A Phase III Single-Arm Open-Label Study to Evaluate the Safety PK ADA and Anti RSV nAb Following Administration of 2 Doses of Nirsevimab Given 5 to 6 Months Apart in Infants With CHD, CLD, Immunocompromise, Down Syndrome, or Born Pre-Term in Japan
Phase: PHASE3
Conditions: Respiratory Syncytial Virus Infections
Sponsor: AstraZeneca

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Clinical Study Protocol 
Study 
Intervention
Nirsevimab (MEDI8897)
Study Code
D5290C00009
Version
Version 2.0
Date
19 May 2023
A Phase III, Single-Arm, Open-Label Study to Evaluate the Safety, 
Pharmacokinetics, Anti-Drug Antibody, and Anti-RSV 
Neutralizing Antibody Following Administration of 2 Doses of 
Nirsevimab Given 5 to 6 Months Apart in Infants with Congenital 
Heart Disease, Chronic Lung Disease, Immunocompromise, Down 
Syndrome, or Born Pre-Term in Japan
Sponsor Name:
AstraZeneca AB 151, 85 Södertälje, Sweden 
In-Country Caretaker for Clinical Trial (ICCC): 
IQVIA Services Japan K.K., 4-10-18 Takanawa, Minato-ku, Tokyo, 108-0074
This protocol has been subject to a peer review according to AstraZeneca Standard 
Procedures. The protocol is publicly registered, and the results are disclosed and/or published 
according to the AstraZeneca Global Standard - Bioethics and in compliance with prevailing 
laws and regulations.
Version Scope: Version 2.0, Japan
Brief Title:
A study to investigate the safety, pharmacokinetics, occurrence of anti-drug antibody, and anti-
RSV neutralizing antibody following 2 doses administration of nirsevimab (MEDI8897) in
infants with certain health conditions or born pre-term in Japan
Study Phase: Phase III

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Study Physician Name and Contact Information including administrative structure will 
be provided separately.
DOCUMENT HISTORY
Document
Date
CSP Version 1.0
22- Mar -2023
CSP Version 2.0
19- May -2023
CSP Version 2.0 [19-May-2023]
Overall Rationale for the Modification:
CSP Version 2.0 (dated 19 May 2023)
The principal reason for this protocol amendment is to revise the period of once 2 weeks 
(Q2W) Telephone Contact after 2nd dose of MEDI8897, aligned to PMDA requirements.
Since this is the first study to evaluate the safety of administration of two doses of MEDI8897 
in one RSV season, period of Q2W Telephone Contact is extended to180 days after 2nd Dose 
to ensure safety of study participants.
Section # and Name
Description of change
Brief Rationale
Substantial/
Non-substantial
1.2 Schema
Figure 1Study Design
Extended period of 
Telephone Contact for once 
2 weeks (Q2W) to 180days 
after Dose 2.
To ensure the safety of subjects as 
this is the first study to evaluate the 
administration of 2 doses of 
MED18897 in a single RSV season.
Substantial
1.3 Schedule of 
Activities
Table 2
Addition of procedures for 
Telephone Contact (Q2W) 
in period of Post-2nd Dose 
Follow-up.
To ensure the safety of subjects as 
this is the first study to evaluate the 
administration of 2 doses of 
MED18897 in a single RSV season.
Substantial
4.1.3 Subsequent Visit
Text added that Telephone 
contact for Q2W during 6 
months after 2nd dose to be 
planned.
To ensure the safety of subjects as 
this is the first study to evaluate the 
administration of 2 doses of 
MED18897 in a single RSV season.
Substantial
6.6 Dose 
Modification/Replace
ment Dose
Text added that Telephone 
contact for Q2W during 6 
months after replacement 
dose to be planned.
To ensure the safety of subjects as 
this is the first study to evaluate the 
administration of 2 doses of 
MED18897 in a single RSV season.
Substantial

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TABLE OF CONTENTS
TABLE OF CONTENTS ...................................................................................................... 3
LIST OF ABBREVIATIONS................................................................................................ 7
1
PROTOCOL SUMMARY ................................................................................ 10
1.1
Synopsis ........................................................................................................... 10
1.2
Schema............................................................................................................. 13
1.3
Schedule of Activities ....................................................................................... 14
2
INTRODUCTION............................................................................................ 17
2.1
Study Rationale ................................................................................................ 17
2.2
Background ...................................................................................................... 17
2.3
Benefit/Risk Assessment................................................................................... 18
2.3.1
Risk Assessment ............................................................................................... 18
2.3.2
Benefit Assessment........................................................................................... 20
2.3.3
Overall Benefit/Risk Conclusion....................................................................... 21
3
OBJECTIVES, ENDPOINTS, AND ESTIMANDS .......................................... 22
4
STUDY DESIGN ............................................................................................. 24
4.1
Overall Design.................................................................................................. 24
4.1.1
Screening Visit.................................................................................................. 25
4.1.2
Visit for Dose.................................................................................................... 25
4.1.3
Subsequent Visit ............................................................................................... 25
4.2
Scientific Rationale for Study Design ............................................................... 26
4.2.1
Rationale for Study Population ......................................................................... 26
4.2.2
Rationale for Study Endpoints .......................................................................... 26
4.3
Justification for Dose........................................................................................ 26
4.4
End of Study Definition.................................................................................... 27
5
STUDY POPULATION.................................................................................... 27
5.1
Inclusion Criteria .............................................................................................. 27
5.2
Exclusion Criteria ............................................................................................. 28
5.3
Lifestyle Considerations ................................................................................... 29
5.4
Screen Failures ................................................................................................. 29
5.5
Criteria for Temporarily Delaying ..................................................................... 29
5.6
Study Suspension or Termination...................................................................... 29
6
STUDY INTERVENTION(S) AND CONCOMINANT THERAPY ................. 30
6.1
Study Intervention(s) Administered................................................................... 30
6.1.1
Study Intervention Administered....................................................................... 30
6.1.2
Dose Preparation Steps and Treatment Administration ...................................... 30
6.1.3
Eligibility for 2nd Dose..................................................................................... 31
6.2
Preparation, Handling, Storage, and Accountability .......................................... 32

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6.3
Assignment to Study Intervention ..................................................................... 32
6.4
Blinding............................................................................................................ 32
6.5
Study Intervention Compliance......................................................................... 32
6.6
Dose Modification/Replacement Dose .............................................................. 33
6.7
Continued Access to Study Intervention After the End of the Study .................. 33
6.8
Treatment of Overdose...................................................................................... 33
6.9
Concomitant Therapies ..................................................................................... 34
6.9.1
Permitted Concomitant Medications or Treatments ........................................... 34
6.9.2
Prohibited Concomitant Medication.................................................................. 34
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANTS 
DISCONTINUATION/WITHDRAWAL........................................................... 34
7.1
Discontinuation of Study Intervention............................................................... 34
7.2
Participants Discontinuation/Withdrawal from the Study .................................. 35
7.3
Lost to Follow-up ............................................................................................. 36
8
STUDY ASSESSMENTS AND PROCEDURES.............................................. 36
8.1
Administrative Procedures................................................................................ 37
8.2
Surveillance for MA-RSV LRTI ....................................................................... 38
8.2.1
Lower Respiratory Tract Infection..................................................................... 38
8.2.2
RSV Hospitalization ......................................................................................... 39
8.2.3
Respiratory Secretions for RSV Detection......................................................... 40
8.2.4
Monitoring for RSV Resistance ........................................................................ 41
8.3
Safety Assessments........................................................................................... 41
8.3.1
Physical Examinations...................................................................................... 41
8.3.2
Vital Signs ........................................................................................................ 42
8.3.3
Electrocardiograms........................................................................................... 42
8.3.4
Clinical Safety Laboratory Tests ....................................................................... 42
8.4
AEs, SAEs, and Other Safety Reporting............................................................ 42
8.4.1
Time Period and Frequency for Collecting AE and SAE Information................ 43
8.4.2
Follow-up of AEs and SAEs ............................................................................. 43
8.4.3
Causality Collection.......................................................................................... 44
8.4.4
AEs Based on Examinations and Tests.............................................................. 44
8.4.5
AEs Based on Signs and Symptoms.................................................................. 44
8.4.6
Hy’s Law.......................................................................................................... 45
8.4.7
Disease Under Study......................................................................................... 45
8.4.8
Definition of Adverse Events of Special Interest ............................................... 45
8.4.8.1
Hypersensitivity, Including Anaphylaxis ........................................................... 45
8.4.8.2
Immune Complex Disease ................................................................................ 46
8.4.8.3
Thrombocytopenia............................................................................................ 46
8.4.9
Definition of New-Onset Chronic Diseases....................................................... 47
8.4.10
Reporting of SAEs............................................................................................ 47
8.4.11
Medication Error............................................................................................... 48
8.4.11.1
Timelines.......................................................................................................... 48
8.4.11.2
Medication Error............................................................................................... 48

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8.4.12
Reporting of Overdose...................................................................................... 48
8.5
Pharmacokinetics.............................................................................................. 49
8.5.1
Collection of Samples for Pharmacokinetics ..................................................... 49
8.5.2
Determination of Drug Concentration ............................................................... 49
8.6
Immunogenicity and Anti-RSV Neutralizing Antibody Assessments................. 50
9
STATISTICAL CONSIDERATIONS................................................................ 50
9.1
Statistical Hypotheses ....................................................................................... 50
9.2
Sample Size Determination............................................................................... 50
9.3
Populations for Analyses................................................................................... 51
9.4
Statistical Analyses ........................................................................................... 51
9.4.1
General Considerations..................................................................................... 51
9.4.2
Safety ............................................................................................................... 51
9.4.3
Secondary Endpoints ........................................................................................ 52
9.4.3.1
Pharmacokinetics.............................................................................................. 52
9.4.3.2
Anti-Drug Antibody.......................................................................................... 52
9.4.3.3
Anti-RSV Neutralizing Antibody Evaluation..................................................... 53
9.4.4
Exploratory Endpoint(s).................................................................................... 53
9.4.4.1
Occurrence of MA-RSV LRTI .......................................................................... 53
9.4.4.2
Monitoring RSV Resistance to Nirsevimab....................................................... 53
9.5
Deviations from Clinical Study Protocol........................................................... 53
10
SUPPORTING 
DOCUMENTATION 
AND 
OPERATIONAL
CONSIDERATIONS ........................................................................................ 54
11
REFERENCES................................................................................................. 74
LIST OF FIGURES
Figure 1
Study Design ........................................................................................... 13
LIST OF TABLES
Table 1
Study Plan Detailing the Procedures at Screening .................................... 14
Table 2
Study Plan Detailing the Procedures during Treatment and Follow-up 
Period...................................................................................................... 15
Table 3
Objectives and Endpoints/Estimand......................................................... 22
Table 4
Investigational Intervention ..................................................................... 30
Table 5
Estimated Volume of Blood to be Collected............................................. 37
Table 6
Criteria for Meeting the Protocol-defined Endpoint of Medically 
Attended RSV LRTI................................................................................ 39
Table 7
Populations for Analysis .......................................................................... 51

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LIST OF APPENDICES
Appendix A
Regulatory, Ethical, and Study Oversight Considerations......................... 55
Appendix B
AEs: Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting .......................................................................................... 61
Appendix C
Handling of Human Biological Samples .................................................. 66
Appendix D
Actions Required in Cases of Increases in Liver Biochemistry and 
Evaluation of Hy’s Law........................................................................... 68

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LIST OF ABBREVIATIONS
Abbreviation or special term
Explanation
aa
Amino acid 
Ab
Antibody
ADA
Anti-Drug Antibody
AE
Adverse Event
AESI
Adverse Event of Special Interest
ALT
Alanine aminotransferase 
AST
Aspartate aminotransferase
BUN
Blood urea nitrogen
CFR
Code of Federal Regulations
CHD
Congenital Heart Disease
CI
Confidence Interval
CIOMS
Council for International Organizations of Medical Sciences
CLD
Chronic Lung Disease
CONSORT
Consolidated Standards of Reporting Trials
CPAP
Continuous Positive Airway Pressure
CRF
Case Report Form
CRO
Contract Research Organization
CSP
Clinical Study Protocol
CSR
Clinical Study Report
CTCAE
Common Terminology Criteria for Adverse Events
DILI
Drug-Induced Liver Injury
DUS
Disease under Study 
E/D
Early Study Intervention Discontinuation
eCRF
electronic Case Report Form
EDC
Electronic Data Capture
EEA 
European Economic Area 
ER
Emergency Room
FDA
(US) Food and Drug Administration
GA
Gestation age
GCP
Good Clinical Practice
GMFR
Geometric Mean Fold-Rise

