A Phase 2a Randomized, Observer-blind, Placebo-controlled, Dosage Optimization, Multi-center Clinical Trial to Evaluate the Safety and Immunogenicity of IVX-A12, a Respiratory Syncytial Virus and Human Metapneumovirus Bivalent Combination Virus-like Particle Protein Subunit Vaccine, in Adults 60 to 85 Years of Age
Phase: PHASE2
Conditions: Healthy
Sponsor: Icosavax, Inc.

IVX-A12 
Trial Protocol No. ICVX-12-201 
Version 5.0 
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CONFIDENTIAL 
 
 
 
 
 
A Phase 2a Randomized, Observer-blind, Placebo-controlled, Dosage 
Optimization, Multi-center Clinical Trial to Evaluate the Safety and 
Immunogenicity of IVX-A12, a Respiratory Syncytial Virus and Human 
Metapneumovirus Bivalent Combination Virus-like Particle Protein 
Subunit Vaccine, in Adults 60 to 85 Years of Age  
(Safety and Immunogenicity of IVX-A12 in Adults 60 to 85 Years of Age) 
 
 
Sponsor: 
Icosavax Inc. 
1930 Boren Avenue, Suite 1000 
Seattle, WA 98101 
USA 
Protocol Number: 
ICVX-12-201 
IND Number: 
28672 
Investigational 
Medicinal Products: 
• 
IVX-A12 (a bivalent vaccine comprised of IVX-121 
[respiratory syncytial virus-like particle protein 
subunit vaccine] and IVX-241 [human 
metapneumovirus virus-like particle protein 
subunit vaccine]) 
• 
Placebo 
Synopsis Date: 
02 April 2024 
Version: 
5.0 
 
 
 
 
This document is the property of Icosavax, Inc. No information contained 
herein will be published or disclosed without written authorization from 
Icosavax, Inc. 

I V X - A 1 2  
T ri al  P r o t o c ol  N o.  I C V X - 1 2 - 2 0 1 
V e r si o n 5. 0  
P a g e 2  of  1 0 3  
0 2  A p ril  2 0 2 4  
C O N F I D E N T I A L  
 
 
1. 0  
A D M I N I S T R A T I V E  I N F O R M A T I O N   
1. 1  
S af e t y  C o n t a c t  I nf o r m ati o n   
e -m ail :  s af et yr e p orti n g @ s y n e o s h e alt h. c o m  
F a x: 1 -8 7 7 - 4 6 4 -7 7 8 7  
1. 2  
A p p r o v al 
R E P R E S E N T A T I V E S  O F  I C O S A V A X   
T hi s  tri al will  b e  c o n d u ct e d  i n a c c or d a n c e  wit h  t hi s cli ni c al  tri al pr ot o c ol a n d  wit h 
t h e f oll o wi n g: 
•  
T h e  D e cl ar ati o n  of  H el si n ki  [1 ]. 
•  
I nt er n ati o n al C o u n cil  f or H ar m o ni s ati o n  (I C H )  of  T e c h ni c al  R e q uir e m e nt s  f or 
P h ar m a c e uti c al s f or H u m a n U s e E 6 ( R 2 ) G o o d Cli ni c al Pr a cti c e ( G C P ) : 
C o n s oli d at e d G ui d eli n e [ 2 ].  
•  
All  a p pli c a bl e  l a w s a n d  r e g ul ati o n s, i n cl u di n g, b ut  n ot  li mit e d t o t h o s e r el at ed 
t o d at a pri v a c y a n d cli ni c al tri al di s cl o s ur e. 
 
A P P R O V A L   
 
 
 
 
 
D at e  
P P D

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INVESTIGATOR AGREEMENT  
I confirm that I have read and that I understand this protocol, the investigator’s 
brochure (IB), and any other product information provided by the sponsor. I 
agree to conduct this trial in accordance with the requirements of this protocol 
and protect the rights, safety, privacy, and well-being of trial subjects in 
accordance with the following: 
• 
The Declaration of Helsinki [1]. 
• 
ICH, E6 (R2) GCP: Consolidated Guideline [2]. 
• 
All applicable laws and regulations, including, but not limited to those 
related to data privacy and clinical trial disclosure. 
• 
Regulatory requirements for reporting serious adverse events (SAEs) 
defined in Section 10.4.4 of this protocol. 
• 
Terms outlined in the clinical trial site agreement. 
• 
Appendix A – Responsibilities of the investigator. 
 
 
 
Signature of Investigator 
Date 
 
 
 
Investigator Name (print or type) 
 
 
 
Investigator’s Title 
 
 
 
Location of the Site (City, Country) 

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1.3 
Protocol Version History  
Changes from Version 4.0 dated 03 November 2023 to Version 5.0 dated 
02 April 2024 
 
Rationale: 
Section 
Description 
Protocol synopsis 
Modifications were made consistent with the protocol body 
Section 2.2 
Removal of time and events schedule for Part 2 – 
replaced with time and events schedule for the extension 
Section 2.3 
Update of trial schematic to remove Part 2 and instead 
include the trial extension 
Section 4.4 
Rationale of the trial updated to reflect the inclusion of the 
extension 
Section 5.0 
Objectives and endpoints added for the observational 
extension 
Section 6.1 
Trial design updated to remove Part 2 and instead include the 
observational extension 
Section 6.3 
Planned duration updated to reflect the additional time for 
those subjects included in the extension 
Section 7.1 and 
Section 7.2 
Inclusion / exclusion criteria related to Part 2 removed. 
Section 7.3 
New section: Trial Observational Extension 
Section 8.1, 8.2, 8.4 
Investigational medicinal products sections updated to remove 
references to Part 2 
Section 8.5 
Inclusion of unblinding at Day 365 visit, prior to extension 
Section 9.1, 9.1.1 
Trial procedures and informed consent updated to reflect trial 
extension instead of Part 2. 
Section 9.1.5 
Vital signs updated to confirm that SpO2 will not be performed 
during trial extension unless clinically indicated. 
Section 9.1.6 
Immunogenicity assessments updated to reflect removal of 
Part 2 and inclusion of trial observational extension 
Section 9.1.8 
Safety assessments updated to reflect removal of Part 2 and 
inclusion of trial observational extension 
Section 9.1.10 
Processing, labeling and storage of biological samples updated 
to reflect removal of Part 2 and inclusion of trial observational 
extension 
Section 9.2 
Time and events schedule updated to reflect removal of Part 2 
and inclusion of trial observational extension 
Section 10.4.3 
Updated to reflect collection of MAAEs through to Day 730 

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Section 10.4.4 
Updated to reflect collection of SAEs through to Day 730 
Section 11.2 
Remove SMC review prior to initiation of Part 2 
Section 13.1.1 
Update to definition of the Per Protocol Set and the addition of 
the Extension Enrolled Set 
Section 13.1.3 
Update to immunogenicity analyses section to reflect the 
removal of Part 2 but the inclusion of the observational trial 
extension 
Section 13.1.4 
Update to efficacy analyses section to reflect the removal of 
Part 2 but the inclusion of the observational trial extension 
Section 13.1.5 
Update to safety analyses section to reflect the removal of 
Part 2 but the inclusion of the observational trial extension 
Section 13.2 
Update to Interim Analysis / Data Reviews section to reflect 
the removal of Part 2 but the inclusion of the observational 
trial extension 
Section 13.3 
Update to Primary / Secondary Analyses for the CSR section to 
reflect the removal of Part 2 but the inclusion of the 
observational trial extension 

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TABLE OF CONTENTS  
1.0 
ADMINISTRATIVE INFORMATION ................................................... 2 
1.1 
Safety Contact Information ...................................................... 2 
1.2 
Approval ............................................................................... 2 
1.3 
Protocol Version History .......................................................... 4 
TABLE OF CONTENTS ........................................................................... 6 
LIST OF IN-TEXT TABLES .................................................................... 10 
LIST OF APPENDICES ......................................................................... 10 
2.0 
SUMMARY ............................................................................... 11 
2.1 
Time and Events Schedule for ICVX-12-201: Main Trial ............... 25 
2.2 
Time and Events Schedule for ICVX-12-201: Extension ............... 27 
2.3 
Trial Design Schematic .......................................................... 28 
3.0 
TRIAL REFERENCE INFORMATION ................................................ 29 
3.1 
Trial-related Responsibilities ................................................... 29 
3.2 
Principal Investigator ............................................................ 29 
3.3 
List of Abbreviations ............................................................. 30 
3.4 
Corporate Identification ......................................................... 31 
4.0 
INTRODUCTION ........................................................................ 32 
4.1 
Respiratory Syncytial Virus .................................................... 32 
4.2 
Human Metapneumovirus ...................................................... 32 
4.3 
IVX-A12 .............................................................................. 33 
4.4 
Rationale for the Proposed Trial .............................................. 34 
5.0 
OBJECTIVES AND ENDPOINTS .................................................... 36 
6.0 
TRIAL DESIGN AND DESCRIPTION ............................................... 40 
6.1 
Clinical Trial Design .............................................................. 40 
6.2 
Justification for Trial Design, Dosage Level, and Endpoints .......... 42 
6.3 
Planned Duration of Subject’s Participation in the Trial ................ 42 
6.4 
Premature Termination or Suspension of Trial or Trial Site ........... 43 
6.4.1 
Criteria for Premature Termination or Suspension of the Trial 
. ................................................................................ 43 
6.4.2 
Criteria for Premature Termination or Suspension of Trial 
Sites .......................................................................... 43 
6.4.3 
Procedures for Premature Termination or Suspension of the 
Trial or the Participation of Trial Sites .............................. 43 
7.0 
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS .... 44 
7.1 
Inclusion Criteria .................................................................. 44 
7.2 
Exclusion Criteria ................................................................. 44 
7.3 
Trial Observational Extension ................................................. 46 

I V X - A 1 2  
T ri al  P r o t o c ol  N o.  I C V X - 1 2 - 2 0 1 
V e r si o n 5. 0  
P a g e 7  of  1 0 3  
0 2  A p ril  2 0 2 4  
C O N F I D E N T I A L  
 
 
7. 4  
Crit eri a f or D el a y of I n v e sti g ati o n al M e di ci n al Pr o d u ct  
A d mi ni str ati o n a n d/ or Bl o o d S a m pli n g  ..................................... 4 6  
7. 5  
Crit eri a  f or E arl y  T er mi n ati o n  of  a  S u bj e ct’ s  Tri al  P arti ci p ati o n  ...... 4 7  
8. 0  
C LI NI C A L  T RI A L  M A T E RI A L  M A N A G E M E N T  ..................................... 4 8  
8. 1  
I n v e sti g ati o n al M e di ci n al  Pr o d u ct s  ........................................... 4 8  
8. 1. 1  
I V X-A 1 2 ...................................................................... 4 8  
8. 1. 2  
Pl a c e b o  ...................................................................... 4 8  
8. 1. 3  
L a b eli n g  ..................................................................... 4 8  
8. 1. 4  
I n v e nt or y a n d  St or a g e  .................................................. 4 8  
8. 1. 5  
D o s a g e  L e v el  a n d  D o si n g  R e gi m e n  .................................. 4 9  
8. 2  
I n v e sti g ati o n al M e di ci n al Pr o d u ct A s si g n m e nt a n d Di s p e n si n g 
Pr o c e d ur e s  .......................................................................... 4 9  
8. 2. 1  
Pr e c a uti o n s t o b e O b s er v e d W h e n A d mi ni st eri n g t h e 
I n v e sti g ati o n al M e di ci n al  Pr o d u ct  .................................... 5 0  
8. 3  
R a n d o mi z ati o n  C o d e  Cr e ati o n  a n d  St or a g e  ............................... 5 0  
8. 4  
I n v e sti g ati o n al M e di ci n al  Pr o d u ct  Bli n d  M ai nt e n a n c e  ................... 5 0  
8. 5  
U n bli n di n g  Pr o c e d ur e  ............................................................ 5 0  
8. 6  
A c c o u nt a bilit y a n d D e str u cti o n of S p o n s or -s u p pli e d I n v e sti g ati o n al 
M e di ci n al  Pr o d u ct s,  a n d  Ot h er  Cli ni c al  Tri al  M at eri al s  .................. 5 1  
9. 0  
T RI A L  P L A N  ............................................................................. 5 2  
9. 1  
Tri al  Pr o c e d ur e s  ................................................................... 5 2  
9. 1. 1  
I nf or m e d C o n s e nt  a n d  Eli gi bilit y  ...................................... 5 2  
9. 1. 2  
D e m o gr a p hi c s,  M e di c al  Hi st or y  a n d  M e di c ati o n  Hi st or y  ....... 5 2  
9. 1. 3  
D o c u m e nt ati o n  of  Tri al  E ntr y/ R a n d o mi z ati o n  ..................... 5 3  
9. 1. 4  
P h y si c al  E x a mi n ati o n  .................................................... 5 4  
9. 1. 5  
Vit al  Si g n s  .................................................................. 5 4  
9. 1. 6  
I m m u n o g e ni cit y A s s e s s m e nt s  ......................................... 5 4  
 
 
9. 1. 8  
S af et y  A s s e s s m e nt s  ...................................................... 5 7  
9. 1. 9  
Cli ni c al  S af et y  L a b or at or y  V ari a bl e s  ................................. 5 7  
9. 1. 1 0  
Pr o c e s si n g,  L a b eli n g  a n d  St or a g e  of  Bi ol o gi c al  S a m pl e s  ...... 5 8  
9. 1. 1 1  
C o ntr a c e pti o n  Pr o c e d ur e s  .............................................. 5 9  
9. 2  
Ti m e  a n d  E v e nt s  S c h e d ul e  ..................................................... 5 9  
9. 2. 1  
S cr e e ni n g  ( D a y s  - 2 8  t o - 1)  ............................................ 5 9  
9. 2. 2  
Pr e v a c ci n ati o n  Pr o c e d ur e s  ( D a y  0)  .................................. 5 9  
9. 2. 3  
V a c ci n ati o n  Pr o c e d ur e s  ( D a y  0)  ...................................... 6 0  
9. 2. 4  
P o st - v a c ci n ati o n  Pr o c e d ur e s  ( D a y 0) ................................ 6 0  
9. 2. 5  
M ai n  Tri al  Sit e  Vi sit s  aft er  V a c ci n ati o n  ( D a y s  7,  2 8,  9 0,  1 8 0,  
a n d  3 6 5)  .................................................................... 6 2  
C CI

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9.2.6 
Main Trial Phone Contacts – Safety Calls (Days 3, 14, 56, 
135, and 270) ............................................................. 62 
9.2.7 
Visit Day 365 ............................................................... 63 
9.2.8 
Observational Extension: Phone Contact (Day 545) and Site 
Visit (Day 730) ............................................................ 63 
9.2.9 
Unscheduled Visits ....................................................... 64 
9.2.10 
Post-trial Care ............................................................. 64 
9.3 
Biological Sample Retention and Destruction ............................. 65 
10.0 ADVERSE EVENTS ..................................................................... 66 
10.1 Definitions ........................................................................... 66 
10.1.1 
Adverse Events ............................................................ 66 
10.1.2 
Solicited Adverse Events................................................ 66 
10.1.3 
Clinical Events of Special Interest .................................... 70 
10.1.4 
Medically-attended Adverse Events ................................. 72 
10.1.5 
Serious Adverse Events ................................................. 72 
10.1.6 
Suspected Unexpected Serious Adverse Reaction ............... 73 
10.2 Causality of Adverse Events ................................................... 73 
10.2.1 
Relationship to Trial Procedures ...................................... 73 
10.2.2 
Outcome of Adverse Events ........................................... 74 
10.3 Additional Points to Consider for Adverse Events ........................ 74 
10.4 Procedures .......................................................................... 75 
10.4.1 
Collection and Reporting of Adverse Events ...................... 75 
10.4.2 
Collection and Reporting of Solicited Adverse Reactions ...... 76 
10.4.3 
Collection and Reporting of Clinical Events of Special Interest 
and Medically-attended Adverse Events ........................... 76 
10.4.4 
Collection and Reporting of Serious Adverse Events ........... 77 
10.5 Follow-up Procedures ............................................................ 77 
10.5.1 
Adverse Events ............................................................ 77 
10.5.2 
Serious Adverse Events ................................................. 77 
10.5.3 
Safety Reporting to Investigators, Independent Ethics 
Committees or Investigational Review Boards, and Regulatory 
Authorities .................................................................. 78 
10.5.4 
Post-trial Events .......................................................... 78 
11.0 TRIAL-SPECIFIC REQUIREMENTS ................................................. 79 
11.1 Stopping Rules ..................................................................... 79 
11.2 Safety Review Committee and Safety Monitoring Committee ........ 80 
12.0 DATA HANDLING AND RECORD KEEPING ...................................... 81 
12.1 Electronic CRFs .................................................................... 81 
12.2 Record Retention .................................................................. 81 

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13.0 STATISTICAL METHODS ............................................................. 83 
13.1 Statistical and Analytical Plans ................................................ 83 
13.1.1 
Analysis Sets ............................................................... 83 
13.1.2 
Analysis of Disposition, Demographics, Other Baseline 
Characteristics, Medical History and Medications ................ 83 
13.1.3 
Immunogenicity Analyses .............................................. 84 
13.1.4 
Efficacy Analysis .......................................................... 84 
13.1.5 
Safety Analyses ........................................................... 84 
13.2 Interim Analysis/Data Reviews ............................................... 85 
13.3 Primary and Secondary Analyses for the CSR ............................ 85 
13.4 Sample Size Justification ....................................................... 86 
14.0 QUALITY CONTROL AND QUALITY ASSURANCE .............................. 87 
14.1 Trial Site Monitoring Visits ..................................................... 87 
14.2 Protocol Deviations ............................................................... 87 
14.3 Quality Assurance Audits and Regulatory Agency Inspections ....... 87 
14.4 Risk Management ................................................................. 87 
15.0 ETHICAL ASPECTS .................................................................... 88 
15.1 Independent Ethics Committee and/or Institutional Review Board 
Approval ............................................................................. 88 
15.2 Subject Information, Informed Consent and Subject Authorization 
. ....................................................................................... 89 
15.3 Subject Confidentiality .......................................................... 90 
15.4 Clinical Trial Registration, Publication and Disclosure Policy .......... 91 
15.4.1 
Clinical Trial Registration ............................................... 91 
15.4.2 
Clinical Trial Results Disclosure ....................................... 91 
15.4.3 
Publication of Trial Results ............................................. 91 
15.4.4 
Insurance and Compensation for Injury ........................... 91 
16.0 REFERENCES ........................................................................... 92 
APPENDIX A RESPONSIBILITIES OF THE INVESTIGATOR .......................... 96 
APPENDIX B 
TOXICITY TABLES ........................................................ 97 
APPENDIX C 
DALHOUSIE UNIVERSITY CLINICAL FRAILY SCALE ........... 101 
APPENDIX D 
ADVERSE EVENTS OF SPECIAL INTEREST AND POTENTIAL 
IMMUNE-MEDIATED CONDITIONS ............................................... 97 

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LIST OF IN-TEXT TABLES  
Table 1 
Clinical Trial Schema ........................................................ 41 
Table 2 
Sponsor-supplied IMP ....................................................... 49 
Table 3 
Phase 2a Core Clinical Bioanalytical Assays........................... 55 
Table 4 
Clinical Safety Laboratory Tests .......................................... 58 
Table 5 
Blood Volumes ................................................................ 58 
Table 6 
Solicited Local (Injection Site) Reactions and Systemic ARs ..... 67 
Table 7 
Solicited Local (Injection Site) Reactions .............................. 68 
Table 8 
Solicited Systemic ARs ...................................................... 69 
Table 9 
FDA Toxicity Grading Scales for Clinical Laboratory 
Abnormalitiesa ......................................................................................................... 98 
Table 10 
FDA Toxicity Grading Scale for Vital Sign Abnormalities .......... 99 
Table 11 
FDA Toxicity Grading Scale for Urinalysis Abnormalities ........ 100 
 
 
LIST OF APPENDICES  
Appendix A Responsibilities of the Investigator ....................................... 96 
Appendix B Toxicity Tables ................................................................ 97 
Appendix C Dalhousie University Clinical Fraily Scale ............................ 101 
Appendix D  Adverse Events of Special Interest (AESIs): Potential Immune- 
mediated Conditions (pIMCs) ........................................... 102 

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2.0 
SUMMARY  
 
Name of Sponsor: 
Icosavax Inc. 
1930 Boren Avenue, Suite 
1000 
Seattle, WA 98101 
USA 
Protocol Number: 
ICVX-12-201 
Generic Name of Trial Vaccine: 
IVX-A12 (respiratory syncytial virus 
and human metapneumovirus 
bivalent combination virus-like 
particle protein subunit vaccine) 
Title of the Trial: A Phase 2a Randomized, Observer-blind, Placebo-controlled, Dosage 
Optimization, Multi-center Clinical Trial to Evaluate the Safety and Immunogenicity of 
IVX-A12, a Respiratory Syncytial Virus and Human Metapneumovirus Bivalent 
Combination Virus-like Particle Protein Subunit Vaccine, in Adults 60 to 85 Years of Age. 
Trial Period: Approximately 12 months; 
extended to 24 months in a subset of 
subjects. 
Clinical Phase: Phase 2a 
IND No.: 28672 
EudraCT No.: Not applicable. 
Indication: Active immunization for the prevention of acute illness (ARI) and lower 
respiratory tract illness (LRTI) caused by respiratory syncytial virus (RSV) and human 
metapneumovirus (hMPV) in older adults ≥60 years of age. 
Background and Rationale: 
RSV is a single-strand, negative sense ribonucleic acid (RNA) virus belonging to the 
Orthopneumovirus genus of the family Pneumoviridae (Rima et al., 2017). There are 
two major genetic lineages, A and B (subgroups A and B, respectively), which are 
antigenically related, and cross-neutralizing antibodies are induced upon infection with 
either subgroup. RSV is a major cause of LRTI worldwide in all age groups. 
Epidemiological data suggest that in the USA alone, RSV may cause 
>170,000 hospitalizations and ~14,000 deaths annually (Colosia et al., 2017). RSV is 
also an important cause of respiratory disease in Europe, South Africa, and Australia 
(Falsey and Walsh, 2000; Htar et al., 2019; Cattoir et al., 2019; Langedijk et al., 2020; 
Broberg et al., 2018). Clinical data has identified a substantial disease burden in adults 
comparable to influenza, with most of the hospitalization and mortality occurring in 
older adults over 65 years of age (Fleming et al., 2015). The incidence and severity of 
RSV disease is particularly high in the frail elderly and in adults with cardiopulmonary 
conditions, who are considered at high risk for complications and hospitalization due to 
RSV (Falsey et al., 2005). 
RSV infections are ubiquitous with lifelong reinfections in all age groups indicating that 
immunity is neither sustained nor complete (Karron, 2008; Hall et al., 1991; 
Bergeron and Tripp, 2021). RSV spreads by respiratory droplets and close contact with 
infected persons or fomites. In temperate climates there is an annual winter epidemic 
(Brandt et al., 1973), whereas in tropical areas seasonality is less distinct, but infection 
is most common during the rainy season (Weber et al., 1998). The severity of RSV 
disease is largely determined by the extent of viral replication following infection 
(Graham, 2011). The production of neutralizing antibodies (NAbs) should be the goal of 
vaccination as it is associated with protection against disease. However, seropositivity 
only confers partial protection against infection (Graham, 2011). 
hMPV is a single-strand, negative sense RNA virus of the Metapneumovirus genus in the 
Pneumoviridae family (Rima et al., 2017), and was first described in 2001 when it was 
isolated from children with respiratory disease (van den Hoogen et al., 2001). The most 

