deviation. 
The use of prohibited medications and/or vaccines does not always require a withdrawal of the 
participant from the study but may determine a participant’s evaluability in the 
immunogenicity analysis set. 
 Receipt of any licensed or investigational RSV and/or hMPV vaccine prior to 
administration of study intervention and through to completion of Visit 4. 

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Participants choosing to receive a licensed and/or authorized RSV vaccine outside the 
study should inform the Investigator so it can be documented; all doses of RSV 
vaccine must be recorded. 
- 
Participants who receive a licensed and/or authorized RSV vaccine outside the study 
should be encouraged to continue study conduct to be followed for safety reporting 
and all assessments 
 Receipt of any licensed or investigational vaccine (other than licensed influenza or 
COVID-19 vaccines) within 28 days prior to, or receipt within 28 days after, 
administration of study intervention  
- 
Licensed influenza or COVID-19 vaccines are permitted beginning >14 days before 
and >14 days after administration of study intervention. 
 Investigational products indicated for the treatment of RSV/hMPV 
- 
Note: For participants who become hospitalized with RSV or hMPV, participation in 
investigational treatment studies is permitted. 
 Glucocorticoids at a dose of ≥20 mg/day of prednisone or equivalent given daily for 
≥14 consecutive days between randomization and the participant’s scheduled final visit. 
- 
Topical/inhaled steroids or short-term oral steroids are permitted. 
 Immunoglobulins and/or any blood product within 3 months prior to administration of 
study intervention and through the participant’s scheduled final visit. 
 Other systemically administered drugs with significant immunosuppressive activity, such 
as azathioprine, mycophenolate, tacrolimus, cyclosporine, methotrexate, or cytotoxic 
chemotherapy, between randomization and the participant’s scheduled final visit.  
7 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix A. 
7.1 
Discontinuation of Study Intervention 
Each participant will receive one dose of study intervention. An individual participant will not 
receive study intervention if any of the following occur in the participant in question:  
 Participant withdraws consent after signing the ICF  
 Participant meets any of the exclusion criteria or fails to meet all inclusion criteria for 
study participation (see Section 5.1 and 5.2) 
Each participant who has received study intervention will be followed for the full study period 
unless consent is withdrawn specifically from further study participation, or the participant is 
lost to follow-up. 

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Note that discontinuation from study intervention is not the same thing as a discontinuation or 
withdrawal from the study (see Section 7.2). 
7.2 
Participant Discontinuation/Withdrawal From the Study 
Discontinuation of the participant from the study by the Investigator: 
 
A participant may be discontinued from the study at any time at the discretion of the 
Investigator for behavioral, compliance, or administrative reasons. 
Voluntary withdrawal from the study by the participant 
 
A participant may withdraw from the study at any time at the participant’s own request 
for any reason (or without providing any reason). 
 
A participant who wishes to withdraw from the study must be informed by the 
Investigator about modified follow-up options (eg, telephone contact, a contact with a 
relative or treating physician, or information from medical records). 
 
If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
 
If the participant withdraws from the study, the Sponsor may retain and continue to use 
any samples collected before such a withdrawal of consent for the purposes the 
participant originally consented unless the participant withdraws consent for use of 
samples already collected. If the participant specifically withdraws consent for any use of 
samples, it must be documented in the site study records by the Investigator and the 
Investigator must inform the Sponsor. Destruction of any samples taken and not yet tested 
should be carried out in line with documented sample withdrawal wishes in conjunction 
with what was stated in the informed consent and local regulation. 
7.3 
Lost to Follow-up 
A participant will be considered lost to follow-up if the participant repeatedly fails to return 
for scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the study site for a 
required study visit: 
 
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible. The participant should be counselled on the importance of maintaining the 
assigned visit schedule. At this time ascertain whether the participant should or wishes to 
or continue in the study. 
 
Before a participant is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls, texts, 

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emails, and if necessary, a certified letter to the participant’s last known mailing address 
or local equivalent methods). These contact attempts should be documented in the 
participant’s medical record. 
 
Should the participant continue to be unreachable, the participant will be considered to 
have been lost to follow-up.  
 
Site personnel, or an independent third party, will attempt to collect the vital status of the 
participant within legal and ethical boundaries for all participants randomized, including 
those who did not get study intervention. Public sources may be searched for vital status 
information. If vital status is determined as deceased, this will be documented, and the 
participant will not be considered lost to follow-up. Sponsor personnel will not be 
involved in any attempts to collect vital status information. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the Section 1.3 SoA. Protocol waivers or 
exemptions are not allowed. 
 
Urgent safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to assess course of action. 
 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
 
Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICF may be utilized for screening or baseline 
purposes provided the procedures met the protocol-specified criteria and were performed 
within the time frame defined in the SoA. 
 
Instructions for the collection and handling of human biological samples (HBS) will be 
provided in the study-specific laboratory manual. Samples should be stored in a secure 
storage space with adequate measures to protect confidentiality. For further details on 
handling of HBS see Appendix C. 
The maximum amount of blood collected from each participant, including any extra 
assessments that may be required, will not exceed approximately 190 mL over the duration of 
the study (see Section 8.9.1 for collection of blood samples collected for immunogenicity 
assessment). Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 

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8.1 
Administrative and General/Baseline Procedures 
Study procedures and their timing are summarized in the SoA (Section 1.3). Procedures 
outlined in the SoA are described throughout Section 8. 
8.2 
Efficacy Assessments 
Not applicable. Immunogenicity assessments are described in Section 8.9. 
8.3 
Safety Assessments 
Planned time points for all safety assessments are provided in the Section 1.3 SoA. 
8.3.1 
Physical Examinations 
A targeted physical examination will include areas suggested by medical history. Any 
clinically significant abnormal finding prior to vaccination should be reported as medical 
history in the CRF. Any clinically significant abnormal finding following vaccination will be 
recorded as an AE, if started before Day 29. The day of the AE resolution must also be 
recorded. 
Physical examination will be performed at timepoints as specified in the Section 1.3 SoA.  
8.3.2 
Vital Signs 
Body temperature, blood pressure, height, and weight measurements will be performed at 
timepoints as specified in the Section 1.3 SoA. 
8.3.3 
Electrocardiograms 
There are no scheduled ECGs in this study. Electrocardiograms may be performed as 
clinically indicated based on participant health, medical history, and ongoing AEs.  
8.3.4 
Clinical Safety Laboratory Tests 
There are no scheduled clinical chemistry and hematology tests in this study. Such tests may 
be performed as clinically indicated based on participant health, medical history, and ongoing 
AEs. 
8.3.5 
Other Safety Assessments 
8.3.5.1 
Immediate Post-vaccination Observation 
Participants will be kept under observation for at least 30 minutes after vaccination and 
assessed for immediate unsolicited AEs. The post-vaccination observation should be 
documented in the eCRF. 