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Abbreviation or special term
Explanation
GMP
Good Manufacturing Practice
GMT
Geometric Mean Titer
HBS
Human Biological Sample(s)
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IgG
Immunoglobulin G
IgM
Immunoglobulin M
IM
Intramuscular
IMP
Investigational Medicinal Product
IRB
Institutional Review Board
JMDC
Japan Medical Data Center
LRTI
Lower Respiratory Tract Infection
MA
Medically attended
mAb
Monoclonal antibody
MedDRA
Medical Dictionary for Regulatory Activities
NCI
National Cancer Institute
NIMP
Non-investigational Medicinal Product 
NOCD
New-onset chronic disease
OTC
Over-the-Counter
PI
Principal Investigator
PK
Pharmacokinetic(s)
PT
Preferred term
Q2W
Once every 2 weeks
RRR
Relative Risk Reduction
RSV
Respiratory Syncytial virus
RT-PCR
Reverse transcriptase-polymerase chain reaction
SAE
Serious Adverse Event
SAP
Statistical analysis plan
SoA
Schedule of Activities
SOC
System organ class
TBL
Total Bilirubin

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Abbreviation or special term
Explanation
TEAE
Treatment-Emergent Adverse Event
TESAE
Treatment-Emergent Serious Adverse Event
ULN
Upper Limit of Normal

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Type
Objective
Hypothesis 
tested
Endpoints/Estimand
RSV-resistance 
monitoring
To characterize resistance to 
nirsevimab through genotypic 
and phenotypic analysis
None
•
Genotypic analysis and 
susceptibility of RSV variants to 
neutralization by nirsevimab 
Ab = antibody; ADA = anti-drug antibody; IMP = investigational medical product; MA-LRTI = medically attended lower 
respiratory tract infection; PT = preferred term; RSV = respiratory syncytial virus; RT-PCR = reverse 
transcriptase-polymerase chain reaction; SOC = system organ class
Overall Design Synopsis:
This study is a phase III, single-arm, open-label, 2-dose (Day 1 & Day 150-180) study to 
assess the safety, PK, occurrence of ADA to nirsevimab, and anti-RSV neutralizing Ab in 
infants with CHD, CLD, Down syndrome, immunocompromise, or born premature 
(≤35 weeks gestation age: 35 wks GA) who are ≤12 months of age at enrollment. The study is 
planned to be conducted in Japan.
Brief Summary:
The purpose of this study is to measure the safety, PK, occurrence of ADA to nirsevimab, and 
anti-RSV neutralizing Ab in Japanese children with certain health conditions or pre-term 
infants aged ≤12 months.
Study details include:

The study duration is approximately 21 months with a 2-month enrollment period.

Study intervention is 2 doses administered 5- 6 months apart.

The study has 5 or 6 site visits and several telephone contacts with a 2- or 4-week 
interval.
Disclosure Statement: This is an open-label study with a single arm.
Number of Participants:
Approximately 33 participants will be enrolled to receive 2 IM doses of nirsevimab to 
evaluate the safety, PK, and ADA to nirsevimab, and anti-RSV neutralizing Ab which will be 
assessed descriptively.
Note: ‘enrolled’ means participant’s legally acceptable representative’s agreement to 
participate in a clinical study following completion of the informed consent process, and 
participants have received the first dose of nirsevimab. Potential participants who are screened 
for the purpose of determining eligibility for the study, but are not assigned in the study, are 
considered ‘screen failures’, unless otherwise specified by the protocol.
Study Arms and Duration:
Participants in the first year of life will receive the 1st dose of nirsevimab as a single, fixed 
intramuscular (IM) dose of 50 mg if body weight is <5 kg or 100 mg if body weight is ≥5 kg. 

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A 2nd fixed IM dose of 50 mg if body weight is <5 kg or 100 mg if body weight is ≥5 kg will 
be administered 5 to 6 months following the 1st dose. All participants will be followed until 
the end of the study follow-up period (360 days after the 2nd or last dose administered in the 
study).
Statistical Methods
No statistical hypothesis analysis is planned.
Approximately 33 participants will be enrolled to receive 2 IM doses of nirsevimab to 
evaluate the safety, PK, and ADA to nirsevimab, and anti-RSV neutralizing Ab which will be 
assessed descriptively. The proposed sample size of 33 participants in this study accounts for 
conservative estimate of 7% participant drop-out (based on 5% drop-out observed from the 
previous study) between 1st and 2nd doses to get 30 participants exposed to 2 IM doses of 
nirsevimab in this study will provide about 79% probability of observing at least one AE if the 
true event rate is 5%. Thirty-three participants are considered to provide adequate sample size 
to evaluate the safety and to describe nirsevimab serum concentrations, and ADA to 
nirsevimab, and anti-RSV neutralizing Ab following 2nd dose.
There are 2 planned analyses for this study: a primary analysis and a final analysis. The 
primary analysis will be conducted when all enrolled participants have been followed through 
Visit 5 (ie, around 150 days post 2nd dose). The final analysis will be conducted after all 
participants have completed the last visit of the study (ie, around 360 days post 2nd or last 
dose). Descriptive statistics will be produced for all efficacy, safety, PK, ADA, and anti-RSV 
neutralizing Ab variables.
1.2
Schema
Figure 1
Study Design
Q2W = Once 2 weeks; TC = telephone contact
First telephone contact post 2nd dose occurs 7 days post dose.
Visit 4: 30 days post 2nd dose
Visit 5: 150 days post 2nd dose
Visit 6: 360 days post 2nd dose

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1.3
Schedule of Activities
Refer to Table 1 and Table 2.
Table 1
Study Plan Detailing the Procedures at Screening
Study Period
V1 (Screening)
Procedure/Study Day or Week
Day -30 to Day 1
Written informed consent/assignment of SID number
X
Medical history 
X
Physical examination a
X
Weight
X
Vital signs b
X
Hematology c, d
X
Serum chemistry c, d
X
Blood sample for PK, ADA, anti-RSV neutralizing Ab c
X
Assessment of AEs/SAEs
X
Concomitant medications
X
To verify eligibility criteria
X
Other baseline information e
X
Ab = antibody, ADA = anti-drug antibody; AE = adverse event; LRI = lower respiratory infection; 
PK = pharmacokinetics; RSV = respiratory syncytial virus; SAE = serious adverse event; SID = participant identification.
a
A complete physical examination will be performed. It includes assessments of the following: height, weight, 
general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, and 
throat), lymph nodes, thyroid, musculoskeletal (including spine and extremities), and neurological systems.
b
Vital signs include temperature, blood pressure, heart rate, and respiratory rate.
c
If Visit 1/Screening and Visit 2/Day 1 do not occur on the same day, a blood sample for hematology/serum 
chemistry, and PK/ADA/anti-RSV neutralizing Ab can be collected at either Visit 1/Screening or Visit 2/Day 1 
Predose.
d
Hematology = RBC, WBC, Lymphocyte, Platelet count, and Hemoglobin; Serum chemistry = AST, ALT, Total 
bilirubin, BUN, and Creatinine
e
Baseline information includes breastfeeding, smoking in the household, presence of sibling(s), and if the infant 
attends day care.

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Ab = antibody, ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; D = Day; LRTI = lower respiratory tract infection; 
NOCDs = new-onset chronic disease; PK = pharmacokinetic; Q2W = once every 2 weeks; RSV = respiratory syncytial virus; SAE = serious adverse event; 
TC = telephone contact; V = visit.
a
V2/D1 and V1/Screening can occur on the same day. Blood sample to be drawn prior to the administration.
b
A complete physical examination will be performed on the dosing day (prior to dosing at Visit 2 and 3). It includes assessments of the followings: height, weight, general 
appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal (including spine 
and extremities), and neurological systems. On other visits, symptom targeted physical examination will be performed.
c
Body weight will be measured prior to dose on the dosing day.
d
On the dosing day, vital signs (temperature, blood pressure, heart rate, and respiratory rate) should be obtained within 60 minutes before dose, and at 30 minutes 
(± 5 minutes) and 60 minutes (± 5 minutes) post-dose. In addition, participants will be carefully monitored for at least 60 minutes after each dose.
e
Hematology = RBC, WBC, Lymphocyte, Platelet count, and Hemoglobin; Serum chemistry = AST, ALT, Total bilirubin, BUN, and Creatinine
f
If V1/Screening and V2/D1 do not occur on the same day, blood sample for hematology/serum chemistry, and PK/ADA/anti-RSV neutralizing Ab can be collected at 
either V1/Screening or V2/D1.
g
Respiratory secretion (nasal swab, or nasopharyngeal washes/tracheal aspirates are also acceptable if it has been collected) samples will be collected from all participants 
with LRTIs (inpatient or outpatient) and from all hospitalized participants with any new respiratory infection (upper or lower) within 2 days after the initial healthcare 
provider assessment and diagnosis. Blood samples will be collected from all participants hospitalized with LRTI or any respiratory infection within 2 days following 
hospital admission to measure PK/ADA/anti-RSV neutralizing Ab.
h
Telephone contact must be verbal communication. Written communication via text, email, or other written forms is not acceptable.
i
7 ± 2 days post 2nd dose
j
30 ± 7 days post 2nd dose
k
150 ± 15 days post 2nd dose
l
360 ± 15 days post 2nd dose
m
Blood sample to be drawn prior to the administration of 2nd dose
n
If the replacement dose is administered, participants will receive the same procedures on replacement dose day as those listed for 2nd dose (V3/D151-180). In the case 
that participants receive replacement dose prior to administration of the 2nd dose, they will not receive further dose (See Section 6.1.3). All participants that receive a 
replacement dose will be followed through 360 days post replacement dose (the same follow-up/procedures that are outlined through 360 days post 2nd dose in the above 
table, See Section 6.6.
Refer to Section 6.1.3 on eligible criteria for 2nd dose.

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2
INTRODUCTION
Nirsevimab is a recombinant human immunoglobulin G (IgG)1 kappa (IgG1κ) monoclonal 
antibody (mAb) directed against the prefusion conformation of F protein of the respiratory 
syncytial virus (RSV) and provides protection from serious RSV disease by binding with RSV.
2.1
Study Rationale
Pre-term birth (≤35 wks GA), congenital heart disease (CHD), chronic lung disease (CLD), 
Down syndrome, and compromised immune status are important risk factors for RSV-related 
morbidity and mortality in infants and young children.
Nirsevimab is a recombinant human IgG 1 kappa mAb with a longer efficacy than 
palivizumab, and safety and efficacy for at least 5 months after a single intramuscular (IM) 
dose has been already established together with pharmacokinetic (PK), and occurrence of 
anti-drug antibody (ADA) in previous pivotal phase III studies in pre-term infants and young 
children with CHD, CLD or Down syndrome (D5290C00003/MELODY and MEDLEY 
studies). In addition, no safety issues were reported after a single IM dose of nirsevimab in 
Japanese children with compromised immune system.
This study has been planned to assess safety, PK, ADA, and anti-RSV neutralizing Ab after 
2nd dose of nirsevimab 5 to 6 months after the 1st dose in Japanese infants with certain health 
conditions or born pre-term.
2.2
Background
RSV is the most common cause of lower respiratory tract infection (LRTI) among infants and 
young children, resulting in annual epidemics worldwide (Hall et al, 2009; Shi et al, 2017). 
Almost all children are infected with RSV in the first 2 years of life. RSV-associated LRTI is 
characterized predominantly as bronchiolitis or pneumonia and represents a serious illness
with acute and perhaps long-term consequences to the developing lungs in these young 
children. In 2015, an estimated 33.1 million (uncertainty range: 21.6 to 50.3 million) new 
episodes of RSV-associated LRTI occurred worldwide in children younger than 5 years 
(28% of LRTI episodes). Of those, a part of children with some underlying conditions, such as 
pre-term, CLD, CHD, or immunodeficiency, are at higher risk of progressing to severe RSV-
associated LRTI leading to hospital admission, with 59600 hospital deaths globally 
(range: 48000 to 74500) (Shi et al, 2017).
The survey of the Japan Medical Data Center (JMDC) reported 9711 and 8509 children 
≤2 years of age had RSV infection in 2017 and 2018, respectively. These numbers are 
estimated to correspond to 119000 and 138000 diagnoses each year in Japan, and it has been 
reported that 25% of participants, including those with high risk, required hospitalization 
(Kobayashi et al, 2022). In 2022 (as of 14 December), over 100000 RSV cases with at least 
approximately 300 cases per week has been reported, and this report suggested annual 