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closely related human pathogen is RSV. As with RSV, there are two major genetic 
lineages of hMPV, A and B (subgroups A and B, respectively), which are antigenically 
related and cross-neutralizing antibodies are induced upon infection with either 
subgroup (van den Hoogen, 2004; Skiadopoulos, 2004). hMPV represents one of the 
leading causes of acute respiratory tract infections in infants, children, 
immunosuppressed patients, and the elderly (Jagusic et al., 2019; Gálvez et al., 2021). 
Several studies have shown that hMPV is highly prevalent worldwide, and in the USA 
alone, approximately 20,000 hospitalizations are registered every year due to this virus 
(Divarathna et al., 2019; Williams et al., 2010). In older adults, hMPV is responsible for 
a significant proportion of serious respiratory infections, with similar rates of infection as 
RSV. In the Etiology of Pneumonia in the Community (EPIC) trial, hMPV was confirmed 
in 4% of adults hospitalized with community-acquired pneumonia whereas RSV was 
confirmed in 3% of adults (Jain et al., 2014). Similar to RSV, NAbs alone can protect 
against hMPV infection (Williams, 2007; Hamelin, 2008). In mouse models, infection 
with hMPV protects against near term re-infection (MacPhail, 2004); macaques infected 
with hMPV demonstrated seroconversion and temporary protection from subsequent 
infection that waned over several months (van den Hoogen, 2007). As with RSV, in the 
presence of positive hMPV antibody titers, reinfections may occur in both healthy and 
immunocompromised adults (Madhi et al., 2007; Williams et al., 2006). 
In May 2023, the US Food and Drug Administration (FDA) approved the first RSV 
vaccine (Valero, 2023) with a second vaccine approved shortly thereafter 
(Walsh, 2023). . Currently, there are no approved vaccines for hMPV. The Icosavax 
candidate vaccine, IVX-A12, is a bivalent combination formulation containing IVX-121 
and IVX-241 virus-like particles (VLPs), computationally designed recombinant protein 
subunit vaccines for RSV and hMPV, respectively. Each VLP is composed of two 
recombinant proteins, Component A (CompA) and Component B (CompB-01), which 
have been designed to cooperatively assemble to form an icosahedral virus-like 
structure. Component A is a fusion protein-specific for each vaccine candidate (either 
CompA-RSV-02 or CompA-hMPV-01 for RSV and hMPV, respectively) and is expressed 
with the prefusion F (Pre F) protein from the respective virus, which has been shown to 
induce robust NAb responses in nonclinical models. The IVX-121 and IVX-241 VLPs 
display 20 copies of the respective Pre F protein trimers on their surface. CompB-01 is a 
common component across both VLPs and provides the structural element that supports 
the multimeric display of CompA-RSV-02 or CompA-hMPV-01. When combined, the two 
components self-assemble into VLPs that show enhanced immunogenicity compared 
with either soluble RSV (DS-Cav1) or hMPV prefusion antigen trimers. The soluble 
DS-Cav1 RSV Pre F protein was recently tested clinically and shown to be tolerable and 
immunogenic (Ruckwardt et al., 2021). 
The candidate IVX-121 and IVX-241 VLPs are manufactured as separate drug 
substances and combined to create the IVX-A12 bivalent formulation containing both 
VLPs. The proposed mechanism of action of IVX-A12 is to increase the proportion of 
RSV- and hMPV-specific NAbs that are associated with protection, compared to 
non-neutralizing antibodies (Ngwuta et al., 2015; Falloon et al., 2017). IVX-A12 is 
intended for active immunization of the target population of older adults who are most 
at risk for disease following infection with RSV and hMPV. 
The candidate vaccine, IVX-A12, is a single-dose liquid formulation (0.5 mL) for 
intramuscular (IM) injection in adults 60 to 85 years of age, the target population. 
Nonclinical studies of IVX-A12 bivalent combinations of the IVX-121 and IVX-241 VLPs 
demonstrated the ability of both Pre F protein antigens on the Icosavax VLP platform to 

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induce strong NAb responses. In addition, preclinical experiments showed the effects of 
IVX-A12 dosage levels, number of doses, and need for adjuvant vary with RSV exposure 
history (either naïve or primed by infection) of the animals. The recent Phase 1/1b 
clinical trial (IVX-121-01) with the RSV monovalent IVX-121 VLP subunit vaccine also 
helped guide selection of IVX-A12 dosage levels formulated as either (i) aqueous 
vaccine or (ii) as adjuvanted vaccine with MF59® for the first-in-human evaluation of 
IVX-A12 vaccine. MF59 is a nanoemulsion adjuvant composed of squalene, polysorbate 
80, sorbitan trioleate, and citrate. MF59 is widely used in the subunit influenza vaccine 
FLUAD® that is licensed in the USA, European countries, and other countries (FLUAD 
Quadrivalent, Product Insert, 2021). In total, approximately 150 million doses of 
vaccines with MF59 have been distributed and no safety concerns have been observed 
related to MF59 (O’Hagan et al., 2013). No safety concerns have been observed related 
to MF59 (O’Hagan et al., 2013). Furthermore, increased dosage levels of MF59 (19.5 mg 
and 29.75 mg of squalene, up to 3 times the normal amount contained in licensed 
vaccines containing MF59) have shown to be well tolerated in adults ≥65 years of age in 
a recent Phase 1 clinical trial (Otten, et al., 2020). 
Boosting immunity in RSV-and hMPV-seropositive individuals with IVX-A12, a 
combination bivalent vaccine, may be challenging if one antigen interferes with the 
immune response to the other antigen. Imbalanced immune responses may require use 
of adjuvant in that scenario. However, studies in RSV- and hMPV-naïve mice and cotton 
rats did not demonstrate significant immune interference after vaccination when RSV 
and hMPV VLPs were administered in varying concentration ratios. 
This Phase 2a clinical trial is evaluating the safety and immunogenicity of an 
unadjuvanted dosage level of 150 µg RSV/ 150 µg hMPV of IVX-A12 (IVX-A12a) and a 
dosage level of 150 µg RSV/150 µg hMPV of IVX-A12 adjuvanted with MF59 (IVX-A12d) 
compared to placebo in adults 60 to 85 years of age. Safety and immunogenicity data 
from this proposed Phase 2a clinical trial will allow the selection of an optimal dosage 
level and formulation of IVX-A12 for adults 60 to 85 years of age in future clinical trials. 
The dosage level and formulations of IVX-A12 for this Phase 2a clinical trial were 
selected based on the totality of the IVX-A12 nonclinical data and the interim safety and 
immunogenicity clinical data from the ongoing IVX-A12 Phase 1 clinical trial. Two 
different IVX-A12 formulations, IVX-A12a and IVX-A12d, or placebo were administered 
as a single IM dose to older adult subjects enrolled into two age strata (adults 60 to 
69 years of age and elderly adults 70 to 85 years of age). Eligible older adult subjects 
were randomized to different trial groups to ensure balance among the groups. This 
Phase 2a clinical trial included a sentinel group of 40 subjects (16 subjects per active 
treatment group [n=32]; 8 subjects in the placebo group) to conservatively assess the 
150 µg RSV/150 µg hMPV dosage level in combination with MF59. 
Based on the interim analysis (IA) of Day 28 data from this ongoing trial and data from 
the Phase 1 (ICVX-12-101) trial, the sponsor has determined the trial subjects will be 
unblinded at Day 365. IVX-A12a and placebo recipients will be asked to be followed for 
an additional 12 months for safety and to return to the clinic on visit Day 730 for one 
immunogenicity blood draw (observational extension). 
The Day 28 IA data from this Phase 2 trial demonstrated the following: 
• 
Slightly more reactogenicity was observed in subjects who received IVX-A12 with 
MF59 compared to those who received IVX-A12 without MF59; 

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• 
The inclusion of MF59 did not improve the immunogenicity of 150 µg RSV / 
150 µg hMPV in this older, Phase 2 population relative to the Phase 1 population; 
and 
• 
The overall safety data (i.e., unsolicited adverse events [AEs], and adverse 
reactions [ARs]) between Phase 1 and Phase 2 were similar even with the 
doubling of the IVX-A12 RSV dosage level in the Phase 2 trial compared to 
dosage levels evaluated in the Phase 1. 
IVX-A12a induced neutralizing and binding antibody responses to RSV and hMPV, which 
supports the selection of the unadjuvanted dosage level of 150 µg RSV/150 µg hMPV for 
further clinical evaluation. 
The trial will be conducted in accordance with the protocol, ICH of Technical 
Requirements for Pharmaceuticals for Human Use, GCP Guidelines, Declaration of 
Helsinki, and applicable regulatory requirements. 
Objectives and Endpoints: 
Main Trial 
Primary Safety 
Objective 
Endpoints 
To assess the safety and tolerability of 
the IVX-A12 bivalent candidate vaccine 
compared to placebo up to 1 year 
following a single IVX-A12 vaccination. 
- 
Solicited local (injection site) 
reactions and systemic ARs for 
7 consecutive days starting from 
Day 0 to Day 6 after vaccination. 
- 
Unsolicited AEs from Day 0 to Day 28. 
Primary Immunogenicity 
Objectives 
Endpoints 
- 
To evaluate the serum NAb response 
to IVX-A12 or placebo, measured by 
live virus serum neutralization assays 
(SNA), at Day 28. 
- 
To evaluate the serum 
immunoglobulin G (IgG) binding 
antibody response to IVX-A12 or 
placebo, measured by enzyme-linked 
immunosorbent assays (ELISA), at 
Day 28. 
- 
To evaluate the proportion of subjects 
with a ≥4-fold increase in serum NAb 
and serum IgG binding antibody titers 
to IVX-A12 from 
prevaccination/baseline (Day 0) to 
Day 28. 
- 
Geometric mean titers (GMT) of 
RSV/A-, RSV/B-, hMPV/A-, and 
hMPV/B-specific NAb at Day 28. 
- 
GMT of RSV and hMPV Pre F 
protein-specific IgG antibody titers at 
Day 28. 
- 
Proportion of subjects with a ≥4-fold 
increase in serum anti-RSV/A-, 
RSV/B-, hMPV/A-, and 
hMPV/B-specific NAb from 
prevaccination/baseline (Day 0) to 
Day 28 after vaccination (defined as 
seroresponse rate [SRR]). 
- 
Proportion of subjects with ≥4-fold 
increase (SRR) in RSV- and 
hMPV-specific IgG antibody titers 
from prevaccination/baseline (Day 0) 
to Day 28. 
- 
Geometric mean fold rise (GMFR) at 
Day 28 versus Day 0 in serum anti 

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RSV/A-, RSV/B-, hMPV/A-, and 
hMPV/B-specific Nabs and RSV and 
hMPV Pre F protein-specific IgG 
antibody titers. 
Secondary Safety 
Objective 
Endpoints 
To assess the safety of IVX-A12 
compared to placebo by describing the 
incidence of serious adverse events 
(SAEs), adverse events of special interest 
([AESI],which are potential 
immune-mediated conditions [pIMCs]), 
medically-attended adverse events 
(MAAEs), LRTI cases of any severity 
(mild, moderate, severe) caused by RSV 
and/or hMPV (clinical event of special 
interest [CESI]), LRTI cases of any 
severity (mild, moderate, severe) not 
caused by RSV or hMPV, and adverse 
events (AEs) leading to trial withdrawal 
up to Day 365. 
- 
SAEs, AESIs (which are pIMCs), 
MAAEs, and AEs leading to trial 
withdrawal up to Day 365 (end of 
main trial). 
- 
Mild, moderate, or severe LRTI cases 
caused by RSV or hMPV (CESI) up to 
Day 365. 
- 
Clinical safety laboratory parameters 
at screening, and Days 0, 7, and 28; 
- 
Mild, moderate, or severe LRTI cases 
not caused by RSV or hMPV up to 
Day 365. 
Secondary Immunogenicity 
Objectives 
Endpoints 
- 
To evaluate the serum NAb response 
to IVX-A12 or placebo at Day 0, 
Day 180, and Day 365. 
- 
To evaluate the serum IgG binding 
antibody response to IVX-A12 or 
placebo at Day 0, Day 180, and 
Day 365 after vaccination. 
- 
To evaluate the proportion of subjects 
with a ≥4-fold increase in serum NAb 
and serum IgG binding antibody titers 
at Days 180 and 365 compared to 
baseline (Day 0). 
- 
To evaluate the proportion of subjects 
with an ≥8-fold increase in serum NAb 
and serum IgG binding antibody titers 
at Days 28, 180 and 365 compared to 
baseline (Day 0). 
- 
GMT of RSV/A–, RSV/B-, hMPV/A-, 
and hMPV/B-specific NAb at Days 0, 
180, and 365. 
- 
GMTs of RSV and hMPV prefusion F 
protein-specific IgG antibody titers at 
Days 0, 180, and 365. 
- 
Proportion of subjects with a ≥4-fold 
increase (SRR) in serum anti-RSV/A-, 
RSV/B- hMPV/A-, and hMPV/B-specific 
NAb from prevaccination/baseline 
(Day 0) to Days 180, and 365 after 
vaccination. 
- 
Proportion of subjects with an ≥8-fold 
increase in serum anti-RSV/A-, 
RSV/B-, hMPV/A-, and 
hMPV/B-specific NAb from 
prevaccination/baseline (Day 0) to 
Days 28, 180, and 365 after 
vaccination. 
- 
Proportion of subjects with ≥4-fold 
increase (SRR) in RSV- and hMPV– 
prefusion F protein-specific IgG 
antibody titers from 

I V X - A 1 2  
T ri al  P r o t o c ol  N o.  I C V X - 1 2 - 2 0 1 
V e r si o n 5. 0  
P a g e 1 6  of  1 0 3  
0 2  A p ril  2 0 2 4  
C O N F I D E N T I A L  
 
 
 
  
pr e v a c ci n ati o n / b a s eli n e ( D a y 0 ) t o 
D a y s  1 8 0  a n d  3 6 5  aft er  v a c ci n ati o n.  
-  
G M F R at D a y s 1 8 0 a n d 3 6 5 v er s u s 
D a y  0  i n s er u m  a nti - R S V / A - , R S V / B - , 
h M P V / A - , a n d h M P V / B- s p e cifi c N A b 
a n d R S V a n d h M P V pr ef u si o n F 
pr ot ei n - s p e cifi c I g G a nti b o d y tit er s.  
-  
R e v er s e  c u m ul ati v e  di stri b uti o n  ( R C D ) 
of s er u m N A b a n d I g G a nti b o d y tit er s 
at D a y s 0, 2 8, 1 8 0, a n d 3 6 5.  
 
 
 
 
 
 
 
 
O b s e r v ati o n al  E xt e n si o n  
 
 
S e c o n d a r y  S af et y  
 
 
O bj e cti v e  
E n d p oi nt s  
 
 
T o d e s cri b e t h e i n ci d e n c e of S A E s, A E SI, 
a n d M A A E s i n c o n s e nti n g I V X - A 1 2 a 
v a c ci n e e s  a n d  pl a c e b o  r e ci pi e nt s t hr o u g h 
a n  a d diti o n al  1 2  m o nt h s  ( Vi sit  D a y  7 3 0).  
S A E s,  A E SI s,  a n d  M A A E s  fr o m D a y  3 6 5 
t hr o u g h D a y 5 4 5 a n d u p t o D a y 7 3 0.  
 
 
 
 
C CI
C CI

I V X - A 1 2  
T ri al  P r o t o c ol  N o.  I C V X - 1 2 - 2 0 1 
V e r si o n 5. 0  
P a g e 1 7  of  1 0 3  
0 2  A p ril  2 0 2 4  
C O N F I D E N T I A L  
 
 
 
 
Cli ni c al  T ri al  D e si g n:  
T hi s  P h a s e  2 a  cli ni c al  tri al of  I V X- A 1 2  i s a  r a n d o mi z e d, o b s er v er - bli n d,  
pl a c e b o  - c o ntr oll e d,  d o s a g e  o pti mi z ati o n,  m ulti - c e nt er  tri al t o e v al u at e  t h e s af et y  a n d 
i m m u n o g e ni cit y of t w o f or m ul ati o n s of I V X- A 1 2 : a n u n a dj u v a nt e d d o s a g e l e v el of 
1 5 0 µ g R S V / 1 5 0 µ g h M P V of I V X - A 1 2 (I V X - A 1 2 a ) a n d a d o s a g e l e v el of 1 5 0 µ g  
R S V / 1 5 0 µ g h M P V of I V X - A 1 2 a dj u v a nt e d wit h M F 5 9 (I V X - A 1 2 d ) c o m p ar e d t o pl a c e b o 
( dil u e nt ) i n a d ult s 6 0 t o 8 5 y e ar s of a g e. T h e d o s a g e l e v el a n d f or m ul ati o n s ( eit h er 
a q u e o u s [I V X - A 1 2 a ] or a dj u v a nt e d wit h M F 5 9  [I V X - A 1 2 d ] ) w er e d et er mi n e d b a s e d o n 
t h e t ot alit y of t h e I V X- A 1 2 n o n cli ni c al d at a a n d t h e i nt eri m s af et y a n d i m m u n o g e ni cit y 
cli ni c al d at a fr o m t h e o n g oi n g I V X - A 1 2 P h a s e 1 cli ni c al tri al. A t ot al of 3 0 0 µ g I V X - A 1 2 
( 7 5 µ g  R S V / 2 2 5 µ g  h M P V )  h a s  b e e n  e v al u at e d  wit h  M F 5 9  i n t h e I V X- A 1 2  G o o d  L a b or at or y 
Pr a cti c e ( G L P ) t o xi c ol o g y st u d y a n d u p t o 2 2 5 µ g of I V X - A 1 2 ( 7 5 µ g R S V / 1 5 0 µ g h M P V ) 
h a s b e e n e v al u at e d wit h M F 5 9 i n t h e P h a s e 1 cli ni c al tri al [I C V X - 1 2 - 1 0 1 ] ).  
T hi s  P h a s e  2 a  cli ni c al  tri al h a s  t hr e e tr e at m e nt gr o u p s :  T w o  I V X- A 1 2  gr o u p s  a n d  o n e 
pl a c e b o gr o u p. T h e t ot al a m o u nt of V L P i n t h e t w o I V X - A 1 2 gr o u p s will n ot e x c e e d 
3 0 0 µ g of V L P s.  
G r o u p  A:  I V X- A 1 2 a,  t h e u n a dj u v a nt e d  d o s a g e  l e v el of  1 5 0  µ g  R S V /  1 5 0  µ g  h M P V.  
G r o u p  B:  I V X- A 1 2 d,  t h e d o s a g e  l e v el of  1 5 0  µ g  R S V /  1 5 0  µ g  h M P V  a dj u v a nt e d  wit h 
M F 5 9.  
G r o u p  C:  pl a c e b o.  
A p pr o xi m at el y 2 5 0 s u bj e ct s w er e r a n d o ml y all o c at e d at a r ati o of 2 : 2 : 1 t o r e c ei v e o n e 
of t h e t w o I V X - A 1 2 f or m ul ati o n s (I V X - A 1 2 a [ N = 1 0 0 ] or I V X - A 1 2 d [ N = 1 0 0 ] ) or pl a c e b o 
( N = 5 0 ), r e s p e cti v el y. S u bj e ct s w er e al s o str atifi e d b y a g e gr o u p ( 6 0 t o 6 9 y e ar s of a g e 
a n d 7 0 t o 8 5 y e ar s of a g e). D o si n g of t h e t w o I V X - A 1 2 gr o u p s a n d pl a c e b o gr o u p s 
st art e d  i n p ar all el.  A g e - str atifi e d  r a n d o mi z ati o n  s h o ul d  b al a n c e  a s si g n m e nt  b et w e e n  t h e 
t w o a g e gr o u p s. T h e pl a n n e d s u bj e ct all o c ati o n t o tri al gr o u p s i s pr o vi d e d i n T a bl e S 1 . 
T h e ti m e a n d e v e nt s s c h e d ul e s f or t h e m ai n st u d y a n d f or t h e o b s er v ati o n al e xt e n si o n 
ar e  pr e s e nt e d  i n S e cti o n  2. 1  a n d  S e cti o n  2. 2 , r e s p e cti v el y. T h e  tri al d e si g n  s c h e m ati c  i s 
s h o w n i n S e cti o n 2. 3 . 
C CI

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Table S1 Clinical Trial Schema 
Group 
Dosage Level 
Total (N=250)* 
A 
IVX-A12a (unadjuvanted 150 µg 
RSV/150 µg hMPV) 
100 
B 
IVX-A12d (150 µg RSV/150 µg hMPV 
adjuvanted with MF59) 
100 
C 
Placebo† 
50 
† Placebo will be aqueous diluent 
*Note: The stratified randomization will ensure balanced dosage level group assignment between 
the two age groups (60 to 69 years of age and 70 to 85 years of age, respectively). 
Trial Procedures: 
Approximately 250 adult subjects (60 to 85 years of age) were enrolled. A subject was 
considered to be enrolled upon having signed the informed consent form (ICF). Subjects 
were randomly allocated to receive either IVX-A12 or placebo at a ratio 2:2:1, resulting 
in approximately 100 subjects in each IVX-A12 group and 50 in the placebo group. In 
addition, subjects were stratified by age groups (60 to 69 years of age versus 70 to 
85 years of age). 
Randomization occurred simultaneously into all three trial groups (IVX-A12a, IVX-A12d, 
and placebo). Initial vaccinations were performed in sentinel subjects and then 
expanded to the remaining subjects in each of the three trial groups. In total, there 
were 40 sentinels. In each IVX-A12 group, 16 sentinel subjects received IVX-A12a 
(8 subjects from age stratum 60 to 69 years of age and 8 subjects from age stratum 
70 to 85 years of age); 16 sentinel subjects received IVX-A12d (8 subjects from age 
stratum 60 to 69 years of age and 8 subjects from age stratum 70 to 85 years of age). 
In the placebo group, 8 sentinel subjects received placebo (4 subjects from age stratum 
60 to 69 years of age and 4 subjects from age stratum 70 to 85 years of age). Sentinels 
were closely monitored for a minimum of 48 hours. If no stopping rules were triggered, 
the remaining subjects in the IVX-A12 and placebo groups will be enrolled. 
There are a total of seven scheduled clinic visits required for each subject (at screening, 
then Days 0, 7, 28, 90, 180, and 365), and five phone contacts (on Days 3, 14, 56, 135, 
and 270) for Subjects remaining in the main study which ends on Visit Day 365. At 
Visit Day 365, all trial subjects will be unblinded; IVX-A12a and placebo recipients will 
be invited to enroll into the extension, which includes a telephone call at Day 545 
(approximately 6 months from Day 365) and a clinic visit at approximately 12 months 
(Day 730) after the Day 365 visit for a final blood draw. 
Assessments: 
Safety assessments: All solicited local (injection site) reactions and systemic ARs were 
collected for all subjects for 7 consecutive days, starting from the day of the single-dose 
administration (Day 0) through Day 6 (7 days total); unsolicited AEs through Day 28; 
and safety blood samples (clinical laboratory evaluation at screening, Day 0/baseline, 
Day 7, and Day 28). SAEs, AESIs, MAAEs, AEs leading to trial withdrawal, and CESI are 
captured from the time of randomization to the end of the trial evaluation on Day 365, 
approximately 12 months after vaccination. Clinic staff (a trained healthcare provider) 
contact the subject by phone call or using a digital application (e.g., SMS text) to 
facilitate the collection of relevant safety information such as concomitant medication 
use and occurrence of AEs/SAEs. Throughout the trial (until Day 365), all subjects 

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complete a respiratory symptom surveillance tool approximately twice a week (i.e., 
approximately twice within 7 -day intervals starting on Day 0 post-vaccination) to be 
monitored for the trial-defined CESI of mild, moderate, or severe LRTI caused by RSV 
and/or hMPV, using the established case definition and algorithm for evaluation of ARI 
and using nasopharyngeal (NP) swabs for the detection of RSV, hMPV, and other 
respiratory viruses. Subjects will be instructed to return to the clinic for assessment 
within 3 to 7 days of onset of ARI (ideally within 3 days) to maximize detection of virus. 
After subjects are unblinded to their trial group assignment at Day 365, consenting 
IVX-A12a and placebo recipients will be contacted by clinic staff by phone call or with a 
digital application (e.g., SMS text) to facilitate the collection of MAAEs, AESIs, and SAEs, 
at Day 545; MAAEs, AESIs and SAEs will also be collected at the clinic visit on Day 730. 
Immunogenicity assessments: Blood sampling for immunogenicity will be taken at 
Days 0, 28, 180, and 365. IVX-A12a and placebo subjects consenting to the extension 
portion of the trial will have a single blood sampling for immunogenicity at Day 730. 
Stopping Rules: 
Monitoring of safety signals will be performed throughout the trial by an independent 
Safety Monitoring Committee (SMC). The clinical trial will be halted if there is clear 
evidence of potential harm or harmful effects. Vaccine administration may be paused for 
further review and assessment if any of the following events occur: 
• 
In any trial subject: 
o 
Any death that could be related to vaccine as per the investigator, sponsor, 
or SMC chair occurring during the trial; 
o 
Any vaccine-related SAE during the trial; 
o 
Any life-threatening (Grade 4) vaccine-related AE during the trial, which 
needs medical intervention including: 
• 
Ulceration, abscess or necrosis at the injection site; 
• 
Laryngospasm, bronchospasm or anaphylaxis within 24 hours after 
administration of vaccine. 
o 
An allergic or hypersensitivity reaction such as fever >40°C or generalized 
urticaria (defined as occurring at three or more body parts) within 72 hours 
after administration of vaccine. 
• 
If 2 or more subjects in a single trial group experience the same severe (Grade 3) 
AE/AR (Preferred Term [PT] in a given Medical Dictionary for Regulatory Activities 
[MedDRA] system organ class [SOC]) within the first 7 days following vaccination 
that persists for at least 48 hours and cannot be clearly attributed to another cause: 
o 
Severe (Grade 3) vaccine-related solicited local (injection site) reactions 
(excluding measured grades of erythema and swelling alone) or systemic 
ARs; 
o 
Severe (Grade 3) vaccine-related unsolicited AE during the trial; 
o 
Severe (Grade 3) vaccine-related vital sign(s) abnormality; 
o 
Severe (Grade 3) vaccine-related clinical laboratory abnormality. 
In the case that a pre-defined safety signal is met in any trial group, subsequent dosing 
will be halted to permit a complete evaluation of the reported event(s), and to consult 
the SMC. Based on the review of the data, the SMC may recommend temporary or 
permanent stopping, or continuation of dosing. When dosing resumes after a halt, 
further measures for safety may be introduced. 