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8.4 
AEs, SAEs, and Other Safety Reporting 
The Principal Investigator is responsible for ensuring that all staff involved in the study are 
familiar with the content of this section. 
The definitions of an AE or SAE can be found in Appendix B. 
Participants (or, when appropriate, a caregiver, surrogate, or the participant’s legally 
authorized representative) will notify the Investigator or designees of symptoms. These must 
then be assessed by the Investigator and if considered an AE it will be reported by the 
Investigator. 
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE. 
AE variables 
The following variables will be collected for each AE: 
 
AE (verbatim) 
 
The date when the AE started and stopped 
 
Maximum severity or changes in severity 
 
Whether the AE is serious or not 
 
Investigator causality rating against the IMP(s) (yes or no) 
 
Action taken with regard to IMP(s) 
 
AE caused participant’s withdrawal from the study (yes or no) 
 
Outcome 
In addition, the following information will be collected for SAEs and, where applicable, 
AESIs: 
 
Date AE met criteria for SAE 
 
Date Investigator became aware of SAE 
 
AE description 
 
AE is serious due to 
 
Date of hospitalization 
 
Date of discharge 
 
Probable cause of death 
 
Date of death 
 
Autopsy performed 

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 
Causality assessment in relation to study procedure(s) 
 
Causality assessment to other medication 
 
Medication given to treat SAE/AESI (Yes/No) 
 
8.4.1 
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information 
Immediate unsolicited AEs (those that occur within the 30 minutes after each vaccine) will be 
recorded during the immediate post-vaccination observation period, per Section 8.3.5.1)  
Unsolicited AEs will be collected from time administration of study intervention through 
Day 29. 
SAEs will be recorded from the time of signing of the ICF throughout the study, up to and 
including the last study visit. MAAEs and AESIs will be recorded from time of administration 
of study intervention throughout the study, up to and including the last study visit. 
If the Investigator becomes aware of an SAE with a suspected causal relationship to the IMP 
that occurs after the end of the clinical study in a treated participant, the Investigator shall, 
without undue delay, report the Sponsor. 
8.4.2 
Follow-up of Adverse Events and Serious Adverse Events 
Any AEs that are unresolved at the participant’s last AE assessment in the study are followed 
up by the Investigator for as long as medically indicated, but without further recording in the 
eCRF.  
The Sponsor retains the right to request additional information for any participant with 
ongoing AE(s)/MAAE(s)/AESI(s)/SAE(s) at the end of the study, if judged necessary. 
8.4.3 
Causality Collection 
The Investigator should assess causal relationship between IMP and each AE, and answer 
‘yes’ or ‘no’ to the question ‘Do you consider that there is a reasonable possibility that the 
event may have been caused by the IMP?’ 
For SAEs, causal relationship should also be assessed for other medication and study 
procedures. Note that for SAEs that could be associated with any study procedure the causal 
relationship is implied as ‘yes’. 
A guide to the interpretation of the causality question is found in Appendix B.  

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8.4.4 
Adverse Events Based on Examinations and Tests 
Deterioration as compared to baseline in protocol-mandated vital signs should only be 
reported as AEs if they meet any of the following: 
 Fulfill any of the SAE criteria 
 Are clinically relevant as judged by the Investigator (which may include but is not 
limited to consideration as to whether intervention or non-planned visits were 
required).  
If deterioration in a vital sign is associated with clinical signs and symptoms, the sign or 
symptom will be reported as an AE and the associated vital sign will be considered as 
additional information. In the absence of clinical signs or symptoms, clinically relevant 
deteriorations in non-mandated parameters should be reported as AE(s). 
Any new or aggravated clinically relevant abnormal medical finding at a physical examination 
as compared with the baseline assessment will be reported as an AE as per Section 8.4.1. 
The results from the protocol-mandated vital signs will be summarized in the clinical study 
report (CSR).  
8.4.5 
Adverse Events Based on Signs and Symptoms 
All signs or symptoms spontaneously reported by the participant or care provider or reported 
in response to the open question from the study site staff: ‘Have you had any health problems 
since the previous visit/you were last asked?’, or revealed by observation will be collected and 
recorded in the eCRF.  
When collecting AEs, the recording of diagnoses is preferred (when possible) to recording a 
list of signs and symptoms. However, if a diagnosis is known and there are other signs or 
symptoms that are not part of the diagnosis, the diagnosis and each sign or symptom will be 
recorded separately. 
8.4.6 
Solicited Adverse Reactions (Reactogenicity) 
Solicited injection site and systemic predefined ARs will be collected in a solicited AR 
reactogenicity eDiary for all participants for 7 days after study vaccination, from Day 1 (day 
of vaccination) through Day 8 (for a total of 8 days). 
All participants will be given a standard digital thermometer for measuring daily temperatures, 
a ruler for measuring the size of injection site reactions if any, and an eDiary to capture 
reactogenicity. All participants will be asked to report on signs and symptoms of solicited ARs 
(Table 4) for 7 days following study vaccination and whether medication was taken to relieve 
the symptoms. Investigators will report on solicited ARs that are ongoing beyond the eDiary 

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reporting period (ie, 7 days following study vaccination) through to resolution. Solicited ARs 
should not be reported as unsolicited AEs during the 7 days following vaccination, unless they 
fulfill the criteria for SAEs or MAAEs. If a solicited AE has not resolved by Day 8, the 
solicited AE will be reported as “ongoing” in the eDiary and the investigator or designee must 
obtain the stop date from the participant to record in the eCRF. 
Table 4 
Predefined Solicited Adverse Reactions for Reactogenicity Assessment 
Injection Site 
Systemic  
Injection site pain  
Fever  
Injection site erythema/redness 
Chills 
Injection site swelling  
Headache 
 
Myalgia (muscle aches and pains) 
Fatigue (physical or mental tiredness) 
Severity will be assessed for solicited ARs by the participant according to toxicity grading 
scales modified and abridged from the US FDA Guidance on Toxicity Grading Scale for 
Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (US 
FDA 2007) as defined in Appendix B 4. 
8.4.7 
Adverse Events of Special Interest 
An AESI is an event of scientific and medical interest, specific to the further understanding of 
the safety profile of the investigational vaccine and requires close monitoring and rapid 
communication by the Investigators to the Sponsor. An AESI can be serious or non-serious. 
All AESIs will be collected from the time of administration of study intervention through 
completion of the study, up to and including the last study visit. 
All AESIs will be collected in the eCRF through ongoing observation and questioning per 
Section 8.4.1. Serious AESIs will be recorded and reported per Section 8.4.10. 
The AESIs for IVX-A12, which are based on adverse events reported with other RSV 
vaccines, are immune-mediated neurologic diseases (including Guillain-Barré syndrome) and 
atrial fibrillation. 
8.4.8 
Medically-attended Adverse Events 
MAAEs are defined as AEs leading to medically-attended visits that were not routine visits for 
physical examination or vaccination, such as an emergency room visit, or an otherwise 
unscheduled visit to or from medical personnel (medical doctor) for any reason.  
MAAEs will be collected according to the timepoints specified in the SoA (Section 1.3). 
MAAEs will be collected from the time of administration of study intervention throughout the 
study, up to and including the last study visit. 

