A PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF STAPHYLOCOCCUS AUREUS 4 ANTIGEN VACCINE (SA4AG) IN ADULTS UNDERGOING ELECTIVE OPEN POSTERIOR SPINAL FUSION PROCEDURES WITH MULTILEVEL INSTRUMENTATION
Phase: PHASE2
Conditions: Staphylococcal Vaccine
Sponsor: Pfizer

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A PHASE 2b, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED 
STUDY TO EVALUATE THE SAFETY AND EFFICACY OF STAPHYLOCOCCUS 
AUREUS 4-ANTIGEN VACCINE (SA4Ag) IN ADULTS UNDERGOING ELECTIVE 
OPEN POSTERIOR SPINAL FUSION PROCEDURES WITH MULTILEVEL 
INSTRUMENTATION 
 
Compound: 
PF-06290510 
Compound Name: 
Staphylococcus aureus 4-Antigen Vaccine 
United States (US) Investigational New 
Drug (IND) Number: 
BB-IND #14705 
European Clinical Trials Database 
(EudraCT) Number:  
2014-002644-40 
Protocol Number: 
B3451002 
Phase: 
2b 
 
 
 
 
 

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Document History 
Document 
Version Date 
Summary of Changes and Rationale 
Amendment 4 05 February 2018 – Protocol Summary-Study Design, Section 3.1 and 
Section 9.1: Changed the expected number of 
enrolled subjects from 2600 to 6000 and target 
number of endpoint cases changed from 42 to 48.  
Added a statement that the final enrollment numbers 
may be varied.  Rationale: Lower than predicted 
post-operative SA infection rate and undetermined 
vaccine efficacy. 
– Table of Contents: Updated to reflect changes. 
– Section 1.2.4.3: Removed the reference to study 
B3451011 data being preliminary and added a 
statement regarding persistence of immune response 
through Month 12 after vaccination.  Rationale: 
B3451011 study results are now available. 
– Section 1.2.4.4: Added results for study B3451014.  
Rationale: Results now available. 
– Section 1.2.5: Appendix 7 (Country-Specific 
Appendix – Required for Sweden) has been 
incorporated into the body of the protocol under the 
title: Benefit-Risk Assessment.  Ethics Committees 
were notified of the addition of Appendix 7 via a 
Protocol Administrative Clarification Letter in 
November 2016.  Minor editorial updates were also 
made to this section.  Rationale: Satisfies an earlier 
commitment to the Swedish Authorities to 
incorporate this text into Amendment 4. 
– Section 3.2.1: Expanded the definition of spinal 
fusion to include occiput and clarified that vertebrae 
must be adjacent.  Expanded the definition of 
multilevel instrumentation.  Rationale: Added 
specificity and clarity. 
– Section 3.2.2.1: Amended the indication of 
compression to spinal cord compression for clarity.  
Rationale: Added clarity. 
– Section 4.2: Amended an exclusion criterion (No. 3) 
to define the exclusionary period associated with the 
surgical indication of trauma.  Amended an exclusion 
criterion (No. 7) to clarify that subjects with 
rheumatologic disorders that are not being treated 

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with immunosuppressant medications can enter the 
study.  Amended an exclusion criterion (No. 19) to 
include spinal cord stimulators as exclusionary 
devices.  Rationale: Added specificity and clarity. 
– Section 4.4: Added an additional clause to define the 
sub-population expected to use contraception during 
the study.  Rationale: Added specificity and clarity. 
– Section 6.3.1.1: Clarified the timing of visit 2 
procedures for early admissions to hospital.  
Rationale: Allows for subjects admitted to hospital 
more than 1 day prior to surgery. 
– Section 6.3.1.2.1, Section 6.4.3, and Section 7.2.3: 
Clarified requirements for assessment and reporting 
when a subject is suspected of having organ 
dysfunction or failure.  Rationale: Added specificity 
and clarity. 
– Table 8: Clarified requirements for reporting 
nondefined infections.  Rationale: Added clarity. 
– Table 14: Clarified measurements for the assessment 
of respiratory failure and amended the reference for 
the use of a modified SOFA score.  Rationale: Added 
clarity. 
– Section 7.3.3: Modified surgical site wound culture 
requirements.  Rationale: Added inclusivity. 
– Table 14: Changed bilirubin level from >12 to ≥12. 
– Section 8.6: Added statement to define deep venous 
thrombosis as important medical events for this 
study.  Rationale: Added specificity and clarity. 
– Section 8.6.1: Added reference to Study Reference 
Manual for additional reporting requirements.  
Rationale: Added clarity. 
– Protocol Summary and Section 9.1: Modified interim 
analysis case count from 21 to 24; removed all 
references to hierarchical testing of proof of 
principle/high-level efficacy; clarified rules for 
including cases based on time of entry into 
adjudication system; clarified success criteria if 
additional cases are included.  Rationale: Added 
statistical clarity and refinement based on changes to 

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enrollment numbers and case count. 
– Section 9.2: Modified sample size and power 
calculations based on increased sample size, primary 
endpoint case count, vaccine efficacy and incidence 
rates.  Updated vaccine efficacy Figure 3.  Rationale: 
Lower than predicted post-operative SA infection rate 
and undetermined vaccine efficacy. 
– Section 9.3: Clarified that primary and secondary 
endpoint analyses will be repeated for subgroup 
analyses.  Rationale: Added clarity. 
– Section 9.3.1: Made a minor editorial change. 
– Table 15: Updated to reflect the number of cases 
required for the interim and final analyses.  
Rationale:  Internal statistical consistency based on 
changes in primary endpoint case counts. 
Amendment 3 01 June 2016 
– Throughout document:  
• Changed S. aureus to S aureus (style change). 
– Section 1.2.4.4.  Noted that clinical study B3451014 
was completed in April 2016. 
– Section 2.5: Clarified the remit of the endpoint 
adjudication committee (EAC); ie, the remit of the 
EAC is not restricted to S aureus infections. 
– Section 3.2.1: Amended the index surgery definition.  
Made changes throughout the protocol to reflect the 
update.  These include: 
• Protocol title; 
• Primary, secondary, and exploratory objectives 
and associated endpoints; 
• Study design; 
• Inclusion criteria. 
– Table 2, Section 6.3.1.2.1, Section 6.4.2, Section 
7.1.1, Section 7.2.3: Refined evaluation periods for 
protocol-defined infections and organ failure events. 
– Table 4: Added perioperative data collection for 
index surgery reoperation and revision. 
– Section 4.2: Added a new exclusion criterion (No. 2) 
to specify single-level spinal fusions that are 

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exclusionary. 
– Section 4.2: Amended an exclusion criterion (No. 19) 
to exclude subjects with indwelling central nervous 
system shunts and implanted devices. 
– Section 6.1: Clarified subject participation in the 
event that the index surgery is not conducted 
according to the index study procedure definitions. 
– Section 6.2.1: Clarified the timing of the subject 
number being provided by the interactive voice 
response system/interactive Web response. 
– Section 6.4.2: Added instruction that tissue and fluid 
samples for suspected bloodstream and surgical-site 
infections, where possible, should be taken prior to 
commencing administration of antibiotics. 
– Section 6.4.3, Table 4: Added requirement to record 
details of any reoperation and revision of the index 
surgery, and to culture hardware or tissue if removed 
during the reoperation or revision surgery. 
– Section 6.5: Separated the Subject Withdrawal and 
Safety Follow-up section into 2 subsections for 
clarity. 
– Section 7.2.1.3, Section 7.2.1.4, Section 8.8: Added 
clarification regarding the management of Grade 4 
local reactions and systemic events and the 
application of the adverse event severity scale for 
these reactions/events. 
– Table 14: Added phenylephrine to the criteria for 
hypotension. 
– Section 8.14.1: Removed duplicate text. 
– Protocol Summary, Section 9, Section 5.2: Added 
details of periodic checks for study futility that will 
be performed prior to the interim analysis.  This 
includes the data monitoring committee’s role in 
these assessments. 
– Section 9.1: Revised to clarify the rules for inclusion 
of events in case-driven study analyses.  Reference 
added (credit to source). 
– Section 9: Revised wording to clarify that there is 

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more than 1 mITT population. 
– Section 9.3.1: Updated to allow vaccinated subjects 
who undergo spinal surgery that does not meet the 
index study procedure definition to be included in a 
modified intent-to-treat population. 
– Table 15: Revised the examples of the estimated 
efficacy and associated CIs for a selected number of 
SA4Ag cases. 
– Section 9.3.2.1: Clarified the management of cases 
identified after the primary analysis. 
– Section 3.1, Section 6.3.1.2.1, Section 7.1.1, Section 
7.2.1.3, Section 7.2.1.4, Section 7.2.2.1, Section 
7.2.3.1, Section 9.1, Section 9.3, Section 9.3.2, 
Section 9.6, Section 15, Section 16: Made editorial 
changes. 
– Single-page Appendix 6 added to the last page of the 
protocol and is applicable to Japan only.  Addresses 
consent/assent issues for minors, and postvaccination 
temperature management. 
Amendment 2 15 September 
2015 
– Protocol Summary, Section 2.4.1, Section 7.4, 
Section 9.3.4.1: Exploratory endpoint 
immunogenicity assays revised from a 4-plex to a 
2-plex assay (requested by Pfizer Vaccine Research 
& Development [VRD]). 
– Table 1, Section 4.3, Section 6.3.1.3, Section 9.3.4.1: 
Visit windows added to swab and blood sample 
collections (negates the need to repeat sample 
collection if discharge is postponed or vaccination is 
delayed). 
– Section 2.5, Section 7.1.1.2: All invasive infections 
will now be adjudicated by the event adjudication 
committee (EAC); previously only those associated 
with S aureus were to be adjudicated (change 
requested by the EAC). 
– Section 3.2, Section 9.2: Assumptions regarding 
subject numbers removed (text was confusing). 
– Section 3.3.2.1: Indications for surgery amended 
(requested by principal investigator). 
– Section 3.3.2.3: Any preexisting spinal 

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instrumentation or tissue removed during a revisional 
surgical procedure, must be cultured (to detect 
preexisting pathogens) 
–  Section 4.1, Section 7.2.1.1: In the event that surgery 
occurs on Day 10 after vaccination, the  
e-diary does not need to be completed for that day 
(clarification). 
– Section 4.3: Temporary delay criteria clarified with 
respect to the use of systemic steroids (clarification). 
– Section 5.4: Spinal steroids added to concomitant 
medications (may have an effect on the immune 
response). 
– Section 5.4.1: Minor editorial changes. 
– Section 6.2.1: Added text on inclusion of the spinal 
condition in the medical history; noted that surgery 
may occur on Day 10 after vaccination (clarification). 
– Table 1, Section 6.2.1, Section 7.2.4: Noted that 
serum samples may be used for pregnancy 
(clarification). 
– Section 6.4.1.1.1: Pain at the injection site added 
(previous omission). 
– Section 7.1.1: Revision of text in the last bullet point 
(clarification). 
– Figure 1: Legend added (previous omission). 
– Section 7.1.1.2: Added text and Table 8 regarding the 
EAC adjudication of other invasive infections (EAC 
request). 
– Section 8.2, Section 8.4, Section 8.5, Section 8.6.1: 
Minor editorial changes (Pfizer protocol template 
language updates). 
– Section 8.10, Section 8.11: Minor revisions (Pfizer 
protocol template language updates). 
– Table 9: Severe pain added to footnote (previous 
omission). 
– Table 12: Revision of mathematical symbol (correct 
typographical error). 
– Table 13: Reference added (give credit to source). 

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– Table 14: Vasopressin added to the scoring system 
for categorizing hypotension; dialysis added to the 
scoring system for categorizing renal failure 
(requested by the EAC). 
– Section 9.2: Figure 3 added with explanatory text 
(displays power vs true efficacy). 
– Section 9.3.2: Added Table 15 showing estimated 
efficacy and CI by analysis stage (additional 
clarification). 
– Section 9.5: Safety analysis and association with 
S aureus reworded (clarification). 
– Section 15: Text revisions (Pfizer protocol template 
language updates). 
– Appendix 1: Added missing text to criteria for 
vertebral disc space infection and superficial SSI 
(previous omissions). 
– Appendix 3: Added collection of data regarding  
composition of implanted devices (request by 
investigators). 
Amendment 1 13 May 2015 
Single-page Appendix 5 added to the last page of the 
protocol and is applicable to France only.  Addresses 
contractual agreements not covered in the French Contrat 
Unique. 
Administrative letter: Section 8.6.2:  Added Hy’s law 
language for reporting changes in liver function.  This 
protocol addition was communicated to investigators via 
an administrative letter on 12 April 2015.  (This 
mandatory text is applicable to all Pfizer interventional 
clinical trials, irrespective of whether or not liver 
function tests are monitored in the study.  There are no 
known or suspected negative associations between 
SA4Ag and liver function.) 
Original 
protocol 
07 November 
2014 
Not applicable (N/A) 
 
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities, institutional review boards/ethics committees 
(IRBs/ECs), etc. 

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ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
ANCOVA 
analysis of covariance 
ASA 
American Society of Anesthesiologists  
BMI  
body mass index 
BSI 
bloodstream infection 
CBER 
Center for Biologics Evaluation and Research 
CCI 
Charlson comorbidity index 
CDC  
Centers for Disease Control and Prevention 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
ClfA 
clumping factor A  
cLIA 
competitive Luminex immunoassay  
CP5 
capsular polysaccharide serotype 5  
CP5-CRM197 
capsular polysaccharide serotype 5 conjugated to cross-reactive material 197 
(nontoxic mutant form of diphtheria toxin)  
CP8 
capsular polysaccharide serotype 8  
CP8-CRM197 
capsular polysaccharide serotype 8 conjugated to cross-reactive material 197 
(nontoxic mutant form of diphtheria toxin)  
CRF 
case report form 
CRM197 
cross-reactive material 197 (nontoxic mutant form of diphtheria toxin) 
CRP 
C-reactive protein  
CSA 
clinical study agreement 
CSF  
cerebrospinal fluid 
CT 
computed tomography 
CTA 
clinical trial application 
DMC 
data monitoring committee 
DNA 
deoxyribonucleic acid 
EAC 
event adjudication committee 
EACC 
event adjudication committee charter 
ECG 
electrocardiographic 
eCRF 
electronic case report form 
e-diary 
electronic diary 
EDP 
exposure during pregnancy 
ESR  
erythrocyte sedimentation rate  
EudraCT 
European Clinical Trials Database 
FDA 
Food and Drug Administration (United States) 
FDAAA 
Food and Drug Administration Amendments Act (United States) 
FIH 
first-in-human  
FiO2 
fraction of inspired oxygen 
GCP 
Good Clinical Practice 
GCS 
Glasgow Coma Scale  

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Abbreviation 
Term 
GMFR 
geometric mean fold rise 
GMT 
geometric mean titer 
HAI 
healthcare-associated infection 
HAP 
hospital-acquired pneumonia  
IB 
investigator’s brochure 
ICD  
informed consent document  
ICH 
International Conference on Harmonisation 
ICU  
intensive care unit 
IEC 
independent ethics committee 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
IRB 
institutional review board 
ISA 
invasive Staphylococcus aureus 
IST 
independent statistical team 
IUD 
intrauterine device 
IVRS 
interactive voice response system 
IWR 
interactive Web response 
LP305A 
lipoprotein 305A 
LRT 
lower respiratory tract 
LS 
least squares 
LSLV 
last subject last visit 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat  
MntC 
manganese transporter C 
MOF 
multiple-organ failure 
MRI 
magnetic resonance imaging 
MRSA 
methicillin-resistant Staphylococcus aureus 
MSSA 
methicillin-sensitive Staphylococcus aureus 
NHSN  
National Health Surveillance Network 
NIS 
Nationwide Inpatient Sample 
OF 
organ failure 
OPA 
opsonophagocytic activity  
PaO2 
partial pressure of oxygen in arterial blood 
PCD 
primary completion date 
PDA 
personal digital assistant 
PDI  
protocol-defined infection 
PMN 
polymorphonuclear neutrophil  
RCDC 
reverse cumulative distribution curve 
rClfAm 
recombinant clumping factor A mutant (a component of the initial formulation of 
SA3Ag) 
rmClfA 
recombinant clumping factor A mutant (a component of SA4Ag) 
rP305A 
recombinant protein 305A  

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Abbreviation 
Term 
RR 
relative risk  
SA3Ag 
Staphylococcus aureus 3-antigen vaccine 
SA4Ag 
Staphylococcus aureus 4-antigen vaccine 
S aureus  
Staphylococcus aureus 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SCIP 
Surgical Care Improvement Project  
SOFA  
Sequential Organ Failure Assessment 
SpO2 
saturation of peripheral oxygen  
SRM 
study reference manual 
SRSD 
single reference safety document  
SSI 
surgical-site infection 
SSTI 
skin and soft tissue infection 
Tdap 
tetanus, diphtheria, and acellular pertussis 
VE  
vaccine efficacy 
WBC 
white blood cell  
 

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PROTOCOL SUMMARY 
INTRODUCTION 
Staphylococcus aureus is among the most prevalent pathogens responsible for 
healthcare-associated infections (HAIs) in numerous healthcare settings.  Based on data from 
the Nationwide Inpatient Sample (NIS), from 2000 to 2001 approximately 0.8% of all US 
hospitalizations involved S aureus infections, and in 2001, 1.1% of US surgical 
hospitalizations involved S aureus infections.  Inpatients with S aureus infection have an 
estimated 3 times the length of hospital stay and 5 times the risk of in-hospital death as 
patients without S aureus infection.  The risk of developing S aureus infection is dependent 
on factors related to both the patient and the type of healthcare exposure.  At-risk populations 
include patients undergoing surgery, patients with end-stage renal disease, patients in 
intensive care units (ICUs), transplant recipients, and other immunocompromised 
individuals.  Medically or surgically managed conditions associated with increased exposure 
to the healthcare system place individuals at further risk of acquiring healthcare-associated 
S aureus infection. 
S aureus has been demonstrated to be the leading cause of bloodstream infection (BSI), 
responsible for 20% to 26% of infections overall among North American, European, and 
Latin American countries, and for 19% of infections among developing countries globally.  
S aureus is the leading cause of both hospital-acquired (34%) and ventilator-associated 
(27%) pneumonia, and is commonly identified as the predominant organism isolated among 
intensive care patients and hospitalized pediatric patients. 
The incidence of postoperative S aureus disease in surgical patients has led to vigorous 
efforts to develop specific preventive and therapeutic measures directed against this 
pathogen, including intranasal administration of mupirocin and chlorhexidine bathing to 
eliminate carriage, and the administration of prophylactic antibiotics prior to surgery.  
Despite these efforts, postoperative S aureus infection remains a common and serious 
occurrence.  Unlike the long-term risk of healthcare-associated invasive S aureus (ISA) 
disease in patients with chronic medical conditions, postoperative ISA disease in the elective 
surgery population is usually directly attributable to the surgical incision.  In this setting, high 
ISA disease incidence and burden are encountered during a relatively brief and predictable 
time frame.  Elective surgery therefore presents an appropriate setting for evaluation of the 
safety and efficacy of investigational vaccine for prevention of ISA disease among 
immunocompetent patients. 
Among elective surgery populations and procedures, investigational vaccine efficacy (VE) is 
ideally evaluated in a clearly defined elective surgery population with well-characterized 
patient demographics and comorbidities, and procedural characteristics that are highly 
representative of a broad array of elective surgery populations with respect to risk factors and 
mechanisms of pathogenesis of postoperative S aureus disease.  The elective spinal surgery 
population is similar to other elective surgical populations with regard to both patient and 
procedural characteristics.  Elective spinal surgery is largely performed in patients with low 
overall morbidity, as demonstrated by Charlson comorbidity index scores. 

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Elective spinal surgery patients generally require a brief index hospitalization and experience 
a low incidence of postoperative morbidity and mortality in the absence of postoperative 
infection, facilitating evaluation of Staphylococcus aureus 4-antigen vaccine (SA4Ag) safety. 
OBJECTIVES AND ENDPOINTS 
Primary Efficacy Objective 
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus BSI and/or 
deep incisional or organ/space surgical-site infection (SSI) occurring within 90 days of 
elective open posterior spinal fusion procedures with multilevel instrumentation, in adults 
aged 18 to <86 years. 
Primary Efficacy Endpoint 
• The number of subjects in each vaccine group with postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 90 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation, as confirmed by the event 
adjudication committee (EAC). 
Primary Safety Objective 
• To describe the safety and tolerability of a single vaccination of SA4Ag in adults aged 18 
to <86 years undergoing elective open posterior spinal fusion procedures with multilevel 
instrumentation, by measuring local reactions, systemic events, and adverse events (AEs). 
Primary Safety Endpoints 
• Number and proportion of subjects in each vaccine group with local reactions (redness, 
swelling, and pain) occurring within the 10-day period following study vaccination. 
• Number and proportion of subjects in each vaccine group with systemic events 
(fever, fatigue, headache, vomiting, diarrhea, muscle or joint pain) occurring within the 
10-day period following study vaccination. 
• Number and proportion of subjects in each vaccine group with AEs reported during the 
following time periods:  
• From vaccination until the day of surgery  
• From vaccination until the Day 42 postoperative evaluation 
• From the day of surgery until the Day 42 postoperative evaluation 
• From the Day 42 postoperative evaluation until the Day 180 postoperative evaluation 
(newly diagnosed chronic medical disorders) 

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• Number and proportion of subjects in each vaccine group with serious adverse events 
(SAEs) reported during the following time periods:  
• From vaccination until the Day 180 postoperative evaluation 
• From vaccination until the day of surgery  
• From the day of surgery until the Day 180 postoperative evaluation 
Secondary Efficacy Objectives 
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 180 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation, in adults 18 to <86 years of age. 
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus SSI 
occurring within 90 days of elective open posterior spinal fusion procedures with 
multilevel instrumentation, in adults 18 to <86 years of age. 
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus SSI 
occurring within 180 days of elective open posterior spinal fusion procedures with 
multilevel instrumentation, in adults 18 to <86 years of age. 
Secondary Efficacy Endpoints 
• The number of subjects in each vaccine group with postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 180 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation. 
• The number of subjects in each vaccine group with postoperative S aureus SSI occurring 
within 90 days of elective open posterior spinal fusion procedures with multilevel 
instrumentation. 
• The number of subjects in each vaccine group with postoperative S aureus SSI occurring 
within 180 days of elective open posterior spinal fusion procedures with multilevel 
instrumentation. 
Exploratory Objectives 
• To assess the efficacy of SA4Ag in the prevention of postoperative ISA disease occurring 
within 90 days of elective open posterior spinal fusion procedures with multilevel 
instrumentation, in adults 18 to <86 years of age. 
• To assess the efficacy of SA4Ag in the prevention of postoperative ISA disease occurring 
within 180 days of elective open posterior spinal fusion procedures with multilevel 
instrumentation, in adults 18 to <86 years of age. 

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• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 90 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation, in adults 18 to <86 years of age, 
based on baseline S aureus colonization status. 
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 180 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation, in adults 18 to <86 years of age, 
based on baseline S aureus colonization status. 
• To describe the immunogenicity of SA4Ag in adults aged 18 to <86 years undergoing 
elective open posterior spinal fusion procedures with multilevel instrumentation. 
• To describe S aureus colonization in adults aged 18 to <86 years undergoing elective 
open posterior spinal fusion procedures with multilevel instrumentation, before and after 
SA4Ag administration. 
• To compare healthcare utilization data between vaccine groups. 
Exploratory Endpoints 
• The number of subjects in each vaccine group with postoperative ISA disease occurring 
within 90 days of elective open posterior spinal fusion procedures with multilevel 
instrumentation. 
• The number of subjects in each vaccine group with postoperative ISA disease occurring 
within 180 days of elective open posterior spinal fusion procedures with multilevel 
instrumentation. 
• The number of subjects in each vaccine group with postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 90 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation,, based on baseline S aureus 
colonization status. 
• The number of subjects in each vaccine group with postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 180 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation, based on baseline S aureus 
colonization status. 
• The proportion of subjects at each time point who achieve specific antibody thresholds in 
antibody assays that assess functional activity.  These may include, for example, 
opsonophagocytic activity (OPA) assays using an S aureus capsular polysaccharide 
serotype 5 (CP5)-expressing strain and a capsular polysaccharide serotype 8 
(CP8)-expressing strain, and competitive Luminex immunoassays (cLIAs) for clumping 
factor A (ClfA) and manganese transporter C (MntC).  Additional exploratory assays to 
measure immune responses may also be conducted on all 4 antigens. 

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• The proportion of subjects at each time point who achieve specific antibody thresholds to 
all 4 antigens both individually and combined using immunological assays. 
• The number of subjects in each vaccine group determined to be colonized with S aureus 
on each occasion that swab samples are collected. 
• From subjects with S aureus infection, the association between S aureus strain or strains 
identified as colonizing the subject and the S aureus strain or strains recovered from the 
infection. 
• Healthcare utilization data, including days in hospital, days in an ICU, discharge 
disposition, inpatient days in rehabilitation facilities or skilled nursing facility after 
discharge, number of hospital readmissions and reoperations, days of antibiotic use, and 
number of rehabilitation/physical therapy outpatient visits. 
STUDY DESIGN 
This is a Phase 2b, multicenter, parallel-group, placebo-controlled, randomized, double-blind 
study to evaluate SA4Ag safety and efficacy in the prevention of postoperative S aureus 
disease in adults aged 18 to <86 years who are undergoing elective open posterior spinal 
fusion procedures with multilevel instrumentation. 
This is an event-driven study with a total target of 48 primary endpoint S aureus cases 
(meeting the case definition described in Section 9.1); it is anticipated that approximately 
6,000 subjects will be enrolled globally to accumulate these 48 cases.  However, the total 
enrollment number may vary based on the incidence rate of the primary endpoint, true 
underlying VE, and a potential early stop for efficacy or futility.  In the event that efficacy is 
demonstrated at the interim analysis, enrollment may continue in order to complete the safety 
evaluations in this surgical population. 
There are 5 scheduled study visits and 1 scheduled telephone contact during 6 to 8 months of 
subject participation.  Study-eligible subjects who provided consent will be randomized in a 
1:1 ratio to receive a single dose of SA4Ag or placebo at Visit 1, which occurs 10 to 60 days 
prior to undergoing elective open posterior spinal fusion procedures with multilevel 
instrumentation (index surgical procedure).  Visit 2 is a longitudinal visit and is to monitor 
the index hospital admission period from the day of surgery (Day 1) until the day of 
discharge.  A telephone contact with the subject will occur on Day 21, while postoperative 
evaluation study visits will occur on Day 42, Day 90, and Day 180 after surgery. 
Unscheduled telephone contacts will be conducted for assessment of severe local reactions, 
severe fever, and severe systemic events after vaccination.  Severe fever and severe local 
reactions may warrant an unscheduled severe local reaction or fever assessment visit. 
Following the index hospital admission, unscheduled visits will be conducted for assessment 
of suspected BSI and/or SSI events, and to assess hospitalization(s) subsequent to the index 
hospital admission. 

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Staphylococcus aureus 4-Antigen Vaccine (SA4Ag) (PF-06290510)  
B3451002 
Final Protocol Amendment 4, 05 February 2018 
 
 
Page 18 
Immunogenicity: Geometric mean titers (GMTs) and geometric mean fold rises (GMFRs) 
relative to baseline, and corresponding 95% confidence intervals (CIs), will be descriptively 
summarized at each visit by vaccine group. 
• AEs will be summarized in each vaccine group for the following intervals: 
• From the day of vaccination (Day -60 to Day -10) until the day of surgery (Day 1) 
• From the day of surgery (Day 1) until the Day 42 postoperative evaluation  
• From the day of vaccination (Day -60 to Day -10) until the Day 42 postoperative 
evaluation 
• From the Day 42 postoperative evaluation until the Day 180 postoperative evaluation 
(newly diagnosed chronic medical disorders) 
• From the day of vaccination (Day -60 to Day -10) until the Day 180 postoperative 
evaluation (SAEs) 
AEs will be summarized using 3-tier methodology.  Local reactions and systemic events 
reported in the electronic diary (e-diary) will be summarized by the maximum severity across 
the 10-day observation period. 
 