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Subject Population: 
Subject Population (age range): Adults 60 to 85 years of age. 
Planned Number of Subjects: Approximately 250 total; approximately 100 in each of the 
two IVX-A12 groups and 50 in the placebo group. 
Planned Number of Groups: A total of three trial groups: two IVX-A12 groups and one 
placebo group. 
From Day 365, IVX-A12a and placebo recipients who consent to follow-up for an 
additional 12 months are also defined as the trial “extension population subset.” 
Inclusion Criteria: 
1. Male or female subjects, 60 to 85 years of age, who must be in stable health based 
on medical history, vital signs, physical examination, and laboratory evaluation prior 
to vaccination, in the investigator’s clinical judgment; 
2. Subjects may have ongoing chronic conditions (comorbidities such as hypertension, 
congestive heart failure, chronic obstructive pulmonary disease, type 2 diabetes 
mellitus, hyperlipoproteinemia, or hypothyroidism) who are, in the investigator’s 
opinion, medically compensated and without recent exacerbation (for example, no 
emergency room [ER] visits and no change to medical treatments or medications to 
better control the condition) within the prior 3 months; 
3. Subjects able to voluntarily give written informed consent and can comply with trial 
procedures including follow-up for approximately 12 months after vaccination; 
4. Body mass index 17 to <40 kg/m2 at screening; 
5. Before randomization, female subjects must be unable to conceive (e.g., 
menopausal, i.e., 12 consecutive months without menstruation, hysterectomy, 
oophorectomy, etc.) and not intending to conceive by any method; 
6. Subject must agree not to donate blood from the time of vaccination through 
3 months after vaccination; 
7. Subject must be willing to provide verifiable identification and have the means to be 
contacted and to contact the investigator or the site’s staff during the entire clinical 
trial. 
Exclusion Criteria: 
1. Subjects with moderate or severe liver disease, metastatic solid tumor, and acquired 
immunodeficiency syndrome (AIDS) are to be excluded. In addition, subjects with 
underlying significant illness or condition(s) or ongoing treatment that, in the opinion 
of the investigator, could (i) interfere with the conduct of the trial, (ii) pose an 
unacceptable risk to the subject in this trial, (iii) interfere with the subject’s ability to 
comply with the trial procedures or abide by the trial restrictions, (iv) interfere with 
the ability to interpret safety data, or (v) prevent completion of the trial are to be 
excluded; 
2. Older adults who meet frail elderly criteria (older persons with medical, nutritional, 
cognitive, emotional, or activity impairments, as defined by the Dalhousie Clinical 
Frailty Score ≥4 (Rockwood et al., 2005), See Appendix C; 
3. Prior receipt of any licensed or investigational RSV or hMPV vaccine within the past 
12 months; 

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4. Prior receipt of another investigational medicinal product (IMP; trial drug, biologic, or 
device) not authorized for use in the USA and European Union within the past 
3 months; 
5. Laboratory-confirmed RSV or hMPV infection within 12 months prior to enrollment; 
6. Currently enrolled or plan to participate in another clinical trial with an 
investigational agent (including licensed or unlicensed vaccine, drug, biologic, 
device, blood product, or medication) to be received during the trial period; 
7. History of malignancy within 5 years before screening not in the following 
categories: (i) subjects with squamous and basal cell carcinomas of the skin and 
carcinoma in situ of the cervix may be enrolled at the discretion of the investigator, 
(ii) subjects with a history of malignancy within 5 years before screening, with 
minimal risk of recurrence per the investigator's judgment, can be enrolled; 
8. Per medical history, subjects with chronic active hepatitis B or hepatitis C infection, 
human immunodeficiency viruses type 1 or type 2 infection, acute polyneuropathy 
(such as Guillain-Barré syndrome), or chronic idiopathic demyelinating 
polyneuropathy; subjects whose hepatitis C antibody test is positive but whose viral 
loads are negative may be enrolled; 
9. Acute illness, with or without fever at the time of planned vaccination; 
10. History of hypersensitivity or serious adverse reactions to vaccines, such as 
anaphylaxis or angioedema, or any known allergies to any component of the 
IVX-121 and/or IVX-241 vaccine, or hypersensitivity to latex; 
11. Abnormal function of the immune system resulting from clinical conditions including 
chronic administration of systemic corticosteroids (oral/intravenous/IM at a daily 
dose equivalent of >20 mg prednisone in a period of more than 14 days), or 
administration of immunosuppressive chemotherapy, biologics, or radiotherapy 
within the past 3 months prior to planned vaccination; 
12. Subjects who have received treatment with immunoglobulins or other biologics, such 
as immunosuppressive therapies expected to modify immune response to 
vaccination (including monoclonal antibodies [MAbs] for chronic underlying 
conditions) within the past 3 months prior to planned vaccination; 
13. Trial personnel as an immediate family or household member; 
14. For licensed vaccines: 
a) Receipt of licensed inactivated vaccines (including seasonal influenza vaccine) 
within 14 days prior to trial vaccine administration on Day 0, or licensed 
replicating vaccines such as RNA or live-attenuated virus vaccines within 30 days 
prior to Day 0. 
b) Receipt of licensed vaccines is permitted after completion of the Day 28 visit. 
c) Receipt of any licensed COVID-19 vaccines is permitted if dosing regimen 
completed within 21 days prior to Day 0 or after completion of the Day 28 visit. 
Investigational Medicinal Products: 
IVX-A12: The two investigational IVX-A12 formulations for testing will be composed of a 
constant IVX-121 RSV VLP dosage level (150 µg) with one constant IVX-241 hMPV VLP 
dosage level (150 µg). 

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The two formulations of IVX-A12 will be: 
- 
An unadjuvanted dosage level of 150 µg RSV/150 µg hMPV of IVX-A12 
(IVX-A12a); and 
- 
A dosage level of 150 µg RSV/150 µg hMPV of IVX-A12 adjuvanted with MF59 
(IVX-A12d) 
These two formulations will be compared to placebo (diluent). 
The final investigational IVX-A12 drug product will be administered either as an aqueous 
vaccine (IVX-A12a) or with MF59 to be mixed 1:1 in the clinic (IVX-A12d). The amount 
of MF59 (squalene) per dose will not exceed 9.75 mg. Specific instructions for 
preparation of vaccine will be provided in the pharmacy manual. 
The intended volume for administration of IVX-A12 is 0.5 mL for IM administration. 
Placebo: Sterile aqueous diluent, delivered as a 0.5 mL dose. The placebo does not 
contain preservatives. 
Route of Administration: IM administration of a single IVX-A12 or placebo dose into the 
deltoid of the non-dominant arm. 
Duration Subject Participation: 
The duration of subject participation in the main trial will be approximately 12 months. 
The trial will be unblinded at Visit Day 365, where subjects who received IVX-A12a or 
placebo will be invited to consent to another 12 months of follow-up. 
Statistical Considerations: 
Analysis sets: 
Safety Set: The safety set will consist of all subjects who received a dose of IVX-A12 or 
placebo. Subjects will be analyzed as treated. 
Full Analysis Set (FAS): The FAS will include all randomized subjects who received a 
dose of IVX-A12 or placebo. Subjects will be analyzed as randomized. 
Per-Protocol Set (PPS): The PPS will include all subjects in the FAS who received a dose 
of IVX-A12 or placebo and have no major protocol deviations that have a significant 
impact on immunogenicity results. which may exclude subjects from the PPS. Subjects 
will be analyzed as randomized. 
Extension Enrolled Set: The Extension Enrolled Set will consist of all subjects who 
consented to participate in the extension portion of the trial. Subjects will be analyzed 
as initially treated. 
Analysis of Disposition, Demographics, Other Baseline Characteristics, Medical 
History, and Medications: 
Age, gender, race, and other baseline characteristics (including baseline RSV and hMPV 
NAb titers) will be summarized descriptively by treatment group for all randomized 
subjects. 
Immunogenicity Analyses: 
Immunogenicity data will be summarized for each treatment group and strain (RSV/A, 
RSV/B, both RSV strains and either RSV strain; hMPV/A, hMPV/B, both hMPV strains and 
either hMPV strain). The GMT will be calculated for RSV/A, RSV/B, hMPV/A and hMPV/B 
titers separately along with their 95% confidence interval (CI). The adjusted GMT and 
corresponding 95% CI will be obtained from an analysis of covariance (ANCOVA) model, 
which will include log-transformed baseline titers, age group, and treatment group as 

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terms. Durability will be assessed at Days 180 and 365 by comparing to Day 28 data. 
The geometric mean of fold changes and corresponding 95% CI will be calculated. 
Proportion of subjects with ≥4-fold increase (SRR), 8-fold increase, and GMFR from 
prevaccination/baseline (Day 0) will be summarized for Days 28, 180, and 365 after 
vaccination. RCD curves will be generated. Respective data will also be summarized for 
Day 730. 
The VLP core-specific IgG titers will be summarized at Days 0, 28, 180, 365, and in the 
extension population subset at Day 730 with GMT and 95% CI. 
Separate summaries will be provided for subjects that agreed to participate in the 
extension portion of the trial and will include these subjects’ data from the beginning of 
the trial through Day 730. 
All immunogenicity data will be listed. 
Efficacy analysis: 
Cases of mild, moderate, or severe LRTI and any severity LRTI due to RSV and/or hMPV 
(CESIs), meeting the protocol-specified definitions, will be summarized by vaccine group 
and placebo group starting on Day 14 through the end of the trial (Day 365). Listings 
will be provided. 
Safety Analyses: 
Solicited local (injection site) reactions and solicited systemic ARs: Solicited ARs will be 
summarized for 7 days starting from the day of dosing (Day 0) through Day 6 (total of 
7 days). The summary will be by day and overall, within 7 days. Solicited ARs by 
maximum severity will also be summarized. 
Unsolicited AEs: Unsolicited AEs will be assessed from day of dosing (Day 0) through 
28 days post-vaccination and coded according to MedDRA and summarized by SOC and 
PT. The summary tables will include the number and percentage of subjects reporting 
unsolicited AEs by SOC and PT, and by SOC, PT, and maximum severity. Subjects 
reporting ≥Grade 3 and vaccine-related unsolicited AEs will also be summarized. 
SAEs, AESIs, MAAEs, AEs leading to withdrawal, CESI (mild, moderate, or severe LRTI 
caused by RSV and/or hMPV) and mild, moderate, or severe LRTI cases not caused by 
RSV or hMPV: Will be assessed throughout the trial (from randomization on Day 0) and 
coded using MedDRA and summarized by SOC and PT. Separate summaries will be 
provided for subjects that agreed to participate in the extension portion of the trial and 
will include these subjects’ data from the beginning of the trial through Day 730. 
All solicited local and systemic ARs and unsolicited AEs will be listed. 
Clinical laboratory tests including hematology, chemistry, and urinalysis will be 
summarized by vaccine groups. For numeric laboratory parameters, the observed value 
and change from baseline will be summarized by visit. For categorical laboratory 
parameters, the number of subjects and percentages will be summarized by visit. Shift 
tables may be provided as well. All laboratory data will be listed. 
All vital signs observed value and change from baseline will be summarized by vaccine 
groups. Listing will also be provided. 
Physical examination results will be listed. 
Sample Size Justification: 
Sample size for this trial is not based on any formal hypothesis testing. Analyses of 
safety, efficacy, and immunogenicity will be primarily descriptive in nature. An 
approximate total of 250 subjects (approximately 100 subjects in each of the IVX-A12 

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groups and 50 subjects in the placebo group) will be randomized. With 100 subjects in 
each IVX-A12 group, there is an 63.4% probability of observing at least 1 subject with 
an AE if the true incidence of the AE is 1%, and 86.7% probability of observing at least 
1 subject with an AE if the true incidence of the AE is 2%. The trial will have more than 
90% power to detect a difference of 20% or more in SRR or detect a 2-fold increase or 
more in GMT or GMFR (assuming standard deviation at 0.5 log10), between the two 
IVX-A12 groups (or between the IVX-A12 group and placebo group), with two--sided 
type-1 error rate at 0.05. 
Interim Analysis/Data Reviews: 
Two interim analyses (IAs) will be performed: The first IA was performed after all 
subjects completed the Day 28 safety assessments and when all Day 28 immunogenicity 
data are available; the second IA was performed after all subjects completed the 
Day 180 safety assessments, and when all Day 180 secondary immunogenicity data 
were available. These analyses further support evaluation of safety and immunogenicity 
of IVX-A12 in older adults. These IA will be used for confirmation of dosage level and 
formulation selected for further evaluation in older adults 60 years of age or older. 
A final analysis of main trial will be performed after Day 365, and an analysis of the 
observational extension will be performed after Day 730. 
Clinical Study Report (CSR): 
A CSR will be prepared when Day 365 analyses have been completed for the primary 
and secondary objectives of the trial. Additional analyses including safety and 
immunogenicity through Day 730 may be provided in a Clinical Study Addendum. 
Safety Review and Safety Monitoring Committee: 
An independent SMC was constituted to monitor the safety of all subjects enrolled in the 
trial, including solicited local (injection site) reactions, solicited systemic ARs, unsolicited 
AEs, and clinical laboratory data. The SMC reviewed safety data collected during the 
7 consecutive days following vaccination for all subjects, focusing on the interpretation 
of solicited local (injection site) reactions and solicited systemic ARs, unsolicited AEs, 
and clinical laboratory data in the first week after dosing when most reactogenicity is 
expected to occur. Details of the membership, roles and functioning of the committee 
are available in the SMC charter. 
ICVX-12-201 Version 5.0 
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2.1 
Time and Events Schedule for ICVX-12-201: Main Trial  
 
Day 
Screen 
0 
3 
7 
14 
28 
56 
90 
135 
180 
270 
Unsch m 
365 n 
Window (Days) 
-28 to -1 n/a 
±1 -2 to +2 
±3 
±5 
±7 
±10 
±10 
±14 
±14 
- 
±21 
Clinic Visit (or home-health visit) a 
SMS/Phone Call/Digital App 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Screening Informed consent b 
X 
Main Study Informed consent b 
Eligibility criteria 
Demographics 
Medical history 
Medication history c 
Urinalysis d 
Physical examination e 
Vital signsf 
Safety blood draw 
Testing for RSV/hMPV/other respiratory 
pathogens (NP swab/PCR) 
Serology blood draw for SNA, ELISA h 
Confirm Eligibility 
Randomization 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X g 
X g 
X g 
X g 
X g 
X g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vaccine administration 
X 
Post-vaccination assessment i 
Diary distribution and training 
Solicited ARs/post-vaccination diary 
completion and review j 
Unsolicited AEs 
Concomitant medications 
RSS tool completion k 
AEs leading to withdrawal 
Assess for SAE, AESIs (including 
pIMC), MAAE, and CESI l 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AE, adverse event; AR, adverse reaction; AESIs, adverse event of special interest; pIMC, potential immune-mediated condition; 
CESI, clinical event of special interest; ELISA, enzyme-linked immunosorbent assay; LRTI, lower respiratory tract illness; MAAE, medically-attended 
AE; NP, nasopharyngeal; PCR, polymerase chain reaction; RSS, respiratory symptom surveillance; RSV, respiratory syncytial virus; SAE, serious AE; 
SNA, serum neutralization assay (live virus neutralization assay); Unsch, unscheduled. 
Notes on the next page. 

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Notes: 
a Home-health visits may be performed in lieu of clinic visit if permissible by local regulations and/or institutional/clinic standard operating procedures. 
b Confirm consent form signed prior to any procedures. 
c Medication history includes prior vaccinations. 
d Urine dipstick test at screening. An abnormal result for glucose, ketones, pH, protein, specific gravity, and/or urobilinogen will trigger urine 
microscopy. 
e Full physical exam (PE) at screening; symptom-directed PE at subsequent visits. 
f Collection of vital signs to include blood oxygen (SpO2) measurement 
g Procedure to be performed prior to dosing. 
h Collection of blood for serology (SNA and ELISA): Day 0, 28, 180, and 365. 
i Post-vaccination observation for 60 minutes. 
j Post-vaccination diary entry ends on Day 6. Diary review done with site personnel occurs on Day 7.k Respiratory Symptom Surveillance (RSS) tool to 
be completed twice a week by subjects throughout the trial, starting on Day 0 post-vaccination. 
l The trial-defined CESI is mild to severe LRTI caused by RSV or hMPV. 
m Perform unscheduled visits and procedures as applicable. 
n Trial termination visit; subjects who terminate the trial early are recommended to complete certain trial-related procedures.. 

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2.2 
Time and Events Schedule for ICVX-12-201: Extension  
 
Day 
365 
545 
730 
Unsch 
Window (Days) 
N/A 
±28 
±28 
- 
Clinic Visit (or home-health visit) a 
SMS/Phone Call/Digital App 
X 
X 
X 
X 
Unblinding of subjects b 
X 
Informed consent for extension c 
X 
Concomitant medications d 
X 
X 
X 
Assess for SAEs, AESIs, MAAEs e 
X 
X 
X 
Vital signs 
X 
X 
Physical examination f 
X 
X 
Safety blood draw 
Serology blood draw for SNA / ELISA 
X 
X 
X 
Abbreviations: AESIs, adverse event of special interest; ELISA, enzyme-linked immunosorbent assay; MAAE, medically-attended adverse event; N/A, 
not applicable; SAE, serious adverse event; SNA, serum neutralization assay (live virus neutralization assay); Unsch, unscheduled. 
a Home-health visits may be performed in lieu of clinical visits if permissible by local regulations and/or institutional/clinic standard operating 
procedures. 
b Unblinding of all subjects will occur after they have completed their Day 365 assessments. 
c Informed Consent for extension applicable only for selected Subjects in trial groups IVX-A12a or placebo. 
d For the trial extension, record concomitant medications and treatments only for self-reported SAEs and AESIs. 
e For the trial extension, document self-reported SAEs, AESIs, and MAAEs. 
f Symptom-directed physical examination, if needed. 

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Healthy adults aged 60 to85 years (N=approximately 250) 
Group A (A12) / Group B (A12) / Group C (Placebo) 
Age Stratification: 60 to 69 years / 70 to 85 years 
2.3 
Trial Design Schematic  
 
 
 

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3.0 
TRIAL REFERENCE INFORMATION  
3.1 
Trial-related Responsibilities  
The roles and responsibilities of all parties for trial-related activities are described in 
the project plan. 
3.2 
Principal Investigator  
The sponsor will select a principal investigator from the investigators who 
participate in the trial. Selection criteria for this investigator will include significant 
knowledge of the protocol, the investigational vaccine, their expertise in the 
therapeutic area and the conduct of clinical research as well as participation. The 
principal investigator will be required to review and sign the clinical study report 
(CSR) and by doing so agrees that it accurately describes the results of the trial. 

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3.3 
List of Abbreviations  
Abbreviations used in the body of the protocol. 
AE 
AESI 
AR 
adverse event 
adverse event of special interest 
adverse reaction 
AIDS 
acquired immunodeficiency syndrome 
ALT 
alanine aminotransferase 
ANVOCA 
analysis of covariance 
ARI 
acute respiratory illness 
AST 
aspartate aminotransferase 
BUN 
blood urea nitrogen 
CESI 
clinical event of special interest 
CI 
confidence interval 
CompA 
component A 
CompB-01 
component B-01 
CSR 
clinical study report 
CTM 
clinical trial material 
DS-Cav1 
soluble RSV 
eCRF 
electronic case report form 
EDC 
electronic data capture 
ELISA 
enzyme-linked immunosorbent assay 
EPIC 
Etiology of Pneumonia in the Community trial 
ER 
emergency room 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GMFR 
geometric mean fold rise 
GMT 
geometric mean titer 
hMPV 
human metapneumovirus 
IA 
interim analysis 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
independent ethics committee 
IgG 
immunoglobulin G 
IM 
intramuscular 
IMP 
investigational medicinal product 
IRB 
IVX-A12a 
Institutional Review Board 
unadjuvanted IVX-A12 formulation 

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IVX-A12d 
IVX-A12 formulation adjuvanted with MF59® 
IWRS 
interactive web response system 
LRTI 
lower respiratory tract illness 
MAAE 
medically-attended adverse events 
Mab 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHRA 
Medicines and Healthcare Products Regulatory Agency 
NAb 
neutralizing antibody 
NP 
nasopharyngeal 
PCR 
pIMC 
polymerase chain reaction 
potential immune-mediated condition 
PMDA 
Pharmaceuticals and Medical Devices Agency 
PPS 
per-protocol set 
PT 
preferred term 
RBC 
red blood cells 
RCD 
reverse cumulative distribution 
RNA 
ribonucleic acid 
RSS 
respiratory symptom surveillance 
RSV 
respiratory syncytial virus 
RT-PCR 
reverse transcription polymerase chain reaction 
SAE 
serious adverse event 
SMC 
safety monitoring committee 
SNA 
serum neutralization assay 
SOC 
system organ class 
SpO2 
blood oxygen saturation 
SRR 
seroresponse rate 
SUSAR 
suspected unexpected serious adverse reaction 
VLP 
virus-like particle 
WBC 
white blood cells 
Abbreviations used without expansion: 
°C 
degree Centigrade 
Ig 
immunoglobulin 
mL 
milliliter 
USA 
United States of America 
3.4 
Corporate Identification  
ICVX 
Icosavax, Inc. 