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circulation with variable epidemic peak and duration depend on prefectures (IDWR 
Surveillance data, 2022).
Variation and extended duration of RSV season has been reported globally (Bermudez 
Barrezueta et al, 2022), and necessity of a longer protection period from RSV is suggested in 
some children in certain regions (American Academy of Pediatrics, 2022; Bermudez 
Barrezueta et al, 2022). In Japan, the RSV epidemic period varies depending on the year and 
prefecture, and extended duration or change of onset epidemic season has been reported 
(Miyama et al, 2021; IDWR Surveillance data, 2022). For these reasons, sustained protection 
against the RSV infection for a longer time from early may be needed in some regions.
Nirsevimab is the mAb directed against the prefusion conformation of the RSV F protein and 
neutralizes RSV by binding the prefusion conformation of the RSV F protein. Nirsevimab has 
a longer half-life and is more potent than palivizumab, and only one administration can 
provide protection for at least 5 months. Given the need for optimal protection beyond a 5-
month period in higher risk infants in some regions, this study evaluates the repeat dose at 5 to 
6 months after the first dose.
In Oct 2022, nirsevimab was approved for the prevention of RSV lower respiratory tract 
disease in the European Economic Area (EEA), and it is under review by the US Food and 
Drug Administration (FDA).
2.3
Benefit/Risk Assessment
Nirsevimab is a recombinant human IgG1κ mAb directed against the prefusion conformation 
of the RSV F protein. Nirsevimab has a similar mechanism of action as the Sponsor-approved 
mAb for RSV prophylaxis, palivizumab (Synagis®).
More detailed information about the known and expected benefits and risks and reasonably 
predicted adverse events (AEs) of nirsevimab may be found in the Investigator’s Brochure 
(IB).
2.3.1
Risk Assessment
Potential Risks
There are important potential risks associated with administration of any immunoglobulin, 
including polyclonal immunoglobulin preparations and mAbs. The important potential risks 
include, but are not limited to, immediate (type I) hypersensitivity reactions including 
anaphylaxis, immune complex disease, and thrombocytopenia.
Anaphylaxis is an acute onset and may cause a serious drop in blood pressure, difficulty in 
breathing, severe hives, and sometimes death. It is distinct from simple allergic reactions (eg, 

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rash, pruritus) because of the simultaneous involvement of several organ systems. A 
hypersensitivity reaction may be defined as an acute onset of an illness with involvement of 
the skin, mucosal tissue, or both, but it does not meet the definition of anaphylaxis. On 
guidance for anaphylaxis diagnosis, see Appendix B 4.
There were no events of serious hypersensitivity including anaphylaxis, immune complex 
disease or thrombocytopenia related to the investigational product reported during completed 
clinical studies.
Injection site reactions may be observed and may manifest as local inflammation, redness, 
itching, pain, bruising, infection, or excessive bleeding at the site of injection.
Safety profile of nirsevimab has been demonstrated from a series of clinical studies in infants 
and young children.
1
Term and late pre-term infants
Safety profile of nirsevimab was based on 2 placebo-controlled clinical trials Study 3 
(D5290C00003 – all participants) and MELODY (D5290C00004 – all participants) where 
2966 infants received a single IM dose of nirsevimab in the broad population of healthy at 
term and pre-term infants born (≥29 wks GA). The types and frequencies of AEs were 
generally balanced between the nirsevimab and placebo groups within 1, 3, 7, 14, and 30 days 
post-dose timepoints and through 360 days post dose. Frequency of adverse drug reactions 
observed in these trials are rash including rash macular and rash maculopapular within 14 
days (0.7% in nirsevimab arm as compared to 0.5% in placebo arm), injection site reactions 
within 7 days (0.3% in nirsevimab arm as compared to 0.0% in placebo arm) and pyrexia 
within 7 days (0.5% in nirsevimab arm as compared to 0.7% in placebo arm). The majority of 
events were non-serious with mild/moderate in severity.
2
For infants and children’s vulnerable to severe RSV disease
Safety was evaluated in MEDLEY (D5290C00005) study in infants at higher risk for severe 
RSV disease, including extremely pre-term infants (≤28 wks GA) and infants with CLD, or 
CHD entering their first RSV season, who received nirsevimab or palivizumab. The safety 
profile of nirsevimab in infants who received nirsevimab in their first RSV season was 
comparable to the palivizumab and consistent with the safety profile of nirsevimab in term 
and pre-term infants ≥29 wks GA (D5290C00003 and MELODY). Safety was evaluated in 
MEDLEY in children with CLD or CHD who received nirsevimab or palivizumab in their 
first RSV season and went on to receive nirsevimab entering their second RSV season. The 
safety profile of nirsevimab in children who received nirsevimab in their first and second RSV 
season was comparable to that in children who received palivizumab in their first RSV season 
and then nirsevimab in their second RSV season. The safety profile of nirsevimab in these 
children from both arms was consistent with the safety profile of nirsevimab in term and 
pre-term infants ≥29 wks GA (D5290C00003 and MELODY) and comparable to children who 

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received palivizumab for both RSV seasons.
3
Immunocompromised population
Nirsevimab was also well tolerated in vulnerable, immunocompromised infants and children 
up to 24 months of age who received nirsevimab in RSV Season 1 or RSV Season 2 in 
MUSIC (D5290C00008). The safety profile of nirsevimab was consistent with that expected 
for a population of immunocompromised children and with the safety profile in infants of 
term and pre-term ≥29 wks GA (D5290C00003 and MELODY).
2.3.2 Benefit Assessment
The efficacy of nirsevimab was established in late pre-term and term infants. Efficacy findings 
were extrapolated based on PK data to infants and children ≤24 months of age at higher risk.
In Study D5290C00003 in pre-term infants, participants were followed-up through Day 361. A 
single dose of 50 mg IM nirsevimab resulted in a relative risk reduction (RRR) in the 
occurrence of medically attended (MA)-RSV LRTI through Day 151 of 70.1% (95% CI: 
52.3%, 81.2%) when compared to placebo. The occurrence of MA-LRTI through Day 151 in 
participants who received the proposed dose was 17.4% in the nirsevimab group and 24.8% in 
the placebo group. In addition, a single dose of 50 mg IM nirsevimab resulted in an RRR in 
the occurrence of RSV LRTI hospitalization through Day 151 of 78.4% (95% CI: 51.9%, 
90.3%) when compared to placebo.
In Study D5290C00004 (MELODY) in healthy late pre-term and term infants, all participants 
received a single IM dose of nirsevimab 50 mg or 100 mg depending on body weight (50 mg 
in infants with <5 kg body weight, or 100 mg with ≥5 kg body weight), and infants from the 
primary cohort were followed-up through Day 361. Primary analysis data showed that the 
occurrence of MA-RSV LRTI through Day 151 was 1.2% of participants in the nirsevimab 
group and 5.0% of participants in the placebo group, corresponding to efficacy of 74.5% (95% 
CI 49.6, 87.1; P< 0.0001), thus meeting the primary endpoint. The secondary endpoint of RSV 
LRTI hospitalization through Day 151 occurred in 0.6% of participants in the nirsevimab 
group and 1.6% of participants in the placebo group (efficacy 62.1% [95% CI -8.6, 86.8]; 
p = 0.0708). A pre-specified pooled analysis (data from participants weighing <5 kg in Study 
D5290C00003 with healthy late pre-term and term infants and all primary cohort participants 
from Study D5290C00004) demonstrated efficacy of 77.3% (95% CI 50.3, 89.7; p = 0.0002) 
in reducing hospitalization due to RSV in the target population (pre-term and normal term 
infants) on commercial dose. Post-baseline ADAs were detected in only 6.1% of participants 
in the nirsevimab group. ADAs were also detected in the placebo group.
In Study D5290C00005 (MEDLEY) in infants with CHD/CLD and pre-term infants who 
received the same single IM dose as that in MELODY study, the data-lock point of the 
primary analysis corresponded to all participants having been followed through their first RSV 

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season (Day 151). Seven presentations of respiratory illness met the per-protocol definition of 
MA-RSV LRTI. These were balanced by treatment group (nirsevimab 0.6%, palivizumab 
1.0%) and 2 in each arm required hospitalization. The proportion of ADA-positive participants
at Season 1 Day 151 was low for both treatment arms (nirsevimab 0.4%, palivizumab 3.7%).
2.3.3 Overall Benefit/Risk Conclusion
Based on the favorable efficacy and safety profile across the broad population of infants 
entering their first RSV season, and for children up to 24 months of age who remain 
vulnerable to severe RSV disease in their second RSV season, combined with the advantage 
of a single dose, nirsevimab offers the ability to provide protection against RSV lower 
respiratory tract disease and significantly reduce the disease burden for all infants.

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4
STUDY DESIGN
4.1
Overall Design
This study is a phase III, open-label, uncontrolled 2-dose (Day 1 & Day 150-180) study to 
assess the safety, PK, occurrence of ADA to nirsevimab, and anti-RSV neutralizing Ab in 
infants with CHD, CLD, immunocompromise, Down syndrome, or born pre-term ≤35 wks 
GA. The study is planned to be conducted in Japan. Approximately 30participants will be 
enrolled. Participants in the first year of life will receive the 1st dose of nirsevimab as a single, 
fixed IM dose of 50 mg if body weight is <5 kg or 100 mg if body weight is ≥5 kg. A 2nd 
fixed IM dose of 50 mg if body weight is <5 kg or 100 mg if body weight is ≥5 kg will be 
administered 5 to 6 months following the 1st dose. All participants will be followed until the 
end of study follow-up period (360 days after 2nd dose or last dose administered in the study). 
Refer to Figure 1 for an outline of the study plan. If a participant requires cardiac surgery with 
cardiopulmonary bypass during the study, replacement dose may be administered after bypass 
surgery (see Section 6.6 in detail).
Participants will be monitored for treatment-emergent adverse events (TEAEs), 
treatment-emergent serious AEs (TESAEs), adverse event of special interests (AESIs), 
new-onset chronic diseases (NOCDs), PK, ADA, anti-RSV neutralizing Ab, and MA-RSV 
LRTI throughout the study.
All participants seeking medical attention for a respiratory illness (inpatient or outpatient 
setting) will be evaluated for the occurrence of LRTI.
All participants found to have a LRTI and all participants who require hospitalization for a 
respiratory infection, even if there is not a diagnosis of LRTI, should have respiratory 
secretion samples (nasal swab, or nasopharyngeal washes/tracheal aspirates is also acceptable 
if it can be collected) obtained and respiratory assessment completed. Samples should be 
collected for all participants with these respiratory events even those not meeting the protocol-
defined endpoint of LRTI. Participants who have a primary hospitalization for a respiratory 
infection (ie, upper or lower respiratory tract), a respiratory deterioration during a 
hospitalization, or who seek outpatient medical attention (including emergency room [ER] 
visits) for a lower respiratory illness, will be assessed clinically for the presence of LRTI and 
for RSV by central laboratory diagnostic testing of respiratory secretions. For participants 
with hospitalization (upper or lower respiratory tract illness), additional blood samples will be 
collected to measure PK, ADA, and anti-RSV neutralizing Ab.
In addition to the clinical assessment of LRTI, there is a protocol definition using objective 
criteria for the determination of a protocol-defined MA-LRTI. To meet the protocol-defined 
endpoint of MA-LRTI, participants should have sign of lower respiratory tract involvement 
with an indicator of disease severity present. Refer to Section 8.2.1, Table 6.
Testing for RSV will be performed centrally using the US FDA-cleared and Conformité 

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Européenne or European Conformity-marked in vitro diagnostic real-time reverse 
transcriptase-polymerase chain reaction (RT-PCR) assay (Lyra RSV + hMPV Assay, Quidel, 
San Diego, CA; www.quidel.com). A diagnosis of RSV LRTI requires having a respiratory 
sample positive for RSV by the central laboratory RT-PCR.
4.1.1
Screening Visit
All potential participants will have a screening visit, which may take place up to 30 days prior 
to Day 1. Informed consent will be obtained from participant's parent(s)/legally authorized 
representative(s) prior to performing any protocol-related procedures, including screening 
evaluations.
A complete medical history and other baseline information will be obtained at screening. 
Assessment will include history and current medical conditions, past or present 
cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine, lymphatic, 
hematologic, immunologic, dermatological, developmental, and genitourinary disorders, drug 
and surgical history, and any other diseases or disorders.
Screening visit can occur on the same day as the 1st dose visit (Visit 2).
On screening visit, see Section 1.3 Schedule of Activities (SoA), Table 1 in detail.
4.1.2
Visit for Dose
Participants will be considered enrolled into the trial at the point of nirsevimab dose. Before 
1st dose, a medical history update will be obtained, and the eligibility of participants will be 
reviewed. The eligibility of criteria will be also reviewed prior to 2nd dose (refer to Section 
6.1.3).
Body weight, a complete physical examination, and vital signs will be evaluated before 
dosing. Vital signs will be measured pre- and post- dose. And participants will be carefully 
monitored for at least 60 minutes after each dose. Vital signs (temperature, blood pressure, 
heart rate, and respiratory rate) should be obtained within 60 minutes before dose, and at 30 
minutes (± 5 minutes), and 60 minutes (± 5 minutes) post-dose.
4.1.3
Subsequent Visit
Follow-up visits will take place as per the schedule of assessment described in Table 2. All 
participants will be assessed for local and systemic AE, and symptom target physical 
examination at pre-specified time points as detailed in the schedule of assessment (Section 1.3
SoA, Table 2). At specified visits, blood will be taken for assessment of hematology and 
chemistry, PK, ADA, and anti-RSV neutralizing Ab.
Telephone contact will be conducted once 2 weeks (Q2W) after 1st dose and during 6 months 
after 2nd dose, and monthly thereafter.