Staphylococcus aureus 4-Antigen Vaccine (SA4Ag) (PF-06290510)  
B3451002 
Final Protocol Amendment 4, 05 February 2018 
 
PFIZER CONFIDENTIAL 
Page 19 
SCHEDULE OF PRIMARY ACTIVITIES 
The Schedule of Primary Activities table provides an overview of the protocol visits and procedures.  Refer to the Study Procedures 
and Assessments sections of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed below in order to conduct evaluations or assessments 
required to protect the well-being of the subject. 
Table 1. 
Schedule of Primary Activities 
Visit ID 
1 
2 
3 
4 
5 
6 
Protocol Activity 
Study 
Enrollment 
and 
Day of 
Vaccination 
Index Hospital Admissiona 
Day 21 
Telephone 
Contact 
Day 42 
Post- 
operative 
Evaluation 
Day 90 
Post- 
operative 
Evaluation 
Day 180 
Post-
operative 
Evaluationc 
Day of 
Surgery 
Day After 
Surgery 
Day of 
Dischargeb 
Study Stage 
Vaccination 
Stage 
Surgery Stage 
Study Day 
Day -60 to 
Day -10 
Day 1 
Day 2 
(Day 
Variable) 
Day 21 
Day 42 
Day 90 
Day 180 
Visit Window 
Day -60 to 
Day -10 
N/A 
N/A 
N/A 
Day 18 to 
Day 26 
Day 35 to 
Day 49 
Day 83 to 
Day 97 
Day 178 to 
Day 192 
Informed consentd 
X 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
Medical and surgical history 
X 
 
 
 
 
 
 
 
Smoking/alcohol use 
X 
 
 
 
 
 
 
 
Record concomitant vaccinations and 
medicationse 
X 
X 
 
X 
X 
X 
X 
X 
Record height and weight 
X 
 
 
 
 
 
 
 
Vital signsf 
X 
 
 
 
 
 
 
 
Blood glucoseg 
 
X 
X 
 
 
 
 
 
Physical examinationh 
X 
 
 
 
 
 
 
 
Pregnancy testi 
X 
 
 
 
 
 
 
 
Contraceptive use discussion 
X 
 
 
 
 
 
 
 
Inclusion and exclusion criteria 
X 
 
 
 
 
 
 
 

Staphylococcus aureus 4-Antigen Vaccine (SA4Ag) (PF-06290510)  
B3451002 
Final Protocol Amendment 4, 05 February 2018 
 
PFIZER CONFIDENTIAL 
Page 20 
Table 1. 
Schedule of Primary Activities 
Visit ID 
1 
2 
3 
4 
5 
6 
Protocol Activity 
Study 
Enrollment 
and 
Day of 
Vaccination 
Index Hospital Admissiona 
Day 21 
Telephone 
Contact 
Day 42 
Post- 
operative 
Evaluation 
Day 90 
Post- 
operative 
Evaluation 
Day 180 
Post-
operative 
Evaluationc 
Day of 
Surgery 
Day After 
Surgery 
Day of 
Dischargeb 
Study Stage 
Vaccination 
Stage 
Surgery Stage 
Study Day 
Day -60 to 
Day -10 
Day 1 
Day 2 
(Day 
Variable) 
Day 21 
Day 42 
Day 90 
Day 180 
Visit Window 
Day -60 to 
Day -10 
N/A 
N/A 
N/A 
Day 18 to 
Day 26 
Day 35 to 
Day 49 
Day 83 to 
Day 97 
Day 178 to 
Day 192 
Record planned index surgical procedurej 
X 
 
 
 
 
 
 
 
Record actual index surgical procedurej 
 
 
X 
 
 
 
 
 
Charlson comorbidity  score 
X 
 
 
 
 
 
 
 
Temporary vaccination delay criteria 
X 
 
 
 
 
 
 
 
Immunogenicity blood drawk 
24 mL 
24 mL 
 
24 mL 
 
24 mL 
24 mL 
24 mL 
Nasal and oropharyngeal S aureus 
colonization swab collectionk 
X 
X 
 
X 
 
X 
X 
X 
Randomization 
X 
 
 
 
 
 
 
 
Investigational product administration 
X 
 
 
 
 
 
 
 
Postvaccination observation (30 minutes), 
assessment of acute reactions 
X 
 
 
 
 
 
 
 
E-diary training, baseline data entry by 
subject; dispense measuring device 
(eg caliper), thermometer, study 
participant/emergency contact card 
X 
 
 
 
 
 
 
 
Review subject reminders & instructionsl 
X 
 
 
X 
X 
X 
X 
 
Schedule next study visit 
X 
 
 
X 
 
X 
X 
 
Daily event monitoringm 
 
 
--------------X-------------- 
 
 
 
 
Monitor  for  protocol-defined infections 
 
 
See Daily event 
monitoring 
X 
X 
X 
X 
Review e-diary data, collect e-diaryn 
 
--------------------X---------------------- 
 
 
 
 
Preoperative data collection 
 
X 
 
 
 
 
 
 
Perioperative data collection 
 
 
X 
X 
 
 
 
 

Staphylococcus aureus 4-Antigen Vaccine (SA4Ag) (PF-06290510)  
B3451002 
Final Protocol Amendment 4, 05 February 2018 
 
PFIZER CONFIDENTIAL 
Page 21 
Table 1. 
Schedule of Primary Activities 
Visit ID 
1 
2 
3 
4 
5 
6 
Protocol Activity 
Study 
Enrollment 
and 
Day of 
Vaccination 
Index Hospital Admissiona 
Day 21 
Telephone 
Contact 
Day 42 
Post- 
operative 
Evaluation 
Day 90 
Post- 
operative 
Evaluation 
Day 180 
Post-
operative 
Evaluationc 
Day of 
Surgery 
Day After 
Surgery 
Day of 
Dischargeb 
Study Stage 
Vaccination 
Stage 
Surgery Stage 
Study Day 
Day -60 to 
Day -10 
Day 1 
Day 2 
(Day 
Variable) 
Day 21 
Day 42 
Day 90 
Day 180 
Visit Window 
Day -60 to 
Day -10 
N/A 
N/A 
N/A 
Day 18 to 
Day 26 
Day 35 to 
Day 49 
Day 83 to 
Day 97 
Day 178 to 
Day 192 
Healthcare utilization data collectiono 
 
 
 
X 
X 
X 
X 
X 
Abbreviations: AE = adverse event; e-diary = electronic diary; N/A = not applicable; PDI = protocol-defined infection; S aureus = Staphylococcus aureus. 
a. 
Index hospital admission: The day of admission is either prior to or the day of surgery.  In either case, the day of surgery is defined as Day 1. 
b. If the index hospital admission day of discharge coincides with the day after surgery (Day 2), Visit 3, Visit 4, or Visit 5, the study procedures may be 
performed as a single visit.  Procedural windows are described in Section 6.3.1.3. 
c. 
May be conducted by telephone provided that arrangements are made for blood and colonization sample collection (eg, home nursing visit). 
d. Informed consent must be obtained before the conduct of any study procedures. 
e. 
Includes nonstudy vaccines, antibiotics, systemic and intraspinal steroids, and blood products.  Refer to Section 5.4. 
f. 
Vital signs include temperature (°C or °F), pulse rate, respiratory rate, and blood pressure. 
g. Serum or capillary; fasting value required preoperatively. 
h. Physical examination includes general appearance; musculoskeletal; skin; head, eyes, ears, nose, and throat; heart; lungs; abdominal; neurological; and 
lymph nodes. 
i. 
Only applicable for women of childbearing potential.  Pregnancy testing may be performed on urine or serum samples. 
j. 
Record the surgical indication and the planned index surgical procedure.  Postoperatively, record the actual index surgical procedure. 
k. Immunogenicity blood draw and colonization swabs must be collected before vaccination at Visit 1 (window: 7 days) and before surgery at Visit 2. 
l. 
Refer to the respective study visit as detailed in Section 6. 
m. Daily observation for PDIs, AEs, and organ failure events as detailed in Section 6.3.1.2.1. 
n. The e-diary should be collected and AE data reviewed with the subject prior to surgery. 
o. Refer to Appendix 4. 
 

Staphylococcus aureus 4-Antigen Vaccine (SA4Ag) (PF-06290510)  
B3451002 
Final Protocol Amendment 4, 05 February 2018 
 
PFIZER CONFIDENTIAL 
Page 22 
SCHEDULE OF ACTIVITIES FOR ADVERSE AND STUDY EVENT REPORTING 
The Schedule of Activities for Adverse and Study Event Reporting table provides an overview of the protocol safety reporting 
requirements.  Refer to the Study Procedures (Section 6.1) and Assessments (Section 7) sections of the protocol for detailed 
information on each procedure and assessment required for compliance with the protocol. 
Table 2. 
Schedule of Activities for Adverse and Study Event Reporting 
Visit ID 
1 
2 
3 
4 
5 
6 
Protocol Activity 
Enrollment and 
Day of 
Vaccination 
Index Hospital Admission 
Day 21 
Telephone 
Contact 
Day 42 
Postoperative 
Evaluation 
Day 90 
Postoperative 
Evaluation 
Day 180 
Postoperative 
Evaluation 
Day of 
Surgery 
Day After 
Surgery 
Day of 
Discharge 
Study Day 
Day -60 to 
Day -10 
Day 1 
Day 2 
(Day 
Variable) 
Day 21 
Day 42 
Day 90 
Day 180 
Visit Window 
Day -60 to 
Day -10 
N/A 
N/A 
N/A 
Day 18 to 
Day 26 
Day 35 to 
Day 49 
Day 83 to 
Day 97 
Day 178 to 
Day 192 
Local reactions and systemic 
events collected in the 
e-diary 
From the day of 
vaccination for a 
total of 10 daysa 
 
Adverse events 
AEs from informed consent to the Day 42 postoperative evaluation 
 
 
Newly diagnosed chronic medical disorders 
from the Day 42 postoperative evaluation to 
the Day 180 postoperative evaluation 
Serious adverse events 
SAEs from informed consent to the Day 180 postoperative evaluation 
Protocol-defined infection 
events 
 
PDI events from after surgery to the Day 180 postoperative evaluation 
Organ failure events 
 
Organ failure events from  after surgery to Day 180 
(applicable during any hospitalization) 
Abbreviations: AE = adverse event; N/A = not applicable; PDI = protocol-defined infection; SAE = serious adverse event. 
a. 
If surgery occurs on Day 10 after vaccination, the e-diary need not be completed on the day of surgery. 
 

Staphylococcus aureus 4-Antigen Vaccine (SA4Ag) (PF-06290510)  
B3451002 
Final Protocol Amendment 4, 05 February 2018 
 
PFIZER CONFIDENTIAL 
Page 23 
UNSCHEDULED STUDY VISITS, CONTACTS, AND SURVEILLANCE PERIODS 
Table 3 shows the list of unscheduled visits that are to occur when certain conditions are met.  Refer to Table 4 for unscheduled visit 
procedures. 
Table 3. 
Unscheduled Study Visits, Contacts, and Surveillance Periods 
Visit ID 
1 
2 
3 
4 
5 
6 
Protocol Activity 
Enrollment and 
Day of 
Vaccination 
Index Hospital Admission 
 
Telephone 
Call 
Day 42 
Postoperative 
Evaluation 
Day 90 
Postoperative 
Evaluation 
Day 180 
Postoperative 
Evaluation 
Day of 
Surgery 
Day After 
Surgery 
Day of 
Discharge 
Study Day 
Day -60 to  
Day -10 
Day 1 
Day 2 
(Day 
Variable) 
Day 21 
Day 42 
Day 90 
Day 180 
Visit Window 
Day -60 to  
Day -10 
N/A 
N/A 
N/A 
Day 18 to 
Day 26 
Day 35 to 
Day 49 
Day 83 to 
Day 97 
Day 178 to 
Day 192 
UNSCHEDULED VISITS AND CONTACTS 
Severe local reaction or  
fever telephone contact 
(Section 6.4.1.1.1) 
May occur 
within 10 days 
after vaccination 
 
Severe systemic event 
telephone contact 
(Section 6.4.1.1.2) 
May occur 
within 10 days 
after vaccination 
 
Severe local reaction or fever 
assessment visit 
(Section 6.4.1.2) 
May occur 
within 10 days 
after vaccination 
 
BSI/SSI assessment visit 
(Section 6.4.2) 
 
• 
May occur postoperatively during the index hospital admission 
• 
May occur after discharge from the index hospital 
Hospitalization visit 
(Section 6.4.3) 
 
May occur at any time after discharge from the index hospital 
Abbreviations: BSI = bloodstream infection; N/A = not applicable; SSI = surgical-site infection. 
 

Staphylococcus aureus 4-Antigen Vaccine (SA4Ag) (PF-06290510)  
B3451002 
Final Protocol Amendment 4, 05 February 2018 
 
PFIZER CONFIDENTIAL 
Page 24 
STUDY PROCEDURES ASSOCIATED WITH UNSCHEDULED STUDY VISITS 
The Study Procedures Associated With Unscheduled Study Visits table provides an overview of the unscheduled visit requirements.  
Refer to the Study Procedures (Section 6.4) and Assessments (Section 7) sections of the protocol for detailed information on each 
procedure and assessment required for compliance with the protocol. 
Table 4. 
Study Procedures Associated With Unscheduled Study Visits 
Protocol Procedure 
Severe Local 
Reaction or 
Fever 
Telephone 
Contact 
Severe 
Systemic 
Event 
Telephone 
Contact 
Severe Local 
Reaction or 
Fever 
Assessment 
Visit 
BSI/SSI 
Assessment 
Visit 
Hospital-
ization  
Visit 
Determine whether a severe local reaction or fever assessment visit is required 
X 
 
 
 
 
Determine whether the severe systemic event meets Grade 4 and/or SAE criteria 
 
X 
 
 
 
Measure temperature (°C or °F) 
 
 
X 
 
 
Measure redness and swelling 
 
 
X 
 
 
Grade pain 
 
 
X 
 
 
Assess lymphadenopathy 
 
 
X 
 
 
Collect colonization swab samples from the nose and throat 
 
 
 
X 
 
Collect blood culture samples 
 
 
 
X 
 
For an SSI that is operatively incised and/or spontaneously draining, collect a 
wound culture swab 
 
 
 
X 
 
Collect a blood sample for immunogenicity 
 
 
 
24 mL 
24 mLa 
Record antibiotic therapy 
 
 
 
X 
X 
Adverse event collection as appropriate 
 
 
 
X 
X 
Collect healthcare utilization data 
 
 
 
 
X 
If a PDI event is suspected, complete PDI event requirementsb 
 
 
 
X 
X 
If a BSI and/or SSI is identified or suspected, complete all procedures for a BSI/SSI 
assessment visitc 
 
 
 
 
X 
Assess for organ failured 
 
 
 
 
X 
Perioperative data collection for index surgery reoperation and revision 
 
 
 
 
X 
Abbreviations: BSI = bloodstream infection; PDI = protocol-defined infection; SAE = serious adverse event; SSI = surgical-site infection. 
a. 
Collect only if subject has multiple-organ failure. 
b. Refer to Section 7.1.1 for PDI events. 
c. 
Refer to Section 6.4.2 for the BSI/SSI assessment visit. 
d. Refer to Section 7.2.3 for assessment of organ failure. 

Staphylococcus aureus 4-Antigen Vaccine (SA4Ag) (PF-06290510)  
B3451002 
Final Protocol Amendment 4, 05 February 2018 
 
 
Page 25 
TABLE OF CONTENTS 
ABBREVIATIONS ...................................................................................................................9 
PROTOCOL SUMMARY .......................................................................................................12 
INTRODUCTION ...................................................................................................................12 
LIST OF TABLES ...................................................................................................................30 
LIST OF FIGURES .................................................................................................................31 
APPENDICES .........................................................................................................................31 
1. INTRODUCTION ...............................................................................................................32 
1.1. Mechanism of Action/Indication .............................................................................32 
1.2. Background and Rationale ......................................................................................32 
1.2.1. Healthcare-Associated S aureus Disease ....................................................32 
1.2.1.1. Postoperative S aureus Disease .................................................33 
1.2.2. Rationale for Evaluation of SA4Ag Efficacy in the Prevention of 
Postoperative S aureus Disease in Patients Undergoing Elective Surgery ......34 
1.2.3. Vaccine Antigen Composition ....................................................................35 
1.2.4. Clinical Experience .....................................................................................35 
1.2.4.1. First-in-Human Trial of SA3Ag (Phase 1, Study 
B2251002) .........................................................................................35 
1.2.4.2. First-in-Human Trial of SA4Ag (Phase 1/2a, Study 
B3451001) .........................................................................................36 
1.2.4.3. Trial of SA4Ag in Elderly Subjects (Phase 1/2a, Study 
B3451011) .........................................................................................36 
1.2.4.4. Duration-of-Immunogenicity Study (Phase 2, Study 
B3451014) .........................................................................................36 
1.2.5. Summary of Benefit-Risk Assessment .......................................................37 
1.3. rP305A Dose Level Selection for SA4Ag Phase 2b Evaluation .............................37 
2. STUDY OBJECTIVES AND ENDPOINTS .......................................................................38 
2.1. Primary Efficacy Objective .....................................................................................39 
2.1.1. Primary Efficacy Endpoint .........................................................................39 
2.2. Primary Safety Objective ........................................................................................39 
2.2.1. Primary Safety Endpoints ...........................................................................39 
2.3. Secondary Efficacy Objectives ...............................................................................40 
2.3.1. Secondary Efficacy Endpoints ....................................................................40 

Staphylococcus aureus 4-Antigen Vaccine (SA4Ag) (PF-06290510)  
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Final Protocol Amendment 4, 05 February 2018 
 
 
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2.4. Exploratory Objectives ............................................................................................40 
2.4.1. Exploratory Endpoints ................................................................................41 
2.5. Endpoint Adjudication ............................................................................................42 
3. STUDY DESIGN.................................................................................................................43 
3.1. Subject Numbers and Duration of Subject Participation ........................................44 
3.2. Study Population .....................................................................................................44 
3.2.1. Index Study Procedure Definitions .............................................................44 
3.2.2. Surgical Indications ....................................................................................45 
3.2.2.1. Permitted Indications for the Index Surgical Procedure ...........45 
3.2.2.2. Prohibited Indications for the Index Surgical Procedure ..........45 
3.2.2.3. Previous or Revisional Spinal Surgery ......................................46 
4. SUBJECT SELECTION ......................................................................................................46 
4.1. Inclusion Criteria .....................................................................................................46 
4.2. Exclusion Criteria ....................................................................................................47 
4.3. Criteria for Temporarily Delaying Vaccine Administration ...................................48 
4.4. Lifestyle Guidelines ................................................................................................49 
4.5. Sponsor’s Qualified Medical Personnel ..................................................................50 
4.5.1. Study Participant/Emergency Contact Card ...............................................50 
5. INVESTIGATIONAL PRODUCTS ...................................................................................50 
5.1. Allocation to Investigational Product ......................................................................50 
5.2. Breaking the Blind ..................................................................................................51 
5.3. Investigational Product Supplies .............................................................................51 
5.3.1. Formulation and Packaging ........................................................................51 
5.3.1.1. Staphylococcus aureus 4-Antigen Vaccine ...............................51 
5.3.1.2. Placebo ......................................................................................52 
5.3.2. Preparation and Dispensing ........................................................................52 
5.3.3. Administration ............................................................................................52 
5.3.4. Compliance .................................................................................................53 
5.3.5. Investigational Product Storage ..................................................................53 
5.3.6. Investigational Product Accountability ......................................................53 
5.4. Concomitant Medication(s), Vaccinations, and Blood Products ............................54 
5.4.1. Restrictions to Concomitant Vaccinations and Medications ......................54 

Staphylococcus aureus 4-Antigen Vaccine (SA4Ag) (PF-06290510)  
B3451002 
Final Protocol Amendment 4, 05 February 2018 
 
 
Page 27 
6. STUDY PROCEDURES .....................................................................................................55 
6.1. Scheduled Study Visits ............................................................................................55 
6.2. Stage 1: Vaccination Stage ......................................................................................55 
6.2.1. Visit 1, Day of Vaccination (Day -60 to Day -10) .....................................55 
6.3. Stage 2: Surgery Stage ............................................................................................58 
6.3.1. Visit 2, Index Hospital Admission ..............................................................58 
6.3.1.1. Day of Surgery (Day 1) .............................................................58 
6.3.1.2. Day After Surgery (Day 2) ........................................................58 
6.3.1.3. Day of Hospital Discharge (Day Variable) ...............................60 
6.3.2. Visit 3, Day 21 Telephone Contact (Window: Days 18-26) ......................60 
6.3.3. Visit 4, Day 42 Postoperative Evaluation (Window: Days 35-49) .............61 
6.3.4. Visit 5, Day 90 Postoperative Evaluation (Window: Days 83-97) .............62 
6.3.5. Visit 6, Day 180 Postoperative Evaluation (Window: Days 178-192) .......62 
6.4. Unscheduled Study Visits .......................................................................................63 
6.4.1. Assessment of Postvaccination Severe Reactions and Systemic 
Events ...............................................................................................................63 
6.4.1.1. Unscheduled Telephone Contacts .............................................63 
6.4.1.2. Severe Local Reaction or Fever Assessment Visit (Up to 
10 Days After Study Vaccination) ....................................................64 
6.4.2. BSI/SSI Assessment Visit ...........................................................................64 
6.4.3. Hospitalization Visit ...................................................................................65 
6.5. Subject Withdrawal and Safety Follow-up .............................................................66 
6.5.1. Subject Withdrawal From the Study ...........................................................66 
6.5.2. Safety Follow-up ........................................................................................67 
7. ASSESSMENTS ..................................................................................................................67 
7.1. Efficacy Assessments ..............................................................................................68 
7.1.1. PDI Events ..................................................................................................68 
7.1.1.1. BSI and SSI Events ...................................................................69 
7.1.1.2. ISA Events .................................................................................69 
7.2. Safety Assessments .................................................................................................71 
7.2.1. Local Reactions and Systemic Events ........................................................71 
7.2.1.1. Electronic Diary ........................................................................71 
7.2.1.2. Grading Scales for Local Reactions and Systemic Events ........72 

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7.2.1.3. Local Reactions .........................................................................72 
7.2.1.4. Systemic Events ........................................................................73 
7.2.1.5. Fever ..........................................................................................74 
7.2.2. Preoperative and Perioperative Subject Status Assessments ......................75 
7.2.2.1. Charlson Comorbidity Index .....................................................75 
7.2.2.2. American Society of Anesthesiologists (ASA) Physical 
Status Classification Score ................................................................75 
7.2.3. Assessment of Organ Failure ......................................................................76 
7.2.3.1. Assessment of Deaths ................................................................78 
7.2.4. Pregnancy Testing ......................................................................................78 
7.3. Microbiology Assessments .....................................................................................78 
7.3.1. Microbiological Laboratory Procedures .....................................................78 
7.3.2. Blood Cultures ............................................................................................79 
7.3.3. Operative (Surgical Site) Wound Cultures .................................................79 
7.3.4. Swabs for Colonization ...............................................................................79 
7.4. Immunogenicity Assessments .................................................................................79 
7.5. Biological Samples ..................................................................................................80 
7.6. Healthcare-Utilization Assessment .........................................................................80 
8. ADVERSE EVENT REPORTING......................................................................................80 
8.1. Adverse Events ........................................................................................................80 
8.2. Reporting Period .....................................................................................................81 
8.3. Definition of an Adverse Event ...............................................................................81 
8.4. Medication Errors ....................................................................................................82 
8.5. Abnormal Test Findings ..........................................................................................82 
8.6. Serious Adverse Events ...........................................................................................83 
8.6.1. Protocol-Specified Serious Adverse Events ...............................................84 
8.6.2. Potential Cases of Drug-Induced Liver Injury ............................................85 
8.7. Hospitalization ........................................................................................................86 
8.8. Severity Assessment ................................................................................................88 
8.9. Causality Assessment ..............................................................................................88 
8.10. Exposure During Pregnancy ..................................................................................89 
8.11. Occupational Exposure .........................................................................................90 

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8.12. Withdrawal Due to Adverse Events (See Also the Section on Subject 
Withdrawal) ...............................................................................................................90 
8.13. Eliciting Adverse Event Information ....................................................................90 
8.14. Reporting Requirements ........................................................................................90 
8.14.1. Serious Adverse Event Reporting Requirements .....................................90 
8.14.2. Nonserious Adverse Event Reporting Requirements ...............................91 
8.14.3. Medical Device Complaint Reporting Requirements ...............................91 
8.14.4. Sponsor’s Reporting Requirements to Regulatory Authorities ................92 
9. DATA ANALYSIS/STATISTICAL METHODS ...............................................................92 
9.1. Hypotheses and Acceptance Criteria .......................................................................92 
9.2. Sample Size Determination .....................................................................................93 
9.3. Efficacy Analysis ....................................................................................................95 
9.3.1. Efficacy Analysis Populations ....................................................................95 
9.3.2. Analysis of the Primary Endpoint ...............................................................95 
9.3.2.1. Supplementary Analysis ............................................................96 
9.3.3. Analysis of Secondary Endpoints ...............................................................96 
9.3.3.1. Efficacy .....................................................................................96 
9.3.4. Analysis of Exploratory Endpoints .............................................................96 
9.3.4.1. Immunogenicity Analysis .........................................................96 
9.3.4.2. Colonization Analysis ...............................................................98 
9.4. Other Analysis .........................................................................................................99 
9.4.1. Demographics and Clinical Characteristics ................................................99 
9.4.2. Healthcare Utilization .................................................................................99 
9.5. Safety Analysis ........................................................................................................99 
9.6. Analysis Timing ....................................................................................................101 
9.7. Data Monitoring Committee .................................................................................101 
10. QUALITY CONTROL AND QUALITY ASSURANCE ...............................................102 
11. DATA HANDLING AND RECORD KEEPING ...........................................................102 
11.1. Case Report Forms/Electronic Data Record .......................................................102 
11.2. Record Retention .................................................................................................103 
12. ETHICS............................................................................................................................103 
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ..........103 

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12.2. Ethical Conduct of the Study ..............................................................................104 
12.3. Subject Information and Consent ........................................................................104 
12.4. Subject Recruitment ............................................................................................104 
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .........................................................................................................................105 
13. DEFINITION OF END OF TRIAL .................................................................................105 
13.1. End of Trial in a Member State ...........................................................................105 
13.2. End of Trial in All Other Participating Countries ...............................................105 
14. SPONSOR DISCONTINUATION CRITERIA ..............................................................105 
15. PUBLICATION OF STUDY RESULTS ........................................................................105 
15.1. Communication of Results by Pfizer ..................................................................105 
15.2. Publications by Investigators ..............................................................................106 
16. REFERENCES ................................................................................................................108 
 
LIST OF TABLES 
Table 1. 
Schedule of Primary Activities .............................................................................19 
Table 2. 
Schedule of Activities for Adverse and Study Event Reporting ..........................22 
Table 3. 
Unscheduled Study Visits, Contacts, and Surveillance Periods ...........................23 
Table 4. 
Study Procedures Associated With Unscheduled Study Visits ............................24 
Table 5. 
Staphylococcus aureus Vaccine Antigen Levels ..................................................35 
Table 6. 
BSI and SSI Events Requiring an Unscheduled Assessment Visit ......................69 
Table 7. 
PDIs Contributing to ISA Disease (in Addition to BSI and Deep Incisional 
and/or Organ/Space SSI) ......................................................................................70 
Table 8. 
Other Invasive Infections ......................................................................................70 
Table 9. 
Local Reaction Grading Scale ..............................................................................73 
Table 10. Systemic Event Grading Scale..............................................................................74 
Table 11. Scale for Fever ......................................................................................................74 
Table 12. Charlson Comorbidity Score ................................................................................75 
Table 13. American Society of Anesthesiologists (ASA) Physical Status 
Classification ........................................................................................................76 
Table 14. Sequential Organ Failure Assessment Score ........................................................77 
Table 15. Estimated Efficacy and Associated Confidence Intervals for a Select 
Number of SA4Ag Cases ......................................................................................95 

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LIST OF FIGURES 
Figure 1. 
Protocol-Defined Infections (Venn Diagram) ......................................................68 
Figure 2. 
Protocol-Specified SAE Reporting .......................................................................85 
Figure 3. 
Probability of Rejecting the Null Hypothesis of No Efficacy for a Range of 
True Efficacy Values at the Final Analysis (48 Cases) ........................................94 
 
APPENDICES 
Appendix 1. Protocol-Defined Infection Events ....................................................................113 
Appendix 2. Preoperative Assessment ...................................................................................126 
Appendix 3. Perioperative Assessment..................................................................................126 
Appendix 4. Healthcare-Utilization Assessment ...................................................................127 
Appendix 5. Country-Specific Appendix – Applicable to France Only ................................128 
Appendix 6. Country-Specific Appendix – Applicable to Japan Only ..................................129 
 

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1. INTRODUCTION 
Staphylococcus aureus (S aureus) is a gram-positive coccus and a commensal organism that 
colonizes the nares, axillae, pharynx, and other mucosal and skin surfaces of approximately 
20% to 50% of humans.1,2  S aureus is an opportunistic pathogen2 and a leading cause of 
healthcare-associated infections (HAIs), including bloodstream infection (BSI), surgical-site 
infection (SSI), and hospital-acquired pneumonia (HAP),2,3 and is an increasingly common 
cause of community-associated infections in the United States (US), Europe, and globally.  
Among North American, Latin American, European, and Western Pacific nations, S aureus is 
recognized as the leading cause of HAIs.4  In the United States, S aureus is estimated to 
represent 15% of all HAIs.5  In the outpatient setting, S aureus has been estimated to be 
responsible for 11.6 million skin and soft tissue infections (SSTIs) annually in the United 
States, affecting 411/10,000 persons.6  Likewise, globally S aureus is the predominant cause 
of SSTI, representing 45% of North American, 34% of Latin American, and 38% of 
European isolates.7 
The widespread disease manifestations of S aureus and its substantial burden to the 
healthcare system present a serious unmet medical need.  Infections due to 
methicillin-sensitive S aureus (MSSA) as well as those due to methicillin-resistant S aureus 
(MRSA) contribute to disease morbidity, mortality, and economic burden, as well as the 
increasing need for more rigorous infection control practices.  Despite the availability of 
antibiotics indicated for the prevention and treatment of S aureus infections, outcomes 
remain suboptimal for many patients.2  Given the failure of the current standards of care to 
address the global epidemic of S aureus disease, the need for a preventive vaccine is clear. 
1.1. Mechanism of Action/Indication 
S aureus 4-antigen vaccine (SA4Ag) is intended for active immunization for the prevention 
of postoperative invasive disease caused by S aureus in adults 18 years of age and older who 
are undergoing elective surgery. 
1.2. Background and Rationale 
1.2.1. Healthcare-Associated S aureus Disease 
S aureus is among the most prevalent pathogens responsible for HAIs in numerous 
healthcare settings.  Based on data from the Nationwide Inpatient Sample (NIS), from 2000 
to 2001 approximately 0.8% of all US hospitalizations involved S aureus infections,8 and in 
2001, 1.1% of US surgical hospitalizations9 involved S aureus infections.  Inpatients with 
S aureus infection have an estimated 3 times the length of hospital stay and 5 times the risk 
of in-hospital death as patients without S aureus infection.8  The risk of developing S aureus 
infection is dependent on factors related to both the patient and the type of healthcare 
exposure.  At-risk populations include patients undergoing surgery, patients with end-stage 
renal disease, patients in intensive care units (ICUs), transplant recipients, and other 
immunocompromised individuals.10,11,12  Medically or surgically managed conditions 
associated with increased exposure to the healthcare system place individuals at further risk 
of acquiring healthcare-associated S aureus infection.13,14 