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Any AEs (including abnormal vital signs) identified on a routine study visit will not be 
considered MAAEs. 
8.4.9 
Hy’s Law 
Liver biochemistry are not required for routine safety monitoring as part of this study or for all 
participants in this study. However, the Investigator should be vigilant for Potential Hy’s Law 
case from laboratory tests (performed for other reasons) or AEs or clinical signs and 
symptoms suggestive of liver injury. Such cases where a participant shows elevations in liver 
biochemistry may require further evaluation. 
8.4.10 
Reporting of Serious Adverse Events 
All SAEs must be reported, whether or not considered causally related to the IMP. All SAEs 
will be recorded in the eCRF. 
If any SAE occurs during the study, Investigators or other site personnel will inform the 
appropriate Sponsor representatives within 1 day, ie, immediately but no later than 24 hours 
of when they become aware of it. 
The designated Sponsor representative will work with the Investigator to ensure that all the 
necessary information is provided to the Sponsor’s Patient Safety data entry site within 
1 calendar day of initial receipt for fatal and life-threatening events and within 5 calendar 
days of initial receipt for all other SAEs. 
For fatal or life-threatening AEs where important or relevant information is missing, active 
follow-up will be undertaken immediately. Investigators or other site personnel will inform 
Sponsor representatives of any follow-up information on a previously reported SAE within 
1 calendar day, ie, immediately but no later than 24 hours of when they become aware of it. 
Once the Investigators or other site personnel indicate an AE is serious in the Electronic Data 
Capture (EDC) system, an automated email alert is sent to the designated Sponsor 
representative. 
If the EDC system is not available, then the Investigator or other study site staff reports the 
SAE via secure method to the appropriate Sponsor representative. 
When the EDC is temporarily not accessible, the Sponsor Study Representative should 
confirm that the Investigator/site staff enters the SAE in the EDC when access resumes. 
For further guidance on the definition of an SAE, see Appendix B. 
The reference document for definition of expectedness/listedness is the IB for IVX-A12 and 
the USPI for AREXVY.  

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8.4.11 
Pregnancy 
Not applicable for this population. 
8.4.12 
Medication Error and Study Intervention Misuse 
8.4.12.1 
Timelines 
If an event of medication error or study intervention misuse occurs during the study, then the 
Investigator or other site personnel informs the appropriate Sponsor representatives within 
1 calendar day, ie, immediately but no later than 24 hours of when they become aware of it.  
The designated Sponsor representative works with the Investigator to ensure that all relevant 
information is completed within 1 (initial fatal/life-threatening or follow-up 
fatal/life-threatening) or 5 (other serious initial and follow-up) calendar days if there is an 
SAE associated with the event of medication error or study intervention misuse (see 
Section 8.4.6) and within 30 days for all other events. 
8.4.12.2 
Medication Error 
For the purposes of this clinical study a medication error is an unintended failure or mistake 
in the treatment process for an IMP or Sponsor NIMP that either causes harm to the 
participant or has the potential to cause harm to the participant. 
The full definition and examples of medication error can be found in Appendix B 4. 
8.4.12.3 
Study Intervention Misuse 
Study intervention misuse is the intentional and inappropriate use (by a study participant) of 
IMP or Sponsor NIMP for medicinal purposes outside of the unauthorized product 
information, or for unauthorized IMPs or Sponsor NIMPs, outside the intended use as 
specified in the protocol and includes deliberate administration of the product by the wrong 
route. 
The full definition and examples of study intervention misuse can be found in Appendix B 4. 
8.4.13 
Reporting of Overdose 
Refer to Section 6.8 for definition and treatment of overdose. 
 An overdose with associated AEs is recorded as the AE diagnoses/symptoms on the 
relevant AE modules in the eCRF and on the Overdose eCRF module. 
 An overdose without associated symptoms is only reported on the Overdose eCRF 
module. 
If an overdose on an IMP or Sponsor NIMP occurs in the course of the study, the Investigator 
or other site personnel inform appropriate Sponsor representatives immediately, but no later 

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than 24 hours of when he or she becomes aware of it. 
The designated Sponsor representative works with the Investigator to ensure that all relevant 
information is provided to the Sponsor Patient Safety data entry site within 1 or 5 calendar 
days for overdoses associated with an SAE (see Section 8.4.6) and within 30 days for all 
other overdoses. 
8.5 
Pharmacokinetics  
Pharmacokinetic parameters are not evaluated in this study. 
8.6 
Pharmacodynamics  
Pharmacodynamic parameters are not evaluated in this study. 
8.7 
Optional Genomics Initiative  
Optional Genomics Initiative research is not applicable in this study.  
8.8 
Biomarkers 
Collected samples associated with cell-mediated immunity (CMI) and cellular biomarker 
analyses are described in Section 8.9.2. 
8.9 
Immunogenicity Assessments 
Blood samples for immunogenicity assessments in serum will be collected according to the 
SoA (Section 1.3). Samples will be collected, labelled, stored, and shipped as detailed in the 
Laboratory Manual. For storage, re-use, and destruction of samples see Appendix C.  
The results from exploratory analyses may not be reported in the CSR. 
8.9.1 
Neutralizing Antibody Responses 
Blood sampling for immunogenicity will be collected from all participants at Days 1, 29, and 
181 (see Section 1.3). Neutralizing antibody responses to RSV A and RSV B will be measured 
using green fluorescence protein (GFP) neutralization assays at 
 
. Additional exploratory assessment will be performed using RSV A and B 
microneutralization assay at Viroclinics Biosciences (Rotterdam, Netherlands). Neutralizing 
responses to hMPV A and hMPV B will also be evaluated. Collected samples may also be 
utilized to investigate additional humoral immune responses, as determined by the Sponsor 
based upon emerging safety, efficacy, immunobridging, and immunogenicity data. 
8.9.2 
Cellular Mediated Immune Responses and Exploratory Analyses 
Participants will have additional blood samples drawn on Days 1, 8, 29, and Day 181 for CMI 
and exploratory cellular biomarker analyses. Immune responses will be assessed by 