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4.2
Scientific Rationale for Study Design
4.2.1
Rationale for Study Population
A single dose of nirsevimab is effective at preventing RSV LRTI for at least 5 months and has 
an acceptable safety profile. RSV seasons in temperate regions are typically less than 
5 months duration but longer seasons predictably occur in certain regions in Japan. An 
additional dose of nirsevimab administered 5 to 6 months after the 1st dose may optimize 
protection for infants at higher risk living in certain regions with extended RSV seasons. 
Therefore, it is necessary to give participants 2nd dose of nirsevimab would prevent RSV 
infection for whole RSV season in such regions. There is no data on safety or PK of 
nirsevimab after 2 doses 5-6 months apart, although safety of nirsevimab at 1st and 2nd RSV 
season of life one year apart has been established.
This study will evaluate the safety, PK, occurrence of ADA, and anti-RSV neutralizing Ab 
after 2 doses of nirsevimab.
The target population in this study is higher risk infants with CLD, CHD, immunodeficiency, 
or Down syndrome, or born pre-term, according to Japanese palivizumab dosing guideline.
4.2.2
Rationale for Study Endpoints
The primary objectives for this study are safety and tolerability. The standard measures of 
TEAEs, TESAEs, AESIs, and NOCDs will be used as endpoints. All participants will be 
followed up for approximately one year after a 2nd dose or last dose.
Serum concentrations of nirsevimab at selected time points will be measured as a secondary 
endpoint to evaluate the PK of a 2nd dose of nirsevimab administered 5 to 6 months after the 
first dose. In addition, ADA and anti-RSV neutralizing Ab levels will be also measured at the 
same time points as serum concentrations of nirsevimab. For infants and children who require 
hospitalization for LRTI or any respiratory infection, an additional serum sample will be 
obtained contemporaneous with time of hospitalization for measurement of serum nirsevimab 
concentration, ADA, and anti-RSV neutralizing Ab.
Exploratory endpoints include occurrence of MA-LRTI and hospitalization due to RT-PCR 
confirmed RSV infection. In addition, to monitor for RSV resistance, the F protein from 
collected RSV isolates will be genetically characterized and novel variants will be 
phenotypically characterized for nirsevimab susceptibility.
4.3
Justification for Dose
Dose level is dependent on body weight. Participants will receive the 1st dose of nirsevimab 
as a single, fixed IM dose of 50 mg if body weight is <5 kg or 100 mg if body weight is ≥5 kg. 
These participants will receive a 2nd fixed IM dose of 50 mg if body weight is <5 kg or 100 
mg if body weight is ≥5 kg 5 to 6 months following 1st dose. Dose based on body weight was 

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adopted in previous studies, and the efficacy and safety of nirsevimab after a single IM dose at 
the regimen based on body weight were demonstrated.
All participants will be followed until the end of study follow-up period (360 days after 2nd 
dose or last dose administered in the study).
4.4
End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study including their last scheduled procedure.
The end of the study is defined as the date of the last scheduled procedure for the last 
participant in the study.
5
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, is not permitted.
5.1
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
1.
Written informed consent and any locally required authorization obtained from the 
participant’s parent(s)/legally authorized representative(s) before performing any 
protocol-related procedures, including screening evaluations
2.
Japanese infants of ≤12 months of age eligible to receive palivizumab in accordance with 
national or local guidelines and those who must meet at least one of the following 
conditions at the time of informed consent.
(a) Immunodeficiency
i)
Diagnosed with combined immunodeficiency (severe combined immunodeficiency, 
X-linked hyper-immunoglobulin M [IgM] syndrome, etc.); Ab deficiency (X-linked 
agammaglobulinemia, common variable immunodeficiency, non-X-linked hyper-
IgM syndromes, etc.); or other immunodeficiencies (Wiskott-Aldrich syndrome, 
DiGeorge syndrome, etc.), or
ii) Diagnosed with human immunodeficiency virus infection, or
iii) History of organ or bone marrow transplantation, or
iv) Participant is receiving immunosuppressive chemotherapy, or
v) Participant is receiving systemic high-dose corticosteroid therapy (prednisolone 
equivalents ≥0.5 mg/kg every other day, other than inhaler or topical use), or
vi) Participant is receiving other immunosuppressive therapy (eg, azathioprine, 
methotrexate, mizoribine, mycophenolate mofetil, cyclophosphamide, cyclosporine, 
tacrolimus, cytokine inhibitors, etc.)

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(b) CLD
i)
Diagnosed with CLD of prematurity requiring medical intervention/management (ie, 
supplemental oxygen, bronchodilators, or diuretics) within 6 months prior to 
screening
(c) CHD
i)
Diagnosed with hemodynamically significant CHD (must be unoperated or partially 
corrected CHD)
Note: Children with hemodynamically significant acyanotic cardiac lesions must 
have pulmonary hypertension (≥40 mmHg measured pressure in the pulmonary 
artery) or the need for daily medication to manage CHD
(d) Down syndrome
(e) Born pre-term ≤28 wks GA and aged ≤12 months, or born pre-term >28 wks and 
≤35 wks GA and aged ≤6 months
3.
The participant’s parent(s)/legally authorized representative(s) can understand and 
comply with the requirements of the protocol including follow-up visits as judged by the 
investigator.
4.
The participant is available to complete the follow-up period for approximately 
19 months, which will be approximately 1 year after receipt of 2nd dose of nirsevimab.
5.2
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1
Requirement for mechanical ventilation, extracorporeal membrane oxygenation, 
continuous positive airway pressure (CPAP), or other mechanical respiratory or cardiac 
support at the time of enrollment
2
A current, active RSV infection at the time of screening and investigational product 
administration
3
Any fever (≥100.4°F [≥38.0°C], regardless of route) or acute illness at the time of prior to 
investigational product administration
4
Any serious concurrent medical condition (except those resulting in an immune 
deficiency condition), including:
(a) Known renal impairment
(b) Known hepatic dysfunction including known or suspected active or chronic hepatitis 
infection
(c) Any seizure disorder or evolving or unstable neurological condition
5
Anticipated cardiac surgery within 5-6 months after enrollment
6
Prior history of a suspected or actual acute life-threatening event
7
Receipt or intended use of palivizumab in the current enrollment season

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8
Any known allergy or history of allergic reaction to any component of nirsevimab
9
Any known allergy or history of allergic reaction to immunoglobulin products, blood 
products, or other foreign proteins
10 Concurrent enrollment in another interventional study, or prior receipt of any 
investigational agent
11 Anticipated survival of less than 1 year at the time of informed consent
12 Any condition that, in the opinion of the investigator, would interfere with the evaluation 
of the investigational product or interpretation of study results
13 Children of employees of the Sponsor, clinical study site, or any other individuals 
involved with the conduct of the study, or immediate family members of such individuals
5.3 Lifestyle Considerations
There are no specific lifestyle restrictions identified for this study. Restrictions related to 
concomitant medications can be found in Section 6.9.2. However, it is desirable for children to 
avoid situations susceptible to infectious diseases as much as possible.
5.4
Screen Failures
A screen failure occurs when a participant who has consented to participate in the clinical 
study is not subsequently entered in the study. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any serious adverse event (SAE).
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Rescreened participants will be assigned the same participant number as for the 
initial screening.
5.5
Criteria for Temporarily Delaying
Not applicable
5.6
Study Suspension or Termination
The study may be put on temporary hold (defined as a pause in enrollment of participants into 
the study) pending further safety data analysis because of any reason, eg, but not limited to;

Death of any participant in which the cause of death is assessed as related to study 
intervention.

Any event that, in the judgment of the sponsor or the investigator, are deemed serious 
enough to warrant immediate review.

Sponsor decides to suspend/terminate the study.

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6
STUDY INTERVENTION(S) AND CONCOMINANT THERAPY
6.1
Study Intervention(s) Administered
Study intervention is defined as any investigational intervention(s), marketed product(s) or 
placebo intended to be administered to or medical device(s) utilized by a study participant 
according to the study protocol. For this study, only nirsevimab is defined as study 
intervention.
6.1.1
Study Intervention Administered
Refer to Table 4.
Table 4
Investigational Intervention
Intervention Name
Nirsevimab (MEDI8897)
Type 
Monoclonal antibody. 
Dose Formulation
The solution contains 100 mg/mL nirsevimab, 30 mM 
histidine/histidine-HCl, 80 mM arginine-HCl, 120 mM sucrose, 
0.02% (w/v) polysorbate 80, pH 6.0. The nominal fill volume is 
0.5 mL.
Unit Dose Strength(s)
Supplied as 50 mg (nominal) per vial solution.
Dosage Level(s)
See Section 6.1.2.
Route of Administration
Intramuscular
Use
Experimental
IMP and NIMP
IMP
Sourcing
Provided centrally by the Sponsor. 
Packaging and Labelling
Will be provided in vials within a carton. 
Each carton and vial will be labelled as required per country 
requirement.
IMP = investigational medicinal product; NIPM = non-investigational medicinal product.
The investigational medicinal product (IMP) should be stored at 2°C to 8°C.
Labels will be prepared in accordance with Good Manufacturing Practice (GMP) and local 
regulatory guidelines.
The IMP will be supplied to the site in open-labelled kits. Each kit has a unique number 
printed on all labels within the kit (ie, the outer carton label and the label of each vial).
6.1.2
Dose Preparation Steps and Treatment Administration
The dose administration steps are as follows:
1.
Dose level

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(a) Infants <5 kg body weight at time of dosing:
o
A dose of 50 mg (ie, 0.5 mL) nirsevimab will be obtained by withdrawing the entire 
contents of 1 investigational product vial with an appropriately sized syringe, and 
administered as 1 single (ie, 0.5 mL) injection, regardless of 1st and 2nd dose.
(b) Infants ≥5 kg body weight at time of dosing:
o
A dose of 100 mg (ie, 1.0 mL) nirsevimab will be obtained by withdrawing the 
entire contents of 2 investigational product vials with an appropriately sized syringe 
and administered as 1 single (ie, 1.0 mL) injection, regardless of 1st and 2nd dose.
2.
Switch the needle to a higher gauge prior to administration. Nirsevimab should be 
administered using the appropriate size needle ranging from 22 to 25 gauge and 5/8 to 
1.0 inches based on muscle size and weight of the participant.
3.
Nirsevimab should be administered in the anterolateral aspect of the thigh according to 
standard practice procedures for IM injections. The injection should be given using 
standard aseptic technique.
4.
Nirsevimab should be administered within 4 hours at room temperature from needle 
puncture of the investigational product vial to administration. If the time exceeds these 
limits, a new vial should be used (refer to Section 6.2). If there is a delay in the 
administration of nirsevimab such that it will not be administered within the specified 
timeframe, the study monitor must be notified immediately.
6.1.3
Eligibility for 2nd Dose
Participants who received 1st dose and do not meet any of the below exclusion criteria's:
1. Participants who undergo cardiac surgery with cardiopulmonary bypass after receipt of 1st 
dose but prior to receipt of 2nd dose (see Section 6.6)
2. Any allergic reaction to 1st dose of nirsevimab
3. A current, active infection, including RSV infection, or any ongoing AE at the time of 
investigational product administration
4. Any fever (≥100.4°F [≥38.0°C], regardless of route) or acute illness within 7 days prior to 
investigational product administration.
5. Any condition, that in the opinion of investigator, would interfere with the evaluation of 
the investigational product or interpretation of study results
If participants cannot be dosed because they meet criteria 3 and/or 4 above, they may still be 
eligible to receive a 2nd dose. Participants may be reassessed for 2nd dose eligibility, and 
assuming none of the above criteria are met upon reassessment, they may receive the 2nd dose 
as long as more than one week have been passed after the recovery and the 2nd dose is 
administered within 6 months (+14 days) after the 1st dose.