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S aureus has been demonstrated to be the leading cause of BSI, responsible for 20% to 26% 
of infections overall among North American, European, and Latin American countries,15 and 
for 19% of infections among developing countries globally.16  A large international study 
recently estimated the population incidence of S aureus BSI to be 26.1/100,000 among 
several developed nations.17  S aureus is the leading cause of both hospital-acquired (34%) 
and ventilator-associated (27%) pneumonia,18 and is commonly identified as the predominant 
organism isolated among intensive care patients12,19 and hospitalized pediatric patients.20 
1.2.1.1. Postoperative S aureus Disease 
SSI is an important cause of patient morbidity and healthcare cost, representing 
approximately 38% of infectious complications among surgical patients in the United 
States.21  Based on 2012 US dollars, each SSI is estimated to result in overall healthcare costs 
of $20,785.  Collectively, SSIs account for 34% of the estimated $9.8 billion burden of US 
HAIs.22  About 2% to 5%23 of US surgeries are complicated by SSI, of which S aureus is 
estimated to be responsible for at least 20% overall.21,22,23,24,25  SSI can result in secondary 
BSI which places the patient at substantially greater risk of postoperative morbidity and 
mortality.  S aureus SSI is far more likely to result in secondary BSI, representing 66% of 
such cases.26 
1.2.1.1.1. Patient Risk Factors for Postoperative Infection 
The individual risk of acquiring postoperative S aureus infection, while directly attributable 
to the surgical incision itself, can be influenced by both patient and procedural factors across 
the spectrum of surgical practice.  Advanced age,27,28 diabetes mellitus,29 obesity,30-33 and 
tobacco use34 are among the most relevant of numerous patient risk factors for acquiring 
postoperative infection.  The incidence of healthcare-associated S aureus infection correlates 
directly with age, as demonstrated by an overall MRSA incidence of 31.8/100,000 for the 
general US population but 127.7/100,000 for those aged 65 years and older.35  Advanced age 
is likewise a well-established risk factor for postoperative infection.27,28  Hyperglycemia has 
been shown to negatively impact neutrophil chemotactic, phagocytic, and bactericidal 
activity29 and is associated with increased risk of postoperative infection among 
cardiothoracic36 and noncardiothoracic37,38 surgery populations.  Obesity is associated with 
comorbidities such as insulin resistance, hyperglycemia, and metabolic syndrome, and has 
substantial direct impacts on the surgical wound, such that obese patients undergoing spinal, 
arthroplasty, general, cardiothoracic, and vascular surgeries are at substantial risk of 
postoperative infection relative to nonobese patients.27,30-33,39,40  Tobacco use is a 
well-established risk factor for postoperative infectious as well as noninfectious 
complications across a broad range of surgeries.  The profound multisystem effects of 
tobacco use result in higher rates of SSI, wound dehiscence and rupture, and delayed wound 
healing, in addition to greater risk of pulmonary infection.34,41 
1.2.1.1.2. Procedural Risk Factors for Postoperative Infection 
Across the spectrum of surgical practice, wound-related factors such as wound class, 
operative duration, suture length, implantation of prosthetic material, and insertion of drains 
may increase the risk of SSI.42-45 

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Based on the large body of evidence that supports preoperative shaving, patient hypothermia, 
and hyperglycemia as consistent risk factors for infection across surgical practice, the 
Surgical Care Improvement Project (SCIP), an initiative of the US Centers for Disease 
Control and Prevention (CDC), recommends preoperative hair removal using clippers and 
avoidance of shaving, and maintenance of patient normothermia and euglycemia during the 
first 48 postoperative hours.46  Perioperative hypothermia is associated with significantly 
increased SSI risk thought to result from a decrease in subcutaneous tissue perfusion 
mediated by vasoconstriction.47  For both diabetic and nondiabetic patients, perioperative 
hyperglycemia is associated with increased length of hospital and ICU stay, increased risk of 
bloodstream, respiratory, and urinary tract infections, and increased risk of death.48 
1.2.2. Rationale for Evaluation of SA4Ag Efficacy in the Prevention of Postoperative 
S aureus Disease in Patients Undergoing Elective Surgery 
The incidence of postoperative S aureus disease in surgical patients has led to vigorous 
efforts to develop specific preventive and therapeutic measures directed against this 
pathogen, including intranasal administration of mupirocin and chlorhexidine bathing to 
eliminate carriage, and the administration of prophylactic antibiotics prior to surgery.46,49  
Despite these efforts, postoperative S aureus infection remains a common and serious 
occurrence.  Unlike the long-term risk of healthcare-associated invasive S aureus (ISA) 
disease in patients with chronic medical conditions, postoperative ISA disease in the elective 
surgery population is usually directly attributable to the surgical incision.  In this setting, high 
ISA disease incidence and burden are encountered during a relatively brief and predictable 
time frame.  Elective surgery therefore presents an appropriate setting for evaluation of the 
safety and efficacy of investigational vaccine for prevention of ISA disease among 
immunocompetent patients. 
Among elective surgery populations and procedures, investigational vaccine efficacy (VE) is 
ideally evaluated in a clearly defined elective surgery population with well-characterized 
patient demographics and comorbidities, and procedural characteristics that are highly 
representative of a broad array of elective surgery populations with respect to risk factors and 
mechanisms of pathogenesis of postoperative S aureus disease.  The elective spinal surgery 
population is similar to other elective surgical populations with regard to both patient and 
procedural characteristics.  Elective spinal surgery is largely performed in patients with low 
overall morbidity, as demonstrated by Charlson comorbidity index (CCI) scores.50  Elective 
spinal surgery patients generally require a brief index hospitalization and experience a low 
incidence of postoperative morbidity and mortality in the absence of postoperative 
infection,51 facilitating evaluation of SA4Ag safety. 
The demographics and comorbidities associated with postoperative infection among elective 
spinal surgery patients are similar to those reported among other orthopedic and plastic 
surgery populations and among patients undergoing clean, general surgery.50  Spinal surgery 
involves surgical violation of anatomical layers, including the dermis, soft tissue, and fascial 
layers, as well as bony structures, frequently involving the implantation of prosthetic 
materials and bone grafting.  These procedural characteristics are common to arthroplasty 
and other elective orthopedic surgeries.  Clean abdominal, general, and plastic surgical 
procedures also involve the violation of dermal, soft tissue, and fascial planes where bacterial 

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inoculation leading to postoperative infection is most likely to occur, and often involve the 
implantation of prosthetic material (eg, hernia repair, breast reconstruction).  Despite these 
similar demographic and procedural characteristics, the incidence of postoperative ISA 
disease in patients undergoing elective spinal surgery is relatively high51,52 compared with 
other procedures such as arthroplasty.53  As such, this higher incidence of ISA disease will 
facilitate evaluation of SA4Ag efficacy in a clinical trial setting. 
1.2.3. Vaccine Antigen Composition 
Pfizer’s investigational SA4Ag is designed to be protective across the range of clinical 
S aureus disease isolates, including MSSA and MRSA, regardless of their antibiotic 
resistance profiles or geographical origin. 
SA4Ag contains the following 4 antigens, each of which elicits immune responses targeting 
surface-expressed, conserved, and globally represented S aureus components that are used by 
S aureus to facilitate infection: 
• CP5-CRM197 and CP8-CRM197: capsular polysaccharide serotype 5 (CP5) and 
serotype 8 (CP8), each conjugated to the nontoxic mutant form of diphtheria toxin, 
cross-reactive material 197 (CRM197); 
• rmClfA: a truncated recombinant form of clumping factor A (ClfA) with a single 
amino-acid substitution (Y338A) that abolishes human fibrinogen binding; and 
• rP305A: a recombinant form of the manganese transporter C (MntC) or lipoprotein 305A 
(LP305A); the recombinant protein is a nonlipidated form of MntC. 
The quantities of each vaccine antigen are shown in Table 5: 
Table 5. 
Staphylococcus aureus Vaccine Antigen Levels 
 
Antigen 
CP5-CRM197 
CP8-CRM197 
rmClfA 
rP305A (MntC) 
Volume in 0.5 mL water 
30 µg 
30 µg 
60 µg 
200 µg 
Abbreviations: CP5-CRM197 = capsular polysaccharide serotype 5 conjugated to cross-reactive material 197; 
CP8-CRM197 = capsular polysaccharide serotype 8 conjugated to cross-reactive material 197;  
rmClfA = recombinant clumping factor A mutant; rP305A = recombinant protein 305A;  
MntC = manganese transporter C. 
 
1.2.4. Clinical Experience 
1.2.4.1. First-in-Human Trial of SA3Ag (Phase 1, Study B2251002) 
Study B2251002, conducted in Australia, was a first-in-human (FIH) Phase 1 study 
evaluating the safety and immunogenicity of a preliminary S aureus 3-antigen vaccine 
(SA3Ag).  In this completed study, 406 healthy subjects aged 18 to 24 or 50 to 85 years 
received 1 of 3 dose levels of SA3Ag (low dose level [10 μg CP5-CRM197, 10 μg 
CP8-CRM197, and 20 μg rClfAm], mid dose level [30 μg CP5-CRM197, 30 μg CP8-CRM197, 

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and 60 μg rClfAm], or high dose level [100 μg CP5-CRM197, 100 μg CP8-CRM197, and 
200 μg rClfAm]) or placebo.  SA3Ag was shown to be safe, well tolerated, and capable of 
eliciting robust functional (bacterial killing) immune responses at postvaccination Day 15 
after a single administration of 1 of 3 dose levels of SA3Ag.  Substantial antibody titers to 
each of the 3 SA3Ag antigens were sustained through postvaccination Month 12.  Immune 
responses to CP5-CRM197 and CP8-CRM197 were comparable for the groups receiving the 
mid and high dose levels of SA3Ag, with lower responses observed for the low-dose-level 
group.  For rClfAm, responses were similar across the dose level groups.  While each dose 
level had an acceptable safety profile, local reactions were reported at an increased incidence 
and severity in the high-dose-level group; therefore, the mid dose level of SA3Ag (30 μg 
CP5-CRM197, 30 μg CP8-CRM197, and 60 μg rmClfA) was selected to be included as a fixed 
dose level in the SA4Ag formulations evaluated in subsequent studies, along with 
3 escalating dose levels of rP305A (20 μg, 60 μg, or 200 μg). 
1.2.4.2. First-in-Human Trial of SA4Ag (Phase 1/2a, Study B3451001) 
Study B3451001, conducted in the United States, was an FIH Phase 1/Phase 2a study 
evaluating the safety and immunogenicity of SA4Ag.  In this completed study, 456 healthy 
subjects aged 18 to <65 years received either placebo or 1 of 3 formulations of SA4Ag 
(ie, 3 dose levels of rP305A antigen).  SA4Ag formulations used in the study each included 
the original 3 antigens in SA3Ag at the dose levels selected based on results from Study 
B2251002 (30 μg CP5-CRM197, 30 μg CP8-CRM197, and 60 μg rmClfA), in addition to 
rP305A at 1 of 3 dose levels: low (20 μg), mid (60 μg), or high (200 μg). 
Safety data demonstrated that SA4Ag was well tolerated at all rP305A dose levels evaluated.  
Immunogenicity results showed that all 4 vaccine antigens elicited robust immune responses 
at postvaccination Day 29, which gradually waned but remained substantially above 
prevaccination levels through Month 12 after vaccination. 
1.2.4.3. Trial of SA4Ag in Elderly Subjects (Phase 1/2a, Study B3451011) 
Study B3451011, conducted in the United States, was a Phase 1/2a study similarly evaluating 
safety and immunogenicity of SA4Ag in elderly adults.  In this study, 283 healthy subjects 
aged 65 to <86 years received 1 of the 3 above formulations of SA4Ag, placebo, or SA3Ag 
(containing the CP5-CRM197, CP8-CRM197, and ClfA components at the same dose levels 
used in the SA4Ag formulations, without the rP305A component) as a comparator.  As with 
Study B3451001, safety data demonstrated that SA4Ag was well tolerated at all rP305A dose 
levels evaluated.  Likewise, similarly robust immune responses to all 4 vaccine antigens were 
observed at postvaccination Day 29, and immune responses were sustained through 
Month 12 after vaccination. 
1.2.4.4. Duration-of-Immunogenicity Study (Phase 2, Study B3451014) 
Study B3451014, conducted in the United States, was a Phase 2 study evaluating the 
persistence of the immune responses to SA4Ag antigens in previously vaccinated B3451001 
and B3451011 study subjects.  Antibody levels to each of the 4 vaccine antigens were 
measured through 36 months after single-dose SA4Ag administration in the primary study.  
Results showed persistent functional immune responses to CP5, CP8, and ClfA through 

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Month 36 after vaccination.  Immune responses to rP305A had declined at Month 36, 
however remained above baseline levels. 
1.2.5. Summary of Benefit-Risk Assessment 
S aureus is an opportunistic pathogen2 and a leading cause of healthcare-associated 
infections, including bloodstream infections, surgical-site infections, and hospital-acquired 
pneumonia,3, 4 and is an increasingly common cause of community-associated infections.4  
The widespread disease manifestations of S aureus and its substantial burden to the 
healthcare system present a serious unmet medical need.  Despite the availability of 
antibiotics indicated for the prevention and treatment of S aureus infections, outcomes 
remain suboptimal for many patients; therefore, there is a need to develop a vaccine to 
prevent S aureus infections. 
Results from the Phase 1/2a studies of SA3Ag and SA4Ag conducted in healthy adults aged 
18 to <86 years demonstrated an acceptable safety profile.  Local vaccine reactions (redness, 
swelling, and pain at the injection site) and systemic events (fever, vomiting, diarrhea, 
headache, fatigue, muscle pain, and joint pain) were generally mild or moderate in severity 
and resolved within a few days after vaccination.  Similar incidences of adverse events were 
reported across the study groups (vaccine recipients and placebo recipients) and were 
consistent with what is expected in adults.  The majority of subjects demonstrated normal 
hematology, biochemistry, and coagulation profiles at baseline, Day 5, and Day 15 after 
vaccination.  There were no notable trends in laboratory abnormalities within or across 
vaccine or age groups. 
Immunogenicity results showed that all 4 vaccine antigens elicited robust immune responses 
at postvaccination Day 15 and Day 29 as demonstrated by functional assays in all age groups 
and that the immune response persisted through at least 36 months after vaccination. 
For this study, the data monitoring committee meets on a quarterly basis to review safety data 
(blinded and unblinded) and to date has not identified any safety signal and has 
recommended to continue the study. 
Pfizer considers the available information from Phase 1/2a clinical trials to support a 
favorable benefit-risk profile for studies administering a single dose of SA4Ag as a potential 
prevention against invasive S aureus disease in adults undergoing elective open, posterior 
spinal fusion surgery with multilevel instrumentation. 
1.3. rP305A Dose Level Selection for SA4Ag Phase 2b Evaluation 
Results from the B3451001 and B3451011 studies were used to determine the dose level of 
rP305A for inclusion in the final formulation of SA4Ag.  The highest dose level of rP305A 
evaluated (200 µg) was selected for further SA4Ag clinical development because (1) immune 
responses to rP305A were dose dependent, with the high-dose-level group demonstrating 
highest responses to rP305A, which were sustained out to 12 months (B3451001); 
(2) increasing the rP305A dose level did not impact the immune response to the other 
3 antigens; (3) local reactions and systemic events did not increase with increasing rP305A 
dose levels; and (4) the incidence of adverse events (AEs) in the high-dose-level group was 

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similar to that of the placebo group in the younger subjects (26.8% vs 25.9%, respectively), 
and lower than that of the placebo group in the older subjects (29.8% vs 36.7%, 
respectively). 
Complete information for this compound may be found in the single reference safety 
document (SRSD), which for this study is the IB. 
2. STUDY OBJECTIVES AND ENDPOINTS 
The study objectives and endpoints employ the following definitions:  
• Protocol-defined infection (PDI):  Postoperative infections that occur following elective 
spinal surgery, particularly those frequently caused by S aureus, will be prospectively 
evaluated in this study.  PDI clinical and microbiological criteria are based upon CDC 
National Health Surveillance Network (NHSN) criteria; complete case definitions 
provided in Appendix 1 will be applied for case identification and confirmation.  
Summaries of the PDIs that, when microbiologically confirmed as being due to S aureus, 
will contribute to study objectives and endpoints are provided below. 
• Bloodstream infection (BSI):  Clinical infection involving a recognized pathogen 
(eg, S aureus) cultured from 1 or more blood cultures, or a commensal organism 
cultured from 2 or more blood cultures, whether primary or secondary to infection at 
another site. 
• Surgical-site infection (SSI):  Infection at a surgical incision, whether involving the 
primary posterior incision or a secondary (eg, anterior) incision associated with the 
spinal fusion procedure itself or with the harvesting of autologous bone graft material.  
SSI is further classified as: 
• Superficial SSI: Infection involves only skin and subcutaneous tissue of the 
incision. 
• Deep incisional SSI: Infection involves deep soft tissues of the incision  
(eg, fascial and muscle layers). 
• Organ/space SSI: Infection involves any part of the body, excluding the skin 
incision, fascia, or muscle layers, that is opened or manipulated during the 
operative procedure.  Specific to spinal fusion surgery, osteomyelitis, vertebral 
disc space infection, meningitis, and spinal abscess without meningitis when 
directly attributable to a surgical incision will be classified as organ/space SSIs.  
Likewise, intra-abdominal infection, when directly attributable to a secondary 
anterior intra-abdominal incision, and joint and bursa infection, when directly 
attributable to a surgical incision (eg, harvesting autologous bone), will be 
considered organ/space SSIs. 
• Invasive S aureus (ISA) disease: ISA disease is defined as culture of S aureus from 
a normally sterile location, with clinical evidence of disease.  With the exception of 

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superficial SSI, all microbiologically confirmed S aureus PDIs defined in Appendix 1 
will be considered ISA disease. 
2.1. Primary Efficacy Objective 
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 90 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation, in adults aged 18 to <86 years. 
2.1.1. Primary Efficacy Endpoint 
• The number of subjects in each vaccine group with postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 90 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation, as confirmed by the event 
adjudication committee (EAC). 
2.2. Primary Safety Objective 
• To describe the safety and tolerability of a single vaccination of SA4Ag in adults aged 
18 to <86 years undergoing elective open posterior spinal fusion procedures with 
multilevel instrumentation, by measuring local reactions, systemic events, and AEs. 
2.2.1. Primary Safety Endpoints 
• Number and proportion of subjects in each vaccine group with local reactions (redness, 
swelling, and pain) occurring within the 10-day period following study vaccination. 
• Number and proportion of subjects in each vaccine group with systemic events (fever, 
fatigue, headache, vomiting, diarrhea, muscle or joint pain) occurring within the 10-day 
period following study vaccination. 
• Number and proportion of subjects in each vaccine group with AEs reported during the 
following time periods:  
• From vaccination until the day of surgery  
• From vaccination until the Day 42 postoperative evaluation 
• From the day of surgery until the Day 42 postoperative evaluation 
• From the Day 42 postoperative evaluation until the day 180 postoperative evaluation 
(newly diagnosed chronic medical disorders) 
• Number and proportion of subjects in each vaccine group with serious adverse events 
(SAEs) reported during the following time periods:  
• From vaccination until the Day 180 postoperative evaluation 
• From vaccination until the day of surgery  

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• From the day of surgery until the Day 180 postoperative evaluation 
2.3. Secondary Efficacy Objectives 
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 180 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation, in adults 18 to <86 years of age. 
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus SSI 
occurring within 90 days of elective open posterior spinal fusion procedures with 
multilevel instrumentation, in adults 18 to <86 years of age. 
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus SSI 
occurring within 180 days of elective open posterior spinal fusion procedures with 
multilevel instrumentation, in adults 18 to <86 years of age. 
2.3.1. Secondary Efficacy Endpoints 
• The number of subjects in each vaccine group with postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 180 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation. 
• The number of subjects in each vaccine group with postoperative S aureus SSI occurring 
within 90 days of elective open posterior spinal fusion procedures with multilevel 
instrumentation. 
• The number of subjects in each vaccine group with postoperative S aureus SSI occurring 
within 180 days of elective open posterior spinal fusion procedures with multilevel 
instrumentation. 
2.4. Exploratory Objectives 
• To assess the efficacy of SA4Ag in the prevention of postoperative ISA disease occurring 
within 90 days of elective open posterior spinal fusion procedures with multilevel 
instrumentation, in adults 18 to <86 years of age. 
• To assess the efficacy of SA4Ag in the prevention of postoperative ISA disease occurring 
within 180 days of elective open posterior spinal fusion procedures with multilevel 
instrumentation, in adults 18 to <86 years of age. 
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 90 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation, in adults 18 to <86 years of age, 
based on baseline S aureus colonization status. 
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 180 days of elective open posterior 

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spinal fusion procedures with multilevel instrumentation, in adults 18 to <86 years of age, 
based on baseline S aureus colonization status. 
• To describe the immunogenicity of SA4Ag in adults aged 18 to <86 years undergoing 
elective open posterior spinal fusion procedures with multilevel instrumentation. 
• To describe S aureus colonization in adults aged 18 to <86 years undergoing elective 
open posterior spinal fusion procedures with multilevel instrumentation, before and after 
SA4Ag administration. 
• To compare healthcare utilization data between vaccine groups. 
2.4.1. Exploratory Endpoints 
• The number of subjects in each vaccine group with postoperative ISA disease occurring 
within 90 days of elective open posterior spinal fusion procedures with multilevel 
instrumentation. 
• The number of subjects in each vaccine group with postoperative ISA disease occurring 
within 180 days of elective open posterior spinal fusion procedures with multilevel 
instrumentation. 
• The number of subjects in each vaccine group with postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 90 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation, based on baseline S aureus 
colonization status. 
• The number of subjects in each vaccine group with postoperative S aureus BSI and/or 
deep incisional or organ/space SSI occurring within 180 days of elective open posterior 
spinal fusion procedures with multilevel instrumentation, based on baseline S aureus 
colonization status. 
• The proportion of subjects at each time point who achieve specific antibody thresholds in 
antibody assays that assess functional activity.  These may include, for example, 
opsonophagocytic activity (OPA) assays using an S aureus capsular polysaccharide 
serotype 5 (CP5)-expressing strain and a capsular polysaccharide serotype 8 
(CP8)-expressing strain, and competitive Luminex immunoassays (cLIAs) for ClfA and 
MntC.  Additional exploratory assays to measure immune responses may also be 
conducted on all 4 antigens. 
• The proportion of subjects at each time point who achieve specific antibody thresholds to 
all 4 antigens both individually and combined using immunological assays. 
• The number of subjects in each vaccine group determined to be colonized with S aureus 
on each occasion swab samples are collected. 

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• From subjects with S aureus infection, the association between S aureus strain or strains 
identified as colonizing the subject and the S aureus strain or strains recovered from the 
infection. 
• Healthcare utilization data, including days in hospital, days in an ICU, discharge 
disposition, inpatient days in rehabilitation facilities or skilled nursing facility after 
discharge, number of hospital readmissions and reoperations, days of antibiotic use, and 
number of rehabilitation/physical therapy outpatient visits. 
2.5. Endpoint Adjudication 
To maintain the scientific integrity, this protocol will use an independent EAC for 
adjudication of all primary and secondary efficacy endpoints, exploratory endpoints of ISA 
disease (Section 7.1.1.2), multiple-organ failure (MOF), and death, as summarized below.  
The EAC’s assessment of these events will represent the final confirmed classification of the 
event. 
The primary and/or secondary efficacy-related events for adjudication include all reported 
BSI and SSI events.  The EAC is responsible for adjudicating whether BSI and SSI events 
fulfill the protocol-defined clinical criteria, and whether the confirmed infections are 
attributable to microbiologically confirmed S aureus, attributable to other pathogen(s), or 
without microbiological confirmation. 
Furthermore, the EAC is responsible for adjudicating all other reported PDI events.  As with 
BSI and SSI events, the EAC will confirm whether these events fulfill the protocol-defined 
clinical criteria, and whether these events represent microbiologically confirmed S aureus 
infection. 
In addition, any other invasive infection (irrespective of the causative pathogen) will be 
adjudicated by the EAC. 
The most adverse outcomes of postoperative infections are MOF and death.  Therefore, in 
addition to the PDI adjudication responsibilities mentioned above, the EAC is also 
responsible for adjudicating whether reported organ failure (OF) events meet the 
protocol-defined clinical criteria for OF/MOF, and whether the confirmed OF/MOF events 
and all reported deaths are attributable to microbiologically confirmed S aureus, attributable 
to other pathogen(s), or without microbiological confirmation (Section 7.2.3). 
The detailed event adjudication criteria, documentation requirements, responsibilities, EAC 
membership requirements, and training are found in the event adjudication committee charter 
(EACC).  The EAC will remain blinded to subject vaccine assignments.  To facilitate EAC 
adjudication, in addition to the data captured in the case report form (CRF), documents that 
support the clinical and microbiological criteria specified in Appendix 1 will be provided by 
investigators in conjunction with the sponsor’s study team. 
Any SAE that is adjudicated by the EAC and determined NOT to meet endpoint criteria is 
reported back to the investigative site of incidence; the investigator at the study site must 

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evaluate and report that SAE to Pfizer, in accordance with the time frames described in the 
Serious Adverse Event Reporting Requirements (Section 8.14.1).  The investigator’s SAE 
awareness date in this instance is identified as the date on which the investigative site of 
incidence receives the determination that the SAE does not meet endpoint criteria back from 
the EAC.  Handling these SAEs in this manner will allow Pfizer to meet its sponsor reporting 
obligations to regulatory authorities upon receipt of such SAEs. 
However, when the investigator has judged an SAE to have a causal relationship with the 
investigational product, the investigator must additionally report the event to the sponsor as 
described in the Serious Adverse Event Reporting Requirements (Section 8.14.1), even if that 
event is a component of the endpoint. 
Any events that remain unadjudicated at the annual safety report cutoff date are not to be 
included in the safety tables of the report. 
3. STUDY DESIGN 
This is a Phase 2b, multicenter, parallel-group, placebo-controlled, randomized, double-blind 
study to evaluate SA4Ag safety and efficacy in the prevention of postoperative S aureus 
disease in adults aged 18 to <86 years who are undergoing elective open posterior spinal 
fusion procedures with multilevel instrumentation. 
There are 5 scheduled study visits and 1 scheduled telephone contact during 6 to 8 months of 
subject participation.  Study-eligible subjects who provided consent will be randomized in a 
1:1 ratio to receive a single dose of SA4Ag or placebo at Visit 1, which occurs 10 to 60 days 
prior to undergoing elective open posterior spinal fusion procedures with multilevel 
instrumentation (index surgical procedure).  Visit 2 is a longitudinal visit and is to monitor 
the index hospital admission period from the day of surgery (Day 1) until the day of 
discharge. 
A telephone contact with the subject will occur on Day 21 (window: Days 18 to 26), while 
postoperative evaluation study visits will occur on Day 42 (window: Days 35 to 49), Day 90 
(window: Days 83 to 97), and Day 180 (window: Days 178 to 192) after surgery. 
Additional reminders will be communicated to study subjects instructing them to contact the 
investigational site whenever there is a suspicion of a PDI or a severe postvaccination local 
reaction or fever. 
Unscheduled telephone contacts will be conducted for assessment of severe local reactions, 
severe fever, and severe systemic events after vaccination.  Severe fever and severe local 
reactions may warrant an unscheduled severe local reaction or fever assessment visit. 
Following the index hospital admission, unscheduled visits will be conducted for assessment 
of suspected BSI and/or SSI events, and to assess hospitalization(s) subsequent to the index 
hospital admission. 

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3.1. Subject Numbers and Duration of Subject Participation 
It is anticipated that approximately 6000 subjects will be enrolled globally to accumulate 
48 per-protocol cases.  As this is an event-driven study, the final enrollment number may 
vary depending on the incidence rate of the primary endpoint, the true underlying VE, and a 
potential early stop for efficacy or futility (see Section 9.1).  In the event that efficacy is 
demonstrated at the interim analysis, enrollment may continue in order to complete the safety 
evaluations in this surgical population. 
Each subject is expected to participate in the study for approximately 6 to 8 months. 
The end of the study is defined as last subject last visit (LSLV) for the purposes of closing 
out sites, informing the institutional review board/independent ethics committee (IRB/IEC), 
and stopping the sending of Council for International Organizations of Medical Sciences 
(CIOMS) reports; however, for other purposes the end of the study will be defined as the last 
serology sample assayed or characterization of the last strain isolate. 
3.2. Study Population 
3.2.1. Index Study Procedure Definitions 
Subjects undergoing elective, spinal fusion procedures with multilevel instrumentation 
performed via an open posterior incision will be considered eligible for participation in this 
study, where 
• An elective surgical procedure is defined as a nonemergency inpatient surgical procedure 
scheduled to occur 10 to 60 days after receiving the study vaccination. 
• An open posterior incision is defined as a posterior midline, posterolateral, or transverse 
exposure of the vertebrae to be fused or instrumented.  Subjects undergoing procedures 
involving additional surgical access, whether via open incision, minimally invasive, or 
laparoscopic technique (eg, anterior or lateral interbody fusion procedures), may be 
eligible, provided that the procedure involves open posterior exposure.  Subjects 
undergoing staged fusion procedures requiring operations performed on separate days or 
procedures performed exclusively by a minimally invasive technique are not eligible for 
inclusion. 
• For this study, spinal fusion is defined as a surgical arthrodesis procedure that includes at 
least 2 adjacent intervertebral levels/motion segments, ie, a minimum of: 
• 3 adjacent vertebrae (any region of spine), or 
• 2 adjacent cervical vertebrae plus the occiput, or 
• 2 adjacent lumbar/sacral vertebrae plus the pelvis 

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• A single fusion that includes 1 intervertebral level/motion segment is permitted only if 
the instrumentation inserted spans at least 2 adjacent intervertebral levels/motion 
segments (ie, multilevel instrumentation). 
• For this study, multilevel instrumentation is defined as the surgical implantation of 
prosthetic material (eg, rods, screws, plates, hooks, wires, and/or bone cages) involving at 
least 2 intervertebral levels/motion segments, ie, a minimum of: 
• 3 adjacent vertebrae (any region of spine), or 
• 2 adjacent cervical vertebrae plus the occiput, or 
• 2 adjacent lumbar/sacral vertebrae plus the pelvis 
3.2.2. Surgical Indications 
3.2.2.1. Permitted Indications for the Index Surgical Procedure 
Subjects presenting with 1 or more of the following surgical indications for their index 
surgery may be eligible for inclusion. 
• Intervertebral disc disease (eg, herniation, rupture, postdiscectomy syndrome) 
• Facet joint arthritis, facet joint syndrome 
• Vertebral instability (eg, spondylolysis, spondylolisthesis, true instability)  
• Adjacent segment syndrome 
• Transitional lumbosacral anomaly 
• Spinal stenosis 
• Spinal deformity (eg, scoliosis, kyphosis)  
• Spinal cord compression 
• Other 
3.2.2.2. Prohibited Indications for the Index Surgical Procedure 
Subjects presenting with 1 or more of the following surgical indications for their index 
surgery are not eligible for inclusion.  Further details are provided in the study exclusion 
criteria (Section 4.2). 
• Infection 
• Malignancy 

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• Acute or emergency trauma 
3.2.2.3. Previous or Revisional Spinal Surgery 
Subjects with a history of previous spinal surgery at least 6 months prior to study enrollment, 
including subjects undergoing previous fusion of the same or adjacent vertebrae, may be 
eligible for inclusion, provided that other study eligibility criteria are met.  Subjects with a 
history of postoperative BSI and/or SSI following previous spinal surgery are not eligible for 
inclusion. 
If, during a revision surgery, hardware or tissue is removed, the hardware and/or tissue 
should be cultured. 
4. SUBJECT SELECTION 
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom protocol treatment is considered 
appropriate.  All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether this protocol is suitable for a particular subject. 
4.1. Inclusion Criteria 
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study. 
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study: 
1. Subject must personally sign and date the informed consent document (ICD) indicating 
that the subject has been informed of all pertinent aspects of the study. 
2. Subject must be aged 18 to <86 years at the time of enrollment. 
3. Subject must be scheduled to undergo an elective open posterior spinal fusion procedure 
with multilevel instrumentation 10 to 60 days after study vaccination.  (For additional 
details, see Section 3.2.1). 
4. Subject must be available for the entire duration of the study, and willing and able to 
comply with scheduled visits, treatment plan, laboratory tests, and other study 
procedures, including completion of the electronic diary (e-diary) for 10 days after study 
vaccination (If surgery occurs on Day 10, then the e-diary does not need to be completed 
for that day). 
5. Subject must be able to be contacted by telephone during study participation. 
6. Male subjects and female subjects of childbearing potential and at risk for pregnancy 
must agree to use a highly effective method of contraception throughout the study. 