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characterizing peripheral blood mononuclear cells (PBMCs) using functional and phenotypic 
profiling methods that may include intracellular cytokine staining to evaluate Th1 and Th2 
responses, activation induced marker assays, B-cell and innate immune cell phenotyping, 
single-cell RNA sequencing, and T and B-cell receptor sequencing. 
8.10 
Health Economics OR Medical Resource Utilization and Health 
Economics  
Health economics / medical resource utilization and health economics parameters are not 
evaluated in this study. 
8.11 
Study Participant Feedback Questionnaire  
This section is not applicable to this study. 
9 
STATISTICAL CONSIDERATIONS 
The first version of the Statistical Analysis Plan (SAP) will be finalised prior to the earliest 
occurrence of the following milestones: 90 days after First Subject In or the first Dry Run; and 
it will include a more technical and detailed description of the planned statistical analyses. 
This section is a summary of the planned statistical analyses of the most important endpoints 
including primary and key secondary endpoints. 
9.1 
Statistical Hypotheses 
There is no formal statistical hypothesis testing planned for this study. Descriptive analyses 
will support evaluation of immunogenicity and safety, and qualitative comparison between 
groups. 
9.2 
Sample Size Determination 
Approximately 140 participants will be randomized to IVX-A12 or AREXVY. Because all 
analyses will be descriptive in nature and no hypothesis is being tested statistically, no formal 
sample size calculations were performed. The sample size is considered sufficient for an 
assessment of immunogenicity and safety. 
9.3 
Populations for Analyses 
The following populations are defined (Table 5): 
 
 

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Table 5 
Populations for Analysis 
Population/analysis set 
Description 
Safety analysis set (SAF) 
All randomized participants who receive one dose of study intervention, 
irrespective of their protocol adherence and continued participation in the 
study. Participants who withdraw consent to participate in the study will be 
included up to the date of their study withdrawal. For analyses and displays 
based on the SAF, participants will be classified according to the study 
intervention they actually received. 
The SAF is to be used for safety analyses. 
Immunogenicity analysis set 
(IAS) 
All participants in the SAF who have no eligibility-related protocol 
deviations judged to have the potential to interfere with the generation or 
interpretation of an immune response.  
The IAS is to be used for the analysis of immunogenicity endpoints. 
9.4 
Statistical Analyses 
9.4.1 
General Considerations 
Data will be provided in data listings sorted by vaccination group and participant number. 
Tabular summaries will be presented by vaccination group. 
Categorical variables will be summarized using frequency and percentages, where the 
denominator for calculation is the underlying analysis set population, unless otherwise stated. 
Continuous variables will be summarized with descriptive statistics of number of available 
observations, mean, standard deviation, median, minimum and maximum, and quartiles where 
more appropriate.  
All point estimates will be presented with a two-sided 95% confidence interval (CI), unless 
otherwise stated. 
Immunogenicity summaries for a specific endpoint will include participants in the 
immunogenicity analysis set with a baseline and at least one post-baseline quantifiable result 
for that endpoint. 
9.4.2 
Immunogenicity  
9.4.2.1 
Primary and Secondary Endpoint(s) 
Geometric mean titer (GMT) will be calculated as the anti-logarithm Σ(log2 transformed 
titer)/n, ie, as the anti-logarithm transformation of the mean of the log-transformed titer, where 
n is the number of participants with titer information. The 95% CI about the GMT will be 
calculated as the anti-logarithm transformation of the upper and lower limits for a two-sided 
CI for the mean of the log-transformed titers. 
The fold rise is calculated as the ratio of the post-dose titer level to the pre-dose titer level. 

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Geometric mean fold rise (GMFR) will be calculated as anti-logarithm of Σ(log2 transformed 
(post-dose titer/ pre-dose titer)/n. The 95% CIs for GMFR will be calculated similarly to those 
for GMT. 
Seroresponse is a binary outcome where a success is when the fold rise in titers compared to 
baseline is ≥4. The number and percentage of participants with post-vaccination seroresponse, 
and 95% CIs, calculated using the Clopper-Pearson exact method, will be provided. In the 
event of a 0% or 100% seroresponse, a one-sided 97.5% CI will be reported. 
For the Day 29 primary analysis, adjusted GMTs and GMT ratios, along with their 
corresponding 95% CIs, will be estimated using an analysis of covariance (ANCOVA) model 
that includes a dependent variable of log titers, study arm as a fixed effect, and log baseline 
titer and age group as covariates. For the final analysis, model-adjusted GMTs and GMT ratios 
at Days 29 and 181, along with their corresponding 95% CIs, will be estimated using an 
mixed model for repeated measures (MMRM) that includesa dependent variable of log 
titers,study arm as a fixed effect, log baseline titer, age group (60 to 69, 70 to 79, and 
≥80 years of age), visit indicators (Days 29 and 181) as covariates, and a study arm by visit 
interaction term.  
Model-adjusted GMTs and GMT ratios will be used for analyses of the nAb response 
endpoints, while raw unadjusted values will be summarized as supportive analyses. GMFR 
and seroresponse will be unadjusted.  
The unadjusted and model-adjusted GMTs and GMT ratios, along with their corresponding 
95% CIs will be calculated for each study arm and summarized by visit based on the 
immunogenicity analysis set. The unadjusted GMFR and seroreponse along with their 
corresponding 95% CIs, will be calculated for each study arm and summarized by visit. 
Descriptive statistics will include number of participants, geometric mean, 95% CI, minimum 
and maximum. Summaries may be repeated by pre-specified subgroups, including, but not 
limited to: age group. The final list of subgroup variables will be provided in the SAP. 
Primary immunogenicity analyses will be conducted on data reported from samples analyzed 
by the GFP RSV A neutralization assay conducted at 
. 
Supportive analyses will be performed on results reported by other exploratory assays, with 
more details provided in the SAP. 
9.4.2.2 
Exploratory Endpoint(s) 
The analysis of exploratory endpoints will be described in the SAP. 
9.4.3 
Safety 
Each solicited AR will be summarized overall and by study arm, study day, and severity 
grading. In addition, the number of days participants reported experiencing each event will be 

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presented. The duration of solicited ARs will be calculated as the last day of the AR – the first 
day of the AR + 1. If the event is ongoing on Day 8, the total number of days will include the 
days beyond Day 8 through the stop date for the event. 
An overall summary of safety will be presented by study arm, including the number and 
percentage of participants who experience at least one AE (including immediate AEs), SAEs, 
AESIs and MAAEs. Summaries will present number and percentage of AEs in the categories 
listed that are related to study intervention as assessed by the Investigator, severe in intensity, 
serious, and resulting in death. A listing will cover details for each AE. 
9.4.4 
Other Analyses  
Not applicable. 
9.5 
Planned Analyses 
A Primary Analysis will be performed after all participants have completed Day 29 (Visit 3) 
safety assessments and when all Day 29 primary immunogenicity data for RSV A (measured 
in GFP RSV Neutralization Assay, 
) are available. This analysis will support 
further evaluation of immunogenicity and safety of IVX-A12 in older adults.  
A final analysis will be performed after all participants complete the study. 
The SAP will describe the planned analyses in greater detail. 
9.6 
Data Monitoring Committee  
Not applicable.  
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
 
