A Phase 1, Randomized, Recipient- and Observer-Blinded, Dose-Escalation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Two Doses of Rabies-Vectored Monovalent Lassa Fever Vaccine (LASSARAB) Administered With 3D-(6-Acyl) PHAD-SE (aPHAD-SE) Adjuvant in Healthy Adults
Phase: PHASE1
Conditions: Lassa Fever
Sponsor: Wilbur Chen, MD, MS

 
 
 
 
A Phase 1, Randomized, Recipient- and Observer-Blinded, Dose- 
Escalation Study to Evaluate the Safety, Reactogenicity, and 
Immunogenicity of Two Doses of Rabies-Vectored Monovalent 
Lassa Fever Vaccine (LASSARAB) Administered with 3D-(6-Acyl) 
PHAD-SE (aPHAD-SE) Adjuvant in Healthy Adults 
 
DMID Protocol Number: 23-0015 
IND Number: 30607 
IND Sponsor: 
Center for Vaccine Development and Global Health,  
University of Maryland, Baltimore 
IND Sponsor Representative: 
Wilbur Chen, MD, MS 
Center for Vaccine Development and Global Health,  
University of Maryland, Baltimore 
Principal Investigator: 
Justin R. Ortiz, MD, MS 
Center for Vaccine Development and Global Health,  
University of Maryland, Baltimore 
 
Version Number: 6.0 
13 June 2025 
 
 

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STATEMENT OF COMPLIANCE 
 
Each institution engaged in this research will hold a current Federalwide Assurance (FWA) 
issued by the Office of Human Research Protection (OHRP) for federally funded research. The 
IRB/IEC must be registered with OHRP as applicable to the research. 
The study will be carried out in accordance with the following as applicable: 
• United States Code of Federal Regulations (CFR) 45 CFR Part 46: Protection of Human 
Subjects 
• Food and Drug Administration (FDA) Regulations: 21 CFR Part 50 (Protection of 
Human Subjects), 21 CFR Part 54 (Financial Disclosure by Clinical Investigators), 21 
CFR Part 56 (Institutional Review Boards), 21 CFR Part 11, and 21 CFR Part 312 
(Investigational New Drug Application), and/or 21 CFR 812 (Investigational Device 
Exemptions) 
• The International Council for Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use (ICH) E6(R2) Good Clinical Practice, and the 
Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects 
of Research, Report of the National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research 
• The policies and procedures of National Institutes of Health (NIH) Office of Extramural 
Research and DMID 
• The National Institute of Allergy and Infectious Diseases (NIAID) Terms of Award 
• Any additional Federal, State, and Local Regulations and Guidance 
The signature below provides the necessary assurance that this study will be conducted 
according to all stipulations of the protocol including statements regarding confidentiality, and 
according to local legal and regulatory requirements, US federal regulations, and ICH E6(R2) 
Good Clinical Practice (GCP) guidelines. 
 
Site Investigator Signature: 
 
 
Signed: 
 
Date: 
 
 
Justin R. Ortiz, MD MS 
Principal Investigator 
Professor of Medicine 
Center for Vaccine Development and Global Health 
University of Maryland, Baltimore 
 
 
 
 
 

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TABLE OF CONTENTS 
IND Sponsor: ............................................................................................................................ 1 
IND Sponsor Representative: .................................................................................................... 1 
Principal Investigator: ............................................................................................................... 1 
Version Number: 6.0 ................................................................................................................. 1 
STATEMENT OF COMPLIANCE .............................................................................................. 2 
TABLE OF CONTENTS .............................................................................................................. 3 
LIST OF TABLES ........................................................................................................................ 6 
1. PROTOCOL SUMMARY ...................................................................................................... 7 
1.1 
Synopsis ........................................................................................................................ 7 
1.2 
Schedule of Activities (SoA) ....................................................................................... 17 
1.3 
Study Schema .............................................................................................................. 19 
2. INTRODUCTION ................................................................................................................ 20 
2.1 
Study Rationale ........................................................................................................... 20 
2.2 
Background ................................................................................................................. 20 
2.2.1 
Purpose of Study ......................................................................................................... 20 
2.3 
Risk/Benefit Assessment ............................................................................................. 21 
2.3.1 
Known Potential Risks ................................................................................................ 21 
2.3.2 
Known Potential Benefits ........................................................................................... 23 
2.3.3 
Assessment of Potential Risks and Benefits ............................................................... 23 
3. OBJECTIVES AND ENDPOINTS ...................................................................................... 23 
4. STUDY DESIGN.................................................................................................................. 23 
4.1 
Overall Design ............................................................................................................. 23 
4.2 
Scientific Rationale for Study Design .......................................................................... 25 
4.3 
Justification for Dose ................................................................................................... 26 
5. STUDY POPULATION ....................................................................................................... 26 
5.1 
Inclusion Criteria ......................................................................................................... 26 
5.2 
Exclusion Criteria ........................................................................................................ 26 
5.2.1 
Exclusion of Specific Populations .............................................................................. 27 
5.3 
Inclusion of Vulnerable Participants ............................................................................ 27 
5.4 
Lifestyle Considerations .............................................................................................. 27 
5.5 
Screen Failures ............................................................................................................ 27 
5.6 
Strategies for Recruitment and Retention .................................................................... 28 
5.6.1 
Recruitment ................................................................................................................. 28 
5.6.2 
Retention ..................................................................................................................... 28 
5.6.3 
Compensation Plan for Participants ............................................................................ 28 
5.6.4 
Costs ............................................................................................................................ 28 
6. STUDY PRODUCT.............................................................................................................. 28 
6.1 
Study Product(s) and Administration ........................................................................... 28 
6.1.1 
Study Product Description .......................................................................................... 28 
6.1.2 
Dosing and Administration ......................................................................................... 30 
6.1.3 
Dose Escalation ........................................................................................................... 30 

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6.1.4 
Dose Modifications ..................................................................................................... 30 
6.2 
Preparation/Handling/Storage/Accountability ............................................................. 30 
6.2.1 
Acquisition and Accountability .................................................................................. 30 
6.2.2 
Formulation, Appearance, Packaging, and Labeling .................................................. 31 
6.2.3 
Product Storage and Stability...................................................................................... 32 
6.2.4 
Preparation .................................................................................................................. 32 
6.2.5 
Treatment Assignment Procedures ............................................................................. 33 
6.2.6 
Randomization and Blinding ...................................................................................... 33 
6.2.7 
Blinding and Masking Procedures .............................................................................. 33 
6.3 
Unblinding ................................................................................................................... 34 
6.4 
Study Intervention Compliance ................................................................................... 34 
6.5 
Concomitant Therapy .................................................................................................. 35 
6.5.1 
Rescue Medicine ......................................................................................................... 35 
7. STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL............................................................................. 35 
7.1 
Halting Criteria and Discontinuation of Study Intervention ......................................... 36 
7.1.1 
Study Halting Criteria ................................................................................................. 36 
7.1.2 
Individual Halting Criteria .......................................................................................... 36 
7.1.3 
Criteria for redosing .................................................................................................... 36 
7.1.4 
Follow up for participants that discontinued study intervention ................................ 36 
7.1.5 
Follow up for Participants with a Suspicion for Sensorineural Hearing Loss ............ 36 
7.2 
Participant Withdrawal from the Study and Replacement ........................................... 37 
7.3 
Lost to Follow-Up ....................................................................................................... 38 
8. STUDY ASSESSMENTS AND PROCEDURES ................................................................ 38 
8.1 
Screening Procedures .................................................................................................. 38 
8.1.1 
Procedures to be Followed in the Event of Abnormal Laboratory Test Values or 
Abnormal Clinical Findings ........................................................................................ 39 
8.2 
Immunogenicity Assessments ..................................................................................... 40 
8.2.1 
Immunogenicity Evaluations ...................................................................................... 40 
8.2.2 
Exploratory Assessments ............................................................................................ 40 
8.3 
Safety and Other Assessments ..................................................................................... 40 
8.3.1 
Scheduled Phone Visits for Safety Assessment .......................................................... 41 
8.3.2 
Procedures to be Followed in the Event of Abnormal Laboratory Test Values or 
Abnormal Clinical Findings ........................................................................................ 42 
8.3.3 
Unscheduled Visit ....................................................................................................... 42 
8.3.4 
Early Termination Visit .............................................................................................. 42 
8.4 
Adverse Events and Serious Adverse Events ............................................................... 42 
8.4.1 
Definition of Adverse Events (AE)............................................................................. 42 
8.4.2 
Definition of Serious Adverse Events......................................................................... 44 
8.4.3 
Classification of an Adverse Event ............................................................................. 45 
8.4.4 
Time Period and Frequency for Event Assessment and Follow-Up ........................... 46 
8.4.5 
Adverse Event Reporting ............................................................................................ 46 
8.4.6 
Serious Adverse Event Reporting ............................................................................... 46 
8.4.7 
Reporting Events to Participants ................................................................................. 48 
8.4.8 
Adverse Events of Special Interest ............................................................................. 48 

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8.4.9 
Medically-Attended Adverse Events .......................................................................... 48 
8.4.10 New-Onset Chronic Medical Conditions .................................................................... 48 
8.4.11 Potentially Immune-Mediated Medical Conditions .................................................... 48 
8.4.12 Reporting of Pregnancy .............................................................................................. 48 
8.5 
Adverse Unanticipated Problems (UP) ........................................................................ 49 
8.5.1 
Definition of Unanticipated Problems (UP) ................................................................ 49 
8.5.2 
Unanticipated Problem Reporting............................................................................... 49 
8.5.3 
Reporting Unanticipated Problems to Participants ..................................................... 49 
9. STATISTICAL CONSIDERATIONS.................................................................................. 50 
9.1 
Statistical Hypotheses .................................................................................................. 50 
9.2 
Sample Size Determination ......................................................................................... 50 
9.3 
Populations for Analyses ............................................................................................. 50 
9.4 
Statistical Analyses ...................................................................................................... 51 
9.4.1 
General Approach ....................................................................................................... 51 
9.4.2 
Secondary Immunogenicity Analysis ......................................................................... 52 
9.4.3 
Exploratory Immunogenicity Analyses ...................................................................... 53 
9.4.4 
Baseline Descriptive Statistics .................................................................................... 53 
9.4.5 
Planned Interim and Early Analyses ........................................................................... 53 
9.4.6 
Sub-Group Analyses ................................................................................................... 54 
9.4.7 
Tabulation of Individual Participant Data................................................................... 54 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ....... 54 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................... 54 
10.1.1 Informed Consent Process .......................................................................................... 54 
10.1.2 Study Termination and Closure .................................................................................. 56 
10.1.3 Confidentiality and Privacy ........................................................................................ 56 
10.1.4 Future Use of Stored Specimens and Data ................................................................. 57 
10.1.5 Key Roles and Study Governance .............................................................................. 59 
10.1.6 Safety Oversight.......................................................................................................... 59 
10.1.7 Clinical Monitoring ..................................................................................................... 60 
10.1.8 Quality Assurance and Quality Control ...................................................................... 60 
10.1.9 Data Handling and Record Keeping ........................................................................... 61 
10.1.10 Protocol Deviations ..................................................................................................... 62 
10.1.11 Publication and Data Sharing Policy .......................................................................... 63 
10.1.12 Human Data Sharing Plan ........................................................................................... 63 
10.1.13 Genomic Data Sharing Plan ........................................................................................ 63 
10.1.14 Publication .................................................................................................................. 63 
10.1.15 Conflict of Interest Policy ........................................................................................... 63 
10.2 
Additional Considerations ........................................................................................... 64 
10.2.1 Research Related Injuries ........................................................................................... 64 
10.3 
Abbreviations .............................................................................................................. 65 
11. PROTOCOL AMENDMENT HISTORY ............................................................................ 68 
12. REFERENCES ..................................................................................................................... 70 
13. APPENDICES ...................................................................................................................... 72 
Appendix 1. Sentinel Subgroup Halting Criteria, Individual Halting Criteria, and General 