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4.2. Exclusion Criteria 
Subjects presenting with any of the following will not be included in the study: 
1. Planned spinal fusion procedure requiring separate operations performed on separate days 
(ie, staged procedure). 
2. Single-level spinal fusions without insertion of multilevel instrumentation (ie, surgical 
implantation of prosthetic material involving 2 or more motion segments).  
(For additional details, see Section 3.2.1.)  
3. Surgical indication of malignancy, infection, or acute or emergency trauma (ie, related to 
a traumatic incident occurring within 6 months prior to study enrollment). 
4. History of major surgery (specifically, an open procedure that enters a body cavity, 
organ, or joint space) within 3 months prior to enrollment, or anticipated major surgery 
other than the index surgical procedure between study enrollment and completion of 
study participation. 
5. History of any spinal surgery performed within 6 months prior to study enrollment. 
6. History of any previous spinal surgery resulting in postoperative BSI or SSI. 
7. Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other 
illness requiring chronic treatment with known immunosuppressant medications, 
including monoclonal antibodies, within the year prior to enrollment or the use of 
systemic corticosteroids (equivalent of ≥10 mg/day of prednisone) for >14 days within 
30 days prior to study enrollment. 
8. History of leukemia, lymphoma, or underlying bone marrow disorder 
(eg, myelodysplasia, myeloma, myeloproliferative disorder) or history of bone marrow 
transplant. 
9. Malignancy that required treatment with chemotherapy, immunotherapy, radiation 
therapy, or other antineoplastic target therapies within 24 months prior to study 
enrollment. 
10. Any known or suspected malignancy to the spine. 
11. Congenital, functional, or surgical asplenia. 
12. End-stage renal disease (defined as requiring or anticipating requirement for 
hemodialysis, peritoneal dialysis, or renal transplant) or nephrotic syndrome. 
13. Any contraindication to vaccination or vaccine components, including history of 
anaphylactic reaction to any vaccine or vaccine-related component. 

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14. Receipt of blood products or immunoglobulins (including monoclonal antibodies) within 
6 months prior to study enrollment OR anticipated receipt of blood products or 
immunoglobulins (including monoclonal antibodies) prior to the index hospital 
admission. 
15. Previous administration of S aureus vaccine or S aureus/Candida vaccine. 
16. Antibiotic therapy for microbiologically confirmed ISA disease within 12 months prior to 
enrollment. 
17. Participation in other studies involving investigational drug(s) (Phases 1-4) within 
30 days before the current study begins and/or anticipated participation during the study. 
18. Pregnant females, breastfeeding females, and males and females of childbearing potential 
who are unwilling or unable to use a highly effective method of contraception, as 
outlined in Section 4.4, for the duration of the study. 
19. Presence of a colostomy, urostomy, tracheostomy, percutaneous gastrostomy tube, 
indwelling vascular or urinary catheter, central nervous system shunt, central nervous 
system implanted device, or spinal cord stimulator; OR anticipated presence of a 
colostomy, urostomy, tracheostomy, percutaneous gastrostomy tube, indwelling vascular 
or urinary catheter, central nervous system shunt, central nervous system implanted 
device, or spinal cord stimulator prior to the index hospital admission. 
20. Other severe acute or chronic medical or psychiatric condition (including drug and 
alcohol dependencies) or laboratory abnormality that may increase the risk associated 
with study participation or investigational product administration or may interfere with 
the interpretation of study results and, in the judgment of the investigator, would make 
the subject inappropriate for entry into this study. 
21. Subjects who are investigational site staff members directly involved in the conduct of 
the study and their family members, site staff members otherwise supervised by the 
investigator, or subjects who are Pfizer employees directly involved in the conduct of the 
study. 
4.3. Criteria for Temporarily Delaying Vaccine Administration 
The following conditions are temporary or self-limiting and a subject may be vaccinated 
once the condition(s) has/have resolved and no other exclusion criteria are met, provided that 
the scheduled surgical procedure remains within the 10- to 60-day window from the day of 
vaccination to the day of surgery. 
• Current febrile illness (oral temperature of ≥38.0°C [100.4°F]) or other acute illness 
within 48 hours prior to investigational product administration. 

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• Receipt of any nonlive vaccine within 14 days or any live vaccine within 28 days prior to 
vaccination; anticipated administration of any nonlive vaccine within 14 days or any live 
vaccine within 28 days after study vaccination. 
• Systemic antibiotic therapy for an acute illness within 72 hours prior to investigational 
product administration. 
• If systemic corticosteroids (equivalent of ≥10 mg/day of prednisone) have been 
administered short term (≤14 days) for treatment of an acute illness, investigational 
product administration should be delayed until systemic corticosteroid use has been 
discontinued for at least 28 days.  Locally administered (eg, intraspinal), inhaled, or 
topical steroids do not require temporary delay of investigational product administration. 
If a subject meets any delay criteria for vaccination as specified above, study procedures, 
relating to that visit will be delayed until the rescheduled day of vaccination.  Blood and 
swab samples, however, may be collected up to 7 days prior to vaccination. 
4.4. Lifestyle Guidelines 
All male and female subjects who, in the opinion of the investigator, are biologically capable 
of having children and are sexually active and at risk for pregnancy with their partner(s), 
must agree to use a highly effective method of contraception consistently and correctly for 
the duration of the study.  The investigator or his/her designee, in consultation with the 
subject, will determine the most appropriate method of contraception for the individual 
subject from the permitted list of contraception methods (see below) and instruct the subject 
in its consistent and correct use.  Subjects need to affirm that they meet at least 1 of the 
selected methods of contraception. 
The investigator or his/her designee will discuss with the subject the need to use highly 
effective contraception consistently and correctly and document such conversation in the 
subject’s chart.  In addition, the investigator or his/her designee will instruct the subject to 
call immediately if the selected contraception method is discontinued or if pregnancy is 
known or suspected. 
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following: 
• Established use of oral, inserted, injected, or implanted hormonal methods of 
contraception is allowed provided the subject plans to remain on the same treatment 
throughout the entire study and has been using that hormonal contraceptive for an 
adequate period of time to ensure effectiveness. 
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• Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream, or 
suppository).  For countries where spermicide is not available or condom plus spermicide 
is not accepted as highly effective contraception, this option is not appropriate. 
• Male sterilization with absence of sperm in the postvasectomy ejaculate. 
• Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label). 
4.5. Sponsor’s Qualified Medical Personnel 
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the study reference manual (SRM). 
4.5.1. Study Participant/Emergency Contact Card 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card.  The contact card contains, 
at a minimum, protocol and investigational compound identifiers, subject study numbers, 
contact information for the investigational site, and contact details for a help desk in the 
event that the investigational site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study.  The help desk number can also be used by 
investigational staff if they are seeking advice on medical questions or problems; however, it 
should only be used in the event that the established communication pathways between the 
investigational site and the study team are not available.  It is therefore intended to augment, 
but not replace, the established communication pathways between the investigational site and 
the study team for advice on medical questions or problems that may arise during the study.  
The help desk number is not intended for use by the subject directly, and if a subject calls 
that number, he or she will be directed back to the investigational site. 
5. INVESTIGATIONAL PRODUCTS 
5.1. Allocation to Investigational Product 
All eligible subjects will be randomized to receive a single injection of investigational 
product (SA4Ag or placebo) at Visit 1 (-60 to -10 days prior to the day of surgery). 
Allocation of subjects to vaccine groups will proceed through the use of an interactive voice 
response system (IVRS) or interactive Web response (IWR) system.  The site personnel are 
required to enter or select information including but not limited to the user name and 
password, protocol, and subject number.  The site personnel will be provided with a vaccine 
assignment and container number when the investigational product is being supplied via the 
IVRS/IWR.  The IVRS/IWR will provide a confirmation report containing the subject 
number and container number assigned.  The confirmation report must be stored in the site’s 
files. 
There is a 24-hour-a-day, 365-days-a-year IVRS/IWR help desk available for any questions 
or issues.  The study-specific IVRS/IWR reference manual will provide the contact 

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5.3.4. Compliance 
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigative site. 
5.3.5. Investigational Product Storage 
The investigational product will be shipped at +2°C to +8°C to each study site after required 
regulatory and legal documents have been received by the sponsor.  Upon receipt at the study 
site, the investigational product should be immediately transferred to a +2°C to +8°C 
temperature-monitored refrigerator for storage.  The refrigerator where the investigational 
product is stored must be secure and have limited access. 
The investigator, or an approved representative, eg, pharmacist, will ensure that all 
investigational products, including any comparative agents and/or marketed products, are 
stored in a secured area with controlled access under recommended storage conditions and in 
accordance with applicable regulatory requirements. 
Investigational product should be stored in its original container and in accordance with the 
vaccine label. 
Storage conditions stated in the SRSD (IB) will be superseded by the storage conditions 
stated in the labeling. 
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations 
(as applicable, including frozen, refrigerated, and/or room-temperature products).  This 
should be captured from the time of investigational product receipt throughout the study.  
Even for continuous-monitoring systems, a log or site procedure that ensures active daily 
evaluation for excursions should be available.  The operation of the temperature-monitoring 
device and storage unit (for example, refrigerator), as applicable, should be regularly 
inspected to ensure it is maintained in working order. 
Any excursions from the product-label storage conditions should be reported upon discovery.  
The site should actively pursue options for returning the product to the storage conditions 
described on the product label, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to the sponsor. 
Once an excursion is identified, the investigational product must be quarantined and not used 
until the sponsor provides documentation of permission to use the investigational product.  
Specific details regarding information the site should report for each excursion will be 
provided to the site. 
5.3.6. Investigational Product Accountability 
The investigator’s site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies (SA4Ag and placebo). 

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The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site). 
5.4. Concomitant Medication(s), Vaccinations, and Blood Products 
The following concomitant medications, vaccinations, and blood products will be recorded in 
the CRF: 
• Antibiotics, including all antibiotic use from study enrollment until completion of study 
participation, start and stop dates, name of antibiotic, dose, route, and frequency. 
• Systemic steroids, from study enrollment until completion of study participation, start 
and stop dates, medication name, dose, units, route, frequency, and indication for use. 
• Intraspinal steroids, from 6 months prior to study enrollment until completion of study 
participation, including medication name and date administered. 
• Nonstudy vaccines administered from 6 months prior to study enrollment until 
completion of study participation, including name of vaccine and date administered. 
• Blood products, including number of units and type (eg, whole blood, red blood cells, 
platelets, clotting factors, cryoprecipitate, white blood cells, immunoglobulins, albumin, 
and plasma).  In addition, whole blood and red blood cells should be identified as 
heterologous or autologous donations.  If a cell saver is used to return the subject’s red 
blood cells during the index surgical procedure, this information will be recorded.  All 
blood product use should be recorded from study vaccination through study completion. 
5.4.1. Restrictions to Concomitant Vaccinations and Medications  
• Prophylactic use of antipyretic medications at the time of study vaccination will be 
discouraged. 
• Licensed vaccines may be given if, in the opinion of the investigator, they are medically 
appropriate and necessary (eg, seasonal influenza vaccine; age-appropriate pneumococcal 
vaccine; tetanus, diphtheria, and acellular pertussis [Tdap] vaccine; or postexposure 
tetanus vaccine).  When possible, concomitant administration of licensed vaccines should 
be avoided during the periods specified in Section 4.3. 
• Where possible, systemic corticosteroid therapy of >14 days (equivalent of ≥10 mg/day 
prednisone) should not be used during the study.  Short-term systemic steroids (≤14 days) 
and inhaled, topical, or localized injections of corticosteroids are permitted. 
• The use of antipyretics and other pain medication to treat symptoms associated with 
investigational product administration or ongoing conditions is permitted, unless 
otherwise stated. 

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• The use of medications required for treatment of stable preexisting conditions is 
permitted, unless otherwise stated. 
6. STUDY PROCEDURES 
6.1. Scheduled Study Visits 
An overview of the study stages, visits, and procedures is presented in the Schedule of 
Primary Activities in Table 1.  An overview of activities for Adverse Event and Study Event 
Reporting is presented in Table 2. 
Before any study-related procedures are performed, voluntary, written study-specific 
informed consent will be obtained from the subject.  Each signature on the ICD must be 
personally dated by the signatory.  A copy of the signed and dated ICD must be given to the 
subject.  The source data must reflect that the informed consent was obtained before 
commencement of subject participation in the study. 
Before randomization, the investigator or a medically qualified designee will review the 
subject’s medical history and medications to ensure that the subject meets all of the inclusion 
criteria, none of the exclusion criteria, and none of the temporary delay criteria. 
In the event that the subject’s index surgery is not conducted according to the index study 
procedure definitions (Section 3.2.1), the subject will continue to participate in all study 
procedures. 
The procedures required at each visit are detailed below. 
6.2. Stage 1: Vaccination Stage 
The vaccination stage of the study covers the period from Visit 1 (day of vaccination) 
through the period prior to admission to hospital for the index surgical procedure.  It does 
not include Visit 2. 
6.2.1. Visit 1, Day of Vaccination (Day -60 to Day -10) 
• Obtain written informed consent prior to performing any protocol-required procedures. 
• Enter the subject into the IVRS/IWS and obtain a subject number. 
• Record the subject’s demography (including date of birth, sex, race, and ethnicity). 
• Record significant medical history including chronic medical conditions, all 
conditions requiring hospital admission, including the spinal condition precipitating 
the index surgery, and all previous documented S aureus infections, including 
antibiotic treatments if known. 
• Record previous surgical procedures (excluding outpatient dermatological 
procedures). 

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• Record smoking status (smoker, past smoker, never smoked). 
• Record alcohol use status (drinker, nondrinker) and number of standard drinks per 
week. 
• Record nonstudy vaccinations received in the previous 6 months and concomitant 
medications as described in Section 5.4. 
• Record height and weight. 
• Perform vital sign measurements including blood pressure, pulse rate, respiratory 
rate, and temperature (°C or °F).  When multiple measurements are taken at the same 
time (eg, blood pressure is measured twice), the most out-of-range (eg, highest or 
lowest) value must be reported. 
• Perform a physical examination noting any clinically significant abnormalities within 
the following body systems: general appearance; musculoskeletal; skin; head, eyes, 
ears, nose, and throat; heart; lungs; abdominal; neurological; and lymph nodes. 
• Conduct a urinary (or serum) pregnancy test on all women of childbearing potential. 
• Discuss contraceptive use and record discussion in source documents. 
• Ensure that all inclusion criteria and none of the exclusion criteria are met 
(Section 4). 
• Record the indication for the index surgical procedure, and the planned surgical 
procedure, including anatomical approach and vertebral levels to be fused.  The 
planned date of surgery is to be recorded in the source documents. 
• Determine the Charlson comorbidity score (Section 7.2.2.1). 
• If the subject meets the temporary delay criteria, vaccination may be rescheduled, 
provided that rescheduling will not encroach upon the 10-day minimum window 
between the day of vaccination and the day of surgery.  Surgery may occur on Day 10 
after vaccination. 
• Collect a blood sample of approximately 24 mL for immunogenicity assessments.  
This sample must be collected prior to vaccination 
• Collect colonization swab samples from the nose and throat. 
• After all eligibility criteria are confirmed, the investigator or designee will use the 
IVRS/IWS to obtain the subject’s randomization number and investigational product 
kit assignment.  Refer to the SRM for further instructions and requirements for 
recording screen failure subjects. 

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• Issue a subject e-diary, and provide instructions on its completion.  After completing 
e-diary training and setup, ensure that the subject records a baseline assessment in the 
e-diary prior to vaccination.  Ask the subject to record systemic events, local 
reactions, and fever in the e-diary each evening from the day of vaccination for 10 
consecutive days. 
• Administer a single 0.5-mL intramuscular injection of the assigned investigational 
product into the deltoid muscle of the nondominant arm, unless medically 
contraindicated, in which case the injection may be administered in the dominant arm. 
• Observe the subject for at least 30 minutes after investigational product 
administration for any acute reactions.  Record any events observed within the 
30 minutes as immediate AE(s) on the CRF.  Capture date and time of vaccination 
and date and time of onset of the event (if any) in the CRF.  Record and report AEs 
(relative to the time of vaccination) as described in Section 8 and in the Schedule of 
Activities for Adverse and Study Event Reporting (Table 2). 
• Issue a measuring device (caliper) and a digital thermometer and provide instructions 
on their use. 
• Issue a study participant/emergency contact card. 
• Instruct the subject to contact the site staff or investigator immediately if he or she 
experiences fever ≥39.0°C (≥102.1°F), redness or swelling at the injection site 
measuring greater than 10 cm (≥21 caliper units), or severe pain at the injection site, 
within 10 days following vaccination, to determine if a severe local reaction or fever 
assessment visit is required (Section 6.4.1.2). 
• Instruct the subject to contact the site staff or investigator immediately if any 
medically attended illness or hospitalization occurs prior to the index hospital 
admission. 
• Remind the subject to bring the e-diary with them when they are admitted to hospital 
for their spinal surgery. 
• Schedule the next study visit to occur upon commencement of the index hospital 
admission so that preoperative study procedures required prior to surgery are 
conducted.  Instruct the subject to contact the site staff or investigator in the event that 
their surgery is rescheduled. 
• Report study participation and study details to the subject’s primary care physician, if 
applicable. 
• Complete the source documents and the investigational product accountability record. 
• Complete the CRF. 

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6.3. Stage 2: Surgery Stage 
The surgery stage of the study covers the period from Visit 2 (index hospital admission) to 
Visit 6 (Day 180 postoperative evaluation). 
6.3.1. Visit 2, Index Hospital Admission 
6.3.1.1. Day of Surgery (Day 1) 
The day of admission may occur prior to or on the day of surgery.  In either case, the day of 
surgery (the day on which the index surgical procedure is performed) is defined as Day 1 of 
the study. 
If the subject is admitted to hospital prior to the day of surgery, the visit procedures may be 
performed on the day prior to surgery.  If the subject is admitted to hospital on the day of 
surgery and time is limited, the procedures noted below as “prior to surgery” must be 
performed before the surgical procedure.  Other requirements (eg, preoperative assessment 
and concomitant medication review) may be completed in the postoperative recovery period. 
• Prior to surgery, collect a blood sample of approximately 24 mL for immunogenicity 
assessments. 
• Prior to surgery, collect colonization swab samples from the nose and throat. 
• Prior to surgery, obtain the subject’s fasting blood glucose level (eg, glucose meter or 
serum). 
• Prior to surgery, collect and review e-diary data and follow up on any ongoing 
symptoms.  If the subject has any ongoing symptoms reported on the last day of e-diary 
reporting, record the stop date(s). 
• Prior to surgery, determine whether any AEs or SAEs have occurred or require updating 
since the last study visit.  Record and report AEs as described in Section 8 and the 
Schedule of Activities for Adverse and Study Event Reporting (Table 2). 
• Record nonstudy vaccinations and concomitant medications as described in Section 5.4. 
• Record the information required for the preoperative assessment as shown in Appendix 2. 
• Complete the source documents and CRF. 
6.3.1.2. Day After Surgery (Day 2) 
• Record the actual index surgical procedure.  Record excursions from the planned index 
surgical procedure, taking into account the study protocol inclusion and exclusion 
criteria. 
• Obtain the subject’s postoperative blood glucose level (eg, glucose meter or serum). 

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• Record the information required for the perioperative assessment as shown in 
Appendix 3. 
• Determine whether any AEs or SAEs have occurred since the last subject assessment.  
Record and report AEs as described in Section 8 and the Schedule of Activities for 
Adverse and Study Event Reporting (Table 2). 
• Complete the source documents and CRF. 
6.3.1.2.1. Daily Monitoring During the Index Hospitalization 
• Following surgery, on each day of hospitalization through the day of discharge, the 
following assessments will be conducted: 
• Determine whether any AEs or SAEs have occurred or require updating since the last 
review.  Record and report AEs as described in Section 8 and the Schedule of 
Activities for Adverse and Study Event Reporting (Table 2). 
• Determine whether the subject has a suspected PDI; if so, record and report the PDI 
event as described in Section 7.1.1, and 
• If the suspected PDI represents BSI and/or SSI, perform the procedures required for a 
BSI/SSI assessment visit described in Section 6.4.2. 
• If the suspected PDI does not represent a BSI and/or SSI, the BSI/SSI assessment 
visit procedures are not required. 
• Determine whether the subject meets the protocol-defined criteria for organ failure 
(eg, via review of medical and nursing records, clinical findings, and laboratory results) 
as described in Section 7.2.3.  When a subject is identified as having organ dysfunction:  
• Record a daily Sequential Organ Failure Assessment (SOFA) score on the SOFA 
worksheet, as described in Section 7.2.3, until the event is resolved (normal or 
baseline), or for the duration of the hospitalization if not resolved. 
• When a SOFA score of ≥3 is recorded for any single organ, record the SOFA score in 
the CRF on a daily basis until the failing organ system(s) returns to normal/baseline 
or stabilizes. 
• Record the OF events (SOFA ≥3) as AEs/SAEs as appropriate.  SOFA Scores <3 
should be assessed to determine if AE reporting is required as per Section 8. 
• If the subject develops MOF, ie, OF in 2 or more body systems concurrently, collect a 
24-mL blood sample for immunogenicity. 
• Complete a MOF event report and submit the event for adjudication as detailed in the 
SRM. 

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6.3.1.3. Day of Hospital Discharge (Day Variable) 
If discharge is scheduled for a weekend/holiday, visit procedures may be conducted within 
3 days prior to discharge. 
If discharge procedures are conducted and the subject’s discharge is subsequently postponed 
by more than 3 days, blood and swab samples must be re-collected. 
• If the day of hospital discharge coincides with the timing of the day after surgery (Day 2), 
the Day 21 telephone contact, or the Day 42 or Day 90 postoperative evaluation, 
coincident study procedures (eg, collection of the 24-mL blood sample for 
immunogenicity, colonization swabs) may be combined as a single visit. 
• Record nonstudy vaccinations and concomitant medications as described in Section 5.4. 
• Collect and process a blood sample of approximately 24 mL for immunogenicity 
assessments. 
• Collect colonization swab samples from the nose and throat. 
• Determine whether any AEs or SAEs have occurred or require updating since the last 
subject assessment.  Record and report AEs as described in Section 8 and the Schedule of 
Activities for Adverse and Study Event Reporting (Table 2). 
• Review the subject’s medical record for any new or additional perioperative information 
described in Appendix 3. 
• Record the information (where applicable) contained in the healthcare-utilization 
assessment described in Appendix 4. 
• Remind the subject to contact the investigator immediately if he or she develops signs 
and symptoms of postoperative infection (eg, fever, chills, increased pain, redness, 
swelling, or discharge at the wound) or is hospitalized or treated with antibiotic therapy. 
• Schedule the next study appointment within the allowed visit window. 
• Complete the source documents and CRF. 
6.3.2. Visit 3, Day 21 Telephone Contact (Window: Days 18-26) 
• Record nonstudy vaccinations and concomitant medications as described in Section 5.4. 
• Determine whether any AEs or SAEs have occurred or require updating since the last 
subject assessment.  Record and report AEs as described in Section 8 and the Schedule of 
Activities for Adverse and Study Event Reporting (Table 2). 
• Determine whether the subject has or has had a suspected PDI; if so, record and report 
the PDI event as described in Section 7.1.1, and 

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• If the suspected PDI represents BSI and/or SSI, arrange an unscheduled visit and perform 
the procedures required for a BSI/SSI assessment visit described in Section 7.1.1.1. 
• If the suspected PDI does not represent a BSI and/or SSI the BSI/SSI assessment visit 
procedures are not required. 
• Record the number of visits to a physical or rehabilitation specialist or days in a skilled 
nursing home or rehabilitation hospital (Appendix 4). 
• Remind the subject to contact the investigator immediately if he or she develops signs 
and symptoms of postoperative infection (eg, fever, chills, increased pain, redness, 
swelling, or discharge at the wound) or is hospitalized or treated with antibiotic therapy. 
• Complete the source documents and CRF. 
6.3.3. Visit 4, Day 42 Postoperative Evaluation (Window: Days 35-49) 
• Record nonstudy vaccinations and concomitant medications as described in Section 5.4. 
• Collect and process a blood sample of approximately 24 mL for immunogenicity 
assessments. 
• Collect colonization swab samples from the nose and throat. 
• Determine whether any AEs or SAEs have occurred or require updating since the last 
subject assessment.  Record and report any events as described in Section 8 and the 
Schedule of Activities for Adverse and Study Event Reporting (Table 2). 
• Determine whether the subject has or has had a suspected PDI; if so, record and report 
the PDI event as described in Section 7.1.1, and 
• If the suspected PDI represents BSI and/or SSI, perform the procedures required for a 
BSI/SSI assessment visit described in Section 6.4.2. 
• If the suspected PDI does not represent a BSI and/or SSI the BSI/SSI assessment visit 
procedures are not required. 
• Perform a healthcare-utilization assessment as specified in Appendix 4. 
• Remind the subject to contact the investigator immediately if he or she develops signs 
and symptoms of postoperative infection (eg, fever, chills, increased pain, redness, 
swelling, or discharge at the wound) or is hospitalized or treated with antibiotic therapy. 
• Schedule the next study appointment within the allowed time window. 
• Complete the source documents and CRF. 

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6.3.4. Visit 5, Day 90 Postoperative Evaluation (Window: Days 83-97) 
• Record nonstudy vaccinations and concomitant medications as described in Section 5.4. 
• Collect and process a blood sample of approximately 24 mL for immunogenicity 
assessments. 
• Collect colonization swab samples from the nose and throat. 
• Determine whether any SAEs or newly diagnosed chronic medical disorders have 
occurred since the last subject assessment.  Record and report any events as described in 
Section 8 and the Schedule of Activities for Adverse and Study Event Reporting 
(Table 2). 
• Determine whether the subject has or has had a suspected PDI; if so, record and report 
the PDI event as described in Section 7.1.1, and 
• If the suspected PDI represents BSI and/or SSI, perform the procedures required for a 
BSI/SSI assessment visit described in Section 6.4.2. 
• If the suspected PDI does not represent a BSI and/or SSI, the BSI/SSI assessment 
visit procedures are not required. 
• Perform a healthcare-utilization assessment as specified in Appendix 4. 
• Remind the subject to contact the investigator immediately if he or she develops signs 
and symptoms of postoperative infection (eg, fever, chills, increased pain, redness, 
swelling, or discharge at the wound) or is hospitalized or treated with antibiotic therapy. 
• Schedule the next study appointment within the allowed time window. 
• Complete the source documents and CRF. 
6.3.5. Visit 6, Day 180 Postoperative Evaluation (Window: Days 178-192) 
The Day 180 postoperative evaluation visit may be conducted at the study site or may be 
conducted via telephone interview, with collection of blood and colonization samples by a 
home nursing visit or by other arrangement.  If it is suspected that the subject has a BSI/SSI, 
a site visit will be required. 
• Record nonstudy vaccinations and concomitant medications as described in Section 5.4. 
• Collect and process a blood sample of approximately 24 mL for immunogenicity 
assessments. 
• Collect colonization swab samples from the nose and throat. 

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• Determine whether any SAEs or newly diagnosed chronic medical disorders have 
occurred since the last subject assessment.  Record and report any events as described in 
Section 8 and the Schedule of Activities for Adverse and Study Event Reporting 
(Table 2). 
• Determine whether the subject has or has had a suspected PDI; if so, record and report 
the PDI event as described in Section 7.1.1, and 
• If the suspected PDI represents BSI and/or SSI, perform the procedures required for a 
BSI/SSI assessment visit described in Section 6.4.2. 
• If the suspected PDI does not represent a BSI and/or SSI the BSI/SSI assessment visit 
procedures are not required. 
• Perform a healthcare-utilization assessment as specified in Appendix 4. 
• Complete the source documents and CRF. 
6.4. Unscheduled Study Visits 
A list of unscheduled visits which are to occur when certain conditions are met is presented 
in Table 3.  A list of procedures for these visits is presented in Table 4. 
6.4.1. Assessment of Postvaccination Severe Reactions and Systemic Events 
6.4.1.1. Unscheduled Telephone Contacts 
6.4.1.1.1. Severe Local Reaction or Fever Telephone Contact (Up to 10 Days After 
Study Vaccination) 
If a severe local reaction (redness, swelling, or pain [at the injection site]) or fever ≥39.0°C 
(≥102.1°F) is reported in the e-diary within 10 days of study vaccination, a telephone contact 
between the subject and the investigator will be conducted as soon as possible to assess 
whether a severe local reaction or fever assessment visit is required.  In the event the subject 
does not call the investigator, the investigator will call the subject. 
A severe local reaction or fever assessment visit (Section 6.4.1.2) will be scheduled as soon 
as possible to assess the extent of the reaction, unless: 
• The reaction is no longer present at the time of the telephone contact, or 
• The investigator confirms that the data were entered into the e-diary in error, or 
• The subject is unable to attend the severe local reaction or fever assessment visit.  In this 
event, reactions (if still present) will be assessed at the next scheduled visit; findings will 
be documented in the source notes. 
This telephone contact will be recorded in the source documents and CRF. 

