Clinical trial NCT05118386
Conditions: RSV Infection
Keywords: Monoclonal antibody
Sponsor: Gates Medical Research Institute
Start date: 2021-11-16; Completion date: 2022-12-07
Enrollment: 56 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Gates MRI-RSM01-101 was a Phase 1, randomized, double-blind, placebo-controlled, dose-escalation study to evaluate the safety and tolerability, pharmacokinetics, occurrence of Anti-drug antibody (ADA), and assessment of neutralizing antibody against RSV after administration of single intravenous or intramuscular doses of RSM01 to healthy adults.

Detailed description:
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) among infants and young children, resulting in annual epidemics worldwide.

RSM01, a monoclonal antibody targeting RSV, may potentially provide an effective method to protect infants from RSV disease based on its potency and an extended half-life that is expected to support once-per-RSV-season administration.

This study was a first-in-human evaluation of RSM01 in healthy male and female adults with the goal of characterizing the safety and tolerability of a range of single doses of RSM01 to enable determination of appropriate dose(s) to be administered to infants in a future study. Enrollment was planned at a single study center in the United States. 56 participants were enrolled; 48 participants received RSM01 and 8 participants received Placebo. Participants were followed for approximately 5 months (151 days) after dosing.

Arms: arm 1: Participants were randomized to receive different dose levels of RSM01. Participants were randomized in a ratio of 6:1 where for every 6 participants received active drug (RSM01), 1 participant received Placebo. arm 2: Participants received Placebo matched to RSM01.
Interventions: intervention 1: RSM01 intervention 2: Placebo
Intervention descriptions: intervention 1: Cohort 1: RSM01 300 mg IV

Cohort 2: RSM01 300 mg IM

Cohort 3: RSM01 1000 mg IV

Cohort 4: RSM01 3000 mg IV

Cohort 5: RSM01 600 mg IM intervention 2: Cohort 1: Placebo IV

Cohort 2: Placebo IM

Cohort 3: Placebo IV

Cohort 4: Placebo IV

Cohort 5: Placebo IM

Protocol documents:
Prot_000.pdf: 
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Title Page 
Protocol Title: A Phase 1 Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Safety, 
Tolerability, and Pharmacokinetics of Single Ascending Doses of RSM01, a Monoclonal Antibody 
Targeting Respiratory Syncytial Virus, in Healthy Adults 
Protocol Number: Gates MRI-RSM01-101, Version (v)4.0 
Short Title: Safety, Tolerability, and Pharmacokinetics of RSV Monoclonal Antibody RSM01 in 
Healthy Adults 
Compound Number: RSM01 
Study Phase: 1 
Sponsor Name: Bill & Melinda Gates Medical Research Institute (Gates MRI) 
Legal Registered Address: 
One Kendall Square 
Building 600, Suite 6-301 
Cambridge, MA 02139 
Medical Monitor and other important study personnel information will be provided in a separate 
document. 
v4.0; Approval Date: 21 January 2022 
                                                   NCT Number: NCT05118386
This NCT number has been applied to the document for purposes of posting on Clinicaltrials.gov


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Document History 
 
Document 
Date 
v4.0 
21 January 2022 
v3.0 
10 December 2021 
v2.0 
20 July 2021 
Original Protocol v1.1 
09 June 2021 
 
Refer to Section 12 for the rationale for v4.0 and a complete list of changes. 
 


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Sponsor Signature Page 
Version 3.0 
 
See appended electronic signature page 
 
 
 
___________________________________  
____________________ 
Sponsor Signatory 
 
 
 
 
Date 
MD, PhD, MPH 
Clinical Development Leader 
Bill & Melinda Gates Medical Research Institute 
 
 


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Table of Contents 
Table of Contents ...........................................................................................................................4 
List of Tables ..................................................................................................................................7 
List of Figures .................................................................................................................................7 
1. 
Protocol Summary ........................................................................................................10 
1.1. 
Synopsis ..........................................................................................................................10 
1.2. 
Schema ............................................................................................................................16 
1.3. 
Schedule of Activities (SoA) ..........................................................................................17 
2. 
Introduction ...................................................................................................................20 
2.1. 
RSV and Burden of Disease ...........................................................................................20 
2.2. 
RSV Prevention- Monoclonal Antibodies ......................................................................21 
2.3. 
RSM01 mAb Candidate ..................................................................................................22 
2.3.1. 
Non-Clinical Development of RSM01 ...........................................................................22 
2.4. 
Study Rationale ...............................................................................................................23 
2.5. 
Justification for Dose ......................................................................................................23 
2.5.1. 
Doses for Escalation Phase Cohorts ...............................................................................23 
2.5.2. 
Dose for Expansion Phase Cohort ..................................................................................24 
2.6. 
Benefit/Risk Assessment ................................................................................................25 
3. 
Objectives and Endpoints ............................................................................................27 
4. 
Study Design ..................................................................................................................28 
4.1. 
Design Overview ............................................................................................................28 
4.2. 
End of Study Definition ..................................................................................................30 
5. 
Study Population ...........................................................................................................30 
5.1. 
Inclusion Criteria ............................................................................................................31 
5.2. 
Exclusion Criteria ...........................................................................................................32 
5.3. 
Lifestyle Considerations .................................................................................................33 
5.4. 
Screen Failures ................................................................................................................34 
6. 
Study Intervention ........................................................................................................35 
6.1. 
RSM01 Drug Product .....................................................................................................35 
6.2. 
Placebo Drug Product .....................................................................................................36 
6.3. 
Study Intervention Preparation and Administration .......................................................36 
6.3.1. 
IM Injection ....................................................................................................................36 
6.3.2. 
IV Infusion ......................................................................................................................37 
6.4. 
Handling/Storage/Accountability ...................................................................................37 
6.5. 
Measures to Minimize Bias: Randomization and Blinding ............................................38 
6.5.1. 
Randomization ................................................................................................................38 
6.5.2. 
Masking...........................................................................................................................39 
6.5.3. 
Blind Break .....................................................................................................................40 
6.6. 
Study Intervention Compliance ......................................................................................40 
6.7. 
Concomitant Therapy .....................................................................................................40 
6.8. 
Dose Modification ..........................................................................................................40 


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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................40 
7.1. 
Discontinuation of Study Intervention ............................................................................40 
7.1.1. 
Pausing Rules ..................................................................................................................41 
7.2. 
Participant Discontinuation or Withdrawal from the Study ...........................................41 
7.3. 
Lost to Follow-up............................................................................................................43 
7.4. 
COVID-19 Contingency Plans .......................................................................................43 
8. 
Study Assessments and Procedures.............................................................................44 
8.1. 
Safety Assessments .........................................................................................................44 
8.1.1. 
Confinement Period and Sentinel Participants ...............................................................45 
8.1.2. 
Full Physical Examination and Medical History ............................................................45 
8.1.3. 
Focused Physical Examination and Medications/Vaccinations ......................................46 
8.1.4. 
Pregnancy Status Assessment .........................................................................................46 
8.1.5. 
HIV Antibody Assessment .............................................................................................47 
8.1.6. 
Electrocardiogram, Hepatitis Screening and Urine Drug 
Screening.........................................................................................................................47 
8.1.7. 
Clinical Safety Laboratory Assessments ........................................................................47 
8.1.8. 
Pre- and Post-Study Intervention Safety Monitoring......................................................48 
8.1.9. 
Diary Card, Memory Aid and Daily Monitoring ............................................................49 
8.1.10. Participant Follow-Up .....................................................................................................49 
8.2. 
Adverse Events and Serious Adverse Events .................................................................50 
8.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information .....................................................................................................................51 
8.2.2. 
Method of Detecting AEs and SAEs ..............................................................................51 
8.2.3. 
Follow-up of AEs ............................................................................................................51 
8.2.4. 
Regulatory Reporting Requirements for SAEs ...............................................................52 
8.2.5. 
Death Events ...................................................................................................................52 
8.2.6. 
Safety Review Team .......................................................................................................53 
8.2.7. 
Independent Data Monitoring Committee ......................................................................53 
8.3. 
Treatment of Overdose ...................................................................................................53 
8.4. 
Blood Sampling ..............................................................................................................53 
8.5. 
Pharmacokinetics ............................................................................................................54 
8.6. 
Pharmacodynamics .........................................................................................................54 
8.7. 
Genetics ..........................................................................................................................55 
8.8. 
Biomarkers ......................................................................................................................55 
8.9. 
Immunogenicity ..............................................................................................................55 
9. 
Statistical Considerations .............................................................................................55 
9.1. 
Sample Size Determination ............................................................................................55 
9.2. 
Populations for Analyses ................................................................................................56 
9.3. 
Statistical Analyses .........................................................................................................56 
9.3.1. 
Safety Primary Endpoints ...............................................................................................58 
9.3.2. 
Safety Secondary Laboratory Assessments ....................................................................58 
9.3.3. 
Other Safety Measures ....................................................................................................59 
9.3.4. 
Pharmacokinetics ............................................................................................................59 
9.4. 
Serum and Capillary Blood Immunogenicity .................................................................59 
9.5. 
Serum and Capillary Blood RSV Neutralizing Antibody ...............................................59 


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9.6. 
Demographic and Compliance Analyses ........................................................................59 
9.7. 
Interim Analyses .............................................................................................................60 
9.8. 
National Regulatory Authority .......................................................................................60 
10. 
Supporting Documentation and Operational Considerations ..................................61 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................61 
10.1.1. Regulatory and Ethical Considerations ...........................................................................61 
10.1.2. Study Oversight ..............................................................................................................61 
10.1.3. Financial Disclosure........................................................................................................62 
10.1.4. Informed Consent Process ..............................................................................................62 
10.1.5. Data Protection................................................................................................................63 
10.1.6. Dissemination of Clinical Study Data.............................................................................63 
10.1.7. Data Quality Assurance ..................................................................................................64 
10.1.8. Source Documents ..........................................................................................................64 
10.1.9. Record Retention ............................................................................................................65 
10.1.10. Study and Site Closure ....................................................................................................65 
10.1.11. Publication Policy ...........................................................................................................65 
10.2. 
Appendix 2: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .........................................................66 
10.2.1. Definition of AE .............................................................................................................66 
10.2.2. Definition of SAE ...........................................................................................................67 
10.2.3. Definition of Serious Adverse Drug Reaction (Serious ADR) .......................................68 
10.2.4. Definition of AESI ..........................................................................................................68 
10.2.5. Recording and Follow-Up of AE, SAE, AESI ...............................................................68 
10.2.6. SAEs, AESIs, and Serious ADR Reporting ....................................................................72 
10.3. 
Appendix 3: Contraceptive Guidance and Collection of 
Pregnancy Information ...................................................................................................73 
10.4. 
Appendix 4: Toxicity Tables ..........................................................................................75 
11. 
References ......................................................................................................................80 
12. 
Protocol Version History ..............................................................................................82 
 


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List of Tables 
 
Table 1: Objectives and Endpoints ............................................................................................... 11 
Table 2: Schedule of Activities for the Dose Escalation Phase (Cohorts 1-4) ............................. 17 
Table 3: Schedule of Activities for the Expansion Phase (Cohort 5) ........................................... 19 
Table 4: Objectives and Endpoints ............................................................................................... 27 
Table 5: Study Interventions ......................................................................................................... 35 
Table 6: Populations for Analyses ................................................................................................ 56 
Table 7: Summary of Primary and Secondary Endpoints and Analyses ...................................... 57 
Table 8: FDA Toxicity Grading Scale- Clinical Abnormalities ................................................... 75 
Table 9: FDA Toxicity Grading Scale- Laboratory Abnormalities .............................................. 77 
Table 10: FDA Toxicity Grading Scale- Urine ............................................................................. 79 
 
List of Figures 
Figure 1: Outline of Study Dosing Procedures ............................................................................. 16 
 


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List of Abbreviations 
ADA 
Anti-drug antibody 
ADR 
Adverse drug reaction 
AE 
Adverse event 
AESI 
Adverse event of special interest 
AUC 
Area under the (time) curve (e.g., capillary blood-concentration time curve 
for RSM01)  
CD91 
Day 91 capillary blood-concentration of RSM01 
CD151 
Day 151 capillary blood-concentration of RSM01  
Cmax 
Maximum capillary blood-concentration of RSM01 
Cmin 
Minimum capillary blood-concentration of RSM01 
CFR 
Code of Federal Regulations 
CL 
Systemic clearance 
CRF 
Case report form 
CSR 
Clinical study report 
EC90 
Effective concentration that leads to 90% maximal response (or the logarithm 
of the EC90) 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
ELISA 
Enzyme-linked immunosorbent assay 
GCP 
Good clinical practices 
Gates MRI 
Bill & Melinda Gates Medical Research Institute 
GGT 
Gamma glutamyl transferase 
HIV 
Human immunodeficiency virus 
ICH 
International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IM 
Intramuscular 
IRB 
Institutional Review Board 
IUD 
Intrauterine device 
IV 
Intravenous 
IXRS 
Interactive voice/web response system  
LTRI 
Lower respiratory tract infection 
mAb 
Monoclonal antibody 
Mg 
Milligram 
mL 
Milliliter 
mITT 
Modified intention to treat 
NA 
Not applicable 
NCA 
Noncompartmental analysis  
NCT 
National (U.S.) Clinical Trial Identifier 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 
PP 
Per protocol 


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Pre-F 
Prefusion conformation of the Respiratory Syncytial Virus F glycoprotein 
RSM01 
Monoclonal antibody targeting Respiratory Syncytial Virus, Drug Product for 
use in the clinical trial 
RSV 
Respiratory Syncytial Virus 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SoA 
Schedule of activities 
SRT 
Safety Review Team 
t1/2 
Apparent terminal half-life  
Tmax 
Time to maximum capillary blood-concentration of RSM01 
ULN  
Upper limit of normal 
U.S. 
United States 
VAMS 
Volumetric absorptive microsampling 
Vz 
Volume of distribution  
WBC 
White blood cell count 
WHO 
World Health Organization 
YTE 
Triple amino acid substitutions 
 


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1. 
Protocol Summary 
1.1. Synopsis 
Protocol Title: A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Evaluate the 
Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of RSM01, a Monoclonal 
Antibody Targeting Respiratory Syncytial Virus, in Healthy Adults 
Short Title: Safety, Tolerability, and Pharmacokinetics of RSV Monoclonal Antibody RSM01 
in Healthy Adults 
Rationale: The high and continued burden of Respiratory Syncytial Virus (RSV) infection, 
especially among infants and young children, underscores the need for safe and effective 
prevention against RSV disease that is affordable in low- and middle-income countries (LMICs). 
This study will evaluate the safety, tolerability, and pharmacokinetics in adults of an RSV 
monoclonal antibody (mAb) candidate engineered to be highly neutralizing and long acting, and 
to determine an appropriate dose with acceptable safety profile in adults, prior to administration 
to infants in a future clinical study. 
Proof of concept for passive immunization of infants with a mAb has been demonstrated for 
palivizumab, a commercial mAb product indicated to prevent RSV disease in premature infants. 
Palivizumab, however, must be administered monthly during the RSV season and is very costly. 
Two (2) next generation RSV mAb candidates are in clinical development: Merck’s MK-1654 
and AstraZeneca’s MEDI8897 (nirsevimab). In completed trials, nirsevimab shows promise in 
reducing the incidence of medically-attended lower respiratory tract infection (LRTI) and 
hospitalizations caused by RSV, in healthy preterm infants. Both of these 2 mAb candidates 
were well-tolerated. Regardless, the cost of these candidates when commercialized may not 
allow for global access to the product. 
RSM01 is a fully human IgG1 mAb that targets glycoprotein F of RSV and binds to the antigenic 
site Ø of the prefusion conformation of the F protein (a region considered to be highly sensitive 
to neutralization). The major mode of action for RSM01 is virus neutralization. RSM01 has the 
same half-life extension, triple amino acid substitutions (YTE) M252Y/S254T/T256E (European 
Union numbering), mutation in its crystallizable fragment (Fc) domain, as do the MK-1654 and 
nirsevimab RSV mAb candidates. 
In this study, healthy adults will receive either intravenous (IV) or intramuscular (IM) doses of 
RSM01, which will enable assessment of the safety profiles together with estimation of human 
bioavailability following IM injection, which is the intended route of administration in infants. 
 


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Table 1: Objectives and Endpoints 
Objectives 
Endpoints (Endpoints apply to all cohorts unless noted) 
Primary 
To characterize the safety and 
tolerability of a single dose of 
RSM01  
• Unsolicited adverse events (AEs) through Day 151 
• All serious adverse events (SAEs) and AE of special 
interest (AESIs) through Day 151 
• Solicited systemic AEs for 7 days after dose 
administration 
• Solicited local AEs for injection site reactions for 7 days 
after dose administration (only applies to IM doses) 
Secondary 
To characterize safety 
laboratory parameters following 
RSM01 administration 
• Safety laboratory parameters Grade 1 and above through 
Day 151 
To characterize the 
pharmacokinetics (PK) 
following RSM01 
administration  
PK parameters including: 
• Area under the capillary blood-concentration time curve 
from zero to infinity (AUC0-∞) 
• Day 91 capillary blood-concentration and area under the 
capillary blood-concentration time curve (CD91 and AUC0-
D91) 
• Day 151 capillary blood-concentration and area under the 
capillary blood-concentration time curve (CD151 and 
AUC0-D151) 
• Maximum capillary blood-concentration (Cmax following 
IM administration and C0 following IV) administration), 
minimum concentration (Cmin) 
• Time to maximum capillary blood-concentration (Tmax) 
apparent terminal half-life (t1/2) 
• Systemic clearance (CL) 
• Volume of distribution (Vz) of RSM01 through Day 151 
To characterize the formation of 
anti-drug antibodies (ADAs) 
following RSM01 
administration 
• Incidence of ADAs to RSM01 through Day 151 
Exploratory 
 To characterize RSV 
neutralizing antibody activity 
following RSM01 
administration 
• Capillary blood RSV neutralizing antibody levels through 
Day 151 


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Overall Design 
Disclosure statement: This is a First-in-Human (FiH) trial of RSM01, administered to adults. It 
is a randomized, double-blind, placebo-controlled study of RSM01. 
Study Population and Number of Participants: Adult participants between 18 and 49 years of 
age (inclusive) of both sexes who are capable of and willing to provide informed consent may be 
eligible for the study. 
Candidates will be screened to enroll at least 56 eligible participants. 
Assuming that all cohorts are allowed to undergo treatment, approximately 48 participants will 
be exposed to RSM01 and approximately 8 participants will receive Placebo. 
Interventional model: The study will be conducted in 2 parts: A Dose Escalation Phase (N=28) 
with 4 dosing cohorts, followed by an Expansion Phase (N=28) with a single cohort. 
Dose Escalation Phase: 
The Dose Escalation Phase will include 28 participants. 
The first participant in each Dose Escalation Phase cohort will not be randomized and will 
receive the RSM01 dose level appropriate to the assigned cohort to serve as a sentinel exposure 
participant. 
The remaining 6 participants in each of Cohorts 1, 2, 3, and 4 will be randomized 5:1 to receive 
either RSM01 or Placebo. The overall ratio of RSM01 to Placebo will be 6:1 in each cohort. 
The Dose Escalation Phase will occur sequentially in 2 escalation steps. 
• 
Cohort 1: 7 participants will receive RSM01 300mg IV (n=6 total including sentinel 
participant) or Placebo IV (n=1) 
First escalation step: from Cohort 1 to Cohorts 2 and 3, conducted in parallel 
• 
Cohort 2: 7 participants will receive RSM01 300mg IM (n=6 total including sentinel 
participant) or Placebo IM (n=1) 
• 
Cohort 3: 7 participants to receive RSM01 1000mg IV (n=6 total including sentinel 
participant) or Placebo IV (n=1) 
Second escalation step: from Cohorts 2 and 3 to Cohort 4 
• 
Cohort 4: 7 participants will receive RSM01 3000mg IV (n=6 total including sentinel 
participant) or Placebo IV (n=1). 
For the Dose Escalation Phase cohorts, all participants will be confined at the study site from 
Day -1 (i.e., the day before dosing) to after completion of the Day 3 assessments (a total of 3 
nights). 
After the sentinel participant in each cohort receives RSM01, the next participant can be dosed 
24 hours later, if there is no safety concern. After the 24-hour post-dose period for the sentinel 
participant in each cohort, participants in the Dose Escalation Phase cohorts should be dosed at 
least 2 hours apart regardless of route of administration (IM or IV). The ≥2-hour interval 
between administering IV infusions is to begin at the end of the previous infusion. For 
participants receiving the IM dose of study drug in Cohort 2, the ≥2-hour interval between 
administering IM injections to successive participants is to begin at the time of the previous 


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participant’s IM injection. If RSM01 is administered using 2 injections, the ≥2-hour interval 
begins at the time of the second injection. 
Each dose escalation step will proceed after all participants in the prior cohort have completed 
Day 15, and the Safety Review Team (SRT) has reviewed the data and determined that a pausing 
rule has not been met. 
Dose Expansion Phase: 
Enrollment in the Dose Expansion Phase cohort (Cohort 5) will begin after Day 15 for all 
participants in Cohort 4, and after the SRT has reviewed the data and determined that a pausing 
rule has not been met. Cohort 5 will include 28 participants randomized 6:1. 
• 
Cohort 5: participants will receive RSM01 IM (n=24) or Placebo IM (n=4). 
For Cohort 5, participants will be asked to present to the clinic within 24 hours of the Day 1 visit 
for Day -1 (Pre-V1) confinement. 
On Day 1 after dosing, participants will be observed for at least 4 hours post-dose at the study 
site for safety monitoring. Based on investigator’s decision, a participant may be asked to remain 
at the study site, for an additional overnight stay on the night of Day 1. 
Final selection of the dose of RSM01 to be administered to Cohort 5 will be made by the sponsor 
and informed by available RSM01 PK data from the Dose Escalation Phase. 
The tentatively determined dose to be evaluated in the Expansion Phase cohort is ≥300 mg to 
≤600 mg IM. This determination is based on predictions of RSM01 human PK exposures made 
using extrapolation from the RSM01 non-human primate PK and on published data from the 
other RSV mAbs nirsevimab and MK-1654 administered to healthy adults [Griffin 2017, 
Aliprantis 2020]. The predictions suggest that the concentration of RSM01 will be above the 
efficacy threshold (EC90) on Day 151 following a RSM01dose of 300 or 600 mg IM. 
Pausing Rules 
Pausing rules (reasons for pausing the study) are in effect during the active enrollment and 
dosing period. Any one of the following will prompt a study pause: 
• death in any participant in whom the event causing death is judged to be related to the 
study drug by the investigator. 
• any occurrence in any participant of a SAE judged to be related by the investigator. 
• any occurrence in any participant of an AESI (anaphylaxis, hypersensitivity reaction, 
and/or infusion reaction resulting in permanent discontinuation of study drug infusion 
during IV administration). 
• any occurrence of Grade 3 or higher toxicity assessed to be related to the study drug by 
the investigator. 
• any occurrence of a clinically significant Grade 3 or higher laboratory abnormality 
assessed to be related to the study drug by the investigator. 


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If any of the pausing criteria are met, enrollment/patient accrual as well as dosing of enrolled 
participants will be suspended pending IDMC’s review of all available safety data and the U.S. 
Food and Drug administration (FDA) will be notified in an expedited manner. 
IDMC: The IDMC will review safety data if a pausing rule is met and make a recommendation 
on how to proceed (See Section 8.2.7.). The IDMC will be provided unblinded data by an 
independent statistician. 
Safety Review Team: A SRT will be established as the team responsible for recommending 
dose escalation or dose expansion to the sponsor’s Chief Medical Officer. Meetings of the SRT 
to provide a recommendation on dose escalation or dose expansion will occur during the Dose 
Escalation Phase when all participants in the currently dosed cohort have completed Day 15. The 
SRT will also meet approximately every 8 weeks during the Dose Expansion Phase (See Section 
8.2.6). The SRT will review blinded data only. 
Visits: After the Screening Visit, and the Day -1 Visit, there will be a total of 11 visits over 151 
days for the Dose Escalation Phase and a total of 5 visits over 151 days for the Dose Expansion 
Phase. 
Note that when participants arrive for the Day -1 clinic visit, they will stay overnight at the 
clinic. Participants in the Dose Escalation Phase cohorts will remain at the clinic for Visits 1, 2, 
and 3, on Day 1, Day 2, and Day 3, respectively. 
The participants in the Dose Expansion Phase cohort will remain at the clinic for at least 4 hours 
after dosing on Day 1, and possibly for the night of Day 1, based on investigator’s decision. 
The study Schema is shown in Figure 1 and the Schedule of Activities (SoA) is shown in Table 
2, and Table 3 for Dose Escalation Phase and Dose Expansion Phase, respectively. 
Blood Sampling: Dose Escalation Phase cohorts: On Day 1, PK blood draw will occur pre-
dosing 1 hour (+/- 30 minutes) before administration of IM injection or beginning of IV 
infusion, at 5 minutes (± 1 minute) after end of infusion for IV dosing only, and at 8-hours (±0.5 
hour) and 24-hours (±1 hour) after end of infusion for IV doses and at 8-hours (±0.5 hour) and 
24-hours (±1 hour) after IM dose. ADA and RSV neutralizing antibody activity samples will be 
obtained pre-dose only 1 hour (+/- 30 minutes) before administration of IM injection or 
beginning of IV infusion. 
Dose Expansion Phase cohort: On Day 1, the blood collection for PK, ADA and RSV 
neutralizing antibody activity will occur pre-dosing only 1 hour (+/- 30 minutes) before 
administration of IM injection. 
Serum will be collected as shown in the SoA (Section 1.3), for screening and safety laboratories. 
Venous serum and capillary volumetric absorptive microsampling (VAMS) will be collected as 
shown in the SoA (Table 2 and Table 3) for PK, ADA testing and RSV neutralizing antibody 
testing. 
A maximum of approximately 200 mL of whole blood will be collected from each participant 
during the entire study period, assuming all planned samples are collected, according to the SoA. 
Masking: The study is double-blind. Participants and all study personnel will be blinded to the 
randomization, with one exception: the first sentinel participant in each Dose Escalation Phase 


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cohort will be single-blinded (participant-blinded) and will receive the respective dose of 
RSM01. Authorized study site personnel will administer doses. 
Analysis: An interim analysis will occur after all participants in the Dose Escalation Phase 
cohorts (Cohorts 1 through 4), have reached Day 91. The primary analysis will occur after all 
participants in all 5 cohorts complete Day 151. 
Total duration of study participation: The study duration for each participant is 151 days, in 
addition to a maximum of 30 days for screening and Day -1. 
Study site/s: The study will be conducted at 1 site in the United States (U.S.). 
 
 


1.2. Schema 
Figure 1: Outline of Study Dosing Procedures 
Cohort 1: 300 mg IV 
N=7 {6:1) RSM:placebo 
dose • 
1 0 15 
SRT review 
Cohort 2: 300 mg IM 
N=7 {6:1) 
dose • 
01 
SRT review 
Cohort 4: 3000 mg IV 
N=7 {6:1) 
Cohort 5: 
dose 
ti 
SRT review 
Between 300 mg and 600 mg IM (6:1) 
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interim analysis 
dose • 
01 
0 9 
1 
09 
primary analysis 
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1.3. Schedule of Activities (SoA) 
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Gates MRI-RSM01-101 Protocol v4.0 
The SoA for the Dose Escalation Phase (Coho1ts 1-4) is presented in Table 2 and the SoA for the Expansion Phase (Coho1t 5) is 
presented in Table 3. 
Table 2: Schedule of Activities for the Dose Escalation Phase (Cohorts 1-4) 
Visits 
Study Day and Visit window days ( d) 
Activities: 
Informed consent 
Check/verify eligibility c1iteria 
Confinement1 
Demography, full medical history, PE, heicllt, weicllt 
Focused PE 
Sennn premancy test2 
HIV antibody and Hepatitis B & C test 
Urine drng screen 
Urinalysis 
Safety laboratory assessments3 
12-lead electrocardioeram (ECG), triplicate4 
Vital si2Us5 
Randomization6 
Study intervention administration7 
Distribute/review diarv cards 
Collect diary card 
Distribute memo1y aid 
Collect memory aid 
Record solicited AEs (local for IM doses only, & 
systemic) through Day 7 
Record unsolicited AEs, AESis, and SAEs 
Record concomitant medications 
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Screen 
D-30 to 
D-2d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pre- Vl V2 V3 
Vl 
D-1 Dl D2 
D3 
±Od ±Od ±Od ±Od 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
V4 
vs 
V6 
V7 
V8 
V9 
VlO 
Vll Dis-
con 
D6 
D8 
D15 
D29 
D61 
D91 D121 D151 Visit9 
±ld Day 8-10 ±3d Day 29-35 ±7d 
±7d 
±7d 
±7d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
17 


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Table 2 continued: Schedule of Activities for the Dose Escalation Phase (Cohorts 1-4) 
Visits Screen Pre- Vl V2 V3 
V4 
vs 
V6 
V7 
vs 
V9 V10 vn 
Vl 
Study Dav and Visit window days ( d) 
-30 to D-1 DI D2 D3 
D6 
D8 
D15 
D29 
D61 D91 D121 D151 
Activities: 
-2d 
±0d ±0d ±Od ±Id Day8-
±3d Day29- ±7d ±7d ±7d 
±7d 
10 
35 
Semm and V AMS sample for PK8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Sennn and V AMS sample for ADAs8 
X 
X 
X 
X 
X 
X 
X 
Sennn and V AMS sample for RSV nAb levels8 
X 
X 
X 
V = Visit; D= Day; PE= physical examination; HIV= Human immunodeficiency virus; IM= intramuscular; AE=adverse event, SAE=serious adverse event; 
AESI=AE of special interest 
PK= phannacokinetics; ADA = anti-dtug antibodies; V AMS = volumetric abso1ptive microsampling 
RSV mAb = Respiratory Syncytial Vims neutralizing antibody 
1 Confinement- pa1ticipants will be confined to study site from Day -1 to after completion of Day 3 assessment (a total of3 nights). 
All Day 1 assessments and sample collections are prior to study intervention. 
2 In addition to scheduled pregnancy tests in female pa1ticipants, if pregnancy is suspected during the study, a sernm test will be done. 
3 Safety laborato1y testing includes sernm chemistty and hematology. 
Dis-
con 
Visit9 
X 
X 
X 
4 All 12-lead ECGs will be obtained after the pa1ticipant has rested in a supine position for at least 10 minutes. Triplicate ECGs will be taken approximately one minute apart. 
Refer to Section 8.1.6 for details. The window for obtaining the initial ECG is± 15 minutes. 
5 Day 1 vital signs will be taken pre-dose before blood sample collection, and 1 hour, 4 hours and 8 hours after IM dose and at pre-dose, 15, 30 and 45 minutes, 1 hour, 1.5 
hours, 2 hours, 4 hours, and 8 hours after IV dose. The window for vital signs measurements is± 3 minutes. Refer to Section 8.1.2. l for details. 
On Day 2, vital signs will be taken at 24 hours post-dose. The window for these measurements is± 0.5 hours. 
On Day 3, vital signs will be taken at 48 hours after dosing. The window for these measurements is± 1.0 hours. 
6 The first participant in each coho1t (Coho1ts 1-4) will receive RSM0l without being randomized. 
7 On any given day, participants should be dosed at least 2 hours apa1t, after the first sentinel paiticipant is dosed v.iith RSM0l, and 24 hours has passed. 
The :C::2-hour wait time between IV infusions is to begin at the end of the previous infusion. 
8 Blood samples for PK assessments on Day 1 (Visit 1) will be drawn at pre-dosing 1 hour ( +/- 30 minutes) before adtninistt·ation of IM injection or beginning of infusion, at 
5 minutes(± 1 minute) after end of infusion for IV doses only, and at 8-hours (±0.5 how) and 24-hours (±1 how) after end of infusion for IV doses and at 8-hours (±0.5 how) 
and 24-hours (±1 how) after IM doses. 
ADA and RSV neutralizing antibody on Day 1 (Visit 1) will be drawn pre-dose only 1 hour(+/- 30 minutes) before administration ofIM injection or beginning of infusion. 
9 Early Discon= A discontinuation visit will be scheduled for participants who discontinue or withdt·aw, whenever possible. 
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Table 3: Schedule of Activities for the Expansion Phase (Cohort 5) 
Visits 
Screen 
Pre-Vl 
V l 
V2 
V3 
V 4 
Study Day and Visit window days (d) 
D-30 to 
Day -1 
Dl 
D8 
D29 
D91 
Activities: 
D-ld 
±0 
Days 
Days 
±7d 
8-10 
29-35 
Infonned consent 
X 
Check/verifv eligibilitv criteria 
X 
X 
X 
Confinement1 
X 
(X) 
Demography, full medical history, PE, height, weis4lt 
X 
Focused history!PE 
X 
X 
X 
X 
Senun pre211ancy test2 
X 
X 
HIV antibody, Hepatitis B and C 
X 
Urine dmg screen 
X 
X 
Urinalysis 
X 
X 
X 
X 
Safety laboratory assessments3 
X 
X 
X 
X 
12-lead ECG (performed in triplicate)4 
X 
Vital si211s5 
X 
X 
Randomization 
X 
Study intervention administration6 
X 
Distribute/review diary cards 
X 
Collect diary cards 
X 
Distribute memory aid 
X 
X 
X 
X 
Collect memory aid 
X 
X 
X 
Record solicited AEs (local & systemic) 
X 
Record unsolicited AEs, AESis and SAEs 
X 
X 
X 
X 
X 
X 
Record concomitant medications 
X 
X 
X 
X 
X 
Senun and V AMS sample for PK7 
X 
X 
X 
X 
Senun and V AMS sample for ADAs7 
X 
X 
X 
Senun and V AMS for RSV nAb levels 7 
X 
X 
V = Visit; D= Day; PE= physical examination; HIV= Human immunodeficiency vims; IM= intramuscular; 
AE=adverse event, SAE=serious adverse event; AESI=AE of special interest 
vs 
DlSl 
±7d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Discon 
visit8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1Confinement = participant should present to the clinic within 24 hours of Day -1 visit and will stay at the clinic on the Pre-Vl , 
Day -l(i.e., the night before the Day 1 visit). 
(X)= A second overnight stay for the night of Day 1 is optional, based on investigator's decision. If pa1ticipant is confined on the 
night of Day 1, vital signs will be taken 24 hours post-dose. 
PK= phannacokinetics; ADA = anti-dmg antibodies; V AMS = volumetric absorptive 1nicrosampling; 
RSV mAb = Respirato1y Syncytial Virus neutralizing antibody 
2 In addition to scheduled pregnancy tests in female pa1ticipants, if pregnancy is suspected at any time during the study, a serum 
test will be done. 
3 Safety laboratory assessments includes serum che1nistiy and hematology. 
4 12-lead ECGs will be obtained after the paiticipant has rested in a supine position for at least 10 minutes. Triplicate ECGs will 
be taken approximately one minute apart. Refer to Section 8.1.6 for details. 
5 Day 1 vital signs will be taken before dose and again 4 hours after dose. The window for vital signs measurements is ± 3 
minutes. Refer to Section 8.1.2. l for details. 
6 All Day 1 safety assessments and sample collections will be done prior to study intervention. Symptom assessments will be 
done after dosing. Following dose administration, if the participant will not be confined overnight for the optional night of Day 
1, they will be observed for at least 4 how·s at the study site after receiving the study intervention, for safety monitoring. 
7 Blood sainples for PK, ADA and RSV neutralizing antibody at Day 1 will be drawn at pre-dose only 1 hour ( +/- 30 
minutes) before administi·ation ofIM injection. 
8 Early Discon = A discontinuation visit will be scheduled for pa1ticipants who discontinue or withdraw, when possible. 
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2. 
Introduction 
2.1. RSV and Burden of Disease 
RSV is the most common pathogen identified in young children with acute LRTI. Most children 
acquire an RSV infection by the time they are 2 years old, causing a mild, cold-like illness within 
4 to 6 days after infection. However, in some children it leads to a more severe illness such as 
bronchiolitis and pneumonia and may also increase the risk of developing subsequent asthma 
and/or recurrent wheezing episodes in early childhood. The highest childhood RSV acute LRTI 
burden occurs during the first year of life when children are most vulnerable. 
RSV is a global disease that also places high burdens on the economy and health care services. 
Estimates show that approximately 33.1 million episodes occurred globally in 2015, resulting in 
about 3.2 million hospital admissions in children younger than 5 years, and 1.4 million 
hospitalizations in children younger than 6 months. Healthy term infants 3 months of age and 
younger account for more RSV-associated hospitalizations than any other age group. The 
hospital admission rate from RSV in LMICs is 15.9 per 1000 neonates per year with incidence 
rates being 3 times greater in preterm than term infants [Shi 2017]. 
Globally, there are approximately 120,000 RSV-associated acute LRTI deaths among children 
<5 years of age each year [Obando-Pacheco 2018] which account for a third of all LRTIs, with 
most deaths occurring in LMICs [Shi 2017]. Approximately 45% of in-hospital deaths due to 
RSV-associated acute LRTI occur in children younger than 6 months (median age of RSV-
related deaths is 4-7 months [Shi 2017, Scheltema 2017]), indicating that these infants constitute 
a critically important target group for prevention. However, the need for immediate protection 
and the difficulty of achieving protective efficacy via active immunization of these infants have 
refocused research efforts toward maternal immunization and passive immune-prophylaxis as 
key priorities. Either of these strategies could be followed with active infant immunization later 
in life as maternal/passive antibody titers wane [Higgins 2016]. 
The burden of RSV infection, especially among infants and young children, underscores the need 
for safe and effective prevention against RSV disease that is affordable in LMICs. 