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Study Halting Criteria ................................................................................................. 72 
Appendix 2. Schedule of Blood Draws and Volumes ............................................................. 74 
Appendix 3: Grading Scale for Clinical Laboratory Values ................................................... 75 
Appendix 4: Grading Scale for Local Injection Site Reactions............................................... 76 
Appendix 5: Grading Scale for Determining the Severity of Abnormal Vital Signs .............. 77 
Appendix 6: Grading Scale for Determining the Severity of Clinical AEs ............................ 78 
Appendix 7: List of PIMMCs ................................................................................................. 79 
 
LIST OF TABLES 
Table 1. Study Treatment Arms ...................................................................................................... 7 
Table 2. Dose Escalation Schedule ................................................................................................. 9 
Table 3. Formulations of LASSARAB +aPHAD-SE by Treatment Group .................................. 32 
Table 4. Probability to Detect One or More Safety Events ........................................................... 50 
 
 
 
 
 
 
 

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1. PROTOCOL SUMMARY 
1.1 
Synopsis 
Rationale for Proposed Clinical Study 
Lassa fever is a zoonotic infection endemic in West Africa and is spread by the Lassa virus, an 
arenavirus causing hemorrhagic fever. Up to 300,000 Lassa fever infections occur annually and 
while disease is often mild, in a subset of individuals disease is characterized by severe anemia, 
bleeding, encephalopathy, respiratory failure, shock, and high mortality.1 In some regions of 
West Africa, up to 15% of hospital admissions are secondary to Lassa fever, and an estimated 
5,000 deaths occur annually.2 During epidemics of disease, case-fatality rates may reach as high 
as 50% in hospitalized patients.1 Approximately one-third of infected individuals will develop 
hearing loss regardless of disease severity, and in a proportion of patients, permanent deafness 
occurs.1 
Prevention of illness through vaccination is a critical goal in reducing the burden of disease from 
Lassa fever. There are currently no vaccines or therapeutics demonstrated to be efficacious in the 
prevention or treatment of Lassa fever.3 
This study proposes the evaluation of a novel, first-in-human Lassa fever vaccine based on the 
complete Lassa glycoprotein complex (GPC) antigen. The antigen will be presented on a 
genetically modified and attenuated rabies vector expressing both the rabies glycoprotein (GP) 
antigen and the Lassa GPC. The inactivated chimeric virus is delivered with a toll-like receptor 4 
(TLR-4)-activating oil-in-water emulsion adjuvant. Studies using this vaccine administered as a 
prime-boost series in mice and non-human primates, and then challenged with Lassa virus 
demonstrated significant protection against Lassa fever.4-6 Given that the vaccine backbone is an 
attenuated and inactivated rabies virus expressing rabies GP, this vaccine will also be evaluated 
for immunogenicity against rabies virus. 
Study Design 
This is a phase 1, randomized, controlled, recipient- and observer-blinded, dose-escalation 
clinical trial to evaluate the safety, tolerability, and immunogenicity of LASSARAB+aPHAD-SE 
vaccine candidate compared to a licensed rabies virus vaccine control (HDCV), each 
administered as intramuscular (IM) doses on Days 1 and 29 in adult participants aged 18 through 
50 years. The trial will enroll up to 55 healthy participants. The study treatment groups are 
summarized in Table 1. If all 55 participants are enrolled and vaccinated, the randomization will 
be 3:3:3:2 of LASSARAB 700rU dose, LASSARAB 1400rU dose, LASSARAB 2800rU dose (2 
injections of 1400rU), and HDCV comparator. 
Table 1. Study Treatment Arms 
Treatment 
Group 
Number of 
Participants 
Product 
Antigen Dose 
Adjuvant Dose 
Frequency of 
Administration 
A 
15 
LASSARAB+ aPHAD-SE 
700rU 
5µg 
D1, D29 

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B 
15 
LASSARAB+ aPHAD-SE 
1400rU 
5µg 
D1, D29 
C 
15 
LASSARAB+ aPHAD-SE 
1400rU per 
injection 
(2 injections) 
5µg per injection 
(2 injections) 
D1, D29 
D 
10 
HDCV 
≥2.5 IU rabies 
antigen 
N/A 
D1, D29 
Note: Treatment Group C will receive two simultaneous injections of the LASSARAB 1400rU dose vaccine. 
Therefore, each participant in treatment Group C will receive a total 2800rU LASSARAB and 10µg aPHAD-SE. 
Some Group D participants will receive an injection of normal saline placebo simultaneous to HDCV to maintain 
blinding of Group C. See Table 2 for details. 
Participants will be recruited from the greater Washington/Baltimore Metropolitan Area. The 
trial will be conducted by a single center, the Center for Vaccine Development and Global 
Health (CVD) at the University of Maryland, Baltimore (UMB). Participants will be screened to 
determine eligibility for enrollment. Screening will include evaluations for general health, factors 
that may increase the risk to participants in the trial, and factors that could confound 
interpretation or execution of the study. Eligible participants will be enrolled and randomized to 
treatment groups using block randomization for each cohort generated by the unblinded study 
statistician. Participants will then be vaccinated in a dose escalating process as shown in Table 2 
and in Section 1.3. The investigators, study staff (excluding vaccine administrators), and study 
participants will be blinded to the treatment each participant receives. Adverse events (AEs) will 
be assessed by blinded study clinicians for severity using relevant DMID toxicity tables and for 
the relationship of the event to the study product treatment. 
For this trial, a conservative dose escalation design is used in which each treatment group of 15 
vaccine recipients is split into two subgroups. The first subgroup, termed the “sentinel 
subgroup,” includes 4 vaccine recipients. The second subgroup, termed the “expanded 
subgroup,” includes the remaining 11 vaccine recipients. In each of the three initial treatment 
groups (Group A, Group B, and Group C), enrollment is paused for 7 days after vaccination of 
the sentinel subgroup for safety review. 
Study participants will be divided into four vaccination cohorts.  
• In Cohort 1, there will be 4 LASSARAB 700rU dose recipients (Group A sentinel 
subgroup) and 1 HDCV control recipient. If no Sentinel Subgroup Halting Criteria are 
met after 7 days of safety monitoring, an Independent Safety Monitor (ISM) will 
recommend proceeding to vaccinate Cohort 2. 
• In Cohort 2, there will be 4 LASSARAB 1400rU dose recipients (Group B sentinel 
subgroup), 3 HDCV control recipients, and 11 LASSARAB 700rU dose recipients 
(Group A expanded subgroup). If no Sentinel Subgroup Halting Criteria are met after 7 
days of safety monitoring, the ISM will recommend proceeding to vaccinate Cohort 3. 
• In Cohort 3, there will be 4 recipients of two simultaneous injections of LASSARAB 
1400rU dose product (Group C sentinel subgroup), 3 HDCV control recipients, and 11 
single-injection LASSARAB 1400rU dose recipients (Group B expanded subgroup). If no 
Sentinel Subgroup Halting Criteria are met after 7 days of safety monitoring, the ISM 

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will recommend proceeding to vaccinate Cohort 4. 
• In Cohort 4, there will be 3 HDCV control recipients, and 11 recipients of two 
simultaneous injections of LASSARAB 1400rU dose product (Group C expanded 
subgroup). 
Table 2. Dose Escalation Schedule 
Cohort 
Group 
Number of 
Participants 
Group Type 
Injection #1 Treatment 
Injection #2 Treatment 
1 
A 
4 
Sentinel 
LASSARAB 700rU Dose 
N/A 
D 
1 
Control 
HDCV control 
N/A 
Total 
5 
2 
A 
11 
Expanded 
LASSARAB 700rU Dose 
N/A 
B 
4 
Sentinel 
LASSARAB 1400rU Dose 
N/A 
D 
3 
Control 
HDCV control 
N/A 
Total 
18 
3 
B 
11 
Expanded 
LASSARAB 1400rU Dose 
N/A 
D 
2 
Control 
HDCV control 
N/A 
C 
4 
Sentinel 
LASSARAB 1400rU Dose  
LASSARAB 1400rU Dose  
D 
1 
Control 
HDCV control 
Normal saline placebo 
Total 
18 
4 
C 
11 
Expanded 
LASSARAB 1400rU Dose 
LASSARAB 1400rU Dose 
D 
3 
Control 
HDCV control 
Normal saline placebo 
Total 
14 
Note: Treatment Group C will receive two vaccine injections administered in bilateral arms simultaneously. 
Therefore, each participant in treatment Group C will receive a total 2800rU LASSARAB and 10 µg aPHAD-SE. 
To maintain blinding of participants in Cohorts 3 and 4, one dose of normal saline placebo will be administered in 
the contralateral arm to one participant receiving HDCV control in Cohort 3 and to all three participants receiving 
HDCV control in Cohort 4. 
There will be no further planned ISM safety reviews for dose escalation after Cohort 4, although 
study investigators will continue to monitor for safety and apply relevant Individual Halting 
Criteria and General Study Halting Criteria and safety procedures when applicable. To maintain 
blinding of participants in Cohort 3 and 4, one dose of normal saline placebo will be 
administered simultaneously in the contralateral arm in some participants receiving HDCV 
control (See Table 2 for details). 
Participants will be monitored for one year following the second study vaccination (through Day 
394). A paper Diary Card will be used to collect solicited and unsolicited AE information 
covering the 7-day period following each study vaccination. Safety laboratory analyses will be 
performed on Day 8 and Day 36 (7 days following each study treatment), as well as on Day 61. 
Blood samples will be obtained for immunological assays at Days 1, 8, 29, 36, 61, 121 and 394. 
Left-over and additional blood specimens will also be retained and collected for future use. 
Unsolicited adverse events will be collected through Day 61 (32 days after the last study 
treatment). Only a subset of AEs will be collected beyond Day 61; these are serious adverse 

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events (SAEs), medically-attended adverse events (MAAEs), new-onset chronic medical 
conditions (NOCMCs), potential immune-mediated medical conditions (PIMMCs), and an 
adverse event of special interest (AESI) – new onset sensorineural hearing loss (SNHL). SNHL 
will be assessed by audiometry at screening, after the first vaccine dose at Day 22, after the 
second vaccine dose at Day 61, upon completion of the study at Day 394, and at any time if the 
participant reports change in hearing or at the discretion of the Principal Investigator (PI). SAEs, 
MAAEs, NOCMCs, PIMMCs, and the AESI will be collected through Day 394 (the end of the 
study, approximately one year after the second study vaccination). See Section 7.1.5 for SNHL 
definitions and evaluation procedures and see Appendix 7 for the list of specific PIMMCs to be 
reported. 
An interim analysis of the Primary and Secondary Endpoints will be performed with all data and 
samples collected through Day 61. These analyses will be reported in an interim clinical study 
report (CSR). To maintain blinding of principal investigator, sponsor, and blinded study staff, 
results will be presented in summary tables by Treatment Arm. Data and studies from blood 
samples collected after Day 61 will be reported in separate CSRs. Assessed exploratory 
endpoints will also be included in the final CSR. 
Study Objectives and Endpoints 
Primary Objective 
Primary Endpoint 
To assess the safety 
and reactogenicity of 
escalating doses of the 
LASSARAB+ aPHAD-
SE vaccine candidate 
administered at Day 1 
and Day 29 
• 
Number and percentage of participants experiencing solicited local and systemic 
reactogenicity AEs through 7 days after each study vaccination (From Day 1 through 
Day 8 for the first vaccination and from Day 29 through Day 36 for the second 
vaccination) 
• 
Number and percentage of participants experiencing any unsolicited AEs from Day 1 
through Day 61 
• 
Number and percentage of participants experiencing any of the following from Day 1 
through Day 394: 
• 
Serious Adverse Events (SAEs), 
• 
Medically-Attended Adverse Events (MAAEs), 
• 
New-Onset Chronic Medical Conditions (NOCMCs), 
• 
Potential Immune-Mediated Medical Conditions (PIMMCs), 
• 
Adverse Event of Special Interest (AESI)—new onset sensorineural hearing loss 
(SNHL) 
• 
Number and percentage of participants experiencing clinical laboratory AEs through 
Day 61 
 