 

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Appendix A Regulatory, Ethical, and Study Oversight Considerations 
A 1 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
 Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki as amended at 64th WMA General Assembly, Fortaleza, 
Brazil, October 2013 and Council for International Organizations of Medical Sciences 
International Ethical Guidelines 
 Applicable ICH GCP Guidelines 
 Applicable laws and regulations 
The protocol, revised protocol, ICF, IB, and other relevant documents (eg, advertisements) 
must be submitted to an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) by the Investigator and reviewed and approved by the IRB/IEC before the study is 
initiated. 
Any revised protocol will require IRB/IEC and applicable Regulatory Authority approval 
before implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants. 
The Sponsor will be responsible for obtaining the required authorizations to conduct the study 
from the concerned Regulatory Authority. This responsibility may be delegated to a Contract 
Research Organization (CRO), but the accountability remains with the Sponsor. 
The Investigator will be responsible for providing oversight of the conduct of the study at the 
site and adherence to requirements of 21 CFR 312.120, ICH guidelines, the IRB/IEC, 
European Regulation 536/2014 for clinical studies (if applicable), European Medical Device 
Regulation 2017/745 for clinical device research (if applicable), and all other applicable local 
regulations. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting 
to the regulatory authority, IRB/IEC, and Investigators. 
For all studies except those utilizing medical devices, Investigator safety reports must be 
prepared for suspected unexpected serious adverse reactions (SUSAR) according to local 
regulatory requirements and Sponsor policy and forwarded to Investigators as necessary. 
Adherence to European Medical Device Regulation 2017/745 for clinical device research (if 
applicable), and all other applicable local regulations 

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An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will review and then 
file it along with the IB and will notify the IRB/IEC, if appropriate according to local 
requirements. 
Regulatory Reporting Requirements for Serious Breaches of Protocol or GCP 
Prompt notification by the Investigator to the Sponsor of any (potential) serious breach of the 
protocol or regulations is essential so that legal obligations and ethical obligations are met. 
A “serious breach” means a breach likely to affect to a significant degree the safety and rights 
of a participant or the reliability and robustness of the data generated in the clinical study. 
The Sponsor will comply with country-specific regulatory requirements relating to serious 
breach reporting to the regulatory authority, IRB/IEC, and Investigators. 
Where the EU Clinical Trials Regulation 536/2014 applies, the Sponsor has in place processes 
to enter details of serious breaches into the European Medicines Agency Clinical Trials 
Information System (CTIS). It is important to note that redacted versions of serious breach 
reports will be available to the public via CTIS. 
If any (potential) serious breach occurs in the course of the study, Investigators or other site 
personnel will inform the appropriate Sponsor representatives immediately. 
In certain regions/countries, the Sponsor has a legal responsibility to notify both the local 
regulatory authority and other regulatory agencies about such breaches. 
The Investigator should have a process in place to ensure that: 
The site staff or service providers delegated by the Investigator/institution are able to identify 
the occurrence of a (potential) serious breach 
A (potential) serious breach is promptly reported to the Sponsor or delegated party, through 
the contacts (email address or telephone number) provided by the Sponsor. 
A 2 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the study and for one 
year after completion of the study. 
A 3 
Informed Consent Process 
The Investigator or their representative will explain the nature of the study to the participant or 
their legally authorized representative and answer all questions regarding the study. 
Participants must be informed that their participation is voluntary, and they are free to refuse 
to participate and may withdraw their consent at any time and for any reason during the study. 

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Participants or their legally authorized representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, privacy and data protection requirements, where applicable, and the IRB/IEC or 
study center. 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF. 
If new information requires changes to the ICF, consider if participants must be re-consented 
and if so, this must be to the most current version of the ICF(s) during their participation in the 
study. 
A copy of the ICF(s) must be provided to the participant or the participant’s legally authorized 
representative. 
A participant who is rescreened is not required to sign another ICF if the rescreening occurs 
within 28 days from the previous ICF signature date. 
A 4 
Data Protection 
Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names 
or any information which would make the participant identifiable will not be transferred. 
The participant must be informed that their personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure and use of their 
data must also be explained to the participant in the informed consent.  
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
The participant must be informed that data will be collected only for the business needs. We 
will only collect and use the minimum amount of personal data to support our business 
activities and will not make personal data available to anyone (including internal staff) who is 
not authorized or does not have a business need to know the information.  
The participant must be informed that in some cases their data may be pseudonymized. The 
General data Protection Regulation defines pseudonymization as the processing of personal 
data in such a way that the personal data can no longer be attributed to a specific individual 
without the use of additional information, provided that such additional information is kept 
separately and protected by technical and organizational measures to ensure that the personal 
data are not attributed to an identified or identifiable natural person. 
Personal Data Breaches 
A ‘personal data breach’ means a breach of security leading to the accidental or unlawful 
destruction, loss, alteration, unauthorized disclosure of, or access to, personal data transmitted, 
stored or otherwise processed. 

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In compliance with applicable laws, the Data Controller1 for the processing activity where the 
personal data breach occurred (the Sponsor or respectively the site), will notify the data 
protection authorities without undue delay within the legal terms provided for such 
notification and within the prescribed form and content. 
While the Sponsor has processes in place to deal with personal data breaches it is important 
that Investigators that work with the Sponsor have controls in place to protect patient data 
privacy. 
The Investigator should have a process in place to ensure that: 
allow site staff or service providers delegated by the Investigator/institution to identify the 
occurrence of a (potential) personal data breaches. 
Any (potential) personal data breach is promptly reported to the Sponsor or delegated party, 
through the contacts (email address or telephone number) provided by the Sponsor. 
The Sponsor and the site must demonstrate that they: 
have taken all necessary steps to avoid personal data breaches and  
have undertaken measures to prevent such breaches from occurring in the first place and to 
mitigate the impact of occurred data breaches (eg, applying encryption, maintaining and 
keeping systems and IT security measures up-to-date, regular reviews and testing, regular 
training of employees, and developed security policies and standards). 
where possible, have developed an internal data breach reporting and investigation process 
and internal protocols with guidance on how to respond swiftly and diligently to the 
occurrence of a personal data breach. 
where it has not been possible to develop an internal data breach reporting and investigation 
process, the site follows the Sponsor’s instructions. 
Notification of personal Data Breach to participants: 
notification to participants is done by the site for the data breaches that occurred within the 
processing activities for which the site is the Data Controller and for data breaches occurred 
within the processing activities of the Sponsor as the Data Controller, the notification is done 
in collaboration with the site and is performed by the site and/or Principal Investigator, acting 
 