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2.2. RSV Prevention- Monoclonal Antibodies 
There is an unmet medical need for an effective, durable, cost effective RSV prevention strategy 
for all infants and children. The World Health Organization (WHO) Product Development for 
Vaccines Advisory Committee (PDVAC) indicates that RSV immunoprophylaxis with a 
monoclonal antibody (mAb) is a priority intervention. There is no approved vaccine against RSV 
currently- the majority of candidates in clinical evaluation incorporate alternative antigens or 
constructs and target maternal or pediatric immunization strategies. 
Administration of a mAb directly to the infant at birth or at any time during the primary 
immunization series presents an attractive alternative to maternal immunization. The mAb would 
only need to be used in infants up to 6 months of age or those at risk of LRTIs during the local 
RSV season, which would reduce the overall programmatic cost of RSV disease prevention. 
Critical success factors intrinsic to a candidate mAb include high potency, product safety, high 
barrier to virus resistance, and stability / PK that gives adequate duration of protection. 
There is one approved RSV mAb, palivizumab, which is indicated for the prevention of serious 
LRTI caused by RSV and has been used in the past 2 decades. Palivizumab is an RSV fusion 
(F)-specific immunoglobulin G monoclonal antibody (Synagis®, Swedish Orphan Biovitrum) 
that requires monthly injections and is cost prohibitive for LMICs. It is approved for use in high-
risk children, including 1) preterm infants born at ≤ 35 weeks gestational age and who are ≤ 6 
months old at the beginning of RSV season; 2) children with bronchopulmonary dysplasia that 
required medical treatment within the previous 6 months and who are ≤ 24 months old at the 
beginning of RSV season; and 3) children with hemodynamically significant congenital heart 
disease and who are ≤ 24 months old at the beginning of RSV season. Among preterm infants, 
the American Academy of Pediatrics issued an updated guidance in 2014 to limit its 
recommendation for palivizumab to preterm infants born before 29 weeks gestational age and 
who are ≤ 12 months old, who would most likely benefit from this preventive agent [Brady, 
2014]. 
Motavizumab, a derivative of palivizumab with higher affinity for RSV, was not pursued by 
MedImmune for licensure after the Phase 3 trial failed to secure FDA approval for lack of clear 
superiority to palivizumab and a trend for a higher rate of skin rash [Feltes, 2011]. A mAb 
manufactured by Regeneron (REGN2222 or suptavumab) did not meet efficacy endpoints in 
Phase 3, and clinical development was also discontinued. This was due to escape mutants in the 
predominantly circulating RSV B that affected the overall performance of REGN2222 [Simões 
2020]. 
Two other RSV mAbs are in clinical development, with MEDI8897 (nirsevimab), being the most 
advanced. Nirsevimab binds to the same antigenic site Ø of RSV prefusion F but different 
epitope than RSM01. In a Phase 2b trial of 1453 premature infants 29- to 34-week gestational 
age who were ≤1 year old, nirsevimab administration reduced the incidence of RSV-associated 
medically-attended LRTI by 70% and hospitalizations by 78% compared to Placebo [Griffin 
2020]. The nirsevimab program has initiated enrollment of a Phase 2b/3 in preterm infants ≤35 
weeks gestational age with either chronic lung diseases or congenital heart disease or 
bronchopulmonary dysplasia [Clinicaltrials.gov NCT No. 03959488], and a Phase 3 study in 
term and late preterm infants ≥35 weeks gestational age [Clinicaltrials.gov NCT No. 03979313]. 


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The primary endpoint of a statistically significant reduction in the incidence of medically-
attended RSV LRTIs was met in this trial [AstraZeneca 2021]. 
The other RSV mAb candidate, MK-1654, targets site IV of the RSV pre- and post-fusion F. A 
Phase 2 study of safety and PK study in infants is ongoing [Clinicaltrials.gov NCT No. 
03524118]. An RSV challenge study in healthy adults was completed in August 2020 and no 
results are available to date [Clinicaltrials.gov NCT No. 04086472]. However, these mAb 
candidates in development are targeted primarily for high-income countries, with costs likely too 
high to allow affordable global access to the product. 
Evidence from the Novavax maternal RSV F nanoparticles vaccine trial suggests that prevention 
of RSV early in life can also result in 25% reduction in all-cause LRTI hospitalization up to one 
year of age [Madhi 2020]. An efficacious RSV immunization product could have significant 
public health impact in preventing pneumonia deaths in young infants, with potential benefits 
that may extend longer. 
2.3. RSM01 mAb Candidate 
RSM01(also designated as ADI-15618-IVNS YTE) is a fully human IgG1 neutralizing 
monoclonal antibody that targets site Ø (zero) of the prefusion conformation of the RSV F 
glycoprotein (pre-F), which has high neutralizing potency. RSM01 has a molecular weight of 
approximately 150 kilodaltons. 
RSM01 has the same half-life extension YTE mutation (M252Y/S254T/T256E, European Union 
numbering) in its crystallizable fragment (Fc) domain as 2 other next generation RSV mAb 
candidates, Merck’s MK-1654 and AstraZeneca’s nirsevimab, which are being evaluated in 
Phase 2 and 3 clinical trials, respectively. Both have a favorable safety profile in previous 
clinical trials [Aliprantis 2020, Griffin 2017], and nirsevimab was shown to reduce the incidence 
of RSV-associated medically-attended LRTI and hospitalizations in a Phase 2b study [Griffin 
2020]. 
2.3.1. 
Non-Clinical Development of RSM01 
The non-clinical development of RSM01 focused on non-clinical safety studies in rats and 
monkeys, in vitro potency against RSV A and B assessments and efficacy studies in a cotton rat 
RSV challenge model. These studies are considered sufficient to support entry into Phase 1 FiH 
study in adults, followed by age de-escalation into a Phase 1b/2a study in infants. 
The non-clinical pivotal safety package for RSM01 conducted to support FiH studies consists of 
a 4-week Good Laboratory Practice (GLP) study in monkeys and a cross-reactivity GLP study in 
human tissues. 


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Overall, RSM01 was well-tolerated in non-GLP single dose studies in rats and monkeys, and in a 
4-week repeat-dose GLP study in cynomolgus monkeys. In the 4-week study, RSM01 was 
administered weekly plus one for a total of 5 doses at 30, 100, and 300 mg/kg, IV and at 100 mg 
total dose in 1mL, IM. There were no identified target organs of toxicity or test-article-related 
adverse local reactions; there were also no test-article-related effects on the cardiovascular, 
respiratory or the central nervous systems at all doses The No-Observed-Adverse-Effect-Level 
(NOAEL) in the 4-week study was 300 mg/kg/dose, IV (area under the curve [AUC]0-
168h :1,420,000 µg*h/mL; C0: 11,900 µg/mL) and 100 mg/dose, IM (AUC0-168h :264,000 µg 
*h/mL; maximum plasma concentration [Cmax]:1760 µg/mL). A tissue cross-reactivity study with 
biotinylated RSM01 found no risk for off-target binding of RSM01 in human tissues. The non-
clinical safety profile of RSM01 supports dosing of humans in Phase I clinical trials. No local 
toxicity was observed in monkeys following IM administration at the same concentration of 
mAb (approximately 100 mg/mL) intended for use in humans. 
The NOAEL of 300 mg/kg, IV supports a Maximum Recommended Starting Dose (MRSD) of 
582 mg [FDA 2005] with an applied safety factor of 10. This supports the proposed starting dose 
of 300 mg, IV, in adults. 
In vitro cell-based neutralization studies showed that RSM01 performed as well or better than 
other RSV mAbs to neutralize both RSV A and RSV B clinical isolates including important 
sequence variants that are critical for epitope binding. RSM01 potency was comparable to that of 
nirsevimab and more potent than REGN2222 and palivizumab. 
In cotton rat challenge studies, RSM01 reduced lung and nasal viral titers in a dose-dependent 
manner. Protection in the lower respiratory tract upon challenge with RSV A and B was greater 
with RSM01 compared to palivizumab. 
In summary, there were no test-article related target organ toxicities, no effects on vital systems, 
and no adverse local reactions reported in non-clinical safety studies. RSM01 demonstrated a 
favorable efficacy and safety profile supporting its progression for clinical development to 
prevent RSV disease. 
2.4. Study Rationale 
The burden of RSV infection, especially among infants and young children underscores the need 
for safe and effective prevention against RSV disease that is affordable in LMICs. The goal of 
the clinical development program for RSM01 is to develop a safe, effective, affordable mAb to 
prevent severe RSV disease in infants in LMICs. The clinical development approach for RSM01 
is to first study a wide dose range in healthy adults to assess safety and to cover target exposures 
in infants that will allow for pharmacokinetic (PK)/pharmacodynamic (PD) modeling to provide 
confidence in predicting efficacious doses in infants. 
Refer to Section 2.5 for justification of dose levels. 
2.5. Justification for Dose 
2.5.1. 
Doses for Escalation Phase Cohorts 
The selection of the dosing strategy for dose escalation is based on non-clinical safety data and in 
vivo pharmacological evaluation in the cotton rat RSV prophylactic model. This approach is 


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supported by assessments of the PK profile of other RSV mAbs with YTE mutations. The wide 
dose range, from 300mg to 3000mg, in healthy adults would cover target exposures in infants 
and support PK/PD modeling to predict infant dosing. 
RSM01 and nirsevimab were evaluated in the RSV cotton rat model. Collectively, the conclusion 
from those experiments is that the EC90s for RSM01 is similar to nirsevimab in term of PK/lung 
RSV titers. In the literature, nirsevimab has been reported to have a EC90 of 6.8 µg/mL [Zhu 
2017]. 
The human PK exposure of RSM01 in healthy participants was projected based on extrapolation 
made from the non-human primate PK in the toxicology studies and published reports of the PK 
characteristics of competitor monoclonal antibodies (nirsevimab and MK-1654) in healthy 
volunteers. 
These projections suggest that following RSM01 doses of ≥ 300 mg the RSM01 concentration is 
predicted to be above the target EC90 threshold at Day 151. 
RSM01 was well-tolerated in a definitive study in monkeys with a NOAEL of 300 mg/kg/dose 
or 100 mg/dose following IV or IM administration, respectively. The NOAEL at 300 mg/kg, IV, 
provided safety margins of approximately 10-fold and 1.1-fold to the starting dose of 300 mg IV 
and ending dose of 3000 mg IV, respectively, based on predicted human AUC. There were no 
test-article-related local reactions following administration of 100 mg/mL of RSM01 by IM 
injection in monkeys, which supports dosing of 600 mg, IM in humans at 100 mg/mL of RSM01. 
Safety and PK data from the FiH study in adults are required to support proceeding to the target 
population of infants. The wide fixed-dose ranges to be tested in healthy adults will cover the 
anticipated target exposures in infants. The 300 mg dose in adults is estimated to correspond to 
the target dose of 50 mg in infants. Importantly, the maximum dose for the escalation cohorts 
(3000 mg IV) and the maximum dose for the Expansion Phase cohort (600mg IM) will provide 
necessary safety information to inform selection of doses in infants. 
2.5.2. 
Dose for Expansion Phase Cohort 
Final selection of the dose to be administered to Cohort 5 will be made by the sponsor and 
informed by available RSM01 PK data, as well as relevant safety data, from the Dose Escalation 
Phase. 
Available interim PK data from the Dose Escalation Phase cohorts, combined with published 
data from previous studies of monoclonal antibodies, will be used to develop a population PK 
model to describe the individual concentration time profiles of RSM01. Subsequently, the model 
will be used in a simulation mode to predict the proportion of participants that are expected to 
have RSM01 concentrations above the EC90 on Day 151. 
The tentatively determined dose to be tested in the Dose Expansion Phase cohort is ≥300 mg and 
≤600 mg IM, based on available pre-clinical and clinical PK data from nirsevimab and MK-1654 
(Griffin 2017, Aliprantis 2020). The 600mg IM dose in adults is expected to provide additional 
margin for meeting the EC90 threshold at Day 151, even in the case that the t1/2 of RSM01 is 
shorter than those of nirsevimab and MK-1654. It will also provide additional information for 
infant dose selection for the planned Phase 1b/2a study. 


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The 600 mg IM dose is anticipated to be equivalent to the maximum possible infant dose of 
100mg IM (based primarily on the IM volume constraint of 1mL). 
2.6. Benefit/Risk Assessment 
The non-clinical safety of RSM01 has been evaluated in GLP-compliant studies in monkeys of 
up to 4 weeks in duration. RSM01 was well-tolerated at all doses tested; there were no test-
article related target organ toxicities, no effects on vital systems, and no adverse local reactions. 
Juvenile monkeys are commonly used in toxicology studies including studies conducted with 
RSM01. A tissue cross-reactivity study with biotinylated RSM01 found no risk for off-target 
binding of RSM01 in human tissues. 
Clinical risks and benefits have not been established for RSM01 when administered to humans. 
However, it is expected that RSM01 will have a similar benefit/risk profile to nirsevimab. 
There have not been safety concerns identified to date from the 3 clinical trials of nirsevimab that 
had 102 adults and 1039 infants exposed to nirsevimab. No SAE related to the compound 
occurred during these studies. A Phase 1 FiH study in adults in the U.S. evaluated a single dose 
of nirsevimab or Placebo administered as an IV dose of 300mg, 1000mg, or 3000mg or as an IM 
dose of 100mg or 300mg [Griffin, 2017] and did not have any study discontinuations due to AEs 
or SAEs. The most frequently reported nirsevimab-related AEs were headaches (all mild), 
occurring in 3 (2.9%) participants. The safety profile was similar to that of the Placebo. 
In the second clinical trial, a Phase 1b/2a study evaluated a single IM dose of 10mg, 25mg or 
50mg of nirsevimab or Placebo in infants in the U.S., South Africa, and Chile [Domachowske, 
2018]. Five infants (7.0%) who received nirsevimab experienced product-related AEs, which 
included nasal congestion, pyrexia, gastroenteritis, upper respiratory tract infection and wheezing 
(all Grade 1), and 5 experienced medically-attended LRTIs through Day 150; 1 tested positive 
for RSV (10mg group). 
In the third clinical trial, a Phase 2b study evaluated a single dose of 50mg IM of nirsevimab vs. 
Placebo in 1453 healthy preterm infants (29-34 weeks gestational age, aged 0-12 months). 
Through Day 150 of follow-up, AEs occurred at similar frequencies between the mAb (804/968, 
83%) vs. the Placebo (402/479, 83.9%) groups. SAEs were reported in 108/968 (11.1%) mAb vs. 
81/479 (16.9%) Placebo recipients, and none were considered related to study drug. AESIs 
related to study drug were reported in 5/968 (0.5%) in nirsevimab vs. 3/484 (0.6%) in Placebo. 
There were no anaphylaxis or other notable hypersensitivity reactions. In the nirsevimab group, 4 
infants experienced rash. One infant experienced one day of petechiae occurring 4 months after 
nirsevimab, which was not assessed by a health care provider. All 3 AESI infants in the Placebo 
group had rash. 
AEs attributed to ADAs have not been observed in the nirsevimab trials. In the Phase 1 adult 
trial, ADA occurred at a similar frequency in the mAb and Placebo groups. At the baseline visit, 
5/103 (4.9%) mAb vs. 3/34 (8.8%) Placebo recipients had ADA. During post-dose visits, 14/102 
(13.7%) mAb vs. 5/33 (15.2%) Placebo recipients had ADA. In the nirsevimab Phase 1b/2a 
infant trial none had ADA at baseline and only the mAb group had ADA at post baseline (20/71, 
28.2%) vs. 0/17 in the Placebo group. Aside from 2 infants with transient positive ADA at day 
50, all positive ADAs occurred after the intended coverage duration of 150 days. ADA did not 
impact safety but lowered the drug exposure between days 150 to 360 in some infants. 


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The Phase 1 MK-1654 study randomized 152 healthy adults in a 3:1 ratio to MK-1654 (100mg 
IM, 300mg IM, 300mg IV, 1000mg IV and 3000mg IV) vs. Placebo. The overall safety profile 
of MK‐1654 was similar to that of Placebo. No deaths, SAEs, discontinuations due to AEs, 
clinically significant laboratory AEs, or dose-dependent pattern of drug-related AEs were 
reported [Aliprantis 2020]. 
RSV Mutations 
RSV belongs to the class of ribonucleic acid (RNA) viruses and as such possesses an error-prone 
RNA polymerase. This raises potential concerns about the emergence of antibody resistant 
escape mutants. This is especially relevant for mAb that are considered for wide-spread use and 
target a single epitope on the viral surface. Zhu, et al published data on RSV escape variants 
against nirsevimab, a highly potent, next generation anti-RSV-F antibody that also binds to 
antigenic site Ø that is currently under clinical investigation [Zhu 2018]. 
Escape mutant selection studies with RSM01 were performed by the former sponsor, Arsanis 
(Vienna, Austria). A total of 11 escape mutant selection studies were conducted by Arsanis 
during the selection phase of RSM01. Although previously identified antibody resistant mutants 
against palivizumab and nirsevimab were obtained, not a single resistance associated mutation 
was identified for RSM01, parental mAb 15618, or additional 15618 variants. The data suggest 
that the epitope of RSM01 is more stable and less prone to amino acid substitutions under 
selective pressure compared to nirsevimab. This is interesting since RSM01 and nirsevimab bind 
to the same antigenic site (epitopes differ) on the F protein and have largely comparable 
neutralization potency based on in vitro and in vivo virus neutralization assays. RSM01 
maintained anti-viral activity against a nirsevimab resistant strain, RSV-B9320 N208D [Rouha 
2018]. 
In vitro cell-based neutralization studies showed that RSM01 performed better than other RSV 
monoclonal antibodies palivizumab and REGN222 to neutralize both RSV A and RSV B strains 
including important sequence variants. RSM01 potency was comparable to that of nirsevimab. 
General Risks with MAb Infusion 
Administration of any mAb may carry a risk of immune reactions such as acute anaphylaxis, 
serum sickness and the generation of antibodies against the mAb. However, these reactions are 
rare and more often associated with mAbs targeted to human proteins or with the use of murine 
monoclonal antibodies, which would have a risk of human anti-mouse antibodies. In this regard, 
as RSM01 is targeted to a viral antigen, is a fully human mAb (IgG1), and is expected to have a 
low risk of such side effects. 
Typically, the side effects of mAbs are mild but may include fever, chills, rigors, nausea, 
vomiting, pain, headache, dizziness, shortness of breath, bronchospasm, hypotension, 
hypertension, pruritus, rash, urticaria, angioedema, diarrhea, tachycardia, or chest pain. 
Most infusion-related events occur within the first 24 hours after beginning administration. 
Severe reactions, such as anaphylaxis, angioedema, bronchospasm, hypotension, and hypoxia, 
are infrequent and more often associated with mAbs targeted to human proteins and not 
pathogen-directed human mAbs like RSM01. Immediate infusion reaction is managed by 
temporarily stopping the infusion, administration of histamine blockers and restarting the 
infusion at a slower rate [Vogel 2010]. Delayed allergic reactions to a mAb may include a serum 


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sickness type of reaction, which is characterized by urticaria, fever, lymph node enlargement, 
and joint pains. These symptoms may not appear until several days after the exposure to the mAb 
and are noted to be more common with non-human/human chimeric types of mAbs [Hansel 
2010]. Antibodies containing the YTE mutations in the Fc region have been safe and well-
tolerated in humans [Robbie 2013, Aliprantis 2020, Griffin 2020]. 
No direct benefits are anticipated for the healthy adults enrolled in this Phase 1 study. RSM01is 
expected to have favorable safety profile based on experience with other fully human 
monoclonal antibodies targeting various viruses (e.g., anti-HIV, anti-influenza, and anti-RSV). 
3. 
Objectives and Endpoints 
Table 4: Objectives and Endpoints 
Objectives 
Endpoints (Endpoints apply to all cohorts unless noted) 
Primary 
To characterize the safety and 
tolerability of a single dose of 
RSM01  
• Unsolicited AEs through Day 151 
• All serious adverse events (SAEs) and AESIs through 
Day 151 
• Solicited systemic AEs for 7 days after dose 
administration 
• Solicited local AEs for injection site reactions for 7 
days after dose administration (only applies to IM 
doses) 
Secondary 
To characterize safety laboratory 
parameters following RSM01 
administration 
• Safety laboratory parameters Grade 1 and above 
through Day 151 
To characterize the 
pharmacokinetics (PK) following 
RSM01 administration  
PK parameters including: 
• Area under the capillary blood-concentration time 
curve from zero to infinity (AUC0-∞) 
• Day 91 capillary blood-concentration and area under 
the capillary blood-concentration time curve (CD91 and 
AUC0-D91) 
• Day 151 capillary blood-concentration and area under 
the capillary blood-concentration time curve (CD151 and 
AUC0-D151) 
• Cmax following IM administration and C0 following IV 
administration), Cmin 
• Tmax and t1/2 
• CL 
• Vz of RSM01 through Day 151 
To characterize the formation of 
ADAs following RSM01 
administration 
• Incidence of ADAs to RSM01 through Day 151 


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Exploratory 
 To characterize RSV neutralizing 
antibody activity following 
RSM01 administration 
• Capillary blood RSV neutralizing antibody levels 
through Day 151 
 
4. 
Study Design 
4.1. Design Overview 
Overall Design 
Disclosure statement: This is a FiH trial of RSM01, administered to adults. It is a randomized, 
double-blind, placebo-controlled study of RSM01. 
Study Population and Number of Participants: Adult participants between 18 and 49 years of 
age (inclusive) of both sexes who are capable of and willing to provide informed consent may be 
eligible for the study. The complete list of inclusion and exclusion criteria can be found in 
Section 5.1and Section 5.2, respectively. 
Candidates will be screened to enroll 56 eligible participants. 
Assuming that all cohorts are allowed to undergo treatment, approximately 48 participants will 
receive RSM01 and approximately 8 will receive Placebo. 
Interventional model: The study will be conducted in 2 parts: A Dose Escalation Phase (N=28) 
with 4 dosing cohorts, followed by an Expansion Phase (N=28) with a single cohort. 
Dose Escalation Phase: 
The first participant in each Dose Escalation Phase cohort will not be randomized and will 
receive the RSM01 dose level appropriate to assigned cohort to serve as a sentinel exposure 
(refer to Section 8.1.1). 
The remaining 6 participants in each of Cohorts 1, 2, 3, and 4 will be randomized 5:1 to receive 
either RSM01 or Placebo. The overall ratio of RSM01 to Placebo will be 6:1 in each cohort. 
The Dose Escalation Phase will occur sequentially in 2 escalation steps. 
• 
Cohort 1: 7 participants will receive RSM01 300mg IV (n=6 total including sentinel 
participant) or Placebo IV (n=1) 
First escalation step: from Cohort 1 to Cohorts 2 and 3, conducted in parallel 
• 
Cohort 2: 7 participants will receive RSM01 300mg IM (n=6 total including sentinel 
participant) or Placebo IM (n=1) 
• 
Cohort 3: 7 participants to receive RSM01 1000mg IV (n=6 total including sentinel 
participant) or Placebo IV (n=1) 


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Second escalation step: from Cohorts 2 and 3 to Cohort 4 
• 
Cohort 4: 7 participants will receive RSM01 3000mg IV (n=6 total including sentinel 
participant) or Placebo IV (n=1). 
For the Dose Escalation Phase cohorts, all participants will be confined at the study site from 
Day -1 (i.e., the day before dosing) to after completion of the Day 3 assessments (a total of 3 
nights). 
Dose Escalation Phase, continued: 
After the sentinel participant in each cohort receives RSM01, the next participant can be dosed 
24 hours later, if there is no safety concern. 
After the 24-hour post-dose period for the sentinel participant in each Dose Escalation Phase 
cohort, participants in the Dose Escalation Phase cohorts should be dosed at least 2 hours apart 
regardless of route of administration (IM or IV). The ≥2-hour interval between administering IV 
infusions is to begin at the end of the previous infusion. 
For participants receiving the IM dose of study drug in Cohort 2, the ≥2-hour interval between 
administering IM injections to successive participants is to begin at the time of the previous 
participant’s IM injection. If RSM01 is administered using 2 injections, the ≥2-hour interval 
begins at the time of the second injection. 
Each dose escalation step will proceed after all participants the prior cohort have completed Day 
15, and the SRT has reviewed the data and determined that a pausing rule has not been met. 
Refer to Section 8.2.6 for details regarding the SRT. 
Dose Expansion Phase: 
Enrollment in the Dose Expansion Phase (Cohort 5) will begin after Day 15 for participants in 
Cohort 4, and after the SRT has reviewed the data and determined that a pausing rule has not 
been met. Cohort 5 will include 28 participants randomized 6:1. 
• 
Cohort 5: participants will receive RSM01 IM (n=24) or Placebo IM (n=4). 
For Cohort 5, participants will be asked to present to the clinic within 24 hours of the Day 1 visit 
for Day -1 (Pre-V1) confinement. 
On Day 1 after dosing, participants will be observed for at least 4 hours post-dose at the study 
site for safety monitoring. Based on investigator’s decision, a participant may be asked to remain 
at the study site, for an additional overnight stay on the night of Day 1. 
Final selection of the dose of RSM01 to be administered to Cohort 5 will be made by the sponsor 
and informed by available RSM01 PK data from the Dose Escalation Phase. 
The tentatively determined dose to be evaluated in the Expansion Phase cohort is ≥300 mg to 
≤600 mg IM. This determination is based on predictions of RSM01 human PK exposures made 
using extrapolation from the RSM01 non-human primate PK and on published data from the 
other mAbs nirsevimab and MK-1654 administered to healthy adults [Griffin 2017, Aliprantis 
2020]. The predictions suggest that the concentration of RSM01 will be above the efficacy 
threshold (EC90) on Day 151 following a RSM01dose of either 300 or 600 mg IM. Refer to 
Section 2.5.2 for dose justification. 


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Pausing rules: Refer to Section 7.1.1 
SRT and IDMC: Refer to Sections 8.2.6 and 8.2.7 for information regarding the SRT and 
IDMC, respectively. 
Visits: The study Schema is shown in Figure 1: Outline of Study Dosing Procedures and the SoA 
is shown in Table 2 and Table 3, Dose Escalation Phase and Dose Expansion Phase, respectively. 
Blood Sampling: Refer to Section 8.4. 
Masking: Refer to Section 6.5.2. 
Analyses: An interim analysis will occur after all participants in the Dose Escalation Phase 
cohorts 1-4 have reached Day 91. The primary analysis will occur after all participants in all 5 
cohorts complete Day 151. Refer to Section 9. 
Total duration of study participation: The study duration for each participant is 151 days, in 
addition to a maximum 30 days for screening and Day -1. 
Study site/s: The study will be conducted in at least 1 site in the U.S. 
4.2. End of Study Definition 
A participant is considered to have completed the study if he/she completes the final visit at Day 
151. 
The end of the study is defined as the date of the last visit of the last participant in the study or 
conduct of the last scheduled procedure shown in the SoA for the last participant in the trial. 
5. 
Study Population 
A total of 56 eligible, healthy adult participants between 18 and 49 years of age (inclusive) of 
both sexes who are capable of and willing to provide informed consent will be eligible for the 
study. See Section 5.1 and 5.2 for inclusion and exclusion criteria, respectively. Candidates will 
be screened for eligibility to enroll. 
Prospective approval of deviations to recruitment and protocol enrollment criteria, also known as 
protocol waivers or exemptions, will not be permitted. 
Recruitment 
All recruitment materials will be approved by the appropriate Institutional Review Board/s 
(IRBs) or Independent Ethics Committee/s (IECs). Interested participants will be invited to 
participate in the informed consent process. 
Various methods of recruitment may be used, such as site databases, advertising, referrals, word-
of mouth, or other approved means. 


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5.1. Inclusion Criteria 
Age 
1. Participant must be 18 to 49 years of age (inclusive) at the time of signing the informed 
consent 
Type of Participant and Disease Characteristics 
2. Participants who are healthy as determined by medical evaluation including medical history, 
physical examination, and laboratory tests 
Weight 
3. Body mass index (BMI) 18 to 29.9 kg/m2 (inclusive) 
Sex 
4. Both males and females are eligible to participate. 
Male participants with partners of childbearing potential must agree to use condoms during 
their participation in the study and for 90 days after the participant completes the study. 
Male participants must also agree to refrain from sperm donation for at least 90 days after 
they complete the study. 
Female participants of childbearing potential must not be pregnant, breastfeeding, or 
attempting to become pregnant for 28 days before Screening and throughout the duration of 
their participation in the study. These participants must have a negative serum pregnancy 
test at Screening in order to be eligible for randomization and treatment with study 
intervention. In addition, female participants must be willing to commit to using a consistent 
and acceptable method of contraception for the duration of their participation in the study 
and for 90 days after they complete the study if they engage in intercourse. Acceptable 
methods of contraception are: 
• 
Consistent use of systemic contraception, including birth control pills, transdermal 
patch, vaginal ring, implants, and injectables. 
• 
Consistent use of double barrier method, e.g., condoms, cervical cap, diaphragm, 
vaginal contraceptive film with spermicide. 
• 
Use of intrauterine device with a low failure rate (defined as < 1% risk of pregnancy 
per year) 
• 
Monogamous intercourse with a vasectomized man or has only same-sex partners. 
Female participants who are not sexually active but become so during the study must agree 
to follow the contraceptive requirements above. 
Female participants who are not of childbearing potential must meet at least one of the 
following criteria: 
• 
At least 1 year since the last menstrual period. 
• 
Surgically sterile (tubal ligation, bilateral oophorectomy, salpingectomy, or 
hysterectomy) 
• 
Congenitally sterile 


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• 
Diagnosed as infertile and not undergoing treatment to reverse infertility. 
Refer to Appendix 10.3 for more information. 
Informed Consent 
5. Capable of giving signed informed consent which includes compliance with the requirements 
and restrictions listed in the informed consent form (ICF) and in this protocol 
Additional Requirements: 
6. Participants must agree to stay in contact with the study site for the duration of the study, 
provide updated contact information as necessary, and have no current plans to relocate from 
the study area for the duration of the study. 
5.2. Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Acute illness and/or body temperature ≥37.5°C or ≥99.5°F on Study Day 1 (refer to Section 
5.4 for additional details). NOTE: This is a temporary exclusion for which the participant 
may be re-evaluated. 
2. Evidence and/or history of clinically significant medical condition(s) as judged by the 
investigator, including malignancies, diabetes mellitus, and unstable or uncontrolled 
hypertension 
3. History of any autoimmune disease or immune deficiency or other impairment to the immune 
system, including but not limited to HIV, autoimmune conditions, or immunosuppressive 
therapy. Note: history of Hashimoto’s thyroiditis is not an exclusion criterion. 
4. History of anaphylaxis 
5. Any current medical, psychiatric, occupational, or substance abuse problems that, in the 
opinion of the investigator, will make it unlikely that the participant will comply with the 
protocol 
Prior/Concomitant Therapy 
6. Receiving or plan to receive any medications or other therapies that may impact the immune 
system such as allergy injections, interferon, immunomodulators, cytotoxic drugs or other 
drugs known to be frequently associated with major organ toxicity within 90 days prior to 
Day 1. 
7. Having received any vaccination (including COVID-19 vaccine) within the 15 days before 
Day 1, or planning to receive a dose of any vaccine during the 15-day period following Day 
1. 
8. Receiving or plan to receive immunosuppressive agents including systemic steroids within 
90 days prior to Day 1 (individuals using inhaled or topical corticosteroids, prednisone (or 
equivalent) dose of ≤ 20 mg/day for ≤ 14 days, and intra-articular corticosteroids are 
permitted) 


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9. Receipt or donation of blood or blood products within 90 days prior to Day 1 or planned 
receipt or donation during the study period 
10. Receiving or plan to receive antibody or biologic therapy within 180 days prior to Day 1 or 
any time during the study period, whether licensed or investigational (e.g., immunoglobulin 
products, monoclonal antibodies, or antibody fragments). 
Prior/Concurrent Clinical Study Experience 
11. Participation in an interventional clinical trial and/or receipt of any investigational drug 
within 30 days or 5 half-lives of the investigational drug before the first day of study drug 
dosing in this study, whichever is longer 
12. Concurrent enrollment in another interventional study 
13. Previously having participated and received study intervention in the current study. 
Diagnostic Assessments 
14. Female participants: positive serum pregnancy test 
15. Safety laboratory values outside of normal range, for age and sex that are suggestive of a 
disease state (Grade 1 abnormalities will not lead to exclusion if the investigator considers 
them not clinically significant.) 
16. Urinalysis abnormality greater than Grade 1 (with the exception of hematuria in a 
menstruating female), or urinalysis abnormality judged clinically significant by the 
investigator 
17. Clinically significant ECG abnormalities 
18. Reactive HIV antibody testing 
19. Current hepatitis B and/or hepatitis C infection 
20. Positive urine drug screen at screening or Day-1 (with the exception of prescribed drugs). 
Other Exclusions 
21. History of allergy or hypersensitivity to the study drug, excipients or related substances 
22. Female participants with any one of the following conditions: currently pregnant or 
lactating/nursing; having positive serum pregnancy test during the Screening Phase, planning 
a pregnancy within 1 year after first dose of study drug (Refer to Appendix 3, Section 10.3) 
23. Individuals who are acting as study personnel or immediate family members (brother, sister, 
child, parent) or the spouse/partner of study personnel. 
5.3. Lifestyle Considerations 
No restrictions are required. 


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5.4. Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered into the study and do not receive study intervention. A minimal set of 
screen failure information is required to ensure transparent reporting of criteria for participants 
who are screen failures in order 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 not met, and 
any SAE. 
Rescreening assessments as outlined below may be performed after obtaining informed consent, 
which must be completed prior to any rescreening procedure. 
Rescreening is only permitted under one or more of the following scenarios: 
• 
If a participant presents with an acute illness on the day of planned study intervention, e.g., 
elevated temperature, acute respiratory or gastrointestinal illness, or urinary tract infection 
(UTI), and meets all other eligibility criteria and can be rescreened within the originally 
defined screening window (SoA, Section 1.3). A new participant number is not required. If 
the participant is rescreened during the original screening window, obtaining a second 
informed consent of the participant is not required.  
• 
If there are technical difficulties with phlebotomy at screening (e.g., laboratory reports 
hemolyzed blood), technical error in running the laboratory tests or an abnormal urine 
analysis due to menstruation or UTI, and the participant can be rescreened within the 
originally defined screening window (SoA, Section 1.3). A new participant number is not 
required. If the participant is rescreened during the original screening window, obtaining a 
second informed consent of the participant is not required.  
• 
If a participant is undergoing screening and the study reaches a pausing rule. The participant 
may be rescreened when and if the IDMC recommends, and the Sponsor determines, that the 
study may continue. A new participant number is not required. If the participant is 
rescreened during the original screening window, obtaining a second informed consent of 
the participant is not required. 
• 
If a participant fails to meet eligibility criteria upon initial screening, a one-time only 
rescreening for eligibility may be performed. In this case, the participant must be given a 
new participant number after signing a new informed consent. 