Secondary Objective 
Secondary Endpoint 

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To evaluate the Lassa 
antibody response at 
escalating doses of the 
LASSARAB+aPHAD-
SE vaccine candidate 
administered at Day 1 
and Day 29 
• 
Geometric mean IgG titers (GMT) to LASSA GPC by enzyme linked 
immunosorbent assay (ELISA) at Day 1, 8, 29, 36, and 61 per treatment group 
• 
Percentage of participants seroconverting for Lassa GPC IgG antibodies at Day 8, 
29, 36, and 61 per treatment group (where seroconversion is defined as > 4 fold rise 
in antibody titer at any time point as compared to baseline.) 
To evaluate the rabies 
antibody responses to 
LASSARAB+aPHAD-
SE vaccine candidate 
administered at Day 1 
and Day 29 
• 
Percentage of participants with rabies antibody titers by the RFFIT test (Rapid 
Fluorescent Foci Inhibition Test) at Day 8, 29, 36, and 61 per treatment group 
• 
Geometric mean IgG titers (GMT) to rabies GP by ELISA at Day 8, 29, 36, and 61 
per treatment group 
• 
Percentage of participants seroconverting for rabies antibodies at Day 8, 29, 36, and 
61 per treatment group (where seroconversion is defined as > 4 fold rise in antibody 
titer at any time point as compared to baseline.) 
 
Exploratory Objective 
Exploratory Endpoint 
To evaluate the 
durability of Lassa 
antibody responses to 
LASSARAB+aPHAD-
SE vaccine candidate 
• 
Geometric mean IgG titers (GMT) to LASSA GPC by ELISA at Day 121, and 394 
per treatment group 
• 
Percentage of participants seroconverting for Lassa GCP antibodies at Day 121, and 
394 per treatment group (where seroconversion is defined as > 4 fold rise in 
antibody titer at any time point as compared to baseline). 
To evaluate the rabies 
antibody responses to 
LASSARAB+aPHAD-
SE vaccine candidate 
• 
Percentage of participants with rabies antibody titers by the RFFIT test (Rapid 
Fluorescent Foci Inhibition Test) at Day 121 and 394 per treatment group 
• 
Geometric mean IgG titers (GMT) to rabies GP by ELISA at Day 121 and 394 per 
treatment group 
• 
Percentage of participants seroconverting for rabies antibodies at Day 121 and 394 
(where seroconversion is defined > 4 fold rise in antibody titer at any time point as 
compared to baseline). 
Inclusion criteria: In order to be eligible to participate in this study, an individual must meet all 
of the following criteria: 
1. Provides written informed consent prior to the initiation of any trial procedures. 
2. Able to understand and agrees to comply with all planned trial procedures and be 
available for all study visits. 
3. Age ≥ 18 and ≤50 years at time of enrollment. 
4. In good general health1 and without clinically significant medical, psychiatric, chronic or 
intermittent health conditions including those listed in Exclusion Criteria (Section 5.2). 
1As evidenced by medical history, medication use, and physical examination to 

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evaluate ongoing chronic medical or psychiatric diagnoses or conditions, defined as 
those that have been present for at least 60 days, which would not affect the 
assessment of the safety of participants or the immunogenicity of study vaccinations. 
These medical diagnoses or conditions should be stable for the last 60 days (no 
hospitalizations, emergency room [ER] or urgent care for condition [excluding 
musculoskeletal conditions]), or invasive medical procedure and no adverse 
symptoms that need medical intervention such as medication change/supplemental 
oxygen). This includes no change in chronic prescription medication or dose in the 60 
days prior to enrollment. Any prescription change that is due to change of health care 
provider, insurance company, etc., or that is done for financial reasons, as long as in 
the same class of medication, will not be considered a deviation of this inclusion 
criterion. Participants may be on chronic or as needed (prn) medications if, in the 
opinion of the PI or appropriate sub-investigator, they pose no additional risk to 
participant safety or assessment of reactogenicity and immunogenicity and do not 
indicate a worsening or treatment of continued symptoms of medical diagnosis or 
condition. Note: Low dose topical corticosteroids as outlined in the Participant 
Exclusion Criteria (Section 5.2) as well as herbals, vitamins, and supplements are 
permitted. 
5. Participants of childbearing potential2 must have a negative serum human chronic 
gonadotropin (HCG) pregnancy test at screening and a negative urine HCG pregnancy 
test within 24 hours prior to the study vaccination. 
2Not of childbearing potential - post-menopausal females (defined as having a history 
of amenorrhea for at least one year) or a documented status as being surgically 
sterile (hysterectomy, bilateral oophorectomy, salpingectomy, or Essure® placement 
with history of documented radiological confirmation test at least 60 days after the 
procedure). 
6. Participants of childbearing potential3 in a heterosexual relationship agree to use of 
highly effective contraception4 beginning at the time of the screening visit through Day 
61 (32 days after the last study treatment). 
3Not of reproductive potential means post-menopausal participants born female 
(defined as having a history of amenorrhea for at least one year) or a documented 
status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal 
ligation/salpingectomy, or Essure® placement with history of documented 
radiological confirmation test at least 90 days after the procedure). These criteria 
are applicable to female participants in a heterosexual relationship AND of 
reproductive potential. These criteria do not apply to participants in a same sex 
relationship. 
4Acceptable forms of primary contraception include true abstinence (100% of time 
no insertional sexual intercourse), monogamous relationship with a vasectomized 
partner who has been vasectomized for 180 days or more prior to the participant 

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receiving the vaccination, intrauterine devices, birth control pills, condoms with 
spermicide, and injectable/implantable/insertable/transdermal hormonal birth 
control products. Must use at least one acceptable primary form of contraception for 
at least 30 days prior to enrollment and through the end of the study. 
7. Vital signs5 and Body Mass Index (BMI) are in the following ranges at screening: 
• Oral temperature is less than 100.4°F (38.0°C). 
• Pulse is 47 to 100 beats per minute, inclusive. 
• Systolic blood pressure (SBP) is 85 to 140 mmHg, inclusive. 
• Diastolic blood pressure (DBP) is 55 to 90 mmHg, inclusive. 
• BMI of 18 kilograms/square meter (kg/m2) (inclusive) to <35 kg/m2 
5Vital signs meeting Grade 1 severity criteria (Appendix 5) and not clinically 
significant may be eligible as determined by the investigator. 
8. Has a negative test result for hepatitis B virus (HBV) surface antigen, hepatitis C virus 
(HCV) antibody6, and human immunodeficiency virus (HIV) types 1 or 2 antibodies at 
screening. 
6Persons testing positive for hepatitis C virus antibody with a history of treatment 
and a negative HCV viral load may be acceptable in the opinion of the PI or 
designated clinician licensed to make medical diagnoses and listed on Form FDA 
1572. 
9. Has a negative rabies neutralizing antibody test at screening (< 0.5 IU/mL in RFFIT 
assay) 
10. Screening hematology tests (white blood cells, hemoglobin, and platelets) and screening 
chemistry tests (alanine transaminase, creatine, and total bilirubin) are within acceptable 
parameters7 
7Screening laboratory values within institutional laboratory normal limits or Grade 
1 abnormalities if deemed not clinically significant by the investigator are eligible. 
11. Must agree to the collection and storage of residual biological specimens and additional 
clinical specimens for secondary research use (Section 10.1.4) 
12. Agreement to adhere to Lifestyle Considerations (Section 5.4 during the study.8 
8Deviations of Lifestyle Considerations will be reported as protocol deviations but 
not as eligibility deviations. 
Exclusion criteria: An individual who meets any of the following criteria will be excluded from 
participation in this trial: 
1. A history of anaphylaxis, serum sickness, meningitis; neuroparalytic events such as 
encephalitis, transient paralysis; Guillain-Barré Syndrome; myelitis; retrobulbar neuritis; 
history of prior or current hearing loss as assessed by quantitative audiometry (Section 
7.1.5); or multiple sclerosis 
2. Current use of any medications that may be associated with impaired immune 

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responsiveness1 
1Including, but not limited to, corticosteroids exceeding 10 mg/day of prednisone 
equivalent, allergy injections, immunoglobulin, interferon, immunomodulators, 
cytotoxic drugs, or systemic corticosteroids or other similar or toxic drugs during 
the preceding 4-month period prior to screening. Low dose topical and intranasal 
steroid preparations used for a discrete period of time are permitted. 
3. Allergy treatment with antigen injections within 60 days before first vaccination or that 
are planned through the end of the study. 
4. Receipt of immunoglobulins and/or any blood products within the 60 days before first 
vaccination or that are planned through the end of the study. 
5. Current pregnancy or lactation. 
6. Known allergic reactions to 1) any rabies vaccine; 2) any components of HDCV (human 
albumin, neomycin sulfate, phenol red, beta-propiolactone); 3) any components of 
LASSARAB +aPHAD-SE (LASSARAB, Tris-HCI, L-Arginine, (3D -(6-Acyl) PHAD, 
Squalene Redistilled, DMPC, Vitamin E Dry Powder). 
7. History of severe local or systemic reactions to any vaccination or a history of severe 
allergic reactions to drug or vaccine products. 
8. Has a significant acute illness (with or without fever), as determined by the site PI or 
appropriate sub-investigator, within 72 hours prior to enrollment2 
2If the participant meets all other eligibility criteria, they may be enrolled and dosed 
once they meet this eligibility criterion. If the illness resolves within the 60-day 
screening window, they do not need to be rescreened, otherwise they will need to be 
rescreened. 
9. Receipt of a rabies vaccine or an antibody therapeutic product for treating rabies or a 
Lassa fever vaccine any time before the first planned study vaccination. 
10. Receipt of another experimental agent or intervention within 60 days before first 
vaccination or plans to do so before the end of the study. 
11. Received or plans to receive any other vaccine in the 2 weeks prior to the first 
vaccination through Day 61 (32 days after the last study treatment). 
12. Received or plans to receive any live vaccine in the 4 weeks prior to first vaccination 
through Day 61 (32 days after the last study treatment). 
13. Self-reported or known history of alcoholism within the last 2 years. 
14. Any condition that, in the judgment of the investigator, precludes participation because 
it could affect participant safety or endpoint assessment. 
15. Has tattoos, scars, or other marks which would, in the opinion of the investigator, 
interfere with assessment of the vaccination site. 
Study Phase: Phase 1 
Study Population: Up to 55 generally healthy persons aged 18 through 50 years 