 
 
 
 
1 The data controller determines the purposes for which and the means by which personal 
data is processed, as defined by the European Commission 

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on behalf of the Sponsor, so that the Sponsor has no access to the identifying personal 
information of the participants. The site and/or Principal Investigator shall conduct the 
notification by contacting the participants using the information that they gave for 
communication purposes in clinical research. 
If a personal data breach occurs in a processor’s systems, engaged by the Sponsor, the 
processor under contractual obligations with the Sponsor promptly and in due course after 
discovering the breach notifies the Sponsor and provides full cooperation with the 
investigation. In these cases, to the extent the Sponsor is the Data Controller for the processing 
activity where the breach occurred, it will be responsible for the notification to data protection 
authorities and, if applicable, to participants. If the personal data breach needs to be notified to 
the participants, the notification to participants is done in collaboration with the site and is 
performed by the site and/or Principal Investigator, acting on behalf of the Sponsor, so that the 
Sponsor has no access to the identifying personal information of the participants. 
If a personal data breach involving a Sponsor’s representative device (i.e. Study Monitor 
laptop), the Sponsor representative will provide the Sponsor with all of the information 
needed for notification of the breach, without disclosing data that allows the Sponsor directly 
or indirectly to identify the participants. The notification will be done by the Sponsor solely 
with the information provided by the Study Monitor and in no event with access to 
information that could entail a risk of re-identification of the participants. If the data breach 
must be notified to the data subjects, the notification will be done directly by the Study 
Monitor in collaboration with the site and/or Principal Investigator, acting on behalf of the 
Sponsor, so that the Sponsor has no access to the identifying personal information of the 
participants. The contract between the Sponsor and the Study Monitor shall expressly specify 
these conditions. 
The contract between the site and the Sponsor for performing the clinical research includes the 
provisions and rules regarding who is responsible for coordinating and directing the actions in 
relation to the breaches and performing the mandatory notifications to authorities and 
participants, where applicable. 
A 5 
Committees Structure 
The safety of all Sponsor clinical studies is closely monitored on an ongoing basis by the 
Sponsor representatives in consultation with Patient Safety. Issues identified will be 
addressed; for instance, this could involve members to the Clinical Study Protocol and letters 
to Investigators. 
A 6 
Dissemination of Clinical Study Data 
A description of this clinical study will be available on www.astrazenecaclinicaltrials.com and 
http://www.clinicaltrials.gov as will the summary of the study results when they are available. 
The clinical study and/or summary of study results may also be available on other websites 

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according to the regulations of the countries in which the study is conducted. 
A 7 
Data Quality Assurance 
All participant data relating to the study will be recorded on eCRF unless transmitted to the 
Sponsor or designee electronically (eg, laboratory data). The Investigator is responsible for 
verifying that data entries are accurate and correct by electronically signing the eCRF. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
Monitoring details describing strategy, including definition of study-critical data items and 
processes (eg, risk-based initiatives in operations and quality such as Risk Management and 
Mitigation Strategies and Analytical Risk-based Monitoring), methods, responsibilities and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are included in the Monitoring Plan. 
The Sponsor or designee is responsible for medical oversight throughout the conduct of the 
study which includes clinical reviews of study data in accordance with the currently approved 
protocol. Monitoring details describing clinical reviews of study data from a medical 
perspective are included in more detail in the Monitoring Plan. 
The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
The Sponsor assumes accountability for actions delegated to other individuals (eg, CROs). 
Study monitors will perform ongoing source data verification as per the Monitoring Plan(s) to 
confirm that data entered into the eCRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently approved 
protocol and any other study agreements, ICH GCP, and all applicable regulatory 
requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must 
be retained by the Investigator for a minimum of 25 years after study archiving or as required 
by local regulations, according to the Sponsor’s Global retention and Disposal Schedule. No 
records may be destroyed during the retention period without the written approval of the 
Sponsor. No records may be transferred to another location or party without written 
notification to the Sponsor. 
A 8 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s site. 

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Data entered in the eCRF that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. The Investigator may need to 
request previous medical records or transfer records, depending on the study. Also, current 
medical records must be available. 
Definition of what constitutes source data and its origin can be found in source data 
acknowledgment. 
A 9 
Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site open and will be the study start date. 
The Sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study site closure visit has been performed. 
The Investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or the Investigator may include 
but are not limited to: 
Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor’s procedures, or GCP guidelines 
Inadequate recruitment of participants by the Investigator 
Discontinuation of further study intervention development 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IRBs/IECs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The Investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
Participants from terminated sites will have the opportunity to be transferred to another site to 
continue the study. 
A 10 Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before 

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submission. This allows the Sponsor to protect proprietary information and to provide 
comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements. 
 

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Appendix B AEs: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting 
B 1 
Definition of AEs 
An AE is the development of any untoward medical occurrence in a patient or clinical study 
participant administered a medicinal product, and which does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavourable and unintended sign 
(eg, an abnormal laboratory finding), symptom (for example nausea, chest pain), or disease 
temporally associated with the use of a medicinal product, whether it is considered related to 
the medicinal product.  
The term AE is used to include both serious and non-serious AEs and a deterioration of a pre-
existing medical occurrence. An AE may occur at any time, including run-in or washout 
periods, even if no study intervention has been administered. 
B 2 
Definition of SAEs 
An SAE is an AE occurring during any study phase (ie, run-in, treatment, washout, 
follow-up), that fulfills one or more of the following criteria: 
Results in death. 
Is immediately life-threatening. 
Requires in-patient hospitalization or prolongation of existing hospitalization.  
Results in persistent or significant disability or incapacity.  
Is a congenital anomaly or birth defect. 
Is an important medical event that may jeopardise the participant or may require medical 
treatment to prevent one of the outcomes listed above. 
Adverse Events for malignant tumors reported during a study should generally be assessed 
as SAEs. If no other seriousness criteria apply, the ‘Important Medical Event’ criterion should 
be used. In certain situations, however, medical judgment on an individual event basis should 
be applied to clarify that the malignant tumor event should be assessed and reported as a 
non-SAE. For example, if the tumor is included as medical history and progression occurs 
during the study, but the progression does not change treatment and/or prognosis of the 
malignant tumor, the AE may not fulfill the attributes for being assessed as serious, although 
reporting of the progression of the malignant tumor as an AE is valid and should occur. Also, 
some types of malignant tumors, which do not spread remotely after a routine treatment that 
does not require hospitalization, may be assessed as non-serious; examples in adults include 
Stage 1 basal cell carcinoma and Stage 1A1 cervical cancer removed via cone biopsy. 