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6. 
Study Intervention 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
Placebo, or medical device(s) intended to be administered to a study participant according to the 
study protocol. 
Two interventions will be used in this study: participants will receive either RSM01 or Placebo 
based on randomization as described in Study Design, Section 4. 
Participants in the Dose Escalation Phase cohorts will receive a single dose of either 300mg IV, 
1000mg IV, 3000mg IV or 300mg IM, of RSM01, or Placebo. 
The Expansion Phase cohort will receive a single dose of RSM01 IM or Placebo. The RSM01 
dose will be selected based on review of available PK data from prior cohorts, as well as relevant 
safety data. 
Table 5: Study Interventions 
 
RSM01 Drug Product 
Placebo (Control) 
Intervention 
RSM01 (RSV F neutralizing 
monoclonal antibody) 
Matching formulation buffer 
without API RSM01 
Unit-Dose Strength 
100mg/mL 
N/A  
 Dose Escalation Phase cohorts 
Dosage, Volume and 
Route of 
Administration  
300mg (53mL) IV infusion 
1000mg (60mL) IV infusion 
3000mg (130mL) IV infusion 
300mg (3 mL) IM injection (1 
injection in the anterolateral thigh 
muscle) 
Same volume and number of 
infusions/injections as the 
RSM01 group. 
 Dose Expansion Phase Cohort 
Dosage, Volume and 
Route of 
Administration 
Dose to be determined. Route of 
administration will be IM in the 
anterolateral thigh muscle. 
Same volume and number of 
injections as the RSM01 
group. 
6.1. RSM01 Drug Product 
The RSM01 Drug Product (RSM01) used in this study is manufactured by Just-Evotec Biologics, 
Inc. RSM01 is supplied as a liquid in a single use, sterile filled glass vial at a product 
concentration of 100mg/mL, and 100mg/vial configuration. The volume injected or infused will 
vary depending on the cohort. 
Each vial contains an isotonic, sterile solution that is a colorless to yellow liquid, essentially free 
of visible particles; some opaque or translucent particles may be present. Refer to Pharmacy 
manual for details. 


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6.2. Placebo Drug Product 
The RSM01 Placebo Drug Product (Placebo) control consists of all the excipients without the 
mAb, in the same type of vial/cap/seal fill as the RSM01 presentation. The volume injected or 
infused will depend on the randomized group and will be the same as the volume of the RSM01 
administered to participants within each respective cohort. 
Each vial contains an isotonic, sterile solution that is a colorless to yellow liquid, essentially free 
of visible particles; some opaque or translucent particles may be present. Refer to Pharmacy 
manual for details. 
 
 
6.3. Study Intervention Preparation and Administration 
Refer to Section 4.1 for dose administration within each cohort and Section 6.4 for handling, 
storage, and accountability. 
Unit-dose syringes will be provided for IM administration, and infusion bags for IV 
administration, all of which will be identified with the participant identification number, date and 
time of dose preparation, and the volume prepared. An investigator (i.e., physician) must be 
present in the clinic at the time of administration of the study interventions. 
Visually, RSM01 is transparent and the appearance is comparable to that of the Placebo. 
The Placebo control will be administered in the same manner as the RSM01, within each cohort. 
IM administration into the anterolateral thigh muscle will be performed using standard ’Z-track’ 
technique. Refer to Section 6.3.1. 
IV infusion will be administered over a duration of up to 2 hours using a volumetric pump. The 
infusion rate may vary based on the total volume needed to administer the full dose. The total 
time needed to administer the dose may be longer than 2 hours based on factors such as 
participant tolerance. Refer to Section 6.3.2. 
For the Dose Escalation Phase, the first (sentinel) participant undergoing study intervention 
administration in each cohort will receive RSM01. The next participant in each cohort can be 
dosed at least 24 hours after the sentinel participant. After the 24-hour post-dose period for the 
sentinel participant in each Dose Escalation Phase cohort, participants in the Dose Escalation 
Phase should be dosed at least 2 hours apart regardless of route of administration (IM or IV). The 
≥2-hour wait time between IV infusions is to begin at the end of the previous participant’s 
infusion. The ≥2-hour wait time between IM injections is to begin at the time of the previous 
participant’s IM injection. 
For the Dose Expansion Phase, participants will be observed either overnight or for at least 4 
hours at the study site after receiving the study dose, depending on the investigator’s decision. 
6.3.1. 
IM Injection 
Before administering the injection, the study intervention administrator must inspect the syringe 
and vial volume, checking that the syringe is identified with the correct participant identification 


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number and checking the date and time the dose was prepared. For IM dosing in the Dose 
Escalation Phase, participants in Cohort 2 will receive a total of 3mL administered in 1 injection 
into the anterolateral thigh muscle at the dosing visit, using the ‘Z-track’ technique. The ≥2-hour 
wait time between administration of IM injections to successive participants is to begin at the 
time of the previous participant’s injection. 
The Dose Expansion Phase cohort may receive RSM01 (≥300mg to ≤600mg) or Placebo in the 
anterolateral thigh muscle. If more than 3 mL of study intervention is administered in a single 
dose, the volume and number of injections will be adapted, depending on the dose to be 
administered, and will be decided by the sponsor. 
6.3.2. 
IV Infusion 
The formulation for RSM01 is 100mg/mL, and the appropriate volume, based on group 
randomization, will be added to normal saline to achieve the desired volume for each of the IV- 
dosed cohorts. The total IV infusion volume will be 53mL for Cohort 1, 60 mL for Cohort 3, and 
130mL for cohort 4. The IV infusion time will be approximately 2 hours or less depending on the 
cohort. The ≥2-hour wait time between administration of IV infusions to successive participants 
is to begin at the end of the previous participant’s infusion. 
6.4. Handling/Storage/Accountability 
Further guidance and information for the preparation, handling, storage, and accountability are 
provided in the Pharmacy Manual. 
The study intervention (RSM01 and Placebo) must be stored at 2°C to 8°C in a secure location 
with no access for unauthorized personnel. 
The study pharmacist (or designee) must confirm appropriate temperature conditions have been 
maintained during transit and during site storage for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. Upon receipt of 
study supplies, the study pharmacist must immediately inspect all kits for damage. Any damage 
or discrepancies from the packing list must be documented and promptly discussed with the 
sponsor and the study monitor to determine the appropriate action. 
Only participants enrolled in the study may receive study intervention and only authorized site 
staff may supply or administer study intervention. All study intervention must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the investigator and authorized site 
staff. 
The investigator is responsible for study intervention accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
Authorization for any unused study intervention and supplies to be destroyed is the responsibility 
of the sponsor. At the end of the study, unused supplies will be destroyed according to the 
facility’s Standard Operational Procedures (SOPs) or per local regulations. Any disposal of study 
intervention conducted at the clinical site must be documented in the study file. 


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6.5. Measures to Minimize Bias: Randomization and Blinding 
6.5.1. 
Randomization 
The first participant in each Dose Escalation Phase cohort will not be randomized and will 
receive RSM01 dose level appropriate to the assigned cohort (refer to Section 8.1.1). 
The remaining 6 participants in each Dose Escalation Phase cohort (Cohorts 1, 2, 3 and 4) will 
be randomized 5:1 to receive either RSM01 or Placebo. The overall ratio of RSM01 to Placebo 
will be 6:1 in each cohort. 
The Expansion Phase (Cohort 5) will be randomized 6:1 to receive either RSM01 IM (N=24) or 
Placebo (N=4). 
Randomization will be based on a randomly-generated sequence of participant identification 
(identifier) numbers (randomization schedule) using a validated Interactive Voice/Web Response 
System (IXRS). 
Before the study is initiated, the telephone number and call-in directions for the Interactive Voice 
response system and/or the log in information and instructions for the Interactive web response 
system will be provided to the study sites. 
The randomization schedule will be prepared by a statistician who will not be involved in the 
analysis of the study in order to maintain the blind of the study team. 
Randomization for each participant will take place on Day 1. 


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6.5.2. 
Masking 
The study is double-blind: participants and all study personnel will be blinded to the 
randomization, with one exception: the first sentinel participant in each Dose Escalation Phase 
cohort will be single-blinded (participant-blinded) and receive the respective dose of RSM01. 
Authorized study site personnel will administer doses. 
The unblinded investigational pharmacist will provide the prepared doses of RSM01 and Placebo 
to the clinic appropriately masked to the blinded treating nurse/physician. 
Only the following personnel will have access to the treatment allocation while the study remains 
blinded to other personnel: 
• Pharmacist preparing the RSM01 and Placebo doses 
• Biostatistician preparing the randomization list 
• Biostatistician preparing the IDMC data, as applicable, and for the interim analysis 
• Pharmacometrician preparing the PK data for IDMC (as applicable) and for the interim 
analysis 
• IDMC members, as applicable 
• Unblinded study Monitors. 
Additionally, the supplies manager/designate and quality assurance personnel of the sponsor, 
as well as the IXRS system setup person and PK simulation and modeling vendor will have 
access to unblinding information. 
All unblinded persons must take care to not reveal individual group assignments to any other 
member of the study team. 
Any study staff that become inadvertently unblinded must not participate in the evaluation of 
AEs. A delegation of authority log will be maintained by the site and will identify the 
individual(s) authorized to function as individuals with access to study blinding information. 
The interim analysis will be performed by an unblinded statistician. The investigator will be 
blinded during the entire study. 
Blinding will be maintained during the aggregated PK data review to select the Dose Expansion 
Phase cohort dose and during interim analysis. 
The sponsor will review aggregated safety data by cohort only (data from both RSM01 and 
Placebo participants will be included) and will review aggregated PK data by treatment group 
(RSM01 vs. Placebo) within and across cohorts for the following purposes: 1) selecting dosing 
for the Dose Expansion Phase cohort, and 2) reviewing the interim analysis to inform a decision 
and plan for the infant study. Although the sponsor will be blinded throughout the study, such 
review of aggregated data could potentially lead to individual unblinding. An unblinding plan 
will be prepared to include unblinding details. 


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6.5.3. 
Blind Break 
The IXRS will be programmed with blind-breaking instructions. In addition, instructions on 
emergency unblinding in case of system outage will be provided. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s treatment 
assignment is warranted. Participant safety must always be the first consideration in making such 
a determination. If the investigator decides that unblinding is warranted, the investigator should 
make every effort to contact the sponsor prior to unblinding a participant’s treatment assignment 
unless this could delay emergency treatment of the participant. If a participant’s treatment 
assignment is unblinded at any time during the study, the sponsor must be notified within 24 
hours after breaking the blind. The date and reason that the blind was broken must be recorded in 
the source documentation and case report form (CRF), as applicable. 
6.6. Study Intervention Compliance 
Participant compliance with study intervention will be recorded on his/her CRF. 
6.7. Concomitant Therapy 
Any prescription medication, anti-inflammatory drug, antipyretic drug, or vaccine that the 
participant receives from enrollment through study Day 151 must be recorded along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency. 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
A COVID-19 vaccination may be received by a participant during the study but not within the 15 
days immediately following administration of the study intervention. 
6.8. Dose Modification 
No unplanned dose modifications are allowed. This is a dose escalation and dose expansion 
study. Refer to Section 3 for details regarding dose escalation and dose expansion. 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal 
7.1. Discontinuation of Study Intervention 
A participant withdrawn from the study intervention (i.e., any participant who does not receive 
the study intervention) will be withdrawn from the study. 


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7.1.1. 
Pausing Rules 
Pausing rules (reasons for pausing the study) are in effect during the active enrollment and 
dosing period. Any one of the following will prompt a study pause: 
• 
death in any participant in whom the event causing death is judged to be related to the study 
drug by the investigator. 
• 
any occurrence in any participant of a SAE judged to be related by the investigator. 
• 
any occurrence in any participant of an AESI (anaphylaxis, hypersensitivity reaction, and/or 
infusion reaction resulting in permanent discontinuation of study drug infusion during IV 
administration). 
• 
any occurrence of Grade 3 or higher toxicity assessed to be related to the study drug by the 
investigator. 
• 
any occurrence of a clinically significant Grade 3 or higher laboratory abnormality assessed 
to be related to the study drug by the investigator. 
If any of the pausing criteria are met, enrollment/patient accrual as well as dosing of enrolled 
participants will be suspended pending IDMC’s review of all available safety data and the U.S. 
FDA will be notified in an expedited manner. 
Refer to Section 8.2.6 for the role of SRT and Section 8.2.7 for the role of the IDMC. 
If the investigator and/or the SRT observes that a pausing rule is met, the investigator will inform 
the sponsor and/or the SRT as soon as possible and within 24 hours of the observation. The SRT 
and/or sponsor will notify the investigator and the IDMC members of the pause in enrollment 
and participant dosing as soon as possible and within 24 hours of receiving notification of the 
pausing rule being met. 
When a pausing rule is met, the IDMC members will convene an urgent ad hoc review meeting, 
review all relevant unblinded safety data, and make a recommendation to the sponsor. The FDA 
will be advised of the IDMC actions and recommendations. 
The IDMC may recommend continuation of the study pause or resumption of enrollment and 
dosing with or without changes to the protocol. The final decision to pause or resume study 
activities will always be the responsibility of the sponsor. All IDMC recommendations will be 
stored according to the IDMC Charter. 
All sponsor decisions will be documented in a memorandum to the study file. The sponsor or 
delegate is responsible for prompt communication to the study site of decisions related to 
pausing or resuming the study activities, including notification to the investigator, relevant 
IRBs/IECs and regulatory authorities. 
The clinical site will be allowed to resume activities only upon receipt of written notification 
from the sponsor. 
7.2. Participant Discontinuation or Withdrawal from the Study 
A participant may request withdrawal from the study at any time. A participant may also be 
withdrawn from the study at any time for the following reasons: 


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a. 
at the request of the primary care provider if being in the study is no longer in the best 
interest of the participant 
b. participant is judged by the investigator to be at significant risk of failing to comply with 
the provisions of the protocol as to cause harm to self or seriously interfere with the validity 
of the study results 
c. 
at the discretion of the IRB/IEC or government agencies as part of their duties, investigator, 
or sponsor. 
If possible, a discontinuation visit should be scheduled for any participant who wishes to 
discontinue or withdraw from the study. At this visit, topics around participant safety as well as 
the use of already collected biospecimens will be discussed, and the procedures and specimen 
collection indicated in the SoA (Table 2 and Table 3) will be performed if possible and as 
needed. 
The time and reason for withdrawal should be noted in the space provided for this purpose in the 
CRF. Possible reasons responsible for withdrawal include: 
• 
no receipt of study intervention 
• 
SAE 
• 
non-serious AE 
• 
protocol violation (specify) 
• 
consent withdrawal not due to an AE* 
• 
move from study area 
• 
other (specify). 
*If a participant withdraws consent, the reason, if specified, will be documented in the CRF. 
Participants who are withdrawn because of occurrence of AE should be clearly distinguished 
from participants who are withdrawn for other reasons. Participants who are withdrawn because 
of an AE will be followed until the event resolves or stabilizes. 
Refer to Appendix 1, Section 10.1.4 regarding the informed consent process. 
All data collected until the date of withdrawal/last contact of the participant will be used for the 
analysis, unless the participant requests destruction of any samples taken and not tested. The 
investigator must document this in the site study records and the CRF. If the participant 
withdraws consent for disclosure of future information the sponsor may retain and continue to 
use any data collected before such withdrawal of consent. 
If the participant leaves the study, the participant’s medical information will still be used or 
shared to the extent allowed by law. Any leftover samples will be destroyed after testing is 
completed unless the participant withdraws consent to sample use, in which case the samples 
will be destroyed at that time. Any test results from the samples collected before withdrawal 
can still be included in the analyses. 
A participant who becomes pregnant during the study period will be asked to complete all visits 
and procedures through Day 151 as described in Table 2 or Table 3, as applicable. After she 


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completes Day 151, or in the event that she voluntarily withdraws from the study and agrees to 
provide additional information regarding the pregnancy, the investigator will utilize the 
‘Pregnancy Outcome Form’ during the remaining gestation period to collect information on the 
health of the participant, the outcome of the pregnancy, and the health of the neonate. Neonate 
follow-up will occur for 6 weeks beyond the estimated delivery date (refer to Section 10.3). 
7.3.  Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits (3 failed visits) and is unable to be contacted by the study site (3 failed attempts 
per failed visit). 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in the 
study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, telephone calls and, if 
necessary, a home visit by a member of the study team). These contact attempts should be 
documented in the participant’s medical record and the CRF. 
• 
Should the participant continue to be unreachable, he/she will be considered lost to follow-
up from the study. 
7.4. COVID-19 Contingency Plans 
In the event that SARS-CoV-2 coronavirus disease (COVID-19) affects the conduct of this trial, 
the sponsor will evaluate if in-person visits are necessary to fully ensure the safety of trial 
participants and whether alternative methods for safety assessments (e.g., phone contact, virtual 
visit, alternative location for assessment such as local laboratories or home visits) could be 
implemented when necessary and feasible, and would be sufficient to ensure data integrity and 
safety of participants [FDA, 2020]. 
Any contingency plans must be sufficient to ensure the safety of trial participants. Changes in 
study visit schedules, missed visits, or withdrawal of the study intervention or participant 
discontinuations may lead to missing information (e.g., for protocol-specified procedures) must 
be captured in the CRF that explains the basis of the missing data (i.e., COVID-19). 
Approaches to be used to protect trial participants and manage study conduct during possible 
disruption of the study as a result of COVID-19 control measures at the study site must be 
documented. Depending upon the nature of the changes described above, a protocol amendment 
may be required under the applicable regulations. 
Deviations because of COVID-19 will be described in the clinical study report or in a separate 
study-specific document) including but not limited to the following: 


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• 
Contingency measures implemented to manage study conduct during disruption of the study 
as a result of COVID-19 control measures. 
• 
A listing of all participants affected by the COVID-19 related study disruption by unique 
participant number identifier and by investigational site, and a description of how the 
individual’s participation was altered. 
• 
Analyses and corresponding discussions that address the impact of implemented 
contingency measures (e.g., trial participant discontinuation from investigational product 
and/or study, alternative procedures used to collect critical safety and/or efficacy data) on 
the results reported for the study. 
8. 
Study Assessments and Procedures 
Study procedures and their timing are summarized in the SoA. Adherence to the study protocol, 
including those specified in the SoA, is essential and required for study conduct. 
Prior to any study procedure, all eligible participants will be assigned a unique participant 
identifier. This participant identifier will be used throughout the study for participant 
identification. 
Screening for eligibility assessment will occur after informed consent is obtained. Eligibility for 
randomization will be based on the inclusion and exclusion criteria described in Section 5.1 and 
Section 5.2, respectively. 
Eligibility criteria will be checked during the screening process and prior to RSM01 or Placebo 
administration to ensure that all participants enrolled meet all of the inclusion criteria and none 
of the exclusion criteria. The investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record the reasons for screening failure, as 
applicable. 
To evaluate eligibility criteria, a medical history and physical examination including vital signs 
will be performed. 
In addition, safety laboratory tests (hematology, chemistry, and urinalysis), HIV, hepatitis B and C 
screening, urine drug test, 12-lead ECG, and serum pregnancy test (females only) will be performed. 
The investigator must document confirmation of eligibility prior to randomization. 
8.1. Safety Assessments 
The screening visit will take place between 30 days and 2 days before the planned Day 1 visit. 
All participants will also be required to attend the Day -1 (Pre-V1) visit within 24 hours before 
planned dosing to begin confinement. 
A negative serum pregnancy test (based on the serum sample collected on Day -1) must be 
confirmed prior to study intervention administration on Day 1. 
All Day 1 safety assessments and sample collections are prior to administration of study intervention. 


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Prior to opening Cohorts 2 and 3 together, Cohort 4, and Cohort 5, respectively, to enrollment, 
the SRT will conduct safety assessment of data for the previous cohort/s collected when all 
participants in the currently dosed cohort have completed Day 15. 
During each IV infusion, any infusion reactions will be recorded. 
Planned time points for all safety assessments are provided in the SoA. 
8.1.1. 
Confinement Period and Sentinel Participants 
Details regarding confinement period are provided in the study manual. 
Dose Escalation Phase 
Participants in the Dose Escalation Phase will be confined at the study site from Day -1 to after 
completion of Day 3 assessment (a total of 3 nights). 
On Day -1, participants will undergo safety laboratory assessments and other screening 
procedures (refer to the SoA, Table 2). 
The first participant in each of the Dose Escalation Phase cohorts will be a sentinel participant 
and will receive RSM01 at the respective dose of RSM01 in a participant-blind fashion. 
The next participant in each cohort can be dosed at least 24 hours later, if there is no safety 
concern. 
Dose Expansion Phase 
For the Expansion Phase, participants will be asked to present to the clinic within 24 hours of the 
Day 1 visit. On this Day -1 visit, participants will begin confinement, and undergo safety 
laboratory assessments and other screening procedures (refer to the SoA, Table 3). 
On Day 1 after dosing, participants will be observed for at least 4 hours post-dose at the study 
site for safety monitoring, and based on investigator’s decision, a participant may be asked to 
remain for an additional overnight stay on the night of Day 1. 
8.1.2. 
Full Physical Examination and Medical History 
A full physical examination and medical history will be conducted at screening to assess 
enrollment eligibility. Only participants that are considered as healthy by the investigator will be 
enrolled. 
All conditions that exist prior to administration of study intervention will be recorded in the 
medical history. Day-to-day fluctuations in these conditions that do not represent a clinically 
significant change in the participant’s status will not necessarily be reported as AEs. 
Physical examination at screening will include, at a minimum, assessment of height and weight, 
body temperature, and resting vital signs (including percent oxygen saturation by pulse 
oximetry), in addition to assessments needed to determine eligibility. Assessments will include 
general appearance and specific organ systems (head, eyes, ears, nose, throat/mouth, neck 
(HEENT), respiratory, cardiovascular, gastrointestinal, and neurological systems, psychiatric, 
skin, and lymphatics). 


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8.1.2.1. 
Vital Signs 
Vital signs will be taken at screening and on Day 1, prior to RSM01/Placebo administration. 
Vital sign measurements will be recorded for pulse rate, systolic and diastolic blood pressure, 
respiratory rate, body temperature and percent oxygen saturation by fingertip pulse oximetry. 
Vital signs are to be taken after the participant is seated for at least 5 minutes in a quiet setting 
without distractions. Measurements are to be repeated if clinically significant changes are 
observed or a machine error occurs. 
Vital signs for the Dose Escalation Phase: 
• 
On Day 1 vital signs will be taken pre-dose, and 1 hour, 4 hours and 8 hours after the IM 
dose and at pre-dose, 15, 30 and 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, and 8 hours 
after the IV dose. The window for these measurements is ± 3 minutes. 
• 
On Day 2, vital signs will be taken at 24 hours post-dose. The window for these 
measurements is ± 0.5 hours. 
• 
On Day 3 Visit vital signs will be taken at 48 hours after dosing. The window for these 
measurements is ± 1.0 hours. 
Vital signs for the Dose Expansion Phase: 
 
On Day 1, vital signs will be taken pre-dose and 4 hours post-dose. The window for these measurements is 
± 3 minutes. If the participant stays overnight on Day 1, vital signs will be taken at 24 hours after dosing. 
The window for these measurements is ± 0.5 hours. 
8.1.3. 
Focused Physical Examination and Medications/Vaccinations 
Focused physical examinations, will be performed on Day 1 and all subsequent visits, as 
indicated in the SoA (Table 2 and Table 3). 
A focused physical examination will be performed if indicated by participant’s medical 
complaint and will include assessments of body systems involved in the complaint. Focused 
physical examinations will be symptom directed. 
Throughout the study, any concomitant medications taken, including antipyretics, anti-
inflammatories, and vaccinations will be recorded (refer to Section 6.7). 
8.1.4. 
Pregnancy Status Assessment 
A blood sample will be collected from female participants at screening and at Day -1 for serum 
beta human chorionic gonadotropin (βHCG) testing. 
Serum βHCG testing of female participants should be performed during the study if a pregnancy 
is suspected. 
Serum βHCG testing of female participants of childbearing potential should be performed at the 
discontinuation visit. 
During the study, participants will be asked about pregnancy during each visit. If a pregnancy is 
reported, the investigator should inform the Medical Monitor within 24 hours of learning of the 
pregnancy and should follow the procedures outlined in Appendix 3, Section 10.3. 


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A participant who becomes pregnant during the study period will be asked to complete all visits 
and procedures through Day 151 as described in Table 2 or Table 3, as applicable. After she 
completes Day 151, or in the event that she voluntarily withdraws from the study and agrees to 
provide additional information regarding the pregnancy, the investigator will utilize the 
‘Pregnancy Outcome Form’ during the remaining gestation period to collect information on the 
health of the participant, the outcome of the pregnancy, and the health of the neonate. Neonate 
follow-up will occur for 6 weeks beyond the estimated delivery date (refer to Section 10.3). 
8.1.5. 
HIV Antibody Assessment 
To be eligible for the study, participants must not have reactive anti-HIV antibody at screening. 
A blood sample will be collected to make this assessment. 
8.1.6. 
Electrocardiogram, Hepatitis Screening and Urine Drug Screening 
A 12-lead ECG will be performed at screening using a machine that automatically calculates 
heart rate and determines intervals for PR, QRS, QT and QTc. Triplicate (unmarked) 12-lead 
ECGs will be obtained. For the Dose Escalation Phase, the ECGs will be taken at screening, and 
24 hours post-dose, on Day 2. For the Dose Expansion Phase, the ECGs will be taken at 
screening. 
All 12-lead ECGs will be obtained after the participant has rested in a supine position for at least 
10 minutes. All Triplicate ECGs will be taken approximately one minute apart. Measurements 
that deviate substantially from previous readings will be repeated immediately. 
At the screening visit, a blood sample will be collected to test for the presence of hepatitis B 
surface antigen (HBsAg) and hepatitis C virus antibodies. 
A urine sample will be collected at screening and at Day -1 to screen for evidence of drugs of 
abuse. 
8.1.7. 
Clinical Safety Laboratory Assessments 
Clinical safety laboratory assessments will be performed at screening, on Day -1 (Pre-V1), and 
throughout the study at timepoints specified in the SoA (Section 1.3). 
Blood samples for laboratory assessments will be collected at screening, and at study visits 
indicated in the SoA. 
Laboratory values from the most recent blood sample collected prior to randomization that are 
outside the normal range that are suggestive of a disease state (i.e., clinically significant Grade 1 
abnormalities or values greater than Grade 1 [refer to Section 10.4]) will lead to exclusion from 
study enrollment, with the exception of any grade hematuria in a menstruating female, or a 
urinalysis abnormality judged not clinically significant by the investigator. 
Refer to Section 10.4 for toxicity table for grading for each clinical laboratory test. 
Clinical safety laboratory parameters that will be evaluated include: 
a. 
Hematology: Complete blood count (including hemoglobin, platelet count and white blood 
cell count) and absolute counts for neutrophils, lymphocytes, eosinophils, and monocytes 


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b. Serum chemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
alkaline phosphatase, total bilirubin, gamma glutamyl transferase (GGT), creatinine, blood 
urea nitrogen, lactate dehydrogenase (LDH), glucose, albumin, sodium, potassium, 
chloride, bicarbonate, and calcium. 
c. Urinalysis: Specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, 
nitrite, leukocyte esterase by dipstick. 
Abnormal results and findings that make the participant ineligible for study participation will be 
discussed with the participant and the participant will be referred for follow-up care with their 
health care provider if necessary. 
All screening laboratory specimens will be processed according to laboratory SOPs available 
from the clinical laboratory(ies) designated for the study. 
All protocol-required safety laboratory tests will be performed by the site local laboratory or at 
the point of care. Laboratory safety testing performed at point of care will be documented in 
participant source and captured in the electronic data capture (EDC) database. 
Information about the laboratory(ies), including any instructions for performing and interpreting 
specific tests, will be maintained in the investigator’s study files. 
The investigator must review the laboratory report, document the review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. The 
laboratory reports must be filed with the source documents. 
All protocol-required laboratory assessments must be conducted in accordance with the 
Laboratory Manual and the SoA. 
If laboratory values from non-protocol-specified laboratory assessments require a change in 
participant management or are considered clinically significant by the investigator (e.g., AE or 
SAE), then the results must be recorded in the CRF. 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations. 
8.1.8. 
Pre- and Post-Study Intervention Safety Monitoring 
Participants will remain under observation at the study site for 3 days in the Dose Escalation 
Phase cohorts (24 hours before dosing and 48 hours after dosing). Participants in the Dose 
Expansion Phase cohort will present to the study site before the planned Day 1 visit. After 
treatment on Day1, the participant will be observed for 4 hours at the study site and may remain 
overnight based on investigator’s decision. 
Allergic reactions to RSM01 are possible, therefore, appropriate drugs and medical equipment to 
treat acute anaphylactic reactions must be immediately available and a physician trained to 
recognize and treat anaphylaxis must be present in the clinic during study intervention 
administration and the post-dosing monitoring period. 


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8.1.9. 
Diary Card, Memory Aid and Daily Monitoring 
Diary card 
Before leaving the clinic after dosing and completion of the post-dosing on-site confinement, 
participants will be given a diary card and receive guidance on how to fill in the card. All 
participants will receive a digital thermometer to record temperature. Participants who receive an 
IM dose will also receive a ruler to measure diameter of redness and/or swelling at the injection 
site, if present. 
The diary card will be used by the study participants to record the duration, and intensity (refer to 
Section 8.2.3.1) of solicited injection site AEs (for participants who receive an IM dose) and 
solicited systemic AEs up to Day 7 following injection or infusion for all participants. This 
information should be recorded in the participant diary card at approximately the same time each 
evening, through Day 7 (refer to Section 8.2 for more information). 
The diary card will be collected and reviewed by the investigator (or designee) on the Day 8 
Visit for both the Dose Escalation Phase and the Dose Expansion Phase participants. 
No changes to the diary card will be permitted; however, any verbally recalled information 
provided by the participant during review of the diary card will be documented in the source 
document and reported as an AE as applicable. 
Memory aid 
A memory aid will be utilized by participants to collect unsolicited AEs beginning at discharge 
from the clinic, through Day 151 (end of study participation for an individual). Participants will 
be instructed to record unsolicited AEs whenever they occur, recording such AEs on the memory 
aid. The memory aids will be collected and reviewed by site staff at each subsequent visit 
through the end of the study. 
8.1.10. 
Participant Follow-Up 
Participants will be instructed to contact a study team member to report new or worsening AEs, 
as well as new diagnoses, and to come to the study clinic if medical attention is needed. 
For emergencies and other unscheduled visits to a medical facility other than the study clinic, 
medical records will, to the extent possible, be obtained by the investigator. 
Participants will be asked about the occurrence of AEs, SAEs, AESIs, receipt of concomitant 
prescription medications/vaccinations, and change in general health status and any other change 
in status that may affect the participant’s participation, as indicated in the SoA. 
Any deviation from protocol procedures, evaluations, and/or visits will be documented. 


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8.2. Adverse Events and Serious Adverse Events 
Local injection site solicited AEs will include pain, redness and swelling, and will be assessed 
after dosing at Visit 1 for 7 days (IM recipients only). If more than 1 injection is given, reactions 
will be assessed separately at each injection site. 
Systemic solicited AEs will be assessed in all participants after dosing at Visit 1 and recorded for 
7 days. These will include fever, headache, fatigue, muscle aches, nausea, vomiting, diarrhea, 
and joint pain. 
Site staff will document any AEs in the study source during the confinement for all cohorts. The 
site staff will record solicited injection site AEs (IM doses only) and solicited systemic AEs (all 
participants), including duration and intensity, during confinement. Refer to Section 8.1.9 for 
solicited AEs to be recorded in the diary card by participants, through Day 7. 
Solicited AEs that continue beyond Day 7 will be captured in the unsolicited AEs memory aid 
and marked as continuation of solicited AE. Participants will be asked to record events at the 
same time each evening. 
Unsolicited AEs including AESIs, SAEs, and safety laboratory parameters Grade 1 and above 
will be collected from screening through Day 151 and recorded in the AE log by the study team. 
The definitions of AEs, SAEs, serious adverse drug reactions (ADRs) and AESIs can be found in 
Appendix 2, Section 10.2.1, and 10.2.2, 10.2.3, 10.2.4, respectively. 
Refer to Appendix 2, Section 10.2 for details regarding AEs, AESIs, and SAEs and Section 10.4 
(Table 9) for laboratory parameters. 
Immediate safety concerns should be discussed with the sponsor, and the SRT. The SRT will 
trigger an IDMC review if any pausing rule is met (see Section 8.2.7 for IDMC and Section 
10.2.5 for details regarding AE reporting and follow-up). 
AEs will be reported by the participant (or, as appropriate, the participant's legally authorized 
representative). Clinical chemistry and/or hematology results may also qualify as AEs (Section 
10.4, Appendix 4). 
Study nurses and physicians are responsible for collecting and documenting information and 
events that would potentially meet the definition of an AE. However only the investigator or sub-
investigator is responsible for assessment, including assignment of causality and, for unsolicited 
AEs, the intensity, and for reporting and management of all AEs. The investigator is responsible 
for following up all AEs regardless of their relatedness to study intervention or study procedures, 
or AEs that caused the participant to withdraw from the study (Section 7). 


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8.2.1. 
Time Period and Frequency for Collecting AE and SAE Information 
Type of Event 
Collection Time Period 
All solicited AEs  
Day 1 through Day 7 (inclusive) 
Unsolicited AEs, and SAEs including AESIs  
Screening through end of study (Day 151) 
Distribution and collection days for diary cards and memory aids are shown in the SoA. 
Medical conditions that begin before the start of study intervention but after obtaining informed 
consent will be recorded on the Medical History/Current Medical Conditions section of the CRF, 
not in the AE section. 
All SAEs and AESIs will be reported to the sponsor or designee within 24 hours, as indicated in 
Appendix 2, Section 10.2.6. The investigator will submit any updated SAE and AESI data to the 
sponsor or designees within 24 hours of it being available. 
Investigators are not obligated to actively seek AEs, SAEs or AESIs after a participant concludes 
study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and he/she considers the event to be 
related to the study intervention or study participation, the investigator must notify the sponsor or 
designee within 24 hours. 
8.2.2. 
Method of Detecting AEs and SAEs 
The methods of recording and follow-up of AEs, SAEs and AESIs are provided in detail in 
Appendix 2, Section 10.2.5, which includes assessments of intensity, relationship to the study 
intervention, and outcome of AEs, SAE and AESIs. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading questions are the preferred method to inquire about AE occurrences. 
8.2.3. 
Follow-up of AEs 
After the initial SAE/AESI report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs/AESIs will be followed until resolution, 
stabilization, or the participant is withdrawn/withdraws, or is lost to follow-up or (as defined in 
Section 7.2 and Section 7.3, respectively). Refer to Appendix 2, Section 10.2.5.4. 
8.2.3.1. 
AE Intensity 
The intensity of AEs will be classified by the investigator based on the toxicity grading tables 
(Section 10.4 Appendix 4). In the case of an AE or abnormal clinical laboratory result not 
included in Appendix 4, intensity will be assigned using the Grades described in the U.S. 
Department of Health and Human Services, Common Terminology Criteria for Adverse Events, 
Version 5.0 [US HHS 2017] (See Section 10.2.5.1). 
Local solicited AEs will be recorded on the diary card by the participant and graded and/or 
measured by the participant. An exception is that the study investigators will grade solicited AEs 


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during the confinement period. Any participant-reported Grade 3 or higher adverse event will be 
assessed by the investigator. 
8.2.3.2. 
AE Causality/Relationship to Study Intervention 
All AEs will be evaluated by the investigator or medically qualified designee (i.e., investigator, 
sub-investigator) to assess the relationship between study intervention and the AE (with the 
exception of local injection site reactions, which are assumed to be related to the injection). 
Careful medical judgment should be exercised to determine the level of causal relationship 
between an AE and the study intervention. The causality will be assessed as either related or not 
related. 
The sponsor or designee will have the opportunity to confirm the seriousness and case causality 
based on the clinical judgment of the Medical Monitor or sponsor designee. If a serious adverse 
event is considered unrelated by the investigator but the sponsor believes that there is a 
reasonable possibility that the event is related, the sponsor will upgrade the case to a ‘related’ 
status. The sponsor or designee will never downgrade a case from serious to non-serious or 
change the investigator assessment of causality from related to not related. 
Refer to Appendix 2, Section 10.2.5.2 for details. 
8.2.4. 
Regulatory Reporting Requirements for SAEs 
Refer to Appendix 2, Section 10.2.6 for details regarding SAE reporting. 
The sponsor or delegate has a legal responsibility to notify both the local regulatory authority 
and potentially other regulatory agencies about the safety of the study intervention under clinical 
investigation. Therefore, prompt notification by the investigator to the sponsor of a SAE is 
required. 
The sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/IECs, and investigators. 
In the U.S., the sponsor assumes responsibility for appropriate reporting of AEs to the regulatory 
authorities. The sponsor will also report to the investigator all SAEs including SAEs associated 
with the use of the study intervention. The investigator must report these events to the 
appropriate IRB that approved the protocol, unless otherwise required and documented by the 
IRB. 
AEs reporting, including suspected unexpected serious adverse reactions, will be carried out in 
accordance with applicable local regulations. 
The sponsor will prepare, distribute, and submit Serious ADR reports according to local 
regulatory requirements of participating countries. 
Refer to Appendix 2, Section 10.2.6 for details regarding SAE reporting. 
8.2.5. 
Death Events 
Any untoward medical occurrence (AE) resulting in death is reported as an SAE. The cause of 
death will be appropriately documented in the SAE report form and supporting evidence will be 
provided. 