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Sites: One site, Center for Vaccine Development and Global Health (CVD) University of 
Maryland School of Medicine 
Study Intervention: The investigational vaccine (LASSARAB) is a Lassa virus (LASV) 
glycoprotein complex (GPC) antigen presented on a chemically inactivated and modified rabies 
virus vector (RABV). This study will evaluate the safety, reactogenicity, and immunogenicity 
conferred by two doses of the vaccine LASSARAB (inactivated rabies virus vector, RABV, 
expressing LASV GPC), adjuvanted with a synthetic Toll-like receptor 4 agonist, 3D-(6-acyl) 
PHAD (Monophosphoryl Hexa-acyl Lipid A, 3-Deacyl) in stable oil-in-water emulsion (SE), 
together as aPHAD-SE. The LASSARAB vaccine antigens are presented on a beta-propiolactone 
chemically inactivated and attenuated platform and administered in combination with the 
aPHAD-SE adjuvant formulation in a two-dose series. Pre-clinical studies have shown that 
LASSARAB with a similar adjuvant given to non-human primates, administered on Days 1 and 
29, led to protection upon subsequent Lassa virus challenge, while non-human primates 
administered a different RABV-based vaccine succumbed to illness upon challenge (internal 
data). 
In a dose escalation procedure, three doses of LASSARAB+ aPHAD-SE will be evaluated 
(LASSARAB 700rU dose, LASSARAB 1400rU dose, and LASSARAB 2800rU dose). All 
vaccine components are liquid and will be mixed with a fixed dose PHAD-SE formulation in the 
research pharmacy. The Group A (LASSARAB 700rU dose), Group B (LASSARAB 1400rU), 
and HDCV are administered as 1 mL volume by intramuscular (IM) injection into the deltoid. 
Group C will be administered as two LASSARAB 1400rU doses of 1 mL volume each by IM 
injection given into bilateral deltoids simultaneously. A normal saline placebo will be 
administered as 1 mL volume by IM injection in some HDCV control recipients to maintain 
blinding in Group C. 
Safety, reactogenicity, and immunogenicity of the candidate LASSARAB+aPHAD-SE vaccine 
will be compared to a commercially available rabies vaccine, human diploid cell vaccine 
(HDCV, produced by the Merieux Institute and sold under the name “Imovax”), also 
administered in a two-dose series. Parameters of safety, reactogenicity, and immunogenicity will 
be reported by treatment group. 
Study Duration: Approximately 15 months 
Participant Duration: Approximately 13 months 
Safety: This clinical study will use both a Safety Review Committee (SRC) and an Independent 
Safety Monitor (ISM). The SRC will consist of the PI, a DMID representative, and the 
Investigational New Drug (IND) sponsor Representative. The SRC will evaluate safety data after 
the first study vaccination from Cohorts 1-3 to assess safety of sentinel subgroup participants, 
provide sentinel subgroup safety data to the ISM for concurrence of SRC safety findings, and 
will notify the IND sponsor Representative of intent to proceed if no study Sentinel Subgroup 

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Halting Criteria are met (Appendix 1). Standardized dose escalation criteria and safety 
evaluations will be used. 
The ISM will be an objective, medically qualified physician-scientist who is not involved with 
the conduct of the study. The ISM will be separate and independent of study personnel 
participating in this trial and should not have scientific, financial, or other conflicts of interest 
related to this trial. The primary responsibility of the ISM is to monitor participant safety. The 
ISM considers study-specific data as well as relevant background information about the disease, 
test agent, and target population under study. During scheduled reviews after sentinel subgroup 
vaccinations as well as at any time during the study when the SRC identifies that halting criteria 
may have been met, the ISM will evaluate the data and recommend appropriateness of further 
dosing. Any member of the SRC may request an ISM review at any time. The ISM will have the 
option to be unblinded to treatment group as needed and will have as a resource an unblinded 
statistician to aid in analyses of data. The decision to advance to the next dosing cohort will be 
documented and provided to the SRC. The ISM will be empowered to suspend (halt) the study, 
recommend amendments to the protocol, and/or to request further information for their review. 
See Appendix 1 for Sentinel Subgroup Halting Criteria, Individual Halting Criteria, and General 
Study Halting Criteria. Further information about safety assessments is in Section 8.3, and 
descriptions of SRC and ISM procedures are in Section 10.1.6. 
 

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1.2 
Schedule of Activities (SoA) 
 
Procedures 
Screening Study 
Visit 0 
Vaccination #1 
Study Visit 1 
Day 1 
Study Visit 2 
Day 3 (±1) 
Study Visit 3 
Day 8 (±3) 
Study Visit 4 
Day 22 (±7) 
Vaccination #2 
Study Visit 5 
Day 29 (±3) 
Study Visit 6 
Day 31 (±3) 18 
Study Visit 7 
Day 36 
(±3) 
Study Visit 8 
Day 61 
(±3) 
Study Visit 9 
Day 121 (±14) 
Study Visit 10 
Day 210 (±14) 
Study Visit 11 
Day 394 (±14) 
Unscheduled Visit17
Early Termination 
Visit17 
Type of Visit 
Clinic 
Clinic 
Phone 
Clinic 
Clinic 
Clinic 
Phone 
Clinic 
Clinic 
Clinic 
Phone 
Clinic 
Clinic 
Clinic 
Informed Consent1 
X 
Review/Confirm Eligibility Criteria 
X 
X 
X18 
Demographics 
X 
Medical History2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications Review3 
X 
X 
X 
X 
X 
X 
X 
X 
X3 
X3 
X3 
X3 
X3 
X3 
Complete Physical Exam (including 
height and weight)4 
X 
Targeted Physical Exam5 
X5 
X5 
X5 
X5 
X5 
X5 
X5 
X5 
X5 
Vital Signs6 
X 
X6 
X 
X6 
X 
X 
X 
X5 
X5 
Hematology/Chemistries7 
X 
X 
X18 
X18 
X5 
X5 
HIV, HCV, HbsAg, rabies 
neutralization 
X 
Serum Pregnancy Test8 
X 
Urine Pregnancy Test9 
X 
X18 
Audiometry Test10 
X 
X 
X 
X 
X 
X 
X 
Immunology Blood 
X11 
X 
X11,18 
X 
X 
X 
X 
X5 
X5 
Study Vaccination 
X 
X18 
Vaccination Site Checks 
X 
X 
X18 
X18 
Dispense 7-day Diary Card e-12 
X 
X18 
Review 7-day Diary Card  
X 
X 
X 
X18 
X13 
X13 
Solicited Adverse Events14 
X 
X 
X 
X 
 
X13 
X13 
Unsolicited Adverse Events15 
X 
X 
X 
X 
X 
X 
X 
X 
X13 
X13 
SAEs, MAAEs, NOCMCs, 
PIMMCs, and the AESI16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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1. Prior to any study related procedures, participants will be provided information about the study and informed consent will be obtained from the 
participant. 
2. Eligibility and medical history will be updated on the day of enrollment, before administration of study product. 
3. Medications taken by the participant in the 60 days before enrollment will be recorded. At subsequent visits, updates to previous concomitant 
medications and additional medications taken in the interim will be recorded until Day 61 after which concomitant medications will only be recorded if 
used to treat an MAAE. 
4. Physical examination will occur for all participants at Screening and will include general appearance and the following organs, organ systems and/or 
body areas: abdomen, heart, extremities, head, eyes, ears (including otoscopy), nose, and throat, lymph nodes, neurological, lungs, chest and skin. 
5. Performed at investigator discretion. 
6. Vital signs include pulse, systolic blood pressure, diastolic blood pressure, and oral temperature. On vaccination days, vital signs are performed prior to 
vaccination and at 30 minutes post vaccination. Vital signs meeting Grade 1 severity criteria (Appendix 5) and not clinically significant may be eligible 
as determined by the investigator. 
7. Laboratory tests will include ALT, total bilirubin, creatinine, total WBC count, hemoglobin, and platelet count. For enrollment, values must be within 
normal limits or Grade 1 (Appendix 3) and not clinically significant as determined by the Investigator. Laboratory AEs are defined as abnormal safety 
labs collected from the time of vaccination through Day 61. 
8. Serum Beta hCG for participants of childbearing potential. 
9. Urine pregnancy test will be performed for all participants of childbearing potential within the 24 hours prior to study product administration. Result 
must be negative before study product can be administered. 
10. Audiometry is scheduled to be performed four times: during the screening visit, prior to the second vaccination on Day 22, on Day 61, and on Day 394. 
Evidence of sensorineural hearing loss (SNHL) as assessed by quantitative audiometry at screening would exclude participation, and evidence of new 
onset SNHL before Day 29 would exclude receipt of the second vaccine dose. Evidence of new-onset SNHL after receipt of the first vaccination would 
be evaluated as a potential adverse event of special interest (AESI). The baseline exam may occur at any time from informed consent to immediately 
before first vaccine dose. Additional exams can be performed at the investigator’s discretion. 
11. Sample collection will occur prior to vaccination on Days 1 and 29. Left-over and additional blood specimens will also be retained and collected for 
future use (Appendix 2). 
12. Participants will be trained on the use of the paper 7-day Diary Card. They will also be provided with a thermometer for daily temperature checks and a 
ruler to measure certain local reactogenicity events 
13. If within relevant allowable time windows. 
14. Solicited AEs will first be collected 30 minutes after administration of vaccine (immediate reactogenicity). Additional solicited AEs will be collected by 
the paper 7-day Diary Card for 7 days after each study vaccination. 
15. Non-serious unsolicited AEs will be collected and recorded from Day 1 after administration of vaccine for all participants through Day 61. 
16. SAEs, MAAEs, NOCMCs, PIMMCs, and the AESI, will be collected from Day 1, following vaccination, through the end of the study (Day 394). 
17. Unscheduled Visits and Early Termination Visits may be conducted by phone or IRB-approved telehealth means if in-person visits are not feasible. 
18. Not to be completed for those who did not receive Vaccination #2 but remain in the study for follow-up. 
 
 

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1.3 
Study Schema 
 
 
 
 

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2. INTRODUCTION 
2.1 
Study Rationale 
Lassa fever is a high mortality infectious disease that disproportionately affects low-income 
countries in West Africa.1 There are currently no approved vaccines for Lassa fever in clinical 
use. The World Health Organization (WHO) has identified vaccines against Lassa fever as an 
unmet public health need.7 This vaccine is proposed for disease prevention in Lassa fever 
endemic areas, where transmission is driven primarily by contact with infected rodent urine or 
feces. Additionally, it is proposed for use during Lassa fever outbreaks, in the mitigation of 
disease spread, including via person-to-person contact or nosocomial spread. 
2.2 
Background 
2.2.1 
Purpose of Study 
Lassa fever is a zoonotic infection endemic in West Africa and is spread by the Lassa virus, an 
arenavirus causing hemorrhagic fever. Over 300,000 Lassa fever infections occur annually and 
while disease is often mild, in a subset of individuals disease is characterized by severe anemia 
and bleeding, encephalopathy, respiratory failure, and shock, and with high mortality. In some 
regions of West Africa, up to 15% of hospital admissions are secondary to Lassa fever, and an 
estimated 5,000 deaths occur annually. During epidemics of disease, case-fatality rates may 
reach as high as 50% in hospitalized patients. Approximately one-third of infected individuals 
will develop hearing loss regardless of disease severity, and in a proportion of patients, 
permanent deafness occurs. 
Prevention of illness through vaccination is a critical goal in reducing the burden of disease from 
Lassa fever. While the antiviral ribavirin has shown some benefit in treatment, it is difficult to 
access in the regions where Lassa fever is endemic, and it must be started early in the disease 
course to be effective. There are currently no vaccines in clinical use for the prevention of Lassa 
fever. 
This study proposes the evaluation of a novel, first-in-human Lassa fever vaccine based on the 
complete Lassa glycoprotein complex (GPC) antigen. The antigen (LASSARAB) will be 
presented on a genetically modified and attenuated rabies vector expressing both the rabies 
glycoprotein (GP) antigen and the Lassa GPC. The inactivated chimeric virus is delivered with a 
TLR-4-activating oil-in-water emulsion adjuvant (aPHAD-SE). Studies using this vaccine (called 
LASSARAB+aPHAD-SE) administered as a prime-boost series in mice and non-human 
primates, and then challenged with Lassa virus demonstrated significant protection against Lassa 
fever.4,6,8-10 Given that the vaccine backbone is an attenuated and inactivated rabies virus 
expressing rabies GP, this vaccine will also be evaluated for immunogenicity against rabies 
virus. 