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4.0 
INTRODUCTION  
4.1 
Respiratory Syncytial Virus  
Respiratory syncytial virus (RSV) is a single-strand, negative sense ribonucleic acid 
(RNA) virus belonging to the Orthopneumovirus genus of the family Pneumoviridae 
[3]. There are two major genetic lineages, A and B (subgroups A and B, 
respectively), which are antigenically related, and cross-neutralizing antibodies are 
induced upon infection with either subgroup. RSV is a major cause of lower 
respiratory tract illness (LRTI) worldwide in all age groups. Epidemiological data 
suggest that in the USA alone, RSV may cause >170,000 hospitalizations and 
~14,000 deaths annually [4]. RSV is also an important cause of respiratory disease 
in Europe, South Africa, and Australia [5-9]. Clinical data has identified a 
substantial disease burden in adults comparable to influenza, with most of the 
hospitalization and mortality occurring in older adults over 65 years of age [10]. 
The incidence and severity of RSV disease is particularly high in the frail elderly and 
in adults with cardiopulmonary conditions, who are considered at high risk for 
complications and hospitalization due to RSV [11]. 
RSV infections are ubiquitous with lifelong reinfections in all age groups indicating 
that immunity is neither sustained nor complete [12-14]. RSV spreads by 
respiratory droplets and close contact with infected persons or fomites. In 
temperate climates there is an annual winter epidemic [15], whereas in tropical 
areas seasonality is less distinct, but infection is most common during the rainy 
season [16]. The severity of RSV disease is largely determined by the extent of 
viral replication following infection [17]. The production of neutralizing antibodies 
(NAbs) should be the goal of vaccination as it is associated with protection against 
disease. However, seropositivity only confers partial protection against infection 
[17]. 
4.2 
Human Metapneumovirus  
Human Metapneumovirus (hMPV) is a single-strand, negative sense RNA virus of 
the Metapneumovirus genus in the Pneumoviridae family [3], and was first 
described in 2001 when it was isolated from children with respiratory disease [18]. 
The most closely related human pathogen is RSV. As with RSV, there are two major 
genetic lineages of hMPV, A and B (subgroups A and B, respectively), which are 
antigenically related and cross-neutralizing antibodies are induced upon infection 
with either subgroup [19,20]. hMPV represents one of the leading causes of acute 
respiratory tract infections in infants, children, immunosuppressed patients, and the 
elderly [21,22]. Several studies have shown that hMPV is highly prevalent 
worldwide, and in the USA alone, approximately 20,000 hospitalizations are 
registered every year due to this virus [23,24]. In older adults, hMPV is responsible 
for a significant proportion of serious respiratory infections, with similar rates of 

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infection as RSV. In the Etiology of Pneumonia in the Community (EPIC) trial, hMPV 
was confirmed in 4% of adults hospitalized with community-acquired pneumonia 
whereas RSV was confirmed in 3% of adults [25]. Similar to RSV, NAbs alone can 
protect against hMPV infection [26,27]. In mouse models, infection with hMPV 
protects against near term re-infection [28]; macaques infected with hMPV 
demonstrated seroconversion and temporary protection from subsequent infection 
that waned over several months [29]. As with RSV, in the presence of positive 
hMPV antibody titers, reinfections may occur in both healthy and 
immunocompromised adults [30,31]. 
4.3 
IVX-A12  
The Icosavax candidate vaccine, IVX-A12, is a bivalent combination formulation 
containing IVX-121 and IVX-241 virus-like particles (VLPs), computationally 
designed recombinant protein subunit vaccines for RSV and hMPV, respectively. 
Each VLP is composed of two recombinant proteins, Component A (CompA) and 
Component B (CompB-01), which have been designed to cooperatively assemble to 
form an icosahedral virus-like structure. Component A is a fusion protein-specific 
for each vaccine candidate (either CompA-RSV-02 or CompA-hMPV-01 for RSV and 
hMPV, respectively) and is expressed with the Pre F protein from the respective 
virus, which has been shown to induce robust NAb responses in nonclinical models. 
The IVX-121 and IVX-241 VLPs display 20 copies of the respective Pre F protein 
trimers on their surface. CompB-01 is a common component across both VLPs and 
provides the structural element that supports the multimeric display of 
CompA-RSV-02 or CompA-hMPV-01. When combined, the two components 
self-assemble into VLPs that show enhanced immunogenicity compared with either 
soluble RSV (DS-Cav1) or hMPV prefusion antigen trimers. The soluble DS-Cav1 
RSV Pre F protein was recently tested clinically and shown to be tolerable and 
immunogenic [32]. Based on nonclinical and early ongoing clinical trials, the 
Icosavax VLP high-density, multivalent design is hypothesized to provide 
immunologic advantages over simple subunit protein vaccines such as more 
breadth, magnitude, and persistence of vaccine induced NAb responses [43]. 
The candidate IVX-121 and IVX-241 VLPs are manufactured as separate drug 
substances and are combined to create the IVX-A12 bivalent formulation containing 
both VLPs. The proposed mechanism of action of IVX-A12 is to increase the 
proportion of RSV- and hMPV-specific NAbs that are associated with protection, 
compared to non-neutralizing antibodies [33,34]. IVX-A12 is intended for active 
immunization of the target population of older adults who are most at risk for 
disease following infection with RSV and hMPV. 
The candidate vaccine, IVX-A12, is a single-dose liquid formulation (0.5 mL) for 
intramuscular (IM) injection in adults 60 to 85 years of age, the target population. 
The IVX-A12 candidate vaccine will be formulated as an aqueous vaccine, to be 

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diluted 1:1 (V/V) with diluent. The IVX-A12 candidate vaccine was also formulated 
as an adjuvanted vaccine with MF59, an oil-in-water emulsion for further evaluation 
in this Phase 2 trial, based on interim analysis (IA) of data from the ongoing 
Phase 1 clinical trial (ICVX-12-101) of IVX-A12 (see below). 
Nonclinical studies of IVX-A12 bivalent combinations of the IVX-121 and IVX-241 
VLPs demonstrated the ability of both Pre F protein antigens on the Icosavax VLP 
platform to induce strong NAb responses. In addition, preclinical experiments 
showed the effects of IVX-A12 dosage levels, number of doses, and need for 
adjuvant vary with RSV exposure history (either naïve or primed by infection) of 
the animals. The recent Phase 1/1b clinical trial (IVX-121-01) with the RSV 
monovalent IVX-121 VLP subunit vaccine also helped guide selection of IVX-A12 
dosage levels formulated as either (i) aqueous vaccine or (ii) as adjuvanted vaccine 
with MF59 for the first-in-human evaluation of IVX-A12 vaccine. MF59 is a 
nanoemulsion adjuvant composed of squalene, polysorbate 80, sorbitan trioleate, 
and citrate. MF59 is widely used in the subunit influenza vaccine FLUAD that is 
licensed in the USA, European countries, and other countries [35]. In total, 
approximately 150 million doses of vaccines with MF59 have been distributed and 
no safety concerns have been observed related to MF59 [36]. Furthermore, 
increased dosage levels of MF59 (19.5 mg and 29.75 mg of squalene, up to 3 times 
the normal amount contained in licensed vaccines containing MF59) have shown to 
be well tolerated in adults ≥65 years of age in a recent Phase 1 clinical trial [40]. 
Boosting immunity in RSV-and hMPV-seropositive individuals with IVX-A12, a 
combination bivalent vaccine, may be challenging if one antigen interferes with the 
immune response to the other antigen. Imbalanced immune responses may require 
use of adjuvant in that scenario. However, studies in RSV- and hMPV-naïve mice 
and cotton rats did not demonstrate significant immune interference after 
vaccination when RSV and hMPV VLPs were administered in varying concentration 
ratios. 
4.4 
Rationale for the Proposed Trial  
Elderly adults, especially those with underlying chronic diseases, are highly 
susceptible to viral causes of community-acquired pneumonia caused by influenza 
virus, RSV, and hMPV [25; 11; 31; 40]. Although the US FDA recently approved the 
first two RSV vaccines to prevent RSV disease [41], this proposed trial evaluating 
IVX-A12 remains relevant for the following reasons: to assess immune responses 
induced by A12a to hMPV in addition to RSV, and to describe the persistence of 
those induced immune responses over time. This Phase 2a clinical trial is evaluating 
the safety and immunogenicity of an unadjuvanted dosage level of 150 µg RSV/ 
150 µg hMPV of IVX-A12 (IVX-A12a) and a dosage level of 150 µg RSV/150 µg 
hMPV of IVX-A12 adjuvanted with MF59 (IVX-A12d) compared to placebo in adults 
60 to 85 years of age. Safety and immunogenicity data from this proposed Phase2a 

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clinical trial will allow the selection of an optimal dosage level and formulation of 
IVX-A12 for adults 60 to 85 years of age in future clinical trials. 
The dosage level and formulations of IVX-A12 for this Phase 2a clinical trial have 
been selected based on the totality of the IVX-A12 nonclinical data and the interim 
safety and immunogenicity clinical data from the ongoing IVX-A12 Phase 1 clinical 
trial. Either of the two different IVX-A12 formulations, IVX-A12a and IVX-A12d, or 
placebo will be administered as a single IM dose to older adult subjects enrolled 
into two age strata (adults 60 to 69 years of age and elderly adults 70 to 85 years 
of age). Eligible older adult subjects were randomized to the different trial groups to 
ensure balance among the groups. 
This Phase 2a clinical trial includes a sentinel group of 40 subjects (16 subjects per 
active treatment group [n=32]; 8 subjects in the placebo group) to conservatively 
assess the 150 µg RSV/150 µg hMPV dosage level in combination with MF59. 
Subsequently, based on IA from Day 28 of this trial and from emerging data of the 
IVX-A12 Phase 1 trial (ICVX-12-101), the trial Sponsor has determined that the 
dosage level and formulation of IVX-A12 to be carried forward for further evaluation 
will be IVX-A12a [150 µg RSV/150 µg hMPV with no adjuvant]. Therefore, to 
evaluate the persistence of RSV and hMPV antibodies long term follow-up will be 
offered to the IVX-A12a vaccinees and contemporaneous placebo recipients. 
More specifically, data from the first IA of this Phase 2 trial at Day 28 demonstrated 
that the safety and reactogenicity between Phase 1 and Phase 2 data were similar 
even with the doubling of the IVX-A12 RSV dosage level in the Phase 2 trial. The 
Phase 2 trial data showed that local and systemic reactions were mostly mild with a 
few moderate reactions, and no serious or severe AEs, and no AEs leading to trial 
discontinuation were observed. There were no LRTI cases of any severity (mild, 
moderate, severe) caused by RSV and/or hMPV (CESIs) through Day 28. The 
inclusion of MF59 did not improve the immunogenicity of 150 µg RSV/150 µg hMPV 
in this older Phase 2 population relative to the Phase 1 population, and slightly 
more reactogenicity was observed with the addition of MF59 than with IVX-A12a 
alone. 
In addition, IVX-A12a appeared to generate similar neutralizing and binding 
antibody responses to RSV when compared to those induced by already licensed 
RSV vaccines, which supports the selection of this unadjuvanted dosage level of 
150 µg RSV/150 µg hMPV as the appropriate dosage level and formulation 
composition for further development. 

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5.0 
OBJECTIVES AND ENDPOINTS  
 
Main Trial 
Primary Safety 
Objective 
Endpoints 
To assess the safety and tolerability of 
the IVX-A12 bivalent candidate vaccine 
compared to placebo up to 1 year 
following a single IVX-A12 vaccination. 
- 
Solicited local (injection site) 
reactions and systemic ARs for 
7 consecutive days starting from 
Day 0 to Day 6 after vaccination. 
- 
Unsolicited AEs from Day 0 to Day 28. 
Primary Immunogenicity 
Objectives 
Endpoints 
- 
To evaluate the serum NAb response 
to IVX-A12 or placebo, measured by 
live virus serum neutralization assays 
(SNA), at Day 28. 
- 
To evaluate the serum 
immunoglobulin G (IgG) binding 
antibody response to IVX-A12 or 
placebo, measured by enzyme-linked 
immunosorbent assays (ELISA), at 
Day 28. 
- 
To evaluate the proportion of subjects 
with a ≥4-fold increase in serum NAb 
and serum IgG binding antibody titers 
to IVX-A12 from 
prevaccination/baseline (Day 0) to 
Day 28. 
- 
Geometric mean titers (GMT) of 
RSV/A-, RSV/B-, hMPV/A-, and 
hMPV/B-specific NAb at Day 28. 
- 
GMT of RSV and hMPV Pre F 
protein-specific IgG antibody titers at 
Day 28. 
- 
Proportion of subjects with a ≥4-fold 
increase in serum anti-RSV/A-, 
RSV/B-, hMPV/A-, and 
hMPV/B-specific NAb from 
prevaccination/baseline (Day 0) to 
Day 28 after vaccination (defined as 
seroresponse rate [SRR]). 
- 
Proportion of subjects with ≥4-fold 
increase (SRR) in RSV- and 
hMPV-specific IgG antibody titers 
from prevaccination/baseline (Day 0) 
to Day 28. 
- 
Geometric mean fold rise (GMFR) at 
Day 28 versus Day 0 in serum anti 
RSV/A-, RSV/B-, hMPV/A-, and 
hMPV/B-specific Nabs and RSV and 
hMPV Pre F protein-specific IgG 
antibody titers. 
Secondary Safety 
Objective 
Endpoints 
To assess the safety of IVX-A12 
compared to placebo by describing the 
incidence of serious adverse events 
- 
SAEs, AESIs (which are pIMCs), 
MAAEs, and AEs leading to trial 

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(SAEs), adverse events of special interest 
([AESI],which are potential 
immune-mediated conditions [pIMCs]), 
medically-attended adverse events 
(MAAEs), LRTI cases of any severity 
(mild, moderate, severe) caused by RSV 
and/or hMPV (clinical event of special 
interest [CESI]), LRTI cases of any 
severity (mild, moderate, severe) not 
caused by RSV or hMPV, and adverse 
events (AEs) leading to trial withdrawal 
up to Day 365. 
withdrawal up to Day 365 (end of 
main trial). 
- 
Mild, moderate, or severe LRTI cases 
caused by RSV or hMPV (CESI) up to 
Day 365. 
- 
Clinical safety laboratory parameters 
at screening, and Days 0, 7, and 28; 
- 
Mild, moderate, or severe LRTI cases 
not caused by RSV or hMPV up to 
Day 365. 
Secondary Immunogenicity 
Objectives 
Endpoints 
- 
To evaluate the serum NAb response 
to IVX-A12 or placebo at Day 0, 
Day 180, and Day 365. 
- 
To evaluate the serum IgG binding 
antibody response to IVX-A12 or 
placebo at Day 0, Day 180, and 
Day 365 after vaccination. 
- 
To evaluate the proportion of subjects 
with a ≥4-fold increase in serum NAb 
and serum IgG binding antibody titers 
at Days 180 and 365 compared to 
baseline (Day 0). 
- 
To evaluate the proportion of subjects 
with an ≥8-fold increase in serum NAb 
and serum IgG binding antibody titers 
at Days 28, 180 and 365 compared to 
baseline (Day 0). 
- 
GMT of RSV/A–, RSV/B-, hMPV/A-, 
and hMPV/B-specific NAb at Days 0, 
180, and 365. 
- 
GMTs of RSV and hMPV Pre F 
protein-specific IgG antibody titers at 
Days 0, 180, and 365. 
- 
Proportion of subjects with a ≥4-fold 
increase (SRR) in serum anti-RSV/A-, 
RSV/B- hMPV/A-, and hMPV/B-specific 
NAb from prevaccination/baseline 
(Day 0) to Days 180, and 365 after 
vaccination. 
- 
Proportion of subjects with an ≥8-fold 
increase in serum anti-RSV/A-, 
RSV/B-, hMPV/A-, and 
hMPV/B-specific NAb from 
prevaccination/baseline (Day 0) to 
Days 28, 180, and 365 after 
vaccination. 
- 
Proportion of subjects with ≥4-fold 
increase (SRR) in RSV- and hMPV– 
Pre F protein-specific IgG antibody 
titers from prevaccination/baseline 
(Day 0) to Days 180 and 365 after 
vaccination. 
- 
GMFR at Days 180 and 365 versus 
Day 0 in serum anti-RSV/A-, RSV/B-, 
hMPV/A-, and hMPV/B-specific NAb 

I V X - A 1 2  
T ri al  P r o t o c ol  N o.  I C V X - 1 2 - 2 0 1 
V e r si o n 5. 0  
P a g e 3 8  of  1 0 3  
0 2  A p ril  2 0 2 4  
C O N F I D E N T I A L  
 
 
 
 
a n d  R S V  a n d  h M P V  Pr e  F  
pr ot ei n - s p e cifi c  I g G a nti b o d y  tit er s. 
- 
R e v er s e  c u m ul ati v e  di stri b uti o n  ( R C D ) 
of s er u m N A b a n d I g G a nti b o d y tit er s 
at D a y s 0, 2 8, 1 8 0, a n d 3 6 5.  
O b s e r v ati o n al  E xt e n si o n  
S e c o n d a r y  S af et y  
O bj e cti v e  
E n d p oi nt s  
T o d e s cri b e t h e i n ci d e n c e of S A E s, A E SI, 
a n d M A A E s i n c o n s e nti n g I V X - A 1 2 a 
v a c ci n e e s  a n d  pl a c e b o  r e ci pi e nt s t hr o u g h 
a n  a d diti o n al  1 2  m o nt h s  ( Vi sit  D a y  7 3 0).  
S A E s,  A E SI s,  a n d  M A A E s  fr o m D a y  3 6 5 
t hr o u g h D a y 5 4 5 a n d u p t o D a y 7 3 0.  
C CI
C CI

I V X - A 1 2  
T ri al  P r o t o c ol  N o.  I C V X - 1 2 - 2 0 1 
V e r si o n 5. 0  
P a g e 3 9  of  1 0 3  
0 2  A p ril  2 0 2 4  
C O N F I D E N T I A L  
 
 
 
C CI

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6.0 
TRIAL DESIGN AND DESCRIPTION  
6.1 
Clinical Trial Design  
The IVX-A12 Phase 2a clinical trial is a randomized, observer-blind, 
placebo-controlled, dosage optimization, multi-center trial to evaluate the safety 
and immunogenicity two formulations of IVX-A12: an unadjuvanted dosage level of 
150 μg RSV/150 μg hMPV of IVX-A12 (IVA-A12a) and a dosage level of 150 μg 
RSV/150 μg hMPV adjuvanted with MF59 (IVX-A12d) compared to placebo (diluent) 
in adults 60 to 85 years of age. The dosage level and formulations (either aqueous 
[IVX-A12a] or adjuvanted with MF59 [IVX-A12d]) were determined based on the 
totality of the iVX-A12 nonclinical data and the interim safety and immunogenicity 
clinical data from the ongoing IVX-A12 Phase 1 clinical trial. A total of 300 μg 
IVX-A12 (75 μg RSV/225 μg hMPV) has been evaluated with MF59 in the IVX-A12 
Good Laboratory Practice (GLP) toxicology study and up to 225 μg of IVX-A12 
(75 μg RSV/150 μg hMPV) has been evaluated with MF59 in the Phase 1 clinical trial 
ICVX-12-101. 
This Phase 2a clinical trial has treatment groups: Two IVX-A12 groups and one 
placebo group. The total amount of VLP in the two IVX-A12 groups will not exceed 
300 µg of VLPs. 
• 
Group A: IVX-A12a, the unadjuvanted dosage level of 150 µg RSV/150 μg 
hMPV. 
• 
Group B: IVX-A12d, the dosage level of 150 μg RSV/150 μg hMPV 
adjuvanted with MF59. 
• 
Group C: placebo. 
Approximately 250 subjects were randomly allocated at a ratio of 2:2:1 to receive 
one of the two IVX-A12 formulations (IVX-A12a or IVX-A12d) placebo, respectively. 
Subjects were stratified by age group (60 to 69 years of age and 70 to 85 years of 
age). Dosing of the two IVX-A12 groups and placebo groups started in parallel. 
Age-stratified randomization balanced assignment between the two age groups. 
Subjects were considered randomized when they were assigned to a treatment 
group. The planned subject allocation to trial groups is provided in Table 1. 

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Table 1 
Clinical Trial Schema  
 
Group 
Dosage Level† 
Total (N=250)* 
A 
IVX-A12a (unadjuvanted 150 μg 
RSV/150 μg hMPV) 
100 
B 
IVX-A12d (150 μg RSV/150 μg hMPV 
adjuvanted with MF59) 
100 
C 
Placebo‡ 
50 
‡Placebo is aqueous diluent. 
*Note: The stratified randomization will ensure balanced dosage level group assignment between the 
two age groups (60 to 69 years of age and 70 to 85 years of age, respectively). 
The time and events schedules for the main trial and for the observational 
extension are presented in Section 2.1 and Section 2.2, respectively. The trial 
design schematic is shown in Section 2.3. 
Trial Procedures:  
Approximately 250 adult subjects (60 to 85 years of age) were enrolled. A subject 
was considered enrolled upon having signed the informed consent form (ICF). 
Subjects were randomly allocated to receive either IVX-A12 or placebo at a ratio 
2:2:1, resulting in approximately 100 subjects in each IVX-A12 group and 50 in the 
placebo group. In addition, subjects were stratified by age groups (60 to 69 years 
of age versus 70 to 85 years of age). 
Randomization occurred simultaneously into all three trial groups (IVX-A12a, 
IVX-A12d, and placebo). Initial vaccinations were performed in sentinel subjects 
and then expanded to the remaining subjects in each of the three trial groups. In 
total, there were 40 sentinel subjects. In each IVX-A12 group, 16 sentinel subjects 
received IVX-A12a (8 subjects from age stratum 60 to 69 years of age and 
8 subjects from age stratum 70 to 85 years of age); 16 sentinel subjects received 
IVX-A12d (8 subjects from age stratum 60 to 69 years of age and 8 subjects from 
age stratum 70 to 85 years of age). In the placebo group, 8 sentinel subjects 
received placebo (4 subjects from age stratum 60 to 69 years of age and 4 subjects 
from age stratum 70 to 85 years of age). Sentinels were closely monitored for a 
minimum of 48 hours. If no stopping rules were triggered, the remaining subjects 
in the IVX-A12 and placebo groups were enrolled. 
There are a total of seven scheduled clinic visits required for each subject (at 
screening, then Days 0, 7, 28, 90, 180, and 365), and five phone contacts (on 
Days 3, 14, 56, 135, and 270) for all subjects in the main part of the trial. 
IVX-A12a and placebo subjects consenting to the extension portion of the trial will 
have a phone contact at Day 545 for safety assessments and a clinic visit at 
Day 730 for safety assessments and blood sampling for immunogenicity. 

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The time and events schedules for the main study and for the extension are 
presented in Section 2.1 and Section 2.2, respectively. 
6.2 
Justification for Trial Design, Dosage Level, and Endpoints  
The interim safety and immunogenicity data from the Phase 1 clinical trial 
ICVX-12-101 entitled, “Phase 1 Randomized, Observer-blind, Placebo-controlled, 
Multi-center Trial to Evaluate the Safety and Immunogenicity of IVX-A12, a 
Respiratory Syncytial Virus and human Metapneumovirus Bivalent Combination 
Virus-like Particle Protein Subunit Vaccine, in Healthy Adults, 60 to 75 Years of Age” 
demonstrated that IVX-A12 was well tolerated and immunogenic up to 28 days post 
single-dose vaccination in adults 60 to 75 years of age. The trial evaluated five 
dosage levels/formulations (low dosage level, 75 µg RSV/75µg hMPV ± MF59; 
medium dosage level,75 µg RSV/150 µg hMPV ± MF59; and high dosage level, 
75 µg RSV/225 µg hMPV with no adjuvant) and met primary safety and 
immunogenicity endpoints. 
Based on the totality of nonclinical and clinical data on IVX-A12, including these 
interim Phase 1 safety and immunogenicity data, the following two IVX-A12 dosage 
level and formulations were selected for evaluation in the proposed Phase 2a 
clinical trial: (1) 150 µg RSV/150 µg hMPV unadjuvanted; and (2) 150 µg 
RSV/150µg hMPV adjuvanted with MF59. 
The intent of the selected formulations is to augment RSV-A and RSV-B immune 
responses, while preserving hMPV immune responses. In addition, IVX-121, the 
RSV component of the IVX-A12 RSV/hMPV bivalent vaccine candidate has been 
evaluated in a Phase 1/1b clinical trial in dosage levels up to 250 µg without 
adjuvant with no safety concerns noted up to 180 days post-vaccination. A total of 
300 µg IVX-A12 (75 µg RSV/225 µg hMPV formulation) has been evaluated with 
MF59 in the IVX-A12 GLP toxicology study, and up to 225 µg of IVX-A12 (75 µg 
RSV/150 µg hMPV formulation) was clinically evaluated with MF59 in the 
ICVX-12-101 Phase 1 trial. 
The sample size calculation is provided in Section 13.4. 
6.3 
Planned Duration of Subject’s Participation in the Trial  
The duration of subject participation in the main section of the trial will be 
approximately 12 months. At visit Day 365, after subjects are unblinded, IVX-A12a 
and placebo subjects (who were in the per protocol immunogenicity analysis set) 
will be invited to consent to longer term follow-up for approximately an additional 
12 months. 

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6.4 
Premature Termination or Suspension of Trial or Trial Site  
6.4.1 Criteria for Premature Termination or Suspension of the Trial  
The trial will be completed as planned unless one or more of the following criteria 
that require temporary suspension or early termination of the trial are satisfied. 
• 
New information or other evaluation regarding the safety or efficacy of the 
investigational vaccine that indicates a change in the known risk/benefit 
profile, such that the risk/benefit is no longer acceptable for subjects 
participating in the trial. 
• 
The SMC recommends that the trial should be suspended or terminated. 
• 
Significant deviation from GCP that compromises the ability to achieve the 
primary trial objectives or compromises subject safety. 
• 
The sponsor decides to terminate or suspend the trial. 
6.4.2 Criteria for Premature Termination or Suspension of Trial Sites  
A trial site may be terminated prematurely or suspended if the site (including the 
investigator) is found to be in significant deviation from GCP, protocol, or 
contractual agreement, is unable to ensure adequate performance of the trial, or as 
otherwise permitted by the contractual agreement. 
6.4.3 Procedures for Premature Termination or Suspension of the Trial or 
the Participation of Trial Sites  
In the event that the sponsor, an Independent Ethics Committee (IEC)/Institutional 
Review Board (IRB) or regulatory authority elects to terminate or suspend the trial 
or the participation of a trial site, a trial-specific procedure for early termination or 
suspension will be provided by the sponsor; the procedure will be followed by 
applicable trial sites during the course of termination or trial suspension. 