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6.2
Preparation, Handling, Storage, and Accountability

IMP (nirsevimab) will not be delivered to the study site until the contract is 
completed between the study site and AstraZeneca (and/or designee).

The investigator or designee (eg, pharmacist) must confirm appropriate conditions
(eg, temperature) have been maintained during transit for all study intervention 
received at the site and throughout the entire study until authorization is provided for 
on-site destruction or removal of the IMP, reflecting completion of the study. In the
event of a temperature excursion detected at any time during the study, sites will 
follow the reporting procedures for notifying AstraZeneca (or designated party); 
release of IMP for clinical use can only occur once the event has been reviewed and 
approval is provided by AstraZeneca (or designated party).

Only participants enrolled in the study may receive study intervention, and only 
authorized site staff may supply, prepare, or administer study intervention. Study 
intervention must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labelled storage conditions with 
access limited to authorized site staff.

The head of the study site is responsible for ensuring the control of accountability, 
reconciliation, and return for IMP received at the site. The head of the study site will 
designate designee (eg, pharmacist) to delegate all responsibility, ie, receipt, 
reconciliation, and final disposition records.

Nirsevimab does not contain preservatives and any unused portion must be discarded. 
Total in-use storage time from needle puncture of the investigational product vial to 
start of administration should not exceed 4 hours at room temperature. If storage time 
exceeds these limits, a new vial should be used.
6.3
Assignment to Study Intervention
Not applicable
6.4
Blinding
Not applicable
6.5
Study Intervention Compliance
When participants are dosed at the site, they will receive study intervention(s) directly from 
the investigator or designee, under medical supervision. The date, and time if applicable, of 
dose administered in the clinic will be recorded in the source documents and recorded in the 
electronic case report form (eCRF). The dose of study intervention and study participant 
identification will be confirmed at the time of dosing by a member of the study site staff other 
than the person administering the study intervention.

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6.6
Dose Modification/Replacement Dose
If dose modification/replacement dose is necessary, the study intervention will be 
administered as follows:
Replacement dose in participants who undergo cardiac surgery with cardiopulmonary bypass:
(a) If surgery is done after receipt of 1st dose but prior to 2nd dose, participants will 
receive a replacement dose immediately following the surgery when they are 
determined by the physician to be medically stable for an IM injection. Participants 
who have received a replacement dose do not receive regular 2nd dose.
i)
If surgery is done within 90 days after 1st dose, participants will receive a 
single dose of 50 mg (current body weight <5 kg) or 100 mg (current body 
weight ≥5 kg).
ii) If surgery is done after 90 days of 1st dose, participants will receive a single 
50 mg replacement dose, regardless of body weight, to cover the remainder of 
the RSV season.
(b) If surgery is done after receipt of 2nd dose but prior to end of study follow-up (until 
Day 511-Day 540, ie, 360 days after 2nd dose), the replacement dose for protection 
in the current/ongoing season will be determined by clinical judgment of the 
investigator. When replacement dose is needed at the discretion of the investigator, 
participant will receive 50 mg of nirsevimab IM dose regardless of body weight.
(c) Participants that receive a replacement dose will be followed for 360 days after 
dosing. Follow-up after a replacement dose will be the same as follow-up after 2nd 
dose, as shown below;
i)
Visit: Day 30, Day 150, and Day 360 after a replacement dose
ii) Telephone contact: Day 7, Q2W during 6 months after replacement dose and 
monthly thereafter.
iii) Blood sample will be collected to measure PK, ADA, and anti-RSV 
neutralizing Ab pre-surgery, post surgery (before replacement dose), and 
Day 30, Day 150, and Day 360 after a replacement dose.
(d) During the follow-up period after replacement dose, surveillance for MA-RSV LRTI 
will be maintained until the study end.
Refer to Section 1.3 SoA, Table 2.
6.7
Continued Access to Study Intervention After the End of the 
Study
Study intervention after the end of the study is not planned.
6.8
Treatment of Overdose
For this study, any dose of nirsevimab greater than pre-decided dose in this protocol will be 
considered an overdose, ie, in the case that dose level in each dosing is exceeds 50 mg if body 

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weight is <5 kg or 100 mg if body weight is ≥5 kg.
The sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator and/or participant’s parent(s) should:

Closely monitor the participant for any AE/SAE for at least hour after administration. 
Refer to Section 8.4.12 for details of AE/SAE reporting related to overdose.

Document the quantity of the excess dose.
6.9
Concomitant Therapies
Any medication or vaccine (including over-the-counter [OTC] or prescription medicines) that 
the participant is receiving at the time of enrollment or receives during the study must be 
recorded along with:

Reason for use

Dates of administration including start and end dates

Dosage information including dose and frequency
The Study Clinical Lead should be contacted if there are any questions regarding concomitant 
or prior therapy.
6.9.1 Permitted Concomitant Medications or Treatments
Investigators may prescribe concomitant medications or treatments deemed necessary to 
provide adequate supportive care, including routine vitamins and iron. Specifically, 
participants should receive full supportive care during the study, including transfusions of 
blood and blood products, treatment with antibiotics, anti-emetics, anti-diarrheals, and 
analgesics, and other care, if considered appropriate.
6.9.2
Prohibited Concomitant Medication
Use of any new medications from Day 1 through Day 15 post dose is to be avoided, if 
possible. This includes OTC medications (except for routine vitamins and iron) and herbal 
supplements. Participants’ parent(s)/legal representatives should be instructed not to 
administer any new medications, including OTC products, without first consulting with the 
investigator.
7
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANTS DISCONTINUATION/WITHDRAWAL
Discontinuation of specific sites or of the study are handled as part of Appendix A.
7.1
Discontinuation of Study Intervention
Note that discontinuation from study intervention is not the same thing as a discontinuation or 

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withdrawal from the study (see Section 7.2). If study intervention is permanently 
discontinued, the participant should, if at all possible, remain in the study.
Each participant will receive 2 doses of study intervention. An individual participant will not 
receive 2nd study intervention if any of the following occur in the participant in question:
1.
Withdrawal of consent
2.
Hypersensitivity reaction or SAE assessed as related to study drug or in the judgment of 
the site investigator, is related to study intervention and may jeopardize the safety of the 
study participant
3.
Participants who apply to exclusion criteria (refer to the Section 5.2)
4.
Participants who receive a replacement dose associated with cardiac surgery
Participants who have received any study drug will be followed for protocol-specified 
assessments including follow-up of any AEs unless consent is withdrawn specifically from 
further study participation (Section 7.2) or the participant is lost to follow-up. Participants 
who have not received study drug, regardless of reason, will not be followed.
7.2
Participants Discontinuation/Withdrawal from the Study
Discontinuation of the participant from the study by the investigator:

A participant may be discontinued from the study at any time at the discretion of the 
investigator for medical reasons.
Voluntary withdrawal from the study by the participant (his/her parent[s])/legal 
representative[s]):

A participant may withdraw from the study at any time at his/her parent(s)/legal 
representative(s)'s discretion for any reason (or without providing any reason).

A participant (his/her parent[s]/legal representative[s]) who wishes to withdraw from the 
study must be informed by the investigator about modified follow-up options (e.g., 
telephone contact, a contact with a relative or treating physician, or information from 
medical records).

If the participant (his/her parent[s]/legal representative[s]) withdraws consent for 
disclosure of future information, AstraZeneca may retain and continue to use any data 
collected before such a withdrawal of consent.

If the participant withdraws from the study, AstraZeneca may retain and continue to use 
any samples collected before such a withdrawal of consent for the purposes the 
participant originally consented unless the participant withdraws consent for use of 
samples already collected. If the participant specifically withdraws consent for any use of 
samples, it must be documented in the site study records by the investigator and the 
investigator must inform the Local and Global Study Team. Destruction of any samples 

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taken and not yet tested should be carried out in line with documented sample withdrawal 
wishes in conjunction with what was stated in the informed consent and local regulation.
7.3
Lost to Follow-up
A participant will be considered lost to follow-up if the participant repeatedly fails to return 
for scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the study site for a 
required study visit:

The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible. The participant should be counseled on the importance of maintaining the 
assigned visit schedule. At this time ascertain whether the participant should or wishes to 
continue in the study.

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant’ parent(s)/legal representative(s) (where 
possible, telephone calls, texts, emails, and if necessary, a certified letter to the 
participant’s last known mailing address or local equivalent methods). These contact 
attempts should be documented in the participant’s medical record.

Should the participant continue to be unreachable, the participant will be considered to 
have withdrawn from the study/being lost to follow-up.
8
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in Section 1.3 SoA. Protocol waivers 
or exemptions are not allowed.

Urgent safety concerns should be discussed with AstraZeneca immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study intervention.

Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.

Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the informed consent form (ICF) may be utilized 
for screening or baseline purposes provided the procedures met the protocol-specified 
criteria and were performed within the time frame defined in the SoA (Section 
1.3).Instructions for the collection and handling of human biological sample (HBS) will 

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be provided in the study-specific laboratory manual. Samples should be stored in a secure 
storage space with adequate measures to protect confidentiality. For further details on 
handling of HBS, see Appendix C.In the event of a significant study-continuity issue (eg, 
caused by pandemic), alternate strategies for participant visits, assessments, medication 
distribution and monitoring may be implemented by AstraZeneca or the investigator, as 
per local health authority/ethics requirements.
The amount of blood collected from each participant will be as follows (Table 5):
Table 5
Estimated Volume of Blood to be Collected
Visit/Study Day
Estimated Blood Volume
Visit 1/Screening or Visit 2/Day 1 prior to 1st dose
Target collection depending on body weight;
<3kg – 1.5 mL
3 to <5 kg – 2.5 mL
≥5 kg – 4 mL
Visit 3/Day 151 - 180 prior to 2nd dose
4 mL
Visit 4/Day 181 - 210
4 mL
Visit 5/Day 301 - 330
4 mL
Visit 6/Day 511 - 540
4 mL
Total
Max. 20 mL
Additional blood samples will be collected, eg, at the time of hospitalization due to any 
respiratory infection, at the time of surgery, or when considered to be needed due to 
participant’s safety issues at the discretion of the investigator.
8.1
Administrative Procedures
A complete medical history will be obtained at screening and a medical history update will be 
obtained before 1st dose as defined in Section 1.3 SoA. Assessments will include history and 
current medical conditions, past or present cardiovascular, respiratory, gastrointestinal, renal, 
hepatic, neurological, endocrine, lymphatic, hematologic, immunologic, dermatological, 
developmental, genitourinary, drug and surgical history, or any other diseases or disorders. In 
addition, a physical examination and vital sign assessment will be performed (refer to 
Section 8.3).
Body weight, a complete physical examination, and baseline information on breastfeeding, 
presence of siblings, smoking in the household, and if the infant attends day care, will be 
collected.