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8.2.6. 
Safety Review Team 
A SRT will be established as the team responsible for recommending dose escalation or dose 
expansion to the sponsor’s Chief Medical Officer. The SRT will operate according to the Safety 
Review Team Plan. 
Meetings of the SRT to provide a recommendation on dose escalation or dose expansion will 
occur during the Dose Escalation Phase when all participants in the currently dosed cohort have 
completed Day 15. The SRT will also meet approximately every 8 weeks during the Dose 
Expansion Phase. The SRT will review all available blinded safety data collected at the time of 
the review to determine whether or not any pausing event has occurred (See Section 7.1.1.). If a 
pausing event does not occur, dose escalation or moving to the Dose Expansion Phase cohort 
will be recommended by the SRT. 
If a pausing rule is met, the SRT will ask the IDMC to conduct a review of unblinded safety data. 
The IDMC will make a recommendation to the sponsor regarding the further conduct of the 
study. 
8.2.7. 
Independent Data Monitoring Committee 
The IDMC will operate according to a charter approved by the sponsor and all IDMC members. 
The IDMC structure, participants and other details will be provided in the charter. The charter 
will be approved prior to enrollment of the first study participant. 
The role of the IDMC will be to (a) review unblinded safety data if a pausing rule is met  and (b) 
make recommendations to the sponsor on further conduct of the study if a pausing rule is met. 
The recommendations of the IDMC, along with the sponsor’s decision, will be communicated to 
the investigator, to the responsible IRBs/IECs and to the US FDA. 
8.3. Treatment of Overdose 
Overdose of any study intervention (including Placebo) is unlikely to occur since the injections 
and infusions are administered as a single dose by a trained study staff member. If an overdose 
were to occur, the overdose, including misuse or abuse of the product and medication errors, 
should be reported in in the clinician notes and the eCRF. If an overdose error occurs, the 
participant will be monitored for symptoms and provided with necessary supportive care. 
8.4. Blood Sampling 
Refer to the SoA for blood sample collection at screening for eligibility and safety laboratory 
assessments. Blood samples will be collected for pregnancy test, HIV, hepatitis B, hepatitis C 
and safety laboratory assessments as described in Section 8.1.7. 
Whole blood samples will be collected for measurement of PK, ADA, and RSV neutralizing 
antibodies. At Visit 1, all samples will be collected prior to dosing. 
A total of approximately 200mL of whole blood will be collected from each participant during 
the entire study period assuming all planned samples are collected, according to the SoA. 


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8.5. Pharmacokinetics 
Dose Escalation Phase: At Visit 1, PK blood draw will occur at pre-dosing, 1 hour (+/- 30 
minutes) before administration of IM injection or beginning of infusion, for all participants in 
Cohorts 1-4. For participants who receive IV study intervention, the timing of post-dose blood 
samples begins at the end of the IV infusion. Samples are obtained at 5 minutes (± 1 minute) at 
8-hours (± 0.5 hour) and at 24-hours (± 1 hour) after the end of the infusion. For participants who 
receive IM study intervention, the timing of post-dose blood samples begins at the time of the IM 
injection and samples are obtained at 8-hours (± 0.5 hour) and at 24-hours (± 1 hour) after the IM 
injection. 
Dose Expansion Phase: At Visit 1, only a pre-dose sample, collected 1 hour (+/- 30 minutes) 
before administration of IM injection is obtained at Day 1. 
Blood for PK samples at all visits after Day 1 will be obtained according to the SoA as shown in 
Table 2 and Table 3. 
 
For all samples, the actual date and time (24-hour clock) of each sample will be recorded to 
calculate actual time elapsed since the prior dose administration. 
Whole blood samples in serum separator tubes and VAMS will be collected for measurement of 
RSM01 concentrations in serum and capillary blood, respectively, as specified in the SoA. The 
quantification of RSM01 in serum and capillary blood will be performed using a validated 
immunoassay method. Concentrations will be used to evaluate the PK of RSM01. The PK 
parameters specified in the endpoints will be calculated. 
Remaining samples collected for analyses of RSM01 may also be used to evaluate 
immunogenicity and/or safety aspects related to any concerns arising during or after the study. 
Details on processes for collection and shipment of these samples are in the Laboratory Manual. 
Retention time and possible analyses of samples after the end of the study are specified in the 
ICF. 
8.6. Pharmacodynamics 
For this study, pharmacodynamics is being assessed as an exploratory endpoint. A surrogate 
pharmacodynamic marker will be used, measuring the ex vivo capability of RSM01 to neutralize 
RSV. 
Whole blood samples in serum separator tubes and VAMS devices will be collected for detection 
of RSV neutralizing antibodies in serum and capillary blood respectively, as specified in the 
SoA. Samples on Day 1 will be collected prior to RSM01 administration. 
The quantification of RSV neutralizing antibodies in serum and capillary blood will be 
performed using a validated viral neutralization method. This method will detect both RSM01 
and neutralizing anti-RSV antibodies from prior natural infection. Therefore, the Day 1 sample is 
needed to evaluate changes in neutralization responses, post-treatment. 
Remaining samples collected for analyses of RSV neutralization may also be used to evaluate 
drug concentration, immunogenicity, and safety aspects related to concerns arising during or 
after the study. Details on processes for collection and shipment of these samples are in the 


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Laboratory Manual. Retention time and possible analyses of samples after the end of the study 
are specified in the ICF. 
8.7. Genetics 
No genetic testing will be performed for this trial. 
8.8. Biomarkers 
There are no prospective biomarker analyses planned. 
As dictated by clinical data and emerging science, the non-genetic biomarkers may be added 
during trial execution. These will be clearly documented in the clinical study report (CSR) and/or 
the trial master file (TMF). 
Clinical safety laboratory assessments such as hematology may also be included as exploratory 
biomarkers in pre-specified analysis plans. 
8.9. Immunogenicity 
Whole blood samples in serum separator tubes and VAMS samples will be collected for 
detection of ADA against RSM01 in serum and capillary blood respectively, as specified in the 
SoA. Samples on Day 1 will be collected prior to RSM01 administration. 
The detection of ADA to RSM01 will be performed using a validated immunoassay method with 
tiered testing of screening, confirmatory, and titration. Confirmed positive ADAs may be further 
characterized. 
Remaining samples collected for analysis of anti-RSM01 antibodies may also be used to evaluate 
RSM01 concentration or exploratory biomarkers during or after the study. Details on processes 
for collection and shipment of these samples are in the Laboratory Manual. Retention time and 
possible analyses of samples after the end of the study are specified in the ICF. 
9. 
Statistical Considerations 
9.1. Sample Size Determination 
This trial is an exploratory trial to characterize safety, tolerability, and pharmacokinetics of 
single doses of RSM01 mAb. The trial is designed to be descriptive and is not based on formal 
testing of a null hypothesis. Therefore, this study is not powered to detect any differences in 
potential safety data between treatment groups. Approximately 56 participants will be available 
for analysis: 28 participants in the Dose Escalation Phase and 28 participants in the Dose 
Expansion Phase. 
Assuming that all cohorts are allowed to undergo treatment, approximately 48 participants will 
be exposed to RSM01, and approximately 8 participants will receive Placebo. 


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Safety 
With 6 participants (per RSM01 arm in each Dose Escalation Phase cohorts), there is 
approximately 80% (90%) power to observe at least one AE if the true AE rate is 23.53% 
(31.87%). 
With 24 participants (across all doses of RSM01 in the Dose Escalation Phase cohorts or the 
Dose Expansion Phase cohort), there is approximately 80% (90%) power to observe at least one 
AE if the true AE rate is 6.49% (9.15%). 
Across all doses of RSM01 (48 participants), there is approximately 80% (90%) power to 
observe at least one AE if the true AE rate is 3.3% (4.68%). 
9.2. Populations for Analyses 
Analysis populations are shown in Table 6. 
Table 6: Populations for Analyses 
Population 
Description 
Intention to treat (ITT) PK 
population 
All participants who received the study intervention. Participants 
will be analyzed according to the intervention actually received. 
Per protocol (PP) PK 
population 
All participants who received RSM01 and did not significantly 
deviate from study procedures, and who have at least one, non-
zero PK result available. Participants will be analyzed according 
to the intervention actually received. 
Safety 
All participants who received the study intervention. Participants 
will be analyzed according to the intervention actually received. 
Immunogenicity 
population 
All participants who received the study intervention and have at 
least one valid ADA result. Participants will be analyzed 
according to the intervention actually received. 
9.3. Statistical Analyses 
A detailed statistical analysis plan (SAP) centered on primary and secondary endpoints will be 
developed and finalized prior to unblinding the study and will further describe the participant 
populations to be included in each analysis, details of the statistical methods, including 
procedures for accounting for missing, unused, and spurious data. Some exploratory analyses, 
not associated with exploratory endpoint analyses, may be included in this SAP. Analyses are 
summarized in Table 7. 
Exploratory endpoint analyses, in particular, those centered on exploratory biomarker analyses, 
and details for PD and serum PK/ADA analyses, will be described in a separate exploratory 
scientific and statistical analysis plan (exploratory SSAP). Specific objectives and hypotheses 
related to exploratory biomarker analyses will be documented in this exploratory SSAP prior to 
full data unblinding and analysis. 


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Results from the exploratory analyses may be reported in a separate results memo and included 
as an addendum to the CSR. 
Table 7: Summary of Primary and Secondary Endpoints and Analyses 
Endpoint 
Statistical Analysis  
Primary: 
Unsolicited AEs through 
Day 151 
All SAEs/AESIs through 
Day 151 
Solicited systemic AEs 
through Day 7 
Solicited local AEs for 
injection site reactions for 7 
days after dose 
administration (only applies 
to IM doses) 
The incidence and Clopper-Pearson 95% CIs of AEs and 
SAEs/AESIs will be summarized by treatment group, dose 
levels, routes of administration and overall, and by intensity. 
Duration, day of onset of local and systemic solicited AEs will 
be summarized by group. Relationship of unsolicited AEs and 
SAEs/AESIs to the study intervention will be summarized by 
group. 
Any infusion reactions will be described. 
Secondary: 
Safety laboratory 
parameters Grade 1 and 
above through Day 151 
The incidence of safety parameters outside of normal ranges 
(Grade 1 and above), change from baseline, grades, grade shifts, 
as applicable, will be summarized by treatment group, dose 
levels, routes of administration and overall, and by intensity, 
and relationship to the study intervention.  
PK parameters 
AUC0-∞, CD91, AUC0-D91, 
CD151, AUC0-D151 Cmax, 
Cmin, Tmax, t1/2, CL and 
Vz  
RSM01 capillary blood concentrations and PK parameters will 
be summarized by treatment group using descriptive statistics, 
and the number of participants. Following summaries will be 
provided arithmetic mean, standard deviation, arithmetic 
percent CV, median, minimum, maximum, geometric mean, 
and geometric percent CV. 
 The proportion of participants with observed or predicted 
CD151 concentrations above the EC90 will be summarized by 
treatment group and country, as appropriate. 
Incidence of ADAs to 
RSM01 through Day 151 
ADA incidence will be summarized by treatment group. Exact 
analyses will be pre-specified in the SAP. 


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9.3.1. 
Safety Primary Endpoints 
The primary analysis will occur when all participants reach Day 151. All safety summaries will 
be presented for all participants in the safety population. 
Solicited Local and Systemic AEs 
All solicited local AEs will be considered study intervention-related events and will be 
summarized for each injection site. 
All solicited AEs collected from Day 1 through Day 7 will be collected and summarized as 
described below. 
The number and percentage of participants who experience one or more solicited AE will be 
summarized for each solicited AE, by treatment group, and by intensity, by day after study 
intervention administration, and overall. The first onset of each AE, and the total number of days 
a participant experienced each AE will also be summarized. For participants with more than 1 
episode of the same event, the AE with maximum severity will be used for tabulations. 
Exact 95% confidence intervals will be calculated on the percentages. 
Unsolicited Treatment Emergent AEs, SAEs and AESI 
All unsolicited AEs, serious adverse events (SAEs), and/or AESI will be recorded from 
screening through Day 151. 
Unsolicited AEs, SAEs, AESI will be coded according to the Medical Dictionary for Regulatory 
Activities (MedDRA) and summarized by System Organ Class (SOC), Preferred Term (PT) and 
greatest intensity. Clopper-Pearson exact 95% CIs will be calculated on the percentages. AEs 
leading to withdrawal from the study will also be summarized. 
The number of events reported, the number of participants and percentage of participants who 
experience one or more unsolicited AE through Day 151, one or more SAE, and/or one or more 
AESI from screening through Day 151 will be summarized by treatment group, as appropriate, 
and across all RSM01 dose levels and routes of administration, combined. The intensity of each 
AE, and relationship between the AE and study intervention, will also be summarized. 
For participants with more than 1 episode of the same event, the AE with maximum intensity 
will be used for tabulations. Participants reporting more than one occurrence for the PT term 
level being summarized will be counted only once. 
9.3.2. 
Safety Secondary Laboratory Assessments 
Clinical safety laboratory evaluations are listed in Section 8.1.7. All laboratory values collected 
at visits will be included in the summaries and listings. Descriptive summaries (n, mean, 
standard deviation, median, minimum, and maximum) of observed value and change from 
baseline (last result available on or before Day 1) at each scheduled post baseline visit will be 
presented for each continuous variable test parameter. 
Summaries by toxicity grade and grading shifts in laboratory values from Day1 (baseline) to Day 
8, Day 91, and Day 151 visits will be also presented. 
The frequency of safety laboratory parameters outside the normal range will be summarized by 
treatment group. 


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9.3.3. 
Other Safety Measures 
Vital signs, 12-Lead ECG, medical history, and summary statistics will be tabulated by treatment 
group. Any other relevant information will be presented in participant data listings. Further 
details will be provided in the SAP. 
9.3.4. 
Pharmacokinetics 
All available PK data will be summarized at the time of dose selection for the Dose Expansion 
Phase, and for the interim and primary analyses when all participants reach Day 91 and Day 151, 
respectively. 
RSM01 capillary blood concentrations and the following PK parameters, AUC0-∞, , AUC0-t, Cmin, 
Cmax ,or C0, CD91, CD151, Tmax, t1/2, CL and Vz, will be summarized by treatment group. Each of 
the PK parameters will be summarized using descriptive statistics (e.g., arithmetic mean, 
standard deviation, arithmetic percent CV, median, minimum, maximum, geometric mean, and 
geometric percent CV), and the number of participants, as appropriate. 
The proportion of participants with observed CD151 concentrations above the estimated EC90 for 
RSM01 (based on available pre-clinical data) will be summarized by treatment group. Exact 95% 
confidence interval will be calculated on the percentages. 
PK will be summarized in the PP PK population. 
In addition to calculating the PK parameters using noncompartmental analysis (NCA) methods, 
RSM01 capillary blood and venous serum-concentration data obtained in this study will be used 
to develop a population PK model that will aid in the prediction of dose or doses to be 
administered in infants and to assess potential covariates. The venous serum will be used for 
developing the model and not for the NCA analysis. 
This analysis will be described in an independent analysis plan and reported separately. 
9.4. Serum and Capillary Blood Immunogenicity 
All available ADA results will be summarized for each treatment cohort at the time of the 
primary analyses, when all participants reach Day 151. 
Further details will be specified in the SAP for capillary blood analyses and in the exploratory 
SSAP for serum. 
9.5. Serum and Capillary Blood RSV Neutralizing Antibody 
All available serum RSV neutralizing antibodies will be summarized for each treatment cohort at 
the time of the primary analysis, when all participants reach Day 151 
Analyses will be specified in the exploratory SSAP. 
9.6. Demographic and Compliance Analyses 
Demographic parameters (age, sex, and race/ethnicity) and other baseline characteristics will be 
summarized descriptively by treatment group for all participants in the safety population. 


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Listings of randomized participants with protocol deviations (to be defined in the SAP) will be 
presented by treatment group. 
9.7. Interim Analyses 
An interim analysis is planned for this study when all participants in each of the Dose Escalation 
Phase cohorts have completed Day 91. An Interim Report will be prepared when the results from 
Day 91 become available. Additional interim analyses may occur prior to the primary analysis to 
aid in the development of individual and population PK models to predict dose/s to be 
administered to infants and to assess covariates. 
The purpose of this interim analysis will be to inform on the broader program; no decision 
directly related to this study will be made from the results of this interim analysis. Agreement on 
the analysis plan, unblinding procedures, specific outputs, method of distribution, the level of 
data cleaning and details of to whom the results will be provided to will be outlined in a separate 
document (which will be finalized prior to the interim analysis). 
The interim analysis will be performed by an unblinded statistician. The investigator will be 
blinded. The sponsor and/or sponsor’s designee(s) will review aggregated safety data by cohort 
only (including data from both RSM01 and Placebo participants) and will review aggregated PK 
data by treatment group (RSM01 vs. Placebo) within and across cohorts. Although the sponsor 
will be blinded throughout the study, such review of aggregated data could potentially lead to 
unblinding of the treatment received by individual participants. 
9.8. National Regulatory Authority 
The national regulatory authority will receive all expedited safety reports from the clinical trial 
and have the authority to terminate, suspend or require changes to a clinical trial. 


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10. 
Supporting Documentation and Operational Considerations 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
a. 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines 
b. Applicable International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines 
c. Applicable laws and regulations 
d. The protocol, protocol amendments, ICF, and other relevant documents (e.g., diary cards) 
must be submitted to an IRB/IEC by the investigator and reviewed and approved by the 
IRB/IEC before the study is initiated 
e. Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
10.1.2. 
Study Oversight 
The study sponsor, the institution through which the research is performed and all members of 
the investigator’s clinical team and the national regulatory authority share responsibility for 
ensuring the safety of participants in this trial. 
The investigator will be responsible for the following: 
a. 
Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently, in accordance with the requirements, policies, and procedures established by the 
IRB/IEC 
b. Notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures 
c. Providing oversight of the conduct of the study at the site and adherence to requirements of 
ICH and GCP guidelines, national authority regulations, the IRB/IEC, and all other 
applicable country and local regulations 
d. Closely monitoring study participants and taking whatever measures necessary to ensure 
their safety. The investigator may delay an individual’s study intervention administration or 
pause study intervention administration altogether if the investigator is concerned that the 
study intervention might place a participant or participants at significant risk. Where 
specified, the responsibilities of the investigator may be delegated to a medically qualified 
team member (designee). The investigator determines intensity and causality with respect 
to the study intervention for each AE. 


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The sponsor has an institutional responsibility to ensure participant safety and is ultimately 
accountable for safety oversight. Medical monitors and the IDMC play an important role in this 
regard and support the sponsor. 
The Medical Monitor is the sponsor’s representative and is a physician. The Medical Monitor: 
a. 
reviews the safety of the product for protocols in a specific region and, in consultation with 
the sponsor 
b. is responsible for safety oversight in-country and plays an important role in the reporting of 
Serious ADRs, SAEs, pregnancies, and other important safety information, as described in 
the protocol 
c. in consultation with the sponsor, may assess the intensity and causality for AEs and may 
upgrade the degree of intensity and causality that has been determined by the investigator 
or designee 
The Medical Monitor, like the investigator, will be blinded until primary endpoint analyses are 
completed, unless emergency unblinding is required. 
The Institutional Review Board or Ethics Committee has institutional responsibility for the safety 
of research participants. The Institutional Review Board or Ethics Committee has the authority to 
terminate, suspend or require changes to a clinical trial. 
10.1.3. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
10.1.4. 
Informed Consent Process 
The investigator or designee will explain the study to the participant and answer all questions 
regarding the study. The investigator or designee will conduct the consent discussions on an 
individual basis with each participant. Adequate time will be allowed for all questions to be 
addressed. Potential participants will be interviewed to ensure that they meet all entry criteria 
relating to history. 
Written informed consent will be obtained prior to conducting any study-related procedures. 
Participants must be informed that their participation is voluntary. Participants will be required to 
sign a statement of informed consent that meets the requirements of FDA Code of Regulations 
(CFR) 21 CFR 50, local regulations, International Council for Harmonization of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) guidelines, and the IRB/IEC or study 
center. 
Written informed consent must obtained before the participant is enrolled in the study, and the 
date the written consent was obtained must be documented. The authorized person obtaining the 
informed consent must also sign the ICF. 
A copy of the ICF must be provided to the participant. 


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10.1.4.1. Informed Consent Forms 
Participants will be required to sign a statement of informed consent that meets the requirements 
of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and Accountability 
Act (HIPAA) requirements, where applicable, and the IRB/IEC or study center. 
Participants will be told that they are free to refuse to participate and may withdraw their consent 
at any time and for any reason during the study period. Any test results from the samples 
collected before withdrawing consent may still be used for the study. 
The informed consent form will be obtained by the use of a written ICF approved by the 
IRB/IEC and signed and dated by the participant. 
A copy of the signed consent form/s shall be given to the participant prior to conducting any 
study-related procedures. 
The medical record must include a statement that written informed consent was obtained before 
the participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
If there is a change to the ICF during the conduct of the study, participants must be re-consented 
using the most current version of the ICF. 
Any withdrawal of consent for sample testing will be documented in the CRF. 
If a participant cannot be randomized on the intended day of dosing (e.g., due to elevated 
temperature) he/she is not required to sign another ICF, as long as re-screening and dosing occur 
within the protocol-defined window. 
10.1.5. 
Data Protection 
Participants will be assigned a unique identifier by the sponsor. Any participant record or dataset 
that is transferred to the sponsor will contain the identifier only; participant names or any 
information which would make the participant identifiable will not be transferred to the sponsor. 
The participant must be informed that the participant’s study-related data will be used by the 
sponsor in accordance with local data protection law. The level of data disclosure must also be 
explained to the participant. 
The participant must be informed that the participant’s medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.6. 
Dissemination of Clinical Study Data 
Study information from this protocol will be posted on publicly available clinical trials registers 
(for example, clinicaltrials.gov) before enrollment of participants begins. Summaries of the 
results of the study will also be posted on the same website. 
The final CSR will include all available data through the final study visit. The database will be 
locked prior to preparation of the final CSR when all of the above data have been entered, 
reviewed, and all queries related to the data have been addressed. 


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Modifications or additions to the analyses will be included in the relevant analysis plan. Any 
decisions to deviate from the planned analyses described in the protocol and in the SAP will be 
described in detail in the final CSR. The CSR will be reviewed and approved by the sponsor 
signatory and the lead investigator. 
10.1.7. 
Data Quality Assurance 
All participant data relating to the study will be recorded by an electronic CRF using an EDC 
system or transmitted to the sponsor or designee electronically (e.g., laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
electronically signing the CRF. 
The investigator must maintain accurate documentation that supports the information entered in 
the eCRF. 
The study will be monitored regularly by the sponsor or its designee throughout the study period. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
Monitoring details describing strategy (e.g., risk-based initiatives in operations and quality such 
as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities, and requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided in the Monitoring Plan. 
The sponsor or designee is responsible checking the accuracy and completeness of the data 
reported in the eCRFs and the consistency with the source documents. The sponsor assumes 
accountability for actions delegated to other individuals (e.g., contract research organizations 
[CROs]). 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
10.1.8. 
Source Documents 
Source documentation consists of existing medical records and/or study records developed and 
maintained by the investigator. Source documents provide evidence for the existence of the 
participant and substantiate the integrity of the data collected. 
Data recorded on source documents will be transcribed onto electronic case report forms 
(eCRFs) using an EDC system. 
Data entered in the eCRF that are transcribed from source documents must be consistent with the 
source documents or the discrepancies must be explained. The investigator may need to request 
previous medical records or transfer records, depending on the study. 
For the purpose of monitoring and auditing the study, source documentation will consist of 
existing medical records and/or study records developed and maintained by the investigator. 


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10.1.9. 
Record Retention 
Records and documents pertaining to the conduct of this study must be retained by the 
investigator for a minimum of 10 years after study completion unless local regulations or 
institutional policies require a longer retention period. 
No records may be destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without written notification 
to the sponsor. 
10.1.10. 
Study and Site Closure 
The sponsor reserves the right to close the study site(s) or terminate the study at any time for any 
reason at their sole discretion. Study sites will be closed upon study completion. A study site is 
considered closed when all required documents and study supplies have been collected and a 
study site closure visit has been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
d. Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the sponsor's procedures, or GCP guidelines 
e. Inadequate recruitment of participants by the investigator 
f. Discontinuation of further study intervention development. 
At the discretion of the sponsor, all materials and supplies provided to the investigator will be 
returned or disposed of in compliance with local regulatory requirements upon authorization 
from the sponsor, upon study completion. The investigator or designated clinical site staff will 
notify the IRB/IEC when the study has been completed. 
10.1.11. 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. 
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 


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10.2. 
Appendix 2: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.2.1. 
Definition of AE 
AE Definition 
An AE is any untoward medical occmTence in a patient or clinical study pa1ticipant, 
temporally associated with the use of study intervention, whether or not considered related to 
the study intervention. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abno1mal 
laborato1y finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of study intervention. 
Events Meeting the AE Definition 
Any abno1mal laboratory test results (hematology, clinical chemistry, or minalysis) or other 
safety assessments (e.g., ECG, radiological scans, vital signs measmements), including those 
that worsen from baseline, considered clinically significant in the medical and scientific 
judgment of the investigator (i.e., not related to progression of underlying disease). 
Exacerbation of a chronic or inte1mittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
New conditions detected or diagnosed after study intervention administi·ation even though it 
may have been present before the start of the study. 
Signs, symptoms, or the clinical sequelae of a suspected drng-drng interaction. 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a conc01nitant medication. Overdose per se will not be repo1ted as an AE/SAE unless it is 
an intentional overdose taken with possible suicidal/self-haiming intent Such overdoses 
should be repo1ted regardless of sequelae. 
Events 
Meeting the AE Definition 
Any clinically significant abnonnal laborato1y findings or other abnonnal safety assessments 
which are associated with the underlying disease, unless judged by the investigator to be more 
severe than expected for the paiticipant's condition. 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the pa1ticipant's 
condition. 
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Medical or surgical procedure ( e.g., endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the strut of the study that do not worsen. 
10.2.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
Results in death 
Is life-threatening 
The te1m 'life-threatening' in the definition of 'serious' refers to an event in which the 
paiticipant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the paiticipant has been detained (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician's office or outpatient setting. Complications 
that occur during hospitalization are AEs. If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious. When in doubt as to whether "hospitalization" 
occuned or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
Results in persistent disability/incapacity 
The te1m disability means a substantial disrnption of a person's ability to conduct nonnal life 
functions. 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diaiThea, influenza, and accidental trauma 
(e.g., sprained ankle) which may interfere with or prevent eve1yday life functions but do not 
constitute a substantial disrnption. 
Is a congenital anomaly/biith defect 
Other situations: 
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Medical or scientific judgment should be exercised in deciding whether SAE repo1iing is 
appropriate in other situations such as impo1iant medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant or may 
require medical or surgical inte1vention to prevent one of the other outcomes listed in the 
above definition. These events should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that 
do not result in hospitalization, or development of drng dependency or drng abuse. 
10.2.3. 
Definition of Serious Adverse Drug Reaction (Serious ADR) 
When an AE is judged to be serious and related to an investigational product, it is a Serious 
Adverse Drng Reaction and is subject to expedited repo1iing based on the parameters of this 
study. 
10.2.4. 
Definition of AESI 
AESis are AEs that the sponsor will carefully monitor. The following AEs will be collected and 
repo1ied as AESis: anaphylaxis or hypersensitivity reactions, and/or infusion reactions resulting 
in pennanent discontinuation of study inte1vention infusion during IV administration. 
10.2.5. 
Recording and Follow-Up of AE, SAE, AESI 
Recording 
Care will be taken not to introduce bias when detecting AEs, SAEs and AESis. Open-ended 
and non-leading verbal questioning of the pa1iicipant is the prefe1Ted method to inquire about 
AE occurrences. 
When an AE/SAE/ AES! occurs, it is the responsibility of the investigator to review all 
available documentation ( e.g., hospital progress notes, laboratory repo1is, and diagnostics 
repo1is) related to the event. 
The investigator will record all relevant AE/SAE/AESI info1mation in the CRF. 
AEs will be repo1ied on the AE CRF using a recognized medical te1m or diagnosis that 
accurately reflects the event. 
AE evaluations will be reviewed by the investigator or a medically qualified delegate. AE 
CRF pages are to be completed by members of the study team who are designated to perfo1m 
this task by the investigator. The onset and resolution dates of an AE and action taken in 
response to the AE will be documented. 
After the initial AE/SAE/ AES! report, the investigator is required to proactively follow each 
paiiicipant at subsequent visits/contacts. All SAEs, and non-serious AESis will be followed 
until resolution, stabilization, the event is othe1w ise explained, or the paiiicipant is lost to 
follow-up. 
It is not acceptable for the investigator to send photocopies of the paiticipant's medical 
records to the sponsor in lieu of completion of the AEISAEI AES! CRF page. 
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There may be instances when copies of medical records for ce1iain cases are requested by the 
Medical Monitor, the SRT, the IDMC and/or the sponsor. In this case, all paiiicipant 
identifiers, with the exception of the paiiicipant number, will be redacted on the copies of the 
medical records before submission. 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical info1mation. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE/ AES!. 
AEs/SAEs/ AES Is will be assessed for intensity and causal relationship to the study 
intervention. Note that local AEs repo1ied within the first 7 days after IM dosing ai·e 
considered to be study intervention-related. 
Follow-up and Resolution 
The investigator is obligated to perfo1m or aITange for the conduct of supplemental 
measurements and/or evaluations as medically indicated to elucidate the nature and/or 
causality of the AE/SAE/ AESI as fully as possible. This may include additional laborato1y 
tests or investigations, histopathological examinations, or consultation with other health care 
professionals. 
If a pa1iicipant dies during pa1iicipation in the study or during a recognized follow-up period, 
the investigator will provide the sponsor with a copy of any post-m01iem findings including 
histopathology, if available. 
New or updated info1mation will be recorded in the originally completed CRF. 
The investigator will submit any updated SAE/ AESI data to the sponsor within 24 hours of 
receipt of the info1mation. 
The onset and resolution dates of the event and medical cai·e provided in response to the event 
will be documented. 
AEs will be considered resolved when the condition returns to n01mal or returns to the 
paiiicipant's baseline sta.tus as established on Study Day 1, or when the condition has 
stabilized with the expectation that it will remain chronic. 
If the event has not resolved by the final study visit, it will be documented as "ongoing" on the 
CRF, however, follow-up of the SAE/AESI must continue until resolved or the condition has 
stabilized. Info1mation recorded on the CRF must be substantiated in the source documents. 
The resolution date to be recorded on the CRF is the last date on which the pa1iicipant 
experienced the AE. 
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10.2.5.1. Assessment of Intensity 
The investigator will assess the intensity of each AE reported during the study. In the case of 
local reactions, vital signs, systemic events, and laboratory abnormalities, the Grades 
delineated in Section 10.4, Appendix 4 will be employed. 
In the case of an AE or abnormal clinical laboratory result not included in Appendix 4, 
intensity will be assigned using the Grades described in the U.S. Department of Health and 
Human Services, Common Terminology Criteria for Adverse Events, Version 5.0 [US HHS 
2017] as follows: 
Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL)* 
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL**symptoms, 
causing inability to perform usual social and functional activities with intervention or 
hospitalization indicated 
Grade 4 Life-threatening consequences; urgent intervention indicated 
Notes: 
A semi-colon indicates ‘or’ within the description of the grade. 
*Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc. 
**Self-care ADL refers to bathing, dressing, and undressing, feeding self, using the toilet, 
taking medications, and not bedridden. 


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10.2.5.2. Assessment of Causality 
The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE/AESI. Only AEs that are local reactions to an IM injection are 
automatically assumed to be related to the study intervention, and therefore are not required to 
have causality assessed by the investigator. 
The investigator will assess whether the AE/SAE/AESI is either: 
Related: An AE/SAE/AESI is considered related to study intervention if there is a reasonable 
possibility that the study intervention contributed to the AE. 
or 
Not related: There is no reasonable possibility that the AE/SAE/AESI is causally related to 
administration of the study intervention. There are other more likely causes for the AE. 
The investigator will use clinical judgment to determine the relationship. 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study intervention administration will be 
considered and investigated. 
For each AE/SAE/AESI, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE/AESI and has provided an assessment of causality. 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to assess causality to include in the initial report. However, it is very important that 
the investigator always provide makes an assessment of causality with the initial submission 
of the SAE data. 
The investigator may change his/her assessment of causality when considering additional follow-
up information and submit an SAE follow-up report with the updated causality assessment. 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements applicable to SAEs.  
10.2.5.3. Assessment of Expectedness 
Not applicable  
10.2.5.4. Assessment of Outcome 
The outcome of each SAE/AESI must be reported. For analysis purposes, the outcome for 
serious adverse events will be determined on the final study visit. 
Outcome of all AEs will be classified as one of the following: 
•Resolved 


• Resolved with sequelae 
•Ongoing 
•Death. 
10.2.6. 
SAEs, AESis, and Serious ADR Reporting 
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Reporting to Sponsor or Delegate Via the Electronic Data Collection Tool 
The primary mechanism for reporting an SAE or AESI by the investigator to the sponsor or 
delegate will be the electronic data collection tool. 
The site will enter the SAE or AESI data into the electronic system as soon as it is identified. 
All SAEs (related and unrelated) and AESis are reported to the sponsor or delegate throughout 
the study. 
Serious AD Rs are repo1ied to the sponsor or delegate during the entire study period. Serious 
AD Rs are to be repo1ied after completion of the study, if the investigator becomes aware of a 
serious ADR. 
The investigator must not wait to collect additional infonnation to fully document the event 
before notifying the sponsor or delegate of a SAE or an AESI. The initial notification should 
include the following: 
• 
Protocol number and name and contact number of the investigator 
• 
Paiiicipant ID number (and initials and date of birth, if available) 
• 
Date paiiicipant received study intervention 
• 
SAE/ AESI te1m and date of event onset 
• 
CmTent status of SAE/ AESI 
The investigator is responsible for expedited safety repo1i submission to the sponsor delegate 
and the sponsor delegate repo1is to the national regulato1y authority(ies) within specific time 
periods of being notified of the event. Therefore, it is impo1iant that the investigator subinit 
additional info1mation requested as soon as it becomes available. 
Original and follow-up repo1is must be subinitted according to the requirements of the 
regulato1y authorities. 
If the electronic system is unavailable, the site may use the paper SAE/ AESI data collection 
tool (see next section) instead of the EDC, in order to repo1i the event within 24 hours of 
becoming aware. 
After the study is completed at a given site, the electronic data collection tool, if used, will be 
taken off-line to prevent the entry of new data or changes to existing data .. 
If a site receives a repo1i of a new SAE from a study pa1iicipant or receives updated data on a 
previously repo1ied SAE after the electronic data. collection tool has been taken off-line, then 
the site can repo1i this info1mation on a paper SAE fonn (see next section). 
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Contacts for SAE/AES! repo1iing and for all safety personnel are contained in the Team 
Contact List which will be stored on-site in the Site Regulato1y Binder and maintained by the 
study sponsor. 
Reporting via Paper CRF 
If the eCRF cannot be completed, the Supplemental SAE/ AES! Repo1i (paper fo1m) should be 
completed by the investigator or his/her designee, and scanned and emailed, or faxed to the 
sponsor or delegate. The investigator is responsible for ensuring an adequate transmission of 
the fax and will store the distribution confnmation in the study file. 
In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the SAE/ AES! report form sent by overnight mail or courier service. 
Initial notification via telephone does not replace the need for the investigator to complete and 
sign the SAE/ AES! CRF pages within the designated reporting time frames. 
10.3. 
Appendix 3: Contraceptive Guidance and Collection of 
Pregnancy Information 
Contraceptive Guidance: 
Male paiiicipants with pa1iners of childbearing potential must agree to use condoms during the 
study and for 90 days after the study, and they must refrain from spe1m donation for at least 90 
days after the end of study. 
Female pa1iicipants of childbeai·ing potential must not be pregnant, breastfeeding, or attempting 
to become pregnant for 28 days before Screening and throughout the duration of the study. These 
paiiicipants must have a negative sernm pregnancy test at Screening in order to be eligible for 
randomization and treatment with study intervention. In addition, these female paiiicipants must 
be willing to commit to using a consistent and acceptable method of contraception for the 
duration of the study and for 90 days after study completion if they engage in intercourse. 
Acceptable methods of contraception are: 
• 
Consistent use of systemic contraception, including biith control pills, transde1mal 
patch, vaginal ring, implants, and injectables. 
• 
Consistent use of double banier method, e.g., condoms, cervical cap, diaphragm, 
vaginal contraceptive film with spe1micide. 
• 
Use of intrauterine device with a low failure rate ( defined as < 1 % risk of pregnancy 
per yeai-) 
• 
Monogamous intercourse with a vasectomized man or has only same-sex paiiners. 
Female pa1iicipants who ai·e not sexually active but become so dming the study must agree to 
follow the contraceptive requii·ements above. 
Female pa1iicipants who ai·e not of childbeai·ing potential must meet at least one of the 
following criteria: 
• 
At least 1 year since the last menstrual period. 
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• Surgically sterile (tubal ligation, bilateral oophorectomy, salpingectomy, or 
hysterectomy) 
• Congenitally sterile 
• Diagnosed as infertile and not undergoing treatment to reverse infertility. 
Collection of Pregnancy Information: 
• A participant who becomes pregnant during the study period will be asked to complete all 
visits and procedures through Day 151 as described in Table 2 or Table 3, as applicable. 
After she completes Day 151, or in the event that she voluntarily withdraws from the 
study and agrees to provide additional information regarding the pregnancy, the 
investigator will utilize the ‘Pregnancy Outcome Form’ during the remaining gestation 
period to collect information on the health of the participant, the outcome of the 
pregnancy, and the health of the neonate. Neonate follow-up will occur for 6 weeks 
beyond the estimated delivery date. 
• 
If a participant is determined to be pregnant during the study (after receiving a dose of the 
study intervention), the investigator will report the pregnancy to the sponsor or delegate 
and collect follow-up information on the participant and the neonate. Generally, follow-
up will not be required for longer than 6 weeks beyond the estimated delivery date. Any 
termination of pregnancy will be reported, regardless of fetal status (presence or absence 
of anomalies) or indication for the procedure. 
• 
While pregnancy is not considered to be an AE or a SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or a SAE. Any abnormal 
pregnancy outcome that comes to the attention of the investigator (e.g., spontaneous 
abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) is considered to 
be a SAE. 
• 
Any pregnancy-related SAE that occurs after study participation and is made known to 
the investigator and is assessed as related to the study intervention will be reported to the 
sponsor or the sponsor’s designee. The investigator is not obligated to actively seek such 
information in former study participants who become pregnant during the study. 