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Life-threatening 
‘Life-threatening’ means that the participant was at immediate risk of death from the AE as it 
occurred, or it is suspected that use or continued use of the medicinal product would result in 
the participant’s death. ‘Life-threatening’ does not mean that had an AE occurred in a more 
severe form it might have caused death (eg, hepatitis that resolved without hepatic failure). 
Hospitalization 
Outpatient treatment in an emergency room is not in itself a SAE, although the reasons for it 
may be (eg, bronchospasm, laryngeal oedema). Hospital admissions and/or surgical operations 
planned before or during a study are not considered AEs if the illness or disease existed before 
the participant was enrolled in the study, provided that it did not deteriorate in an unexpected 
way during the study. 
Important Medical Event or Medical Treatment 
Medical and scientific judgment should be exercised in deciding whether a case is serious in 
situations where important medical events may not be immediately life-threatening or result in 
death, hospitalization, disability or incapacity but may jeopardise the participant or may 
require medical treatment to prevent one or more outcomes listed in the definition of serious. 
These should usually be considered as serious. 
Severity Rating Scale: 
Mild (awareness of sign or symptom, but easily tolerated) 
Moderate (discomfort sufficient to cause interference with normal activities 
Severe (incapacitating, with inability to perform normal activities) 
It is important to distinguish between serious and severe AEs. Severity is a measure of 
intensity whereas seriousness is defined by the criteria in Appendix B 2. An AE of severe 
intensity need not necessarily be considered serious. For example, nausea that persists for 
several hours may be considered severe nausea, but not an SAE unless it meets the criteria 
shown in Appendix B 2. On the other hand, a stroke that results in only a limited degree of 
disability may be considered a mild stroke but would be an SAE when it satisfies the criteria 
shown in Appendix B 2. 
B 3 
A Guide to Interpreting the Causality Question 
When assessing causality consider the following factors when deciding if there is a 
‘reasonable possibility’ that an AE may have been caused by the medicinal product. 
Time Course. Exposure to suspect drug. Has the participant received the suspect drug? Did the 
AE occur in a reasonable temporal relationship to the administration of the suspect drug? 

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Consistency with known drug profile. Was the AE consistent with the previous knowledge of 
the suspect drug (pharmacology and toxicology) or drugs of the same pharmacological class? 
Or could the AE be anticipated from its pharmacological properties? 
De-challenge experience. Did the AE resolve or improve on stopping or reducing the dose of 
the suspect drug? 
No alternative cause. The AE cannot be reasonably explained by another aetiology such as the 
underlying disease, other drugs, other host, or environmental factors. 
Re-challenge experience. Did the AE reoccur if the suspected drug was reintroduced after 
having been stopped? The Sponsor would not normally recommend or support a re-challenge. 
Laboratory tests. A specific laboratory investigation (if performed) has confirmed the 
relationship. 
In difficult cases, other factors could be considered such as: 
Is this a recognized feature of overdose of the drug? 
Is there a known mechanism? 
Causality of ‘related’ is made if following a review of the relevant data, there is evidence for a 
‘reasonable possibility’ of a causal relationship for the individual case. The expression 
‘reasonable possibility’ of a causal relationship is meant to convey, in general, that there are 
facts (evidence) or arguments to suggest a causal relationship. 
The causality assessment is performed based on the available data including enough 
information to make an informed judgment. With no available facts or arguments to suggest a 
causal relationship, the event(s) will be assessed as ‘not related’. 
Causal relationship in cases where the disease under study has deteriorated due to lack of 
effect should be classified as ‘no reasonable possibility’. 
B 4 
Toxicity Grading Scales for Solicited Adverse Events 
The toxicity grading scales for the solicited AEs were modified and abridged from the US 
FDA Guidance on Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials (FDA 2007). 
 
Table 6 
Severity Grading for Solicited Injection Site Adverse Reactions  
 
Table 7: Severity Grading for Solicited Injection Site Adverse Reactions 

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Table 6 
Severity Grading for Solicited Injection Site Adverse Reactions  
 
Solicited Injection Site Adverse Reaction Grade 
Mild  
(Grade 1) 
Moderate 
(Grade 2) 
Severe  
(Grade 3) 
Pain 
No interference with 
activity 
Some interference with 
activity 
Prevents daily activity 
Erythema/redness a, b 
25 to 50 mm 
51 to 100 mm 
> 100 mm  
Swelling a, b  
25 to 50 mm 
51 to 100 mm 
> 100 mm  
a 
In addition to grading the measured injection site reaction at the greatest single diameter, the measurement 
should be recorded as a continuous variable. 
b 
Any cases of necrosis and exfoliative dermatitis will be reported as SAEs 
 
Table 7 
Severity Grading for Solicited Systemic Adverse Reactions 
 
Solicited Systemic Adverse Reaction Grade 
 
Mild  
(Grade 1) 
Moderate 
(Grade 2) 
Severe  
(Grade 3) 
Fever (°F) a 
≥ 100.4 to ≤ 101.1 
≥ 101.2 to ≤ 102.0 
≥ 102.1  
Chills 
No interference with activity 
Some interference with 
activity 
Prevents daily activity 
Headache 
No interference with activity 
Some interference with 
activity 
Prevents daily activity 
Fatigue 
No interference with activity 
Some interference with 
activity 
Prevents daily activity 
Myalgia 
No interference with activity 
Some interference with 
activity 
Prevents daily activity 
a 
Oral temperature; no recent hot or cold beverages or smoking.  

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B 5 
Medication Error and Study Intervention Misuse 
Medication Error 
For the purposes of this clinical study a medication error is an unintended failure or mistake in 
the treatment process for an IMP or Sponsor NIMP that either causes harm to the participant 
or has the potential to cause harm to the participant.  
A medication error is not lack of efficacy of the drug, but rather a human or process related 
failure while the drug is in control of the study site staff or participant. 
Medication error includes situations where an error:  
Occurred 
Was identified and intercepted before the participant received the drug 
Did not occur, but circumstances were recognized that could have led to an error 
Examples of events to be reported in clinical studies as medication errors: 
Drug name confusion 
Dispensing error, eg, medication prepared incorrectly, even if it was not actually given to the 
participant 
Drug not administered as indicated, eg, wrong route or wrong site of administration 
Drug not taken as indicated, eg, tablet dissolved in water when it should be taken as a solid 
tablet  
Drug not stored as instructed, eg, kept in the refrigerator when it should be at room 
temperature  
Wrong participant received the medication (excluding IRT/RTSM errors) 
Wrong drug administered to participant (excluding IRT/RTSM errors) 
Examples of events that do not require reporting as medication errors in clinical studies: 
Errors related to or resulting from IRT/RTSM - including those which led to one of the above 
listed events that would otherwise have been a medication error  
Participant accidentally missed drug dose(s), eg, forgot to take medication 
Accidental overdose (will be captured as an overdose) 
Participant failed to return unused medication or empty packaging  
Medication errors are not regarded as AEs but AEs may occur as a consequence of the 
medication error. 