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8.2
Surveillance for MA-RSV LRTI
8.2.1
Lower Respiratory Tract Infection
Participants will be monitored for LRTI throughout the study (refer to Section 1.3 SoA, Table 
2).
All participants seeking medical attention for a respiratory illness (in either the inpatient or 
outpatient setting) will be evaluated for LRTI. Participants who have a primary hospitalization 
for a respiratory infection (ie, upper or lower tract), a respiratory deterioration during a 
hospitalization, or who seek outpatient medical attention (including ER visits) for a lower 
respiratory illness will be assessed clinically for the presence of LRTI and for RSV by central 
laboratory diagnostic testing of respiratory sample. Criteria for meeting the protocol-defined 
endpoint of MA-RSV LRTI is shown in Table 6. They include signs of lower respiratory tract 
involvement, a clinical indicator of disease severity and a respiratory sample positive for RSV 
by the central laboratory RT-PCR assay. Respiratory secretion samples that test positive for 
RSV by the central lab will be sequenced to assess RSV subtype and for RSV F 
polymorphisms.
In infantas without underlying lung disease, to meet the protocol-defined endpoint of MA-
RSV LRTI, participants with signs of LRTI must have documented at least one physical 
examination finding of rhonchi, rales, crackles, or wheeze AND at least one of the following 
clinical signs:

Increased respiratory rate at rest (age: <2 months, ≥60 breaths/min; 2 to 6 months, 
≥50 breaths/min; >6 months, ≥40 breaths/min), OR

Hypoxemia (in room air: oxygen saturation <95% at altitudes ≤1800 meters or <92% at 
altitudes >1800 meters), OR

Clinical signs of severe respiratory disease (eg, acute hypoxic or ventilatory failure, new 
onset apnea, nasal flaring, intercostal, subcostal, or supraclavicular retractions, grunting) 
or dehydration secondary to inadequate oral intake due to respiratory distress (need for 
intravenous fluid).
In infants with underlying lung disease, to meet the protocol-defined endpoint of MA-RSV 
LRTI, participants with signs of LRTI must have documented at least one new or worsened 
physical examination finding of rhonchi, rales, crackles, or wheeze AND at least one of the 
following clinical signs:

Increase in baseline respiratory rate by ≥20% at rest and that rate is greater than the age-
based criteria established for children with no underlying lung disease (age: < 2 months, 
≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; >6 months, ≥40 breaths/min), OR

Hypoxemia (oxygen saturation <95% in room air or oxygen saturation drop of 
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room air, or acute documented need for supplemental oxygen or increased oxygen 
requirement compared with baseline), OR

Clinical signs of severe respiratory disease (eg, acute hypoxic or ventilatory failure, new 
onset apnea, nasal flaring, intercostal, subcostal, or supraclavicular retractions, grunting) 
or dehydration secondary to inadequate oral intake due to respiratory distress (need for 
intravenous fluid), OR

Prescription of new or increased (from baseline) dose of medications including 
bronchodilators, steroids, diuretics, cardiac medications.
Table 6
Criteria for Meeting the Protocol-defined Endpoint of Medically 
Attended RSV LRTI 
RSV 
Lower Respiratory Tract
Medical Significance
RSV Confirmed:
•
Positive by central 
laboratory RT-
PCR assay of 
respiratory 
secretion sample
Documented PE findings 
localizing to lower 
respiratory tract:
•
Rhonchi
•
Rales
•
Crackles
•
Wheeze
Objective measures of clinical severity:
•
Increased respiratory rate
•
Hypoxemia
•
Acute hypoxic or ventilatory failure
•
New onset apnea
•
Nasal flaring
•
Retractions
•
Grunting
•
Dehydration due to respiratory 
distress
•
For infants with underlying lung 
disease: Prescription of new or 
increased (from baseline) dose of 
medications including 
bronchodilators, steroids, diuretics, 
cardiac medication
LRTI = lower respiratory tract infection; PE = physical examination; RSV = respiratory syncytial virus; RT-PCR = reverse 
transcriptase-polymerase chain reaction.
Note: One item from each column is required to meet the protocol-defined endpoint of MA-RSV LRTI.
8.2.2
RSV Hospitalization
An RSV hospitalization is defined as either (1) a respiratory hospitalization with a positive 
RSV test within approximately 2 days of hospital admission (primary) or (2) a new onset of 
respiratory symptoms in an already hospitalized participant, with an objective measure of 
worsening respiratory status and positive RSV test (nosocomial). Primary and nosocomial 
RSV hospitalization are further defined below.

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Primary RSV Hospitalization
RSV diagnostic testing will be performed on respiratory secretion samples (nasal swab, or 
other respiratory aspirates) obtained within 2 days before or after admission for participants 
hospitalized for any respiratory infection (upper or lower respiratory tract infection). If the 
RSV diagnostic test (performed centrally via RT-PCR) is positive, the hospitalization will be 
classified as a primary RSV hospitalization. Deaths that can be attributed to RSV (by autopsy 
or clinical history and virologic evidence) will also be considered primary RSV 
hospitalization endpoints. Whilst a 2-day window for sampling is strongly preferable, a 
sample taken up to 14 days after the event remains useful and should be taken.
Nosocomial RSV Hospitalization
Participants hospitalized for a respiratory illness or non-respiratory illness whose RSV 
diagnostic test is negative may develop nosocomial RSV illness during the hospitalization.
If signs (such as retractions, rhonchi, wheezing, crackles, or rales) of a new lower respiratory 
illness occur during a hospitalization, whatever the reason for hospitalization, and there is an 
objective measure of worsening respiratory status (that is, new requirement for supplemental 
oxygen, increase in supplemental oxygen requirement from prior to the onset of symptoms, or 
need for new or additional mechanical ventilation), any respiratory secretion (nasal swab, or 
other respiratory aspirates) will be collected within 2 days from worsening of respiratory 
status for RSV diagnostic testing by the central laboratory. For any participant who is 
hospitalized for a respiratory infection (upper or lower respiratory tract), the participant must 
return to his/her baseline respiratory status or be clearly resolving from the preceding 
respiratory illness before a subsequent respiratory deterioration for a nosocomial RSV 
hospitalization event can be determined.
If the RSV diagnostic test (performed centrally via RT-PCR) is positive, the subsequent 
hospital days will count as a nosocomial RSV hospitalization. The days of RSV 
hospitalization will be counted beginning with the start of the respiratory deterioration that 
resulted in the RSV diagnostic test.
RSV LRTI Outpatient Events
Participants who seek outpatient medical attention, including ER and urgent care visits, for an 
LRTI, should have respiratory secretions obtained within 2 days after the initial healthcare 
provider assessment. Whilst a 2-day window for sampling is strongly preferable, a sample 
taken up to 14 days after the event remains useful and should be taken.
8.2.3
Respiratory Secretions for RSV Detection
Respiratory secretions for RSV testing will be collected from all participants with LRTIs 
(inpatient or outpatient) and from all hospitalized participants with any new respiratory 

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infection (upper or lower) within 2 days after the initial healthcare provider assessment and 
diagnosis. Whilst a 2-day window for sampling is strongly preferable, a sample taken up to 
14 days after the event remains useful and should be taken. Nasal swab or other tracheal 
aspirates will be obtained.
Respiratory secretions will be tested in a central laboratory for RSV using the US FDA-
cleared and CE-marked in vitro diagnostic real-time RT-PCR assay (Lyra RSV + hMPV assay; 
Quidel Corporation, San Diego, CA, www.quidel.com). Testing may include other respiratory 
pathogens.
8.2.4
Monitoring for RSV Resistance
As an exploratory endpoint, RSV-positive respiratory secretion specimens from all 
participants will be evaluated by genotypic and phenotypic methods to monitor potential 
susceptibility changes to nirsevimab neutralization. The subtype and genotypic determination 
of RSV will be performed directly on the nasal specimens that are collected from all 
participants who are confirmed RSV-positive using the Lyra RSV + hMPV real-time RT-PCR 
assay manufactured by Quidel Corporation (Lyra RSV + hMPV assay; Quidel Corporation, 
San Diego CA, www.quidel.com). The full-length F gene will be sequenced by a Sanger 
and/or next generation sequencing methodology. Amino acid (aa) substitution(s) within the 
nirsevimab binding site (aa 62-69 and aa 196-212) and outside the binding site in the 
extracellular regions of mature F protein (aa 24-109 and aa 137-524) will be reported and 
compared to F protein sequences of contemporary reference RSV strains. In vitro phenotypic 
analysis (susceptibility to nirsevimab neutralization) will be attempted using an RSV 
neutralization assay with either RSV viruses constructed through site-directed mutagenesis of 
the F gene and reverse genetics or by cloning the F gene from the isolate into a laboratory-
adapted RSV strain such as A2 or B9320.
8.3
Safety Assessments
Planned time points for all safety assessments are provided in Section 1.3 SoA.
8.3.1
Physical Examinations
A complete physical examination will be performed on the dosing days (prior to doing at Visit 
1/Visit 2, and Visit 3) and include assessments of the following: height, weight, general 
appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, 
nose, and throat), lymph nodes, thyroid, musculoskeletal (including spine and extremities), 
and neurological systems. On other visits, symptom targeted physical examination will be 
performed. All physical examinations will be performed by a licensed healthcare provider 
(eg, physician).
Physical examination will be performed at timepoints as specified in Section 1.3 SoA.

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8.3.2
Vital Signs
Vital signs will be performed at timelines as specified in Section 1.3 SoA.
Vital signs (temperature, blood pressure, heart rate, and respiratory rate) will be collected at 
screening and the day of administration. On days when study intervention is administered, 
vital signs will be obtained within 60 minutes prior to dose, and at 30 minutes (± 5 minutes) 
and 60 minutes (± 5 minutes) post dose.
8.3.3
Electrocardiograms
No regular ECG assessments are planned during the study.
8.3.4
Clinical Safety Laboratory Tests
Blood samples will be collected for centrally measuring hematology and clinical chemistry 
parameters. Additional samples may be collected if clinically indicated at the discretion of the 
investigator. The date, time of collection and results (values, units, and reference ranges) will 
be recorded on the appropriate eCRF.
The following clinical laboratory variables will be measured at screening and during the study 
period as pre-specified in Section 1.3 SoA.
Serum Chemistry
•
Aspartate aminotransferase (AST)
•
Creatinine
•
Alanine aminotransferase (ALT)
•
Blood urea nitrogen (BUN)
•
Total bilirubin (TBL)
Hematology
•
White blood cell count 
•
Hemoglobin
•
Lymphocyte count
•
Platelet count
•
Red blood cell
8.4
AEs, SAEs, and Other Safety Reporting
The Principal Investigator (PI) is responsible for ensuring that all staff involved in the study 
are familiar with the content of this section.
The definitions of an AE or SAE can be found in Appendix B.
Participants (or, when appropriate, a caregiver, surrogate, or the participant’s legally 
authorized representative) will notify the investigator or designees of symptoms. These must 
then be assessed by the investigator, and if considered an AE, it will be reported by the 
investigator.

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The investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE.
AE Variables
The following variables will be collected for each AE:

AE (verbatim)

The date and time when the AE started and stopped

Maximum intensity or changes in intensity (on intensity, refer to Appendix B 2)

Whether the AE is serious or not

Investigator causality rating against the IMP(s) (yes or no)

Action taken regarding IMP(s)

AE caused participant’s withdrawal from the study (yes or no)

Outcome
In addition, the following variables will be collected for SAEs:

Date AE met criteria for SAE

Date investigator became aware of SAE

AE description

AE is serious due to

Date of hospitalization

Date of discharge

Probable cause of death

Date of death

Autopsy performed

Causality assessment in relation to study procedure(s)

Causality assessment to other medication
8.4.1
Time Period and Frequency for Collecting AE and SAE Information
AEs and SAEs will be collected from time of signature of the ICF throughout the follow-up 
period.
If the investigator becomes aware of an SAE with a suspected causal relationship to the IMP 
during the study in a participant, the investigator shall, without undue delay, report the SAE to 
AstraZeneca.
8.4.2
Follow-up of AEs and SAEs
Any AE that is unresolved at the participant’s last AE assessment in the study is followed up 

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by the investigator for as long as medically indicated, but without further recording in the 
eCRF. AstraZeneca retains the right to request additional information for any participant with 
ongoing AE(s)/SAE(s) at the end of the study, if judged necessary.
8.4.3 Causality Collection
The investigator should assess causal relationship between IMP and each AE, and answer 
‘yes’ or ‘no’ to the question ‘Do you consider that there is a reasonable possibility that the 
event may have been caused by the IMP?’
For SAEs, causal relationship should also be assessed for other medication and study 
procedures. Note that for SAEs that could be associated with any study procedure the causal 
relationship is implied as ‘yes’.
A guide to the interpretation of the causality question is found in Appendix B
8.4.4 AEs Based on Examinations and Tests
Deterioration as compared to baseline in protocol-mandated assessments, such as vital sign, 
should only be reported as AEs if they meet any of the following:

fulfill any of the SAE criteria

are the reason for discontinuation of the IMP

are clinically relevant as judged by the investigator (which may include but is not limited 
to consideration as to whether intervention or non-planned visits were required or other 
action was taken with the IMP, eg, dose adjustment or drug interruption).
If deterioration is associated with clinical signs and symptoms, the sign or symptom will be 
reported as an AE, and the unscheduled test results associated with AEs, if any, or vital sign 
will be considered as additional information. Wherever possible, the reporting investigator 
uses the clinical term (eg, anemia vs low hemoglobin value). In the absence of clinical signs 
or symptoms, clinically relevant deteriorations in non-mandated parameters should be 
reported as AE(s).
Any new or aggravated clinically relevant abnormal medical finding at a physical examination 
as compared with the baseline assessment will be reported as an AE unless unequivocally 
related to the disease under study (DUS).
The results from the tests specified in the study protocol and vital signs will be summarized in 
the clinical study report (CSR).
8.4.5 AEs Based on Signs and Symptoms
All signs or symptoms spontaneously reported by legal representative(s)/parent(s)/care 
provider or reported in response to the open question from the study site staff: ‘Has the child 
had any health problems since the previous visit/you were last asked?’ or revealed by 