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10.4. 
Appendix 4: Toxicity Tables 
The following toxicity tables are extracted from the FDA Guidance for Industry [FDA 2007]. 
Table 8: FDA Toxicity Grading Scale- Clinical Abnormalities 
 Local Reactions 
Local Reaction to 
Injectable Product 
Mild 
(Grade 1) 
 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Pain  
Does not interfere 
with activity  
Repeated use of 
non-narcotic pain 
reliever > 24 hours 
or interferes with 
activity  
Any use of narcotic 
pain reliever or 
prevents daily 
activity  
Emergency room 
(ER) visit or 
hospitalization  
Tenderness  
Mild discomfort to 
touch  
Discomfort with 
movement  
Significant 
discomfort at rest  
ER visit or 
hospitalization  
Erythema/Redness *  2.5 – 5 cm  
5.1 – 10 cm  
> 10 cm  
Necrosis or 
exfoliative 
dermatitis  
Induration/Swelling 
**  
2.5 – 5 cm and does 
not interfere 
with activity  
5.1 – 10 cm or 
interferes with 
activity  
> 10 cm or 
prevents daily 
activity  
Necrosis  
* In addition to grading the measured local reaction at the greatest single diameter, the measurement should be 
recorded as a continuous variable. 
** Induration/Swelling should be evaluated and graded using the functional scale as well as the actual measurement. 
Table 8:  
FDA Toxicity Grading Scale- Clinical Abnormalities- 
Vital Signs 
Vital Signs * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Fever (°C) ** 
(°F) **  
38.0 – 38.4 
100.4 – 101.1  
38.5 – 38.9 
101.2 – 102.0  
39.0 – 40 
102.1 – 104  
> 40 
> 104  
Tachycardia - beats 
per 
minute  
101 – 115  
116 – 130  
> 130  
ER visit or 
hospitalization for 
arrhythmia  
Bradycardia - beats 
per 
minute***  
50 – 54  
45 – 49  
< 45  
ER visit or 
hospitalization for 
arrhythmia  
Hypertension 
(systolic) - 
mm Hg  
141 – 150  
151 – 155  
> 155  
ER visit or 
hospitalization for 
malignant 
hypertension  
Hypertension 
(diastolic) - 
mm Hg  
91 – 95  
96 – 100  
> 100  
ER visit or 
hospitalization for 
malignant 
hypertension  
Hypotension 
(systolic) – 
mm Hg  
85 – 89  
80 – 84  
< 80  
ER visit or 
hospitalization for 
hypotensive shock  


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Respiratory Rate – 
breaths 
per minute  
17 – 20  
21 – 25  
> 25  
Intubation  
* Participant should be at rest for all vital sign measurements. 
** Oral temperature; no recent hot or cold beverages or smoking. 
*** When resting heart rate is between 60 – 100 beats per minute. Use clinical judgment when characterizing bradycardia 
among some healthy populations, for example, conditioned athletes. 
Table 8:  
FDA Toxicity Grading Scale- Clinical Abnormalities, continued… 
Systemic Events 
Systemic 
 (General) 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Nausea/vomiting  
No interference 
with activity or 1 – 
2 
episodes/24 hours  
Some interference 
with activity or > 2 
episodes/24 hours  
Prevents daily 
activity, requires 
outpatient IV 
hydration  
ER visit or 
hospitalization for 
hypotensive shock  
Diarrhea  
2 – 3 loose stools 
or 
< 400 gms/24 hours 
4 – 5 stools or 
400 – 800 gms/24 
hours  
6 or more watery 
stools or 
> 800gms/24 hours 
or requires 
outpatient IV 
hydration  
ER visit or 
hospitalization  
Headache  
No interference 
with 
activity  
Repeated use of 
non- 
narcotic pain 
reliever > 24 hours 
or 
some interference 
with activity  
Significant; any 
use of narcotic 
pain reliever or 
prevents daily 
activity  
ER visit or 
hospitalization  
Fatigue  
No interference 
with 
activity  
Some interference 
with activity  
Significant; 
prevents daily 
activity  
ER visit or 
hospitalization  
Myalgia  
No interference 
with 
activity  
Some interference 
with activity  
Significant; 
prevents daily 
activity  
ER visit or 
hospitalization  
Systemic Illness  
Mild 
(Grade 1)  
Moderate 
(Grade 2) 
Severe 
(Grade 3)  
Potentially Life 
Threatening 
(Grade 4)  
Illness or clinical 
adverse 
event (as defined 
according to applicable 
regulations)  
No interference 
with 
activity  
Some interference 
with activity not 
requiring medical 
intervention  
Prevents daily 
activity and 
requires medical 
intervention  
ER visit or 
hospitalization  
 


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Table 9: FDA Toxicity Grading Scale- Laboratory Abnormalities 
Serum * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4)** 
Sodium – Hyponatremia mEq/L  
132 – 134  
130 – 131  
125 – 129  
< 125  
Sodium – Hypernatremia mEq/L  
144 – 145  
146 – 147  
148 – 150  
> 150  
Potassium – Hyperkalemia mEq/L  
5.1 – 5.2  
5.3 – 5.4  
5.5 – 5.6  
> 5.6  
Potassium – Hypokalemia mEq/L  
3.5 – 3.6  
3.3 – 3.4  
3.1 – 3.2  
< 3.1  
Glucose – Hypoglycemia mg/dL  
65 – 69  
55 – 64  
45 – 54  
< 45  
Glucose – Hyperglycemia 
Fasting – mg/dL 
Random – mg/dL  
100 – 110 
110 – 125  
111 – 125 
126 – 200  
>125 
>200  
Insulin requirements 
or hyperos-molar 
coma  
Blood Urea Nitrogen 
BUN mg/dL  
23 – 26  
27 – 31  
> 31  
Requires dialysis  
Creatinine – mg/dL  
1.5 – 1.7  
1.8 – 2.0  
2.1 – 2.5  
> 2.5 or requires 
dialysis  
Calcium – hypocalcemia mg/dL  
8.0 – 8.4  
7.5 – 7.9  
7.0 – 7.4  
< 7.0  
Calcium – hypercalcemia mg/dL  
10.5 – 11.0  
11.1 – 11.5  
11.6 – 12.0  
> 12.0  
Magnesium – hypomagnesemia 
mg/dL  
1.3 – 1.5  
1.1 – 1.2  
0.9 – 1.0  
< 0.9  
Phosphorous – hypophosphatemia 
mg/dL  
2.3 – 2.5  
2.0 – 2.2  
1.6 – 1.9  
< 1.6  
CPK – mg/dL  
1.25 – 1.5 x 
ULN***  
1.6 – 3.0 x ULN  
3.1 –10 x 
ULN  
> 10 x ULN  
Albumin – Hypoalbuminemia g/dL  
2.8 – 3.1  
2.5 – 2.7  
< 2.5  
--  
Total Protein – Hypoproteinemia 
g/dL  
5.5 – 6.0  
5.0 – 5.4  
< 5.0  
--  
Alkaline phosphate – 
increase by factor  
1.1 – 2.0 x 
ULN  
2.1 – 3.0 x ULN  
3.1 – 10 x 
ULN  
> 10 x ULN  
Liver Function Tests –ALT, AST 
increase by factor  
1.1 – 2.5 x 
ULN  
2.6 – 5.0 x ULN  
5.1 – 10 x 
ULN  
> 10 x ULN  
Bilirubin – when accompanied 
by any increase in Liver Function 
Test increase by factor  
1.1 – 1.25 x 
ULN  
1.26 – 1.5 x 
ULN  
1.51 – 1.75 x 
ULN  
> 1.75 x ULN  
Bilirubin – when Liver Function Test 
is normal; increase by factor  
1.1 – 1.5 x 
ULN  
1.6 – 2.0 x ULN  
2.0 – 3.0 x 
ULN  
> 3.0 x ULN  
Cholesterol  
201 – 210  
211 – 225  
> 226  
---  
Pancreatic enzymes – amylase, lipase  1.1 – 1.5 x 
ULN  
1.6 – 2.0 x ULN  
2.1 – 5.0 x 
ULN  
> 5.0 x ULN  
* The laboratory values provided in the tables serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate. 
** The clinical signs or symptoms associated with laboratory abnormalities might result in 
characterization of the laboratory abnormalities as potentially life-threatening (Grade 4). For 
example. a low sodium value that falls within a Grade 3 parameter (125-129 mE/L) should be 
recorded as a Grade 4 hyponatremia event if the participant had a new seizure associated with the 
low sodium value. 
***ULN is the upper limit of the normal range. 


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Table 9: FDA Toxicity Grading Scale- Laboratory Abnormalities, continued… 
Hematology * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening (Grade 4) 
Hemoglobin (Female) - gm/dL  
11.0 – 12.0  
9.5 – 10.9  
8.0 – 9.4  
< 8.0  
Hemoglobin (Female) 
change from baseline value - 
gm/dL  
Any decrease 
– 1.5  
1.6 – 2.0  
2.1 – 5.0  
> 5.0  
Hemoglobin (Male) - gm/dL  
12.5 – 13.5  
10.5 – 12.4  
8.5 – 10.4  
< 8.5  
Hemoglobin (Male) 
change from baseline value – 
gm/dL  
Any decrease 
– 1.5  
1.6 – 2.0  
2.1 – 5.0  
> 5.0  
WBC Increase - cell/mm
3 
10,800 – 
15,000  
15,001 – 
20,000  
20,001 – 25, 
000  
> 25,000  
WBC Decrease - cell/mm
3 
2,500 – 3,500  
1,500 – 2,499  1,000 – 1,499  
< 1,000  
Lymphocytes Decrease - 
cell/mm
3 
750 – 1,000  
500 – 749  
250 – 499  
< 250  
Neutrophils Decrease - cell/mm
3 
1,500 – 2,000  
1,000 – 1,499  500 – 999  
< 500  
Eosinophils - cell/mm
3 
650 – 1500  
1501 - 5000  
> 5000  
Hypereosinophilic  
Platelets Decreased - cell/mm
3 
125,000 – 
140,000  
100,000 – 
124,000  
25,000 – 
99,000  
< 25,000  
PT – increase by factor 
(prothrombin time)  
1.0 – 1.10 x 
ULN**  
1.11 – 1.20 
x ULN  
1.21 – 1.25 x 
ULN  
> 1.25 ULN  
PTT – increase by factor 
(partial thromboplastin time)  
1.0 – 1.2 x 
ULN  
1.21 – 1.4 x 
ULN  
1.41 – 1.5 x 
ULN  
> 1.5 x ULN  
Fibrinogen increase - mg/dL  
400 – 500  
501 – 600  
> 600  
--  
Fibrinogen decrease - mg/dL  
150 – 200  
125 – 149  
100 – 124  
< 100 or associated 
with gross bleeding or 
disseminated intravascular 
coagulation (DIC)  
WBC= white blood cell count 
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate. 
** “ULN” is the upper limit of the normal range. 
GGT grading is not provided in the FDA toxicity grading scale tables. The following grading 
scale is from the U.S. Department of Health and Human Services, Common Terminology 
Criteria for Adverse Events, Version 5.0 [US HHS 2017]: 
• 
Grade 1:  >ULN - 2.5 x ULN if baseline is normal; 2.0 - 2.5 x baseline if baseline is 
abnormal 
• 
Grade 2: >2.5 - 5.0 x ULN if baseline is normal; >2.5 - 5.0 x baseline if baseline is abnormal 
• 
Grade 3: >5.0 - 20.0 x ULN if baseline is normal; >5.0 - 20.0 x baseline if baseline is 
abnormal 
• 
Grade 4: >20.0 x ULN if baseline is normal; >20.0 x baseline if baseline is abnormal. 
 


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


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11. 
References 
AstraZeneca. Nirsevimab MELODY Phase III trial met primary endpoint of reducing RSV lower 
respiratory tract infections in healthy infants. 26 April 2021. 
https://www.astrazeneca.com/media-centre/press-releases/2021/nirsevimab-phase-iii-trial-met-
primary-endpoint.html 
Aliprantis A, Wolford D, Caro L, Maas BM, et al. A Phase 1 Randomized, Double-Blind, 
Placebo-Controlled Trial to Assess the Safety, Tolerability, and Pharmacokinetics of a 
Respiratory Syncytial Virus Neutralizing Monoclonal Antibody MK-1654 in Healthy Adults. 
Clin Pharmacol Drug Dev. 2020 Oct 30. doi: 10.1002/cpdd.883. Epub ahead of print. PMID: 
33125189. 
Brady M, Byington C, Davies H, et al. Updated Guidance for Palivizumab Prophylaxis Among 
Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus 
Infection. Pediatrics. 2014;134(2):415-20. 
Clinicaltrials.gov NCT No. 03979313. A Study to Evaluate the Safety and Efficacy of 
MEDI8897 for The Prevention of Medically-Attended RSV LRTI in Healthy Late Preterm and 
Term Infants (MELODY). June 2019. 
Clinicaltrials.gov NCT No. 03959488. A Study to Evaluate the Safety of MEDI8897 for The 
Prevention of Medically-Attended RSV Lower Respiratory Tract Infection (LRTI) in High-Risk 
Children. May 2019. 
Domachowske J, Khan AA, Esser M, et al. Safety, Tolerability and Pharmacokinetics of 
MEDI8897, an Extended Half-life Single-dose Respiratory Syncytial Virus Prefusion F-targeting 
Monoclonal Antibody Administered as a Single Dose to Healthy Preterm Infants. Pediatr Infect 
Dis J. 2018;37:886–892. 
Food and Drug Administration (FDA) 2020. FDA Guidance on Conduct of Clinical Trials of 
Medical Products during COVID-19 Pandemic Guidance for Industry, Investigators, and 
Institutional Review Boards. 
FDA CDER (U.S. Department of Health and Human Services Food and Drug Administration, 
Center for Drug Evaluation and Research). Guidance for Industry: Estimating the Maximum 
Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. July 
2005. 
FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials. September 2007 
Feltes T, Sondheimer H, Tulloh R, et al. A Randomized Controlled Trial of Motavizumab Versus 
Palivizumab for the Prophylaxis of Serious Respiratory Syncytial Virus Disease in Children with 
Hemodynamically Significant Congenital Heart Disease. Pediatric Research. 2011:70(2):186-91. 
Griffin MP, Khan AA, Esser M, et al. Safety, Tolerability, and Pharmacokinetics of MEDI8897, 
the Respiratory Syncytial Virus Prefusion F-Targeting Monoclonal Antibody with an Extended 
Half-Life, in Healthy Adults. Antimicrob Agents Chemother. 2017;61(3)e017:14-16. 
Griffin P, Yuan Y, Takas T, Domachowske J, et al. Single-Dose Nirsevimab for Prevention of 
RSV in Preterm Infants. NEJM. 2020;383(5):415-25. 


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Hansel T, Kropshofer H, Singer T, et al. The safety and Side Effects of Monoclonal Antibodies. 
Nat Rev Drug Discov. 2010;9(4):325-38. 
Higgins D, Trujillo C, Keech C. Advances in RSV Vaccine Research and Development – A 
Global Agenda. Vaccine. 2016;34:2870-75. 
Madhi S, Polack F, Piedra P, et al. Respiratory Syncytial Virus Vaccination during Pregnancy 
and Effects in Infants. N Engl J Med. 2020;383:426-39. 
Obando-Pacheco P, Justicia-Grande A, Rivero-Calle I, et al. Respiratory Syncytial Virus 
Seasonality: A Global Overview. Clin Inf Dis. 2018:217:1356-64. 
Robbie G, Criste R, Dall’Acqua W, et al. A Novel Investigational Fc-Modified Humanized 
Monoclonal Antibody, Motavizumab-YTE, Has an Extended Half-Life in Healthy Adults. 
Antimicrobial Agents and Chemotherapy. 2013;57(12):6147–6153. 
Rouha H, Badarau A, Mirkina I, et al. Characterization of highly potent human monoclonal 
antibodies targeting different antigenic sites on the prefusion RSV-F protein. RSV 2018. 11th 
International Respiratory Syncytial Virus Symposium; Ashville NC. 
Scheltema N, Gentile A, Lucion F, et al. Global Respiratory Syncytial Virus-Associated 
Mortality in Young Children (RSV GOLD): A Retrospective Case Series. Lancet Glob Health. 
2017;5:e984–91. 
Shi T, McAllister DA, O'Brien KL, 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. The Lancet. 
2017;390(10098):P946-958. 
Simões E, Forleo-Neto E, Geba G, et al. Suptavumab for the Prevention of Medically Attended 
Respiratory Syncytial Virus Infection in Preterm Infants. Clin Infect Dis. Published online 08 
Sept 2020.p1-9. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa951/5902774. 
Vogel WH. Infusion Reactions: Diagnosis, Assessment, And Management. Clinical J Oncology 
Nursing. 2010;14(2): E10-21. 
U.S. Department of Health and Human Services (US HHS), Common Terminology Criteria for 
Adverse Events (CTCAE) Version 5.0. November 27, 2017. 
Zhu Q, McLellan J, Kallewaard N, Ulbrandt N, et al. A Highly Potent Extended Half-Life 
Antibody as a Potential RSV Vaccine Surrogate for All Infants. Sci Transl Med. 
2017;9(388):eaaj1928. 
Zhu Q, Lu B, McTamney P, et al. Prevalence and Significance of Substitutions in The Fusion 
Protein of Respiratory Syncytial Virus Resulting in Neutralization Escape from Antibody 
MEDI8897. J. Infect. Dis. 2018; 218:572–80. 


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12. 
Protocol Version History 
The Protocol Version updates and amendment summary of changes is provided below. 
• 
Version 1, dated 26 May 2021 
• 
Version 1.1, dated 09 June 2021 
• 
Version 2.0, dated 20 July 2021 
• Version 3.0, dated 10 December 2021 
• 
Version 4.0, dated 21 January 2022 


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Version 1.1, dated 09 June 2021 
Rationale for changes to V1: The update from Version 1 to Version 1.1 was made prior to study start 
and prior to IRB approval, and was issued as a response to a preliminary review by the IRB, and internal 
reviews of supporting documents. For this reason, the update was not considered as a protocol 
amendment. 
• 
Section 5.1 Inclusion Criteria; recommendation: Since the apparent terminal half-life of the 
drug in monkeys is around 20 days, the Board recommends ensuring male contraception is 
used for duration of the study (5 months) to surpass the 5x t1/2 time window. 
text added: For male participants who have a female partner of childbearing potential or a 
pregnant partner: condom use for the duration of the study period (approximately 5 months). 
• 
Section 5.4 Screen Failures; edited as follows: 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomized to entered into the study and do not receive study 
intervention/entered in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure criteria for participants who are screen failures in 
order 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 not met, and any SAE. 
Screening assessments can be done at any time during the screening interval,window (Day -30 to 
Day -2; SoA, Section 1.3), except for the written informed consent, which must be completed 
prior to any screening procedure. 
Re-screening is only permitted under one or more of the following conditions: 
• If a participant presents with an acute illness on the day of first planned study 
intervention, e.g., elevated temperature, acute respiratory or gastrointestinal illness, or 
urinary tract infection (UTI), and meets all other inclusion/exclusion eligibility criteria 
and can be rescreened within the originally defined screening window (SoA, Section 1.3). 
• WhenIf there are technical difficulties with phlebotomy at screening (e.g., laboratory 
reports hemolyzed blood), technical error in running the laboratory tests or an abnormal 
urine analysis due to menstruation or UTI, and the participant can be rescreened within 
the originally defined screening window (SoA, Section 1.3). 
• If a participant is undergoing screening period and the study reaches a pausing rule. The 
participant may rescreenre-screen when and if the IDMC provides approval to restart 
recommends, and the Sponsor determines, that the study may continue. 
Repeat screening procedures may be performed as long as they are completed within the 
screening window. Rescreened participants should be assigned the same participant number as 
for the initial screening. 
 
• 
Section 7.2 Participant discontinuation or withdrawal. 


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Text added to be in line with changes made to ICF. If the participant leaves the study, the 
participant’s medical information will still be used or shared to the extent allowed by law. Any 
leftover samples will be destroyed after testing is completed unless the participant withdraws 
consent to sample use, in which case the samples will be destroyed at that time. Any test results 
from the samples collected before withdrawal can still be included in the analyses. 
Text regarding diary cards and memory aids was clarified as requested by the IRB. Edits are 
shown below (new text= bold italics and old text= strike-through) 
• 
Section 8.1.9 Diary card and Memory aid, edited as follows: 
Diary Card 
Before leaving the clinic after dosing (Dose Escalation Phase, on Day 3 and Expansion Phase on 
Day 1 or Day 2 depending on whethercompletion of the participant is kept overnight),post-
dosing on-site confinement, participants will be given a diary card and receive guidance on how 
to fill in the card. All participants will receive a digital thermometer to record temperature. 
Participants who receive an IM dose will also receive a digital thermometer, mirror, and a ruler 
to measure diameter of redness and/or swelling at the injection site, if present. 
The diary card will be used by the study participants to record the duration, and intensity (refer to 
Section 8.2.3.1) of solicited local injection site AEs (for participants who receive an IM doses 
only) dose), and solicited systemic AEs up to Day 7 following injection/ or infusion. Unsolicited 
AEs will also for all participants. This information should be recorded if any occur during up to 
in the participant diary card at approximately the same time each evening, through Day 7, 
including any local reactions reported after Day 7. The site staff will record duration and 
intensity of solicited local AEs (IM doses only) and solicited AEs while the participant is under 
confinement. This documentation of this information should be collected at approximately the 
same time each evening up to Day 7. 
Memory aid 
A memory aid will be distributed to the participant on the Day 8 visit and at each subsequent 
visit through Day 121 for Dose Escalation Phase cohorts and through Day 91 for the Expansion 
Phase cohort. Participants will be instructed to record unsolicited AEs whenever they occur, 
using the aid. The memory aids will be collected and reviewed with site staff at each subsequent 
visit through the end of the study. 
• 
Section 8.2 Adverse Events and Serious Adverse Events 
Site staff will document the local in the study source during the confinement for all cohorts. 
The site staff will record solicited injection site AEs (IM doses only) and solicited systemic 
solicited AEs in the study source on Day 1AEs (all participants), including duration and 2 for 
Cohort 2 and the systemic solicited AEs in the study source on Day 1 and 2intensity, during 
confinement. Refer to Section 8.1.9 for Cohorts 1, 3, and 4. Site staff will document the local 
injection site and systemic solicited AEs in the study source on Day 1 for Cohort 5 if the 
participant is confined from Day 1 to Day 2. Participants will record their information on a to be 
recorded in the diary card (starting on Day 3 for the Dose Escalation Phase and on Day 1 in the 


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Expansion Phase or Day 2 if the participant is confined overnight) and will return the diary card 
to the site on Day 8. by participants, through Day 7. 
Unsolicited AEs including AESIs, SAEs, and safety laboratory parameters Grade 1 and above 
will be collected from screening through Day 151 and recorded in the AE log by the study team. 
• 
Section 8.2.6 Safety Review Team 
Edits made during review of the SRT plan. Members changed to 4 and added AESIs in text to be 
consistent with other text. 
An ad hoc SRT meeting will occur immediately if any Grade 3 or higher AE, or SAE, or AESI, 
is reported, regardless of relationship to the study intervention. If the event is determined to be 
study intervention-related, the IDMC review will be triggered, and pausing will occur with 
enrollment and further dosing, until after the IDMC review. 
The SRT will consist of a panel of at least 34 members, including the Gates MRI study physician 
clinical lead, a the Gates MRI pharmacovigilance physician safety lead, the study Medical 
Monitor, and the site principal investigator. The SRT members are part of the study team and 
will review blinded safety data. 
• 
Section 8.8 Biomarkers 
Text removed: Samples collected during this clinical study may be transferred to a biobank and 
used for exploratory research outside the clinical protocol as described in the ICF. Transfer to the 
biobank will be documented and any testing of coded biobank samples will not be reported in the 
CSR. 
• 
Section 10.1.4 and 10.1.14.1 
 Informed Consent and Process, deleted text that no longer applies to the study 
Removed text that is no longer applicable: The ICF will contain a separate section that addresses 
the use of remaining mandatory samples for optional exploratory research. The investigator or 
authorized designee will explain to each participant the objectives of the exploratory research. 
Participants will be told that they are free to refuse to participate and may withdraw their consent 
at any time and for any reason during the storage period. A separate signature will be required to 
document a participant's agreement to allow any remaining specimens to be used for exploratory 
research. Participants who decline to participate in this optional research will not provide this 
separate signature. Refer to (section deleted) for sample retention. 
The ICF will contain a separate section that addresses the use of remaining mandatory samples 
for research not described in the protocol, e.g., assay development and assay quality control. A 
separate signature will be required to document a participant's agreement to allow any remaining 
specimens to be used for research not described in the protocol. 
Samples collected for storage for exploratory endpoint testing are included in the protocol and 
are not optional. However, consent for storage and testing of samples for research not described 
in the protocol is optional, and if not signed, would not exclude the participant from the study. 
 


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Version 2.0, dated 20 July 2021 
Rationale for changes to V1: The update from Version 1.1 (v1.1) to Version 2 (v2), was 
prepared following FDA review and comments after IND submission. The major changes 
include the following: 
In response to FDA’s comment that all adverse events should be collected throughout the dosing 
and follow-up period irrespective of who is collecting and documenting the event (i.e., 
participant vs. study site staff), the protocol was amended and text was aligned throughout.  All 
adverse events (both solicited and unsolicited) will be collected throughout the dosing and 
follow-up periods (up to Day 151 for all participants) irrespective of who is 
collecting/documenting the event.  
In response to the FDA’s comment to use the same standardized toxicity grading scale 
consistently throughout entire protocol. The Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers enrolled in Preventive Vaccine Clinical Trials, September 2007 was 
referenced consistently throughout the protocol and added textual reference to CTCAE version 
5.0 for events not covered by the vaccine grading scales.  
The pausing rules and contraceptive requirements were modified as recommended by the FDA. 
Exclusion criteria were added for COVID-19 vaccine and for participants who previously 
received the study intervention in this study, based on Data Management and study team review 
regarding safety of the participant. 
Other changes were considered minor to improve readability and clarity. 
Complete List of Changes: 
Title page and footer and header: change v1.1 to v2.0. 
Added a page for Document History (Page 2) 
Document History 
Document 
Date 
Version 2.0 
20 July 2021 
Original Protocol v1.1 
09 June 2021 
 
Signature page: added v2 
List of Abbreviations: Added for RSMO1 to abbreviation for AUC, and of RSM01 to abbreviations for 
CD91, CD151, Cmax, Cmin and Tmax, deleted AKA for AUC, added NCT National (U.S.) Clinical Trial 
 
Synopsis: 
Dose Escalation Phase: 


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After the sentinel participant in each Dose Escalation Phase cohort receives RSM01, the next 
participant can be dosed 24 hours later, if there is no safety concern. After the 24-hour post-dose 
period for the sentinel participant in each cohort On any given day, individual participants in 
the Dose Escalation Phase cohorts should be dosed at least 2 hours apart regardless of route 
mode of administration (IM or IV). The ≥2-hour interval between administering IV infusions is 
to begin at the end of the previous infusion. For participants receiving the IM dose of study drug 
in Cohort 2, the ≥2-hour interval between administering IM injections to successive participants 
is to begin at the time of the previous participant’s IM injection. If RSM01 is administered using 
2 injections, the ≥2-hour interval begins at the time of the second injection. 
Each dose escalation step will proceed after all participants in the prior cohort haves completed 
Day 15, and the Safety Review Team (SRT) has reviewed the data and determined that a 
pausing rule has not been met. there are no events necessitating a pause. 
Dose Expansion Phase: 
Enrollment in the Dose Expansion Phase cohort (Cohort 5) will begin after Day 15 for all 
participants in Cohort 4, and after the SRT has reviewed the data and determined that a pausing 
rule has not been met. no pausing event has occurred Cohort 5 will include 28 participants 
randomized 6:1. 
Theose predictions suggests that the concentration of RSM01 will be above the efficacy 
threshold (EC90) on Day 151 following a RSM01dose of 300 or 600 mg IM. 
Synopsis 
Pausing Rules: Pausing rules include: 
Pausing rules (reasons for pausing the study) are in effect during the active enrollment and 
dosing period. Any one of the following will prompt a study pause: 
• death in any participant in whom the event causing death is judged to be related to the 
study drug by the investigator. 
• any occurrence in any participant of a SAE judged to be related by the investigator. 
• any occurrence in any participant of an AESI (anaphylaxis, hypersensitivity reaction, 
and/or infusion reaction resulting in permanent discontinuation of study drug infusion 
during IV administration). 
• any occurrence of Grade 3 or higher toxicity assessed to be related to the study drug by 
the investigator. 
• any occurrence of a clinically significant Grade 3 or higher laboratory abnormality 
assessed to be related to the study drug by the investigator. 
If any of the pausing criteria are met, enrollment/patient accrual as well as dosing of enrolled 
participants will be suspended pending IDMC’s review of all available safety data and the U.S. 
Food and Drug administration (FDA) will be notified in an expedited manner. 