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6.4.1.1.2. Severe Systemic Event Telephone Contact (Up to 10 Days After Study 
Vaccination) 
If a severe systemic event (fatigue, headache, muscle pain, and joint pain) is reported in the 
e-diary within 10 days of study vaccination, the investigator must contact the subject by 
phone as soon as possible to determine whether the systemic event meets Grade 4 and/or 
SAE reporting criteria (refer to Section 7.2.1.4 and Section 8.6). 
This telephone contact will be recorded in the source documents. 
6.4.1.2. Severe Local Reaction or Fever Assessment Visit (Up to 10 Days After Study 
Vaccination) 
At the severe local reaction or fever assessment visit, the following procedures will be 
conducted by the investigator or medically qualified member of the study staff.  For the 
purpose of severe reaction assessment, a medically qualified member of the study staff is a 
study physician, physician assistant, or study nurse, as applicable to the investigator’s local 
practice. 
• Measure the subject’s temperature (°C or °F). 
• Measure the minimum and maximum diameter of redness at the site of vaccination. 
• Measure the minimum and maximum diameter of swelling at the site of vaccination. 
• Assess the subject’s pain in accordance with the grades provided in Section 7.2.1.3. 
• Assess the subject for lymphadenopathy associated with the reaction. 
• Complete the source documents and CRF. 
6.4.2. BSI/SSI Assessment Visit 
At any time after surgery until completion of study participation, when a subject is suspected 
of having a BSI and/or SSI, a BSI/SSI assessment visit will be conducted. 
If the BSI/SSI assessment visit occurs during the index study admission, or is coincident with 
the Day 21 telephone contact or the Day 42, Day 90, or Day 180 postoperative assessment 
visit, the BSI/SSI assessment visit study procedures common to both visits may be combined. 
The following procedures will be conducted: 
• Complete a PDI event report for BSI and /or SSI, as appropriate for the PDI(s), as 
described in Section 7.1.1. 
• Collect and process a blood sample of approximately 24 mL for immunogenicity 
assessments. 
• Collect colonization swab samples from the nose and throat. 

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• Collect blood culture sample(s) for any suspected BSI or deep incisional or organ/space 
SSI and, when clinically indicated, for a superficial SSI. 
• For an SSI that is operatively incised and/or spontaneously draining, collect a wound 
culture swab as per local clinical laboratory guidance.  Where possible, tissue and fluid 
samples are to be taken prior to commencing administration of antibiotics. 
• Record antibiotic therapy as concomitant medication(s) as described in Section 5.4. 
• Determine whether any AEs or SAEs have occurred or require updating since the last 
subject assessment.  Record and report AEs as described in Section 8 and according to 
the Schedule of Activities for Adverse and Study Event Reporting (Table 2). 
• Complete the source documents and CRF. 
In the event that a subject is identified as having a suspected BSI and/or SSI and it is not 
possible to complete the BSI/SSI assessment visit (eg, in the event that the investigator is 
made aware of an infection that has already been treated to resolution by medical personnel 
external to the study team, and where there are no active signs or symptoms of infection), a 
PDI event report will be completed regardless. 
6.4.3. Hospitalization Visit 
Hospitalization(s) subsequent to the index hospital admission will be evaluated as 
hospitalization visit(s). 
A hospitalization visit will be required for any admission (including short-stay [<24 hours] 
admissions) to a hospital or equivalent healthcare facility that occurs subsequent to discharge 
from the index hospital. 
On admission to hospital, the investigator will assess whether the indication for 
hospitalization represents a postoperative complication of the index surgical procedure 
(eg, postoperative infection, increased pain at the surgical site, loose or broken hardware) or 
is coincidental to the index surgical procedure. 
On each day of hospitalization, the investigator will assess: 
• Whether the subject has or has had a suspected PDI; if so, record and report the PDI 
event as described in Section 7.1.1, and 
• If the suspected PDI represents BSI and/or SSI, perform the procedures required for a 
BSI/SSI assessment visit described in Section 6.4.2. 
• If the suspected PDI does not represent a BSI and/or SSI, the BSI/SSI assessment 
visit procedures are not required. 

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• Whether the subject meets the protocol-defined criteria for organ failure as described in 
Section 7.2.3.  When a subject is identified as having organ dysfunction: 
• Record daily SOFA scores on the SOFA worksheet, as described Section 7.2.3, until 
the event is resolved (normal or baseline) or until hospital discharge if the event 
remains unresolved. 
• When a SOFA score of ≥3 is recorded for any single organ, record the SOFA score in 
the CRF on a daily basis until the failing organ system(s) returns to normal/baseline 
or stabilizes. 
• Record the OF events (SOFA ≥3) as AEs/SAEs as appropriate.  SOFA Scores <3 
should be assessed to determine if AE reporting is required as per Section 8. 
• If the subject develops MOF, ie, OF in 2 or more systems concurrently, collect a 
24-mL blood sample for immunogenicity. 
• Complete a MOF event report and submit the event for adjudication as detailed in the 
SRM. 
• If the index surgical procedure requires subsequent spine surgery reoperation and 
revision (eg, for loose hardware, debridement, decompression, dural tear repair), record 
the details of the subsequent surgery as listed in the perioperative assessment shown in 
Appendix 3.  If, during a reoperation and revision of the index surgery, hardware or tissue 
is removed, the hardware and/or tissue should be cultured. 
• Determine whether any AEs or SAEs have occurred or require updating since the last 
subject assessment.  Record and report AEs as described in Section 8 and according to 
the Schedule of Activities for Adverse and Study Event Reporting (Table 2). 
• Record antibiotic therapy as concomitant medication(s) as described in Section 5.4. 
• At hospital discharge, perform a healthcare-utilization assessment as specified in 
Appendix 4. 
• Complete the source documents and CRF. 
6.5. Subject Withdrawal and Safety Follow-up 
6.5.1. Subject Withdrawal From the Study 
Subjects will be withdrawn from the study under the following circumstances: 
• If the subject was enrolled but did not receive the investigational product (SA4Ag or 
placebo). 
• At any time at their own request. 

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• At the discretion of the investigator or sponsor for safety or behavioral reasons, or the 
inability of the subject to comply with the protocol-required schedule of study visits or 
procedures at a given study site. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  Details for contacting lost-to-follow-up subjects are provided in the SRM.  In any 
circumstance, every effort should be made to document subject outcome, if possible.  The 
investigator should inquire about the reason for withdrawal, request that the subject return for 
a final visit, if applicable, and follow up with the subject regarding any unresolved AEs. 
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent. 
6.5.2. Safety Follow-up 
Any vaccinated subject who undergoes the index surgical procedure and who withdraws 
from the study, and provided the subject is agreeable, will receive safety follow-up as 
follows: 
• AEs will be monitored until the Day 42 postoperative evaluation. 
• SAEs will be monitored for at least 6 months after vaccination. 
Any vaccinated subject who does not undergo the index surgical procedure within 6 months 
after vaccination or any vaccinated subject who withdraws from the study prior to the index 
surgical procedure, and provided the subject is agreeable, will receive safety follow-up as 
follows: 
• AEs will be monitored for at least 28 days after vaccination. 
• SAEs will be monitored for at least 6 months after vaccination. 
7. ASSESSMENTS 
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances, outside of the control of the investigator, that may make it unfeasible to 
perform the test.  In these cases, the investigator will take all steps necessary to ensure the 
safety and well-being of the subject.  When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible.  The 
study team will be informed of these incidents in a timely fashion. 

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7.1. Efficacy Assessments 
7.1.1. PDI Events 
All subjects who undergo the index surgical procedure will be monitored for PDIs after 
surgery until the Day 180 postoperative evaluation. 
The investigator will review all suspected PDIs against the clinical criteria provided in 
Appendix 1.  Where the clinical criteria are met, the following procedures will be conducted: 
• Notify the sponsor that a PDI event has occurred. 
• Complete the requirements for a BSI/SSI event (Section 6.4.2) or an ISA event 
(Section 7.1.1.2). 
• Report the PDI event in the CRF. 
If an infection occurs after discharge from the index hospital, and the infection is managed or 
treated by a noninvestigator physician or at a nonstudy hospital, the study investigator will 
contact the treating noninvestigator physician/hospital to obtain the information required 
(eg, medical or hospital records, clinical, diagnostic, and microbiological data) to determine 
whether the infection meets PDI clinical criteria.  If the clinical criteria are met, the 
investigator will complete the PDI event report noted above and notify the sponsor. 
For the purposes of this study, PDIs will include all the infections listed in Table 6 and 
Table 7.  As shown in Figure 1, the relationships between ISA, BSI, and SSI overlap, insofar 
as all BSI and SSI, with the exception of superficial SSI, are considered to be ISA disease. 
Figure 1. Protocol-Defined Infections (Venn Diagram) 
 
 

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7.1.1.1. BSI and SSI Events 
All BSI and SSI listed in Table 6 require an unscheduled BSI/SSI assessment visit 
(Section 6.4.2). 
Specific to spinal fusion surgery, osteomyelitis, vertebral disc space infection, meningitis, 
and spinal abscess without meningitis, when directly attributable to posterior midline or 
posterolateral surgical incisions, will be reported as organ/space SSIs.  Likewise, 
intra-abdominal infection, when directly attributable to an intra-abdominal incision, and 
joint and bursa infection, when directly attributable to a surgical incision (eg, harvesting 
autologous bone), will be reported as organ/space SSIs. 
The EAC will confirm that the clinical and microbiological criteria shown in Appendix 1 
have been met before events are acknowledged as confirmed S aureus BSI or SSI cases.  
Microbiologically confirmed S aureus BSI and SSI cases will contribute to the study 
endpoints. 
Table 6. 
BSI and SSI Events Requiring an Unscheduled Assessment Visit 
Bloodstream infection  
Superficial SSI 
Deep incisional SSI 
Organ/space SSI  
Osteomyelitisa 
Vertebral disc space infectiona 
Meningitisa 
Spinal abscess without meningitisa 
Intra-abdominal infectiona 
Joint or bursa infectiona 
Abbreviations: BSI = bloodstream infection; SSI = surgical-site infection. 
a. 
Report as organ/space SSI when the infection involves tissue that was opened or manipulated during the 
index surgical procedure. 
 
7.1.1.2. ISA Events 
The PDIs listed in Table 7 do not require an unscheduled assessment visit.  However, the 
investigator will review the clinical and microbiological data listed in Appendix 1 specific 
for the suspected PDI. 
Osteomyelitis, vertebral disc space infections, spinal abscess without meningitis, meningitis, 
intra-abdominal infections, and joint or bursa infections, will be evaluated as potential ISA 
events when they do not fulfill the requirements for an organ/space SSI described in 
Section 7.1.1.1. 
All PDIs will be reported for adjudication by the EAC.  Designation of an ISA event as 
“confirmed” is the responsibility of the EAC, based upon defined criteria listed in 
Appendix 1. 

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For ISA events, the documentation to support elements of respective PDI criteria as specified 
in respective PDI definitions in Appendix 1 will be provided for adjudication. 
All PDIs in Table 7 should be reported as an AE/SAE irrespective of whether or not the 
infectious pathogen is shown to be S aureus (eg, meningococcal meningitis, Pseudomonas 
pneumonia, Streptococcus viridans endocarditis). 
Table 7. 
PDIs Contributing to ISA Disease (in Addition to BSI and Deep Incisional 
and/or Organ/Space SSI) 
Osteomyelitis  
Spinal abscess without meningitis  
Joint or bursa infection  
Pneumonia  
Periprosthetic infection  
Intra-abdominal infection 
Vertebral disc space infection 
Endocarditis  
Meningitis 
 
Abbreviations: BSI = bloodstream infection; ISA= invasive Staphylococcus aureus; PDI = protocol-defined 
infection; S aureus = Staphylococcus aureus; SSI = surgical-site infection. 
 
When osteomyelitis, vertebral disc space infections, spinal abscess without meningitis, meningitis, 
intra-abdominal infections, and joint or bursa infections do not involve tissue that was opened or manipulated 
during the index surgical procedures (and therefore are organ/space SSI as per Table 6), but are positive for 
S aureus, they are reported as ISA disease using the verbatim term. 
 
When a subject with an S aureus BSI develops any of the ISA events shown in this table, the BSI will 
contribute to the primary or secondary endpoint. 
 
In the event that a subject develops any other invasive infection such as those listed in 
Table 8 the clinical criteria for the infection should be reviewed against the NHSN criteria 
provided in the SRM. 
All other invasive infections will be reported for adjudication by the EAC.  Evidential 
clinical and microbiological data are to be provided to support the adjudication process. 
Table 8. 
Other Invasive Infections 
Intracranial infections (brain abscess, 
subdural or epidural infection, encephalitis) 
Mediastinitis 
Myocarditis  
Mastoiditis 
Pericarditis 
Ventilator-acquired pneumonia 
Nondefined,a eg, necrotizing fasciitis  
 
a. 
The nondefined infection category includes any invasive infection that is not defined in Appendix 1 or the 
study reference manual.  For any invasive infection reported under this category, the adjudication criteria 
and required supportive data will be provided by the event adjudication committee. 
- Contact the medical monitor for guidance when reporting under this category. 
- Deep SSI unrelated to the index surgery are reported to the EAC and assessed using the NHSN criteria. 
 

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7.2. Safety Assessments 
Safety parameters will be assessed as described in the Schedule of Primary Activities 
(Table 1) and below.  Any subject who receives the investigational product will be included 
in the evaluation for safety. 
A medical history, physical examination, and measurement of vital signs will be performed 
on all subjects prior to vaccination to determine subject eligibility and to establish a clinical 
baseline.  Significant medical and surgical history and observations from the physical 
examination and vital sign measurement will be documented and recorded in the CRF. 
The postvaccination safety parameters include assessments of local reactions and systemic 
events occurring within 10 days following investigational product administration.  They will 
be graded as described in Section 7.2.1.3 and Section 7.2.1.4. 
Reactions occurring within 30 minutes after investigational product administration will be 
documented and recorded in the AE CRF. 
AEs, SAEs, and newly diagnosed chronic medical disorders will be collected as described in 
Table 2 and reported as described in Section 8.14.  A newly diagnosed chronic medical 
disorder is defined as a disease or medical condition, not previously identified, that is 
expected to be persistent or otherwise long-lasting in its effects. 
7.2.1. Local Reactions and Systemic Events 
7.2.1.1. Electronic Diary 
The subject will be issued an e-diary, based on a personal digital assistant (PDA) or 
equivalent technology.  Prior to vaccination, a baseline assessment (fatigue, headache, 
muscle pain, or joint pain over the previous month) will be recorded in the e-diary.  Starting 
on the day of vaccination, the subject will monitor and record local reactions, systemic 
events, and any antipyretics or pain medication used to treat symptoms, for 10 days.*  The 
e-diary allows recording of these assessments only within a fixed time window, thus 
providing the accurate representation of the subject’s experience at that time.  Data on local 
reactions, systemic events, and antipyretics/pain medication used to treat symptoms reported 
in the e-diary will be transferred electronically to the e-diary vendor, where they will be 
available for review by investigators via an Internet-based portal.  At intervals agreed to by 
the vendor and Pfizer, the data will be transferred electronically into Pfizer's event database 
for analysis and reporting. 
Investigators (or appropriately qualified designee) are required to review the daily e-diary 
data online at frequent intervals during active vaccination periods, as part of the ongoing 
safety review. 
The investigator or designee will obtain from the subject stop dates for any symptoms 
ongoing on the last day that the e-diary was completed.  The stop dates will be documented 
in the source documents and the information entered in the CRF. 

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*In the event that surgery occurs on the 10th day after vaccination, the e-diary data for 
Day 10 does not need to be completed. 
7.2.1.2. Grading Scales for Local Reactions and Systemic Events 
The grading scales used in this study to assess local reactions and systemic events as 
described below are derived from the Food and Drug Administration (FDA) Center for 
Biologics Evaluation and Research (CBER) guidelines on toxicity grading scales for healthy 
adult volunteers enrolled in preventive vaccine clinical trials.54 
7.2.1.3. Local Reactions 
For 10 consecutive days starting on the day of vaccination, subjects will be asked to assess 
redness, swelling, and pain at the injection site and to record the symptoms in the e-diary.  
Redness and swelling will be measured and recorded in caliper units (range: 1 to 21+), and 
then categorized as mild, moderate, or severe based on the grading scale in Table 9.  
Caliper units can be converted to centimeters according to the following formula: 
1 caliper unit = 0.5 cm. 
Pain at the injection site will be assessed by the subject as mild, moderate, or severe 
according the grading scale in Table 9.  A subject with a severe/Grade 3 local reaction will be 
instructed to contact the investigator to assess the reaction and perform a severe local 
reaction or fever assessment visit as appropriate.  In the event that the subject does not call, 
the investigator will call the subject. 
7.2.1.3.1. Management of Grade 4 Local Reactions 
Only an investigator is able to classify a subject’s local reaction as Grade 4, after physical 
examination of the subject or telephone contact with the subject.  Confirmed Grade 4 local 
reactions require immediate notification to the sponsor and include: 
• Skin necrosis or exfoliative dermatitis (for redness) or skin necrosis (for swelling): 
Consider whether the reaction is an important medical event (Section 8.6).  If yes, report 
the reaction as an SAE; if no, report it as an AE.  Grade the severity of the necrosis or 
exfoliative dermatitis using the AE severity grading scale in Section 8.8. 
• An emergency room visit for management of pain at the injection site:  
Consider whether the reaction is an important medical event (Section 8.6).  If yes, report 
the reaction as an SAE; if no, report it as an AE.  Grade the severity of the injection site 
pain using the AE severity grading scale in Section 8.8. 
• Hospitalization for management of pain at the injection site:  
Report the hospitalization for injection site pain management as an SAE and grade the 
severity of the injection site pain using the AE severity grading scale in Section 8.8. 

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Table 9. 
Local Reaction Grading Scale 
 
GRADE 1 
mild 
GRADE 2 
moderate 
GRADE 3a 
severe 
GRADE 4b 
 
Redness 
5 to 10 caliper units 
(or measuring device 
units) 2.5 to 5.0 cm 
11 to 20 caliper units 
(or measuring device 
units) 5.5 to 10.0 cm 
≥21 caliper units 
(or measuring device 
units) ≥10.5 cm 
Necrosis 
or exfoliative 
dermatitisb 
Swelling 
5 to 10 caliper units 
(or measuring device 
units) 2.5 to 5.0 cm 
11 to 20 caliper units 
(or measuring device 
units) 5.5 to 10.0 cm 
≥21 caliper units 
(or measuring device 
units) ≥10.5 cm 
Necrosisb 
Pain at the 
injection site 
Does not interfere with 
activity 
Interferes with activity Prevents daily activity Emergency room visit 
or hospitalization 
Abbreviations: AE = adverse event; CRF = case report form; e-diary = electronic diary. 
a. 
Subjects experiencing local reactions ≥21 caliper units (≥10.5 cm) or severe pain at the injection site will 
telephone the study site.  In the event that the subject does not call, the investigator will call the subject. 
b. Grade 4 assessment should be made by the investigator and recorded as an AE on the CRF.  Manage as 
shown in Section 7.2.1.3.1 and Section 8.8. 
If the size of the redness and/or swelling falls between 2 caliper units, the higher caliper unit number will be 
recorded in the e-diary. 
 
7.2.1.4. Systemic Events 
Prior to vaccination, subjects will consider whether they generally experience fatigue, 
headache, muscle pain, or joint pain.  If so, the symptoms will be graded as mild, moderate, 
or severe and recorded in the e-diary as baseline symptoms.  The Systemic Event Grading 
Scale in Table 10 will be used. 
Starting on the day of vaccination, and for 10 consecutive days, postvaccination systemic 
events will be assessed by the subject each day, and if present, they will be graded as mild, 
moderate, or severe and recorded in the e-diary, using the grading scale in Table 10. 
A subject with a severe/Grade 3 systemic event will be instructed to contact the investigator 
who will assess the reaction.  In the event that the subject does not call, the investigator will 
call the subject. 
7.2.1.4.1. Management of Grade 4 Systemic Events 
Only an investigator is able to classify a subject’s systemic event as Grade 4, after physical 
examination of the subject or telephone contact with the subject.  Confirmed Grade 4 
systemic events require immediate notification to the sponsor and include: 
• An emergency room visit for management of a systemic event: 
Consider whether the systemic event is an important medical event (Section 8.6).  If yes, 
report the event as an SAE; if no, report it as an AE.  Grade the severity of the systemic 
event using the AE severity grading scale in Section 8.8. 
• Hospitalization for management of a systemic event: 

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Report hospitalizations for management of a systemic event as an SAE and grade the 
severity of the systemic event according to the AE severity grading scale in Section 8.8. 
Table 10. Systemic Event Grading Scale 
 
GRADE 1 
mild 
GRADE 2 
moderate 
GRADE 3a 
severe 
GRADE 4b 
Fatigue 
(Tiredness) 
Does not interfere 
with activity 
Some interference 
with activity 
Prevents daily routine 
activity 
Emergency room visit 
or hospitalization 
Headache 
Does not interfere 
with activity 
Some interference 
with activity 
Prevents daily routine 
activity 
Emergency room visit 
or hospitalization 
Vomiting 
1 to 2 times in 
24 hours 
>2 times in 24 hours 
Requires intravenous 
hydration 
Emergency room visit 
or hospitalization 
Diarrhea 
2 to 3 loose stools in 
24 hours 
4 to 5 loose stools in 
24 hours 
6 or more loose stools 
in 24 hours 
Emergency room visit 
or hospitalization 
Muscle pain 
Does not interfere 
with activity 
Some interference 
with activity 
Prevents daily routine 
activity 
Emergency room visit 
or hospitalization 
Joint pain 
Does not interfere 
with activity 
Some interference 
with activity 
Prevents daily routine 
activity 
Emergency room visit 
or hospitalization 
Abbreviations: AE = adverse event; CRF = case report form. 
a. 
Subjects experiencing severe systemic events will telephone the study site.  In the event that the subject 
does not call, the investigator will call the subject. 
b. Grade 4 assessment should be made by the investigator and recorded as an AE on the CRF.  Manage as 
shown in Section 7.2.1.4.1 and Section 8.8. 
 
7.2.1.5. Fever 
To record fever, a digital thermometer will be given to the subject with instructions on how 
to measure his or her oral temperature.  Starting on the day of vaccination, temperature will 
be measured each evening for 10 consecutive days and at any time during the 10 days that 
fever is suspected.  Fever is defined as an oral temperature of ≥38.0°C (100.4°F).  The 
highest temperature for each day will be recorded in the e-diary.  In the event of a fever, 
temperature will be collected daily until fever has resolved (1 day with a temperature less 
than 38.0°C [100.4°F]).  Temperature will be measured and recorded to 1 decimal place and 
then categorized during analysis according to the scale shown in Table 11. 
Where a fever ≥39.0°C (≥102.1°F) is recorded, the subject will contact the investigator by 
telephone and the investigator will assess whether a severe local reaction or fever assessment 
visit is required (refer to Section 6.4.1.1.1).  If the subject does not call the investigator, the 
investigator will contact the subject. 
Table 11. Scale for Fever 
38.0 to 38.4°C (100.4 to 101.1°F) 
38.5 to 38.9°C (101.2 to 102.0°F) 
39.0 to 40.0°C (102.1 to 104.0°F)  
>40.0°C (>104.0°F)  

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7.2.2. Preoperative and Perioperative Subject Status Assessments 
7.2.2.1. Charlson Comorbidity Index 
The Charlson comorbidity index (CCI) is a validated prognostic indicator for which factors, 
individually or in combination, may increase the risk of short-term mortality for patients 
enrolled in longitudinal studies.55  On completion of the physical examination at Visit 1, the 
investigator or designee will record the presence of each comorbid condition and age cohort 
as presented in Table 12 in the CRF. 
The sum of the values for each comorbid condition is added to the subject’s value for age to 
obtain the CCI.  Both the CCI and the Charlson probability (10-year survival) will be derived 
programmatically. 
CCI = sum of comorbid conditions + value for age (on the date of assessment) 
Table 12. Charlson Comorbidity Score 
Comorbid Condition 
Score 
Age Cohort and Value for Age 
(on the Date of Assessment) 
History of prior myocardial infarction (not ECG changes only) 
1 
Age ≤40 years: 0 points 
Congestive heart failure 
1 
Age 41-50 years: 1 point 
Peripheral vascular disease  
1 
Age 51-60 years: 2 points 
Cerebrovascular disease 
1 
Age 61-70 years: 3 points 
Dementia 
1 
Age 71-80 years: 4 points 
Diabetes 
1 
Age 81-90 years: 5 points 
Mild liver disease 
1 
 
Chronic pulmonary disease 
1 
 
Gastric/duodenal ulcer 
1 
 
Connective tissue disease 
1 
 
Hemiplegia 
2 
 
Moderate or severe renal disease 
2 
 
Diabetes with end-organ damage 
2 
 
Tumor 
2 
 
Leukemia 
2 
 
Lymphoma 
2 
 
Moderate or severe liver disease 
3 
 
Metastatic solid tumor 
6 
 
AIDS 
6 
 
Abbreviations: AIDS = acquired immunodeficiency syndrome; ECG = electrocardiographic. 
 
7.2.2.2. American Society of Anesthesiologists (ASA) Physical Status Classification 
Score 
The American Society of Anesthesiologists (ASA) physical status classification system is 
utilized by anesthesiologists to assess the fitness of surgical patients prior to undergoing 
surgery.  ASA scores correlate with patient morbidity and postoperative infection risk.56  At 
Visit 2 and prior to surgery, the subject’s physical status will be assessed and classified by 
the anesthesiologist using the ASA score shown in Table 13. 

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Table 13. American Society of Anesthesiologists (ASA) Physical Status Classification 
Score 
Description 
1 
Healthy patient 
2 
Mild systemic disease with no functional limitation 
3 
Severe systemic disease with definite functional limitation 
4 
Severe systemic disease that is a constant threat to life 
5 
Moribund patient unlikely to survive 24 hours with or without operation 
Adapted from American Society of Anesthesiologists.  ASA physical status classification system.  Available: 
http://www.asahq.org/Home/For-Members/Clinical-Information/ASA-Physical-Status-Classification-System.  
18 Jun 2014. 
 
7.2.3. Assessment of Organ Failure 
All subjects who undergo the index surgical procedure will be monitored for OF events 
across the following time periods: 
• during the index hospital admission from after surgery until discharge  
• during any subsequent hospitalization(s) that occur over the course of the study 
including, where possible, those that occur at any outside hospital 
As OF is sequential and progressive, subject monitoring will occur on a daily basis while the 
subject is hospitalized.  There is no protocol requirement to perform the procedures required 
to calculate a daily SOFA score; rather, the investigator will review the subject’s clinical care 
records (eg, laboratory results, nursing and medical progress notes) to determine whether or 
not the subject meets the criteria for an OF event.  If the data required to score an organ are 
not available on the day of assessment, by default the score for that variable will be zero (0). 
A clinical diagnosis of organ failure will be established for each of the 6 organ 
systems-respiratory, cardiovascular, renal, hematological, neurological, and hepatic—on the 
basis of SOFA scores57 (Table 14).  OF is defined as a SOFA score ≥3 in any 1 organ system, 
while MOF is defined as OF in 2 or more organ systems simultaneously. 
If the subject develops organ system dysfunction, daily SOFA scores are recorded on the 
SOFA worksheet until organ function returns to normal/baseline or until hospital discharge if 
the event remains unresolved. 
When a SOFA score of ≥3 (OF) is recorded for any single organ, SOFA scores will be 
entered into the CRF on a daily basis until the failing organ system(s) returns to 
normal/baseline or stabilizes. 
Organ dysfunction and OF events will be reported as AEs or SAEs as appropriate. 
All MOF events will be adjudicated by the EAC to determine whether the protocol-defined 
clinical criteria have been met, whether confirmed events are PDI related or due to 
noninfectious causes, and whether the PDI-related events are attributable to 

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microbiologically confirmed S aureus, attributable to other organism(s), or without 
microbiological confirmation. 
Additional guidance for obtaining and reporting the SOFA scores and reporting MOF is 
provided in the SRM. 
Table 14. Sequential Organ Failure Assessment Score 
Variables 
SOFA Score 
 
0 
1 
2 
3 
4 
Respiratory 
PaO2/FiO2, mm Hg 
           or 
SpO2/FiO2, mm Hga 
>400 
 
>400 
≤400 
 
≤400 
≤300 
 
≤315 
≤200b 
 
≤230 
≤100b 
 
≤150 
Coagulation 
Platelets x 103/µL 
>150 
≤150 
≤100 
≤50 
≤20 
Liver 
Bilirubin, mg/dL 
<1.2 
1.2-1.9 
2.0-5.9 
6.0-11.9 
≥12 
Cardiovascular 
Hypotension 
No 
hypotension 
Mean arterial 
pressure <70 
mm Hg 
Dop ≤5 
or dob 
(any dose)c 
Dop >5, 
epi ≤0.1, or 
norepi ≤0.1 
or 
phenylephrine
≤0.1c; or 
vasopressin 
<0.04 U/min 
Dop >15 epi 
>0.1, or norepi 
>0.1 or 
phenylephrine 
>0.1c; or 
vasopressin 
≥0.04 U/min 
Central nervous system 
Glasgow Coma Scale 
(GCS) scored 
15 
13-14 
10-12 
6-9 
<6 
Renal 
Creatinine, mg/dL or 
urine output, mL/d 
<1.2 
1.2-1.9 
2.0-3.4 
3.5-4.9 
or <500 
>5 or <200e 
Abbreviations: dob = dobutamine; Dop = dopamine; epi = epinephrine; FiO2 = fraction of inspired oxygen; 
norepi = norepinephrine; PaO2 = partial pressure of oxygen in arterial blood; SOFA = Sequential Organ Failure 
Assessment; SpO2 = saturation of peripheral oxygen. 
a. 
The preferred measurement for the assessment of respiratory failure is the partial pressure of oxygen in 
arterial blood (PaO2) from arterial blood gas data.  If that is unavailable, respiratory failure may also be 
evaluated using a modified respiratory SOFA score based on saturation of peripheral oxygen (SpO2) and 
available FiO2 measurements (eg, face mask, bilevel positive airway pressure, continuous positive airway 
pressure).58  If the direct FiO2 measurement is not available (eg, nasal cannula), a respiratory score should 
not be calculated. 
b. Values are with respiratory support. 
c. 
Adrenergic agents administered for at least 1 hour (doses given are in µg/kg per minute). 
d. In patients receiving sedation or muscle relaxants, normal brain function will be assumed for neurological 
assessment unless there is evidence of altered mentation. 
e. 
Or patient is receiving intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement 
therapy. 
 