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7.0 
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS  
All eligibility criteria, including test results, need to be confirmed prior to 
randomization. 
7.1 
Inclusion Criteria  
Subject eligibility is determined according to the following criteria: 
1) 
Male or female subjects, 60 to 85 years of age, who must be in stable health 
based on medical history, vital signs, physical examination, and laboratory 
evaluation prior to vaccination, in the investigator’s clinical judgment; 
2) 
Subjects may have ongoing chronic conditions (comorbidities such as 
hypertension, congestive heart failure, chronic obstructive pulmonary disease, 
type 2 diabetes mellitus, hyperlipoproteinemia, or hypothyroidism) who are, in 
the investigator’s opinion, medically compensated and without recent 
exacerbation (for example, no emergency room [ER] visits and no change to 
medical treatments or medications to better control the condition) within the 
prior 3 months; 
3) 
Subjects able to voluntarily give written informed consent and can comply with 
trial procedures including follow-up for approximately 12 months after 
vaccination; 
4) 
Body mass index 17 to <40 kg/m2 at screening; 
5) 
Before randomization, female subjects must be unable to conceive (e.g., 
menopausal, i.e., 12 consecutive months without menstruation, hysterectomy, 
oophorectomy, etc.) and not intending to conceive by any method; 
6) 
Subject must agree not to donate blood from the time of vaccination through 
3 months after vaccination; 
7) 
Subject must be willing to provide verifiable identification and have the means 
to be contacted and to contact the investigator or the site’s staff during the 
entire clinical trial. 
7.2 
Exclusion Criteria  
Any subject who meets any of the following criteria will not qualify for entry into the 
trial: 
1) 
Subjects with moderate or severe liver disease, metastatic solid tumor, and 
acquired immunodeficiency syndrome (AIDS) are to be excluded. In addition, 
subjects with underlying significant illness or condition(s) or ongoing treatment 
that, in the opinion of the investigator, could (i) interfere with the conduct of 
the trial, (ii) pose an unacceptable risk to the subject in this trial, (iii) interfere 
with the subject’s ability to comply with the trial procedures or abide by the 

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trial restrictions, (iv) interfere with the ability to interpret safety data, or (v) 
prevent completion of the trial are to be excluded; 
2) 
Older adults who meet frail elderly criteria (older persons with medical, 
nutritional, cognitive, emotional, or activity impairments, as defined by the 
Dalhousie Clinical Frailty Score ≥4 [37] See Appendix C; 
3) 
Prior receipt of any licensed or investigational RSV or hMPV vaccine within the 
past 12 months; 
4) 
Prior receipt of another investigational medicinal product ([IMP]; trial drug, 
biologic, or device) not authorized for use in the USA and European Union 
within the past 3 months; 
5) 
Laboratory-confirmed RSV or hMPV infection within the 12 months prior to 
enrollment; 
6) 
Currently enrolled or plan to participate in another clinical trial with an 
investigational agent (including licensed or unlicensed vaccine, drug, biologic, 
device, blood product, or medication) to be received during the trial period; 
7) 
History of malignancy within 5 years before screening not in the following 
categories:(i) subjects with squamous and basal cell carcinomas of the skin 
and carcinoma in situ of the cervix may be enrolled at the discretion of the 
investigator, (ii) subjects with a history of malignancy within 5 years before 
screening, with minimal risk of recurrence per investigator’s judgment, can be 
enrolled; 
8) 
Per medical history, subjects with chronic active hepatitis B or hepatitis C 
infection, human immunodeficiency viruses type 1 or type 2 infection, acute 
polyneuropathy (such as Guillain-Barré syndrome), or chronic idiopathic 
demyelinating polyneuropathy; subjects whose hepatitis C antibody test is 
positive but whose viral loads are negative may be enrolled; 
9) 
Acute illness, with or without fever at the time of planned vaccination; 
10) History of hypersensitivity or serious adverse reactions to vaccines, such as 
anaphylaxis or angioedema, or any known allergies to any component of the 
IVX-121 and/or IVX-241 vaccine, or hypersensitivity to latex; 
11) Abnormal function of the immune system resulting from clinical conditions 
including chronic administration of systemic corticosteroids 
(oral/intravenous/IM at a daily dose equivalent of >20 mg prednisone in a 
period of more than 14 days), or administration of immunosuppressive 
chemotherapy, biologics, or radiotherapy within the past 3 months prior to 
planned vaccination; 

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12) Subjects who have received treatment with immunoglobulins or other 
biologics, such as immunosuppressive therapies expected to modify immune 
responses to vaccination (including monoclonal antibodies [MAbs] for chronic 
underlying conditions) within the past 3 months prior to planned vaccination; 
13) Trial Personnel as an immediate family or household member 
14) For licensed vaccines: 
a) Receipt of licensed inactivated vaccines (including seasonal influenza vaccine) 
within 14 days prior to trial vaccine administration on Day 0, or licensed 
replicating vaccines such as RNA or live-attenuated virus vaccines within 
30 days prior to Day 0. 
b) Receipt of licensed vaccines is permitted after completion of the Day 28 visit. 
c) Receipt of any licensed COVID-19 vaccines is permitted if dosing regimen 
completed within 21 days prior to Day 0 or after completion of the Day 28 
visit. 
There may be instances when individuals meet all eligibility criteria except one that 
relates to transient clinical circumstances (e.g., fever or recent use of excluded 
medication[s] or vaccine[s]). Under these circumstances, eligibility for enrollment 
may be considered if the appropriate window for delay has passed, 
inclusion/exclusion criteria have been rechecked, and if the subject is confirmed to 
be eligible (Section 7.4). 
7.3 
Trial Observational Extension  
After approximately 12 months, trial subjects will be unblinded at their Day 365 
visit. IVX-A12a and placebo subjects, whose data has not been excluded from 
immunogenicity analyses in the main part of the trial and who consent to be 
followed for safety and immunogenicity, will continue in the trial for an additional 
12 months. 
7.4 
Criteria for Delay of Investigational Medicinal Product Administration 
and/or Blood Sampling  
After enrollment, subjects may encounter clinical circumstances that warrant a 
delay in the administration of IMP. These situations are listed below: 
1) Subjects with a clinically significant active infection (as assessed by the 
investigator) or body temperature >38.0°C (>100.4°F), within 3 days of 
planned IMP administration. 
2) Subjects who have used antipyretics and/or analgesic medications within 
24 hours prior to vaccination. The reason for their use (prophylaxis versus 

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treatment) must be documented. IMP administration should be delayed to allow 
for a full 24 hours to have passed between having used antipyretics and/or 
analgesic medications and IMP administration. 
In the event that a subject meets a criterion for delay of IMP administration, the 
subject may receive the IMP once the window for delay has passed as long as the 
subject is otherwise eligible for trial participation. 
7.5 
Criteria for Early Termination of a Subject’s Trial Participation  
Under some circumstances, a subject’s trial participation may be terminated early. 
This means that no further trial procedures (including data collection) will be 
performed on that subject beyond the specific date of early termination of trial 
participation. The primary reason for early termination of the subject’s trial 
participation should be documented using the following categories: 
1. Adverse event: The subject has experienced an AE/AR (irrespective of being 
related/unrelated to the IMP or trial-related procedures) that requires early 
termination because continued participation imposes an unacceptable risk to 
the subject’s health and/or the subject is unwilling to continue participation 
because of the AE/AR. The subject will be encouraged to remain in the trial to 
be followed for safety observations; with no additional trial procedures 
conducted. If the subject is unwilling to continue because of the AE/AR, the 
primary reason for early termination of trial participation in this case will be 
‘withdrawal due to AE/AR’ and not ‘withdrawal of consent’, see below. 
2. Lost to follow-up: The subject did not return to the clinic and at least 
three attempts to contact the subject were unsuccessful. 
3. Withdrawal of consent: The subject wishes to withdraw from the trial. The 
primary reason for early termination will be ‘withdrawal of consent” if the 
subject withdraws from participation due to a non-medical reason (i.e., reason 
other than AE/AR). While the subject has no obligation to provide a reason for 
withdrawing consent, attempts should be made to determine the underlying 
reason for the withdrawal and, where possible, the primary underlying reason 
should be documented. 
4. Premature trial termination by the sponsor, a regulatory agency, the 
IEC/IRB, or any other authority: If the clinical trial is prematurely 
terminated by the sponsor, the investigator is to promptly inform the trial 
subjects and local IEC/IRB and should assure appropriate follow-up for the 
subjects. The primary reason for early termination in this case will be ‘trial 
termination’. 
5. Subject’s death during trial participation. 

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8.0 
CLINICAL TRIAL MATERIAL MANAGEMENT  
This section contains information regarding the IMP, placebo, and materials 
provided directly by the sponsor, and/or sourced by other means, that are required 
by the trial protocol, including important sections describing the management of 
clinical trial materials (CTM). 
Details regarding the dosage form description and strengths, or composition for the 
extemporaneous preparation of the IMP can be found in the pharmacy manual. 
8.1 
Investigational Medicinal Products  
8.1.1 IVX-A12  
The two investigational IVX-A12 formulations for testing are composed of a 
constant IVX-121 RSV VLP dosage level (150 µg) with a constant IVX-241 hMPV 
VLP dosage level (150 µg). 
The two formulations of IVX-A12 are: 
• 
An unadjuvanted dosage level of 150 µg RSV/150 µg hMPV of IVX-A12 
(IVX-A12a); and 
• 
A dosage level of 150 µg RSV/150 µg hMPV of IVX-A12 adjuvanted with 
MF59 (IVX-A12d) 
Both formulations will be compared to placebo (diluent). 
The final investigational IVX-A12 drug product is administered either as an aqueous 
vaccine (IVX-A12a) or with MF59 to be mixed 1:1 in the clinic (IVX-A12d). The 
amount of MF59 (squalene) per dose will not exceed 9.75 mg. Specific instructions 
for preparation of vaccine are provided in the pharmacy manual. 
The intended volume for administration of IVX-A12 is 0.5 mL for IM administration. 
8.1.2 Placebo  
Sterile aqueous diluent, delivered as a 0.5 mL dose. The placebo does not contain 
preservatives. 
8.1.3 Labeling  
A clinical label will be affixed to IMP containers in accordance with local regulatory 
requirements. 
8.1.4 Inventory and Storage  
Environmental storage conditions for sponsor-supplied IMPs and CTM used to 
administer the IMP (e.g., temperature, humidity, away from sunlight or heat) are 
described in the trial pharmacy manual. IVX-A12 formulations and placebo must be 

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stored at 2-8°C, and never frozen. Sponsor-supplied IMP should be stored under 
the specified conditions and remain in the original container until dispensed. 
All CTM must be kept in an appropriate, limited-access, secure place until it is used 
or returned to the sponsor or designee for destruction. Receipt and dispensing of 
IMP must be recorded by authorized personnel at the trial site. A temperature log of 
the vaccine storage area must be maintained. Temperature excursions must be 
reported to the sponsor as soon as possible and use of these vaccines requires 
sponsor approval. 
Additional details for inventory, storage and handling can be found in the pharmacy 
manual. 
8.1.5 Dosage Level and Dosing Regimen  
Subjects received a single IM dose of IMP Table 2 on Day 0. The criteria for dosage 
level escalation versus trial groups are described in Section 6.1 and the stopping 
rules are provided in Section 11.1. 
Table 2 describes the doses that will be provided to each group. 
Table 2 
Sponsor-supplied IMP  
 
Trial Group 
Formulation 
Route 
IVX-A12 
VLP (µg) 
MF59 
(mg squalene) 
RSV 
hMPV 
A 
IVX-A12a 
150 
150 
0 
IM 
B 
IVX-A12d 
150 
150 
9.75 
IM 
C 
Placebo 
- 
- 
0 
IM 
Abbreviations: hMPV, human metapneumovirus; IM, intramuscular; RSV, respiratory 
syncytial virus; VLP, virus-like particle. 
8.2 
Investigational Medicinal Product Assignment and Dispensing 
Procedures  
Subject randomization was conducted using an interactive web randomization 
system (IWRS). The system ensures proper distribution of subjects across trial 
groups at each stage. 
Preparation and administration of the IMP and the placebo was performed by 
unblinded trial personnel/pharmacists/administrators. These people, identified prior 
to trial dosing on Day 0, do not perform any trial assessments for the duration of 
the trial. 
If sponsor-supplied IMP is lost or damaged, the site can request a replacement. 
Expired IMP must not be administered. 

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8.2.1 Precautions to be Observed When Administering the Investigational 
Medicinal Product  
Prior to IMP administration, a subject must be determined to be eligible to receive 
IMP (Sections 7.1 and 7.2), and it must be clinically appropriate in the judgment of 
the investigator to administer the IMP. IVX-A12 or placebo are injected by the IM 
route into the deltoid of the non-dominant arm. Standard immunization practices 
are to be observed and care should be taken when administering an IMP 
intramuscularly. As with all injectable vaccines, trained medical personnel and 
appropriate medical treatment should be readily available in case of anaphylactic 
reactions following vaccination. 
8.3 
Randomization Code Creation and Storage  
Randomization as conducted using an IWRS. The system ensures proper 
distribution of subjects across group assignments; treatment assignments known 
only to the responsible unblinded trial personnel/vaccine administrators at the 
study center. Subjects and the main study team and clinical staff will remain 
blinded for the duration of the study unless emergency unblinding is necessary. 
Randomization information is stored in a secured area, accessible only by 
authorized personnel. 
8.4 
Investigational Medicinal Product Blind Maintenance  
This trial is an observer-blind trial. Assignment to IMP is known only to the 
responsible unblinded trial personnel/vaccine administrators at the trial sites. The 
subjects, data collectors (e.g., investigator) and data evaluators are blinded to the 
material administered. Randomization and IMP administration must be done by 
designated unblinded site staff who must not be involved with data collection of any 
sort including safety evaluation of the subject after administration of IMP. 
All care must be taken to ensure that the unblinded reports and documents are 
shared only with unblinded personnel and properly stored in a secured area, 
accessible only by authorized personnel. 
8.5 
Unblinding Procedure  
The IMP blind shall not be broken by the investigator unless information concerning 
the IMP is necessary for the medical treatment of a subject, or if a subject requests 
it. In the event of a medical emergency, if possible, the medical monitor should be 
contacted before the IMP blind is broken to discuss the need for unblinding. 
For unblinding a subject, the IMP blind can be obtained by the investigator, by 
accessing the IWRS. 

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The sponsor’s pharmacovigilance department must be notified as soon as possible if 
the IMP blind is broken by the investigator and the completed SAE form, if 
applicable, must be sent within 24 hours. The date, time, and reason the blind is 
broken must be recorded in the source document. 
If any subject is unblinded, the subject should continue to be monitored for safety 
follow-up. 
All subjects will be unblinded at their Day 365 visit. 
8.6 
Accountability and Destruction of Sponsor-supplied Investigational 
Medicinal Products, and Other Clinical Trial Materials  
The investigator or designee must ensure that the sponsor-supplied IMP are used in 
accordance with the approved protocol and is administered only to subjects enrolled 
in the trial. To document appropriate use of sponsor-supplied IMP, the investigator 
must maintain records of all sponsor-supplied IMP delivery to the site, site 
inventory, administration and use by each subject, and destruction or return to the 
sponsor or designee. 
The investigator must maintain 100% accountability for all sponsor-supplied IMPs 
and other CTM (including ancillary materials, as applicable) received and 
administered during their entire participation in the trial. Inventory, tracking and 
accountability forms will be maintained in the pharmacy files. 
Prior to site closure or at appropriate intervals throughout the trial, before any IMP, 
or CTM are destroyed or returned to the sponsor or designee for destruction, a 
representative from the sponsor will perform CTM accountability and reconciliation. 

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9.0 
TRIAL PLAN  
9.1 
Trial Procedures  
The following sections describe the trial procedures and data to be collected. The 
time and events schedules for the main trial and for the extension are located in 
Section 2.1 and Section 2.2, respectively. All procedures must be performed by 
qualified and trained staff. 
9.1.1 Informed Consent and Eligibility  
The requirements of the ICF are described in Section 15.2. 
Informed consent must be obtained before any protocol-directed procedures are 
performed. 
A unique subject number is assigned to each subject after informed consent is 
obtained. If all eligibility criteria are fulfilled and the subject is randomized, this 
subject number is used throughout the trial. Subject numbers assigned to subjects 
who are not randomized should not be reused. 
IVX-A12a and placebo recipients must sign a second consent if they agree to 
participate in the trial extension period. 
9.1.2 Demographics, Medical History and Medication History  
Demographic information to be obtained will include age/date of birth (if 
applicable), sex, race (and ethnicity) as described by the subject. 
Medical history is also collected, including but not limited to any medical history 
that may be relevant to subject eligibility for trial participation such as prior 
vaccinations, medication history, concomitant medications, and previous and 
ongoing illnesses and/or injuries. Relevant medical history can also include any 
medical history that contributes to the understanding of an AE that occurs during 
trial participation if it represents an exacerbation of an underlying 
disease/pre-existing problem. Information about the participant’s household 
makeup and interactions with people of different age groups is collected. History of 
the use of alcohol, tobacco, and marijuana will also be collected. 
Medical history (including corresponding medication) to be obtained includes any 
significant conditions or diseases that have disappeared or resolved at or prior to 
signing of the ICF. 
Adverse medical occurrences emerging during the time between signing of the ICF 
and the administration of IMP are recorded in the AE electronic case report form 
(eCRF). If such an adverse medical occurrence is assessed as related to a screening 
procedure this should be recorded as an AE related to trial procedure in the eCRF. 

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All medications, vaccines and blood products taken or received by the subjects are 
collected as prior and concomitant medications (Section 7.2): 
a) Medications: 1 month prior to screening. 
b) Vaccines: 1 year prior to screening for any investigational, for any 
non-registered vaccines and for any licensed vaccines. 
c) Blood products: 3 months prior to screening. 
The use of antipyretics and/or analgesic medications within 24 hours prior to 
vaccination must be identified and the reason for their use (prophylaxis versus 
treatment*) must be documented. Administration of the IMP should be delayed by 
24 hours. 
*Medications taken for prophylaxis are those intended to prevent the onset of AEs 
following vaccination. Medications taken for treatment are intended to reduce or 
eliminate the presence of symptoms that are present. 
Assess and record concomitant therapy (prescription medications ONLY) and 
vaccine history as described above in the source documents. 
See Section 9.2.8 for recording of medications during the trial extension, i.e., 
12-month observational follow-up. 
9.1.3 Documentation of Trial Entry/Randomization  
Only subjects who have a signed ICF and meet all of the inclusion criteria and none 
of the exclusion criteria are eligible for randomization/entry into the active phase. 
The randomization specification was approved by the sponsor’s trial statistician, or 
designee. 
If the subject is ineligible for randomization, the investigator should record the 
primary reason for failure on the subject screening and enrollment log using the 
following categories: 
• 
Screen failure (did not meet one or more inclusion criteria or did meet one or 
more exclusion criteria); 
• 
Withdrawal by subject; 
• 
Enrollment target reached; 
• 
Trial terminated by the sponsor. 
Subject numbers assigned to subjects who fail screening cannot be reused. 
In the event of major protocol violations/deviations (such as failure to collect Day 0 
samples for serology or safety analyses) occurring during the active phase of 
entry/randomization leading to dosing of eligible subjects, replacement of an 
approximate equal number of subjects is allowed. 

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9.1.4 Physical Examination  
Physical examinations must be performed by a qualified health professional in 
accordance with local regulations and as listed within the site responsibility 
delegation log. A complete physical exam is performed at screening according to 
the investigator’s standard practice. Additional physical examinations may be 
performed if indicated by review of the subject’s medical history. The findings 
should be documented in the subject’s source document. 
Symptom-directed physical examination may be performed at subsequent visits if 
deemed necessary. 
9.1.5 Vital Signs  
A subject will have their vital signs measured at the screening visit, prior to dosing, 
and at all regularly scheduled clinic visits, including body temperature, blood 
pressure, heart rate, respiratory rate, oxygen level (SpO2), weight (at screening 
only) and height (at screening only). Follow standard of care for trial population and 
operational feasibility. SpO2 will not be performed during the trial extension unless 
clinically indicated. 
9.1.6 Immunogenicity Assessments  
Blood sampling for immunogenicity is taken at Days 0, 28, 180, and 365, and for 
the trial extension population subset at Day 770. All subjects are followed for 
persistence of antibody responses through the entire duration of the clinical trial 
(approximately 12 months), and then antibody responses will be checked in the 
trial extension subset at Day 730. All samples must be collected in accordance with 
acceptable laboratory procedures. 
In the event of local or national health related closures and limited ability for travel 
(e.g., as a consequence of SARS-CoV-2 circulation), the clinic may default to their 
institution guidelines to continue follow-up assessments with subjects as necessary. 
The assays are described in Table 3. Refer to Table 5 for maximum volume of blood 
collected at any single visit. 

I V X - A 1 2  
T ri al  P r o t o c ol  N o.  I C V X - 1 2 - 2 0 1 
V e r si o n 5. 0  
P a g e 5 5  of  1 0 3  
0 2  A p ril  2 0 2 4  
C O N F I D E N T I A L  
 
 
T a bl e  3  
P h a s e  2 a  C o r e  Cli ni c al  Bi o a n al y ti c al  A s s a y s   
 
A s s a y  
P u r p o s e  
C o m m e nt  
R S V  n e utr ali z ati o n 
( R S V / A, R S V / B )  
1 ° a n d 2 ° 
i m m u n o g e ni cit y 
e n d p oi nt s  
N e utr ali z ati o n tit er s d efi n e m a g nit u d e of 
f u n cti o n al i m m u n e r e s p o n s e t o R S V / A  a n d 
R S V/ B  
h M P V  n e utr ali z ati o n 
( h M P V / A, h M P V / B )  
1 ° a n d 2 ° 
i m m u n o g e ni cit y 
e n d p oi nt s  
N e utr ali z ati o n tit er s d efi n e m a g nit u d e of 
f u n cti o n al i m m u n e r e s p o n s e t o h M P V / A  a n d 
h M P V/ B  
R S V  pr e  F  pr ot ei n 
bi n di n g E LI S A  
1 ° a n d 2 ° 
i m m u n o g e ni cit y 
e n d p oi nt s  
T ot al I g G r e s p o n s e f or u s e i n a n al y si s of 
q u alit y  m etri c  a s  d efi n e d  b y  r el ati v e ri s e i n 
‘ bi n di n g t o n e utr ali zi n g’ r ati o 
h M P V  pr e  F  pr ot ei n 
bi n di n g E LI S A  
1 ° a n d 2 ° 
i m m u n o g e ni cit y 
e n d p oi nt s  
T ot al I g G r e s p o n s e f or u s e i n a n al y si s of 
q u alit y  m etri c  a s  d efi n e d  b y  r el ati v e ri s e i n 
‘ bi n di n g t o n e utr ali zi n g’ r ati o 
A nti - V L P  c or e  I g G 
E LI S A  ( V L P  C or e)  
E x pl or at or y 
e n d p oi nt  
A n al y si s of r e s p o n s e t o V L P c or e ( wit h o ut 
D S - C a v 1  a nti g e n )  aft er  v a c ci n ati o n  t o i nf or m 
pl atf or m t e c h n ol o g y, i nt er pr et ati o n of s af et y 
a n d i m m u n e r e s p o n s e s t o D S- C a v 1 a nti g e n.  
Bi o Fir e  R e s pir at or y 
P a n el 2. 1 ( R P. 1 )  
2 °  s af et y  e n d p oi nt 
a n d e x pl or at or y 
effi c a c y e n d p oi nt  
Di a g n o sti c a s s a y t o d et e ct a n d i d e ntif y 
n u cl ei c  a ci d t ar g et s  i n r e s pir at or y s p e ci m e n s 
fr o m vir ol o gi c al a g e nt s t h at c a u s e t h e R S V 
a n d / or  h M P V  r e s pir at or y  i nf e cti o n ( a n d  ot h er 
a g e nt s).  
A b br e vi ati o n s : E LI S A, e n z y m e - li n k e d i m m u n e a b s or b e nt a s s a y; I g G, i m m u n o gl o b uli n G; 
h M P V,  h u m a n  m et a p n e u m o vir u s ;  R S V,  r e s pir at or y  s y n c yti al  vir u s ;  V L P,  vir u s - li k e p arti cl e.  
S er ol o gi c al  s a m pl e s  will  b e  a s s e s s e d  f or pri m ar y  or  s e c o n d ar y  i m m u n o g e ni cit y 
e n d p oi nt s u si n g t h e f oll o wi n g a s s a y s :  
o  R S V / A – s p e cifi c  a n d  h M P V / A - s p e cifi c  N A b  a s s a y;  
o  R S V / B – s p e cifi c  a n d  h M P V / B - s p e cifi c  N A b  a s s a y;  
o  A nti - R S V  a n d  a nti - h M P V  Pr e  F  pr ot ei n - s p e cifi c  I g G E LI S A s.  
 
 
 
 
 
 
 
T h e a nti - R S V Pr e F pr ot ei n I g G E LI S A a n d a nti - h M P V Pr e F pr ot ei n I g G E LI S A h a v e 
b e e n  q u alifi e d  f or t h e q u a ntifi c ati o n of  bi n di n g  I g G a nti b o di e s  t o t h e Pr e  F  pr ot ei n  i n 
h u m a n s er u m s a m pl e s.  
C CI

I V X - A 1 2  
T ri al  P r o t o c ol  N o.  I C V X - 1 2 - 2 0 1 
V e r si o n 5. 0  
P a g e 5 6  of  1 0 3  
0 2  A p ril  2 0 2 4  
C O N F I D E N T I A L  
 
 
S er ol o gi c al  s a m pl e s  will  b e  a s s e s s e d  f or e x pl or at or y  i m m u n o g e ni cit y e n d p oi nt s 
u si n g t h e f oll o wi n g a s s a y s :  
•  
A nti - V L P  c or e  I g G E LI S A.  
A n  a nti - V L P  c or e  E LI S A  w a s  q u alifi e d  f or t h e q u a ntifi c ati o n  of  bi n di n g  I g G a nti b o di e s 
t o V L P c or e i n h u m a n s er u m s a m pl e s. 
C CI

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9.1.8 Safety Assessments  
Safety assessments: All solicited local (injection site) reactions and systemic ARs 
are collected for all subjects for 7 consecutive days, starting from the day of the 
single-dose administration (Day 0) through Day 6 (7 days total); unsolicited AEs 
through Day 28; and safety blood samples (clinical laboratory evaluation at 
screening, Day 0/baseline, Day 7, and Day 28). 
AEs, SAEs, AESIs (Section 10.4.4.1 and Appendix D), MAAEs, AEs leading to trial 
withdrawal, and CESI are captured from the time of randomization to Day 365, 
approximately 12 months after vaccination. After the Day 365 visit, SAEs, AESIs, 
and MAAEs will be collected up to the Day 730 visit. Clinic staff (a trained 
healthcare provider) will contact the subject by phone call or using a digital 
application (e.g., SMS text) to facilitate the collection of relevant safety information 
such as concomitant medication use and occurrence of AEs/SAEs. Up to Visit Day 
365, all subjects will complete a respiratory symptom surveillance tool 
approximately twice a week (i.e., approximately twice within 7-day intervals 
starting on Day 0 post-vaccination) to be monitored for the trial-defined CESI of 
mild, moderate, or severe LRTI caused by RSV or hMPV, using the established case 
definition and algorithm for evaluation of ARI and using NP swabs for the detection 
of RSV, hMPV, and other respiratory viruses. Subjects are instructed to return to 
the clinic for assessment within 3-7 days of onset of ARI (ideally within 3 days) to 
maximize detection of virus. 
After subjects are unblinded to their trial group assignment at Day 365, consenting 
IVX-A12a and placebo recipients will be contacted by clinic staff by phone call or 
with a digital application (e.g., SMS text) to facilitate the collection of MAAEs, 
AESIs, and SAEs, at Day 545; MAAEs, AESIs and SAEs will also be collected at the 
clinic visit on Day 730. 
Refer to Section 10.1 for safety definitions. Details on collection and reporting of 
AEs are in Section 10.5. 
The solicited ARs included in the safety assessments are listed in Table 8. 
9.1.9 Clinical Safety Laboratory Variables  
All samples will be collected in accordance with acceptable laboratory procedures. 
The maximum volume of blood collected for clinical safety evaluation is 
approximately 10 mL and will be collected by the trial staff or designee and 
laboratory values will be determined at the central or local laboratory. Samples 
must be collected, prepared, and arranged for transport according to the 
instructions provided by the local laboratory. 
Table 4 lists the clinical safety laboratory tests that will be performed. 