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2.3 
Risk/Benefit Assessment 
2.3.1 
Known Potential Risks 
LASSARAB +aPHAD-SE 
This is the first study in humans of the investigational vaccine, LASSARAB +aPHAD-SE, and 
therefore risks are unknown. No clinical studies have been conducted. 
Risks of study antigen (LASSARAB): Inactivated rabies virus has been used to vaccinate 
humans since 1978, and thus has a significant established history of manufacturing, safety, and 
efficacy.4-6,8,10 The RABV-vectored vaccine used in this trial is inactivated and therefore its 
safety profile is anticipated to be similar. Local and systematic reactions from vaccination with 
rabies vaccine are common, generally mild, and self-limited. 
Risks of study adjuvant (aPHAD-SE): The adjuvant SE is in vaccines in clinical use.11-22 MPLA 
is in vaccines in clinical use.11-22 Both agents are considered safe in vaccines. aPHAD is a variant 
of MPLA. 
Risks of LASSARAB+aPHAD-SE on Pregnant Women: The possible effects of LASSARAB on 
a fetus or nursing infant are unknown. 
Theoretical risk of sensorineural hearing loss (SNHL): SNHL has been identified in 
approximately 25% of people recovered from Lassa fever.23 While SNHL has not been identified 
in clinical trials of Lassa virus vaccine candidates10, there is a theoretical risk with 
LASSARAB+aPHAD-SE. Participants will undergo screening audiometry to exclude persons 
with clinically significant, pre-existing SNHL, and they will undergo after the first vaccine dose, 
after the second vaccine dose, and upon completion of the study to assess any changes from 
baseline. Further, audiometry can be performed for any participant by trained study staff in the 
event of concerns of changes in hearing. In the event of abnormal audiometry post-vaccination, 
participants will be referred for clinical evaluation and their medical records will be collected 
and reviewed. New onset SNHL is an adverse event of special interest (AESI) in this study. 
HDCV 
HDCV risks include local reactions (e.g., pain at the injection site, redness, swelling, induration), 
reported among the majority of recipients. Most local reactions were mild and resolved 
spontaneously within a few days.24 Mild systemic reactions (e.g., fever, headache, dizziness, 
gastrointestinal symptoms) were reported in 6.8-55.6% of recipients.24 
Immediate systemic hypersensitivity reactions are possible but are less likely during the primary 
vaccination series compared to booster vaccination.24 Systemic allergic reactions have been 
associated with the presence of betapropiolactone-altered human albumin in HDCV and the 
development of antibodies to this allergen.24 No deaths resulting from these reactions have been 
reported. 

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HDCV is contraindicated for anyone with a known life-threatening systemic hypersensitivity 
reaction to any component of the vaccine when used for preexposure prophylaxis.24 Participants 
with a prior history of severe allergic reaction to any rabies vaccine or to any component of 
HDCV will be excluded from study enrollment. Should a severe allergic reaction occur 
immediately following vaccination, medications to treat such a reaction will be immediately 
available for administration according to standard guidelines at the study site. 
The risk HDCV during pregnancy is not thought to outweigh the benefits in the setting of rabies 
exposure or high risk preexposure prophylaxis, but the risk-benefit balance of HDCV in the 
setting of pregnancy and low rabies risk is uncertain.24 Several studies have shown no indication 
of increased incidence of abortion, premature births, or fetal abnormalities associated with rabies 
vaccination.24 
General Vaccine Risks 
Participants will be counseled on possible side effects following vaccination and followed 
closely in the immediate post-vaccination period and during the following week for assessment of 
moderate to severe local or systemic reactogenicity. 
Some people get severe pain in the shoulder and have difficulty moving their arm after a 
vaccination has been given. This happens very rarely and can be prevented by assuring that the 
IM injection is done in the appropriate area of the deltoid muscle. 
Syncope (fainting) can occur in association with administration of injectable vaccines. In the 
immediate post-vaccination period, all participants will be monitored in a sitting or lying position 
for 30 minutes following vaccination to help prevent fainting and injuries caused by a fall. 
Blood Drawing 
Drawing blood may cause transient discomfort and fainting. Fainting is usually managed by 
having the participant lie down. Bruising at the blood draw site may occur but can be prevented 
or lessened by applying pressure to the draw site for several minutes. Drawing blood may also 
cause infection. The use of aseptic techniques will reduce this risk. Risks for blood drawn may 
include anemia. 
Risk of loss of privacy or confidentiality 
Participants will be asked to provide, in a private setting, Personally Identifying Information 
(PII) and Protected Health Information (PHI). All attempts will be made to keep PII and PHI 
confidential within the limits of the law. However, there is a chance that unauthorized persons 
will gain access to a participant’s PII or PHI. All hard copy research records will be kept in a 
locked file cabinet or maintained in a locked room at the participating Vaccine Treatment and 
Evaluation Unit (VTEU) site. Electronic files and access to the central clinical and laboratory 
websites at which study-related data are stored will be password protected. Only people who are 
involved in the conduct, oversight, monitoring, or auditing of this study will be allowed access to 

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the confidential information that is collected. Any publications from this study will not use 
information that will identify participants by name. Organizations that may inspect and/or copy 
research records for quality assurance and data analysis include groups such as National Institute 
of Allergy and Infectious Diseases (NIAID) and the Food and Drug Administration (FDA) and 
their contractors. They also include the Human Research Protections Office (HRPO) at the 
University of Maryland, Baltimore (UMB) and its IRB, and the Office of Accountability and 
Compliance (OAC) at UMB. 
Unknown risks 
There may be unknown risks, discomforts, or side effects. 
2.3.2 
Known Potential Benefits 
Participation in this study provides no known direct benefit to the individual participants. 
Participants will be advised as part of the informed consent process that receipt of the 
comparator vaccine, HDCV, according to the study schedule is not sufficient to be considered to 
be protective against rabies virus or to have completed the pre-exposure prophylaxis (PrEP) 
vaccination series. 
2.3.3 
Assessment of Potential Risks and Benefits 
This study may not benefit participants directly. As this is a first-in-human trial, it is unknown 
whether the study product, LASSARAB +aPHAD-SE, will help to protect participants from 
Lassa fever or rabies, or, if it does, how long that protection may last. 
The immunogenicity comparator HDCV given at two doses is insufficient to prevent rabies virus 
infection. 
Study risk is minimized by using a dose escalation procedure, as well as a sentinel subgroup 
approach within each dose group. Group safety reviews occur between sentinel and expanded 
subgroups. 
While individual participants may not benefit from involvement in this study, their participation 
is crucial to the larger societal benefit of improved medical interventions. By participating in this 
study, participants are enabling the development of a potential advancement to address whether 
LASSARAB +aPHAD-SE may provide protection against Lassa fever. 
3. OBJECTIVES AND ENDPOINTS 
Refer to Section 1.1 for Study Objectives and Endpoints. 
4. STUDY DESIGN 
4.1 
Overall Design 

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This is a phase 1, randomized, controlled, recipient- and observer-blinded, dose-escalation 
clinical trial to evaluate the safety, tolerability, and immunogenicity of LASSARAB+aPHAD-SE 
vaccine candidate compared to a licensed rabies virus vaccine control (HDCV), each 
administered as two intramuscular (IM) doses on Days 1 and 29 in adult participants aged 18 
through 50 years. The trial will enroll up to 55 healthy participants. The study treatment groups 
are summarized in Table 1. If all 55 participants are enrolled and vaccinated, the randomization 
will be 3:3:3:2 of LASSARAB 700rU dose, LASSARAB 1400rU dose, LASSARAB 2800rU 
dose (2 injections of 1400rU), and HDCV comparator. 
Participants will be recruited from the greater Washington/Baltimore Metropolitan Area. The 
trial will be conducted by a single center, the Center for Vaccine Development and Global 
Health (CVD) at the University of Maryland, Baltimore (UMB). Participants will be screened to 
determine eligibility for enrollment. Screening will include evaluations for general health, factors 
that may increase the risk to participants in the trial, and factors that could confound 
interpretation or execution of the study. Eligible participants will be enrolled and randomized to 
treatment group using block randomization for each cohort generated by the unblinded study 
statistician. Participants will then be vaccinated in a dose escalating process as shown in Table 2. 
The investigators, study staff (excluding vaccine administrators), and study participants will be 
blinded to the treatment each participant receives. Adverse events (AEs) will be assessed by 
blinded study clinicians for severity using relevant DMID toxicity tables and for the relationship 
of the event to the study product treatment. 
For this trial, a conservative dose escalation design is used in which each treatment group of 15 
vaccine recipients is split into two subgroups. The first subgroup, termed the “sentinel 
subgroup,” includes 4 vaccine recipients. The second subgroup, termed the “expanded 
subgroup,” includes the remaining 11 vaccine recipients. In each of the three initial treatment 
groups (Group A, Group B, and Group C), enrollment is paused for 7 days after vaccination of 
the sentinel subgroup for safety review. 
Study participants will be divided into four vaccination cohorts.  
• In Cohort 1, there will be 4 LASSARAB 700rU dose recipients (Group A sentinel 
subgroup) and 1 HDCV control recipient. If no Sentinel Subgroup Halting Criteria are 
met after 7 days of safety monitoring, an Independent Safety Monitor (ISM) will 
recommend proceeding to vaccinate Cohort 2. 
• In Cohort 2, there will be 4 LASSARAB 1400rU dose recipients (Group B sentinel 
subgroup), 3 HDCV control recipients, and 11 LASSARAB 700rU dose recipients 
(Group A expanded subgroup). If no Sentinel Subgroup Halting Criteria are met after 7 
days of safety monitoring, the ISM will recommend proceeding to vaccinate Cohort 3. 
• In Cohort 3, there will be 4 recipients of two simultaneous injections of LASSARAB 
1400rU dose product (Group C sentinel subgroup), 3 HDCV control recipients, and 11 
single-injection LASSARAB 1400rU dose recipients (Group B expanded subgroup). If 

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no Sentinel Subgroup Halting Criteria are met after 7 days of safety monitoring, the ISM 
will recommend proceeding to vaccinate Cohort 4. 
• In Cohort 4, there will be 3 HDCV control recipients, and 11 recipients of two 
simultaneous injections of LASSARAB 1400rU dose product (Group C expanded 
subgroup). 
There will be no further planned ISM safety reviews for dose escalation after Cohort 4, although 
study investigators will continue to monitor for safety and apply relevant Individual Halting 
Criteria and General Study Halting Criteria and safety procedures when applicable. To maintain 
blinding of participants in Cohort 3 and 4, one dose of normal saline placebo will be 
administered simultaneously in the contralateral arm in some participants receiving HDCV 
control (See Table 2 for details). 
Participants will be monitored for one year following the second study vaccination (through Day 
394). Paper Diary Cards will be used to collect solicited and unsolicited AE information 
covering the 7-day period following each study vaccination. Safety laboratory analyses will be 
performed on Day 8 and Day 36 (7 days following each study treatment), as well as on Day 61. 
Blood samples will be obtained for immunological assays at Days 1, 8, 29, 36, 61, 121 and 394. 
Left-over and additional blood specimens will also be retained and collected for future use. 
Unsolicited adverse events will be collected through Day 61 (32 days after the last study 
treatment). Only a subset of AEs will be collected beyond Day 61; these are serious adverse 
events (SAEs), medically-attended adverse events (MAAEs), new-onset chronic medical 
conditions (NOCMCs), potential immune-mediated medical conditions (PIMMCs), and an 
adverse event of special interest (AESI) – new onset sensorineural hearing loss (SNHL). SNHL 
will be assessed by audiometry at screening, after the first vaccine dose at Day 22, after the 
second vaccine dose at Day 61, upon completion of the study at Day 394, and at any time if the 
participant reports change in hearing or at the discretion of the Principal Investigator (PI). SAEs, 
MAAEs, NOCMCs, PIMMCs, and the AESI will be collected through Day 394 (the end of the 
study, approximately one year after the second study vaccination). See Section 7.1.5 for SNHL 
definitions and evaluation procedures and see Appendix 7 for the list of specific PIMMCs to be 
reported. 
An interim analysis of the Primary and Secondary Endpoints will be performed with all data and 
samples collected through Day 61. These analyses will be summarized in tables by vaccine 
group and reported in an interim clinical study report (CSR). Data and studies from blood 
samples collected after Day 61 will be reported in separate CSRs. Assessed exploratory 
endpoints and data line listings will also be included in the final CSR. 
4.2 
Scientific Rationale for Study Design 
For this Phase 1 first-in-human trial, a conservative dose escalation design will be used in which 
each treatment group of 15 vaccine recipients is split into two subgroups. The first subgroup, 