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• at least 1 participant with a Grade 3 or higher AE (other than solicited AEs), considered 
related to the study intervention, 
• at least 1 participant with a SAE that is considered related to the study intervention 
• at least 1 participant with an AESI (AESIs include anaphylaxis, hypersensitivity reaction, 
and infusion reactions resulting in permanent discontinuation of the study intervention 
infusion during IV administration). 
If a pausing rule is met, this will trigger a pause in enrollment and any dosing of participants, and 
an IDMC review of safety data will be conducted 
IDMC: added: See Section 8.2.7. 
Safety Review Team: Meetings to decide on proceeding to each subsequent Dose Escalation 
Phase cohort will occur when all participants in the current cohort completes Day 15. The SRT 
will also meet approximately every 8 weeks during the Dose Expansion Phase (See Section 
8.2.6). The SRT will also receive an alert for any Grade 3 or higher AE or SAE and will 
determine if the AE/SAE is related to study intervention in order to trigger an IDMC review. 
Visits: The participants in the Dose Expansion Phase cohort will remain at the clinic for at least 
4 hours after dosing on Day 1, and possibly for the night of Day 1, based on investigator 
decision. 
Blood Sampling: Dose Escalation Phase cohorts: On Day 1, PK blood draw will occur pre-
dosing 1 hour (+/- 30 minutes before administration of IM injection or beginning of infusion), 
at within 5 minutes (± 1 minute) after end of infusion for IV dosing only, and at 8-hours (±0.5 
hour) and 24-hours (±1 hour) after end of infusion for IV doses and at 8-hours (±0.5 hour) and 
24-hours (±1 hour) after IM dose and at 8 hours post dose for both the IV and IM dosing ADA 
and RSV neutralizing antibody activity samples will be obtained pre-dose only (+/- 30 minutes) 
before administration of IM injection or beginning of infusion 
Dose Expansion Phase cohort: On Day 1, the blood collection for PK, ADA and RSV 
neutralizing antibody activity will occur pre-dosing only 1 hour (+/- 30 minutes) before 
administration of IM injection. 
Masking: Participants and all study personnel will be blinded to the randomization, with one 
exception: the first sentinel participant in each Dose Escalation Phase cohort will be single-
blinded (participant-blinded) and will receive the respective dose of RSM01. Authorized study 
site personnel will administer doses 


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Figure 1 :Removed tag for Day 15 Coho1i 5 visit then and moved a1Tow for interim analysis to 
appear below Coho1i 4 instead of below Coho1i 5. Removed ve1iical line at Day 91 for interim 
analysis and added a diagonal line and removed ve1iical line from Day 151 and added a diagonal 
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Schedule of Activities (SoA) 
Table 2: Schedule of Activities for the Dose Escalation Phase (Cohorts 1-4) 
Added distribute memo1y aid to V3 and V 4 and collect memo1y aid to V 4 and VS for Table 2 
and distribute to Vl and collect to V8 for Table 3 
Table 2: Schedule of Activities for the Dose Escalation Phase (Coho1is 1-4) 
Visits Sere 
en 
Distribute memo1y aid 
Collect memory aid 
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Vl 
V2 V3 V4 vs 
X X 
X 
X 
X 
89 


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Table 3: Schedule of Activities for the Expansion Phase (Cohort 5) 
Visits Screen 
Pre-Vt 
Vl 
V2 
Distribute memo1y aid 
X 
X 
Collect memory aid 
X 
Added an X for pregnancy test and vital signs, for discontinuation visit for both Table 2 and 
Table 3 
Visits Discon 
Studv Dav and Visit window davs ( d) Visit 
Activities: 
Sennn pregnancy test2 
X 
Vital siims 
X 
Table 2 Footnote 8: Blood samples for PK assessments on Day 1 (Visit 1) will be drawn at pre-
dosing J hour(+/- 30 minutes) before administration of IM injection or beginning of infusion, 
after end of infusion for IV doses and at 8-hours (±0.5 hour) and 24-hours (±1 hour) after IM 
doses past dase fer eatli IV aad IM dases 
ADA and RSV neutralizing antibody on Day 1 (Visit 1) will be drawn pre-dose only 1 hour (+l-30 
minutes) before administration of IM 
Table 3 Footnote 7: Blood samples for PK, ADA and RSV neutralizing antibody at Day 1 will be 
drawn at pre-dose only 1 hour (+/- 30 minutes) before administration of IM 
Section 2.1 RSV and Burden of Disease 
RSV is the most common pathogen identified in young children with acute LRTI. Most children 
acquire~ an RSV infection by the time they are 2 years old, causing a mild, cold-like illness 
within 4 to 6 days after infection. However, in some children it leads to a more severe illness 
such as bronchiolitis and,lpneumonia and may also increase theif risk of developing subsequent 
asthma and/or recunent wheezing episodes in early childhood. 
Section 2.3 RSM01 mAb Candidate 
RSM0l(also designated as alffi.ADI-15618-IVNS YTE) 
Section 2.3.1 Non-Clinical Development of RSM01 
In summary, there were no test-aiiicle related target organ,s....ef toxicities~, no effects on vital 
systems, 
Section 2.5.1 Edited text: 
The.ese projections suggest that following aa RSM0l doses ~
300 mg is predieted the RSM0l 
concentration is predicted to be above the tai·get EC90 threshold at Day 151. 
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Section 2.5.2: Edited text: 
Final selection of the dose to be administered to Cohort 5 will be made by the sponsor and 
informed by available RSM01 PK data, as well as relevant safety data, from the Dose Escalation 
Phase. 
Available interim Any available PK data from the Dose Escalation Phase cohorts from earlier 
s, combined with published data from previous studies of monoclonal antibodies, will be used 
to develop a population PK model to describe the individual concentration time profiles of 
RSM01. Subsequently, the model will be used in a simulation mode to predict the proportion of 
participants that are expected to have RSM01 concentrations be above the EC90 on Day 151. 
The tentatively determined dose to be tested in the Dose Expansion Phase cohort is between 
≥300 mg and ≤600 mg IM, based on… 
Section 2.6 Benefit/Risk Assessment 
However, it is we expected that RSM01 will have a similar benefit/risk profile to nirsevimab. 
A Phase 1 FiH study in adults in the U.S. evaluated a single dose of nirsevimab or Placebo 
administered as an IV dose of 300mg, 1000mg, or 3000mg or as an IM dose of 100mg or 300mg 
[Griffin, 2017] and did not have any study discontinuations due to AEs or SAEs. The most 
frequently reported nirsevimab-related AEs were headaches (all mild), occurring in 3 (2.9%) 
participants. 
There were no anaphylaxis or other notable hypersensitivity reactions. In the nirsevimab group, 4 
infants experienced cases reported rash. One infant experienced case reported one day of 
petechiae occurring 4 months after nirsevimab, which was not assessed by a health care provider. 
All 3 AESI infants cases in the Placebo group had rash. 
In the nirsevimab Phase 1b/2a infant trial: none no one had ADA at baseline and only the mAb 
group… 
The Phase 1 MK-1654 study randomized 152 healthy adults in a at 3:1 ratio 
RSV Mutations 
Escape mutant selection studies with RSM01 were performed… 
… have largely comparable neutralization potency based on in vitro and in vivo virus 
neutralization assays… 
In vitro cell-based neutralization studies showed that RSM01 performed better than other RSV 
monoclonal antibodies palivizumab 
General Risks with MAb Infusion 
Administration of any mAb may carry a risk of immune reactions such as acute anaphylaxis, 
serum sickness and the generation of antibodies against the mAb.; hHowever, these reactions are 
…. In this regard, as RSM01 is targeted to a viral antigen, and is a fully human mAb (IgG1), and 
it is expected to have … 
Section 4.1 Study Design Overview 


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Dose Escalation Phase, continued: 
After the 24-hour post-dose period for the sentinel participant in each Dose Escalation Phase 
cohort, On any given day, each participants in the Dose Escalation Phase cohorts should be 
dosed at least 2 hours apart regardless of route mode of… 
Each dose escalation step will proceed after all participants in the prior cohort haves completed 
Day 15, and the SRT has reviewed the data and determined that a pausing rule has not been met 
that no pausing event has occurred that no pausing event has occurred. 
Dose Expansion Phase: 
Enrollment in the Dose Expansion Phase (Cohort 5) will begin after Day 15 for participants in 
Cohort 4, and after the SRT has reviewed the data and determined that a pausing rule has not 
been met. 
Those predictions … 
Section 5.1 Inclusion Criteria: (inclusive) 
Sex 
4. Both males and females are eligible to participate. 
Male participants with partners of childbearing potential must agree to use condoms 
during their participation in the study and for 90 days after the participant completes the 
study. Male participants must also agree to refrain from sperm donation for at least 90 
days after they complete the study. 
Female participants of childbearing potential must not be pregnant, breastfeeding, or 
attempting to become pregnant for 28 days before Screening and throughout the duration 
of their participation in the study. These participants must have a negative serum 
pregnancy test at Screening in order to be eligible for randomization and treatment with 
study intervention. In addition, female participants must be willing to commit to using a 
consistent and acceptable method of contraception for the duration of their participation 
in the study and for 90 days after they complete the study if they engage in intercourse. 
Acceptable methods of contraception are: 
• 
Consistent use of systemic contraception, including birth control pills, transdermal 
patch, vaginal ring, implants, and injectables. 
• 
Consistent use of double barrier method, e.g., condoms, cervical cap, diaphragm, 
vaginal contraceptive film with spermicide. 
• 
Use of intrauterine device with a low failure rate (defined as < 1% risk of pregnancy 
per year) 
• 
Monogamous intercourse with a vasectomized man or has only same-sex partners. 
Female participants who are not sexually active but become so during the study must 
agree to follow the contraceptive requirements above. 
Female participants who are not of childbearing potential must meet at least one of the 
following criteria: 


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• 
At least 1 year since the last menstrual period. 
• 
Surgically sterile (tubal ligation, bilateral oophorectomy, salpingectomy, or 
hysterectomy) 
• 
Congenitally sterile 
• 
Diagnosed as infertile and not undergoing treatment to reverse infertility. 
For female participants: not pregnant and agree to avoid pregnancy throughout the study. For 
male participants who have a female partner of childbearing potential or a pregnant partner: 
condom use for the duration of the study period (approximately 5 months). 
Women physically capable of pregnancy must agree to use an acceptable method of avoiding 
pregnancy during the study. Acceptable methods of avoiding pregnancy include sexual 
abstinence (not engaging in sexual intercourse), a confirmed sterile partner, or at least 2 
contraception methods from the following list: male or female condom, diaphragm, 
intrauterine devices (IUDs), hormonal contraceptive (oral, injection, transdermal patch, or 
implant). Adequate contraception does not apply to participants of childbearing potential 
with same sex partners, when this is their preferred and usual lifestyle. 
Additional Requirements: Participants must who … 
Section 4.2 End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the study or 
conduct of the last scheduled procedure shown in the SoA for the last participant in the trial. 
Section 5.2 Exclusion Criteria: restarted numbering at 1 (previously started at 7) and 
renumbered after adding new criteria. 
Prior Concomitant Therapy: added the following criterion 
Added 7. Having received any vaccination (including COVID-19 vaccine) within the 15 days 
before Day 1, or planning to receive a dose of any vaccine during the 15-day period following 
Day 1. 
Prior/Concurrent Clinical Study Experience 
Added: 13. Previously having participated and received study intervention in the current study. 
 
 


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Section 6. Study Intervention 
Table 5 
Dosage, Volume and 
Route of 
Administration  
300mg (53mL) (50mL) per IV 
infusion 
1000mg (60mL) (50mL) per IV 
infusion 
3000mg (130mL) (100mL) per IV 
infusion 
300mg (3mL) IM injection (1 
injection of 3mL in the anterolateral 
thigh muscle) 
Same volume and number of 
infusions/injections as the 
RSM01 group. 
 Dose Expansion Phase Cohort 
 
Section 6.1 RSM01 Drug Product 
Deleted Vials with visible particles at the end of the thaw procedure should not be used. Refer to 
Pharmacy manual for details. 
Section 6.2 Placebo Drug Product 
Each vial contains an isotonic, sterile solution that is a colorless to yellow liquid, essentially 
free of visible particles; some opaque or translucent particles may be present. Refer to 
Pharmacy manual for details. 
Section 6.3 Study Intervention Preparation and Administration 
For the Dose Escalation Phase, the first (sentinel) participant undergoing study intervention 
administration in each cohort will receive be in the RSM01 arm. The next participant in each 
cohort can be dosed at least 24 hours after the sentinel participant. After the 24-hour post-dose 
period for the sentinel participant in each Dose Escalation Phase cohort On any given day, 
participants in the Dose Escalation Phase only should be dosed at least 2 hours apart regardless 
of route mode of administration (IM or IV). The ≥2-hour wait time between IV infusions is to 
begin at the end of the previous participant’s infusion. The ≥2-hour wait time between IM 
injections is to begin at the time of the previous participant’s IM injection. 
Section 6.3.1 IM Injection 
For IM dosing in the Dose Escalation Phase, participants in Cohort 2 the 300mg Cohort will… 
The Dose Expansion Phase cohort may receive RSM01 (≥300mg to ≤ 600mg) or Placebo up to 
600mg IM of RSM01 in the anterolateral thigh muscle. If more than 3 mL of study intervention 
300mg is administered in a single dose, the volume and number of injections will be adapted… 
Section 6.3.2 IV Infusion 
The total IV infusion volume will be 53mL for Cohort 1, 60 mL for Cohort 3, and 130mL for 
Cohort 4. 50mL for the 300mg cohort and the 1,000mg cohort, and 100mL for the 3,000mg 


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cohort The IV infusion time will be approximately 2 hours or less depending on the cohort. The 
≥2-hour wait time between administration of IV infusions to successive participants is to begin at 
the end of the previous participant’s infusion. 
Section 6.4. Handling/Storage/Accountability 
The study intervention (RSM01 and and Placebo) must be stored at 2°C to 8°C in a secured 
location with no access for unauthorized personnel. 
At the end of the study, u Unused supplies will be destroyed… 
Section 6.5.1. Randomization 
The remaining 6 participants in each Dose Escalation Phase cohort (Cohorts 1, 2, 3 and 4) will 
be… 
Section 6.5.2 Masking 
Deleted duplicate text The first sentinel participant in each of the Dose Escalation Phase cohorts 
will each receive the respective dose of RSM01 in a single blind fashion: participants will be 
observer blind (the study personnel will know their study assignment). 
Section 6.7 Concomitant Therapy 
anti-inflammatory drugs and, antipyretic drug, or… 
A COVID-19 vaccination may be received by a participant during the study but not within the 
15 days immediately following administration of the study intervention. Note that any planned 
COVID 19 vaccination may be given, but it is recommended to defer vaccination until at least 7 
days following study intervention administration 
Section 6.8 Dose Modification 
This is a dose escalation and dose expansion study. Refer to Section 3 for details regarding dose 
escalation and dose expansion 
Section 7.1.1. Pausing Rules 
Pausing rules (reasons for pausing the study) are in effect during the active enrollment and 
dosing period. Any one of the following will prompt a study pause: 
• 
death in any participant in whom the event causing death is judged to be related to the 
study drug by the investigator. 
• 
any occurrence in any participant of a SAE judged to be related by the investigator. 
• 
any occurrence in any participant of an AESI (anaphylaxis, hypersensitivity reaction, 
and/or infusion reaction resulting in permanent discontinuation of study drug infusion 
during IV administration). 
• 
any occurrence of Grade 3 or higher toxicity assessed to be related to the study drug by 
the investigator. 
• 
any occurrence of a clinically significant Grade 3 or higher laboratory abnormality 
assessed to be related to the study drug by the investigator. 


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If any of the pausing criteria are met, enrollment/patient accrual as well as dosing of enrolled 
participants will be suspended pending IDMC’s review of all available safety data and the U.S. 
FDA will be notified in an expedited manner. 
Refer to Section 8.2.6 for the role of SRT and Section 8.2.7 for the role of the IDMC. 
If the investigator and/or the SRT observes that a pausing rule is met, the investigator will 
inform the sponsor and/or the SRT as soon as possible and within 24 hours of the observation. 
The SRT and/or sponsor will notify the investigator and the IDMC members of the pause in 
enrollment and participant dosing as soon as possible and within 24 hours of receiving 
notification of the pausing rule being met. 
When a pausing rule is met, the IDMC members will convene an urgent ad hoc review 
meeting, review all relevant unblinded safety data, and make a recommendation to the 
sponsor. The FDA will be advised of the IDMC actions and recommendations. 
The IDMC may recommend continuation of the study pause or resumption of enrollment and 
dosing with or without changes to the protocol. The final decision to pause or resume study 
activities will always be the responsibility of the sponsor. All IDMC recommendations will be 
stored according to the IDMC Charter. 
All sponsor decisions will be documented in a memorandum to the study file. The sponsor or 
delegate is responsible for prompt communication to the study site of decisions related to 
pausing or resuming the study activities, including notification to the investigator, relevant 
IRBs/IECs and regulatory authorities. 
The clinical site will be allowed to resume activities only upon receipt of written notification 
from the sponsor. 
If an investigator observes that a pausing rule is met, the investigator will inform the sponsor or 
delegate as soon as possible and within 24 hours of the observation. The sponsor or delegate will 
notify the investigator and the IDMC members of the pause in enrollment and participant dosing 
as soon as possible and within 24 hours of receiving notification of the condition being met. 
The IDMC members will review all relevant safety data, convene an urgent ad hoc review 
meeting and make a recommendation to the sponsor with regards to maintaining the pause or 
resuming enrollment/participant dosing. 
If the SRT observes that a pausing rule is met, the SRT will inform the sponsor and the IDMC 
as soon as possible and within 24 hours of the identification of the condition being met. 
The SRT will notify the study investigator of the pause in enrollment and dosing as soon as 
possible and within 24 hours of the observation. 
If the sponsor or delegate observes that a pausing rule is met, the sponsor will notify the study 
investigator and the IDMC of the pause in enrollment and dosing as soon as possible and within 
24 hours. The IDMC will review all relevant safety data, convene an urgent ad hoc review 
meeting and make a recommendation to the sponsor with regards to lifting or maintaining the 
pause in enrollment/participant dosing. 
The IDMC may recommend resumption of enrollment and dosing with or without changes to the 
protocol. The final decision to pause or resume study activities will always be the responsibility 
of the sponsor. All IDMC recommendations will be stored according to the IDMC Charter. 


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All sponsor decisions will be documented in a memorandum to the study file. The sponsor or 
delegate is responsible for prompt communication to all relevant study sites of decisions related 
to pausing or resuming the study activities, including notification to the investigator, relevant 
IRBs/IECs and regulatory authorities. 
The clinical sites will be allowed to resume activities only upon receipt of written notification 
from the sponsor. 
 Section 7.2 Participant Discontinuation or Withdrawal from the Study 
At this visit, topics around participant safety as well as the use of already collected biospecimens 
will be discussed, and the procedures and specimen collection indicated in the SoA… 
A participant who becomes pregnant during the study period will be asked to complete all 
visits and procedures through Day 151 as described in Table 2 or Table 3, as applicable. After 
she completes Day 151, or in the event that she voluntarily withdraws from the study and 
agrees to provide additional information regarding the pregnancy, the investigator will utilize 
the ‘Pregnancy Outcome Form’ during the remaining gestation period to collect information 
on the health of the participant, the outcome of the pregnancy, and the health of the neonate. 
Neonate follow-up will occur for 6 weeks beyond the estimated delivery date (refer to Section 
10.3). 
Neonate follow-up will occur for 6 weeks beyond the estimated delivery date (refer to 
Section10.3). 
A participant who becomes pregnant will be followed for safety as described in the protocol, 
without any of the protocol required blood draws. She will be followed up during the gestation 
period and after the delivery to collect information on the health of the participant and the 
newborn. The results of the outcome of pregnancy will be captured in a ‘Pregnancy Outcome 
Form’ and the sponsor will be notified. 
 
Section 7.4 COVID-19 Contingency Plans 
Assure changed to ensure 3 times 
At the study sites study site 
Section 8. Study Assessments and Procedures 
described in Sections 5.1 and Section 5.2, respectively. 
Section 8.1 Safety Assessments 
All Day 1 safety assessments and sample collections are prior to administration of study 
intervention. 
Prior to opening each of Cohorts 2, 3, and 4 to enrollment, the SRT will conduct safety 
assessment of data for the previous cohort collected for all participants through Day 15, 
Section 8.1.1 Confinement Period and Sentinel Participants 
Participants in the Dose Escalation Phase will be confined at the study site after informed 
consent is signed,… 


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On Day -1, participants will undergo a serum pregnancy test, safety laboratory assessments and 
other screening procedures 
The first participant in each of the Dose Escalation Phase cohorts will be a sentinel participant 
and will receive RSM01 at the respective dose of RSM01 in a participant-blind an observer
blind fashion. 
The next participant in each cohort can be dosed at least 24 hours later., if there is no safety 
concern. 
Dose Expansion Phase 
On this Day -1 visit,… participants will begin confinement, and undergo a serum pregnancy test, 
safety laboratory assessments and… 
Section 8.1.2 
Physical examination at screening will include, at a minimum, assessment of height and weight, 
body temperature, and resting vital signs (including percent oxygen saturation by pulse 
oximetry),… 
Section 8.1.2.1 Vital Signs 
Vital sign measurements will be recorded for pulse rate, systolic and diastolic blood pressure, 
respiratory rate, and body temperature and percent oxygen saturation by fingertip pulse 
oximetry. 
Section 8.1.3 Focused Physical Examination and Medications/Vaccinations 
A fFocused physical examinations, will be performed on Day 1 and all subsequent visits, as 
indicated in the SoA if indicated by participant’s medical complaint and will include 
assessments of body systems involved in the complaint. Focused physical examinations will be 
symptom directed. 
Throughout the study, any concomitant medications taken, including antipyretics, and anti-
inflammatories, and vaccinations will be recorded 
Section 8.1.4 Pregnancy Status Assessment 
A blood sample will be collected from female participants at screening and at Day -1 for serum 
beta human chorionic gonadotropin (βHCG) testing. 
Serum βHCG testing of female participants should be performed during the study if a pregnancy 
is suspected. 
Serum βHCG testing of female participants of childbearing potential should be performed at 
the discontinuation visit. 
A participant who becomes pregnant during the study period will be asked to complete all 
visits and procedures through Day 151 as described in Table 2 or Table 3, as applicable. After 
she completes Day 151, or in the event that she voluntarily withdraws from the study and 
agrees to provide additional information regarding the pregnancy, the investigator will utilize 
the ‘Pregnancy Outcome Form’ during the remaining gestation period to collect information 
on the health of the participant, the outcome of the pregnancy, and the health of the neonate. 


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Neonate follow-up will occur for 6 weeks beyond the estimated delivery date (refer to Section 
10.3). 
If a participant becomes pregnant during the study, she will be withdrawn from all study 
procedures going forward, i.e., blood draws and laboratory evaluations described in the SoA will 
not be performed once a participant is known to be pregnant. However, she will be encouraged to 
continue in the study for safety follow up. 
Section 8.1.6 Electrocardiogram, Hepatitis Screening and Urine Drug Screening 
Triplicate (unmarked) 12-lead ECGs will be obtained and averaged. For the Dose Escalation 
Phase, the ECGs will be taken at screening, and 24 hours post-dose, on Day 2. For the Dose 
Expansion Phase, the ECGs will be taken at screening. 
Section 8.1.7. Clinical Safety Laboratory Assessments 
Clinical safety laboratory parameters that will be evaluated include: 
g. Hematology: Complete blood count (hemoglobin, hematocrit, red blood cell count, 
platelets count and white blood cells count) and absolute counts for neutrophils, 
lymphocytes, eosinophils and monocytes 
h. Serum chemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
alkaline phosphatase, total bilirubin, gamma glutamyl transferase (GGT), creatinine, blood 
urea nitrogen, lactate dehydrogenase (LDH), and glucose, albumin, sodium, potassium, 
chloride, bicarbonate, and calcium 
The investigator must review the laboratory report, document thise review 
Section 8.1.9 
Diary Card 
The diary card will be collected and reviewed by the investigator (or designee) on the Day 8 
Visit 
Memory Aid 
A memory aid will be utilized by participants to collect unsolicited AEs beginning at discharge 
from the clinic, through Day 151 (end of study participation). Participants will be instructed to 
record unsolicited AEs whenever they occur, recording such AEs on the memory aid. 
A memory aid will be distributed to the participant on the Day 8 visit and at each subsequent 
visit through Day 121 for Dose Escalation Phase cohorts and through Day 91 for the Expansion 
Phase cohort. Participants will be instructed to record unsolicited AEs whenever they occur, 
using the aid. 
Section 8.2 Adverse Events and Serious Adverse Events 
Site staff will document any AEs in the study 
Solicited AEs that continue beyond Day 7 will be captured in the unsolicited AEs memory… 
Immediate safety concerns should be discussed with the sponsor, and the SRT. The SRT will 
trigger an IDMC review if any pausing rule is met event occurs 


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Clinical Biochemistry and/or hematology results findings may also qualify as AEs (Section 
10.4, Appendix 4). if the investigator considers them as such. 
However only the investigator or sub-investigator study physician is responsible for assessment, 
including assignment of causality and, for unsolicited AEs, the intensity, and for reporting and 
management of all AEs. The investigator is responsible for following up all AEs regardless of 
their relatedness to study intervention or study procedures, or AEs that caused the participant to 
withdraw from discontinue the study… 
Medical History/Current Medical Conditions section of the CRF, not in the AE section. 
Investigators are not obligated to actively seek AEs, SAEs or AESIs after a participant 
concludes conclusion of study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, and he/she 
considers the event to be related to the study intervention or study participation, the investigator 
must notify the sponsor or designee within the same 24 hours. timeline. 
Section 8.2.3.1 AE Intensity 
The intensity of AEs will be classified by the investigator based on the toxicity grading tables 
(Section 10.4 10.4 Appendix 4). In the case of an AE or abnormal clinical laboratory result 
not included in Appendix 4, intensity will be assigned using the Grades described in the U.S. 
Department of Health and Human Services, Common Terminology Criteria for Adverse 
Events, Version 5.0 [US HSS 2017] (See Section 10.2.5.1.) 
Local solicited AEs will be recorded on the diary card by the participant and graded and/or 
measured by the participant. An exception is that the study investigators will grade solicited 
AEs during the confinement period. Any participant-reported Grade 3 or higher adverse event 
will be assessed by the investigator. 
Unsolicited AEs will be classified by the investigator as mild (Grade 1, not interfering with 
normal daily activities), moderate (Grade 2, interfering with normal daily activities), severe 
(Grade 3, preventing normal daily activities) or potentially life threatening (Grade 4). Refer to 
Appendix 2, Section 10.2.5.1 and Section 10.4 for toxicity grading tables. Local solicited AEs 
will be recorded on the diary card by the participant and either graded and/or measured by the 
participant. An exception is that the study investigators will grade solicited AEs during the 
confinement period for the Dose Escalation Phase. 


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Section 8.2.3.2 AE Causality/Relationship to Study Intervention 
All AEs will be evaluated by the investigator or medically qualified designee (i.e., investigator, 
sub-investigator study physician) to assess characterize the relationship between study 
intervention and the AE… 
The causality will be assessed as either related… 
the Medical Monitor or and sponsor designee 
The sponsor or designee will never downgrade a case from serious to non-serious or change the 
investigator assessment of causality from related to not related. 
Any participant-reported Grade 3 or higher adverse event will be assessed by the investigator. 
Section 8.2.6 Safety Review Team 
Meetings of the SRT to decide on proceeding to each subsequent cohort will occur when all 
participants in the current cohort have completed Day 15. The SRT will also meet 
approximately every 8 weeks during the Dose Expansion Phase. The SRT will review all 
available blinded safety data collected at the time of the review to determine whether or not 
any pausing event has occurred (See Section 7.1.1.). If a pausing event does not occur, dose 
escalation or moving to the Dose Expansion Phase cohort can occur. 
If a pausing rule is met, the SRT will ask the IDMC to conduct a review of unblinded safety 
data. The IDMC will make a recommendation to the sponsor regarding the further conduct of 
the study. 
Meetings to decide on proceeding to each subsequent cohort will occur when the current cohort 
completes Day 15. The SRT will review all available safety data collected at the time of the 
review to determine whether or not any pausing event occurs that would trigger an IDMC 
review. If a pausing event does not occur, dose escalation or moving to the Dose Expansion 
Phase cohort can occur. 
An ad hoc SRT meeting will occur immediately if any Grade 3 or higher AE, or SAE, or AESI, 
is reported, regardless of relationship to the study intervention. If the event is determined to be 
study intervention related, the IDMC review will be triggered, and pausing will occur with 
enrollment and further dosing, until after the IDMC review. 
Section 8.2.7 Independent Data Monitoring Committee 
The IDMC will operate according to a charter approved by the sponsor and all IDMC members. 
The IDMC structure, participants, and other details will be provided in the charter. The charter 
will be approved prior to enrollment of the first study participant. 
The role of the IDMC will be to (a) monitor the progress of the study, (b) review blinded safety 
data provided by the SRT, (c) review unblinded safety data if a pausing rule is met, and (d) 
make recommendations to the sponsor on further conduct of the study if a pausing rule is met. 
review unblinded safety data and make recommendations if events necessitating a pause in 
enrollment and in participant dosing occur. Refer to Section 7.1.1 for pausing rules. 


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If a pausing rule is met, the IDMC may request additional information. 
The IDMC will make a formal recommendation to the sponsor on the continued enrollment into 
the trial if a pausing rule was met. Immediate safety concerns should be discussed among 
sponsor representatives and the SRT, and if needed the IDMC. 
If RSM01administration is paused by the Medical Monitor or the investigator, the IDMC will 
convene on an ad hoc basis. 
The recommendations of the IDMC, along with the sponsor’s decision, will be communicated to 
the investigator, to the responsible IRBs/IECs and to the US FDA. the investigators and the 
IRBs/IECs and the national regulatory authorities as required. The sponsor or its designee agrees 
to abide by any directives issued by the national regulatory authority or the IRB/IEC. 
Section 8.3. Treatment of Overdose 
If an overdose it were to occur, the overdose, including misuse or abuse of the product and 
medication errors, … 
Section 8.4 Blood Sampling 
Whole blood samples will be collected for measurement of PK, ADA, and RSV 
8.,5 Pharmacokinetics 
Dose Escalation Phase: At Visit 1, PK blood draw will occur pre-dosing, 1 hour (+/- 30 
minutes) before administration of IM injection or beginning of infusion, for all participants in 
Cohorts 1-4. For participants who receive IV study intervention, the timing of post-dose blood 
samples begins at the end of the IV infusion. Samples are obtained at 5 minutes (± 1 minute) 
at 8-hours (± 0.5 hour) and at 24-hours (± 1 hour) after the end of the infusion. For 
participants who receive IM study intervention, the timing of post-dose blood samples begins 
at the time of the IM injection and samples are obtained at 8-hours (± 0.5 hour) and at 24-
hours (± 1 hour) after the IM injection. 
Dose Expansion Phase: At Visit 1, only a pre-dose sample collected 1 hour (+/- 30 minutes) 
before administration of IM injection is obtained at Day 1. 
is obtained at Day 1. 
Blood for PK samples at all visits after Day 1 will be obtained according to the SoA as shown 
in Table 2 and Table 3. 
Dose Escalation Phase: At Visit 1, PK blood draw will occur pre dosing, within 5 minutes (± 1 
minute) after end of infusion for IV dosing only, and at 8 hours (± 0.5 hours) and 24 hours (± 1 
hours) post dose for both IV and IM doses. 
Dose Expansion Phase: Blood samples at Day 1 will be drawn at pre-dose only. 
Remaining samples collected for analyses of RSM01 may also be used to evaluate 
immunogenicity and/or safety aspects or efficacy aspects related to any concerns arising during 
or after the study. 


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Section 8.6 Pharmacodynamics 
Whole blood samples in serum separator tubes and VAMS devices will be 
Remaining samples collected for analyses of RSV neutralization may also be used to evaluate 
drug concentration, immunogenicity, and safety or efficacy aspects 
Section 9.1 Sample Size Determination 
 
This trial is an exploratory trial to characterize safety, tolerability, and pharmacokinetics of 
single doses of RSM01 mAb. 
Section 9.2 Populations for Analyses 
Table 6 
Modified Intention to treat (mITT) PK population 
Participants will be analyzed according to the intervention they actually received. 
Section 9.3 Statistical Analyses 
A detailed statistical analysis plan (SAP) centered on primary and secondary endpoints will be 
developed and finalized prior to unblinding the study and will further 
Section 9.3.1 Safety Primary Endpoints 
All solicited systemic AEs collected from Day 1 through Day 7 will be collected and 
summarized as described below. 
For participants with more than 1 episode of the same event, the AE with maximum severity will 
be used for tabulations. 
All unsolicited AEs, serious adverse events (SAEs), and/or AESI will be recorded from 
screening through Day 151. 
…Preferred Term (PT) and greatest highest intensity. 
The number of events reported, the number of participants and percentage of participants who 
experience one or more unsolicited AE through Day 151, and one or more SAE, and/or one or 
more AESI from screening through Day 151 will be summarized 
For participants with more than 1 episode of the same event, the AE with maximum intensity 
will be used for tabulations. 
Section 9.7 Interim Analysis 
Although the sponsor will be blinded throughout the study, such review of aggregated data could 
potentially lead to unblinding of the treatment received by individuals participants. 
Section 10.1.4.1 Informed Consent Forms 
If a participant cannot be randomized on the intended day of dosing (e.g., due to if elevated 
temperature) 
Section 10.2.4 Definition of AESI 


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The following AEs will be collected and reported as AESIs: anaphylaxis or hypersensitivity 
reactions, and/or infusion reactions resulting in permanent discontinuation of study intervention 
infusion during IV administration.of a participant who receives an IV dose of the study 
intervention 
Section 10.2.5 Recording and Follow-Up of AE, SAE, AESI 
There may be instances when copies of medical records for certain cases are requested by the 
Medical Monitor, the SRT, the IDMC and/or the sponsor. 
The investigator will then record all relevant AE/SAE/AESI information in the CRF. 
There may be instances when copies of medical records for certain cases are requested by the 
Medical Monitor, the SRT, the IDMC and/or the sponsor. 
Whenever possible, the diagnosis (not the individual signs/symptoms) will be documented as the 
AE/SAE/AESI. 
Note that local AEs reported within the first 7 days after IM dosing are considered to be study 
intervention-related. 
Follow-up and Resolution 
The onset and resolution dates of the event and medical care provided taken in response to the 
event will be documented. 
Section 10.2.5.1 Assessment of Intensity 
The investigator will assess the intensity of each AE reported during the study. In the case of 
local reactions, vital signs, systemic events, and laboratory abnormalities, the Grades 
delineated in Section 10.4, Appendix 4 will be employed. 
In the case of an AE or abnormal clinical laboratory result not included in Appendix 4, 
intensity will be assigned using the Grades described in the U.S. Department of Health and 
Human Services, Common Terminology Criteria for Adverse Events, Version 5.0 [USHSS 
HSS 2017] as follows: 
Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL* 
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL**symptoms, 
causing inability to perform usual social and functional activities with intervention or 
hospitalization indicated 
Grade 4 Life-threatening consequences; urgent intervention indicated 
A semi-colon indicates ‘or’ within the description of the grade. 
Notes: 
*Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc. 


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**Self-care ADL refers to bathing, dressing, and undressing, feeding self, using the toilet, 
taking medications, and not bedridden. 
The investigator will make an assessment of intensity for each AE reported during the study and 
assign it to 1 of 4 categories, as defined in Appendix 4, Section 10.4 
Grade 1 Mild symptoms, causing no or minimal interference with usual social and functional 
activities with intervention not indicated 
Grade 2 Moderate symptoms, causing greater than minimal interference with usual social and 
functional activities with intervention indicated 
Grade 3 Severe symptoms, causing inability to perform usual social and functional activities 
with intervention or hospitalization indicated 
Grade 4 Potentially life threatening symptoms, causing inability to perform basic self care 
functions with intervention indicated to prevent permanent impairment, persistent disability, or 
death 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as described 
in the definition of an SAE, NOT when it is rated as severe. 
Section 10.2.5.2 Assessment of Causality 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements applicable to SAEs. 
Section 10.2.5.4. Assessment of Outcome 
The outcome of each SAE/AESI must be reported to the sponsor. 
Section 10.2.6 SAEs, AESIs, and Serious ADR Reporting 
Reporting to Sponsor’s or Delegate’s (CRO Safety Team) Via the Electronic Data 
Collection Tool 
Serious ADRs are reported to the sponsor or delegate during and to the CRO Safety Team for 
the entire study period. Serious ADRs are to be reported after completion of the study, if the 
investigator becomes aware of a serious ADR. even after the trial is over, if the sponsor, 
Medical Monitor or investigator become aware of them 
The investigator must not wait to collect additional information to fully document the event 
before notifying the CRO Safety Team of an the sponsor or delegate of a SAE or an AESI. 
• SAE/AESI term and date of event onset 
Contacts for SAE/AESI reporting and for all safety personnel 
Reporting via Paper CRF 
If the eCRF cannot be completed, the Supplemental SAE/AESI Report (paper form) should be 
completed by the investigator or his/her designee, and scanned and emailed, or faxed to the 
sponsor or delegate. CRO Safety Team. 
Other Events Requiring Immediate Reporting 


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The investigator must report the following events by scanning and emailing, or faxing the 
appropriate form to the sponsor or delegate CRO Safety Team within 24 hours of becoming 
aware of the event: 
Section 10.3 Appendix 3 Contraceptive Guidance and Collection of Pregnancy Information 
Contraceptive Guidance: 
Male participants with partners of childbearing potential must agree to use condoms during 
the study and for 90 days after the study, and they must refrain from sperm donation for at 
least 90 days after the end of study. 
Female participants of childbearing potential must not be pregnant, breastfeeding, or 
attempting to become pregnant for 28 days before Screening and throughout the duration of 
the study. These participants must have a negative serum pregnancy test at Screening in order 
to be eligible for randomization and treatment with study intervention. In addition, these 
female participants must be willing to commit to using a consistent and acceptable method of 
contraception for the duration of the study and for 90 days after study completion if they 
engage in intercourse. Acceptable methods of contraception are: 
• Consistent use of systemic contraception, including birth control pills, transdermal 
patch, vaginal ring, implants, and injectables. 
• Consistent use of double barrier method, e.g., condoms, cervical cap, diaphragm, 
vaginal contraceptive film with spermicide. 
• Use of intrauterine device with a low failure rate (defined as < 1% risk of 
pregnancy per year) 
• Monogamous intercourse with a vasectomized man or has only same-sex partners. 
Female participants who are not sexually active but become so during the study must 
agree to follow the contraceptive requirements above. 
Female participants who are not of childbearing potential must meet at least one of the 
following criteria: 
• At least 1 year since the last menstrual period. 
• Surgically sterile (tubal ligation, bilateral oophorectomy, salpingectomy, or 
hysterectomy) 
• Congenitally sterile 
• Diagnosed as infertile and not undergoing treatment to reverse infertility. 
Collection of Pregnancy Information: 
• 
If a participant is determined to be pregnant during the study (after receiving a dose of 
the study intervention), the investigator will report the pregnancy to the sponsor or 
delegate and collect follow-up information on the participant and the neonate. 
Generally, follow-up will not be required for longer than 6 weeks beyond the estimated 
delivery date. Any termination of pregnancy will be reported, regardless of fetal status 
(presence or absence of anomalies) or indication for the procedure. 


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• 
While pregnancy is not considered to be an AE or a SAE, any pregnancy complication 
or elective termination of a pregnancy will be reported as an AE or a SAE. Any 
abnormal pregnancy outcome that comes to the attention of the investigator (e.g., 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) 
is considered to be a SAE. 
• 
Any pregnancy-related SAE that occurs after study participation and is made known to 
the investigator and is assessed as related to the study intervention will be reported to 
the sponsor or the sponsor’s designee. The investigator is not obligated to actively seek 
such information in former study participants who become pregnant during the study. 
Contraception Guidance: 
Women physically capable of pregnancy must agree to use an acceptable method of avoiding 
pregnancy for one year after study intervention. 
Acceptable methods of avoiding pregnancy include at least one of the following: 
• 
sexual abstinence (not engaging in sexual intercourse) 
• 
a confirmed sterile partner 
• 
use of at least 2 of the contraceptive methods shown below: 
o hormonal contraceptives (oral, injection, transdermal patch, or implant) 
o IUD 
o male or female condom 
o diaphragm. 
Adequate contraception does not apply to participants of childbearing potential with same sex 
partners, when this is their preferred and usual lifestyle. 
i. The investigator will collect follow up information on the participant and the neonate and 
the information will be forwarded to the sponsor. Generally, follow up will not be required 
for longer than 6 weeks beyond the estimated delivery date. Any termination of pregnancy 
will be reported, regardless of fetal status (presence or absence of anomalies) or indication 
for the procedure. 
j. While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication 
or elective termination of a pregnancy will be reported as an AE or SAE. Abnormal 
pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, 
ectopic pregnancy) are considered SAEs. 
• 
Any pregnancy related SAE that occurs after study participation and is made known to 
the investigator and is assessed as related to the study intervention will be reported to the 
sponsor or the sponsor’s designee. The investigator is not obligated to actively seek this 
information in former study participants.