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Table 4 
Clinical Safety Laboratory Tests  
 
Hematology 
Blood Chemistry 
Urine† 
Other Safety 
Variables 
Complete blood 
count: 
• 
Red blood cells 
(RBC) 
• 
Hemoglobin 
• 
Hematocrit 
• 
White blood 
cells (WBC) 
with differential 
• 
Platelet count 
• 
Alanine 
aminotransferase 
(ALT) 
• 
Aspartate 
aminnotransferase 
(AST) 
• 
Creatinine 
• 
Blood urea 
nitrogen (BUN) 
• 
Total bilirubin 
• 
pH 
• 
Glucose 
• 
Protein 
• 
Ketones 
• 
Urobilinogen 
• 
Specific 
gravity 
• 
RBC / 
Erythrocytes* 
• 
WBCs / 
Leukocytes* 
• 
Human 
immunodeficiency 
virus (screening) 
• 
Hepatitis B virus 
(screening) 
• 
Hepatitis C virus 
serology 
(screening) 
†Urine dipstick test will be performed at screening. An abnormal result for glucose, ketones, pH, 
protein, specific gravity, and/or urobilinogen will trigger urine microscopy. 
*Urine microscopy, if required. 
 
9.1.10 
Processing, Labeling and Storage of Biological Samples  
All biological samples (e.g., blood, urine, etc.) will be processed, labeled, and 
stored according to the laboratory manual or other appropriate guideline provided 
to the site. 
Subjects who complete all scheduled trial visits for the main portion of the trial will 
provide approximately 80 mL of blood in total for clinical safety and immunology 
(Table 5) by the end of the trial. Subjects in the extension subset population will 
provide an additional 10 mL of blood for immunology, for a total of approximately 
90 mL of blood by the end of the trial. See Sections 9.1.6 and 9.1.9 for additional 
details. 
Table 5 
Blood Volumes  
 
Day 
Clinical Safety 
Laboratory 
Immunogenicity 
Assessments 
Total 
Screening 
10 mL 
- 
10 mL 
Day 0 
10 mL 
10 mL 
20 mL 
Day 7 
10 mL 
- 
10 mL 
Day 28 
10 mL 
10 mL 
20 mL 
Day 180 
- 
10 mL 
10 mL 

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Day 365 
- 
10 mL 
10 mL 
Day 730* 
10 mL 
10mL 
Total for Trial 
40 mL 
40- 50* mL 
80- 90 *mL 
*Day 730, extra 10 mL of blood only for subjects in the trial extension period. 
9.1.11 
Contraception Procedures  
Male subjects will be provided with information on acceptable methods of 
contraception as part of the subject informed consent process. Male subjects of 
childbearing potential will be required to use condoms from vaccination until 
3 months afterwards, and to refrain from sperm donation during the same period. 
Male subjects not of child-bearing potential are permanently sterile by bilateral 
orchiectomy or vasectomy. 
9.2 
Time and Events Schedule  
The time and events schedules for all trial-related procedures for all evaluations for 
the main study and for the extension are shown in Section 2.1 and Section 2.2, 
respectively. Assessments should be completed at the designated time points. 
Specific information related to vaccination and post-vaccination procedures are 
outlined below. 
9.2.1 Screening (Days -28 to -1)  
• 
Informed consent (Section 9.1.1); 
• 
Eligibility criteria (Section 7.1 and Section 7.2); 
• 
Demographics (Section 9.1.2); 
• 
Medical history (Section 9.1.2); 
• 
Medication history (Section 9.1.2); 
• 
Urine sample (Section 9.1.9); 
• 
Physical examination (Section 9.1.4); 
• 
Vital signs (Section 9.1.5); 
• 
Safety blood sampling (Section 9.1.9); 
• 
Concomitant medications (Section 9.1.2). 
9.2.2 Prevaccination Procedures (Day 0)  
• 
Physical examination (Section 9.1.4); 
• 
Vital signs (Section 9.1.5); 

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• 
Safety blood sampling (Section 9.1.9); 
• 
Serology blood draw for SNA (live virus neutralization assay), ELISA 
(Section 9.1.6); 
• 
Confirm eligibility (Section 9.1.1); 
• 
Randomization (Day 0 only; Section 9.1.3). 
9.2.3 Vaccination Procedures (Day 0)  
After confirming eligibility (Day 0) and randomizing the subject (Day 0), perform 
IMP administration according to the procedures described in Section 8.2. 
9.2.4 Post-vaccination Procedures (Day 0)  
The following post-vaccination procedures will be performed on Day 0: 
After vaccination, the subject will be observed in the clinic for at least 60 minutes 
including observation for unsolicited AEs, solicited local (injection site) reactions, 
and body temperature measurement. Information should be recorded in the eCRF. 
The investigator or delegate will take the opportunity to remind the subject how to 
measure solicited local (injection site) reactions and body temperature as part of 
this observation period. All safety data will be collected in the subject’s source 
documents. 
Diary distribution and training: 
• 
Training of the subject on how to measure solicited local (injection site) 
reactions and body temperature, how to complete the diary and how often to 
complete the diary. Training should be directed at the individual(s) who will 
perform the measurements of solicited local (injection site) reactions and those 
who will enter the information into the diary. This individual may or may not be 
the subject, but if a person other than the subject enters information into the 
diary, this person’s identity must be documented in the source and this person 
must receive training on the diary. Training of the subject on how to measure an 
injection site reaction and how to take their temperature, as well as how to 
record the information in the diary, should be performed while the subject is 
under observation after vaccination. 
Diary instructions must include the following: 
• 
The individual(s) who will enter the information into the diary must understand 
that timely completion of the diary on a daily basis is a critical component of 
trial participation. 

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Please note: 
There are two types of diaries utilized for the trial: 
• 
Diary used for the collection of solicited local (injection site) reactions and 
systemic ARs (including body temperature measurements). The diary will be the 
only source document allowed for remote collection of solicited ARs. 
• 
Any new unsolicited safety information would be recorded in the subject source 
document as a verbally reported event and therefore captured as an AE and 
recorded in the AE eCRF. 
• 
Starting on the day of vaccination, the subject will check for specific types of 
events at the injection site, any specific generalized symptoms (solicited 
systemic ARs), body temperature (any method), any other symptoms or change 
in the subject’s health status, and any medications taken (excluding vitamins 
and minerals). These solicited ARs and body temperature will be recorded in the 
diary. Assessments should preferably take place in the evening. 
• 
Temperature measurement is to be performed using the thermometer provided 
by the site. If the subject feels unusually hot or cold during the day, the subject 
should check their temperature. If the subject has fever, the highest body 
temperature observed that day should be recorded in the diary. 
• 
The measurements of solicited local (injection site) reactions are to be 
performed using the ruler provided by the site. 
• 
The collection on the diary of body temperature, solicited local (injection site) 
reactions, and solicited systemic ARs will start from the day of the single-dose 
administration (Day 0) through Day 6 (7 days total). 
• 
Subjects will be prompted by the diary to contact the site to report any 
unsolicited AEs and medications throughout the trial: 
o For 28 days following vaccine administration, any new unsolicited safety 
information would be recorded in the subject source document as a verbally 
reported event and therefore captured as an AE and recorded in the AE 
eCRF. 
o Throughout the main portion of the trial (through Day 365), any events 
reported in the diary will be evaluated to determine whether MAAE, SAE, 
AESIs, or CESI criteria are met. If these criteria are met, the information 
would be captured in the subject source document, recorded in the applicable 
eCRF, and reported to the sponsor’s (or sponsor’s designee’s) 
pharmacovigilance department as applicable. 

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• 
Diary for Respiratory Surveillance Survey (RSS) for the collection symptoms that 
may meet the definition of an ARI. See Section 10.1.3. 
o Starting on the day of vaccination and through visit Day 365, the subject will 
be prompted twice a week to record the incidence of any symptoms meeting 
ARI criteria. 
The site should schedule the next trial activity. 
The subject will be reminded to complete the diary daily and to contact the site if 
there are any questions and to contact the site immediately (or as soon as the 
subject is medically stable) if the subject has a medical condition that leads to a 
hospitalization or an ER visit. All contact details will be provided to the subject. 
Refer to Section 10.4 for the reporting of AEs, SAEs, AESIs, MAAEs, LRTI cases of 
any severity not caused by RSV or hMPV, AEs leading to withdrawal, and CESIs 
(mild, moderate, or severe LRTI caused by RSV and/or hMPV). 
9.2.5 Main Trial Site Visits after Vaccination (Days 7, 28, 90, 180, and  
365) 
Site visits that do NOT include a vaccination will be performed on Days 7, 28, 90, 
180, and 365. At the site visit for Day 7, the diary will be reviewed. The healthcare 
professional reviewing these data will discuss the AEs/ARs (if any) reported by the 
subject and will determine if any additional diagnoses and/or AEs are present 
and/or if concomitant medications have been used. 
The site should: 
• 
Schedule the next site visit or other trial activity with the subject; 
• 
Provide a reminder of the next planned trial activity; 
• 
Remind the subject to contact the site if there are any questions and to 
contact the site immediately (or as soon as the subject is medically stable) if 
the subject has a medical condition that leads to a hospitalization or an ER 
visit. 
Refer to Section 10.4 for the reporting of AEs, SAEs, AESIs, MAAEs, LRTI cases of 
any severity not caused by RSV or hMPV, AEs leading to withdrawal, and CESIs 
(mild, moderate, or severe LRTI caused by RSV and/or hMPV). See 
Section 10.4.4.1 and Appendix D for AESIs. 
9.2.6 Main Trial Phone Contacts – Safety Calls (Days 3, 14, 56, 135, and  
270) 
A safety call will be performed on Days 3, 14, 56, 135, and 270. Safety calls are 
calls made to the subject by a trained healthcare provider. These calls will facilitate 
the collection of relevant safety information including concomitant medication, and 

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any AEs/SAEs the subject may have experienced since receiving the IMP. All safety 
information described by the subject must be written down and kept with the 
subject’s source documents. Safety data may also be entered into an electronic 
data capture (EDC) system (Section 12.1). Sites should contact the subject if data 
has not been entered in the EDC system within 1 day of the prompt. Sites will 
follow-up with subjects if relevant safety information is captured. The site should 
schedule the next clinic visit with the subject. The subject will be reminded to 
contact the site if there are any questions and to contact the site immediately (or 
as soon as the subject is medically stable) if the subject has a medical condition 
that leads to a hospitalization or an ER visit. 
Refer to Section 10.4 for the reporting of AEs, SAEs, AESIs, MAAEs, LRTI cases of 
any severity not caused by RSV or hMPV, AEs leading to withdrawal, and CESI 
(mild, moderate, or severe LRTI caused by RSV or hMPV). 
9.2.7 Visit Day 365  
The last visit for the main part of the trial will be performed on Day 365. If a 
subject terminates earlier, the final (end of trial) visit procedures should be 
performed at their last trial visit, if possible. The investigator must complete the 
end of trial eCRF for all subjects who received IMP. 
Refer to Section 10.4 for the reporting of AEs, SAEs, AESIs, MAAEs, LRTI cases of 
any severity not caused by RSV or hMPV, AEs leading to withdrawal, and CESIs 
(mild, moderate, or severe LRTI caused by RSV and/or hMPV). Only after all Visit 
Day 365, assessments are performed will the Subject be unblinded to their vaccine 
group. 
9.2.8 Observational Extension: Phone Contact (Day 545) and Site Visit 
(Day 730)  
A safety call will be performed on Day 545 by a trained healthcare provider to 
collect any MAAEs, AESI or SAEs since Visit Day 365. This call will collect relevant 
safety information. All concomitant medications used immediately prior to and for 
treating the respective AE will be recorded in the source documents. All designated 
safety data and medications (except for MAAEs) must also be entered into the EDC 
system (Section 12.1). Resolution of the MAAE or SAE should also be captured in 
the EDC. Sites will follow-up with subjects if relevant safety information is captured 
and should schedule a clinic visit with the subject if deemed medically relevant. The 
subject will be reminded to contact the site if with any questions and to contact the 
site immediately (or as soon as the subject is medically stable) if the subject has a 
medical condition that leads to a hospitalization or an ER visit. 
Refer to Section 10.4 and Appendix D for the reporting of AESIs. A reminder should 
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Day 730. A scheduled Site visit will occur at Visit Day 730 to perform a blood 
collection for immunogenicity; the subject should also be queried about any safety 
information, specifically MAAEs, AESI or SAEs since the Day 545 phone call. Record 
all ongoing concomitant medications and those used to treat the respective AE in 
the source documents. In addition, all designated safety data and medications 
(except for MAAEs) must be entered into the EDC system (Section 12.1). Resolution 
of the MAAE or SAE should also be captured in the EDC. All SAEs should be followed 
up until there is either a resolution or a permanent outcome to the event, or the 
outcome is otherwise explained. 
9.2.9 Unscheduled Visits  
For Study Day 0 through Day 365 Only 
An unscheduled visit describes a non-routine trial visit triggered by a specific 
anticipated or unanticipated AE, missed intervention or any investigator-determined 
need outside of the scheduled trial visits. The following assessments may be 
performed as appropriate: 
• 
Collect vital signs including: heart rate, respiratory rate, oxygen level (SpO2) 
blood pressure, and/or temperature, height (if applicable) and weight (if 
applicable); 
• 
A symptom-directed physical examination may be performed by a qualified 
health care practitioner; 
• 
The subject may be evaluated to assess any SAEs, AESIs, MAAEs, and AEs 
leading to withdrawal, and concomitant medications or vaccinations associated 
with SAEs and AESIs will also be collected; 
• 
Blood may be collected for clinical safety assessment for previously-missed visits 
or insufficient amount collected; 
• 
Collection of specimens to test for RSV, hMPV, and other respiratory viruses or 
bacteria by reverse transcriptase polymerase chain reaction (RT-PCR) if the 
unscheduled visit is triggered by suspected ARI. 
Unscheduled Visits For the Trial Observational Extension Only 
• 
The subject may be evaluated at an unscheduled visit to assess any SAEs, 
AESIs, and MAAEs; concomitant medications or vaccinations associated with 
SAEs and AESIs will also be collected. 
9.2.10 
Post-trial Care  
No post-trial care will be provided. 

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9.3 
Biological Sample Retention and Destruction  
In this trial, specimens for immune response testing will be collected as described 
in Section 9.1.6. After blood draw and serum processing, the serum samples will be 
preserved and retained at a central repository for up to but not longer than 
20 years or as required by applicable law. The sponsor has put into place a system 
to protect the subjects’ personal information to ensure optimal confidentiality and 
defined standard processes for sample and data collection, storage, analysis, and 
destruction. 
Serum samples will be used for analyses defined in this protocol. Subjects who sign 
the study consent forms also consent to future specimen use. Specimens may be 
used to assess, improve, or develop tests related to RSV, hMPV, or IVX-A12 that 
will allow for more reliable measurements of immune responses to the 
investigational vaccine. 

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10.0 ADVERSE EVENTS  
10.1 Definitions  
10.1.1 
Adverse Events  
An AE is defined as any untoward medical occurrence in a clinical investigation 
subject administered an IMP; it does not necessarily have to have a causal 
relationship with IMP administration. 
An AE can therefore be any unfavorable and unintended sign (e.g., a clinically 
significant abnormal laboratory finding), symptom, or disease temporally associated 
with the administration of an IMP whether or not it is considered related to the IMP. 
AEs will be graded for severity by the investigator in the following manner (based 
on the Food and Drug Administration (FDA) toxicity grading scale [38]. 
 
Mild 
Grade 1 
Awareness of symptoms that are easily tolerated, causing 
minimal discomfort, and not interfering with everyday 
activities. Relieved with or without symptomatic treatment. 
Moderate 
Grade 2 
Sufficient discomfort is present to cause interference with 
normal activity. Only partially relieved with symptomatic 
treatment or requires repeated use of non-narcotic pain 
reliever >24 hours. 
Severe 
Grade 3 
Extreme distress, causing significant impairment of 
functioning or incapacitation. Prevents normal everyday 
activities. Not relieved with symptomatic treatment or 
requires use of narcotic pain reliever. 
Potentially 
Life-threatening 
Grade 4 
Inability to perform basic self-care functions with 
intervention indicated to prevent permanent impairment, 
persistent disability, or death. 
10.1.2 
Solicited Adverse Events  
The occurrence of selected indicators of safety will be collected for 7 days starting 
from the day of IMP administration (Day 0 through Day 6) of the single IMP dose 
(including the day of administration) and will be recorded in the solicited AR eCRF 
(diary eCRF) as applicable and as listed in Table 6. 
Any solicited local (injection site) reactions or systemic ARs observed as continuing 
on Day 7 following trial vaccination will be recorded as an AE on the AE eCRF for 
follow-up. For these persistent/prolonged solicited ARs the end date will be 
captured on the AE eCRF to permit a separate analysis from the unsolicited AEs 
(see Section 10.4.2). 

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Table 6 
Solicited Local (Injection Site) Reactions and Systemic ARs  
 
Solicited Local (injection site) reactions: 
Pain 
Tenderness 
Erythema 
Swelling 
Solicited Systemic ARs: 
Headache 
Chills 
Fatigue 
Myalgia 
Arthralgia 
Vomiting 
Diarrhea 
Fever* 
*Fever is defined as body temperature greater than or equal to 38°C (100.4°F) 
regardless of method used [39]. 
Body temperature will be collected and recorded. 
The intensity of solicited safety parameters will be assessed as described in Table 7 
and Table 8. 

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Table 7 
Solicited Local (Injection Site) Reactions  
 
Adverse Event 
Intensity Grade 
Intensity 
Pain 
0 
None 
1 
Mild (able to perform duties) 
2 
Moderate (interferes with duties) 
3 
Severe (prevents duties) 
4 
ER visit or hospitalization 
Tenderness 
0 
None 
1 
Mild (discomfort to touch) 
2 
Moderate (discomfort with movement) 
3 
Severe (significant discomfort at rest) 
4 
ER visit or hospitalization 
Erythema (a) 
0 
<25 mm 
1 
Mild: >25 – ≤50 mm 
2 
Moderate: >50 – ≤100 mm 
3 
Severe: >100 mm 
4 
Necrosis or exfoliative dermatitis 
Swelling (a) 
0 
<25 mm 
1 
Mild: >25 – ≤50 mm 
2 
Moderate: >50 – ≤100 mm 
3 
Severe: >100 mm 
4 
Necrosis 
(a) Subjects are to record greatest surface diameter in mm on the diary. 

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Table 8 
Solicited Systemic ARs  
 
Adverse Reaction 
Intensity Grade 
Intensity 
Headache 
0 
None 
1 
Mild (no interference with activity) 
2 
Moderate (some interference with activity) 
3 
Severe (prevents daily activity) 
4 
ER visit or hospitalization 
Chills 
0 
None 
1 
Mild (no interference with activity) 
2 
Moderate (some interference with activity) 
3 
Severe (prevents daily activity) 
4 
ER visit or hospitalization 
Fatigue 
0 
None 
1 
Mild (no interference with activity) 
2 
Moderate (some interference with activity) 
3 
Severe (prevents daily activity) 
4 
ER visit or hospitalization 
Myalgia 
0 
None 
1 
Mild (no interference with activity) 
2 
Moderate (some interference with activity) 
3 
Severe (prevents daily activity) 
4 
ER visit or hospitalization 
Arthralgia 
0 
None 
1 
Mild (no interference with activity) 
2 
Moderate (some interference with activity) 
3 
Severe (prevents daily activity) 
4 
ER visit or hospitalization 
Vomiting 
0 
None 
1 
Mild – No interference with activity or 
1-2 episodes/24 hours 
2 
Moderate – Some interference with activity or 
>2 episodes/24 hours 
3 
Severe – Prevents daily activity, requires 
outpatient intravenous (IV) hydration 
4 
ER visit or hospitalization for hypotensive 
shock 
Diarrhea 
0 
None 
1 
Mild – 2–3 loose stools or <400 g/24 hours 
2 
Moderate – 4–5 stools or 400–800 g/24 hours 
3 
Severe – 6 or more watery stools or 
>800 gms/24 hours or requires outpatient IV 
hydration 
4 
ER visit or hospitalization for hypotensive 
shock 

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Table 8 
Solicited Systemic ARs (continued) 
 
Adverse Reaction 
Intensity Grade 
Intensity 
Fever (a) 
0 
<38.0°C / <100.4°F 
1 
38.0 – 38.4°C / 100.4 – 101.1°F 
2 
38.5 – 38.9°C / 101.2 – 102.0°F 
3 
39.0 – 40.0°C / 102.1 – 104.0°F 
(a) 
 Record body temperature in °C/°F. Fever is defined as body temperature greater 
than or equal to 38°C (100.4°F) regardless of method used [39]. 
10.1.3 
Clinical Events of Special Interest  
The single CESI for this trial that will be specifically highlighted to the investigator is 
mild (Grade 1), moderate (Grade 2), and severe (Grade 3) lower respiratory tract 
illness (mild, moderate, or severe LRTI) due to RSV or hMPV occurring in the 
subjects after vaccination. 
An episode of LRTI caused by RSV or hMPV occurring from Day 0 (day of 
vaccination) to Day 365 (end of trial), is defined as the presence of at least 
two lower respiratory symptoms/signs for at least 24 hours in the category of mild 
or moderate and any single symptom/sign in the category of severe for at least 
24 hours. 
Lower Respiratory Symptoms/Signs: 
Mild (Grade 1)  
i. 
New or increased sputum production 
ii. 
New or increased cough 
iii. 
New or increased wheezing 
iv. 
New or increased dyspnea (shortness of breath) 
Moderate (Grade 2) 
i. 
Decreased oxygenation (SpO2 <94%, in those with baseline above 94%) 
ii. 
Need for oxygen supplementation 
iii. 
A respiratory rate ≥20 breaths/min 
iv. 
Found by an investigator/clinician to have new crackles/rhonchi based on 
chest auscultation 
v. 
Found to have new or lung infiltrates on chest radiography 

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Severe (Grade 3) 
i. 
Any participant meeting the criteria for moderate LRTI requiring 
hospitalization 
ii. 
Any participant meeting the criteria for moderate LRTI requiring positive 
airway pressure therapy 
iii. 
Any participant meeting the criteria for moderate LRTI requiring 
mechanical ventilation 
Plus RT-PCR-confirmed RSV infection, hMPV infection or both RSV and hMPV 
infection, documented within 7 days of symptom onset. 
Careful notation should be made of any medical interventions, including 
hospitalization, for this CESI. 
The algorithm described below will be used to enhance detection for this CESI. The 
purpose of this algorithm is to identify subjects with ARI following vaccination, who 
are at risk for LRTI, and specifically for moderate to severe LRTI. In order to 
facilitate assessment of subjects potentially experiencing LRTI, surveillance for ARI 
will begin after vaccination and continue for the duration of the trial (through 
Day 365). Subjects will record, at a minimum, on a weekly basis, an RSS into an 
e-diary. Subjects will be instructed to notify the clinic should they develop ARI 
symptoms as described below. Any subject meeting the definition of ARI included 
below will be asked to return to the clinic for an unscheduled trial visit for 
evaluation (vital signs, medical history, directed physical exam, laboratories, as 
appropriate) and collection of a NP swab for virologic analysis. The NP swab will be 
sent to a clinical laboratory for multiplex RT-PCR including RSV, hMPV, and other 
respiratory pathogens. The visit evaluation and collection of NP swab should occur 
within 7 days of symptom onset. 
LRTI is distinct from the AE of ARI. An ARI is characterized as a new onset or 
worsening of at least two symptoms (as defined below) that persist for a period of 
≥24 hours, either in a continuous or intermittent manner: 
• 
Two respiratory symptoms: 
o Sore throat (pharyngitis); 
o Stuffy or runny nose [nasal congestion or discharge (rhinorrhea)]; 
o Earache; 
o Cough; 
o Sputum production; 
o Wheezing; 
o Shortness of breath (dyspnea). 