 

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7.2.3.1. Assessment of Deaths 
Any deaths that occur during the study will be assessed by the EAC for potential relationship 
to a PDI and/or association with S aureus.  The DMC will also review deaths during 
scheduled safety data review meetings, or on an ad hoc basis if required, in accordance with 
the DMC charter. 
Any death that occurs from the day of informed consent to 180 days after surgery will be 
reported in the CRF and to the sponsor.  Any death that occurs from the date of informed 
consent will be reported as an SAE. 
7.2.4. Pregnancy Testing 
For female subjects of childbearing potential, a urine or serum pregnancy test, with 
sensitivity of at least 25 mIU/mL, will be performed immediately before administration of 
the vaccine/placebo.  A negative pregnancy test result is required before the subject may 
receive the investigational product.  After randomization and vaccination, if the subject 
becomes pregnant during the study, the subject may continue to participate in the study as it 
remains appropriate to follow a subject who becomes pregnant for the development of 
postoperative PDI and fetal outcome.  Pregnancy tests may be repeated at the request of 
IRBs/independent ethics committees (IECs) or if required by local regulations. 
7.3. Microbiology Assessments 
7.3.1. Microbiological Laboratory Procedures 
All samples for microbial culture from suspected infections, regardless of the source of the 
culture material, will be sent to the local microbiology laboratory for isolation of any 
organisms.  Samples for microbiological cultures will be collected as outlined in the study 
procedure and reference manual.  Each pathogen isolated should be identified to the genus 
and species level, if possible.  S aureus strains will be tested for methicillin sensitivity. 
At the investigational site laboratory, study site personnel are responsible for obtaining all 
S aureus isolates and sending them to the central laboratory for processing and shipment of 
samples to the sponsor. 
If the investigational site laboratory subcontracts with an outside laboratory, study site 
personnel are responsible for obtaining all S aureus isolates from the outside laboratory and 
sending them to the central laboratory for processing and shipment of samples to the sponsor. 
The local or outside microbiology laboratory is expected to retain a duplicate of each isolate 
(eg, stored at -70°C) until the isolate has been received, tested, and reported by the central 
laboratory. 
The central laboratory will coordinate and provide each study site with shipping supplies and 
detailed instructions for the shipment and storage of all microbiological isolates.  In addition 
to species verification, S aureus cultures may be further evaluated for genotypic and possibly 
phenotypic markers by the central laboratory. 

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Sample collection, storage, and shipping information can be found in the laboratory manual. 
7.3.2. Blood Cultures 
For all suspected BSI, deep incisional SSI, and organ/space SSI, and where clinically 
indicated for superficial SSI, 2 sets of blood cultures should be obtained and timed according 
to the local institution’s policy using different sampling sites.  Anaerobic and aerobic 
samples should be collected.  The timing of the repeat culture(s) is at the discretion of the 
investigator.  Whenever possible, blood should be collected from peripheral veins; blood 
drawn through an intravascular catheter will be specifically identified as such in the CRF.  
S aureus isolates will be processed as described above. 
7.3.3. Operative (Surgical Site) Wound Cultures 
Throughout the subject’s participation, bacterial cultures will be obtained at any point during 
the study if the subject undergoes any drainage procedure.  Aerobic and anaerobic cultures 
will be taken from the site of suspected infection during surgical procedures. 
7.3.4. Swabs for Colonization 
Oropharyngeal and nasal swabs for S aureus colonization will be collected from all subjects 
prior to study vaccination, as specified at each postvaccination visit, and at each BSI/SSI 
assessment visit.  Colonization swabs will be sent to a central laboratory for processing and 
culture.  S aureus isolates may be further evaluated by the sponsor or central laboratory for 
genotypic and phenotypic markers.  Colonization by other staphylococcal species isolated 
from the swab samples may also be described. 
7.4. Immunogenicity Assessments 
Blood samples for immunogenicity assessments will be collected from all subjects prior to 
vaccination, prior to the index surgery and at discharge, at each postvaccination clinic visit, 
and at each BSI/SSI assessment visit and in the event of MOF.  Immunoassays will be 
performed at each time point and may include OPA assays using an S aureus CP5-expressing 
strain and CP8-expressing strain, and cLIAs for ClfA and MntC.  Additional exploratory 
assays to measure immune responses may be conducted on all 4 antigens. 
Approximately 24 mL of blood will be drawn at each specified visit.  This will provide 
sufficient serum to conduct the immunogenicity assays and any repeat testing or additional 
immunogenicity assay tests to be performed. 
In case of difficulty in obtaining a blood sample, it is possible to reschedule the sampling as 
long as the date remains in the authorized protocol window for the scheduled study visits. 
Immunogenicity assays will be performed at Pfizer’s Vaccine Research and Development 
Laboratory or at a vendor site.  Sample collection, storage, and shipping information can be 
found in the SRM. 

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7.5. Biological Samples 
Serum samples will be used only for scientific research.  Each sample will be labeled with a 
code so that the laboratory personnel testing the samples will not know the subject’s identity.  
Any remaining sera will be stored by the sponsor, and may be used for additional assays 
and/or analyses to assess immune responses to vaccines or for assay development.  The sera 
will not be used for any unrelated research, and no genetic testing will be performed.  The 
samples will be stored for up to 15 years after the end of the study and then destroyed. 
Each bacterial isolate will be labeled with a code so that the laboratory personnel testing the 
samples will not know the identity of the subject.  Bacterial isolates that are received by the 
sponsor’s central laboratory are considered the property of the sponsor.  (Note that such 
isolates do not contain the subject’s biological material, eg, deoxyribonucleic acid [DNA].) 
The isolates may remain stored beyond study completion (up to 15 years). 
The subject may request that his or her samples, if still identifiable, be destroyed at any time; 
however, any data already collected from those samples will still be used for this research.  
The biological samples will remain the property of the sponsor and may be shared with other 
researchers as long as confidentiality is maintained. 
7.6. Healthcare-Utilization Assessment 
Upon hospital discharge from the index hospital admission, from each subsequent 
hospitalization, and from each postoperative follow-up visit, a healthcare-utilization 
assessment will be conducted (Appendix 4). 
8. ADVERSE EVENT REPORTING 
8.1. Adverse Events 
All observed or volunteered AEs regardless of vaccine group or suspected causal relationship 
to the investigational product(s) will be reported as described in the following sections. 
For all AEs, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as an SAE 
requiring immediate notification to Pfizer or its designated representative.  For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of the 
AE.  The investigator is required to assess causality. 
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment. 
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study. 

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8.2. Reporting Period 
For SAEs, the active reporting period to Pfizer or its designated representative begins from 
the time that the subject provides informed consent, which is obtained prior to the subject’s 
participation in the study, ie, prior to undergoing any study-related procedure and/or 
receiving investigational product, through Visit 6.  SAEs occurring in a subject after the 
active reporting period has ended should be reported to the sponsor if the investigator 
becomes aware of them; at a minimum, all SAEs that the investigator believes have at least a 
reasonable possibility of being related to investigational product will be reported to the 
sponsor. 
AEs will be recorded in the CRF from the signing of the ICD to Visit 4. 
Newly diagnosed chronic medical disorders will be recorded in the CRF from Visit 4 to 
Visit 6. 
8.3. Definition of an Adverse Event 
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage.  Examples of AEs include but are not limited to: 
• Abnormal test findings 
• Clinically significant symptoms and signs 
• Changes in physical examination findings 
• Hypersensitivity 
• Progression/worsening of underlying disease  
• Drug abuse 
• Drug dependency 
Additionally, they may include the signs or symptoms resulting from: 
• Drug overdose 
• Drug withdrawal 
• Drug misuse  
• Drug interactions 
• Extravasation 

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• Exposure during pregnancy (EDP) 
• Exposure via breastfeeding 
• Medication error 
• Occupational exposure 
8.4. Medication Errors 
Medication errors may result, in this study, from the administration or consumption of the 
wrong product, by the wrong subject, at the wrong time, or at the wrong dosage.  Such 
medication errors occurring to a study participant will be captured on the medication error 
CRF, which is a specific version of the AE page, and on the SAE form when appropriate.  In 
the event of medication dosing error, the sponsor should be notified immediately. 
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including: 
• Medication errors involving subject exposure to the investigational product; 
• Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the participating subject. 
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is captured on the medication error version of the AE page 
and, if applicable, any associated AE(s) are captured on an AE CRF page. 
Other examples include, but are not limited to: 
• The administration of expired investigational product 
• The administration of an incorrect investigational product 
• The administration of an incorrect dosage 
• The administration of investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
investigational product under question is acceptable for use. 
8.5. Abnormal Test Findings 
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows: 
• Test result is associated with accompanying symptoms; and/or 
• Test result requires additional diagnostic testing or medical/surgical intervention; and/or 

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• Test result leads to a change in study dosing or discontinuation from the study, significant 
additional concomitant drug treatment, or other therapy; and/or 
• Test result is considered to be an AE by the investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE. 
8.6. Serious Adverse Events 
An SAE is any untoward medical occurrence at any dose that: 
• Results in death 
• Is life-threatening (immediate risk of death) 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions) 
• Results in congenital anomaly/birth defect 
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious. 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse. 
For this study, deep venous thrombosis events are all considered important medical events 
and should be reported as an SAE. 
Medical device complaints may meet the SAE reporting requirement criteria (see section on 
Medical Device Complaint Reporting Requirements).  An incident is any malfunction (ie, the 
failure of a device to meet its performance specifications or to perform as intended; 
performance specifications include all claims made in the labeling for the device) that, 
directly or indirectly, might lead to or might have led to the death of a subject, or user, or of 
other persons, or to a serious deterioration in their state of health. 
A serious injury that can cause a serious deterioration in state of health can include: 
• a life-threatening illness, even if temporary in nature 

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• a permanent impairment of a body function or permanent damage to a body structure 
• a condition necessitating medical or surgical intervention to prevent the above 2 bulleted 
items 
Examples: clinically relevant increase in the duration of a surgical procedure, a condition 
that requires hospitalization or significant prolongation of existing hospitalization 
• any indirect harm as a consequence of an incorrect diagnostic or in vitro diagnostic 
device test results when used within the manufacturer’s instructions for use 
• fetal distress, fetal death, or any congenital abnormality or birth defects 
8.6.1. Protocol-Specified Serious Adverse Events 
Unless the investigator believes that there is a causal relationship between investigational 
product and the efficacy endpoints specified below, the events noted below should not be 
reported by the investigator as SAEs as described in Section 8.14.1. 
The following events are anticipated to occur in a study population following spinal surgery: 
• Suspected or confirmed BSI and/or deep incisional or organ/space SSI 
• Suspected or confirmed superficial SSI 
Any suspected BSI or SSI event has the potential to meet endpoint criteria and is therefore to 
be adjudicated by the EAC.  Reporting requirements (Figure 2) are summarized below while 
additional details are provided in the SRM: 
• If the EAC confirms that the event meets the primary or secondary endpoint criteria, the 
event is not reported as an SAE. 
• If the EAC confirms that the event does not meet the primary or secondary endpoint 
criteria, the event is reported back to the investigator as a nonendpoint SAE.  The 
investigator will evaluate and report the event as an SAE (and AE), in accordance with 
the time frames described in the Serious Adverse Event Reporting Requirements section 
of this protocol (Section 8.14.1) 
Under these circumstances, the investigator’s SAE awareness date is the date that the 
investigator receives the nonendpoint SAE back from the EAC. 
All other events that meet SAE criteria will be reported by the investigator as described in 
previous sections. 

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Figure 2. Protocol-Specified SAE Reporting 
 
 
8.6.2. Potential Cases of Drug-Induced Liver Injury 
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to run LFTs because of clinical 
sign/symptom presentation in a subject, such LFT results should be handled and followed up 
as described below. 
Abnormal values in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 
levels concurrent with abnormal elevations in total bilirubin level that meet the criteria 
outlined below in the absence of other causes of liver injury are considered potential cases of 
drug-induced liver injury (potential Hy’s law cases) and should always be considered 
important medical events. 
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the subject’s individual baseline values and underlying conditions.  Subjects who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values: 
• Subjects with AST or ALT and total bilirubin baseline values within the normal range 
who subsequently present with AST or ALT values ≥3 times the upper limit of normal 
(× ULN) concurrent with a total bilirubin value ≥2 × ULN with no evidence of hemolysis 
and an alkaline phosphatase value ≤2 × ULN or not available; 

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• For subjects with preexisting ALT OR AST OR total bilirubin values above the ULN, 
the following threshold values should be used in the definition mentioned above: 
• For subjects with preexisting AST or ALT baseline values above the normal range: AST 
or ALT values ≥2 times the baseline value and ≥3 × ULN, or ≥8 × ULN (whichever is 
smaller). 
Concurrent with 
• For subjects with preexisting values of total bilirubin above the normal range: Total 
bilirubin level increased from baseline by an amount of at least 1 × ULN or if the value 
reaches ≥3 × ULN (whichever is smaller). 
The subject should return to the investigational site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
In addition to repeating measurements of AST and ALT, laboratory tests should include 
albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl 
transferase, prothrombin time (PT)/international normalized ratio (INR), and alkaline 
phosphatase.  A detailed history, including relevant information, such as review of ethanol, 
acetaminophen, recreational drug, and supplement consumption, family history, occupational 
exposure, sexual history, travel history, history of contact with a jaundiced person, surgery, 
blood transfusion, history of liver or allergic disease, and work exposure, should be collected.  
Further testing for acute hepatitis A, B, or C infection and liver imaging (eg, biliary tract) 
may be warranted.  All cases confirmed on repeat testing as meeting the laboratory criteria 
defined above, with no other cause for LFT abnormalities identified at the time, should be 
considered potential Hy’s law cases irrespective of availability of all the results of the 
investigations performed to determine etiology of the abnormal LFTs.  Such potential Hy’s 
law cases should be reported as SAEs. 
8.7. Hospitalization 
AEs reported from studies associated with hospitalization or prolongations of hospitalization 
are considered serious, with the exception of the index hospital admission. 
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit should be assessed for medical 
importance. 
Hospitalization does not include the following: 
• Rehabilitation facilities 

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• Hospice facilities 
• Respite care (eg, caregiver relief) 
• Skilled nursing facilities 
• Nursing homes 
• Same-day surgeries (as outpatient/same-day/ambulatory procedures) 
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
AE is not in itself an SAE.  Examples include:  
• Admission for treatment of a preexisting condition not associated with the development 
of a new AE or with a worsening of the preexisting condition (eg, for workup of 
persistent pretreatment laboratory abnormality) 
• Social admission (eg, subject has no place to sleep) 
• Administrative admission (eg, for yearly physical examination) 
• Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol) 
• Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery) 
• Hospitalization for observation without a medical AE 
• Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject 
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as AEs.  However, the medical condition for which the procedure was performed 
should be reported if it meets the definition of an AE.  As noted previously, the indication for 
the index surgical procedure is not an AE.  For example, an acute appendicitis that begins 
during the AE reporting period should be reported as the AE, and the resulting appendectomy 
should be recorded as treatment of the AE. 
 

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8.8. Severity Assessment 
GRADE  If required on the AE CRFs, the investigator will use the adjectives MILD, 
MODERATE, SEVERE, or LIFE-THREATENING to describe the maximum 
intensity of the AE.  For purposes of consistency, these intensity grades are 
defined as follows: 
 1 
MILD 
Does not interfere with subject's usual function. 
 2 
MODERATE 
Interferes to some extent with subject's usual function. 
 3 
SEVERE 
Interferes significantly with subject's usual function. 
 4 
LIFE-THREATENING Life-threatening consequences; urgent intervention 
indicated. 
 
The severity grading scale shown above should be used when assessing the severity of any 
AE/SAE, and Grade 4 postvaccination local reactions and systemic events as described in 
Section 7.2.1.3 and Section 7.2.1.4.  Note the distinction between the severity and the 
seriousness of an AE.  A severe event is not necessarily an SAE.  For example, a headache 
may be severe (interferes significantly with the subject's usual function) but would not be 
classified as serious unless it met one of the criteria for SAEs, listed above. 
8.9. Causality Assessment 
The investigator’s assessment of causality must be provided for all AEs (serious and 
nonserious); the investigator must record the causal relationship in the CRF, as appropriate, 
and report such an assessment in accordance with the SAE reporting requirements if 
applicable.  An investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the investigational product caused or contributed to an 
AE; generally the facts (evidence) or arguments to suggest a causal relationship should be 
provided.  If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” for reporting 
purposes, as defined by the sponsor (Section 8.14).  If the investigator's causality assessment 
is "unknown but not related to investigational product," this should be clearly documented on 
study records. 
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable. 

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8.10. Exposure During Pregnancy 
For both unapproved/unlicensed products and for marketed products, an EDP occurs if: 
• A female subject becomes, or is found to be, pregnant either while receiving or having 
been exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female subject becomes, or is found to be, pregnant after discontinuing 
and/or being exposed to the investigational product; 
An example of environmental exposure would be a case involving direct contact with a 
Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has been 
exposed to chemotherapeutic products). 
• A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed during 
his partner’s pregnancy. 
If a study subject or study subject’s partner becomes or is found to be pregnant during the 
study subject’s treatment with the investigational product, the investigator must submit this 
information to the Pfizer drug safety unit on an SAE report form and an EDP supplemental 
form, regardless of whether an SAE has occurred.  In addition, the investigator must submit 
information regarding environmental exposure to a Pfizer product in a pregnant woman  
(eg, a subject reports that she is pregnant and has been exposed to a cytotoxic product by 
inhalation or spillage) using the EDP supplemental form.  This must be done irrespective of 
whether an AE has occurred and within 24 hours of awareness of the exposure.  The 
information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy). 
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer of the outcome as a follow-up 
to the initial EDP supplemental form.  In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) for 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless preprocedure test 
findings are conclusive for a congenital anomaly and the findings are reported). 
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs. 
Additional information about pregnancy outcomes that are reported as SAEs follows:  
• Spontaneous abortion includes miscarriage and missed abortion; 

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• Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the investigational product. 
Additional information regarding the EDP may be requested by the investigator.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the study subject with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the subject was given the Pregnant Partner Release of Information Form to provide to his 
partner. 
8.11. Occupational Exposure 
An occupational exposure occurs when during the performance of job duties, a person 
(whether a healthcare professional or otherwise) comes into unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE. 
An occupational exposure will be reported to the drug safety unit within 24 hours of the 
investigator’s awareness, using the SAE report form, regardless of whether there is an 
associated AE/SAE.  Since the information does not pertain to a subject enrolled in the study, 
the information is not reported on a CRF; however, a copy of the completed SAE report form 
is maintained in the investigator site file. 
8.12. Withdrawal Due to Adverse Events (See Also the Section on Subject Withdrawal) 
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on the appropriate AE CRF 
page. 
When a subject withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below. 
8.13. Eliciting Adverse Event Information 
The investigator will report all directly observed AEs and all AEs spontaneously reported by 
the study subject.  In addition, each study subject will be questioned about AEs. 
8.14. Reporting Requirements 
Each AE will be assessed to determine if it meets the criteria for SAEs.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate. 
8.14.1. Serious Adverse Event Reporting Requirements 
If an SAE occurs, Pfizer will be notified within 24 hours of investigator awareness of the 
event. 

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If an SAE occurs requiring EAC adjudication, Pfizer will be notified within 24 hours of 
notification that an SAE has been deemed a nonendpoint and has been sent back to the site.  
The investigator’s SAE awareness date in this instance is identified as the date that the 
investigator receives the nonendpoint SAE back from the EAC. 
As noted in the Protocol-Specified Serious Adverse Events section (Section 8.6.1), should an 
investigator judge one of the identified protocol-specified SAEs to have a causal relationship 
with the investigational product, the investigator must report the event to the sponsor within 
24 hours of investigator awareness, even if that event is a component of the endpoint. 
In particular, if the SAE is fatal or life-threatening, notification to Pfizer must be made 
immediately, irrespective of the extent of available AE information.  This time frame also 
applies to additional new information (follow-up) on previously forwarded SAE reports as 
well as to the initial and follow-up reporting of EDP, exposure via breastfeeding, and 
occupational exposure cases. 
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study subject initially seeks treatment elsewhere), the 
investigator will report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE. 
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the time frames for reporting specified above.  In addition, an investigator 
may be requested by Pfizer to obtain specific additional follow-up information in an 
expedited fashion.  This information collected for SAEs is more detailed than that captured 
on the AE CRF.  In general, this will include a description of the AE in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Information on other possible causes of the event, such as concomitant 
medications, vaccines, and/or illnesses, must be provided.  In the case of a subject death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative. 
8.14.2. Nonserious Adverse Event Reporting Requirements 
All AEs will be reported on the AE page(s) of the CRF.  It should be noted that the form for 
collection of SAE information is not the same as the AE CRF.  Where the same data are 
collected, the forms must be completed in a consistent manner.  For example, the same AE 
term should be used on both forms.  AEs should be reported using concise medical 
terminology on the CRFs as well as on the form for collection of SAE information. 
8.14.3. Medical Device Complaint Reporting Requirements 
All medical device complaints, regardless of whether the medical device complaint is 
associated with an AE, will be collected on the applicable pages within the CRF.  This 
includes potential incidents or malfunctions associated with the use of a medical device 
product.  An incident or malfunction is an event that might have led to death or serious 
deterioration in health, or if it occurred again might have led to death or serious deterioration 
in health. 

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Pfizer will be notified of all medical device complaints within 24 hours of the investigator’s 
awareness of the event. 
8.14.4. Sponsor’s Reporting Requirements to Regulatory Authorities 
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations. 
9. DATA ANALYSIS/STATISTICAL METHODS 
The section outlines statistical considerations and methodologies.  Detailed methodology for 
summary and statistical analyses of the data collected in this study will be documented in a 
statistical analysis plan (SAP), which will be maintained by the sponsor.  This document may 
modify the plans outlined in the protocol; however, any major modifications of the primary 
endpoint definition and/or its analysis will also be reflected in a protocol amendment. 
The primary comparison is between subjects receiving SA4Ag and subjects receiving 
placebo. 
9.1. Hypotheses and Acceptance Criteria 
Vaccine efficacy (VE) is defined as VE = 1 - RR, where RR is the relative risk in SA4Ag 
compared to placebo, ie, the proportion of SA4Ag recipients meeting the primary endpoint 
relative to the proportion of placebo recipients meeting the primary endpoint.  SA4Ag will be 
compared to placebo testing the hypotheses H0: VE ≤20% vs Ha: VE >20%. 
A conditional power–based59 futility procedure will be implemented during case accrual.  
Periodically the current estimate of VE will be assessed, and there will be a calculation of the 
power of the study at its planned completion at 48 cases conditional upon that value.  The 
DMC will review the calculation and if the conditional power of the study is low, 
corresponding to the critical case splits shown in Table 15, futility may be declared and the 
study may cease enrollment.  It is anticipated that this procedure will be implemented after 
approximately 10 and 15 cases have been accrued, and also at the time of the interim analysis 
at 24 cases.  The assessments after 10 and 15 cases can only result in a possible declaration 
of futility, not efficacy; as such, there is no impact on the overall alpha level of the study.  
Full details of the conditional power–based futility procedure will be provided in the SAP. 
An interim analysis will be performed after accumulating 24 per-protocol cases for review by 
the DMC.  Only the primary endpoint, defined in Section 9.3.2, will be examined.  The 
probability of the number of vaccine cases will be calculated using the binomial distribution 
with 24 trials and p = 0.444 because, under the null hypothesis and 1:1 randomization, the 
probability that a selected case is from SA4Ag is 0.444.  If the number of vaccine cases is 
3 or fewer, then the null hypothesis will be rejected in favor of the vaccine.  If significant 
efficacy is observed at the interim analysis, the study may continue to enroll subjects to 
ensure that the study will provide sufficient safety data for vaccine licensure. 

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A 99.7% confidence interval (CI) will be obtained for VE.  The confidence level is obtained 
from the O’Brien-Fleming60 alpha levels, explained below.  If the study does end for efficacy 
at interim analysis, events collected subsequent to the interim analysis will be reported in a 
supplement in a similar manner to that described in Whitehead61 for overrunning data, 
described below.  Otherwise, the study will continue to the accumulation of 48 cases. 
Once 48 per-protocol cases have accumulated SA4Ag will be compared to placebo for the 
primary endpoint, testing the hypotheses H0: VE ≤20% vs Ha: VE >20%.  SA4Ag will be 
deemed efficacious if it has 14 cases or fewer out of a total of 48 cases (point estimate of 
VE = 58.8% and 2-sided lower 95.1% confidence limit >20%). 
Although the final analysis is expected to have 48 cases, it is possible that additional 
potential cases will be present in the adjudication system (entered into the adjudication 
electronic case report form [eCRF]) on the same day that the 48th per-protocol case is 
reported to the EAC.  These additional cases will be included in the final analysis, if 
confirmed as cases by the EAC.  Therefore, the time order of case entry into the adjudication 
system will determine which cases will be included in the analysis.  O’Brien-Fleming 
boundaries will be maintained for decisions regarding VE.  In other words, in the event that 
more than 48 cases are available for the final analysis, the null hypothesis will be rejected if 
the lower bound of the 95.1% confidence interval is greater than 20%. 
Similarly, although the interim analysis is expected to have 24 cases, it is possible that 
additional potential cases will be present in the adjudication system (entered into the 
adjudication eCRF) on the same day that the 24th per-protocol case is reported to the EAC.  
These additional cases will be included in the interim analysis, if confirmed as cases by the 
EAC.  The time order of case entry into the adjudication system will determine which cases 
will be included in the interim analysis.  O’Brien-Fleming boundaries will be maintained for 
decisions regarding VE.  In other words, in the event that more than 24 cases are available 
for the interim analysis, the null hypothesis will be rejected if the lower bound of the 99.7% 
confidence interval is greater than 20%.  Even if more than 24 cases are included in the 
interim analysis, the final analysis will be performed on 48 cases, unless additional cases are 
available as described in this section.  Similar rules for case inclusion will apply to the 
futility analyses planned at 10 and 15 per-protocol cases. 
No multiplicity adjustments will be applied to the secondary endpoints.  All other secondary 
endpoints will be evaluated at a 2-sided alpha level of 0.05. 
9.2. Sample Size Determination 
This sequential analysis uses O’Brien-Fleming limits.  Comparing 2 treatments in the number 
of cases may be restated as a 1-sample test of proportions.62  The specifications in the 
software package EAST (Version 6.4, Cytel Inc, 2016) were 1-sample test on a binomial 
proportion, 1-sided alpha = 0.025, and an interim analysis, null hypothesis 
proportion = 0.444 (corresponding to VE = 20%), and alternate hypothesis 
proportion = 0.230 (corresponding to VE = 70%).  The first-stage probability for rejecting 
the null hypothesis = 0.0015, the first-stage probability for rejecting the alternate hypothesis 
= 0.2595, and 1-sided probability of rejecting the null hypothesis at the final stage = 0.0245.  

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9.3. Efficacy Analysis 
The per-protocol population will be the primary population for analysis of all efficacy 
objectives.  Efficacy objectives will also be assessed using the modified intent-to-treat 
(mITT) populations.  Subgroup analyses will be performed on both the per-protocol and the 
mITT populations. 
All analyses for the SSI endpoints assume 100% correct classification of suspected S aureus 
cases, ie, no cases are missed and no noncases are included in the statistical analysis.  All 
primary and secondary efficacy analyses will be repeated for sex, race, ethnicity, and age 
subgroups. 
9.3.1. Efficacy Analysis Populations 
Two analysis populations are defined: per-protocol and mITT.  To be included in the 
per-protocol efficacy population, a subject must meet all eligibility criteria, be vaccinated as 
randomized, undergo the index surgery 10 to 60 days after vaccination, undergo surgery 
consistent with study-defined criteria for the index surgery, have no major protocol violations 
prior to reporting of the suspected S aureus infection, and have no infection or malignancy 
identified at the index surgical procedure.  To be included in the mITT population, a subject 
must be vaccinated and undergo spinal surgery.  For both populations, subjects will be 
assigned to the investigational product to which they were randomized (SA4Ag or placebo). 
9.3.2. Analysis of the Primary Endpoint 
For the primary objective, the efficacy of SA4Ag will be based on the number of 
per-protocol subjects in each vaccine group with postoperative S aureus BSI and/or deep 
incisional or organ/space SSI occurring within 90 days of elective open posterior spinal 
fusion procedures with multilevel instrumentation, as confirmed by the EAC.  In case of 
multiple occurrences meeting the primary endpoint from the same subject, only the first 
episode will be used to calculate the VE. 
Examples of the estimated efficacy and associated CIs for a selected number of SA4Ag cases 
are presented in Table 15. 
Table 15. Estimated Efficacy and Associated Confidence Intervals for a Select 
Number of SA4Ag Cases 
Analysis 
Stage 
Total 
Cases 
SA4Ag 
Cases 
Estimated Efficacy and 
Confidence Intervala 
Comments 
Futility 
10 
7 
-133% (-1298%, 46.7%) Conditional power <20%; possible futility declaration 
 
15 
9 
-50% (-412%, 52.3%) Conditional power <20%; possible futility declaration 
 
24 
11 
15.4% (-105%, 66%) Conditional power <20%; possible futility declaration 
Interim 
24 
3 
85.7% (24.9%, 99.0%)  Max number of SA4Ag cases that permits inference 
that true VE is >20% 

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Table 15. Estimated Efficacy and Associated Confidence Intervals for a Select 
Number of SA4Ag Cases 
Analysis 
Stage 
Total 
Cases 
SA4Ag 
Cases 
Estimated Efficacy and 
Confidence Intervala 
Comments 
Final 
48 
8 
80.0% (56.5%, 91.9%) Estimated efficacy = 80% 
 
48 
11 
70.3% (40.3%, 86.4%)  Estimated efficacy =70% 
 
48 
14 
 58.8% (21.0%, 79.6%) Max number of SA4Ag cases that permits inference 
that true VE is >20% 
Abbreviations: N/A = not applicable; VE = vaccine efficacy. 
a. 
99.7% confidence level for interim analysis; 95.1% confidence level for final analysis; 95% confidence 
level for futility. 
 