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Section 10.4 Appendix 4: Toxicity Tables 
The following toxicity tables are extracted from the FDA Guidance for to the Industry 
Notes to Table 9: 
** “ULN” is the upper limit of the normal range. 
GGT grading is not provided in the FDA toxicity grading scale tables. The following grading 
scale is from the U.S. Department of Health and Human Services, Common Terminology 
Criteria for Adverse Events, Version 5.0 [US HSS 2017]: 
Other: 
eg changed to e.g. 
ie changed to i.e. 
added missing comma’s where applicable 
corrected minor spelling errors 
updated table of content 
updated first use of abbreviation as appropriate 
changed subject to participant throughout 


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Version 3.0, dated 10 December 2021 
Rationale for v3.0 (changes to v2, 20 July 2021): The update from v2 to v3, was prepared to 
define the responsibilities of the Safety Review Team, the sponsor Chief Medical Officer, and 
the Independent Data Monitoring Committee.  
Other minor changes were made for correction or clarification. All changes are provided below. 
New text is shown in bold italics and old text is shown with strikethroughs. 
Synopsis 
Safety Review Team: A SRT will be established as the team responsible for recommending 
dose escalation or dose expansion to the sponsor’s Chief Medical Officer dose escalation 
decisions and proceeding to dose expansion.  
Meetings of the SRT to provide a recommendation on dose escalation or dose expansion will 
occur during the Dose Escalation Phase when all participants in the currently dosed cohort 
have completed Day 15to decide on proceeding to each subsequent dose escalation cohort will 
occur when all participants in the current cohort complete Day 15.  
Schedule of Activities, Table 2 continued. 
A correction was made to the visit window for Day 3 Visit 3 in the table header on the second 
page of the table to align with the table header on the first page of the table. The window was 
corrected to ±0 days. 
V3 
D3 
±01d 
Section 8.1 Safety Assessments 
Prior to opening each of Cohorts 2, 3 and 4 2 and 3 together, Cohort 4, and Cohort 5, 
respectively, to enrollment, the SRT will conduct a safety assessment of data for the previous 
cohort/s collected for when all participants in the currently dosed cohort have completed Day 
15., following the study intervention. 
Section 8.2.6 Safety Review Team 
A SRT will be established as the team responsible for recommending dose escalation or 
decisions and decision on proceeding to dose expansion to the sponsor’s Chief Medical Officer. 
The SRT will operate according to the Safety Review Team Plan. 
Meetings of the SRT to provide a recommendation on dose escalation or dose expansion decide 
on proceeding to each subsequent cohort will occur during the Dose Escalation Phase when all 
participants in the currently dosed cohort have completed Day 15.  
If a pausing event does not occur, dose escalation or moving to the Dose Expansion Phase cohort 
will be recommended by the SRT can occur. 
 
If a pausing rule is met, the SRT will ask the IDMC to conduct a review of unblinded safety data. 
The IDMC will make a recommendation to the sponsor regarding the further conduct of the 
study (See Section 8.2.7.).  


21 January 2022 
Gates MRI-RSM01-101 Protocol v4.0 
Tao SRT will eeastst ef a paael ef at least 4 IBembers, melHEhag the Gates ·MRI ehateel leae, the 
Gates MRI safety leae, the stHey Meeteal Meatter, aae the stte prtaetpal tft•resttgater. The SRT 
IBembers ftfO pati ef the stHEl-y teaIB ftfte Vltll r01rt01JI bltaeee safety eata. 
Section 8.2.7 Independent Data Monitoring Committee 
The role of the IDMC will be to (a)-review unblinded safety data if a pausing rule is met 
IBeatter the prngrnss ef the stHEl-y, (a) revte•N bltaeee safety Elate. pt'0'rteee by the SRT, (e) fOYtO'.V 
HB0lraeee safety eata tf a. paasmg mle ts IBet, and (he) make recommendations to the sponsor on 
further conduct of the study if a pausing mle is met. 
Section 10.2.6 SAEs, AESis, and Serious ADR Repo1ting 
Other E•.•eets R:etteirieg lmmetliete R:epertiBg 
Tao tftlresttgater must repe1i the fellewtag e•reats by seaftfttftg aae eIBatltag, er fffirmg the 
a.ppreprtate fetm te the speaser er eelega.te vrtthm 24 heHrs efbeeemtag awafe ef the 01,'eat: 
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Bmergeae=y HB0ltnemg (ItH:tBeetately Repe1iable BYeftt Fetm) 
Prnteeel Ytelatteft affeettag the safety ef a pa1itetpaftt er tBYel•rtftg the stHEl-y tate1veatteft 
aemtfttsfratteft prneess (Ifflffteetately Repetiable B•reftt Fetm) 
,'\By e•reat that, tft the epmteft efthe tw,'esttga.ter, prnelHees :faHtihet· aeffiiBtstt·atteft ef the stHey 
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Bill & Melinda Gates Medical Research Institute 
CONFIDENTIAL 
110 


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Version 4.0, dated 21 January 2022 
Rationale for v4.0 (changes to v3, 10 December 2021): After the study site provided 
information that a large proportion of screening failures has been due to inability to meet the 
body mass index (BMI) requirement, the sponsor agreed to raise the BMI eligibility inclusion 
criterion to reflect real world conditions, without affecting the safety of potential participants. 
The CDC criterion for obesity is a BMI>30; therefore, the updated inclusion criterion kept the 
BMI below this value. In addition, text was clarified for the exclusion criterion regarding timing 
of screening relative to a previous investigational drug.  
The text regarding screening failures was modified after approximately 30% of screen failures in 
Cohort 1 did not meet the BMI eligibility requirement. Therefore, participants previously 
excluded due to BMI ≥25 kg/m2 may be rescreened once, under this amendment. Participants 
who also initially failed screening for other reasons may also be rescreened once. 
All changes are provided below. New text is shown in bold italics and old text is shown with 
strikethroughs. 
Section 5.1 Inclusion Criteria 
Weight 
3. Body mass index (BMI) 18 to 24.9 29.9 kg/m2 (inclusive) 
Section 5.2 Inclusion Criteria 
Prior/Concurrent Clinical Study Experience 
11. Participation in an interventional clinical trial and/or receipt of any investigational drug 
within 30 90 days or 5 half-lives of the investigational drug before the first day of study drug 
dosing in this study, whichever is longer prior to administration of study drug on Day 1. 
Section 5.4 Screen Failures 
ResScreening assessments as outlined below may be performed after obtaining informed 
consent can be done at any time during the screening window (Day 30 to Day 2; SoA, Section 
1.3), except for written informed consent, which must be completed prior to any rescreening 
procedure. 
Rescreening is only permitted under one or more of the following scenarios conditions: 
• 
If a participant presents with an acute illness on the day of planned study intervention, e.g., 
elevated temperature, acute respiratory or gastrointestinal illness, or urinary tract infection 
(UTI), and meets all other eligibility criteria and can be rescreened within the originally 
defined screening window (SoA, Section 1.3). A new participant number is not required. If 
the participant is rescreened during the original screening window, obtaining a second 
informed consent of the participant is not required. 


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• 
If there are technical difficulties with phlebotomy at screening (e.g., laboratory reports 
hemolyzed blood), technical error in running the laboratory tests or an abnormal urine 
analysis due to menstruation or UTI, and the participant can be rescreened within the 
originally defined screening window (SoA, Section 1.3). A new participant number is not 
required. If the participant is rescreened during the original screening window, obtaining 
a second informed consent of the participant is not required. 
• 
If a participant is undergoing screening and the study reaches a pausing rule. The participant 
may be rescreened when and if the IDMC recommends, and the Sponsor determines, that the 
study may continue. A new participant number is not required. If the participant is 
rescreened during the original screening window, obtaining a second informed consent of 
the participant is not required. 
• 
If a participant fails to meet eligibility criteria upon initial screening, a one-time only 
rescreening for eligibility may be performed. In this case, the participant must receive a 
new participant number after signing a new informed consent. 
Repeat screening procedures may be performed as long as they are completed within the 
screening window.  
Minor change: On title page version is represented by v instead of V for consistency with version 
history page and header.  


Signature Page for Gates MRI-RSM01-101 Protocol Version 4.0 (21 Jan 2022) v7.0
Document Number: RSM01-CLIN-000009 v7.0
e-Sig Approval
Clinical Development
25-Jan-2022 19:39:18 GMT+0000

SAP_001.pdf: 
Confidential 
Bill & Melinda Gates Medical Research Institute 
Gates MRI-RSM01-101
A Phase 1 Randomized, Double-blind, Placebo-Controlled Study to Evaluate 
the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of 
RSM01, a Monoclonal Antibody Targeting Respiratory Syncytial Virus, in 
Healthy Adults 
7 Sep 2022 
Final Statistical Analysis Plan 
Version 2.0 
                                    NCT Number: NCT05118386
This NCT number has been applied to the document for purposes of posting on Clinicaltrials.gov


Bill & Melinda Gates Medical Research Institute 
Final Statistical Analysis Plan, Version 2.0 
Gates MRI-RSM01-101 
Date Issued: 7 Sep 2022 
  
Page 2 of 35 
 
 
TABLE OF CONTENTS 
 
 
SIGNATURE PAGE .................................................................................................................................................. 4 
LIST OF ABBREVIATIONS ........................................................................................................................................ 5 
1. 
INTRODUCTION ............................................................................................................................................ 7 
2. 
OBJECTIVES AND ENDPOINTS ....................................................................................................................... 7 
2.1 
PRIMARY OBJECTIVES AND ENDPOINTS ..................................................................................................................... 7 
2.2 
SECONDARY OBJECTIVES AND ENDPOINTS ................................................................................................................. 8 
2.3 
EXPLORATORY OBJECTIVES AND ENDPOINTS .............................................................................................................. 9 
3. 
STUDY DESIGN .............................................................................................................................................. 9 
4. 
GENERAL STATISTICAL CONSIDERATIONS ................................................................................................... 11 
4.1. 
HANDLING OF MISSING DATA .......................................................................................................................... 12 
4.1.1 
Missing or Partial Dates for Adverse Events ....................................................................................................... 12 
4.1.2 
Missing Incomplete Dates for Prior or Concomitant Medications ..................................................................... 13 
4.2. 
SAMPLE SIZE ................................................................................................................................................. 13 
4.3. 
RANDOMIZATION AND BLINDING ...................................................................................................................... 14 
4.4. 
ANALYSIS POPULATIONS ................................................................................................................................. 15 
5. 
PARTICIPANT DISPOSITION ......................................................................................................................... 15 
5.1 
DISPOSITION ..................................................................................................................................................... 15 
5.2 
PROTOCOL DEVIATIONS ....................................................................................................................................... 16 
5.3 
INCLUSION AND EXCLUSION CRITERIA ..................................................................................................................... 16 
6. 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS .................................................................................... 16 
6.1 
DEMOGRAPHICS ................................................................................................................................................. 16 
6.2 
MEDICAL HISTORY .............................................................................................................................................. 17 
7. 
TREATMENTS AND MEDICATIONS .............................................................................................................. 17 
7.1 
PRIOR AND CONCOMITANT MEDICATIONS............................................................................................................... 17 
7.2 
STUDY TREATMENT ............................................................................................................................................. 17 
8. 
PHARMACOKINETICS .................................................................................................................................. 17 
8.1. 
PHARMACOKINETIC CONCENTRATIONS............................................................................................................... 17 
8.2. 
PHARMACOKINETIC PARAMETERS ..................................................................................................................... 18 
8.3. 
STATISTICAL ANALYSIS ..................................................................................................................................... 20 
8.4. 
PHARMACODYNAMIC CONCENTRATIONS ............................................................................................................ 21 
9. 
SAFETY ANALYSIS........................................................................................................................................ 21 
9.1 
ADVERSE EVENTS ............................................................................................................................................... 21 
9.1.1 Adverse Events Definitions and Reporting ................................................................................................................ 21 
9.1.2 Adverse Events of Special Interest (AESI) .................................................................................................................. 23 
9.1.3 Solicited Local and Systemic AEs ................................................................................................................................ 23 
9.1.4 Unsolicited Treatment Emergent AEs, SAEs, and AESI .............................................................................................. 23 
9.2 
CLINICAL LABORATORY EVALUATIONS ..................................................................................................................... 24 
9.3 
VITAL SIGN MEASUREMENTS ................................................................................................................................ 24 
9.4 
PHYSICAL EXAMINATION ...................................................................................................................................... 25 
9.5 
ELECTROCARDIOGRAMS ....................................................................................................................................... 25 
9.6 
IMMUNOGENICITY .............................................................................................................................................. 25 
9.6.1 Terms and Definitions ........................................................................................................................................... 26 
9.6.2 Derivation Rules .................................................................................................................................................... 27 
9.6.3 Potential Association of Immunogenicity with Adverse Events .......................................................................... 29 


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10. 
MISSED ASSESSMENTS DUE TO COVID-19 ................................................................................................... 29 
11. 
INTERIM ANALYSIS ..................................................................................................................................... 29 
12. 
CHANGES IN THE PLANNED ANALYSIS ........................................................................................................ 30 
13. 
CHANGE OF STATISTICAL PROGRAMMING SERVICE PROVIDER .................................................................. 30 
14. 
REFERENCES ............................................................................................................................................... 31 
15. 
SCHEDULE OF ASSESSMENTS ...................................................................................................................... 32 
 
 
 


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Signature Page 
Prepared by: 
 
 
 
Date: 
 
 
Contract Biostatistician, Gates MRI 
 
 
 
 
Approved by: 
 
 
 
Date: 
 
 
Portfolio Statistics Leader, Gates MRI 
 
 
 
 
 
 
 
Date: 
 
 
Head of Biometrics, Gates MRI 
 
 
 
 
 
 
 
Date: 
 
 
Clinical Development Leader, Gates MRI 
 
 
 
 
 
 
 


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List of Abbreviations 
 
ADA 
 
Anti-drug antibody 
ADaM 
Analysis data model 
AE 
Adverse event 
AESI 
Adverse event of special interest 
AUC 
Area under the (time) curve (e.g., capillary blood-concentration time curve) 
BLQ 
Below limit of quantification 
CD91 
Day 91 capillary blood concentration of RSM01 
CD151 
Day 151 capillary blood concentration of RSM01 
Cmax 
Maximum capillary blood concentration of RSM01 
Cmin 
Minimum capillary blood concentration of RSM01 
CL 
Total body clearance 
CL/F 
Apparent total body clearance 
CSR 
Clinical study report 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EC90 
90% maximal effective concentration 
F 
Bioavailability 
Gates MRI 
Bill & Melinda Gates Medical Research Institute 
GGT 
Gamma glutamyl transferase 
HIV 
Human immunodeficiency virus 
ICH 
International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use 
IDMC 
Independent Data Monitoring Committee 
IM 
Intramuscular 
IV 
Intravenous 
IXRS 
Interactive voice/web response system 
mAb 
Monoclonal antibody 
Mg 
Milligram 
mL 
Milliliter 
NA 
Not applicable 
NCA 
Noncompartmental analysis 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 
PP 
Per protocol 
RSM01 
Monoclonal antibody targeting Respiratory Syncytial Virus  
RSV 
Respiratory Syncytial Virus 
Rsq 
R squared 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SRT 
Safety Review Team 
t1/2 
Apparent terminal half-life 
Tmax 
Time to maximum capillary blood-concentration of RSM01 


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VAMS 
Volumetric absorptive microsampling 
Vz 
Volume of distribution 
Vz/F 
Apparent volume of distribution 
λz 
Elimination rate constant 
 
 
 


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1. Introduction 
The high and continued burden of Respiratory Syncytial Virus (RSV) infection, especially 
among infants and young children, underscores the need for safe and effective prevention against 
RSV disease that is affordable in low- and middle-income countries (LMICs).  
This Phase 1 study will evaluate the safety, tolerability, and pharmacokinetics in adults of an 
RSV monoclonal antibody (mAb) candidate engineered to be highly neutralizing and long 
acting, and to determine an appropriate dose with acceptable safety profile in adults, prior to 
administration to infants in a future clinical study. Adult participants will receive either 
intravenous (IV) or intramuscular (IM) doses of RSM01, which will enable the assessment of the 
safety profiles together with estimation of the human bioavailability following IM injection, 
which is the intended route of administration in infants. 
The purpose of this statistical analysis plan (SAP) is to define the planned analyses of the study 
data to address the study objectives. This SAP is written based on protocol Gates MRI-RSM01-
101, Version 4.0, dated 21 Jan 2022. 
2. Objectives and Endpoints 
2.1 
Primary Objectives and Endpoints 
Primary objective 
Endpoint description  
• To characterize the safety and 
tolerability of a single dose of 
RSM01 
• Unsolicited adverse events (AEs) through 
Day 151  
• All serious adverse events (SAEs) and 
AE of special interest (AESIs) through 
Day 151  
• Solicited systemic AEs for 7 days after 
dose administration (applies to both IV 
and IM doses) 
• Solicited local AEs for injection site 
reactions for 7 days after dose 
administration (only applies to IM doses) 


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2.2 
Secondary Objectives and Endpoints 
Secondary objectives 
Endpoint description  
• To characterize safety laboratory 
parameters following RSM01 
administration 
• Safety laboratory parameters through 
Day 151 
• To characterize the 
pharmacokinetics (PK) following 
RSM01 administration 
PK parameters including: 
• Area under the capillary blood-
concentration time curve from zero to 
infinity (AUC0-inf) 
• Day 91 concentration and area under the 
capillary blood-concentration time curve 
(CD91 and AUC0-D91) 
• Day 151 concentration and area under the 
capillary blood-concentration time curve 
(CD151 and AUC0-D151) 
• Maximum capillary blood-concentration 
(Cmax following IM administration and C0 
following IV administration) 
• Minimum concentration (Cmin) 
• Time to maximum capillary blood-
concentration (Tmax) and apparent 
terminal half-life (t1/2) 
• Systemic clearance (CL for IV or CL/F 
for IM) 
• Volume of distribution of RSM01 (Vz for 
IV or Vz/F for IM) through Day 151 
• To characterize the formation of 
anti-drug antibodies (ADAs) 
following RSM01 administration 
• Incidence of ADAs to RSM01 through 
Day 151 
 
 
 


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2.3 
Exploratory Objectives and Endpoints 
 
Exploratory objective 
Endpoint description  
• To characterize RSV neutralizing 
antibody activity following RSM01 
administration 
• Capillary blood RSV neutralizing 
antibody levels through Day 151 
3. Study Design 
This is a First-in-Human (FiH) trial of RSM01, administered to adults. It is a randomized, 
double-blind, placebo-controlled study of RSM01.  
Candidates will be screened to enroll and randomize approximately 56 eligible participants. 
Assuming all cohorts will be open to enrollment, approximately 48 participants will be exposed 
to RSM01, and approximately 8 participants will be exposed to placebo. Within each cohort, 
there will be no replacement participants. 
If a participant fails to meet eligibility criteria upon initial screening, a one-time only rescreening 
for eligibility may be performed. 
The study will be conducted in 2 parts: A Dose Escalation Phase (N=28) with 4 dosing cohorts, 
followed by an Expansion Phase (N=28) with a single cohort. 
The first participant in each Dose Escalation Phase cohort will not be randomized and will 
receive the RSM01 dose level appropriate to the assigned cohort to serve as a sentinel exposure 
participant. The remaining 6 participants in each of Cohorts 1, 2, 3, and 4 will be randomized 5:1 
to receive either RSM01 or Placebo. The overall ratio of RSM01 to Placebo will be 6:1 in each 
cohort. 
The Dose Escalation Phase will have 2 escalation steps. 
• 
Cohort 1: 7 participants to receive RSM01 300mg IV (n=6 total including sentinel 
participant) or placebo (n=1) 
First escalation step: from Cohort 1 to Cohorts 2 and 3, in parallel.  Participants in Cohort 1 are 
to be randomized in a 1:1 manner to either Cohort 2 or Cohort 3. 
• 
Cohort 2: 7 participants to receive RSM01 300mg IM (n=6 total including sentinel 
participant) or placebo (n=1) 
• 
Cohort 3: 7 participants to receive RSM01 1000mg IV (n=6 total including sentinel 
participant) or placebo (n=1) 
Second escalation step: from Cohorts 2 and 3 to Cohort 4 
• 
Cohort 4: 7 participants to receive RSM01 3000mg IV (n=6 total including sentinel 
participant) or placebo (n=1) 


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Each dose escalation step and emolhnent into the Dose Expansion Phase will proceed after the 
prior coho1t has completed Day 15, and the safety review team (SRT) has reviewed the data and 
detennined that there are no events necessitating a pause. 
The dose expansion phase will have one coho1t: 
• 
Coho1t 5: paiticipants to receive RSM0l IM (n=24) at a dose to be detennined (TBD mg 
IM) or placebo (n=4). 
The tentatively detennined dose to be evaluated in the Expansion Phase Coho1t is ~300 mg to 
~600 mg IM. Final selection of the dose administered to Coho1t 5 will be made by the sponsor 
and infonned by available RSM0l PK data from the Dose Escalation Phase. 
Figure 1: Schema of Study Design and Dosing Procedures 
dose 
--...--· 
_l _______ 
D.91 ___ .. 
151 
SRT review 
dose • 
D1 
D 5 
SRTreview 
Cohort4 3000mg IV 
N=7 (6 1) 
Cohort 5 
dose • 
D1 D1 
Between 300mg and 600 mg IM (6 1) 
D 1 
D151 
D 1 
dose • 
D1 
D15 D 9 
interim analysis 
D 51 
D91 
D11 
primary 
lysis 
Pausing rnles (reasons for pausing the study) are in effect during the active emolhnent and 
dosing period. Any one of the following will prompt a study pause: 
• 
death in any paiticipant in whom the event causing death is judged to be related to the 
study drng by the investigator. 
• 
any occurrence in any paiticipant of a SAE judged to be related by the investigator. 
• 
any occurrence in any paiticipant of an AESI (anaphylaxis, hypersensitivity reaction, 
and/or infusion reaction resulting in pennanent discontinuation of study diug infusion 
during IV adininistration). 
• 
any occurrence of Grade 3 or higher severity assessed to be related to the study diug by 
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the investigator. 
• any occurrence of a clinically significant Grade 3 or higher laboratory abnormality 
assessed to be related to the study drug by the investigator. 
If any of the pausing criteria are met, enrollment/patient accrual as well as dosing of enrolled 
participants will be suspended pending IDMC’s review of all available safety data. 
After screening, there will be a total of 11 visits over 151 days for the Dose Escalation Phase and 
a total of 5 visits over 151 days for the Dose Expansion Phase. An interim analysis will occur 
after all participants in the dose escalation cohorts (Cohorts 1 to 4) have reached Day 91. The 
primary analysis will occur after all participants in all 5 cohorts complete Day 151. 
A more detailed Schedule of assessments can be found in Section 15. 
4. General Statistical Considerations 
All statistical analyses will be conducted using statistical analysis system SAS® Version 9.4 or 
higher (SAS Institute, Cary, NC).  
Descriptive statistics for continuous variables will include number of participants, mean, 
standard deviation (SD), median, minimum, and maximum, unless otherwise noted. For 
categorical variables, frequencies and percentages will be presented.  
All tables, listings, and figures will be presented by cohort and treatment group. The treatment 
groups below will be used for presentations: 
o RSM01 – 300 mg IV (Cohort 1) 
o RSM01 – 300 mg IM (Cohort 2) 
o RSM01 – 1000 mg IV (Cohort 3) 
o RSM01 – 3000 mg IV (Cohort 4) 
o RSM01 – TBD mg IM (Cohort 5) 
o Total RSM01 treatment group 
o Placebo IV (Cohorts 1, 3, 4) 
o Placebo IM (Cohorts 2, 5) 
o Total Placebo treatment group 
All data listings will be sorted by cohort, treatment group, and participant number. 
Study days are calculated with respect to study intervention administration date as below: 
• If the assessment/observation date is on or after study intervention administration date, 
then Study Day = Assessment/Observation Date – Study Intervention Administration 
Date + 1. 
• Otherwise, Study Day = Assessment/Observation Date – Study Intervention 
Administration Date. 
Baseline will be defined as the last non-missing assessment (including repeated and unscheduled 
assessments) before study intervention administration, unless otherwise specified. If a patient 


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was rescreened, data from the rescreening period and not the original screening period will be 
used in the analyses as applicable. 
For summary of safety assessments, if there are repeated measurements at a time point, the first 
non-missing assessment at that time point will be used in the summary tables.  
For ADA-positive participants, the date of the first positive ADA result will be considered as the 
start date of ADA response.  
Time to post-baseline ADA detection (weeks) will be calculated as: 
(Date of first positive ADA assessment –  Study Intervention Administration  
Date + 1) / 7 
If the first positive ADA is prior to the start of treatment, the formula is revised to:  
(Date of first positive ADA assessment – Study Intervention Administration Date) / 7 
Duration of ADA immunogenicity response (weeks) is defined as:  
(Date of last positive ADA assessment – date of first positive ADA assessment + 1) / 7 
For participants with pre-existing positive, duration will be calculated from administration date 
of RSM01 rather than from date of first positive assessment.  
The methodology and data handling specifications for PK data are detailed in Section 8. 
4.1. 
Handling of Missing Data 
4.1.1 Missing or Partial Dates for Adverse Events 
Missing or partial AE start dates will be imputed for the purpose of determining whether the AEs 
are treatment emergent. Data handling rules for missing or partial start/stop date for AEs are 
detailed in the table below. The missing or partial dates will be displayed in the data listings as 
reported on the electronic case report form (eCRF) rather the imputed dates. 
Date 
Situation 
Imputation Rule 
AE Start Date 
Only month and year are known, and 
month is prior to first dose date 
Use the first day of the month 
Only month and year are known, and 
month is the same as first dose date 
Use the first dose date 
Only month and year are known, and 
month is after first dose date 
Use the first day of the month 
Only year is known, and year is after 
first dose date 
Use Jan 1 of that year 
AE End Date 
Only month and year are known, and 
month is prior to last dose date 
Use the last day of the month 
Only month and year are known, and 
month is the same as last dose date 
Use the last dose date 
Only month and year are known, and 
Use the first day of the month 


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month is after last dose date 
Only year is known, and year is before 
last dose date 
Use Dec 31 of that year 
The estimated stop date is before a 
complete or imputed AE start date 
Use the last day of the month 
of the AE start date 
AE = adverse event 
Note: Imputation of end date must be later than start date. 
 
4.1.2 
Missing Incomplete Dates for Prior or Concomitant Medications 
Missing or partial medication start or stop dates will be imputed for the purpose of determining 
whether the medication is taken concomitantly. Data handling rules for missing or partial 
start/stop date medications are detailed in the table below. The missing or partial dates will be 
displayed in the data listings as reported on the eCRF rather the imputed dates. 
Imputation rules for missing or partial dates (D=day, M=month, Y=year, T=time) 
Parameter Missing 
Additional conditions 
Imputation Rule 
Start date  
D only 
M and Y same as M and Y of 
first dose of study drug 
Date of first dose of study drug 
M and/or Y not same as M and 
Y of first dose of study drug 
First day of month 
M and D 
Y same as Y of first dose of 
study drug 
Date of first dose of study drug 
Y not same as Y of first dose of 
study drug 
Use Jan 01 of Y 
M, D and Y None--date completely missing 
Date of first dose of study drug 
Stop date  
D only 
M and Y same as M and Y of 
end of study 
Date of end of study 
M and/or Y not same as M and 
Y of end of study 
Last day of month 
M and D 
Y same as Y of end of study 
Date of last dose of study drug 
Y not same as Y of end of study 
Use Dec 31 of Y 
M, D and Y Medications that are not marked 
as ongoing - date completely 
missing 
Date of end of study 
4.2. 
Sample Size 
This is an exploratory trial to characterize safety, tolerability, and pharmacokinetics of single 
dose of RSM01 mAb administered by either IV or IM routes. The trial is designed to be 
descriptive and is not based on evaluation of a formal null hypotheses. Therefore, this study is 
not powered to detect any differences in potential safety observations between treatment groups. 
Data from approximately 56 participants will be available for analysis: 28 participants in the 
Dose Escalation Phase Cohorts and 28 participants in the Dose Expansion Phase Cohort.  


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Assuming that all cohorts are allowed to undergo treatment, approximately 48 participants will 
be exposed to RSM01, and approximately 8 participants will receive Placebo. 
With N=6 participants (per RSM01 arm in Dose Escalation Phase cohorts), there is 
approximately 80% (90%) power to observe at least one AE if the true AE rate is 23.53% 
(31.87%). With N=24 participants (across all active doses of RSM01 in the Dose Escalation 
Phase cohorts or the Dose Expansion Phase Cohort), there is approximately 80% (90%) power to 
observe at least one AE if the true AE rate is 6.49% (9.15%). Across all active doses of RSM01 
(N=48), there is approximately 80% (90%) power to observe at least one AE if the true AE rate is 
3.3% (4.68%). 
4.3. 
Randomization and Blinding 
The first participant in each Dose Escalation Phase cohort will not be randomized and will 
receive RSM01 dose level appropriate to the assigned cohort in a single-blinded fashion: 
participants will be blinded to treatment, but site will not be blinded to treatment.  Subsequent 
participants in the cohort will be double-blinded: participants and site personnel, except for the 
study pharmacist, will be blinded to treatment. The study pharmacist will know assignment to 
provide doses of RSM01 and Placebo to the clinic that are appropriately masked to the blinded 
treating nurse/physician. 
The remaining 6 participants in each cohort (Cohorts 1, 2, 3 and 4) will be randomized 5:1 to 
receive either RSM01 or placebo. Cohorts 2 and 3 will be enrolled in parallel using 1:1 
randomization. The overall ratio of RSM01 to placebo will be 6:1 in each cohort. The Expansion 
Phase cohort (Cohort 5) will be randomized 6:1 to receive either RSM01 IM (N=24) or placebo 
(N=4).   
Randomization in each cohort will be based on a randomly generated sequence of participant 
identification (identifier) numbers (randomization schedule) using a validated Interactive 
Voice/Web Response System (IXRS).  
The randomization schedule will be prepared by a statistician who will not be involved in the 
analysis of the study in order to maintain the blind of the study team. 
With the exception of the first sentinel participant in each of the Dose Escalation Phase cohorts 
who will each receive the respective dose of RSM01, the study is double-blind: participants and 
all study personnel will be blinded to the randomization. 
An interim analysis will be performed after availability of Cohort 2, Cohort 3, and Cohort 4 Day 
30 data (see Section 11). Firewalled roles will be involved in the interim analysis to create 
unblinded datasets and perform analyses. The investigator will remain blinded. The sponsor will 
review blinded (pooled) safety data by cohort and unblinded aggregated PK data by treatment 
group (RSM01 vs. placebo) within and across cohorts. The sponsor will be blinded at the 
participant level throughout the study. For expedited safety reporting to regulatory authorities, 


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pharmacovigilance unblinding will be performed as required. Information regarding unblinding 
for the interim analysis is contained in a separate unblinding plan. 
The IXRS will be programmed with blind-breaking instructions. In addition, instructions on 
emergency unblinding in case of system outage will be provided.  
4.4. 
Analysis Populations 
Population 
Description 
Enrolled population 
All participants enrolled for screening. Participants randomly 
assigned to study treatment will be classified according to the 
intervention they were randomized to receive. 
Safety Population 
All participants who received the study treatment. Participants 
will be analyzed according to the intervention they received. 
Per protocol (PP) 
Population 
All participants who received study treatment and did not have a 
significant protocol deviation. Participants will be analyzed 
according to the intervention they received. 
PK Population 
All participants who received RSM01 who have a baseline and at 
least one post-baseline PK result. Participants will be analyzed 
according to the intervention they received. 
Immunogenicity 
Population 
All participants who received the study treatment and have at 
least one valid post-baseline ADA sample. Participants with no 
baseline ADA assessment are assumed to be negative at baseline. 
Participants will be analyzed according to the intervention they 
received. 
5. Participant Disposition 
5.1 
Disposition 
The following will be summarized for the enrolled population, by treatment group and overall 
for all participants: 
• The number of participants who were randomized in each cohort 
• The number of participants who received each treatment 
• The number of participants who completed the study 
• The number of participants who did not complete the study (both overall and according to 
reasons for study withdrawal) 


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• The number of participants who were unblinded by the site 
• The number of participants in each analysis population 
• The number of participants who screen failed (both overall and according to reasons for 
screen failure) 
Participant disposition and screen failure data will be presented in data listings. 
5.2 
Protocol Deviations 
Significant protocol deviations will be summarized by treatment group. All protocol deviations 
will be presented in a data listing.  Protocol deviations will be maintained in an Excel 
spreadsheet, which will include the deviation description, date of deviation, deviation category, 
and significance (significant/not significant). The protocol deviation spreadsheet will be finalized 
prior to database lock. 
5.3 
Inclusion and Exclusion Criteria 
Inclusion and exclusion criteria deviations will be presented in a data listing. 
6. Demographics and Baseline Characteristics 
6.1 
Demographics 
Demographic and other baseline information collected at screening will be presented in a data 
listing. Descriptive statistics will be calculated for the following continuous demographic and 
other baseline characteristics:  
• Age (years) 
• Weight (kg) 
• Height (cm) 
• Body mass index (BMI) (kg/m2) 
• Pulse rate (beats/minute) 
• Systolic blood pressure (SBP) (mmHg) 
• Diastolic blood pressure (DBP) (mmHg) 
• Temperature (C) 
• Oxygen saturation (%) 
Frequency counts and percentages will be tabulated for the categorical variables: 
• Sex 
• Race 
• Ethnicity 
The summaries will be presented by treatment group and overall for the safety population. 