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termed the “sentinel subgroup,” includes 4 vaccine recipients. The second subgroup, termed the 
“expanded subgroup,” includes the remaining 11 vaccine recipients. In each of the three initial 
treatment groups (Group A, Group B, and Group C), enrollment is paused for 7 days after 
vaccination of the sentinel subgroup for safety review. This allows the opportunity to identify 
early vaccine-related AEs in this subgroup prior to exposing additional participants, a design that 
decreases the risk of multiple serious vaccine-related AEs compared to sequential vaccination of 
the entire dose group without halting. Vaccination will occur in cohorts including participants in 
other study treatment groups (HDCV control or dose groups that have already successfully 
completed sentinel safety reviews) to ensure vaccine assignment blinding by observers and 
participants. Unblinding can be done by the ISM to investigate any potential treatment-related 
AEs in the sentinel subgroups. The HDCV control group allows for comparisons between the 
LASSARAB+aPHAD-SE with a licensed rabies vaccine. Each is expected to elicit immune 
responses to rabies antigen, but only the LASSARAB+aPHAD-SE is expected to elicit immune 
responses to Lassa virus. The safety and tolerability profile for HDCV is well established. 
4.3 
Justification for Dose 
The doses of LASSARAB+aPHAD-SE used in this Phase I clinical study are selected based on 
pre-clinical data. A vaccine candidate using 1400rU LASSARAB administered with TLR4 
activating adjuvant, in SE, was given to nonhuman primates (NHPs) by IM injection at Days 1 
and 29 and was found to be immunogenic and to generate high and persistent titers of antibodies 
against Lassa GPC.4 No severe adverse events were observed in the NHPs monitored daily after 
immunization through one year post-immunization.4 The same dose of vaccine candidate was 
found to highly suppress viremia on Lassa virus challenge in NHPs and to protect NHPs from 
death upon challenge. Thus, this trial will begin with ½ of the NHP dose (700rU antigen in 1 mL 
volume) and escalate as described to a 1400rU dose in 1 mL volume, and subsequently, if all 
safety criteria are met, to the highest dose of 2800rU, administered as two 1 mL injections of 
1400rU each (Table 1). Each 1 mL volume will contain 5ug/mL aPHAD-SE. 
5. STUDY POPULATION 
This study will enroll healthy adult participants from the general population who meet eligibility 
criteria. Subject Inclusion and Exclusion Criteria must be confirmed by a study clinician licensed 
to make medical diagnoses. No exemptions are granted on participant Inclusion/Exclusion 
Criteria. 
5.1 
Inclusion Criteria 
Refer to Section 1.1 for Study Inclusion Criteria. 
5.2 
Exclusion Criteria 
Refer to Section 1.1 for Study Exclusion Criteria. 

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5.2.1 
Exclusion of Specific Populations 
This is a first-in-human study, to be conducted in a healthy adult population. There is no prior 
clinical experience with LASSARAB+aPHAD-SE. We are excluding adults older than 50 years, 
children and adolescents under 18 years of age, as well as persons who are pregnant, planning to 
become pregnant through Day 62, or who are breast-feeding. 
5.3 
Inclusion of Vulnerable Participants 
Not Applicable 
5.4 
Lifestyle Considerations 
During this study, participants are asked to: 
• Participants of childbearing potential in a heterosexual relationship must agree to use of 
highly effective contraception beginning at the time of the screening visit through Day 61 
• Refrain from donating blood through Day 61 
• Refrain from enrolling in any other study with blood draws or any experimental agent or 
other intervention through the end of the study. 
• Refrain from receiving any other vaccine through Day 61 
• Refrain from receiving any live vaccine through Day 61 
• Refrain from participating in another clinical trial or plan to enroll in another clinical trial 
during the study period. 
• Must agree to inform the investigators if there are any potential rabies exposures or 
change in rabies risk for counseling about potential withdrawal from the trial for licensed 
rabies vaccination. 
5.5 
Screen Failures 
Following consent and screening evaluations, the investigator or designee will review the 
inclusion/exclusion criteria and determine the participant’s eligibility for the study and 
administration of the study product. 
Participants who are found to be ineligible will be told the reason for ineligibility. Participants 
who are ineligible and not administered the study product will be replaced. Participants who 
withdraw, who are withdrawn from this study, or who are lost to follow-up after signing the ICF 
but before administration of the study product may be replaced. 
Only the following information will be collected on screen failures: demographics (age, screen 
number, sex, ethnicity, and race) and reason for ineligibility. 
For individuals who do not meet the criteria for participation in this study (screen failure) 
because of a laboratory value that is outside the range of eligibility, but the laboratory value is 
thought to be due to an acute condition or due to laboratory error, the abnormal laboratory 

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assessment may be repeated once. Similarly, for vital signs that fall outside of the range of 
eligibility, but the vital sign is thought be due to an acute condition or measurement error, the 
vital sign may be repeated once. 
5.6 
Strategies for Recruitment and Retention 
5.6.1 
Recruitment 
Potential participants will learn about the study via IRB-approved recruitment strategies, 
including direct mailing, recruitment from an IRB-approved trial registry, internet 
advertisements, and local advertisements/flyers. Recruiting may begin with a brief IRB-approved 
telephone call between study staff and the potential participant. Information about the study will 
be presented to potential participants, and questions about their health and ability to comply with 
the study visit schedule will be asked of potential participants to presumptively determine 
eligibility. Information about the participant may be recorded from interviews or medical 
records. Appointments will be made for potential participants for further screening procedures. 
5.6.2 
Retention 
Study retention strategies will include education and explanation of the study schedule and 
procedures during screening and enrollment visits and restriction of enrollment to persons who 
can attend all study visits. Participants will be reminded of subsequent visits during each visit, 
and study staff will contact participants prior to appointments. Study staff will contact 
participants who miss appointments to encourage them to return for completion of safety 
evaluations. 
5.6.3 
Compensation Plan for Participants 
Participants may be compensated for their participation in this trial. Compensation will be in 
accordance with local IRB requirements, and subject to IRB approval. Reimbursements will be 
disbursed at specific timepoints during the study with the amount contingent on completing 
study procedures. 
5.6.4 
Costs 
There is no cost to participants for the research tests, procedures, and study product while taking 
part in this trial. Procedures and treatment for clinical care may be billed to the participant, 
participant’s insurance or third party. 
6. STUDY PRODUCT 
6.1 
Study Product(s) and Administration 
6.1.1 
Study Product Description 
Product 1: LASSARAB+aPHAD-SE 

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The product is a Rabies-Vectored Monovalent Lassa Fever Vaccine (LASSARAB) with 3D-(6- 
acyl) Phosphorylated Hexaacyl Disaccharides (PHAD)-Stable squalene oil-in-water 
nanoemulsion (aPHAD-SE) adjuvant administered by IM injection. The LASSARAB vaccine 
consists of a chemically inactivated and genetically modified rabies virus (RABV) vector, 
expressing both the rabies glycoprotein (GP) antigen and the full Lassa glycoprotein complex 
(GPC) antigen. The parental RABV vaccine vector, BNSP, is a recombinant derivative of the 
SAD B19 RABV vaccine strain, which has been used as a live oral vaccine for wildlife in 
Europe. LASSARAB contains an Arg to Glu change at amino acid 333 of RABV G, which 
reduces viral neurotropism. Once the sequence is translated into a viral particle, it is then 
chemically inactivated with beta-propiolactone. The inactivated vaccine is delivered with a TLR- 
4-activating stable squalene oil-in-water nanoemulsion adjuvant, aPHAD-SE. The aPHAD 
adjuvant is a fully synthetic form of monophosphoryl lipid A (MPLA), specifically 3D-(6-acyl) 
PHAD®. SE is a stabilized nanoemulsion of squalene and water. The LASSARAB vaccine is 
administered in combination with the aPHAD-SE adjuvant formulation in a two-dose series. The 
LASSARAB vaccine is liquid and will be mixed with the aPHAD-SE formulation to produce 
one dose (1 mL) in the research pharmacy prior to administration. 
In this trial, LASSARAB+aPHAD-SE will be administered in three different treatment dose 
groups: LASSARAB 700rU dose (Group A), LASSARAB 1400rU dose (Group B), or two 
simultaneous injections of LASSARAB 1400rU dose (for total LASSARAB dose of 2800rU ) 
(Group C). The Group A and Group B vaccines will be delivered in a single IM injection of 1 mL 
vaccine product. The Group C vaccines will be delivered in two separate IM injections of the 
LASSARAB 1400rU dose formulation, each with a volume of 1 mL vaccine product. 
Product 2: HDCV Comparator 
HDCV (marketed as “Imovax®” and produced by Sanofi Pasteur SA) is a sterile, stable, freeze- 
dried suspension of rabies virus prepared from strain PM-1503-3M obtained from the Wistar 
Institute, Philadelphia, PA. The virus is harvested from infected human diploid cells, MRC-5 
strain, concentrated by ultrafiltration and is inactivated by beta-propiolactone. The finished, 
freeze-dried vaccine is provided in a single dose vial containing no preservative. The potency of 
one dose (1 mL) of Imovax Rabies vaccine is equal to or greater than 2.5 international units of 
rabies antigen. Imovax Rabies is a vaccine indicated for pre-exposure and post-exposure 
prophylaxis against rabies. In the United States, the Advisory Committee on Immunization 
Practices (ACIP) recommends three IM injections of 1 mL each, one injection on Day 1, one on 
Day 8, and one either on Day 22 or 29. Imovax Rabies vaccine is approved for use in all age 
groups. 
Product 3: Normal Saline Placebo 
Sterile 0.9% sodium chloride for injection, USP, or normal saline, will be administered in IM 
injections simultaneously with HDCV in cohorts that contain Treatment Group C, Cohorts 3 and 
4. The use of normal saline control allows maintenance of treatment assignment blinding in these 

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cohorts, given that Group C requires two IM doses given simultaneously. 
6.1.2 
Dosing and Administration 
 