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observation will be collected and recorded in the eCRF.
When collecting AEs, the recording of diagnoses is preferred (when possible) to recording a 
list of signs and symptoms. However, if a diagnosis is known and there are other signs or 
symptoms that are not generally part of the diagnosis, the diagnosis and each sign or symptom 
will be recorded separately.
8.4.6
Hy’s Law
Cases where a participant shows elevations in liver biochemistry may require further 
evaluation, and occurrences of AST or ALT ≥3 × ULN together with TBL ≥2 × ULN may 
need to be reported as SAEs. Refer to Appendix D for further instruction on cases of increases 
in liver biochemistry and evaluation of Hy’s Law.
8.4.7
Disease Under Study
DUS are those which might be expected to occur as a direct result of procedures to diagnose 
or treat the condition under study. Events which are unequivocally due to DUS should not be 
reported as AEs during the study unless they meet SAE criteria or lead to discontinuation of 
the IMP.
8.4.8
Definition of Adverse Events of Special Interest
AESIs will be collected during the study.
An AESI is one of scientific and medical interest specific to understanding of the 
investigational product and may require close monitoring and rapid communication by the 
investigator to the sponsor. An AESI may be serious or non-serious. The rapid reporting of 
AESIs allows ongoing surveillance of these events to characterize and understand them in 
association with the use of this IMP. It should be informed to appropriate sponsor study 
representatives immediately, or no later than 24 hours of when the investigator becomes 
aware of the event.
8.4.8.1
Hypersensitivity, Including Anaphylaxis
Administration of polyclonal immunoglobulin preparations and mAbs has been associated 
with immediate (type I) hypersensitivity (including anaphylaxis) that occurs during or after 
dosing. Type I hypersensitivity reaction is defined as an acute onset of an illness with 
involvement of the skin, mucosal tissue, or both during administration of investigational 
product (but does not meet the definition of anaphylaxis). Anaphylaxis is a rare event, usually 
occurring after subsequent exposure to antigen, and it is most accompanied by severe systemic 
skin and or mucosal reactions. It is potentially a fatal, systemic allergic reaction that is distinct 
from simple allergic reactions (eg, skin or skin-related reactions, such as rash, pruritus) 
because of the simultaneous involvement of several organ systems (Sampson et al, 2006). A 
full definition of anaphylaxis is provided in Appendix B 4.

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8.4.8.2
Immune Complex Disease
Immune complex disease can manifest in the form of several conditions such as vasculitis, 
endocarditis, neuritis, glomerulonephritis, serum sickness, and arthralgias. Drug-induced 
immune complex (type III) hypersensitivity reactions can occur when host immune system 
generates ADA resulting in soluble circulating antigen-antibody complexes formation and 
their deposition in blood vessels. Subsequently this induces tissue damaging inflammatory 
reactions mediated by complement and/or leukocytes and mast cells. The pathology and 
clinical manifestations are dependent on the tissues/organs involved, with vascular, skin, and 
renal tissues being common sites of injury. Common examples of immune complex 
hypersensitivity reactions are serum sickness (systemic) and Arthus reactions (local). The 
clinical manifestations of serum sickness include skin rash, fever, malaise, and polyarthralgias 
or polyarthritis. Symptoms typically develop 1 to 2 weeks after first exposure to an antigen 
and usually resolve in several weeks after withdrawal of the causative agent. Serum sickness 
needs to be differentiated from other ‘serum-sickness-like’ reactions that have a similar 
clinical presentation (eg, viral infections, anti-seizure drugs), but are believed to have different 
pathogenic mechanisms. Both serum sickness and serum sickness-like reactions have been 
reported with mAbs (eg, rituximab, infliximab). Clinical presentation and time to onset should 
be considered for the diagnosis and differentiation of these reactions. Diagnosis of these 
suspected reactions is best confirmed via biopsy of the affected tissues.
8.4.8.3
Thrombocytopenia
Thrombocytopenia is a disorder in which there is an abnormally low platelet count; a normal 
platelet count ranges from 150,000 to 450,000 platelets per μL. The 3 major causes of low 
platelet counts include: 1) insufficient platelet synthesis in the bone marrow; 2) increased 
breakdown of platelets in the bloodstream; and 3) increased breakdown of platelets in the 
spleen or liver. General symptoms of thrombocytopenia include bleeding in the mouth and 
gums, bruising, nosebleeds, and petechiae (pinpoint red spots/rash). Severe bleeding is the 
major complication, which may occur in the brain or gastrointestinal tract. Drug-induced 
thrombocytopenia is a reversible form of thrombocytopenia that should be suspected in a 
participant who presents with new onset thrombocytopenia or recurrent episodes of acute 
thrombocytopenia, without an obvious alternative etiology. It is commonly induced by 
drug-dependent antibodies that cause platelet destruction or clearance by the 
reticuloendothelial system (drug-induced immune thrombocytopenia), and less commonly by 
drug-induced bone marrow suppression or autoimmune thrombocytopenia that is initiated by 
exposure to the offending drug but persists in its absence. The initial approach to the 
participant with suspected drug-induced thrombocytopenia involves confirming 
thrombocytopenia, establishing a temporal relationship to a drug, and eliminating other causes 
of thrombocytopenia. The diagnosis is made clinically by documenting prompt resolution of 
thrombocytopenia after discontinuation of the suspected drug (typically within 1 week). Most 
participants with drug-induced thrombocytopenia require no specific treatment, as their 

Cli nical St u d y Pr ot oc ol - Versi o n 2. 0
Astra Ze neca
Nirse vi ma b ( M E DI 8 8 9 7) - D 5 2 9 0 C 0 0 0 0 9
C O N FI D E N TI A L A N D P R O P RI E T A R Y
4 7
pl at elet c o u nts will rec o ver pr o m pt l y f ollo wi n g wit h dra wal of t he ca usat i ve a ge nt.
8. 4. 9
D efi niti o n of Ne w-O n set C hr o nic Dise ases
A N O C D is a ne wl y  dia g n ose d me dical c o n ditio n  t hat is of a c hr o nic, o n g oi n g nat ure. It is 
o bser ve d after recei vi n g t he i n vesti gati o nal pr o d uct a n d is assesse d b y  t he i n vesti gat or as 
me dicall y si g nifica nt. E xa m ples of N O C Ds i ncl u de, b ut are n ot li mite d t o dia betes, 
a ut oi m m u ne disease (e g, l u p us, r he u mat oi d art hrit is), a n d ne ur ol o gical disease (e g, e pile ps y). 
E ve nts t hat w o ul d n ot be c o nsi dere d as N O C Ds are mil d ecze ma, di a g n osis of a c o n ge nital 
a n o ma l y prese nt at st u d y e ntr y, or ac ute ill ness (e g, u p per res pirat or y infect i on, oti tis me dia, 
br o nc hit is).
8. 4. 1 0
Re p orti n g of S A Es
All S A Es m ust be re p orte d w het her or n ot c o nsi dere d ca usall y relate d t o t he I M P . All S A Es 
will be rec o r de d i n t he e C R F.
If a n y S A E occ urs d uri n g t he st u d y, i n vestigat ors or ot her si te pers o n nel will i nf or m t he 
a p pr o priate s p o ns or re prese ntati ves wit hi n o ne da y, ie, i m me diatel y b ut n o l ater  t h a n 
2 4 h o urs of  w he n he or s he bec omes a ware of it .
T he desi g nate d s p o ns or re prese ntati ve will w or k with t he i n vest i gat or t o e ns ure t hat all t he 
necessar y  inf or mat i on is pr o vi de d t o t he Astra Ze neca Patie nt Safet y data e ntr y  sit e wit hi n 
o ne c ale n d ar d a y of  init ial recei pt f or fatal a n d life-t hreate ni n g e ve nts a n d wit hi n 5 c ale n d ar
d a ys of  init ial recei pt f or all ot her S A Es.
F or fatal  or life-t hreate ni n g A Es w here i m p orta nt or rele va nt i nf or mat i on is missi n g, acti ve 
f oll ow- u p will be u n derta ke n i m me diatel y . I n vesti gat ors or ot her site pers o n nel will i nf or m t he 
desi g nate d s p o ns or re prese ntati ves of a n y f o ll o w-u p i nf or mat i on o n a pre vi o usl y re p orte d 
S A E wi t hi n o ne cale n dar da y, ie, i m me diatel y but n o l ater  t h a n 2 4 h o urs of  w he n he or s he 
bec o me s a ware of it.
O nce t he i n vest i gat ors or ot her site pers o n nel i n dicate a n A E i s serio us i n t he El ectr o nic Data 
Ca pt ure ( E D C) s y st e m, a n a ut o mat e d e mail alert is se nt t o t he desi g nate d s p o ns or 
re prese ntati ve.
W he n t he E D C is te m p oraril y n ot accessi ble
or t he E D C s yste m is n ot a vaila ble, t he 
i n vesti gat or or ot her st u d y sit e st aff re p orts t o I Q VI A S afet y O perat i ons b y t he c o ntact 
i nf or mat i on bel o w. T he s p o ns or st u d y re prese ntati ve will a d vise t he i n vesti gat or/st u d y sit e 
pers o n nel h o w t o pr ocee d.
I Q VI A S afet y O perati o ns
Fa x: 
E mail: 
P P D
P P D

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For further guidance on the definition of an SAE, refer to Appendix B.
The reference document for definition of expectedness/listedness is the IB for the AstraZeneca 
IMP.
8.4.11
Medication Error
8.4.11.1
Timelines
If an event of medication error, drug abuse, or drug misuse occurs during the study, then the 
investigator or other site personnel informs the appropriate AstraZeneca (or designee) 
representatives within one calendar day, ie, immediately but no later than 24 hours of when 
they become aware of it.
The designated AstraZeneca representative works with the investigator to ensure that all 
relevant information is completed within one (initial fatal/life-threatening or follow-up 
fatal/life-threatening) or 5 (other serious initial and follow-up) calendar days if there is an 
SAE associated with the event of medication error, drug abuse, or misuse (see Section 8.4.10) 
and within 30 days for all other events.
8.4.11.2
Medication Error
For the purposes of this clinical study a medication error is an unintended failure or mistake 
in the treatment process for an IMP that either causes harm to the participant or has the 
potential to cause harm to the participant.
The full definition and examples of medication error can be found in Appendix B 5.
8.4.12
Reporting of Overdose
Refer to Section 6.8 for definition and treatment of overdose.

An overdose with associated AEs is recorded as the AE diagnoses/symptoms on the 
relevant AE modules in the eCRF and on the Overdose eCRF module.

An overdose without associated symptoms is only reported on the Overdose eCRF 
module.
If an overdose on an IMP occurs in the course of the study, the investigator or other site 
personnel inform appropriate AstraZeneca (or designee) representatives immediately, but no 
later than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative works with the investigator to ensure that all 
relevant information is provided to the AstraZeneca Patient Safety data entry site within one 
or 5 calendar days for overdoses associated with an SAE (refer to Section 8.4.10) and within 
30 days for all other overdoses.

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8.5
Pharmacokinetics

Serum samples will be collected for measurement of concentrations of nirsevimab as 
specified in Section 1.3 SoA.

Samples may be collected at additional time points during the study if warranted and 
agreed upon between the investigator and the sponsor, eg, for urgent safety reasons, and 
this may be reflected as a protocol deviation.

The timing of sampling may be altered during the study based on newly available data 
(eg, to obtain data closer to the time of peak or trough matrix concentrations) to ensure 
appropriate monitoring.

Samples collected for analyses of serum concentration may also be used to evaluate safety 
or efficacy aspects related to concerns arising during the study.

Samples will be collected, labelled, stored, and shipped as detailed in the Laboratory 
Manual.

For storage, re-use, and destruction of samples for PK, see Appendix C.

PK samples will be disposed of after the Bioanalytical Report finalization or 6 months 
after issuance of the draft Bioanalytical Report (whichever is earlier), unless consented 
for future use analysis.

Additional analyses may be conducted on the anonymized, pooled, or individual PK 
samples to further evaluate and validate the analytical method. Any results from such 
analyses may be reported separately from the CSR.
8.5.1
Collection of Samples for Pharmacokinetics
Blood samples will be collected for measurement of nirsevimab in serum at specified time 
points in Section 1.3 SoA. In addition, unscheduled blood samples will be collected for 
measuring nirsevimab serum levels from participants hospitalized with LRTI or any 
respiratory infection (regardless of upper or lower infection) within approximately 2 days 
following hospitalization.
8.5.2
Determination of Drug Concentration
Samples for determination of drug concentration in serum will be assayed by bioanalytical test 
sites operated by or on behalf of the sponsor, using an appropriately validated bioanalytical 
method. Full details of the analytical method used will be described in a separate Bioanalytical 
Report.
Incurred sample reproducibility analysis, if any, will be performed alongside the bioanalysis 
of the test samples. The results from the evaluation, if performed, will be reported in a 
separate Bioanalytical Report.