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6.2 
Medical History 
The medical history data will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA, version to be delineated in the clinical study report [CSR]) and summarized by 
treatment group. All medical history data will be presented in a data listing. 
7. Treatments and Medications 
7.1 
Prior and Concomitant Medications 
Medications that are discontinued prior to study intervention administration will be classified as 
prior medication. Medications for which dosing is begun on or after study intervention 
administration will be classified as concomitant. If a medication is begun before study 
intervention administration and is discontinued on or after study intervention administration, then 
the medication will be classified as both prior and concomitant. 
All prior and concomitant medications will be coded according to the World Health Organization 
Drug Dictionary (version to be delineated in the CSR) and presented in a data listing. 
7.2 
Study Treatment 
The study drug administration as collected on eCRF will be presented in the data listings. 
8. Pharmacokinetics 
8.1. 
Pharmacokinetic Concentrations 
Whole blood samples on VAMS and serum samples will be collected for measurement of 
RSM01 concentrations in capillary blood and venous serum as below: 
Dose Escalation Phase:  
• At Visit 1 (Day 1), PK blood draw will occur pre-dosing, within 5 minutes (± 1 minute) 
after end of infusion for IV dosing only, and at 8-hours (± 0.5 hours) post-dose for both 
IV and IM doses. 
• Visit 2 (Day 2): 24-hours (± 1 hours) 
• Visit 3 (Day 3): (± 0 day) 
• Visit 4 (Day 6): (± 1 day) 
• Visit 5 (Day 8): Days 8-10 
• Visit 6 (Day 15): (± 3 days) 
• Visit 7 (Day 29): Days 29-35 
• Visit 8 (Day 61): (± 7 days) 
• Visit 9 (Day 91): (± 7 days) 
• Visit 10 (Day 121): (± 7 days) 
• Visit 11 (Day 151): (± 7 days) 
• Discontinuation visit 
 
Dose Expansion Phase:  
• At Visit 1 (Day 1): pre-dose 


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• Visit 2 (Day 8): Days 8-10 
• Visit 3 (Day 29): Days 29-35 
• Visit 4 (Day 91): (± 7 days) 
• Visit 5 (Day 151): (± 7 days) 
• Discontinuation visit 
 
Individual capillary blood concentration of RSM01 and time deviation data for PK population 
will be presented in data listings.  Capillary blood concentration data will be summarized by 
scheduled time point for the PP population using descriptive statistics (non-missing observations 
(N), arithmetic mean (Mean), standard deviation (SD), coefficient of variation (CV%), median, 
minimum, maximum, Q1 and Q3. Capillary blood concentration data will also be summarized by 
ADA status using the PK population. 
Descriptive statistics of capillary blood concentration of RSM01 data will be calculated using 
values with the same precision as the source data and rounded for reporting purposes only. The 
following conventions will be applied when reporting descriptive statistics of PP PK 
concentration data: 
• Mean, Min, Median, Max, Q1, Q3: 3 significant digits 
• SD: 4 significant digits 
• CV%: 1 decimal place 
Concentrations of RSM01 that are below the lower limit of quantification (BLQ) before the first 
quantifiable concentration will be treated as zero for descriptive statistics. Below the limit of 
quantification values after the first quantifiable concentration will be set as missing and excluded 
for summary statistics.  
Mean (±SD) capillary blood concentrations of RSM01 versus scheduled time profiles will be 
plotted by treatment on both linear and semi-logarithmic scales for PK population. Individual 
capillary blood concentrations versus actual time profiles will be plotted on both linear and semi-
logarithmic scales for the PP population. The ADA status for each subject will be displayed on 
the individual profiles and for ADA positive participants, the titer results will be plotted on the 
secondary Y-axis. 
The same analyses will be performed for venous serum (exploratory objective). 
8.2. 
Pharmacokinetic Parameters 
Individual capillary blood concentration of RSM01 versus actual time data will be used to 
estimate the PK parameters of RSM01 by standard noncompartmental methods using WinNonlin 
(Phoenix) version 8.0 or higher. For the calculation of PK parameters, BLQ values before the 
first quantifiable concentration of RSM01 will be treated as zero.  Below the limit of 
quantification values after the first quantifiable concentration will be set as missing.  Missing 
concentrations will be treated as missing.  If consecutive BLQ concentrations of RSM01 are 


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followed by quantifiable concentrations in the terminal phase, those concentrations after BLQ 
concentrations will be treated as missing.  
The following PK parameters for capillary blood RSM01 will be calculated for dose escalation 
cohorts and dose expansion cohort, if data permit. 
Parameter 
Description 
Cmax 
Maximum observed capillary blood concentration of RSM01 
Cmin 
Minimum observed capillary blood concentration of RSM01 
CD91 
Day 91 capillary blood concentration of RSM01 
CD151 
Day 151 capillary blood concentration of RSM01 
Tmax 
Time to reach maximum observed capillary blood concentration of 
RSM01 
AUC0-inf 
Area under the capillary blood concentration curve for RSM01 from time 
0 to the infinity, calculated using the linear trapezoidal linear 
interpolation method 
AUC0-D91 
Area under the capillary blood concentration curve for RSM01 from time 
0 to Day 91, calculated using the linear trapezoidal linear interpolation 
method 
AUC0-D151 
Area under the capillary blood concentration curve for RSM01 from time 
0 to Day 151, calculated using the linear trapezoidal linear interpolation 
method 
CL 
Total body clearance (for IV); calculated as Dose/AUC0-inf 
CL/F 
Apparent total body clearance (for IM); calculated as Dose/AUC0-inf 
Vz 
Volume of distribution (for IV); calculated as Dose/(AUC0-inf x λz) 
Vz/F 
Apparent volume of distribution (for IM); calculated as Dose/(AUC0-inf x 
λz) 
t1/2 
Apparent terminal half-life; calculated as 0.693/λz 
 
The following PK parameters will be calculated for diagnostic purposes and listed, but they will 
not be summarized. 
 


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Parameter 
Description 
λz 
Elimination rate constant, calculated by linear regression of the 
terminal portion of the natural log capillary blood concentration 
versus time curve. Visual assessment may be used to identify the 
terminal linear phase of the natural log capillary blood concentration 
versus time profile. A minimum of 3 data points (excluding Cmax for 
IM) will be used for calculation. The parameter z will not be 
calculated if the terminal phase of the natural log capillary blood 
concentration versus time profile does not exhibit a linear decline 
phase or if the Rsq < 0.8 
λz lower 
Lower limit of time included in the calculation of λz  
λz upper 
Upper limit of time included in the calculation of λz  
λz N 
Number of data points used in the calculation of λz  
Rsq 
Regression coefficient for calculation of λz.  
 
Additional PK parameters may be calculated. Individual capillary blood RSM01 PK parameters 
will be presented in the data listings for the PP population. The capillary blood RSM01 PK 
parameters will be summarized using the PP population by treatment with the following 
descriptive statistics: N, n, mean, SD, CV, median, minimum, maximum, geometric mean, and 
geometric percent CV.  
Capillary blood PK parameters for RSM01 will be displayed to 3 significant figures in all data 
listings and summary tables, with exception of time variables (Tmax, λz lower, and λz upper) 
which will be displayed to 2 decimal places. λz which will be displayed to 4 decimal places. 
Scatter plots of capillary blood RSM01 PK parameters (AUC0-inf, AUC0-D91, AUC0-D151, and Cmax) 
vs. IV dose will be plotted with an equation and R2 value.   
The same analyses will be performed for venous serum (exploratory objective). 
8.3. 
Statistical analysis 
Dose proportionality for capillary blood RSM01 PK parameters will be tested using the power 
regression model for AUC0-inf, AUC0-D91, AUC0-D151, and Cmax and, defined as:  
ln [PK parameter] = β0 + β1 ln [Dose] 
where the PK parameter is an AUC0-inf, AUC0-D91, AUC0-D151, and Cmax. The null hypothesis 
being tested is that the AUC and Cmax values are dose proportional, or slope (β1) = 1. Dose-
proportionality will be concluded if the 90% CI of the slope β1 lies entirely within 
[1+ln(0.5)/ln(r), 1+ln(2.0)/ln(r)], where r is a ratio that describes the dose range and is defined as 
the ratio of highest dose/lowest dose.  


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Bioavailability of RSM01 following IM injection will be calculated using the ratio of geometric 
mean of AUC0-inf and AUC0-D151 capillary blood RSM01 PK parameters for the comparison of 
IM versus IV dose. Log-transformed AUC0-inf and AUC0-D151 estimates will be analyzed using an 
analysis of variance (ANOVA) model with treatment group as a factor. The parameter estimates 
results will be exponentiated and the ratio of geometric means and 90% CIs will be presented.  
The proportion of participants with observed CD151 concentrations above the estimated EC90 for 
RSM01 (based on available pre-clinical data) will be summarized by treatment group. Exact 95% 
confidence interval will be calculated on the percentages. 
The same analyses will be performed for venous serum (exploratory objective). 
8.4. 
Pharmacodynamic Concentrations 
Whole blood samples on VAMS and serum samples will be collected for measurement of RSV 
neutralizing antibody concentrations in capillary blood and venous serum. 
A listing will be prepared for each cohort with both serum and VAMS data. 
9. Safety Analysis 
All safety summaries and analyses will be based upon the safety population. 
9.1 
Adverse Events 
9.1.1 Adverse Events Definitions and Reporting 
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical 
study participant, temporally associated with the use of study intervention, whether or not 
considered related to the study intervention.  
A treatment-emergent AE (TEAE) is defined as any event not present before study intervention 
administration or any event already present that worsens in severity or frequency after study 
intervention administration. 
A serious AE (SAE) is defined as any AE that results in any of the following outcomes: death, a 
life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant incapacity or substantial disruption of the ability to conduct normal 
activities of daily living, or a congenital anomaly or birth defect. Important medical events that 
may not result in death, be life threatening, or require hospitalization may be considered serious 
when, based upon appropriate medical judgment, they may jeopardize the participant and may 
require medical or surgical intervention to prevent one of the outcomes listed in this definition.  
An AE of special interest (AESI) is a preidentified and predefined event that has the potential to 
be causally associated with a study intervention that the sponsor will carefully monitor. 
The AE’s relationship to study treatment will be evaluated by the investigator or medically 
qualified designee (ie, investigator, study physician). The following relationships will be 
collected on eCRF: related, not related.  


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The severity of AEs will be classified by the investigator as mild, moderate, severe or potentially 
life threatening. An overall AE summary will be generated presenting the frequency and 
percentage of participants and the number of AEs for the following: 
• Any TEAE 
• Any treatment-related TEAE  
• Any grade 1 TEAE 
• Any grade 2 TEAE 
• Any grade 3 or higher TEAE 
• Any treatment-related grade 3 or higher TEAE 
• Any SAE 
• Any treatment-related SAE 
• Any TEAE leading to dose interruption (IV route of administration) 
• Any TEAE leading to study withdrawal 
• Any death  
• Any AESI 
All AEs will be coded using MedDRA (version to be delineated in the CSR). The TEAEs will 
also be summarized by system organ class (SOC), preferred term (PT), by severity and 
relationship to study treatment.  
The TEAE summary tables will be sorted by SOC and PT. System organ class will be displayed 
in descending order of overall frequency then alphabetically. Preferred term will be displayed in 
descending order of overall frequency and then alphabetically within SOC. A participant with 2 
or more events within the same level of summarization will be counted only once in that level 
using the most severe incident or most related incident. Percentages will be based on the number 
of participants in the safety population (unsolicited AE) or the number of participants in the 
safety population that had submitted any data for a solicited AE (solicited AE). 
All AEs will be presented in a data listing. Separate data listings will be generated for Severe or 
Life-threatening AEs, treatment-related AEs, SAEs, AEs leading to study discontinuation, Fatal 
AEs, AESIs, as well as a listing describing a potential association of AE with immunogenicity 
(ADA status). 


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9.1.2 Adverse Events of Special Interest (AESI) 
The following AEs will be collected and reported as AESIs: anaphylaxis or hypersensitivity 
reactions and infusion reactions resulting in permanent discontinuation of infusion in IV 
recipients. 
9.1.3 Solicited Local and Systemic AEs 
Local injection site solicited AEs include pain, redness and swelling. If more than 1 injection is 
given, reactions are to be assessed separately at each injection site. All solicited local AEs will be 
considered study intervention related events and will be summarized for each injection site.  
Systemic solicited AEs include fever, headache, tiredness, joint pain, muscle pain, nausea, 
vomiting and diarrhea.  
All solicited AEs collected from Day 1 through Day 7 will be collected and summarized as 
described below.  
The number and percentage of participants who experience one or more solicited AE will be 
summarized for each solicited AE, by treatment group, and by severity, by day after study 
intervention administration, and overall. The first onset of each AE, and the total number of days 
a participant experienced each AE will also be summarized. For participants with more than 1 
episode of the same event, the maximum severity will be used for tabulations.  
Exact 95% confidence intervals will be calculated on the percentages. 
Solicited local and systemic AEs will be presented in separate data listings. Ongoing AE 7 days 
after dosing will also be listed. 
9.1.4 Unsolicited Treatment Emergent AEs, SAEs, and AESI 
All unsolicited AEs, SAEs, and AESIs will be recorded from screening through Day 151. 
Unsolicited AEs, SAEs, and AESIs will be coded according to MedDRA and summarized by 
System Organ Class (SOC), Preferred Term (PT) and highest severity. Clopper-Pearson exact 
95% CIs will be calculated on the percentages of participants with AESIs. AEs leading to dose 
interruption for cohorts with IV route of administration and AEs leading to withdrawal from the 
study will also be summarized.  
The number of events reported, the number of participants and percentage of participants who 
experience one or more unsolicited AE through Day 151, and one or more SAE, and one or more 
AESI from screening through Day 151 will be summarized by treatment group, as appropriate, 
and across all RSM01 dose levels and routes of administration, combined. The severity of each 
AE, and relationship between the AE and study intervention, will also be summarized. 
For participants with more than 1 episode of the same event, the maximum severity will be used 
for tabulations. Participants reporting more than one occurrence for the PT term level being 
summarized will be counted only once.  


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9.2 
Clinical Laboratory Evaluations 
The following laboratory tests will be performed: 
Hematology 
 
Complete blood count (including hemoglobin, platelet count and 
white blood cell count) and absolute counts for neutrophils, 
lymphocytes, eosinophils, and monocytes. 
Serum Chemistry 
 
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
alkaline phosphatase, total bilirubin, gamma glutamyl transferase 
(GGT), creatinine, blood urea nitrogen, lactate dehydrogenase 
(LDH), glucose, albumin, sodium, potassium, chloride, bicarbonate, 
and calcium.  
Urinalysis 
 
Specific gravity, pH, glucose, protein, blood, ketones, bilirubin, 
urobilinogen, nitrite, leukocyte esterase by dipstick. 
Other tests 
 
HIV, hepatitis B and C, urine drug screen, and serum pregnancy test 
(females only)  
The hematology, serum chemistry, and urinalysis tests will be performed at the timepoints 
indicated in the schedule of assessments (schedule of assessments can be found in Section 15). 
All laboratory values collected at visits will be included in the summaries and listings. 
Descriptive summaries of observed value and change from baseline (last result available on or 
before Day 1) at each scheduled post baseline visit will be presented by treatment group for each 
continuous parameter for the safety population, both in tabular format and as boxplots. For 
participants who have an abnormal on-study laboratory result, longitudinal (spider) plots for 
hematology, serum chemistry, and urinalysis parameters will be produced. 
Tables of the worst shift in FDA Toxicity Grading Scale in laboratory values from Day 1 
(baseline) to visit Day 8, visit Day 91, visit Day 151 will be also presented per parameter, for 
those parameters that have FDA Toxicity Grading Scale grading.  Values that aren’t within any 
toxicity criteria will be presented as ‘Normal’. 
9.3 
Vital Sign Measurements 
Vital signs will include systolic and diastolic blood pressure, pulse rate, and body temperature, 
and percent oxygen saturation and will be measured at the timepoints indicated in the schedule of 
assessments (see Section 15). Vital signs are to be taken after at least 5 minutes of rest in a quiet 
setting without distractions. Measurements are to be repeated if clinically significant changes are 
observed or a machine error occurs. 
All vital sign, body weight, and height measurements will be presented in a data listing. The 
actual values and change from baseline values at each time point will be summarized by 
treatment group for the safety population, both in tabular format and as boxplots. 


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9.4 
Physical Examination 
A full physical examination will be conducted at screening to assess enrollment eligibility. Only 
participants that are considered as healthy by the investigator will be enrolled. 
Physical examination at screening will include, at a minimum, assessment of height and weight, 
body temperature, and resting vital signs (including percent oxygen saturation by pulse 
oximetry), in addition to assessments needed to determine eligibility. Assessments will include 
general appearance and specific organ systems (head, eyes, ears, nose, throat/mouth, neck 
(HEENT), respiratory, cardiovascular, gastrointestinal and neurological systems, psychiatric, 
skin and lymphatics).  
A focused physical examination will be performed to check eligibility criteria again at Visit 1 
(Day 1), and subsequently if indicated by participant’s medical complaint and will include 
assessments of body systems involved in the complaint. Focused physical examinations will be 
symptom directed. 
Full physical examinations will be performed at Screening, and focused physical examinations 
will be performed at the timepoints indicated in the schedule of assessments (see Section 15).  
All physical examination results will be presented in a data listing. 
9.5 
Electrocardiograms 
A 12-lead ECG will be performed at screening using a machine that automatically calculates 
heart rate and determines intervals for PR, QRS, QT and QTc. Triplicate (unmarked) 12-lead 
ECGs will be obtained and averaged. 
All 12-lead ECGs will be obtained after the participant has rested in a supine position for at least 
10 minutes. All Triplicate ECGs will be taken approximately one minute apart. Measurements 
that deviate substantially from previous readings will be repeated immediately. 
Single 12-lead ECG will be performed at the timepoints indicated in the schedule of assessments 
(see Section 15). 
Actual values and changes from baseline for numeric ECG data will be summarized by visit and 
treatment group for participants in the safety population, both in tabular format and as boxplots. 
Shift from baseline to the worst interpretation of ECG results (normal, abnormal (CS), abnormal 
(NCS) over all visits will be summarized by treatment group using the frequency count and 
percentage of participants in each category. 
All ECG data will be presented in a data listing.  
9.6 
Immunogenicity 
Whole blood samples on VAMS and serum samples will be collected for detection of ADA 
against RSM01 in capillary blood and venous serum, as specified in the schedule of assessments 
(Section 15). Samples on Day 1 will be collected prior to RSM01 administration. 


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The detection of ADA to RSM01 will be performed using a validated immunoassay method with 
tiered testing of screening, confirmatory, and titration. Confirmed positive antibodies may be 
further characterized. 
ADA results will be summarized at the time of the primary analyses, when all participants reach 
Day 151. The following analyses will be conducted separately for both VAMS (secondary 
objective) and serum (exploratory objective). 
The overall analysis of immunogenicity will focus on the following key parameters: 
• Immunogenicity incidence and characterization 
• Association with pharmacokinetics 
• Association with TEAEs  
The immunogenicity population used in the analysis is described in Section 4.4.  
9.6.1 Terms and Definitions 
The detection of ADA to RSM01 will be performed using a validated immunoassay method with 
tiered testing of screening, confirmatory, and titration, i.e.: 
1. All samples will undergo a screening test.  
2. If the screening test is positive for ADA, the sample will undergo a confirmatory test. A 
sample that has a negative or not reportable (NR) screening result will not undergo 
further testing. 
3. If the confirmatory test is positive, the sample will be analyzed to determine the titer. A 
titer result can be a quantifiable number or not reportable (“titer not reportable” or 
“TNR”). 
 
The following terms and definitions will be applied in the immunogenicity analyses. 
ADA status of a sample 
• Baseline ADA negative sample: Screening or confirmatory test of the last sample before 
administration of study treatment indicates ADA is not detected. 
• Baseline ADA NR sample: Screening or confirmatory test of the last sample before 
administration of study treatment indicates ADA is not reportable. 
• Baseline ADA missing: No baseline sample was available for testing. 
• Baseline ADA positive sample: Screening and confirmatory tests of the last sample 
before administration of study treatment indicates ADA is detected. The numeric titer 
will be reported unless the titer result is NR, which would be reported as positive TNR. 
• Post-baseline ADA negative sample: Screening or confirmatory test of sample taken after 
administration of study treatment indicates ADA is not detected. 


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• Post-baseline ADA NR sample: Screening or confirmatory test of sample taken after 
administration of study treatment indicates ADA is not reportable. 
• Post-baseline ADA missing: No post-baseline sample was obtained. 
• Post-baseline ADA positive sample: Screening and confirmatory tests of sample taken 
after administration of study treatment indicates ADA is detected. The numeric titer will 
be reported unless the titer result is NR, which would be reported as positive TNR. 
ADA status of a participant 
• Baseline ADA negative participant: A participant with baseline ADA negative sample. A 
participant with NR or no baseline ADA sample is assumed to be baseline ADA negative. 
• Baseline ADA positive participant: A participant with a baseline ADA positive or positive 
TNR sample. 
• Post-baseline ADA positive participant: A participant with at least one post-baseline ADA 
positive or positive TNR sample. An ADA positive participant will be further classified as 
follows: 
o Treatment-emergent positive: Participant had a post-baseline ADA positive or 
positive TNR sample in a participant with a baseline ADA negative sample OR 
participant had a post-baseline ADA positive sample that is ≥ 8-fold increase 
above baseline titer in a participant with a baseline ADA positive sample. Note 
that the baseline sample and at least one post-baseline sample must have 
reportable titer to assess whether pre-existing immunogenicity was treatment-
boosted. 
o Treatment-emergent nonevaluable. 
o Treatment-emergent negative. 
• Post-baseline ADA negative participant: A participant with no post-baseline ADA positive 
or positive TNR sample. 
• Any ADA detected: Subjects in Baseline ADA Positive AND/OR Treatment-emergent. 
• No ADA Detected: Subjects who are Baseline ADA negative AND either Post-baseline 
ADA negative OR no valid post-baseline results (excluded from immunogenicity 
population). 
9.6.2 Derivation Rules 
Based on the definitions provided in Section Error! Reference source not found., 
immunogenicity results will be collected prior to dose administration and at post-treatment 
follow-up visits. Immunogenicity results will be collected prior to dose administration and at 
post-treatment follow-up visits. Sample-level and participant-level derivations are shown in 
Tables 1 and 2, respectively. 


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Table 1: 
Algorithm for Deriving of Anti-Drug Antibody Sample-Level Results 
SDTM raw data 
 
Derived ADaM sample 
result 
ADA Screening Result 
(ISTSTOPO=Screen) 
ADA Confirmatory Result 
(ISTSTOPO=Confirm) 
ADA Titer Result 
(ISTSTOPO=Quantity) 
Negative 
NA 
NA 
Negative 
NR 
NA 
NA 
NR 
Missing 
NA 
NA 
Negative 
Positive 
Negative 
NA 
Negative 
Positive 
NR 
NA 
NR 
Positive 
Positive 
Number 
Number 
Positive 
Positive 
NR 
Positive TNR 
ADaM = analysis data model, NA = not applicable, NR = not reportable, SDTM = study data tabulation model, TNR = titer not reportable. 
Table 2: 
Algorithm for Deriving Anti-Drug Antibody Participant-Level Results 
ADaM data across samples 
Participant-level ADaM result 
Baseline ADA result 
Post-baseline ADA 
results 
Derived 
baseline ADA 
Derived post-
baseline ADA 
Treatment-emergent  
Negative or NR or Missing 
At least one 
Negative, no 
Number or Positive 
TNR 
Negative 
Negative 
Negative 
Negative or NR or Missing 
All NR or Missing 
Negative 
NA 
NA 
Negative or NR or Missing 
At least one Positive 
TNR, no Number 
Negative 
Positive TNR 
Treatment-emergent 
Negative or NR or Missing 
At least one Number 
Negative 
Positive 
Treatment-emergent 
Positive TNR 
At lease one 
Negative, no 
Number of Positive 
TNR 
Positive TNR 
Negative 
Neither 
Positive TNR 
All NR or Missing 
Positive TNR 
NA 
NA 
Positive TNR 
At least one Positive 
TNR, no Number 
Positive TNR 
Positive TNR 
TNR 
Positive TNR 
At least one Number 
Positive TNR 
Positive 
TNR 
Number 
At least one 
Negative, no 
Number or Positive 
TNR 
Positive 
Negative 
Negative 
Number 
All NR or Missing 
Positive 
NA 
NA 
Number 
At least one Positive 
TNR, no Number 
Positive 
Positive TNR 
TNR 
Number 
At least one 
Number, but none ≥ 
Positive 
Positive 
Negative 


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ADaM data across samples 
Participant-level ADaM result 
Baseline ADA result 
Post-baseline ADA 
results 
Derived 
baseline ADA 
Derived post-
baseline ADA 
Treatment-emergent  
8-fold increase 
above baseline titer 
Number 
At least one Number 
≥ 8-fold increase 
above baseline titer 
Positive 
Positive 
Treatment-emergent 
ADaM = analysis data model, NA = not applicable since not in immunogenicity population, NR = not reportable, SDTM = study 
data tabulation model, TNR = titer not reportable. 
 
The number and percentage of participants will be reported as follows: 
• Baseline ADA positive vs. negative in the Immunogenicity Population 
• Post-baseline ADA positive among participants with at least one post-baseline ADA 
sample 
o Treatment-emergent ADA  
o Negative treatment-emergent 
Listings will be prepared with ADA sample-level and participant-level results.  
 
9.6.3 Potential Association of Immunogenicity with Adverse Events 
A summary of AEs showing frequency and percentage of participants with AEs will be produced 
for the following subgroups: 
• Any ADA detected 
• No ADA detected 
10. Missed Assessments due to COVID-19 
All visits or assessments missed due to COVID-19 will be presented in a listing. 
11. Interim Analysis 
An interim analysis is planned after availability of Cohort 2, Cohort 3, and Cohort 4 Day 30 data.  
An interim analysis with a formal Safety report is planned for this study when all participants in 
each of the Dose Escalation Phase cohorts have completed Day 91. In addition, SDTM datasets 
will be prepared for interim PK modeling. An Interim Report will be prepared when the results 
from Day 91 become available. Additional interim analyses may occur prior to the primary 
analysis to aid in the development of individual and population PK models to predict dose levels 
in infants and assess covariates. 
The purpose of this interim analysis will be a strategic review to inform the broader program and 
future development plans, including the determination of the potential dose of RSM01 in infants.  
No decision directly related to this study will be made from the results of this interim analysis. 
Agreement on the analysis plan, unblinding procedures, specific outputs, method of distribution, 


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the level of data cleaning and details of whom the results will be provided to will be outlined in a 
separate unblinding plan (which will be finalized prior to the interim analysis). 
Firewalled roles will be involved in the interim analysis to create unblinded datasets and perform 
analyses. The investigator will remain blinded. The sponsor will review blinded (pooled) safety 
data by cohort and unblinded aggregated PK data by treatment group (RSM01 vs. placebo) 
within and across cohorts. The sponsor will be blinded at the participant level throughout the 
study. An unblinding plan will be prepared to include unblinding details.  
12. Changes in the Planned Analysis 
Any changes from this statistical analysis plan that are not documented in a formal SAP 
amendment will be documented in the CSR for this study. 
13. Change of Statistical Programming Service Provider 
In May 2022, Gates MRI decided to terminate the RSM01-101 biostatistics and statistical 
programming contract with its original service provider. Gates MRI assumed responsibility for 
statistical oversight of the study, including finalization of the SAP, and initiated a new agreement 
with another service provider for the statistical programming of SDTM and ADaM datasets as 
well as tables, figures, and listings. In its statistical oversight, Gates MRI will follow statistical 
principles that are consistent with the International Conference on Harmonisation (ICH) 
guidelines E9 (Statistical Principles for Clinical Trials) and apply the following procedures: 
• Prior to an interim unblinded data review, Gates MRI will finalize an unblinding plan that 
describes the purposes for unblinding, the roles and responsibilities of team members 
who will be involved in the unblinding steps and the preparation and review of unblinded 
analyses, and the level of access each role will have to unblinded interim data (i.e., fully 
blinded, blinded except emergency participant-level unblinding, unblinded to aggregate 
results, or unblinded to participant-level results); 
• Prior to an interim unblinded data review, Gates MRI will finalize a statistical analysis 
plan that describes all analyses that will be included in the clinical study report; and 
• Gates MRI will rely on the new service provider to initiate unblinding as described in 
their SOP, including use of the new service provider’s unblinding authorization form.  
Gates MRI is currently in the process of establishing SOPs associated with unblinding and 
statistical analysis plans.  
New data transfer agreements have been established to allow blinded and unblinded data 
transfers between Gates MRI and the data management, statistical programming, and PK 
vendors, as described in a separate Unblinding Plan. All of the service providers have continued 
to follow their respective standard operating procedures (SOPs) for establishing and maintaining 
the necessary firewalls to protect the study blind.  


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14. References 
Protocol Gates MRI-RSM01-101. A Phase 1 Randomized, Double-blind, Placebo-Controlled 
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of 
RSM01, a Monoclonal Antibody Targeting Respiratory Syncytial Virus, in Healthy Adults, 
Protocol Version 4.0, 21 Jan 2022. 
FDA, Guidance for Industry: Immunogenicity Assessment for Therapeutic Protein Products 
(Silver Spring, MD, August 2014). 
EMA, Guideline on Immunogenicity assessment of therapeutic  
Proteins – Revision 1 (London, UK, May 2017). 
 


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15. 
Schedule of Assessments 
Schedule of Activities for the Dose Escalation Phase (Cohorts 1-4) 
Visits 
Screen Pre-
Vl 
V2 
Vl 
Study Day and Visit window days ( d) D-30 to 
D-1 
Dl 
D2 
D-2d 
±0d 
±Od 
±Od 
Activities: 
Informed consent 
X 
Check/verify eligibility criteria 
X 
X 
X 
Confinement1 
X 
X 
X 
Demography, full medical history, PE, 
X 
heiclit, weight 
Focused PE 
X 
X 
X 
Semm pregnancy tesfl 
X 
X 
HIV antibody and Hepatitis B & C test 
X 
Urine drug screen 
X 
X 
Urinalysis 
X 
X 
Safety laboratory assessmentsj 
X 
X 
12-lead electrocardiogram {ECG), 
X 
X 
oerformed intriolicate4 
Vital signs5 
X 
X 
X 
Randomization6 
X 
Study intervention administration' 
X 
Distribute/review diruy cru·ds 
Collect diary card 
Distribute memory aid 
Collect memory aid 
Record solicited AEs (local for IM 
X 
X 
doses only, &systemic) through Day 7 
Record unsolicited AEs, AESis, and SAEs 
X 
X 
X 
X 
Record concomitant medications 
X 
X 
X 
V3 
D3 
±0d 
X 
X 
X 
X 
X 
X 
X 
X 
V4 
D6 
±Id 
X 
X 
X 
X 
X 
X 
Final Statistical Analysis Plan, Version 2.0 
Date Issued: 7 Sep2022 
vs 
V6 
V 
V8 
V9 
VlO Vll 
7 
D8 
Dl 5 
D2 D61 
D91 
Dl21 Dl51 
Day8- ±3d 
9 Day ±7d 
±7d 
±7d 
±7d 
10 
29-35 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Page 32 of35 
Dis-
con 
Visit9 
X 
X 
X 
X 
X 
X 
X 
X 


Bill & Melinda Gates Medical Research Institute 
Gates MRI-RSM0l-101 
Schedule of Activities for the Dose Escalation Phase (Cohorts 1-4) 
Final Statistical Analysis Plan, Version 2.0 
Date Issued: 7 Sep2022 
Visits Screen Pre- V l V2 V3 V4 vs 
V6 
V7 
V 
V 
Vl 
Vll Dis-
Vl 
8 
9 
0 
con 
Study Day and Visit window days ( d) 
-30 to D-1 D1 D2 D3 
D6 
D8 
D15 
D29 
D61 D91 D121 D151 Visit9 
Activities: 
-2d 
±Od ±Od ±Od ±Id Day 8-
±3d Day29- ±7d ±7d ±7d 
±7d 
10 
35 
Senun and V AMS sample for PK8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Senun and V AMS sample for ADAs8 
X 
X 
X 
X 
X 
X 
X 
Senun and V AMS sample for RSV nAb levels8 
X 
X 
X 
V = Visit; D= Day; PE= physical examination; HIV= Human immunodeficiency virus; IM= intramuscular; AE=adverse event, SAE=serious adverse 
event; AESI=AE of special interest; PK= phannacokinetics; ADA = anti-dmg antibodies; V AMS = volumetric abso1ptive microsampling RSV mAb 
= Respiratory Syncytial Vims neutralizing antibody 
X 
X 
X 
1 Confinement- participants will be confined to study site from Day - 1 to after completion of Day 3 assessment (a total of3 nights). All Day 1 assessments 
and sample collections are prior to study intervention. 
2 In addition to scheduled pregnancy tests in female pa1ticipants, if pregnancy is suspected during the study, a selUlll test will be done. 
3 Safety laboratory testing includes semm chemistry and hematology. 
4 All 12-lead ECGs will be obtained after the participant has rested in a supine position for at least 10 minutes. Triplicate ECGs will be taken 
approximately one minute apart. Refer to Protocol section 8.1.6 for details. The window for obtaining the initial ECG is± 15 minutes. 
5 Day 1 vital signs will be taken pre-dose before blood sample collection, and 1 hour, 4 hours and 8 hours after IM dose and at pre-dose, 15, 30 and 45 
minutes, 1 hour, 1. 5 hours, 2 hours, 4 hours, and 8 hours after IV dose. The window for vital signs measurements is ± 3 minutes. Refer to Protocol 
section 8.1.2.1. Vital Signs for details. On Day 2, vital signs will be taken at 24 hours post-dose. The window for these measurements is± 0.5 hours. 
On Day 3, vital signs will be taken at 48 hours after dosing. The window for these measurements is ± 1.0 hours. 
6 The first participant in each cohort ( Cohorts 1-4) will receive RSM0 1 without being randomized. 
7 On any given day, paiticipants should be dosed at least 2 hours apart, after the first sentinel paiticipant is dosed with RSM0l, 
and 24 hours has passed. The c:::2-hour wait time betv.•een IV infusions is to begin at the end of the previous infusion. 
8 Blood samples for PK assessments on Day 1 (Visit 1) will be drawn at pre-dosing 1 hour(+/- 30 minutes) before administration of IM injection or 
beginning of infusion,, at 5 minutes(± 1 minute) after end of infusion for IV doses only, and at 8-hours (±0.5 hour) and 24-hours (±1 hour) after end 
of infusion for IV doses and at 8-hours (±0.5 hour) and 24-hours (±1 hour) after IM doses. ADA and RSV neutralizing antibody on Day 1 (Visit 1) 
will be drawn pre-dose only 1 hour(+/- 30 minutes) before administration of IM injection or beginning of infusion. 
9 Early Discon= A discontinuation visit will be scheduled for pa1ticipants who discontinue or withdraw, whenever possible. 
Page 33 of35 


Bill & Melinda Gates Medical Research Institute 
Gates MRI-RSM0l-101 
Final Statistical Analysis Plan, Version 2.0 
Date Issued: 7 Sep2022 
Schedule of Activities for the Expansion Phase (Cohort 5) 
Visits 
Screen 
Pre-Vt 
Vl 
V2 
V 3 
V 4 vs 
Discon 
Study Day and Visit window days (d) 
D-30 to 
Day -1 
D1 
D8 
D29 
D91 
D151 visit8 
Activities: 
D-ld 
±0 
Days 
Days 
±7d 
±7d 
8-10 
29-35 
Info1med consent 
X 
Check/verify eligibility criteria 
X 
X 
X 
Confinement1 
X 
(X) 
Demography, full medical history, PE, height, weigh1 
X 
Focused history!PE 
X 
X 
X 
X 
X 
X 
Serum pregnancy test' 
X 
X 
X 
HIV antibody, Hepatitis B and C 
X 
Urine dmg screen 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
X 
Safety lahorato1y assessments:; 
X 
X 
X 
X 
X 
X 
12-lead ECG (performed in triplicate)4 
X 
Vital signs) 
X 
X 
X 
Randomization 
X 
Study intervention administration° 
X 
Distribute/review dia1y cards 
X 
Collect diary cards 
X 
Distribute memory aid 
X 
X 
X 
X 
Collect memory aid 
X 
X 
X 
X 
X 
Record solicited AEs (local & systemic) 
X 
Record unsolicited AEs, AESis and SAEs 
X 
X 
X 
X 
X 
X 
X 
X 
Record concomitant medications 
X 
X 
X 
X 
X 
X 
X 
Serum and V AMS sample for PK7 
X 
X 
X 
X 
X 
X 
Serum and VAMS sample for ADAs7 
X 
X 
X 
X 
X 
Serum and V AMS for RSV nAb levels7 
X 
X 
X 
X 
V = Visit; D= Day; PE= physical examination; HIV= Human immunodeficiency vims; IM= intramuscular; AE=adverse 
event, SAE=serious adverse event; AESI=AE of special interest; PK= phannacokinetics; ADA = anti-drng antibodies; 
V AMS = volumetric abso1ptive microsampling; RSV mAb = Respirat01y Syncytial Vims neutralizing antibody 
1Confinement = paiticipant should present to the clinic within 24 hours of Day -1 visit and will stay at the clinic on the Pre-Vl, Day -l(i.e., the 
night before the Day 1 visit). (X)= A second overnight stay for the night of Day 1 is optional, based on investigator's decision. If participant is 
confined on the night of Day 1, vital signs will be taken 24 hours post-dose. 
2 In addition to scheduled pregnancy tests in female pa1ticipants, if pregnancy is suspected at any time during the study, a semm test will be done. 
Page 34 of35 


 
Bill & Melinda Gates Medical Research Institute 
Final Statistical Analysis Plan, Version 2.0 
Gates MRI-RSM01-101 
Date Issued: 7 Sep2022 
 
 
Page 35 of 35 
 
3 Safety laboratory assessments includes serum chemistry and hematology. 
4 12-lead ECGs will be obtained after the participant has rested in a supine position for at least 10 minutes. Triplicate ECGs will be taken 
approximately one minute apart. Refer to Protocol section 8.1.6 for details. 
5 Day 1 vital signs will be taken before dose and again 4 hours after dose. The window for vital signs measurements is ± 3 minutes. Refer to 
Protocol section 8.1.2.1. Vital Signs for details. 
6 All Day 1 safety assessments and sample collections will be done prior to study intervention. Symptom assessments will be done after dosing. 
Following dose administration, if the participant will not be confined overnight for the optional night of Day 1, they will be observed for at least 
4 hours at the study site after receiving the study intervention, for safety monitoring. 
7 Blood samples for PK, ADA and RSV neutralizing antibody at Day 1 will be drawn at pre-dose only 1 hour (+/- 30 minutes) before 
administration of IM injection. 
8 Early Discon = A discontinuation visit will be scheduled for participants who discontinue or withdraw, when possible.