Treatment 
Group 
Product Name Antigen Dose 
Adjuvant Dose 
Route 
Frequency of 
Administration 
Duration 
of Therapy 
A 
LASSARAB+ 
aPHAD-SE 
700rU 
5µg 
IM 
D1, D29 
N/A 
B 
LASSARAB+ 
aPHAD-SE 
1400rU 
5µg 
IM 
D1, D29 
N/A 
C 
LASSARAB+ 
aPHAD-SE 
1400rU per 
injection 
(2 injections) 
5µg per injection 
(2 injections) 
IM 
D1, D29 
N/A 
D 
HDCV 
≥2.5 IU 
rabies antigen 
N/A 
IM 
D1, D29 
N/A 
Note: Treatment Group C will receive two simultaneous injections of the LASSARAB 1400rU dose vaccine. 
Therefore, each participant in treatment Group C will receive a total 2800rU LASSARAB and 10µg aPHAD-SE. 
Some Group D participants will receive an injection of normal saline placebo simultaneous to HDCV to maintain 
blinding of Group C. 
6.1.3 
Dose Escalation 
For this Phase 1 first-in-human trial, a conservative dose escalation design will be used. 
LASSARAB+aPHAD-SE will be evaluated in three different treatment dose groups, Group A, 
Group B, and Group C in a stepwise dose escalation process. Details of the dose escalation are in 
Table 2, Sections 1.1, and Section 4.1. 
6.1.4 
Dose Modifications 
Not applicable 
6.2 
Preparation/Handling/Storage/Accountability 
6.2.1 
Acquisition and Accountability 
• Product 1: 
o Component 1: LASSARAB (IDT Biologika GmbH) 
o Component 2: aPHAD-SE (Curia) 
o Component 3: Normal Saline buffer (Fisher) 
• Product 2: HDCV (Fisher) 
• Product 3: Normal Saline (Fisher) 
Product 1 Component 1 (LASSARAB) will be distributed by IDT Biologika GmbH. Product 1 
Component 2 (aPHAD-SE) will be distributed by Curia. Product 1 Component 3, Product 2, and 
Product 3 will be procured by the University of Maryland, Baltimore from Fisher BioServices. 
Records will be maintained that document receipt, release for dosing, disposal, or return to the 

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IND sponsor. 
Additional procurement of specific products will be done by University of Maryland, Baltimore. 
This includes but may not be limited to, mixing vials, syringes, needles and shipping supplies for 
this study. 
Accountability: After receipt of the study products, the PI is responsible for study product 
distribution and disposition and has ultimate responsibility for study product accountability. The 
PI may delegate to the research pharmacist responsibility for study product accountability. The 
research pharmacist will be responsible for maintaining complete records and documentation of 
study product receipt, accountability, preparation/dilution, dispensation, storage conditions, and 
final disposition of the study product(s). All study product(s), whether administered or not, must 
be documented on the appropriate study product accountability record or dispensing log. The 
IND sponsor’s monitoring staff will verify the participating site’s study product accountability 
records and dispensing logs per the site monitoring plan. Refer to the protocol-specific Manual 
of Procedures (MOP) for details on storing study products. 
Unused study products will be retained until study conclusion or until accountability via 
verification of inventory or monitoring has occurred and written notification stating retention is 
no longer required is received from the IND sponsor, as applicable per the site’s Standard 
Operating Procedures (SOPs). 
6.2.2 
Formulation, Appearance, Packaging, and Labeling 
Manufacturing and packaging of the formulation ingredients will be performed for the study by 
the UMMC Investigational Drug Pharmacy (heretofore referred to as the “research pharmacy”) 
and will be documented in conformity with Good Manufacturing Practice (GMP) per 
instructions. The study products will be labeled according to manufacturer or regulatory 
specifications and include the statement “Caution: New Drug – Limited by Federal (or United 
States) law to investigational use.” 
Product 1: LASSARAB+aPHAD-SE (Active Product) 
LASSARAB+aPHAD-SE is formulated with LASSARAB at a concentration of 6990 rel. U/mL 
and aPHAD-SE at a concentration of 25µg/mL in a sterile normal saline diluent to produce a 
final dose volume of 1 mL. One dose of LASSARAB+aPHAD-SE will be formulated with 
700rU or 1400rU of LASSARAB antigen and 5µg of aPHAD-SE. Treatment Group C will 
receive two simultaneous vaccinations of the LASSARAB 1400rU dose product in bilateral arms 
(for a total LASSARAB dose of 2800rU). Single dose vials will be produced by the research 
pharmacy and stored at room temperature for use within 4 hours. The drug product will be 
supplied in 1 mL syringes for administration. The final prepared drug product is a colorless, 
slightly cloudy suspension with presence of white particles. Table 3 has specifics of the 
formulation for the three dose levels. 

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Product 2: HDCV Comparator 
The study will use licensed HDCV as a comparator product. HDCV is sold as Imovax Rabies 
Vaccine. The licensed HDCV vaccine is supplied as single-use vials and will be procured 
through commercial sources with storage and administration in accordance with the 
manufacturer’s recommendations. The product is pink to red color after reconstitution. 
Product 3: Normal Saline 
Sterile 0.9% sodium chloride for injection, USP, or normal saline, is a sterile, nonpyrogenic, 
isotonic solution; each mL contains sodium chloride 9 mg. It contains no bacteriostatic agent, 
antimicrobial agent, preservatives, or added buffer and is supplied only in single-dose containers. 
The solution may contain hydrochloric acid and/or sodium hydroxide for pH adjustment (pH 5.3, 
range 4.5-7.0). Normal saline will be supplied as single-use vials. The product is clear. 
Table 3. Formulations of LASSARAB +aPHAD-SE by Treatment Group 
Treatment 
Group 
Product 
Antigen Dose Adjuvant Dose Volume 
Route 
Frequency of 
Administration 
Therapy 
Duration 
A 
LASSARAB+ 
aPHAD-SE 
700rU 
5µg 
1 mL 
IM 
D1, D29 
N/A 
B 
LASSARAB+ 
aPHAD-SE 
1400rU 
5µg 
1 mL 
IM 
D1, D29 
N/A 
C 
LASSARAB+ 
aPHAD-SE 
1400rU per 
injection 
(2 injections) 
5µg per 
injection 
(2 injections) 
1 mL 
(2 injections) 
IM 
D1, D29 
N/A 
Note: Treatment Group C will receive two simultaneous injections of the LASSARAB 1400rU dose vaccine 
Therefore, each participant in treatment Group C will receive a total 2800rU LASSARAB and 10µg aPHAD-SE. 
Some Group D participants will receive an injection of normal saline placebo simultaneous to HDCV to maintain 
blinding of Group C. 
6.2.3 
Product Storage and Stability 
Product 1: LASSARAB+aPHAD-SE (Active Product) 
LASSARAB and aPHAD-SE drug product in storage vials will be characterized for stability 
prior to IND submission to FDA. LASSARAB vials will be stored at ≤-65°C while aPHAD-SE 
vials will be stored 2-8°C. Products will be thawed at ambient temperature prior to mixing – 
LASSARAB for 30 minutes and aPHAD-SE for 15 minutes. Upon mixing, the drug product will 
be kept at room temperature for up to four hours before use. 
Product 2: Licensed HDCV (Comparator) 
The freeze-dried, commercial presentation of HDCV is stable if stored in the refrigerator between 
2°C and 8°C. Upon reconstitution, if should be administered promptly. 
6.2.4 
Preparation 
Product 1: LASSARAB+aPHAD-SE 

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Preparation of LASSARAB+aPHAD-SE will be performed by the research pharmacy and will be 
documented in conformity with Good Manufacturing Practice (GMP) per instructions provided 
in the Study Manual of Procedures. 
The individual participant vaccines are prepared from bulk and stored in capped, glass vials at 
room temperature prior to administration within 4 hours. The vaccine will be prepared in two 
dose levels: LASSARAB 700rU dose, LASSARAB 1400rU dose, each adjuvanted with 5 µg 
aPHAD-SE in normal saline. A third dose level (LASSARAB 2800rU Dose) will be 
accomplished by administering two separate IM injections of the LASSARAB 1400rU Dose 
formulation, each with a volume of 1 mL vaccine product. The individual drug product 
components as shown in Table 3 will be used in the formulation of the LASSARAB+aPHAD-SE 
treatments. 
Product 2: Licensed HDCV 
The HDCV commercial presentation package contains a vial of freeze-dried vaccine, a syringe 
containing diluent, and a sterile reconstitution needle. Preparation of HDCV will be performed 
by the research pharmacy and will be documented in conformity with Good Manufacturing 
Practice (GMP) per instructions provided in the Study Manual of Procedures. The individual 
participant vaccines will be reconstituted following instructions in the product package insert in 
the study vaccination clinic immediately prior to administration. Measures to Minimize Bias: 
Randomization and Blinding 
6.2.5 
Treatment Assignment Procedures 
Participants will be assigned to receive either one of three doses of LASSARAB+aPHAD-SE or 
HDCV comparator depending upon the cohort into which they enroll (Table 2). Some Cohort 3 
and 4 participants will receive an injection of normal saline placebo simultaneous to HDCV to 
maintain blinding of Treatment Group C. Study product will be administered within four hours 
of its preparation. 
6.2.6 
Randomization and Blinding 
Upon verification of study eligibility at the Day 1 visit, participants will be randomized 
according to Table 2. Because this is a dose escalation trial, our study has four stages with one 
cohort receiving vaccines at each stage. Up to 55 participants will be randomized to one of the 
four treatment groups at an assignment ratio depending on the escalation stage. If all participants 
proceed to vaccination, the final vaccine assignment ratio will be 3:3:3:2 of LASSARAB 700rU 
dose, LASSARAB 1400rU dose, LASSARAB 2800rU dose, and HDCV comparator. 
Participants will receive a study vaccination on Days 1 and 29. Randomization will be generated 
by the study statistician using block randomization for each cohort separately. All randomized 
trial subjects will be blinded to their treatment allocation. 
6.2.7 
Blinding and Masking Procedures 

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Trial personnel receiving, storing, dispensing, preparing, and administering the trial study 
product will be unblinded. All other trial personnel, including the investigator and investigator 
staff, will be blinded to trial treatment allocation. In particular, the individuals who evaluate 
participant safety and immunogenicity will be blinded. Because LASSARAB+aPHAD-SE or 
HDCV have different appearances, the trial treatment will be administered in a manner that 
maintains the blinding. For this study blinding tape will be applied to the syringe by unblinded 
study staff before product administration. The participants, the study personnel who perform 
study assessments after administration, data entry personnel at the sites, and laboratory personnel 
performing immunologic assays will be blinded to treatment assignment.  
The investigator will assign the responsibility of the unblinded dispensers/administrators to trial 
personnel who will not participate in the evaluation of any trial endpoint. To ensure adequate 
coverage, at least two unblinded dispensers/administrators will be assigned per trial site. Members 
of the trial site personnel or clinic pharmacy should fulfill these roles. The investigator and trial 
site personnel other than the unblinded dispensers/administrators must not be allowed to know the 
treatment allocation of any trial participant and must not be allowed to see the investigational 
product container contents. In the event of a Quality Assurance audit, the auditor(s) will be 
allowed access to unblinded trial treatment allocation records at the site(s) to verify that 
randomization/dispensing has been done accurately. 
The SRC will receive blinded data in aggregate by cohort. At scheduled timepoints after sentinel 
subgroup vaccinations, and if Individual Halting Criteria and General Study Halting Criteria are 
met at other times during the study, the SRC will refer safety review to the ISM who may choose 
to be unblinded to individual study treatment assignments, as needed, to adequately assess safety 
issues. 
6.3 
Unblinding 
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a trial subject’s treatment allocation is warranted. Trial 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 trial sponsor’s representative 
before unblinding a trial participant’s treatment allocation unless this could delay further 
management of the trial participant. If a participant’s treatment allocation is unblinded, 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). 
Decision on trial continuation of unblinded trial subjects will be made between investigator and 
sponsor’s representative on a case by case basis. 
6.4 
Study Intervention Compliance 
Vaccination of participants will be performed by a member of the clinical research team who is 
licensed to administer the study product, and the administration will be documented on the 