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8.6
Immunogenicity and Anti-RSV Neutralizing Antibody 
Assessments

Blood samples for determination of ADA and anti-RSV neutralizing Ab in serum will be 
assayed by bioanalytical test sites operated by or on behalf of the sponsor, using an 
appropriately validated bioanalytical method. Full details of the methods used will be 
described in a separate report.

Samples will be collected to evaluate ADA responses to nirsevimab in serum. Evaluation 
will be performed using validated immunoassays. Tiered analyses will be performed to 
include screening, confirmatory, and titer assay components, using the previously 
described positive-negative cut points.

Samples for pharmacodynamic (anti-RSV neutralizing Ab) assessments will be collected 
according to the SoA (see Section 1.3 SoA).

Samples collected will be labelled, stored, and shipped as detailed in the Laboratory 
Manual.

For storage, re-use, and destruction of samples, see Appendix C.
Extra blood samples will be collected for measurement of ADA and anti-RSV neutralizing Ab
will be collected from participants hospitalized with LRTI or any respiratory infection within 
2 days following hospitalization.
9
STATISTICAL CONSIDERATIONS
The Statistical Analysis Plan (SAP) will be finalized prior to clinical data lock, and it will 
include a more technical and detailed description of the planned statistical analyses. This 
section is a summary of the planned statistical analyses of the most important endpoints 
including primary and key secondary endpoints. 
9.1
Statistical Hypotheses
No statistical hypothesis analysis is planned.
9.2
Sample Size Determination
Approximately 33 participants will be enrolled to receive 2 IM doses of nirsevimab to 
evaluate the safety, PK, and ADA to nirsevimab, and anti-RSV neutralizing Ab which will be 
assessed descriptively. The proposed sample size of 33 participants in this study accounts for 
conservative estimate of 7% participant drop-out (based on 5% drop-out observed in Season 1 
prior to Day 151 in MEDLEY study) between 1st and 2nd doses to get 30 participants exposed 
to 2 IM doses of nirsevimab in this study will provide about 79% probability of observing at 
least one AE if the true event rate is 5%. Thirty-three participants are considered to provide
adequate sample size to evaluate the safety and to describe nirsevimab serum concentrations, 
and ADA to nirsevimab, and anti-RSV neutralizing Ab following 2nd dose.

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9.3
Populations for Analyses
The following populations are defined in Table 7:
Table 7
Populations for Analysis
Population/analysis set
Description
As-treated set 1
The As-treated set 1 consists of all participants who have received at least 
1 dose of IMP. 
As-treated set 2
The As-treated set 2 consists of all participants who have received the 
2 doses of IMP.
PK Analysis Set
Participants who receive at least 1 dose of IMP and who had at least 1 
quantifiable serum PK observations. Data issues that impact the PK results 
may result in exclusion from the PK summaries. All PK summaries will be 
based on this analysis set.
PK in participants with replacement dose is separately summarized.
ICF = informed consent form; IMP = investigational medicinal product; PK = pharmacokinetics
9.4
Statistical Analyses
9.4.1
General Considerations
There are 2 planned analyses for this study: a primary analysis and a final analysis. The 
primary analysis will be conducted when all enrolled participants have been followed through 
Visit 5 (ie, around 150 days post 2nd dose). The final analysis will be conducted after all 
participants have completed the last visit (Visit 6) of the study (ie, Day 360 post the 2nd dose 
or last dose).
All data, including baseline characteristics, safety, and efficacy, will be summarized as below:

Categorical data will be summarized by the number and percentage of participants in each 
category.

Continuous variables will be summarized by mean, SD, median, Q1, Q3, minimum, and 
maximum. In general, unless stated otherwise, baseline characteristics will be defined as 
the last non-missing value prior to dosing.

In general, unless stated otherwise, baseline will be defined as the last non-missing value 
prior to dosing.
More details on statistical analyses will be provided in the SAP.
Data analyses will be conducted using SAS® System Version 9.4 or higher.
9.4.2
Safety
Adverse events (AEs) will be graded based on of the current version of the National Cancer 
Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) where applicable 

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for pediatric assessments. It is shown in Appendix B 2 ‘Intensity Rating Grade’. AEs will be 
coded according to the current version of Medical Dictionary for Regulatory Activities 
(MedDRA), and the type, incidence, severity, and relationship to the study intervention will be 
summarized. Other safety assessments will include the occurrence of AESIs of immediate 
hypersensitivity reactions (including anaphylaxis), thrombocytopenia, and immune complex 
disease (eg, vasculitis, endocarditis, neuritis, glomerulonephritis) following investigational
product administration, and the occurrence of NOCDs following investigational product 
administration.
The primary estimand is presented below:

Treatment: One dose of nirsevimab as a single, fixed IM dose of 50 mg if body weight 
is <5 kg or 100 mg if body weight is ≥5 kg followed with a 2nd fixed IM dose of 50 
mg if current weight is <5 kg or 100 mg if current weight is ≥5 kg administered 5 to 
6 months following the 1st dose.

Population: As-treated set 2, all participants who have received 2 doses of IMP.

Endpoint: Incidence of TEAEs, TESAEs, AESIs, and NOCDs through 360 days post 
2nd dose.

Intercurrent Events: Intercurrent events are defined as study discontinuations prior to 
Day 151 after 2nd dose. Intercurrent events will be handled using while on treatment 
strategy. That is, for participants with intercurrent events, treatment-emergent AEs, 
SAEs, AESIs, and NOCDs prior to the intercurrent events will be included in the 
analysis.

Population-level Summary: The number and percentage of participants with TEAEs, 
TESAEs, AESIs, and NOCDs will be summarized by SOC and PT overall.
Safety analyses may also be repeated in As-treated set 1 population.
9.4.3
Secondary Endpoints
9.4.3.1
Pharmacokinetics
In PK analysis set, serum concentrations of nirsevimab at the specific timepoints will be 
evaluated following 2 doses of nirsevimab given 5 to 6 months apart. Nirsevimab serum 
concentration data will be presented in descriptive statistics.
9.4.3.2
Anti-Drug Antibody
Based on the As-treated set 2 population, the occurrence of ADA to nirsevimab will be 
assessed and summarized by number and percentage of participants who are ADA-positive. 
The impact of ADA on PK, and association with TEAEs and TESAEs, will be assessed, if data 
permitted.

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9.4.3.3
Anti-RSV Neutralizing Antibody Evaluation
Based on the As-treated set 2 population, analysis of serum anti-RSV neutralizing Ab in 
nirsevimab recipients will be summarized by geometric mean titer (GMT) and geometric 
mean fold-rise (GMFR) with corresponding 95% CI.
9.4.4
Exploratory Endpoint(s)
9.4.4.1
Occurrence of MA-RSV LRTI
Based on the As-treated set 2 population, the number and percentage of participants with MA-
RSV LRTI (inpatient and outpatient) due to RT-PCR-confirmed RSV through 150 days 
(primary timepoint analysis) and 360 days (final timepoint analysis) post 2nd dose will be 
summarized. For participants with multiple MA-RSV LRTI events, only the first occurrence 
will be used in the analysis.
The analysis will be repeated for occurrence of hospitalizations due to RT-PCR-confirmed 
RSV through 150 and 360 days post 2nd dose.
9.4.4.2
Monitoring RSV Resistance to Nirsevimab
Genotypic analysis of the full-length mature F protein will be conducted on all RSV-positive 
isolates confirmed centrally using the Lyra RSV + hMPV real-time RT-PCR assay 
manufactured by Quidel Corporation. RSV genotypic analysis will report the sequence 
changes in the mature F protein from all RSV-positive isolates compared to contemporary 
RSV A and RSV B reference strains. Susceptibility of novel RSV variants to nirsevimab will 
be tested and compared to control viruses.
Results on RSV resistance analyses will be reported separately from CSR.
9.5
Deviations from Clinical Study Protocol
The investigator(s) must not deviate from or make any changes to the protocol without 
documented agreement between PI and the sponsor or the institutional review board (IRB) 
approval based on its deliberations. However, this shall not apply to cases where the deviation 
or change is necessary to avoid an immediate hazard to the participants or for other 
compelling medical reasons, or where the changes involve only logistical or administrative 
aspects of the clinical study (eg, changes to the name/department name of the study site, the 
address or phone number of the study site or the sponsor/designee, and monitors).
The investigator(s) should document any deviation from the protocol regardless of reasons. 
Only when the protocol was not followed in order to avoid an immediate hazard to the 
participants or for other medically compelling reason, the PI must notify details of the 
deviation or change, the reason, and a proposed revision in the protocol if required, to the 
sponsor (or designee), the head of the study site, and IRB via the head of the study site as soon 
as possible, in order to obtain their approval. A certificate of approval by the head of the study 
site as well as the sponsor should be obtained via the head of the study site.

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REFERENCES
American Academy of Pediatrics, 2022
American Academy of Pediatrics. Updated Guidance: Use of Palivizumab Prophylaxis to 
Prevent Hospitalization From Severe Respiratory Syncytial Virus Infection During the 2021-
2022 RSV Season. Available at https://www.aap.org/en/pages/2019-novel-coronavirus-covid-
19-infections/clinical-guidance/interim-guidance-for-use-of-palivizumab-prophylaxis-to-
prevent-hospitalization/. Date accessed: 06/07/2022
Bermudez Barrezueta et al, 2022
Bermudez Barrezueta L, Matias Del Pozo V, Lopez-Casillas P, Bremes Raposo M, Guitterez 
Zamorano M & Pino Vasquez MA. Variation in the seasonality of the respiratory syncytial 
virus during the COVID-19 pandemic. Infection.2022; 1-5. 10.1007/s15010-022-01794-y 
[doi]
Hall et al, 2009
Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA et al. The burden 
of respiratory syncytial virus infection in young children. N Engl J Med. 2009;360(6):588-98.
IDWR Surveillance data, 2022
IDWR Surveillance data table 2022 week 4, https://www.niid.go.jp/niid/en/survaillance-data-
table-english/11682-idwr-sokuho-data-e-2249.html
Kobayashi et al, 2022
Kobayashi Y, Togo K, Agosti Y, McLaughli JM. Epidemiology of respiratory syncytial virus 
in Japan: A nationwide claims database analysis. Pediatrics International. 2022;64:e14957.
Miyama et al, 2021
Miyama T, Iritani N, Nishio T, Ukai T, Satsuki Y, Miyama H et al. Seasonal shift in epidemics 
of respiratory syncytial virus infection in Japan. Epidemiol Infect. 2021;149(e55):1-3.
Sampson et al, 2006
Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Jr., Bock SA, Branum A et al. 
Second symposium on the definition and management of anaphylaxis: summary report--
Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis 
Network symposium. J Allergy Clin Immunol. 2006;117(2):391-7.
Shi et al, 2017
Shi T, McAllister DA, O'Brien KL, Simoes EAF, Madhi SA, Gessner BD et al. Global, 
regional, and national disease burden estimates of acute lower respiratory infections due to 
respiratory syncytial virus in young children in 2015: a systematic review and modelling 
study. Lancet. 2017;390(10098):946-58

SI G N A T U R E P A G E
T his is a re prese nt ati o n of a n electr o nic rec or d t h at w as si g ne d
electr o nic ally a n d t his p a ge is t he m a nifest ati o n of t he electr o nic si g n at ure
D oc u me nt N a me: d 5 2 9 0c 0 0 0 0 9-cs p- v 2
D oc u me nt Title:
D 5 2 9 0 C 0 0 0 0 9 Cli nical St u d y Pr ot oc ol versi o n 2
D oc u me nt I D:
Versi o n L a bel:
4. 0 C U R R E N T L A T E S T A P P R O V E D
Ser ver D ate
( d d- M M M- y y y y H H: m m ‘ U T C’ Z)
Si g ne d b y
Me a ni n g of Si g n at ure
2 5- Ma y- 2 0 2 3 1 4: 3 9 U T C
C o nte nt A p pr o val
2 5- Ma y- 2 0 2 3 1 6: 1 7 U T C
Ma na ge me nt A p pr o val
2 5- Ma y- 2 0 2 3 1 5: 3 9 U T C
C o nte nt A p pr o val
P P D
P P D
P P D
C CI
C CI