The findings at the time of the final analysis will serve as the primary basis for efficacy 
conclusions. 
9.3.2.1. Supplementary Analysis 
After completion of the final protocol analysis, additional cases may be identified and 
submitted for adjudication.  Cases collected after the final analysis 
(ie, overrunning - Whitehead, 1997)61 will be included in supplementary descriptive analyses 
using 95% CIs (as the final number of events is unknown); these analyses are supplementary 
and provided for completeness. 
9.3.3. Analysis of Secondary Endpoints 
9.3.3.1. Efficacy 
All secondary endpoints will be analyzed using the per-protocol population.  The binomial 
methodology described above will be used to test the null hypothesis of no difference 
between treatments, with p = 1/2 and number of trials set to total number of cases from 
SA4Ag and placebo.  Two-sided p-values of the probability of the indicated SA4Ag cases or 
fewer will be calculated. 
As sensitivity analyses, the secondary endpoints will be evaluated in the mITT populations 
with p = 1/2 and number of trials set to total number of cases from SA4Ag and placebo. 
Secondary endpoints will be analyzed only after all subjects have completed the study and 
the database is locked. 
9.3.4. Analysis of Exploratory Endpoints 
9.3.4.1. Immunogenicity Analysis 
The immunogenicity endpoints are the results from antigen-specific functional assays (OPA 
assay for CP5 and CP8, and cLIA antibody titers for ClfA and MntC).  Additional 
exploratory assays to measure immune responses may be conducted on all 4 antigens.  Assay 
titers will be obtained at each applicable visit. 

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The immunogenicity baseline will be Visit 1. 
Windows for obtaining blood samples are:  
• Visit 1: up to 7 days prior to vaccination. 
• Visit 2 (index hospital admission): day of surgery blood sample collection any time from 
admission up to but before the index surgical procedure. 
• Visit 2 (index hospital admission): day of discharge blood sample collection: up to 3 days 
before discharge, but must be after index surgical procedure. 
• Visits 4 and 5: ±7 days. 
• Visit 6: -2 to +12 days. 
There are no windows for unscheduled blood sample collections. 
Missing assay results are not to be replaced or imputed. 
The number and proportion of subjects achieving threshold values will be determined at each 
scheduled time point for each vaccine group.  Two-sided 95% CIs will be calculated.  
Threshold values will be specified in the SAP. 
Geometric mean titers (GMTs), geometric mean fold rises (GMFRs) relative to baseline 
(Visit 1), and the proportion of subjects who achieve specific thresholds to the SA4Ag 
antigens, as well as their corresponding 95% CIs, will be compiled at each visit by vaccine 
group.  Antigen-specific immunoglobulin and OPA titers will be logarithmically transformed 
prior to analysis.  Within each vaccine group and for each antigen separately, GMTs at each 
visit will be calculated.  Two-sided 95% CIs will be constructed by back transformation of 
the CIs for the mean of the logarithmically transformed assay results computed using the 
Student t distribution. 
Two-sided 95% CIs for the GMFR at each postvaccination blood draw visit will be 
constructed by back transformation of the CIs for the mean of the logarithmically 
transformed fold rise on the assay data computed using the Student t distribution. 
In addition, GMTs and CIs will be estimated from an analysis of covariance (ANCOVA), 
also computed using the logarithmically transformed assay results.  The model terms will be 
treatment, site, visit, baseline assay value, and treatment-visit interaction.  ‘Visit’ for the 
index hospital admission will be partitioned into ‘day of surgery’ and ‘day of discharge.’  
The difference between least squares (LS) means for SA4Ag minus placebo will be 
exponentiated to obtain a ratio of the geometric means.  The corresponding 2-sided 95% CIs 
will be obtained. 
For sensitivity purposes, the ANCOVA will be repeated by adding 1 factor and its interaction 
at a time, eg, add sex and treatment-sex interaction to the model.  This will be performed for 

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sex, race, age group, baseline colonization status, and other subgroups as specified in the 
SAP.  Significant interactions of subgroups with treatment, defined as p <0.10, will be 
examined further for synergistic and antagonistic effects. 
The proportions of subjects achieving n-fold rises from baseline to each postbaseline visit 
will be compiled, as well as their 95% CIs.  N-fold rises will be 2-, 4-, 8-, 16-, and 32-fold. 
Reverse cumulative distribution curves (RCDCs) will be generated to present the 
immunogenicity data at baseline and the Day 42 postoperative assessment time point.  
RCDCs may be repeated, but limited to cases. 
All immunogenicity analyses will be performed in the per-protocol and mITT populations, 
but limited to subjects with at least 1 postvaccination assay value.  It is anticipated that the 
immunogenicity analyses will be conducted following database lock; however, an interim 
immunogenicity analysis may be performed on a subset of subjects, if these results are 
required to support regulatory agency interactions to expedite the clinical development of 
SA4Ag. 
If an interim immunogenicity analysis is performed, it will be limited to subjects who have at 
least 1 valid and determinate postvaccination assay value.  The interim analysis will be 
limited to group-level statistics and will be conducted by an unblinded team, independent of 
the sponsor, in order to maintain blinding.  All immunogenicity endpoints are defined as 
exploratory and the study will not be prematurely terminated or altered in any way (eg, no 
design or operational changes) from the interim immunogenicity analysis; therefore, no 
type I error adjustment is proposed. 
9.3.4.2. Colonization Analysis 
Windows for obtaining colonization swabs will be the same as for immunogenicity.  
Colonization swabs at Visit 2 (index hospital admission) will be collected both on admission 
and again, prior to discharge. 
Baseline colonization status is defined as: 
• Positive for any subject with at least 1 positive S aureus colonization swab at either 
Visit 1 or Visit 2 (admission sample only) or both. 
• Negative for any subject with all negative S aureus colonization swabs at both Visit 1 
and Visit 2 (admission sample only) and no missing colonization swabs. 
• Missing for subjects without any colonization swab results from either Visit 1 or Visit 2 
(admission sample only) or subjects with any combination of negative colonization swabs 
and at least 1 missing colonization swab. 
At each postsurgery time point, the proportions of colonization swabs testing positive for 
S aureus at each anatomical site and the RR between the 2 vaccine groups along with its 
exact 2-sided 95% CI will be obtained.  Subgroup compilations will be performed based on 

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age group, sex, baseline colonization status, and primary endpoint status (ie, case or 
noncase).  Statistical significance of treatment-subgroup interactions will be obtained from 
logistic regression.  The logistic regression will include treatment, subgroup, and 
treatment-subgroup interaction.  One subgroup will be examined at a time.  Some subgroups 
may be combined to achieve reasonable sample size.  Anatomical sites will be examined 
separately. 
Analyses will be performed for the per-protocol and mITT populations, further limited to 
subjects having at least 1 nonmissing colonization swab value at any visit. 
9.4. Other Analysis 
9.4.1. Demographics and Clinical Characteristics 
The demographic characteristics to be summarized using descriptive statistics include sex, 
race, and age at time of vaccination.  Other demographic characteristics, such as body mass 
index (BMI), smoking status, etc, will also be compared.  Each vaccine group will be 
summarized separately.  Preoperative and perioperative data will be summarized by vaccine 
group.  Compilations will be performed for the per-protocol, mITT, and safety populations. 
The CCI and ASA scores will be summarized by vaccine group. 
Age group is defined as 18 to <50 years, 50 to <65 years, and 65 years and older.  Age will 
be calculated from the date of randomization. 
9.4.2. Healthcare Utilization 
Healthcare utilization will be determined for each vaccine group and will include days in 
hospital, days in an ICU, discharge disposition, inpatient days in skilled nursing or 
rehabilitation facilities after discharge, number of readmissions to hospital, number of 
reoperations, days of antibiotic use, and outpatient visits for rehabilitation/physical therapy.  
Descriptive statistics will be calculated for each vaccine group.  Two-sided 95% CIs for the 
mean or median difference between vaccine groups will be obtained where applicable (ie, not 
for categorical responses such as postdischarge disposition).  Comparisons of healthcare use 
will be performed between vaccine groups for the per-protocol, mITT, and safety 
populations. 
9.5. Safety Analysis 
All subjects who receive study vaccine will be included in the safety population. 
AEs will be categorized according to the Medical Dictionary for Regulatory Activities 
(MedDRA) and will be summarized by vaccine group.  AEs will be summarized for the 
following intervals: 
• From the day of vaccination until the day of surgery 
• From the day of vaccination until the Day 42 postoperative evaluation 

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• From the day of surgery until the Day 42 postoperative evaluation 
• From the Day 42 postoperative evaluation until the Day 180 postoperative evaluation 
(newly diagnosed chronic medical disorders) 
Subjects may be vaccinated 10 to 60 days before the day of surgery, so the recording period 
for preoperative AEs will vary among subjects.  AEs before surgery will be recompiled, but 
using AEs per 100 or per 1000 days, in order to adjust for varying exposure.  Only AEs that 
start between the day of vaccination and before surgery will be so analyzed.  The 3-tier 
methodology will not be used for preoperative AEs because they will be categorized as rates. 
SAEs will be categorized according to MedDRA and will be summarized by vaccine group 
for all subjects for the following intervals: 
• From the day of vaccination until the Day 180 postoperative evaluation 
• From the day of vaccination until the day of surgery 
• From the day of surgery until the Day 180 postoperative evaluation 
Causes of deaths will be categorized according to MedDRA and descriptively summarized 
for subjects receiving SA4Ag and subjects receiving placebo.  Mortality will be further 
categorized as associated with S aureus infection or not associated with S aureus infection, as 
determined by the EAC. 
AEs will be summarized using 3-tier methodology: 
1. Tier 1 includes all AEs of special interest.  These may be determined by vaccine 
knowledge, experience with similar vaccines, and results from Phase 1 and 2 studies, and 
will be specified in the SAP.  For such AEs, incidence proportions, the difference 
between treatments in proportions, 95% CI on the difference, 2-sided p-value on the 
difference, and graphical displays of the differences will be compiled.  The defined tier 1 
AEs will be specified by the sponsor in a separate safety review plan. 
2. Tier 2 includes all AEs with ≥1% incidence in either treatment in either the preoperative 
period or the postoperative period.  For such AEs, incidence proportions, the differences 
between treatments in proportions, and 95% CIs on the differences will be compiled. 
3. Tier 3 includes all remaining AEs.  For such AEs, only incidence proportions and the 
differences between treatments in proportions will be compiled. 
The CIs on the difference between treatments will be computed using the Chan and Zhang 
method.63 
The reanalysis of AEs before surgery, compiled on the basis of 100 or 1000 days of 
exposure, will be analyzed in terms of RR. 

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Postvaccination local reactions and systemic events reported in the e-diary will be 
summarized by the maximum severity across the 10-day observation period.  Descriptive 
statistics will be compiled by vaccine group. 
All AE safety analyses will be repeated for sex, race, ethnicity, and age subgroups. 
Immunogenicity blood samples will be collected from subjects developing MOF.  
Descriptive statistics will be compiled by vaccine group.  The population is the safety 
population. 
9.6. Analysis Timing 
There will be periodic futility checks after approximately 10 and 15 cases have accrued, and 
an interim analysis performed after the accrual of 24 cases that meet the primary efficacy 
endpoint as confirmed by the EAC.  The DMC will perform these analyses, in association 
with the independent statistical team (IST), as required to discharge its responsibilities. 
It is anticipated that immunogenicity analyses will be conducted following database lock; 
however, an interim immunogenicity analysis may be performed on a subset of subjects, if 
these results are required to support regulatory agency interactions to expedite the clinical 
development of SA4Ag (Section 9.3.4.1). 
All other analyses will be performed after database lock and unblinding, with the exception 
of the primary endpoint analysis (Section 9.3.2). 
9.7. Data Monitoring Committee 
This study will use an independent, external data monitoring committee (DMC).  
Membership and conduct of the DMC is described in a separate DMC charter. 
The DMC is responsible for ongoing monitoring of the safety of subjects in the study, and for 
the assessment of VE/futility, in accordance with the charter.  The DMC is also responsible 
for providing recommendations on the need for adjusting the sample size required to achieve 
48 per-protocol cases.  The DMC is not specifically responsible for evaluating 
immunogenicity or S aureus carriage data collected as part of the protocol. 
The DMC may review unblinded data during closed meeting sessions; however, the sponsor 
will remain blinded and will not be permitted access to the randomization assignments until 
the database is locked. 
The DMC will review efficacy and safety data at defined intervals as specified in the charter.  
The DMC may conduct additional meetings to review safety data at other time points during 
the study, at its discretion, or at the request of the sponsor.  In addition, as determined by the 
sponsor clinician, the DMC may meet on an ad hoc basis to evaluate any SAEs related to 
vaccination, or related AEs that may jeopardize further subject participation, in order to 
determine that the study may be continued safely. 

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The DMC will work in association with the IST in order to conduct both the safety and 
futility/efficacy evaluations.  The IST will include statistician(s) and programmer(s) who are 
independent of the sponsor and who have unrestricted access to the randomization 
assignments during the study.  The IST will perform statistical analysis and prepare 
unblinded data and reports to provide to the DMC for assessment in accordance with the 
DMC charter.  The IST will report the outcome of the planned futility checks (only whether 
the futility rule has been passed or not) to the sponsor and the DMC separately. 
After each meeting, the DMC will make recommendations that may include the following: 
continue the study with or without modification, pause or stop vaccination for safety or other 
reasons, or pause or stop the study for efficacy or futility (assessed at an efficacy/futility 
meeting only).  The recommendations made by the DMC will be forwarded to Pfizer for 
consideration and final decision.  Information on the current efficacy cases (number 
occurring in vaccine and placebo groups) will not be disclosed until a decision is made to 
permanently stop the study.  Pfizer will forward the DMC recommendations and Pfizer’s 
response to regulatory authorities, as appropriate.  Supporting documents forwarded to 
regulatory agencies may include summaries of aggregate analyses of endpoint events and of 
safety data that are not endpoints. 
10. QUALITY CONTROL AND QUALITY ASSURANCE 
During study conduct, Pfizer or its agent will conduct periodic monitoring visits to ensure 
that the protocol and GCPs are being followed.  The monitors may review source documents 
to confirm that the data recorded on CRFs are accurate.  The investigator and institution will 
allow Pfizer monitors/auditors or its agents and appropriate regulatory authorities direct 
access to source documents to perform this verification. 
The study site may be subject to review by the IRB/IEC, and/or to quality assurance audits 
performed by Pfizer, or companies working with or on behalf of Pfizer, and/or to inspection 
by appropriate regulatory authorities. 
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process. 
11. DATA HANDLING AND RECORD KEEPING 
11.1. Case Report Forms/Electronic Data Record 
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study. 
A CRF is required and should be completed for each included subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer. 

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The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true.  Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry. 
In most cases, the source documents are the hospital’s or the physician’s subject chart.  In 
these cases, data collected on the CRFs must match the data in those charts. 
In some cases, the CRF, or part of the CRF, may also serve as source documents.  In these 
cases, a document should be available at the investigator’s site as well as at Pfizer and clearly 
identify those data that will be recorded in the CRF, and for which the CRF will stand as the 
source document. 
11.2. Record Retention 
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator 
agrees to keep records, including the identity of all participating subjects (sufficient 
information to link records, eg, CRFs and hospital records), all original signed ICDs, copies 
of all CRFs, safety reporting forms, source documents, and detailed records of treatment 
disposition, and adequate documentation of relevant correspondence (eg, letters, meeting 
minutes, and telephone call reports).  The records should be retained by the investigator 
according to International Conference on Harmonisation (ICH), according to local 
regulations, or as specified in the clinical study agreement (CSA), whichever is longer. 
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or an independent third party arranged by Pfizer.  
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations. 
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met. 
12. ETHICS 
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, ICDs, and other relevant documents, eg, recruitment advertisements, if 
applicable, from the IRB/IEC.  All correspondence with the IRB/IEC should be retained in 
the investigator file.  Copies of IRB/IEC approvals should be forwarded to Pfizer. 

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The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/IEC and Pfizer in writing immediately after 
the implementation. 
12.2. Ethical Conduct of the Study 
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (CIOMS 2002), Guidelines for GCP (ICH 1996), and 
the Declaration of Helsinki (World Medical Association 1996 & 2008). 
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on GCP, and applicable local regulatory requirements and laws. 
12.3. Subject Information and Consent 
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where 
required by law. 
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by a numerical code consisting 
of a numbering system provided by Pfizer in order to de-identify study subjects.  The study 
site will maintain a confidential list of subjects who participated in the study, linking their 
numerical code to the subject’s actual identity.  In case of data transfer, Pfizer will maintain 
high standards of confidentiality and protection of subject personal data consistent with 
applicable privacy laws. 
The ICDs must be in compliance with ICH GCP, local regulatory requirements, and legal 
requirements, including applicable privacy laws. 
The ICDs used during the informed consent process must be reviewed by the sponsor, 
approved by the IRB/IEC before use, and available for inspection. 
The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study and possible risks associated with participation. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed.  The investigator 
will retain the original of each subject's signed consent document. 
12.4. Subject Recruitment 
Advertisements approved by independent ethics committees and investigator databases may 
be used as recruitment procedures. 

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12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP 
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of. 
13. DEFINITION OF END OF TRIAL 
13.1. End of Trial in a Member State 
End of trial in a Member State of the European Union is defined as the time at which it is 
deemed that a sufficient number of subjects have been recruited and completed the study as 
stated in the regulatory application (ie, clinical trial application [CTA]) and ethics application 
in the Member State.  Poor recruitment (recruiting less than the anticipated number in the 
CTA) by a Member State is not a reason for premature termination but is considered a 
normal conclusion to the study in that Member State. 
13.2. End of Trial in All Other Participating Countries 
The end of the clinical phase of the study will be defined as LSLV.  At this time, sites will be 
closed out, the IRB/IEC will be informed, and no further CIOMS reports will be sent.  For 
other purposes, the end of the study will be defined as the last serology sample assayed or 
characterization of the last strain isolate. 
14. SPONSOR DISCONTINUATION CRITERIA 
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, or drug safety problems, or at the discretion of Pfizer.  In 
addition, Pfizer retains the right to discontinue development of SA4Ag at any time. 
If a study is prematurely terminated or discontinued, Pfizer will promptly notify the 
investigator.  After notification, the investigator must contact all participating subjects and 
the hospital pharmacy (if applicable) immediately.  As directed by Pfizer, all study materials 
must be collected and all CRFs completed to the greatest extent possible. 
15. PUBLICATION OF STUDY RESULTS 
15.1. Communication of Results by Pfizer 
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations. 

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In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted. 
www.clinicaltrials.gov  
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies conducted in patients that evaluate the safety and/or efficacy of a Pfizer 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are submitted for posting within 1 year of the primary completion date for studies in 
adult populations or within 6 months of the primary completion date for studies in pediatric 
populations. 
Primary completion date is defined as the date that the final subject was examined or 
received an intervention for the purposes of final collection of data for the primary outcome, 
whether the clinical study concluded according to the prespecified protocol or was 
terminated. 
EudraCT 
Pfizer posts EU Basic Results on EudraCT for all Pfizer-sponsored interventional studies that 
are in scope of EU requirements.  EU Basic Results are submitted for posting within 1 year 
of the primary completion date for studies in adult populations or within 6 months of the 
primary completion date for studies in pediatric populations. 
www.pfizer.com 
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov. 
15.2. Publications by Investigators 
Pfizer supports the exercise of academic freedom and has no objection to publication by 
principal investigator of the results of the study based on information collected or generated 
by principal investigator, whether or not the results are favorable to the Pfizer product.  
However, to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed. 
The investigator will provide any publication to Pfizer at least 30 days before they are for 
publication or otherwise disclosed.  If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days. 

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The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results. 
If the study is part of a multicenter study, the investigator agrees that the first publication will 
be a joint publication covering all study sites, and that any subsequent publications by the 
principal investigator will reference that primary publication.  However, if a joint manuscript 
has not been submitted for publication within 12 months of completion or termination of the 
study at all participating sites, the investigator is free to publish separately, subject to the 
other requirements of this section. 
For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors. 
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA. 
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues. 

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16. REFERENCES 
1. 
Wertheim HFL, Melles DC, Vos MC, et al.  The role of nasal carriage in 
Staphylococcus aureus infections. Lancet Infect Dis 2005;5(12):751-62. 
2. 
Lowy FD. Staphylococcus aureus infections. N Engl J Med 1998;339(8):520-32. 
3. 
World Health Organization.  Report on the burden of endemic health care-associated 
infection worldwide. Geneva, Switzerland: World Health Organization; 2011. 
4. 
Diekema DJ, Pfaller MA, Schmitz FJ, et al.  Survey of infections due to Staphylococcus 
species: frequency of occurrence and antimicrobial susceptibility of isolates collected in 
the United States, Canada, Latin America, Europe, and the Western Pacific region for 
the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin Infect Dis 
2001;32(Suppl 2):S114-32. 
5. 
Hidron AI, Edwards JR, Patel J, et al.  NHSN annual update: antimicrobial-resistant 
pathogens associated with healthcare-associated infections: annual summary of data 
reported to the National Healthcare Safety Network at the Centers for Disease Control 
and Prevention, 2006–2007. Infect Control Hosp Epidemiol 2008;29(11):996-1011. 
6. 
McCaig LF, McDonald LC, Mandal S, et al.  Staphylococcus aureus–associated skin 
and soft tissue infections in ambulatory care. Emerg Infect Dis 2006;12(11):1715-23. 
7. 
Moet GJ, Jones RN, Biedenbach DJ, et al.  Contemporary causes of skin and soft tissue 
infections in North America, Latin America, and Europe: report from the SENTRY 
Antimicrobial Surveillance Program (1998-2004). Diagn Microbiol Infect Dis 
2007;57:7-13. 
8. 
Noskin GA, Rubin RJ, Schentag JJ, et al.  The burden of Staphylococcus aureus 
infections on hospitals in the United States: an analysis of the 2000 and 2001 
Nationwide Inpatient Sample database. Arch Intern Med 2005;165(15):1756-61. 
9. 
Noskin GA, Rubin RJ, Schentag JJ, et al.  National trends in Staphylococcus aureus 
infection rates: impact on economic burden and mortality over a 6-year period 
(1998-2003). Clin Infect Dis 2007;45:1132-40. 
10. Kluytmans J, van Belkum A, Verbrugh H.  Nasal carriage of Staphylococcus aureus: 
epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev 
1997;10(3):505-20. 
11. Malinas MF, Mawhorter SD, Jain A, et al.  Staphylococcus aureus bacteremia in solid 
organ transplant recipients: evidence for improved survival when compared with 
nontransplant patients. Transplantation 2012;93(10):1045-50. 

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12. Streit JM, Jones RN, Sader HS, et al.  Assessment of pathogen occurrences and 
resistance profiles among infected patients in the intensive care unit: report from the 
SENTRY Antimicrobial Surveillance Program (North America, 2001). Int J Antimicrob 
Agents 2004;24:111-8. 
13. Laupland KB, Ross T, Gregson DB.  Staphylococcus aureus bloodstream infections: 
risk factors, outcomes, and the influence of methicillin resistance in Calgary, Canada, 
2000--2006. J Infect Dis 2008;198:336-43. 
14. Jacobsson G, Dashti S, Wahlberg T, et al.  The epidemiology of and risk factors for 
invasive Staphylococcus aureus infections in western Sweden. Scand J Infect Dis 
2007;39:6-13. 
15. Biedenbach DJ, Moet GJ, Jones RN.  Occurrence and antimicrobial resistance pattern 
comparisons among bloodstream infection isolates from the SENTRY Antimicrobial 
Surveillance Program (1997-2002).  Diagnost Microbiol Infect Dis 2004;50:59-69. 
16. Allegranzi B, Bagheri Nejad S, Combescure C, et al.  Burden of endemic health-care-
associated infection in developing countries: systematic review and meta-analysis. 
Lancet 2011;377:228-41. 
17. Laupland KB, Lyytikainen O, Sogaard M, et al.  The changing epidemiology of 
Staphylococcus aureus bloodstream infection: a multinational population-based 
surveillance study. Clin Microbiol Infect 2013;19:465-71. 
18. Weber DJ, Rutala WA, Sickbert-Bennett EE, et al.  Microbiology of ventilator-
associated pneumonia compared with that of hospital-acquired pneumonia. Infect 
Control Hosp Epidemiol 2007;28(7):825-31. 
19. Jones RN.  Global epidemiology of antimicrobial resistance among community-
acquired and nosocomial pathogens: a five-year summary from the SENTRY 
Antimicrobial Surveillance Program (1997-2001). Semin Resp Crit Care Med 
2003;24(1):121-33. 
20. Fedler KA, Biedenbach DJ, Jones RN.  Assessment of pathogen frequency and 
resistance patterns among pediatric patient isolates: report from the 2004 SENTRY 
Antimicrobial Surveillance Program on 3 continents.  Diagn Microbiol Infect Dis 
2006;56:427-36. 
21. Mangram AJ, Horan TC, Pearson ML, et al. Guideline for prevention of surgical site 
infection, 1999. Infect Control Hosp Epidemiol 1999;20(4):247-78. 
22. Zimlichman E, Henderson D, Tamir O, et al.  Health care-associated infections.  A 
meta-analysis of costs and financial impact on the US health care system. JAMA Intern 
Med 2013;173(22):2039-46. 
23. Anderson DJ. Surgical site infections. Infect Dis Clin North Am 2011;25:135-53. 

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24. Weigelt JA, Lipsky BA, Tabak YP, et al.  Surgical site infections: causative pathogens 
and associated outcomes. Am J Infect Control 2010;38:112-20. 
25. Jernigan JA.  Is the burden of Staphylococcus aureus among patients with surgical-site 
infections growing? Infect Control Hosp Epidemiol 2004;25(6):457-60. 
26. Petti CA, Sanders LL, Trivette SL, et al.  Postoperative bacteremia secondary to 
surgical site infection. Clin Infect Dis 2002;34:305-8. 
27. Harrington G, Russo P, Spelman D, et al.  Surgical-site infection rates and risk factor 
analysis in coronary artery bypass graft surgery. Infect Control Hosp Epidemiol 
2004;25:472-6. 
28. Schuster JM, Rechtine G, Norvell DC, et al.  The influence of perioperative risk factors 
and therapeutic interventions on infection rates after spine surgery: a systematic review. 
Spine 2010;35(9 Suppl):S125-37. doi: 10.1097/BRS.0b013e3181d8342c. 
29. Peleg AY, Weerarathna T, McCarthy JS, et al.  Common infections in diabetes: 
pathogenesis, management and relationship to glycaemic control. Diabetes Metab Res 
Rev 2007;23:3-13. 
30. Pull ter Gunne AF, Cohen DB.  Incidence, prevalence, and analysis of risk factors for 
surgical site infection following adult spinal surgery. Spine 2009;34(13):1422-8. 
31. Dowsey MM, Choong PFM.  Obese diabetic patients are at substantial risk for deep 
infection after primary TKA. Clin Orthop Relat Res 2009;467(6):1577-81. 
32. Choban PS, Heckler R, Burge JC, et al.  Increased incidence of nosocomial infections in 
obese surgical patients.  Am Surg 1995;61:1001-5. 
33. Birkmeyer NJO, Charlesworth DC, Hernandez F, et al.  Obesity and risk of adverse 
outcomes associated with coronary artery bypass surgery. Circulation 1998;97:1689-94. 
34. Moller AM, Villebro N, Pedersen T, et al.  Effect of preoperative smoking intervention 
on postoperative complications: a randomised clinical trial. Lancet 2002;359:114-7. 
35. Klevens RM, Morrison MA, Nadle J, et al.  Invasive methicillin-resistant 
Staphylococcus aureus infections in the United States. JAMA 2007;298(15):1763-71.  
36. Guvener M, Pasaoglu I, Demircin M, et al.  Perioperative hyperglycemia is a strong 
correlate of postoperative infection in type II diabetic patients after coronary artery 
bypass grafting. Endocrine J 2002;49(5):531-7. 
37. Ata A, Lee J, Bestle SL, et al.  Postoperative hyperglycemia and surgical site infection 
in general surgery patients. Arch Surg 2010;145(9):858-64. 

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38. Marchant MH Jr, Viens NA, Cook C, et al.  The impact of glycemic control and 
diabetes mellitus on perioperative outcomes after total joint arthroplasty. J Bone Joint 
Surg Am 2009;91:1621-9. 
39. Smith RL, Bohl JK, McElearney ST, et al.  Wound infection after elective colorectal 
resection. Ann Surg 2004;239:599-607. 
40. Russo PL, Spelman DW.  A new surgical-site infection risk index using risk factors 
identified by multivariate analysis for patients undergoing coronary artery bypass graft 
surgery. Infect Control Hosp Epidemiol 2002;23:372-6. 
41. Moller A, Tonnesen H.  Risk reduction: perioperative smoking intervention. Best Pract 
Res Clin Anaesthesiol 2006;20(2):237-48. 
42. Koutsoumbelis S, Hughes AP, Girardi FP, et al.  Risk factors for postoperative infection 
following posterior lumbar instrumented arthrodesis. J Bone Joint Surg Am 
2011;93:1627-33. 
43. Millbourn D, Cengiz Y, Israelsson LA.  Effect of stitch length on wound complications 
after closure of midline incisions: a randomized controlled trial. Arch Surg 
2009;144(11):1056-9. 
44. Gaynes RP, Culver DH, Horan TC, et al.  Surgical site infection (SSI) rates in the 
United States, 1992-1998: the National Nosocomial Infections Surveillance System 
basic SSI risk index. Clin Infect Dis 2001;33(Suppl 2):S69-77. 
45. Rao SB, Vasquez G, Harrop J, et al.  Risk factors for surgical site infections following 
spinal fusion procedures: a case-control study. Clin Infect Dis 2011;53(7):686-92. 
46. Rosenberger LH, Politano AD, Sawyer RG.  The Surgical Care Improvement Project 
and prevention of post-operative infection, including surgical site infection. Surg Infect 
2011;12(3):163-8. 
47. Kurz A, Sessler DI, Lenhardt R.  Perioperative normothermia to reduce the incidence of 
surgical-wound infection and shorten hospitalization. N Engl J Med 1996;334:1209-15. 
48. Frisch A, Chandra P, Smiley D, et al.  Prevalence and clinical outcome of 
hyperglycemia in the perioperative period in noncardiac surgery. Diabetes Care 
2010;33(8):1783-8. 
49. Perl TM, Cullen JJ, Wenzel RP, et al.  Intranasal mupirocin to prevent postoperative 
Staphylococcus aureus infections. N Engl J Med 2002;346(24):1871-7. 
50. Pfizer analysis of Nationwide Inpatient Sample (NIS), 2009 (USA). 
51. Veeravagu A, Patil CG, Lad SP, et al.  Risk factors for postoperative spinal wound 
infections after spinal decompression and fusion surgeries. Spine 2009;34:1869-72. 