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OR 
• 
One respiratory symptom (from above) and one systemic symptom: 
o Feverishness* (defined as body temperature greater than or equal to 
38°C [100.4°F] regardless of method used); 
o Tiredness (fatigue); 
o Decreased appetite; 
o Headache; 
o Muscle ache (myalgia). 
*The term “feverishness” is used as a symptom to inform subjects of 
their need to measure their temperature for presence of fever 
(temperature ≥ 38.0ºC) or to come to the clinic for ARI evaluation. 
Fever is defined as body temperature greater than or equal to 38°C 
(100.4°F) regardless of method used [36] (see Table 8, 
Section 10.1.2). 
10.1.4 
Medically-attended Adverse Events  
MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare 
professional, including visits to an emergency department, but not fulfilling 
seriousness criteria. 
10.1.5 
Serious Adverse Events  
An SAE is defined as any untoward medical occurrence that at any dose meets any 
of the following criteria: 
1) Results in death. 
2) Is life-threatening (i.e., the subject was, in the opinion of the investigator, at 
immediate risk of death at the time of the event); it does not refer to an 
event that hypothetically might have caused death if it were more severe. 
3) Requires in-patient hospitalization or prolongation of existing hospitalization. 
4) Results in persistent or significant disability/incapacity (i.e., the event causes 
a substantial disruption of a person’s ability to conduct normal life functions). 
5) Congenital anomaly or birth defect in the offspring of a subject. 
6) An important and significant medical event that may not be immediately 
life-threatening or resulting in death or hospitalization but, based upon 
appropriate medical judgment, may jeopardize the subject, or may require 
intervention to prevent one of the other outcomes listed above. 

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AEs which do not fall into these categories are defined as non-serious. 
It should be noted that a severe adverse event need not be serious in nature and 
that an SAE need not, by definition, be severe. 
10.1.6 
Suspected Unexpected Serious Adverse Reaction  
Adverse drug reactions are all untoward and unintended responses to an 
investigational product related to any dose administered. Unexpected adverse 
reactions are suspected unexpected serious adverse reaction (SUSARs) if the 
following three conditions are met: 
1) The event must be serious; 
2) There must be a certain degree of probability that the event is a harmful and 
an undesirable reaction to the medicinal product under investigation, 
regardless of the administered dose; 
3) The adverse reaction must be unexpected, that is to say, the nature and 
severity of the adverse reaction are not in agreement with the product 
information as recorded in the IB for an IMP. 
10.2 Causality of Adverse Events  
Relationship (causality) to the IMP will also be assessed by the investigator. The 
relationship of each AE to the IMP, including solicited systemic ARs (solicited local 
(injection site) reactions are considered as related by default) will be assessed 
using the following categories: 
 
Related: 
There is suspicion that there is a relationship between the IMP and the 
AE (without determining the extent of probability); there is a reasonable 
possibility that the IMP contributed to the AE. 
Not Related: 
There is no suspicion that there is a relationship between the IMP and the 
AE; there are other more likely causes and administration of the IMP is 
not suspected to have contributed to the AE. 
10.2.1 
Relationship to Trial Procedures  
Relationship (causality) to trial procedures should be determined for all AEs. 
The relationship should be assessed as “Yes” if the investigator considers that there 
is a reasonable possibility that an event is due to a trial procedure. Otherwise, the 
relationship should be assessed as “No”. 

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10.2.2 
Outcome of Adverse Events  
 
Resolved: 
The subject has fully recovered from the event or the 
condition has returned to the level observed at Baseline. 
Resolving: 
The event is improving but the subject is still not fully 
recovered. 
Not resolved: 
The event is ongoing at the time of reporting and the 
subject has still not recovered. 
Resolved with sequelae: 
As a result of the AE, the subject suffered persistent and 
significant disability/incapacity (e.g., became blind, deaf or 
paralysed). 
Fatal: 
The subject died due to the event. If the subject died due to 
other circumstances than the event, the outcome of the 
event per se should be stated otherwise (e.g., not resolved 
or resolving). 
Unknown: 
If outcome is not known or not reported. 
10.3 Additional Points to Consider for Adverse Events  
An untoward occurrence generally may: 
• 
Indicate a new diagnosis or unexpected worsening of a pre-existing 
condition. Intermittent events for pre-existing conditions or underlying 
disease should not be considered as AEs. 
• 
Necessitate therapeutic intervention. 
• 
Require an invasive diagnostic procedure. 
• 
Require IMP discontinuation or a change in concomitant medication. 
• 
Be considered unfavorable by the investigator for any reason. 
Diagnoses versus signs and symptoms: 
• 
Each event should be recorded to represent a single diagnosis. Accompanying 
signs (including abnormal laboratory values) or symptoms should NOT be 
recorded as additional AEs. If a diagnosis is unknown, signs or symptoms 
should be recorded appropriately as AEs. 
Worsening of a pre-existing condition: 
• 
If the subject experiences a worsening or complication of a pre-existing 
condition after administration of the IMP, the worsening or complication 
should be recorded as a new AE. Investigators should ensure that the AE 
term recorded captures the change in the condition (e.g., “worsening of…”). 

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Changes in intensity of AEs: 
• 
If the subject experiences a change in intensity of an AE, after administration 
of the IMP the event should be captured once with the maximum severity 
recorded. 
New onset of chronic disease: 
• 
An AE that represents a new diagnosis of a chronic medical condition that 
was not present or suspected in a subject prior to trial enrollment. 
• 
AEs leading to withdrawal: 
• 
AEs leading to discontinuation from the trial or withdrawal of study 
treatment. 
Preplanned or elective procedures: 
• 
Preplanned procedures (surgeries or therapies) that were scheduled prior to 
signing of the ICF are not considered as AEs. Elective procedures performed 
where there is no change in the subject’s medical condition should not be 
recorded as AEs. In either instance the procedure should be documented in 
the subject’s source documents. Complications resulting from any planned or 
elective surgery, therapy or procedure should be reported as AEs. 
Trial procedures: 
• 
Adverse occurrences related to trial procedures after signing of the ICF are 
considered as AEs and should be reported as AEs. 
10.4 Procedures  
10.4.1 
Collection and Reporting of Adverse Events  
All AEs, whether considered related to the use of the IMP or not, must be monitored 
until symptoms subside and any abnormal laboratory values have returned to 
Baseline, or until there is a satisfactory explanation for the changes observed, or 
until death, in which case a full autopsy report should be supplied, if possible. 
All findings must be reported on an AE eCRF and on the SAE form, if necessary (see 
Section 10.4.4). All findings in subjects experiencing AEs must also be documented 
in the subject’s source documents. Any unsolicited AE will be collected through 
Day 28. AEs leading to discontinuation from the trial are collected throughout the 
trial. All efforts should be made to continue the collection of safety data according 
to protocol. 
The following information will be documented for each event: 
i. Reported term for the AE; 

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ii. Start and end date, duration; 
iii. Serious (Y/N); 
iv. Intensity; 
v. Investigator’s opinion of the causality (relationship) between the event and 
administration of IMP (“related” or “not related”); 
vi. Investigator’s opinion of the causality (relationship) to trial procedure(s), 
including the details of the suspected procedure; 
vii. Action taken; 
viii. 
Outcome of event. 
10.4.2 
Collection and Reporting of Solicited Adverse Reactions  
The occurrence of selected indicators of safety will be collected by the subjects for 
7 days, starting from the day of IMP administration and will be recorded on the 
solicited AR eCRF (diary eCRF), as applicable. These will be summarized in the final 
report under the category “solicited ARs” to differentiate them from unsolicited AEs. 
Any solicited local (injection site) reaction or systemic AR observed as continuing on 
Day 7 following trial vaccination will be additionally recorded as an AR on the AE 
eCRF for follow-up. For these persistent/prolonged solicited ARs, the end date will 
be captured on the AE eCRF to permit a separate analysis from the unsolicited AEs. 
Any solicited AR that meets any of the following criteria must be entered as an AE 
on the AE eCRF. 
i. Solicited local (injection site) reactions or systemic ARs that lead the subject 
to withdraw from the trial; 
ii. Solicited local (injection site) reactions or systemic ARs that lead to the 
subject being withdrawn from the trial by the investigator; 
iii. Solicited local (injection site) reactions and systemic ARs that otherwise meet 
the definition of an SAE (see Section 10.1.2); 
iv. Solicited local (injection site) reactions or systemic AR observed as continuing 
on Day 7 following each trial vaccination. 
10.4.3 
Collection and Reporting of Clinical Events of Special Interest 
and Medically-attended Adverse Events  
The CESIs (mild, moderate, or severe LRTI caused by RSV and/or hMPV) and 
MAAEs will be collected from Day 0 up to Day 365. All CESIs and/or MAAEs must be 
recorded on the AE eCRF. The CESIs and/or MAAEs will be summarized separately 
through Day 365. MAAEs will be collected through Day 730. 

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10.4.4 
Collection and Reporting of Serious Adverse Events  
Collection of SAEs and AESIs will commence from the time that the subject is 
administered the dose of IMP (Day 0). Routine collection of SAEs and AESIs will 
continue until Day 365 for subjects in the main trial and Day 730 for subjects in 
the extension. 
SAEs should be reported according to the following procedure: 
A sponsor SAE form must be completed, in English, and signed by the investigator 
immediately or within 24 hours of first onset or notification of the event. The 
information should be completed as fully as possible but contain, at a minimum: 
i. A short description of the event and the reason why the event is categorized 
as serious. 
ii. Causality assessment. 
iii. Protocol number. 
iv. Subject identification number. 
v. Investigator’s name. 
The SAE form should be transmitted within 24 hours to the safety mailbox or Fax: 
e-mail: safetyreporting@syneoshealth.com 
Fax: 1-877-464-7787 
10.4.4.1 
Adverse Events of Special Interest 
Any AESI occurring during the trial will be categorized and reported as an SAE. 
These AESIs include anaphylaxis, thrombocytopenia, and other pIMCs. Appendix D 
provides a list of pIMCs, which includes Guillain Barré syndrome. 
10.5 Follow-up Procedures  
10.5.1 
Adverse Events  
All AEs will be monitored until resolution, or a stable status is reached or until a 
formal diagnosis can be made or until the end of the trial, whichever occurs first. If 
the subject is unwilling to undergo the remaining trial procedures (e.g., blood 
draw[s] or visits), they should be asked whether they agree to continue 
participating for safety reasons. 
10.5.2 
Serious Adverse Events  
If information not available at the time of the first report becomes available later, 
the investigator should complete a follow-up SAE form or provide other written 

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documentation immediately. Copies of any relevant data from the hospital notes 
(e.g., laboratory tests, discharge summary, postmortem results) should be sent to 
the sponsor/sponsor designee, after redaction for privacy. All SAEs should be 
followed up until resolution, permanent outcome of the event, or is otherwise 
explained. The timelines and procedure for follow-up reports are the same as those 
for the initial report. 
10.5.3 
Safety Reporting to Investigators, Independent Ethics 
Committees or Investigational Review Boards, and Regulatory 
Authorities  
The sponsor or designee will be responsible for the reporting of all SUSAR and any 
other SAEs to regulatory authorities, investigators, and IEC/IRB, as applicable, in 
accordance with national regulations in the countries where the trial is conducted. 
Relative to the first awareness of the event by/or further provision to the sponsor 
or designee, SUSARs will be submitted within 7 days for fatal and life-threatening 
events and 15 days for other SUSARs, unless otherwise required by national 
regulations. The sponsor or designee will also prepare an expedited report for other 
safety issues where these might materially alter the current benefit-risk assessment 
of an investigational vaccine or that would be sufficient to consider changes in the 
IMP administration or in the overall conduct of the trial. The trial site will also 
forward a copy of all expedited reports to their IEC/IRB in accordance with national 
regulations. 
10.5.4 
Post-trial Events  
Any SAE that occurs after the end of the trial but is considered to be caused by the 
IMP must be reported to the sponsor. These SAEs will be processed by the 
sponsor’s (or sponsor designee) pharmacovigilance department. Instructions for 
how to submit these SAEs are included on the SAE form. 

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11.0 TRIAL-SPECIFIC REQUIREMENTS  
The following sections provide information on the trial-specific requirements. 
11.1 Stopping Rules  
Monitoring of safety signals will be performed throughout the trial by an 
independent SMC. The clinical trial will be halted if there is clear evidence of 
potential harm or harmful effects. Vaccine administration may be paused for further 
review and assessment if any of the following events occur: 
• 
In any trial subject: 
o Any death that could be related to vaccine as per the investigator, 
sponsor, or SMC chair occurring during the trial; 
o Any vaccine-related SAE during the trial; 
o Any life-threatening (Grade 4) vaccine-related AE/AR during the trial, 
which needs medical intervention including: 
• 
Ulceration, abscess or necrosis at the injection site; 
• 
Laryngospasm, bronchospasm, or anaphylaxis within 24 hours after 
administration of vaccine. 
o An allergic or hypersensitivity reaction such as fever >40°C or 
generalized urticaria (defined as occurring at three or more body 
parts) within 72 hours after administration of vaccine. 
• 
If 2 or more subjects in a single trial group experience the same severe 
(Grade 3) AE/AR (Preferred Term [PT] in a given Medical Dictionary for 
Regulatory Activities [MedDRA] system organ class [SOC]) within the first 
7 days following vaccination that persists for at least 48 hours and cannot be 
clearly attributed to another cause: 
o Severe (Grade 3) vaccine-related solicited local (injection site) 
reactions (excluding measured grades of erythema and swelling alone) 
or systemic AR; 
o Severe (Grade 3) vaccine-related unsolicited AE during the trial; 
o Severe (Grade 3) vaccine-related vital sign(s) abnormality; 
o Severe (Grade 3) vaccine-related clinical laboratory abnormality. 
In the case that a pre-defined safety signal is met in any trial group, subsequent 
dosing will be halted to permit a complete evaluation of the reported event(s), and 
to consult the SMC. Based on the review of the data, the SMC may recommend 
temporary or permanent stopping, or continuation of dosing. When dosing resumes 
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11.2 Safety Review Committee and Safety Monitoring Committee  
An independent SMC will be constituted to monitor the safety of all subjects 
enrolled in the trial, including solicited local (injection site) reactions, solicited 
systemic ARs, unsolicited AEs, and clinical laboratory data. The SMC will review 
safety data collected during the 7 consecutive days following vaccination for all 
subjects, focusing on the interpretation of solicited local (injection site) reactions 
and solicited systemic ARs, unsolicited AEs, and clinical laboratory data in the first 
week after dosing when most reactogenicity is expected to occur. 
Details of the membership, roles, and functioning of the committee will be available 
in the SMC charter. 

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12.0 DATA HANDLING AND RECORD KEEPING  
The full details of procedures for data handling will be documented in the data 
management plan. AEs, medical history, and concurrent medical conditions will be 
coded using MedDRA. Drugs will be coded using the World Health Organization 
Drug Dictionary. 
12.1 Electronic CRFs  
Completed eCRFs are required for each subject. 
The site will maintain adequate source documents for the recording and collection 
of subject data. Data will be entered into an EDC system. The sponsor will make 
arrangements to train appropriate site staff in the use of the EDC for completing 
the eCRFs. These forms are used to transmit the information collected in the 
performance of this trial to the sponsor and regulatory authorities. The eCRFs must 
be completed in English. 
The principal investigator (or designee) must review the eCRFs for completeness 
and accuracy and must sign and date the appropriate eCRFs as indicated. 
Furthermore, the investigator must retain full responsibility for the accuracy and 
authenticity of all data entered on the eCRFs. 
The eCRFs will be reviewed for completeness and acceptability at the trial site 
during periodic visits by trial monitors. The sponsor or designee will be permitted to 
review the subject’s medical and hospital records pertinent to the trial to ensure 
accuracy of the eCRFs. The completed eCRFs are the sole property of the sponsor 
and should not be made available in any form to third parties, except for authorized 
representatives of appropriate governmental health or regulatory authorities, 
without written permission of the sponsor. 
12.2 Record Retention  
The investigator agrees to keep the records stipulated in Appendix A and those 
documents that include (but are not limited to) the trial-specific documents, the 
identification log of all participating subjects, medical records, temporary media 
(e.g., thermal sensitive paper, and should be copied and certified), source 
worksheets, all original signed and dated ICFs, subject authorization forms 
regarding the use of personal health information (if separate from the ICFs), eCRFs, 
including the audit trail, and detailed records of vaccine disposition to enable 
evaluations or audits from regulatory authorities, the sponsor or designee. 
Furthermore, ICH E6 Section 4.9.5 requires the investigator to retain essential 
documents specified in ICH E6 (Section 8) until at least 2 years after the last 
approval of a marketing application for a specified vaccine indication being 
investigated or, if an application is not approved, until at least 2 years after the 
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ICH E6 Section 4.9.5 states that the trial records should be retained until an 
amount of time specified by applicable regulatory requirements or for a time 
specified in the clinical trial site agreement between the investigator and sponsor. 
Refer to the clinical trial site agreement for the sponsor’s requirements on record 
retention. The investigator should contact and receive written approval from the 
sponsor before disposing of any such documents. 

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13.0 STATISTICAL METHODS  
13.1 Statistical and Analytical Plans  
A statistical analysis plan will be prepared and finalized prior to unblinding of the 
trial groups. This document will provide further details regarding the definition of 
analysis variables and analysis methodology to address all trial objectives. 
A (blinded) data review will be conducted prior to unblinding of the trial groups. 
This review will assess the accuracy and completeness of the trial database, subject 
evaluability, and appropriateness of the planned statistical methods. 
13.1.1 
Analysis Sets  
Safety Set: The safety set will consist of all subjects who received a dose of 
IVX-A12 or placebo. Subjects will be analyzed as treated. 
Full Analysis Set (FAS): The FAS will include all randomized subjects who received a 
dose of IVX-A12 or placebo. Subjects will be analyzed as randomized. 
Per-Protocol Set (PPS): The PPS will include all subjects in the FAS who received a 
dose of IVX-A12 or placebo and have no major protocol deviations that have a 
significant impact on immunogenicity results. Subjects will be analyzed as 
randomized. 
Extension Enrolled Set: The Extension Enrolled Set will consist of all subjects who 
consented to participate in the extension portion of the trial. Subjects will be 
analyzed as initially treated. 
13.1.2 
Analysis of Disposition, Demographics, Other Baseline 
Characteristics, Medical History and Medications  
Subject disposition will be summarized for all enrolled subjects which will include 
the number of subjects enrolled, screen failed, and randomized. For subjects who 
are randomized, the number and percentage of subjects in each of the analysis sets 
will be summarized by treatment group. 
Demographics (age, gender, race) and other baseline characteristics (including 
baseline RSV and hMPV NAb titers) will be summarized descriptively by treatment 
group for all randomized subjects. 
Medical and surgical history will be summarized by primary SOC and PT and by 
vaccine group. All medical history data will be listed. 
All prior and concomitant medications will be summarized by Anatomical 
Therapeutic Chemical Level 4 and PT and by treatment group. All medications will 
be listed. 

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13.1.3 
Immunogenicity Analyses  
Immunogenicity data will be summarized for each group and strain (RSV/A, RSV/B, 
both RSV strains and either RSV strain; hMPV/A, hMPV/B, both hMPV strains and 
either hMPV strain). The GMT will be calculated for RSV/A, RSV/B, hMPV/A and 
hMPV/B titers separately along with their 95% CI. The adjusted GMT and 
corresponding 95% CI will be obtained from an analysis of covariance (ANCOVA) 
model, which will include log-transformed baseline titers, age group, and treatment 
group as terms. Durability will be assessed at Days 180,365, and at Day 730 by 
comparing to Day 28 data. The geometric mean of fold changes and corresponding 
95% CI will be calculated. 
Proportion of subjects with ≥4-fold increase (SRR), 8-fold increase, and GMFR from 
prevaccination/baseline (Day 0) will be summarized for Days 28, 180, 365, and at 
Day730. RCD curves will be generated. 
The VLP core-specific IgG titers will be summarized at Days 0, 28, 180, 365, and 
Day 730 with GMT and 95% CI. 
Separate summaries will be provided for subjects that agreed to participate in the 
observational extension portion of the trial and will include these subjects’ data 
from the beginning of the trial through Day 730. 
All immunogenicity data will be listed. 
13.1.4 
Efficacy Analysis  
RSV and/or hMPV cases of mild, moderate, or severe LRTI and any severity LRTI 
due to RSV and/or hMPV (CESIs), meeting the protocol-specified definitions, will be 
summarized by vaccine group and placebo group starting on Day 14 through Day 
365. Listings will be provided. 
Vaccine efficacy will be calculated as 100 × (1 – incidence rate ratio). The incidence 
rate is the number of subjects meeting the case definition divided by cumulative 
follow-up person time among all subjects at risk. The incidence rate ratio is the 
ratio between the incidence rates of vaccine group and placebo group. 
13.1.5 
Safety Analyses  
Solicited local (injection site) reactions and solicited systemic ARs: Solicited ARs will 
be summarized for 7 days starting from the day of dosing (Day 0) through Day 6 
(total of 7 days). The summary will be by day and overall, within 7 days. Solicited 
ARs by maximum severity will also be summarized. 
Unsolicited AEs: Unsolicited AEs will be assessed from day of dosing (Day 0) 
through 28 days post-vaccination and coded according to MedDRA and summarized 
by SOC and PT. The summary tables will include the number and percentage of 

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subjects reporting unsolicited AE by SOC and PT, and by SOC, PT, and maximum 
severity. Subjects reporting ≥Grade 3 and vaccine-related unsolicited AEs will also 
be summarized. 
SAEs, MAAEs, AESIs, AEs leading to withdrawal, and CESI (mild, moderate, or 
severe LRTI caused by RSV and/or hMPV) and mild, moderate, or severe LRTI cases 
not caused by RSV or hMPVwill be assessed throughout the trial (from 
randomization on Day 0) and coded using MedDRA and summarized by SOC and 
PT. For the trial extension, SAEs, MAAEs, and AESIs will be continue to be collected 
and coded. Separate summaries will be provided for subjects that agreed to 
participate in the extension portion of the trial and will include these subjects’ data 
from the beginning of the trial through Day 730. 
All solicited ARs and unsolicited AEs will be listed. 
Clinical laboratory tests including hematology, chemistry, and urinalysis will be 
summarized by vaccine groups. For numeric laboratory parameters, the observed 
value and change from baseline will be summarized by visit. For categorical 
laboratory parameters, the number of subjects and percentages will be summarized 
by visit. Shift tables may be provided as well. All lab data will be listed. 
All vital signs observed value and change from baseline will be summarized by 
vaccine groups. Listing will also be provided. 
Physical examination results will be listed. 
13.2 Interim Analysis/Data Reviews  
Two IAs will be performed: The first IA will be performed after all subjects have 
completed the Day 28 safety assessments and when all Day 28 immunogenicity 
data are available; the second IA will be performed after all subjects have 
completed the Day 180 safety assessments, and when all Day 180 secondary 
immunogenicity data are available. A final analysis of main trial will be performed 
after Day 365 and an analysis of the observational extension will be performed after 
Day 730. These analyses will support further evaluation of safety and 
immunogenicity of IVX-A12 in older adults. 
13.3 Primary and Secondary Analyses for the CSR  
A CSR will be prepared when Day 365 analyses have been completed for the 
primary and secondary objectives of the trial. Additional analyses including safety 
and immunogenicity through Day 730 may be provided in a Clinical Study 
Addendum. 

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13.4 Sample Size Justification  
Sample size for this trial is not based on any formal hypothesis testing. Analyses of 
safety and immunogenicity will be primarily descriptive in nature. An approximate 
total of 250 subjects (approximately 100 subjects in each of the IVX-A12 groups 
and 50 subjects in the placebo group) will be randomized. With 100 subjects in 
each IVX-A12 group, there is a 63.4% probability of observing at least 1 subject 
with an AE if the true incidence of the AE is 1%, and 86.7% probability of observing 
at least 1 subject with an AE if the true incidence of the AE is 2%. The trial will 
have more than 90% power to detect a difference of 20% or more in SRR or detect 
a 2-fold increase or more in GMT or GMFR (assuming standard deviation at 
0.5 log10), between the two IVX-A12 groups (or between the IVX-A12 group and 
placebo group), with two-sided type-1 error rate at 0.05. 