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Study Intervention Misuse 
Study intervention misuse is the intentional and inappropriate use (by a study participant) of 
IMP or Sponsor NIMP for medicinal purposes outside of the authorized product information, 
or for unauthorized IMPs or Sponsor NIMPs, outside the intended use as specified in the 
protocol and includes deliberate administration of the product by the wrong route. 
Events of study intervention misuse, with or without associated AEs, are to be captured and 
forwarded to the DES using the Study Intervention Misuse Report Form. This form should be 
used both if the study intervention misuse happened in a study participant or if the drug 
misuse regards a person not enrolled in the study (such as a relative of the study participant). 
Examples of study intervention misuse include but are not limited to: 
 The study intervention is used with the intention to cause an effect in another person 
 The study intervention is sold to other people for recreational purposes  
 The study intervention is used to facilitate assault in another person 
 The study intervention is deliberately administered by the wrong route 
 Someone who is not enrolled in the study intentionally takes the study intervention 

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Appendix C Handling of Human Biological Samples 
C 1 
Chain of Custody 
A full chain of custody is maintained for all samples throughout their lifecycle. 
The Investigator at each site keeps full traceability of collected biological samples from the 
participants while in storage at the center until shipment or disposal (where appropriate) and 
records relevant processing information related to the samples while at the site. 
The sample receiver keeps full traceability of the samples while in storage and during use until 
used or disposed of or until further shipment, and keeps record of receipt of arrival and 
onward shipment or disposal. 
The Sponsor or delegated representatives will keep oversight of the entire life cycle through 
internal procedures, monitoring of study sites, auditing or process checks, and contractual 
requirements of external laboratory providers 
Samples retained for further use will be stored in the Sponsor-assigned biobanks or other 
sample archive facilities and will be tracked by the appropriate Sponsor team for the 
remainder of the sample life cycle. 
All appropriately consented samples will be retained for maximum 15 years from last subject 
last visit. 
If required, the Sponsor will ensure that remaining biological samples are returned to the site 
according to local regulations or at the end of the retention period, whichever is the sooner. 
C 2 
Withdrawal of Informed Consent for Donated Biological Samples  
The Sponsor ensures that biological samples are returned to the source or destroyed at the end 
of a specified period as described in the informed consent. 
If a participant withdraws consent to the use of donated biological samples, the samples will 
be disposed of/destroyed/repatriated, and the action documented. If samples are already 
analysed, the Sponsor is not obliged to destroy the results of this research. 
Following withdrawal of consent for biological samples, further study participation should be 
considered in relation to the withdrawal processes outlined in the informed consent. 
The Investigator: 
Ensures the participant’s withdrawal of informed consent to the use of donated samples is 
highlighted immediately to the Sponsor or delegate. 

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Ensures that relevant human biological samples from that participant, if stored at the study 
site, are immediately identified, disposed of as appropriate, and the action documented. 
Ensures that the participant and the Sponsor are informed about the sample disposal. 
The Sponsor ensures the organization(s) holding the samples is/are informed about the 
withdrawn consent immediately and that samples are disposed of or repatriated as appropriate, 
and the action is documented, and study site is notified. 
C 3 
International Air Transport Association Guidance Document 62nd 
edition 
LABELLING AND SHIPMENT OF BIOHAZARD SAMPLES 
The International Air Transport Association (IATA) 
(https://www.iata.org/whatwedo/cargo/dgr/Pages/download.aspx) classifies infectious 
substances into three categories: Category A, Category B, or Exempt 
Category A Infectious Substances are infectious substances in a form that, when exposure to 
it occurs, is capable of causing permanent disability, life-threatening or fatal disease in 
otherwise healthy humans or animals.  
Category A Pathogens are, eg, Ebola, Lassa fever virus. Infectious substances meeting these 
criteria which cause disease in humans or both in humans and animals must be assigned to 
UN 2814. Infectious substances which cause disease only in animals must be assigned to 
UN 2900. 
Category B Infectious Substances are infectious substances that do not meet the criteria for 
inclusion in Category A. Category B pathogens are, eg, Hepatitis A, C, D, and E viruses. They 
are assigned the following UN number and proper shipping name: 
UN 3373 – Biological Substance, Category B 
Are to be packed in accordance with UN 3373 and IATA 650 
 
Exempt Substances are substances which do not contain infectious substances, or substances 
which are unlikely to cause disease in humans or animals, are not subject to these regulations 
unless they meet the criteria for inclusion in another class. 
Clinical study samples will fall into Category B or exempt under IATA regulations. 
Clinical study samples will routinely be packed and transported at ambient temperature in 
IATA 650 compliant packaging 
(https://www.iata.org/contentassets/b08040a138dc4442a4f066e6fb99fe2a/dgr-62-en-
pi650.pdf). 

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Biological samples transported in dry ice require additional dangerous goods specification for 
the dry ice content. 
 
 

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Appendix D Protocol Version History 
The Summary of Changes Table for the current revision is located directly before the Table of 
Contents. 
CSP Version 2.0: (11 April 2024) 
Overall Rationale for the Modification 
The main purpose of this protocol modification is to expand on the AESI definition for RSV 
vaccines and to clarify the collection of prohibited medications and vaccinations. 
Summary of Changes: 
List of Substantial Modifications 
Section Number and Name  
Description of Change  
Brief Rationale  
Section 8.4.7 
(Adverse Events of Special 
Interest)  
Updated to specify that AESIs will 
include additional immune-mediated 
neurological disease and atrial 
fibrillation  
To ensure robust assessment of safety  
 
List of Non-Substantial Modifications 
Section Number and Name  
Description of Change  
Brief Rationale  
Section 1.3 
(Schedule of Activities)  
Inclusion of height and weight 
measurement at Visit 1 (pre-dose) 
To calculate BMI  
Footnote d updated to indicate that 
prohibited medications will be recorded 
in the eCRF 
Minor update to align more closely with 
the ICF – clarification that prohibited 
medications will be recorded in the 
eCRF and not just in the source 
documents   
Section 6.9 
(Prior and Concomitant 
Medications)  
Restricted medications’ changed to 
‘prohibited medications’ 
Updated for clarity  
Section 8.3.2 
(Vital Signs)  
Height and weight measurements added 
to the list of parameters assessed as part 
of vital signs  
To calculate BMI  
Section 8.4.12 
(Medication Error and Study 
Intervention Misuse)  
Title updated from ‘Drug Abuse and 
Drug Misuse’ to ‘Study Intervention 
Misuse’ 
Updated for clarity  
Appendix D 
(Protocol Version History)  
Added 
Added to reflect this amendment to the 
protocol  
 

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