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52. Schimmel JJP, Horsting PP, de Kleuver M, et al.  Risk factors for deep surgical site 
infections after spinal fusion. Eur Spine J 2010;19(10):1711- 9. 
53. Urquhart DM, Hanna FS, Brennan SL, et al.  Incidence and risk factors for deep 
surgical site infection after primary total hip arthroplasty: a systematic review. J 
Arthroplasty 2010;25(8):1216-22.  
54. US Department of Health and Human Services, Food and Drug Administration, Center 
for Biologics Evaluation and Research.  Guidance for industry: toxicity grading scale 
for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. 
Rockville, Md: US Department of Health and Human Services; September 2007. 
55. Charlson ME, Sax FL.  The therapeutic efficacy of critical care units from two 
perspectives: a traditional cohort approach vs a new case-control methodology. J Chron 
Dis 1987;40(1):31-9. 
56. American Society of Anesthesiologists.  ASA physical status classification system.  
Available: http://www.asahq.org/Home/For-Members/Clinical-Information/ASA-
Physical-Status-Classification-System. 18 Jun 2014.  
57. Ferreira FL, Bota DP, Bross A, et al.  Serial evaluation of the SOFA score to predict 
outcome in critically ill patients. JAMA 2001;286(14):1754-8. 
58. Grissom et al. Disaster Med Public Health Prep. 2010;4(4):277-84 
59. Halperin M, Lan KKG, Ware JH, et al.  An aid to data monitoring in long-term clinical 
trials. Control Clin Trials 1982;3(4):311-23. 
60. Jennison C, Turnbull BW.  Group sequential methods with applications to clinical trials. 
Boca Raton, Fla: Chapman & Hall/CRC; 2000: p. 29-39. 
61. Whitehead J.  Underrunning and overrunning.  In: The design and analysis of sequential 
clinical trials.  Chichester, England: John Wiley & Sons; 1997: p. 151-7. 
62. Chow SC, Shao J, Wang H.  Sample size calculations in clinical research. New York: 
Marcel Dekker; 2003: p. 323-4. 
63. Chan ISF, Zhang Z.  Test based exact confidence intervals for the difference of two 
binomial proportions. Biometrics 1999;55:1202-9. 

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Appendix 1. Protocol-Defined Infection Events 
Adapted from: CDC NHSN Surgical Site Infections (SSI), January 2014 Edition 
Reporting Instructions: 
Bone and joint infections (joint or bursa infections, osteomyelitis, vertebral disc space 
infection) meningitis, spinal abscess without meningitis, and intra-abdominal infections 
(relevant only for procedures involving an anterior intra-abdominal incision) which involve 
tissue which was opened or manipulated during the index surgical procedure are to be 
reported as organ/space infection and not according to the PDI term. 
BLOODSTREAM INFECTIONS (BSI) 
– Clinical Criteria 
Confirmed Bloodstream Infection must meet at least 1 of the following criteria: 
1. Patient has a recognized pathogen cultured from one or more blood cultures  
OR 
2. The same common commensal organism is cultured from two or more blood cultures 
drawn on separate occasions.  Criterion elements must occur within a time frame that 
does not exceed a gap of 1 calendar day between two adjacent elements 
AND the Patient has at least one of the following signs or symptoms: 
• Fever (>38°C or >100.4°F) 
• Chills 
• Hypotension  
Microbiological Classification: 
Confirmed bloodstream infection cases are to be classified as: 
• Microbiologically confirmed S aureus bloodstream infection if the subject has S 
aureus cultured from blood, as part of clinical criterion 1 
• Microbiologically confirmed non–S aureus bloodstream infection if the subject 
has only non–S aureus organism(s) cultured from blood, as part of clinical criterion 1 
or 2 
 

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BONE AND JOINT INFECTIONS 
OSTEOMYELITIS 
An osteomyelitis directly attributable to an infection via the index surgery incision site is to 
be classified as an organ/space SSI.  If no such attribution exists, the event is reported as 
osteomyelitis. 
– Clinical Criteria 
Confirmed osteomyelitis must meet at least 1 of the following criteria: 
1. Patient has organisms cultured from bone. 
2. Patient has evidence of osteomyelitis on direct examination of the bone during an 
invasive procedure or histopathologic examination. 
3. Patient has at least 2 of the following signs or symptoms (*with no other recognized 
cause): 
• Fever (>38°C or >100.4°F) 
• Localized swelling* 
• Tenderness* 
• Heat* 
• Drainage at suspected site of bone infection*  
AND   At least 1 of the following:  
a. Organisms cultured from blood  
b. Positive laboratory test on blood (eg, antigen tests for H. influenzae or 
S pneumoniae) 
c. Imaging test evidence of infection (eg, abnormal findings on x-ray, CT scan, 
MRI, radiolabel scan [gallium, technetium, etc]) 
Microbiological Classification 
Confirmed osteomyelitis cases are to be classified as: 
• Microbiologically confirmed S aureus osteomyelitis if the subject has S aureus 
cultured from bone (clinical criterion 1), or from blood as part of clinical criterion 3 
• Microbiologically confirmed non–S aureus osteomyelitis if the subject has only 
non–S aureus organism(s) cultured from bone (clinical criterion 1), or from blood as a 
component of clinical criterion 3 
• Non–microbiologically confirmed osteomyelitis if the above criteria for 
microbiologically confirmed osteomyelitis are not met. 

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VERTEBRAL DISC SPACE INFECTION 
A vertebral disc space infection directly attributable to an infection via the index surgery 
incision site is to be classified as an organ/space SSI.  If no such attribution exists, the event 
is reported as vertebral disc space infection. 
– Clinical Criteria 
Confirmed vertebral disc space infection must meet at least 1 of the following criteria: 
1. Patient has organisms cultured from vertebral disc space tissue obtained during an 
invasive procedure 
2. Patient has evidence of vertebral disc space infection seen during an invasive procedure 
or histopathologic examination 
3. Patient has fever (>38°C or >100.4°F) or pain at the involved vertebral disc space, with 
no other recognized cause  AND  
Imaging test evidence of infection, (eg, abnormal findings on x-ray, CT scan, MRI, 
radiolabel scan [gallium, technetium, etc]) 
4. Patient has fever (>38°C or >100.4°F) and pain at the involved vertebral disc space, with 
no other recognized cause  AND 
Positive laboratory test on blood or urine (eg, antigen tests for H. influenzae, 
S. pneumoniae, N. meningitidis, or group B streptococcus). 
Microbiological Classification 
Confirmed vertebral disc space infection cases are to be classified as 
• Microbiologically confirmed S aureus vertebral disc space infection if the subject 
has S aureus cultured from vertebral disc space (clinical criterion 1) 
• Microbiologically confirmed non–S aureus vertebral disc space infection if the 
subject has only non–S aureus organism(s) cultured from vertebral disc space 
(clinical criterion 1) 
• Non–microbiologically confirmed vertebral disc space infection if the above 
criteria for microbiologically confirmed vertebral disc space infection are not met 
 
 
 

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JOINT OR BURSA INFECTION 
A joint and bursa infection attributable to infection via the index surgery incision site 
(eg, harvesting bone from the iliac crest) is to be classified as an organ/space SSI.  If no such 
attribution exists, the event is reported as a joint and bursa infection. 
– Clinical Criteria 
Confirmed joint or bursa infection must meet at least 1 of the following criteria:  
1. Patient has organisms cultured from joint fluid or synovial biopsy 
2. Patient has evidence of joint or bursa infection seen during an invasive procedure or 
histopathologic examination 
3. Patient has at least 2 of the following signs or symptoms with no other recognized cause: 
• Joint pain 
• Swelling 
• Tenderness 
• Heat 
• Evidence of effusion 
• Limitation of motion 
AND at least 1 of the following: 
a. Organisms and white blood cells seen on Gram stain of joint fluid  
b. Positive laboratory test on blood culture or appropriate antigen test on blood, 
urine, or joint fluid 
c. Cellular profile and chemistries of joint fluid compatible with infection and not 
explained by an underlying rheumatologic disorder  
d. Imaging test evidence of infection (eg, abnormal findings on x-ray, CT scan, 
MRI, radiolabel scan [gallium, technetium, etc]) 
Microbiological Classification 
Confirmed joint or bursa infection cases are to be classified as 
• Microbiologically confirmed S aureus joint or bursa infection if the subject has 
S aureus cultured from joint fluid or synovial biopsy (clinical criterion 1) 
• Microbiologically confirmed non–S aureus joint or bursa infection if the subject 
has only non–S aureus organism(s) cultured from joint fluid or synovial biopsy 
(clinical criterion 1) 
• Non–microbiologically confirmed joint or bursa infection if the above criteria for 
microbiologically confirmed joint or bursa infection are not met 

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PERIPROSTHETIC JOINT INFECTION 
– Clinical Criteria 
Confirmed periprosthetic joint infection must meet at least 1 of the following criteria: 
1. Two positive periprosthetic (tissue or fluid) cultures with identical organisms  
2. A sinus tract communicating with the joint  
3. Having 3 of the following minor criteria: 
a. Elevated serum C-reactive protein (CRP; >100 mg/L) AND erythrocyte sedimentation 
rate (ESR; >30 mm/hour) 
b.  Elevated synovial fluid white blood cell (WBC; >10,000 cells/μL) count OR ++ (or 
greater) change on leukocyte esterase test strip of synovial fluid 
c.  Elevated synovial fluid polymorphonuclear neutrophil percentage (PMN% >90%) 
d. Positive histological analysis of periprosthetic tissue (>5 neutrophils [PMNs] per high 
power field) 
e. A single positive periprosthetic (tissue or fluid) culture 
 
Microbiological Classification 
Confirmed periprosthetic joint infection cases are to be classified as 
• Microbiologically confirmed S aureus periprosthetic joint infection if the subject 
has 2 S aureus-positive periprosthetic (tissue or fluid) cultures (clinical criterion 1), or 
a single S aureus-positive periprosthetic (tissue or fluid) culture as part of clinical 
criterion 3 
• Microbiologically confirmed non–S aureus confirmed periprosthetic joint 
infection if the subject has 2 non–S aureus-positive periprosthetic (tissue or fluid) 
cultures with identical organisms (clinical criterion 1), or a single  
non–S aureus-positive periprosthetic (tissue or fluid) culture as part of clinical 
criterion 3 
• Non–microbiologically confirmed periprosthetic joint infection if the above 
criteria for microbiologically confirmed periprosthetic joint infection are not met 
 

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CARDIOVASCULAR SYSTEM INFECTIONS 
ENDOCARDITIS 
– Clinical Criteria 
Confirmed endocarditis of a natural or prosthetic heart valve must meet at least 1 of the 
following criteria: 
1. Patient has organisms cultured from valve or vegetation 
2. Patient has 2 or more of the following signs or symptoms (*with no other recognized 
cause) 
• Fever (>38°C or >100.4°F) 
• New or changing murmur* 
• Embolic phenomena* 
• Skin manifestations* (ie, petechiae, splinter hemorrhages, painful subcutaneous 
nodules) 
• Congestive heart failure* 
• Cardiac conduction abnormality*  
AND at least 1 of the following:  
a. Organisms cultured from 2 or more blood cultures  
b. Organisms seen on Gram’s stain of valve when culture is negative or not done  
c. Valvular vegetation seen during an invasive procedure or autopsy  
d. Positive laboratory test on blood or urine (eg, antigen tests for H. influenzae, 
S. pneumoniae, N. meningitidis, or group B streptococcus) 
e. Evidence of new vegetation seen on echocardiogram 
AND if diagnosis is made antemortem, physician institutes appropriate antimicrobial therapy. 
Microbiological Classification 
Confirmed endocarditis cases are to be classified as 
• Microbiologically confirmed S aureus endocarditis if the subject has S aureus 
cultured from a valve or vegetation (clinical criterion 1), and/or from 2 or more blood 
cultures as part of clinical criterion 2 
• Microbiologically confirmed non–S aureus endocarditis if the subject has only 
non–S aureus cultured from a valve or vegetation (clinical criterion 1), and/or from  
2 or more blood cultures as part of clinical criterion 2 
• Non–microbiologically confirmed endocarditis if the above criteria for 
microbiologically confirmed endocarditis are not met  

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CENTRAL NERVOUS SYSTEM INFECTIONS 
MENINGITIS 
When meningitis is directly attributable to an infection via the index surgery surgical 
incision, the meningitis is to be classified as an organ/space SSI.  Where no such attribution 
exists, the infection is reported as meningitis. 
– Clinical Criteria 
Confirmed meningitis must meet at least 1 of the following criteria:  
1. Patient has organisms cultured from cerebrospinal fluid (CSF) 
2. Patient has at least 1 of the following signs or symptoms (*with no other recognized 
cause): 
• Fever (>38°C or >100.4°F) 
• Headache* 
• Stiff neck* 
• Meningeal signs* 
• Cranial nerve signs* 
• Irritability* 
AND at least 1 of the following:  
a. Increased white cells, elevated protein, and decreased glucose in CSF  
b. Organisms seen on Gram stain of CSF  
c. Organisms cultured from blood  
d. Positive laboratory test of CSF, blood, or urine  
e. Diagnostic single antibody titer (IgM) or 4-fold increase in paired sera (IgG) for 
pathogen  
AND if diagnosis is made antemortem, physician institutes appropriate antimicrobial therapy 
Microbiological Classification 
Confirmed meningitis cases are to be classified as 
• Microbiologically confirmed S aureus meningitis if the subject has S aureus cultured 
from cerebrospinal fluid (clinical criterion 1), and/or blood as part of clinical criterion 2 
• Microbiologically confirmed non–S aureus meningitis if the subject has only  
non–S aureus cultured from cerebrospinal fluid (clinical criterion 1), and/or from blood 
as part of clinical criterion 2 
• Non–microbiologically confirmed meningitis if the above criteria for microbiologically 
confirmed meningitis are not met 

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SPINAL ABSCESS WITHOUT MENINGITIS 
When a spinal abscess without meningitis is attributable to the index surgery surgical 
incision, the spinal abscess without meningitis is to be classified as an organ/space SSI.  
Where no such attribution exists, the infection is reported as spinal abscess without 
meningitis. 
– Clinical Criteria 
Confirmed spinal abscess without meningitis (abscess of the spinal epidural or subdural 
space, without involvement of the cerebrospinal fluid or adjacent bone structures), must meet 
at least 1 of the following criteria:  
1. Patient has organisms cultured from abscess in the spinal epidural or subdural space. 
2. Patient has an abscess in the spinal epidural or subdural space seen during an invasive 
procedure or at autopsy or evidence of an abscess seen during a histopathologic 
examination. 
3. Patient has at least 1 of the following signs or symptoms (*with no other recognized 
cause): 
• Fever (>38°C or >100.4°F) 
• Back pain* 
• Focal tenderness* 
• Radiculitis* 
• Paraparesis* 
• Paraplegia*  
AND at least 1 of the following:  
a. Organisms cultured from blood  
b. Imaging test evidence of a spinal abscess (eg, abnormal findings on myelography, 
ultrasound, CT scan, MRI, or other scans [gallium, technetium, etc]). 
AND if the diagnosis is made antemortem, physician institutes appropriate antimicrobial 
therapy.  Microbiological Classification 
Confirmed spinal abscess without meningitis cases are to be classified as 
• Microbiologically confirmed S aureus spinal abscess without meningitis if the subject 
has S aureus cultured from abscess in the spinal epidural or subdural space (clinical 
criterion 1) or from blood (as part of clinical criterion 3) 
• Microbiologically confirmed non–S aureus spinal abscess without meningitis if the 
subject has only non–S aureus organisms cultured from abscess in the spinal epidural or 
subdural space (clinical criterion 1) or from blood (as part of clinical criterion 3) 
• Non–microbiologically confirmed spinal abscess without meningitis if the above 
criteria for microbiologically confirmed spinal abscess are not met 
 

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INTRA-ABDOMINAL INFECTIONS 
When an intra-abdominal infection is attributable to an infection via the index surgery 
incision site, eg, an intraperitoneal incision, the intra-abdominal infection is to be classified 
as an organ/space SSI.  Where no such attribution exists, the infection is reported as an 
intra-abdominal infection using the verbatim term.  Includes infections of the gallbladder, 
bile ducts, liver (excluding viral hepatitis), spleen, pancreas, peritoneum, subphrenic or 
subdiaphragmatic space, or other intra-abdominal tissue. 
– Clinical Criteria 
Confirmed intra-abdominal infection must meet at least 1 of the following criteria 
1. Patient has organisms cultured from abscess and/or purulent material from 
intra-abdominal space obtained during an invasive procedure. 
2. Patient has abscess or other evidence of intra-abdominal infection seen during an invasive 
procedure or histopathologic examination. 
3. Patient has at least 2 of the following signs or symptoms (*with no other recognized 
cause):  
• Fever (>38°C or >100.4°F)  
• Nausea*  
• Vomiting*  
• Abdominal pain*  
• Jaundice*  
AND at least 1 of the following: 
a. Organisms cultured from drainage from an aseptically placed drain (eg, closed 
suction drainage system, open drain, T-tube drain, CT-guided drainage)  
b. Organisms seen on Gram’s stain of drainage or tissue obtained during invasive 
procedure or from an aseptically placed drain  
c. Organisms cultured from blood and imaging test evidence of infection (eg, 
abnormal findings on ultrasound, CT scan, MRI, or radiolabel scans [gallium, 
technetium, etc] or on abdominal x-ray) 
Microbiological Classification 
• Microbiologically confirmed S aureus intra-abdominal infection if the subject has 
S aureus organisms isolated from an aseptically obtained culture of an abscess and/or 
purulent material from the intra-abdominal space obtained during an invasive procedure  
• Microbiologically confirmed non–S aureus intra-abdominal infection if the subject 
has only non–S aureus organisms isolated from a culture of an abscess and/or purulent 
material from the intra-abdominal space obtained during an invasive procedure 
• Non–microbiologically confirmed intra-abdominal infection if the above criteria for 
microbiologically confirmed intra-abdominal infection are not met  

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PNEUMONIA 
– Clinical Criteria 
Confirmed pneumonia must meet the following criteria 
1. Two or more serial chest radiographs with at least 1 of the following (in patients without 
underlying pulmonary or cardiac disease [eg, respiratory distress syndrome, 
bronchopulmonary dysplasia, pulmonary edema, or chronic obstructive pulmonary 
disease], 1 definitive chest radiograph is acceptable): 
• New or progressive and persistent infiltrate 
• Consolidation 
• Cavitation 
2. At least 1 of the following: 
• Fever (>38°C or >100.4°F) 
• Leukopenia (<4000 WBC/mm3) or leukocytosis (≥12,000 WBC/mm3) 
• For adults ≥70 years old, altered mental status with no other recognized cause 
AND at least 2 of the following: 
• 
New onset of purulent sputum, or change in character of sputum, or increased 
respiratory secretions, or increased suctioning requirements 
• 
New-onset or worsening cough, or dyspnea or tachypnea  
• 
Rales or bronchial breath sounds  
• 
Worsening gas exchange (eg, O2 desaturations [eg, PaO2/FiO2 ≤240], increased 
oxygen requirements, or increased ventilator demand)  
Microbiologically confirmed pneumonia must demonstrate at least 1 of the following 
criteria: 
• Positive growth in blood culture not related to another source of infection 
• Positive growth in culture of pleural fluid  
• Positive quantitative culture from minimally contaminated lower respiratory tract 
(LRT) specimen (eg, bronchial alveolar lavage or protected specimen brushing) 
Microbiological Classification 
Confirmed pneumonia cases are to be classified as 
• 
Microbiologically confirmed S aureus pneumonia if the subject has S aureus 
cultured from blood, pleural fluid, and/or minimally contaminated LRT specimen, as 
per microbiologically confirmed pneumonia criteria 
• 
Microbiologically confirmed non–S aureus pneumonia if the subject has only  
non–S aureus organism(s) cultured from blood, pleural fluid, and/or minimally 
contaminated LRT specimen, as per microbiologically confirmed pneumonia criteria 
• 
Non–microbiologically confirmed pneumonia if the above criteria for 
microbiologically confirmed pneumonia are not met 

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SURGICAL-SITE INFECTIONS 
SUPERFICIAL SSI 
Clinical Criteria 
Confirmed superficial SSI must meet the following criteria:  
1. Involves only skin and subcutaneous tissue of the incision 
AND 
2. Patient has at least 1 of the following: 
a. Purulent drainage from the superficial incision  
b. Organisms isolated from an aseptically obtained culture of fluid or tissue from the 
superficial incision 
c. Superficial incision that is deliberately opened by a surgeon or attending physician or 
designee and is culture-positive or not cultured (a culture-negative finding does not 
meet this criterion) 
AND At least 1 of the following signs or symptoms of infection: 
• 
pain or tenderness 
• 
localized swelling 
• 
redness 
• 
heat 
d. Diagnosis of a superficial incisional SSI by the surgeon or attending physician or 
designee 
 
Microbiological Classification 
 
Confirmed superficial SSI cases are to be classified as 
• Microbiologically confirmed S aureus superficial SSI if the subject has S aureus 
cultured from an aseptically obtained culture of fluid or tissue from the superficial 
incision, or from a superficial incision that is deliberately opened, as part of clinical 
criterion 2 
• Microbiologically confirmed non–S aureus superficial SSI if the subject has only 
non–S aureus organism(s) cultured from an aseptically obtained culture of fluid or 
tissue from the superficial incision, or from a superficial incision that is deliberately 
opened, as part of clinical criterion 2 
• Non–microbiologically confirmed superficial SSI if the above criteria for 
microbiologically confirmed superficial SSI are not met 
 

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DEEP INCISIONAL SSI 
– Clinical Criteria 
 
Confirmed deep incisional SSI must meet the following criteria:  
 
1. Involves deep soft tissues of the incision (eg, fascial and muscle layers) 
AND 
2. Patient has at least 1 of the following: 
a. Purulent drainage from the deep incision 
b. A deep incision that spontaneously dehisces or is deliberately opened by a surgeon, 
attending physician or designee and is culture-positive or not cultured 
(culture-negative finding does not meet this criterion) 
AND the patient has at least 1 of the following signs or symptoms: 
• fever (>38°C or >100.4°F) 
• localized pain or tenderness 
c. An abscess or other evidence of infection involving the deep incision that is found on 
direct examination, during invasive procedure, or by histopathologic examination or 
imaging test. 
Microbiological Classification 
 
Confirmed deep incisional SSI cases are to be classified as: 
• Microbiologically confirmed S aureus deep incisional SSI if the subject has a deep 
incision that spontaneously dehisces or is deliberately opened by a surgeon, attending 
physician or designee and is culture-positive for S aureus as part of clinical criterion 2 
• Microbiologically confirmed non–S aureus deep incisional SSI if the subject has a 
deep incision that spontaneously dehisces or is deliberately opened by a surgeon, 
attending physician or designee and is culture-positive for only non–S aureus 
organism(s), as part of clinical criterion 2 
• Non–microbiologically confirmed deep incisional SSI if the above criteria for 
microbiologically confirmed deep incisional SSI are not met 
 

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ORGAN SPACE SURGICAL SITE INFECTION 
– Clinical Criteria 
Confirmed organ space SSI must meet the following criteria:  
1. Infection involves any part of the body, excluding the skin incision, fascia, or muscle 
layers, that is opened or manipulated during the operative procedure  
AND 
2. Patient has at least 1 of the following:  
a. Purulent drainage from a drain that is placed into the organ/space  
b. Organisms isolated from an aseptically obtained culture of fluid or tissue in the 
organ/space 
c. An abscess or other evidence of infection involving the organ/space that is found on 
direct examination, during invasive procedure, or by histopathologic examination or 
imaging test  
AND 
3. Meets at least 1 criterion for an  organ/space infection site listed below: 
• Osteomyelitis 
• Vertebral disc space infection 
• Meningitis 
• Spinal abscess without meningitis 
• Intra-abdominal infection 
• Joint or bursa infection  
 
Microbiological Classification 
 
Confirmed organ/space SSI cases are to be classified as 
• Microbiologically confirmed S aureus organ/space SSI if the subject has S aureus 
organisms isolated from an aseptically obtained culture of fluid or tissue in the 
organ/space, as part of clinical criterion 2 
• Microbiologically confirmed non–S aureus organ/space SSI if the subject has only 
non–S aureus organisms isolated from an aseptically obtained culture of fluid or 
tissue in the organ/space, as part of clinical criterion 2 
• Non–microbiologically confirmed organ/space SSI if the above criteria for 
microbiologically confirmed organ space SSI are not met 

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Appendix 2. Preoperative Assessment 
• American Society of Anesthesiologists (ASA) Physical Status Classification Score 
• Source of admission (other healthcare facility) 
• Wound site preparation method (clippers, shaving, etc) 
• S aureus /MRSA carriage evaluation  
• Decolonization therapy 
• Intranasal mupirocin 
• Chlorhexidine 
• Other  
Appendix 3. Perioperative Assessment 
• Skin preparation (eg, betadine, chlorhexidine) 
• Surgical procedure performed (eg, posterior lumbar interbody fusion) 
• Wound classification (eg, clean, clean contaminated, contaminated) 
• Skin closure type (eg, staples, sutures, other)  
• Primary incision site (eg, midline posterior, posterolateral) 
• Secondary incision(s) 
• Spinal site(s) (anterior, endoscopic, etc.) 
• Graft donor site(s) 
• Intervertebral level(s) fused (eg, lumbar 4 through thoracic 5) 
• Implanted material (type and composition  eg, rod,  titanium) 
Device Type 
 
Composition 
• Rods 
 
• Titanium 
• Plates 
 
• Stainless steel 
• Screws 
 
• Other 
• Cages 
 
 
• Other 
 
 
• Graft type (eg, autograft, allograft, bone morphogenic protein, other) 
• Duration of surgery (knife to skin closure) 
• Surgical site drains, indwelling catheters 

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• Vancomycin powder application to wound 
• Prophylactic antibiotic (name, start and stop time, date, and dose) 
• Estimated blood loss (mL) 
• Blood product transfusion (eg, whole blood, red blood cells, platelets, clotting factors, 
cryoprecipitate, white blood cells, immunoglobulins, albumin, and plasma) and origin 
(heterologous or autologous donation/ transfusion of whole blood or red blood cells) 
• Postoperative patient temperature (°C or °F) (first recorded postoperative value on return 
to ward) 
Appendix 4. Healthcare-Utilization Assessment 
• Number of days in hospital 
• Number of days in an intensive care unit 
• Number of readmissions to hospital  
• Number of reoperations 
• Number of inpatient days in a rehabilitation facility after discharge 
• Number of inpatient days in a skilled nursing care facility/nursing home after discharge 
• Discharge disposition  
• Home  
• Rehabilitation  
• Skilled nursing care facility  
• Death 
• Other 
• Number of rehabilitation/physical therapy visits as an outpatient 
• Days of antibiotic use 

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Appendix 5. Country-Specific Appendix – Applicable to France Only 
The following supplementary text should be read in conjunction with the B3451002 protocol: 
• Prior to enrollment of any subjects, the investigator and any subinvestigators will 
complete the Pfizer-provided Good Clinical Practice (GCP) training course (“Pfizer GCP 
Training”).  Any investigators who later join the study will complete Pfizer GCP Training 
before performing study-related duties.  For studies of applicable duration, the 
investigator and subinvestigators will complete Pfizer GCP Training every 3 years during 
the term of the study, or more often if there are significant changes to the International 
Conference on Harmonisation (ICH) GCP guidelines or course materials. 
• No subjects or third-party payers will be charged for investigational product. 
• The investigator(s) will notify Pfizer or its service provider immediately of any 
regulatory inspection notification in relation to the study.  Furthermore, the investigator 
will cooperate with Pfizer or its service provider to prepare the study site for the 
inspection and will allow Pfizer or its service provider (if not prohibited by law) to be 
present during the inspection.  The study site and investigator will promptly resolve any 
discrepancies that are identified between the study data and the subject's medical records.  
The investigator will promptly provide copies of the inspection findings to Pfizer or its 
service provider.  Before response submission to the regulatory authorities, the 
investigator will provide Pfizer or its service provider with an opportunity to review and 
comment on responses to any such findings. 
• Information relating to the investigator, subinvestigators, and research staff will be held 
in 1 or more databases for the purpose of determining their involvement in future 
research and in order to comply with any regulatory requirements.  All affected personnel 
will be furnished with a form of notice setting out the intended use of the personal data 
and be asked to sign a consent form. 

Staphylococcus aureus 4-Antigen Vaccine (SA4Ag) (PF-06290510)  
B3451002 
Final Protocol Amendment 4, 05 February 2018 
 
 
Page 129 
Appendix 6. Country-Specific Appendix – Applicable to Japan Only 
The following supplementary text should be read in conjunction with the B3451002 protocol: 
• When the subject is a minor under local law, the investigator, or a person designated by 
the investigator, will obtain written informed consent from the subject’s legally 
acceptable representative, or parent(s) or legal guardian, and the subject’s assent 
(affirmative agreement) before any study-specific activity is performed.  The investigator 
will retain the original of each signed consent and assent document. 
• The assent form for a minor must be in compliance with International Conference on 
Harmonisation (ICH) Good Clinical Practice (GCP), local regulatory requirements, 
and legal requirements, including applicable privacy laws. 
• The assent form for a minor used during the informed consent process must be 
reviewed by the sponsor, approved by the institutional review board 
(IRB)/independent ethics committee (IEC) before use, and available for inspection. 
• The investigator must ensure that the subject’s legally acceptable representative, or 
parent(s) or legal guardian, is fully informed about the nature and objectives of the 
study and possible risks associated with participation. 
• The source documents must record that the subject was a minor at the time of signing 
the informed consent document (ICD), how the investigator determined that the 
person signing the consent was the subject’s legally acceptable representative, the 
consent signer’s relationship to the study subject (eg, parent), and that the subject’s 
assent was obtained. 
• When the minor subjects reach the age of majority during the study, as recognized under 
local law, they must reconsent as adults to remain in the study. 
• Axillary temperature will be measured at Visit 1, as required at an unscheduled visit, and 
will be measured by the subject for 10 days following vaccination. 
• An axillary temperature of ≥37.5°C meets the definition of a current febrile illness in the 
criteria for temporarily delaying vaccine administration described in Section 4.3 for 
subjects enrolled in Japan. 
• For the purpose of recording the temperature in the electronic diary (e-diary), fever is 
defined as an axillary temperature of ≥38.0°C (100.4°F) for subjects enrolled in Japan. 
• To facilitate ease of understanding in the e-diary for the subject, the same terms of local 
reactions and systemic events in Table 9 and Table 10 will be described with simple 
wording and pronunciation upon translating them into Japanese.