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14.0 QUALITY CONTROL AND QUALITY ASSURANCE  
14.1 Trial Site Monitoring Visits  
Monitoring visits to the trial site will be made periodically during the trial to ensure 
that all aspects of the protocol are being followed. Source documents will be 
reviewed for verification of data recorded on the eCRFs. Source documents are 
defined as original documents, data, and records. The investigator and institution 
guarantee access to source documents by the sponsor or designee (clinical research 
organization) and by the IEC or IRB. 
14.2 Protocol Deviations  
The investigator should not deviate from the protocol, except where necessary to 
eliminate an immediate hazard to subjects. Should other unexpected circumstances 
arise that will require deviation from protocol-specified procedures, the investigator 
should consult the sponsor (or designee) and/or the medical monitor, if an 
immediate safety issue is identified (and IEC or IRB, as required) to determine the 
appropriate course of action. 
14.3 Quality Assurance Audits and Regulatory Agency Inspections  
The trial site may be subject to quality assurance audits by the sponsor or 
designee. In this circumstance, the sponsor-designated auditor will contact the site 
in advance to arrange an auditing visit. The auditor may ask to visit the facilities 
where laboratory samples are collected, where the vaccine is stored and prepared, 
and any other facility used during the trial. In addition, there is the possibility that 
this trial may be inspected by regulatory agencies, including those of foreign 
governments (e.g., the FDA, the Medicines and Healthcare Products Regulatory 
Agency of United Kingdom [MHRA], the Pharmaceuticals and Medical Devices 
Agency of Japan [PMDA]). If the site is contacted for an inspection by a regulatory 
body, the sponsor should be notified immediately. The investigator and institution 
guarantee access for quality assurance auditors to all trial documents as described 
in Section 14.1. 
14.4 Risk Management  
The ICH E6 addendum (R2) guidance encourages a risk-based approach to the 
management of clinical studies and includes requirements for risk control and risk 
reporting [2]. 
When the primary and secondary analyses are complete, the quality management 
approach implemented will be described in the CSR. If applicable, the CSR will 
summarize important deviations and the remedial actions taken. 

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15.0 ETHICAL ASPECTS  
This trial will be conducted with the highest respect for the subjects according to 
the protocol, the ethical principles that have their origin in the Declaration of 
Helsinki [1], and the ICH Harmonised Tripartite Guideline for GCP E6 (R2) [2]. Each 
investigator will conduct the trial according to applicable local or regional regulatory 
requirements and align his or her conduct in accordance with the “Responsibilities 
of the Investigator” that are listed in Appendix A. The principles of Helsinki are 
addressed through the protocol and through appendices containing requirements 
for informed consent and investigator responsibilities. 
15.1 Independent Ethics Committee and/or Institutional Review Board 
Approval  
IECs and IRBs must be constituted according to the applicable local requirements of 
each participating region. The sponsor or designee will require documentation 
noting all names and titles of members who make up the respective IEC or IRB. If 
any member of the IEC or IRB has direct participation in this trial, written 
notification regarding his or her abstinence from voting must also be obtained. 
The sponsor or designee will supply relevant documents for submission to the 
respective IEC or IRB for the protocol’s review and approval. This protocol, the IB, a 
copy of the ICF and, if applicable, subject recruitment materials and/or 
advertisements and other documents required by all applicable laws and 
regulations, must be submitted to a central or local IEC or IRB for approval. The 
IEC’s or IRB’s written approval of the protocol and subject ICF must be obtained 
and submitted to the sponsor or designee before commencement of the trial 
(i.e., before trial-specific screening activity). The IEC or IRB approval must refer to 
the trial by exact protocol title, number, and version date; identify versions of other 
documents (e.g., ICF) reviewed; and state the approval date. The sponsor will 
notify the site once the sponsor has confirmed the adequacy of site regulatory 
documentation and, when applicable, the sponsor has received permission from the 
competent authority to begin the trial. Until the site receives approval no protocol 
activities, including screening, may occur. 
Sites must adhere to all requirements stipulated by their respective IEC or IRB. This 
may include notification to the IEC or IRB regarding protocol amendments, updates 
to the ICF, recruitment materials intended for viewing by subjects, local safety 
reporting requirements, reports, and updates regarding the ongoing review of the 
trial at intervals specified by the respective IEC or IRB, and submission of the 
investigator’s final status report to IEC or IRB. All IEC and IRB approvals and 
relevant documentation for these items must be provided to the sponsor or 
designee. 

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Incentives should not be used to exert undue influence on subjects for participation. 
Payments to subjects must be approved by the IEC or IRB and sponsor. 
15.2 Subject Information, Informed Consent and Subject Authorization  
For both the main trial and the trial extension, the following applies: 
Written consent documents will embody the elements of informed consent as 
described in the Declaration of Helsinki [1] and the ICH Guidelines for GCP [2] and 
will be in accordance with all applicable laws and regulations. The ICF, subject 
authorization form (if applicable), and subject information sheet describe the 
planned and permitted uses, transfers, and disclosures of the subject’s personal 
and personal health information for the purpose of conducting the trial. The ICF and 
the subject information sheet further explain the nature of the trial, its objectives, 
and potential risks and benefits, as well as the date informed consent is given. The 
ICF will detail the requirements of the subject and the fact that the subject is free 
to withdraw at any time without giving a reason and without prejudice to the 
subject’s further medical care. 
The investigator is responsible for the preparation, content, and IEC or IRB 
approval of the ICF and if applicable, the subject authorization form. The ICF, 
subject authorization form (if applicable), and subject information sheet must be 
approved by both the IEC or IRB and the sponsor prior to use. 
The ICF, subject authorization form (if applicable), and subject information sheet 
must be written in a language fully comprehensible to the prospective subject. It is 
the responsibility of the investigator to explain the detailed elements of the ICF, 
subject authorization form (if applicable), and subject information sheet (if 
applicable) to the subject. Information should be given in both oral and written 
form whenever possible and in the manner deemed appropriate by the IRB or IEC. 
The subject must be given ample opportunity to: (1) inquire about details of the 
trial and (2) decide whether or not to participate in the trial. If the subject 
determines he or she will participate in the trial, then the ICF and subject 
authorization form (if applicable) must be signed and dated by the subject at the 
time of consent and prior to the subject entering into the trial. The subject should 
be instructed to sign using their legal names, not nicknames, using blue or black 
ballpoint ink. The investigator must also sign and date the ICF and subject 
authorization (if applicable) at the time of consent and prior to the subject entering 
into the trial; however, the sponsor may allow a designee of the investigator to sign 
to the extent permitted by applicable law. 
Once signed, the original informed consent, subject authorization form (if 
applicable), and subject information sheet will be stored in the investigator’s site 
file. The investigator must document the date the subject signs the ICF in the 
subject’s medical record and eCRF. Copies of the signed informed consent, the 

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signed subject authorization form (if applicable), and subject information sheet (if 
applicable) shall be given to the subject. 
All revised ICFs must be reviewed and signed by the subject in the same manner as 
the original ICF. The date the revised consent was obtained should be recorded in 
the subject’s medical record and eCRF, and the subject should receive a copy of the 
revised ICF. 
15.3 Subject Confidentiality  
The sponsor and designee affirm and uphold the principle of the subject’s right to 
protection against invasion of privacy. Throughout this trial, a subject’s source data 
will only be linked to the sponsor’s clinical trial database or documentation via a 
unique identification number. As permitted by all applicable laws and regulations, 
limited subject attributes, such as sex, age, or date of birth, and subject initials 
may be used to verify the subject and accuracy of the subject’s unique identification 
number. 
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, 
the sponsor requires the investigator to permit its monitor or designee, 
representatives from any regulatory authority (e.g., FDA, MHRA, PMDA), the 
sponsor’s designated auditors, and the appropriate IECs/IRBs to review the 
subject’s original medical records (source data or documents), including, but not 
limited to, laboratory test result reports, electrocardiogram reports, admission and 
discharge summaries for hospital admissions occurring during a subject’s trial 
participation, and autopsy reports. Access to a subject’s original medical records 
requires the specific authorization of the subject as part of the ICF process (see 
Section 15.2). 
Copies of any subject source documents that are provided to the sponsor must 
have certain personally identifiable information removed (i.e., subject name, 
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15.4 Clinical Trial Registration, Publication and Disclosure Policy  
15.4.1 
Clinical Trial Registration  
In order to ensure that information on clinical studies reaches the public in a timely 
manner and to comply with applicable law, regulation and guidance, the sponsor 
will, as a minimum register all clinical studies conducted in subjects that it sponsors 
anywhere in the world, on publicly accessible websites such as ClinicalTrials.gov 
and EudraCT, according to local requirements, before trial initiation. The sponsor 
contact information, along with the investigator’s city, country, and recruiting 
status will be registered and available for public viewing. 
15.4.2 
Clinical Trial Results Disclosure  
The sponsor will post the results of this clinical trial within 12 months after end of 
the trial regardless of outcome, on publicly accessible websites such as 
ClinicalTrials.gov and/or EudraCT, as required by applicable laws and/or 
regulations. 
Completion of the trial corresponds to the date on which the final subject was 
examined or received an intervention for the purpose of final collection of data 
(usually corresponds to last subject last visit). 
15.4.3 
Publication of Trial Results  
Publication of trial results will follow Icosavax, Inc publication policies, applicable 
international standards and guidelines for good publication practice, applicable 
laws, and/or regulations. 
15.4.4 
Insurance and Compensation for Injury  
Each subject in the trial must be insured in accordance with the regulations 
applicable to the site where the subject is participating. If a local underwriter is 
required, then the sponsor or sponsor’s designee will obtain clinical trial insurance 
against the risk of injury to clinical trial subjects. Refer to the clinical trial site 
agreement regarding the sponsor’s policy on subject compensation and treatment 
for injury. If the investigator has questions regarding this policy, he or she should 
contact the sponsor or sponsor’s designee. 

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16.0 REFERENCES  
1. WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving 
Human Subjects. http://www.wma.net/en/30publications/10policies/b3 
(accessed 17 February 2022). 
2. International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH). ICH harmonised guideline. Integrated 
Addendum to ICH E6 (R2): Guideline for Good Clinical Practice E6. 
3. Rima, B, Collins, P, Easton, A, Fouchier R, Kurath G, Lamb RA, et al. ICTV Virus 
taxonomy profile: Pneumoviridae. J. Gen Virol, 2017;98:1912-2913. 
4. Colosia AD, Yang J, Hillson E, Mauskopf J, Copley-Merriam C, Shinde V et al. The 
epidemiology of medically attended respiratory syncytial virus in older adults in 
the United States: A systematic review. PLoS One. 2017;12(8):e0182321. 
5. Falsey AR, Walsh EE. Respiratory syncytial virus infection in adults. Clin 
Microbiol Rev. 2000;13(3):371-84. 
6. Tin Tin Htar M, Yerramalla MS, Moïsi JC, Swerdlow DL. The burden of respiratory 
syncytial virus in adults: a systematic review and meta-analysis. Epidemiol 
Infect. 2020;148:e48. 
7. Cattoir L, Vankeerberghen A, Boel A, Van Vaerenbergh K, De Beenhouwer H. 
Epidemiology of RSV and hMPV in Belgium: a 10-year follow-up. Acta Clin Belg. 
2019 ;74(4):229-235. 
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17. Graham BS. Biological challenges and technological opportunities for respiratory 
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virus cpts530 L polymerase mutation. Virology.1999;260(1):125-35. 
21. Jagusic M, Slovic A, Ivancic-Jelecki J, Ljubin-Sternak S, Vilibić-Čavlek T et al. 
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metapneumovirus in hospitalized children with acute respiratory infections in 
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Population-based incidence of human metapneumovirus infection among 
hospitalized children. J Infect Dis. 2010;201(12):1890-8. 

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25. Jain B, Singh AK, Dangi T, Agarwal A, Verma AK, Dwivedi M et al. High 
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26. Williams JV, Chen Z, Cseke G, Wright DW, Keefer CJ, Tollefson SJ et al. A 
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J Virol. 2007;81(15):8315-24. 
27. Hamelin ME, Couture C, Sackett M, Kiener P, Suzich J, Ulbrandt N. The 
prophylactic administration of a monoclonal antibody against human 
metapneumovirus attenuates viral disease and airways hyperresponsiveness in 
mice. Antivir Ther. 2008;13(1):39-46. 
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Identification of small-animal and primate models for evaluation of vaccine 
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vaccine design. J Gen Virol. 2004;85(Pt 6):1655-1663. 
29. van den Hoogen. Respiratory tract infection due to human metapneumovirus 
among elderly patients. Clin Infect Dis. 2007;44(9):1159-60. 
30. Madhi SA, Ludewick H, Kuwanda L, van Niekerk N, Cutland C, Klugman KP. 
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31. Williams JV, Wang CK, Yang CF, Tollefson SJ, House FS, Heck JM et al. The role 
of human metapneumovirus in upper respiratory tract infections in children: a 
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34. Falloon J, Talbot HK, Curtis C, Ervin J, Krieger D, Dubovsky F et al. Dose 
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36. O'Hagan DT, Ott GS, Nest GV, Rappuoli R, Giudice GD. The history of MF59(®) 
adjuvant: a phoenix that arose from the ashes. Expert Rev Vaccines. 
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global clinical measure of fitness and frailty in elderly people. CMAJ. 2005 Aug 
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38. Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent 
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Sindic C. Optimal approaches to data collection and analysis of potential 
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PMID: 37018468. 

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APPENDIX A RESPONSIBILITIES OF THE INVESTIGATOR  
The investigator agrees to assume the following responsibilities: 
1. Conduct the trial in accordance with the protocol. 
2. Supervise the staff that will assist in the trial. 
3. Ensure that trial-related procedures are NOT performed on potential subjects 
prior to the receipt of written approval from relevant governing 
bodies/authorities. 
4. Obtain approval for the trial and any changes by an appropriate IEC/IRB that 
conforms to ICH, and local regulatory requirements. 
5. Report all changes in research activity and all anticipated risks to subjects to the 
IEC/IRB. 
6. Ensure that requirements for informed consent, as outlined in ICH and local 
regulations, are met. 
7. Obtain valid informed consent from each subject who participates in the trial, 
and document the date of consent in the subject’s medical chart. 
8. Maintain adequate documentation of all persons entered into the trial, including 
eCRFs, hospital records, laboratory results, etc., for a minimum of 2 years 
following notification by the sponsor that all investigations have been 
discontinued or that the regulatory authority has approved the marketing 
application. The investigator should contact and receive written approval from 
the sponsor before disposing of any such documents. 
9. Allow possible inspection and copying by the regulatory authority of 
GCP-specified essential documents. 
10. Maintain current records of the receipt, administration, and disposition of 
sponsor-supplied vaccines, and return all unused sponsor-supplied vaccines to 
the sponsor. 
11. Report AEs leading to withdrawal, SAEs, and pregnancies to the sponsor 
promptly. 
12. Review and provide a signature as approval of the content of the CSR, if needed. 

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APPENDIX B 
TOXICITY TABLES  
Standard Toxicity Grading Scales: adapted from Guidance for industry: toxicity 
grading scale for healthy adult and adolescent volunteers enrolled in preventive 
vaccine clinical trials. Food and Drug Administration [38]. 

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Table 9 
FDA Toxicity Grading Scales for Clinical Laboratory 
Abnormalitiesa  
 
Serum Chemistry and 
Hematology* 
Mild 
Moderate 
Severe 
Potentially 
Life- 
threatening 
Grade 1 
Grade 2 
Grade 3 
Grade 4** 
Urea (i.e., BUN) (mg/dL) 
23 – 26 
27 – 31 
>31 
Requires dialysis 
Creatinine (mg/dL) 
1.5 – 1.7 
1.8 – 2.0 
2.1 – 2.5 
>2.5 or requires 
dialysis 
Total protein – 
hypoproteinemia 
(g/dL) 
5.5 – 6.0 
5.0 – 5.4 
<5.0 
– 
Liver function tests – 
ALT, AST; increase by 
factor 
1.1 – 2.5 × 
ULN*** 
2.6-5.0 × ULN 
5.1 – 10 × 
ULN 
>10 × ULN 
Total bilirubin – when 
accompanied by any 
increase in liver function 
test; increase by factor 
1.1 – 1.25 
× ULN 
1.26 – 1.5 × 
ULN 
1.51 – 1.75 × 
ULN 
>1.75 × ULN 
Total bilirubin – when 
liver function test is 
normal; increase by 
factor 
1.1 – 1.5 × 
ULN 
1.6 – 2.0 × 
ULN 
2.0 – 3.0 × 
ULN 
>3.0 × ULN 
Hemoglobin (Female) 
(g/dL) 
11.0 – 12.0 
9.5 – 10.9 
8.0 – 9.4 
<8.0 
Hemoglobin (Female) 
change from baseline 
value (g/dL) 
Any 
decrease – 
1.5 
1.6 – 2.0 
2.1 – 5.0 
>5.0 
Hemoglobin (Male) 
(g/dL) 
12.5 – 13.5 
10.5 – 12.4 
8.5 – 10.4 
<8.5 
Hemoglobin (Male) 
change from baseline 
value (g/dL) 
Any 
decrease – 
1.5 
1.6 – 2.0 
2.1 – 5.0 
>5.0 
WBC increase (cell/mm3) 
10,800 – 
15,000 
15,001 – 
20,000 
20,001 – 
25,000 
>25,000 
WBC decrease (cell/mm3) 
2,500 – 
3,500 
1,500 – 2,499 
1,000 – 1,499 
<1,000 
Lymphocytes 
Decrease - cell/mm3 
750 – 
1,000 
500 – 749 
250 – 499 
<250 
Neutrophils 
Decrease - cell/mm3 
1,500 – 
2,000 
1,000 – 1,499 
500 – 999 
<500 
Eosinophils - cell/mm3 
650 – 1500 
1501 – 5000 
>5000 
Hypereosinophilic 
syndrome 
Platelets decreased 
(cell/mm3) 
125,000 – 
140,000 
100,000 – 
124,000 
25,000 – 
99,000 
<25,000 

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Abbreviations: ALT, alanine transaminase, AST; aspartate transaminase; BUN, blood urea 
nitrogen; WBC, white blood cell. 
* The laboratory values provided in the tables serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate. 
** The clinical signs or symptoms associated with laboratory abnormalities might result in 
characterization of the laboratory abnormalities as Potentially Life Threatening (Grade 4). 
For example. a low sodium value that falls within a Grade 3 parameter (125-129 mE/L) 
should be recorded as a grade 4 hyponatremia event if the subject had a new seizure 
associated with the low sodium value. 
***“ULN” is the upper limit of the normal range. 
Values provided in this table will be included in vaccination pause rules for the trial. 
Table 10 
FDA Toxicity Grading Scale for Vital Sign Abnormalities  
 
Vital Sign 
Abnormalities* 
Mild 
Moderate 
Severe 
Potentially Life- 
threatening 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Tachycardia (bpm) 
101 – 115 
116 – 130 
>130 
ER visit or hospitalization 
for arrhythmia 
Bradycardia (bpm)** 
50 – 54 
45 – 49 
<45 
ER visit or hospitalization 
for arrhythmia 
Hypertension 
(systolic) (mm Hg) 
141 – 150 
151 – 155 
>155 
ER visit or 
hospitalization for 
malignant hypertension 
Hypertension 
(diastolic) (mm Hg) 
91 – 95 
96 – 100 
>100 
ER visit or 
hospitalization for 
malignant hypertension 
Hypotension (systolic) 
(mm Hg) 
85 – 89 
80 – 84 
<80 
ER visit or hospitalization 
for hypotensive shock 
Respiratory Rate 
(breaths per minute) 
17 – 20 
21 – 25 
>25 
Intubation 
Abbreviations: bpm, beats per minute; ER, emergency room. 
* Subject should be at rest for all vital sign measurements. 
** When resting heart rate is between 60 – 100 beats per minute. Use clinical judgment 
when characterizing bradycardia among some healthy subject populations, for example, 
conditioned athletes. 

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Table 11 
FDA Toxicity Grading Scale for Urinalysis Abnormalities  
 
Urinalysis 
Abnormalities* 
Mild 
Moderate 
Severe 
Potentially Life- 
threatening 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Protein 
Trace 
1+ 
2+ 
Hospitalization or dialysis 
Glucose 
Trace 
1+ 
2+ 
Hospitalization for 
hyperglycemia 
Blood (microscopic) 
– (rbc/hpf) 
1 - 10 
11 - 50 
>50 and/ or 
gross 
hematuria 
Hospitalization or PRBC 
transfusion 
Abbreviations: hpf, high power field; PRBC, packed red blood cells; RBC, red blood cells. 
* The laboratory values provided in the tables serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate. 

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APPENDIX C 
DALHOUSIE UNIVERSITY CLINICAL FRAILY SCALE  
 

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Appendix D  
Adverse Events of Special Interest (AESIs): Potential 
Immune-mediated Conditions (pIMCs)  
(Defined according to the MEDRA preferred terms) 
 
Gastrointestinal 
conditions 
• 
Autoimmune pancreatitis 
• 
Celiac disease 
• 
Crohn's disease 
• 
Microscopic colitis 
• 
Ulcerative colitis 
• 
Ulcerative proctitis 
Liver conditions 
• 
Autoimmune cholangitis 
• 
Autoimmune hepatitis 
• 
Primary biliary cirrhosis 
• 
Primary sclerosing cholangitis 
Metabolic & endocrine 
conditions 
• 
Addison's disease 
• 
Autoimmune hypophysitis 
• 
Autoimmune thyroiditis (including Hashimoto thyroiditis) 
• 
Diabetes mellitus type I 
• 
Grave's or Basedow's disease 
Musculoskeletal and 
connective tissue 
conditions 
• 
Ankylosing spondylitis 
• 
Antisynthetase syndrome 
• 
Cutaneous lupus 
• 
Dermatomyositis 
• 
Juvenile chronic arthritis (including Still’s disease) 
• 
Juvenile rheumatoid arthritis 
• 
Mixed connective tissue disorder 
• 
Polymyalgia rheumatica 
• 
Polymyositis 
• 
Psoriatic arthropathy 
• 
Reactive arthritis 
• 
Relapsing polychondritis 
• 
Rheumatoid arthritis 
• 
Scleroderma, including diffuse systemic form and CREST syndrome 
• 
Spondyloarthritis, including ankylosing spondylitis, reactive arthritis (Reiter's 
Syndrome) and undifferentiated spondyloarthritis 
• 
Systemic lupus erythematosus 
• 
Systemic sclerosis (with limited or diffuse cutaneous involvement) 
Neuroinflammatory 
conditions 
• 
Acute disseminated encephalomyelitis, including site specific variants (e.g., 
noninfectious encephalitis, encephalomyelitis, myelitis, radiculomyelitis) 
• 
Cranial nerve inflammatory disorders, including paralyses/paresis (e.g., Bell's 
palsy) 
• 
Demyelinating disease 
• 
Encephalitis 
• 
Guillain-Barré syndrome, including Miller Fisher syndrome and other variants 
• 
Immune-mediated peripheral neuropathies and plexopathies, including chronic 
inflammatory demyelinating polyneuropathy, multifocal motor neuropathy and 

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polyneuropathies associated with monoclonal gammopathy 
• 
Multiple sclerosis 
• 
Myasthenia gravis (including Lambert-Eaton myasthenic syndrome) 
• 
Narcolepsy 
• 
Neuritis 
• 
Optic neuritis 
• 
Transverse myelitis 
Skin conditions 
• 
Alopecia areata 
• 
Autoimmune bullous skin diseases (including pemphigus, pemphigoid & 
dermatitis herpetiformis) 
• 
Cutaneous lupus erythematosus 
• 
Erythema nodosum 
• 
Lichen planus 
• 
Morphoea 
• 
Psoriasis 
• 
Sweet’s syndrome 
• 
Vitiligo 
Vasculitides 
• 
Large vessels vasculitis, including giant cell arteritis such as Takayasu's arteritis 
& temporal arteritis 
• 
Medium sized and/or small vessels vasculitis including the following: 
polyarteritis nodosa, Kawasaki's disease, microscopic polyangiitis, Wegener's 
granulomatosis, Churg–Strauss syndrome (allergic granulomatous angiitis), 
Buerger’s disease thromboangiitis obliterans, necrotizing vasculitis and 
antineutrophil cytoplasmic antibody (ANCA) positive vasculitis (type 
unspecified), Henoch-Schonlein purpura, Behcet's syndrome, leukocytoclastic 
vasculitis 
Others 
• 
Antiphospholipid syndrome 
• 
Autoimmune glomerulonephritis (including IgA nephropathy, 
glomerulonephritis rapidly progressive, membranous glomerulonephritis, 
membranoproliferative glomerulonephritis, & mesangioproliferative 
glomerulonephritis) 
• 
Autoimmune hemolytic anemia 
• 
Autoimmune myocarditis/cardiomyopathy 
• 
Autoimmune neutropenia 
• 
Autoimmune pancytopenia 
• 
Autoimmune thrombocytopenia 
• 
Goodpasture syndrome 
• 
Idiopathic pulmonary fibrosis 
• 
Pernicious anemia 
• 
Polyglandular autoimmune syndrome 
• 
Raynaud's phenomenon 
• 
Sarcoidosis 
• 
Sjögren’s syndrome 
• 
Stevens-Johnson syndrome 
• 
Uveitis 
Adapted from Tavares Da Silva (2013) [42]