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Treatment Administration Record and entered into the electronic Case Report Form (eCRF). 
6.5 
Concomitant Therapy 
For this protocol, a prescription medication is defined as a medication that can be prescribed only 
by a properly authorized/licensed clinician. Medications to be reported in the electronic Case 
Report Form (eCRF) are concomitant prescription medications, over-the-counter medications 
and supplements. 
All concomitant medications taken within 60 days prior to signing the ICF will be reviewed with 
participants to determine stability of chronic diseases and eligibility and recorded on the data 
collection forms/source documentation. Concomitant medications will be reviewed at every 
study visit through the end of the study. 
Participants should not have current use of any medications that may be associated with impaired 
immune responsiveness (Exclusion Criterion 2). 
Participants should not have any allergy treatment with antigen injections within 60 days before 
first vaccination or that are planned through the end of the study (Exclusion Criterion 3). 
Participants of childbearing potential in a heterosexual relationship must agree to use highly 
effective contraception beginning at the time of the screening visit through Day 61 (Inclusion 
Criterion 6). 
Participants should not have immunoglobulins and/or any blood products within the 60 days 
before first vaccination or that are planned through the end of the study (Exclusion Criterion 4). 
Participants should not have received rabies vaccine or an antibody therapeutic product for 
treating rabies or a Lassa fever vaccine any time before the first planned study vaccination 
(Exclusion Criterion 9). 
Participants should not have received another experimental agent or other intervention within 60 
days before first vaccination or have plans to do so before the end of the study (Exclusion 
Criterion 10). 
Participants should not have received or have plans to receive any other vaccine in the 2 weeks 
prior to vaccination/enrollment through Day 61 (Exclusion Criterion 11). 
Participants should not have received or have plans to receive any live vaccine in the 4 weeks 
prior to signing ICF through Day 61 (Exclusion Criterion 12). 
6.5.1 
Rescue Medicine 
Not applicable 
7. STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 

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7.1 
Halting Criteria and Discontinuation of Study Intervention 
7.1.1 
Study Halting Criteria 
Sentinel Subgroup Halting Criteria, Individual Halting Criteria, and General Study Halting 
Criteria are in Appendix 1. The primary responsibility of the ISM is to monitor participant 
safety. The ISM will review safety data at scheduled timepoints after sentinel subgroup 
vaccinations. Should any of the Sentinel Subgroup Halting Criteria, Individual Halting Criteria, 
or General Study Halting Criteria be met, the study will be paused, and the ISM will evaluate the 
data and recommend appropriateness of further dosing. The ISM will have the option to unblind 
by treatment group as needed and will have as a resource an unblinded statistician to aid in 
analyses of data. See Section 10.1.6 for details of SRC and ISM responsibilities. 
7.1.2 
Individual Halting Criteria 
This study includes two doses of investigational product. Individual participant halting criteria 
that would preclude a second dose in the event of safety events associated with the first dose are 
included to ensure participant safety. These criteria are in Appendix 1.  
7.1.3 
Criteria for redosing 
Not applicable 
7.1.4 
Follow up for participants that discontinued study intervention 
Discontinuation from study vaccine receipt does not mean discontinuation from the study, and 
remaining study procedures should be completed as indicated by the study schedule of activities. 
If a clinically significant finding is identified (including, but not limited to changes from 
baseline) after enrollment, the investigator or qualified designee will determine if any change in 
participant management is needed. Any new clinically relevant finding will be reported as an 
AE. See Section 1.2 for data to be collected and follow-up evaluations. 
7.1.5 
Follow up for Participants with a Suspicion for Sensorineural Hearing Loss 
Participants will undergo scheduled evaluations for SNHL at screening as part of eligibility 
assessments, after the first vaccination on Day 22, after the second vaccination on Day 61, and 
upon completion of the trial on Day 394. Audiometry will also be performed if the participant 
reports change in hearing or any time at the investigator’s discretion. Evaluation of SNHL as an 
AESI will follow Brighton Collaboration guidance.23 The screening tablet audiometer used in the 
vaccine clinic will be compliant with Brighton guidelines. To follow up on abnormal in-clinic 
tests after enrollment, we will use formal diagnostic sound booth audiometry completed by a 
licensed audiologist and evaluation by an otologist for SNHL diagnosis. SNHL evaluation will 
be detailed in the MOP. 
The threshold for normal hearing is -10 to 15 dB in children and adults.23 Hearing loss is present 
when hearing acuity drops below 30 dB loss.23 The Brighton Collaboration states that the 

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definitive diagnosis of SNHL requires two components: 
• Hearing loss of at least 30 dB in three sequential frequencies in the standard pure tone 
audiogram, and 
• A physical examination to exclude conductive hearing loss.23 
During screening, we will exclude persons with a baseline a hearing level greater than 15 dB in 
three sequential frequencies by tablet audiometry if physical examination confirms conductive 
hearing loss. We will also exclude persons with hearing level of greater than or equal to 20 dB at 
any single frequency by tablet audiometry if physical examination confirms conductive hearing 
loss. If there is an easily reversible cause of conductive hearing loss (such as earwax removal), 
tablet audiometry and/or diagnostic sound booth audiometry may be repeated to assess eligibility. 
New onset SNHL after vaccination will use the Brighton Collaboration definition of SNHL for 
the AESI definition.23 In the event of abnormal screening tablet audiometry after vaccination, all 
participants will be evaluated promptly (within 2 business days) by a co-investigator otologist for 
confirmatory testing and possible initiation of standard of care treatment for sudden SNHL, all of 
which will be documented in the clinical database. Participants will be informed that these 
evaluations are done for safety assessments as part of the clinical trial. In the event of adverse 
events requiring continued monitoring, further assessments, or medical care, participants will be 
referred to appropriate health care facilities. Once SNHL is confirmed by diagnostic sound booth 
audiometry and otologist evaluation, AESI reporting will be done according to Section 8.4.8. 
Results of screening tablet audiometry and diagnostic sound booth audiometry will be confirmed 
by the PI or designated clinician licensed to make medical diagnoses and listed on Form FDA 
1572. Screening tablet audiometry and diagnostic sound booth audiometry readouts will be 
uploaded into the study database. 
In the event of true medical emergencies, stabilizing care will be administered, and arrangements 
will be made to dispatch the participants for emergency care. Relevant information including 
vaccine allocation, study records, clinical data, clinical assessments, and medical 
recommendations will be made available to the participants and their healthcare providers. 
Records will be sought from the healthcare provider encounters to inform AESI data collection 
and reporting. 
7.2 
Participant Withdrawal from the Study and Replacement 
Participants are free to withdraw from participation in the study at any time upon request. An 
investigator may discontinue or withdraw a participant from the study for the following reasons: 
• Participant becomes pregnant prior to study product dosing (Section 8.4.12)) 
• Study non-compliance that in the opinion of the investigator poses an increased risk or 
compromises the validity of the data. 

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• If any clinical AE, laboratory abnormality, or other medical condition or situation occurs 
such that continued participation in the study would not be in the best interest of the 
participant. 
• If the participant meets an exclusion criterion for participation in the study (either newly 
developed or not previously recognized) that precludes further study participation. 
• Medical disease or condition, or new clinical finding(s) for which continued 
participation, in the opinion of the investigator, might compromise the safety of the 
participant, interfere with the participant's successful completion of this study, or 
interfere with the evaluation of responses. 
• Participant lost to follow-up. 
If the participant agrees, every attempt will be made to follow all AEs through resolution. 
Participants who withdraw, or are withdrawn from this study, or are lost to follow-up after 
signing the ICF and after administration of the study product will not be replaced. Participants 
who withdraw, are withdrawn from this study, or are lost to follow-up after signing the ICF but 
before administration of the study product may be replaced. 
The reason for participant discontinuation or withdrawal from the study will be recorded in the 
electronic Case Report Form (eCRF). 
7.3 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she fails to return for scheduled visits 
and is unable to be contacted by the study site staff. 
8. STUDY ASSESSMENTS AND PROCEDURES 
8.1 
Screening Procedures 
Screening procedures may be performed up to 60 days prior to enrollment (Day-60 to Day -1), 
with the exception of screening audiometry which may be performed any time prior to the first 
study vaccination. After informed consent the following assessments are performed to determine 
eligibility and obtain baseline data: 
• Collection of demographic data 
• Take a focused medical history, including the following information: 
o Assess childbearing status 
o History of any chronic medical conditions. 
o History of any medication allergies including history of hypersensitivity to any 
component of the study products. 
o Concomitant medications taken within 60 days prior to signing the ICF will be 
reviewed with participants to determine stability of chronic diseases and 
eligibility. 

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o Assess allergy history 
o Assess vaccination, immunoglobulin or other blood products, antigen injection 
history within 60 days prior to signing the ICF and planned receipt 
• Participants of childbearing potential in a heterosexual relationship should be counseled 
to either practice true abstinence or use at least one primary form of contraception until 
30 days after receipt of the study product. Participants of childbearing potential must 
have a negative serum HCG pregnancy test at screening and a negative urine HCG 
pregnancy test within 24 hours of administration of study product. 
• A physical examination will be performed on all participants, by a study clinician 
licensed to make medical diagnoses and listed on the Form FDA 1572 as the PI or sub-
investigator, to include general appearance and the following organs, organ systems 
and/or body areas: abdomen, heart, extremities, head, eyes, ears (including otoscopy), 
nose, and throat, lymph nodes, neurological, lungs, chest and skin. Height and weight 
measurement (calculation of BMI). 
• Vital signs measurement (including pulse, systolic blood pressure, diastolic blood 
pressure, and oral temperature). 
• Blood for laboratory evaluations. 
o Serology at screening: HIV 1 and 2 antigen/antibody, Hepatitis B surface antigen, 
Hepatitis C antibody, rabies neutralization. 
o Hematology studies at screening: white blood cells (WBC) count, hemoglobin, 
and platelets. 
o Chemistry studies at screening: ALT, total bilirubin, creatinine. 
• Baseline audiometry 
Clinical screening laboratory evaluations will be performed in Frostburg, Maryland by Aeon 
Technologies Laboratories and/or locally at the University of Maryland Medical Center 
laboratories. Urine pregnancy tests and audiometry will be performed by research staff. The 
volume of venous blood to be collected is presented in Appendix 2. 
The overall eligibility of the participant to participate in the study will be assessed when all 
screening values are available. Study participants who qualify will be enrolled and entered into 
the Data Coordinating Center (DCC) and all others will be registered as screen failures. 
8.1.1 
Procedures to be Followed in the Event of Abnormal Laboratory Test Values or 
Abnormal Clinical Findings 
If a physiologic parameter, (e.g., vital signs) is outside of the protocol-specified range, then the 
measurement may be repeated once if, in the judgment of the investigator, the abnormality is the 
result of an acute, short-term, rapidly reversible condition (e.g., stress, anxiety, or “white coat 
syndrome”). A physiologic parameter may also be repeated if there is a technical problem with 
the measurement caused by malfunctioning, or an inappropriate measuring device (i.e., 
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A participant may be re-screened if there is a transient disease status (e.g., participant 
complained of a “cold or fever” and met a temporary delaying enrollment criterion of acute 
illness or fever), or if a protocol eligibility criterion that is not met at the initial time of screening, 
will be met by rescreening at a later date (e.g., a medication taken within exclusionary window at 
the time of first screening that would not be within exclusionary window at a later rescreen). 
Results of screening laboratory testing will be discussed with the participant. Participants will be 
provided the results of any abnormal clinical laboratory results and will be referred to their 
primary healthcare provider. Screening laboratory values that are outside the range of eligibility 
but are thought to be due to an acute condition or due to laboratory error may be repeated once. 
Research laboratory results will not be provided to the participant. 
No participant may be screened more than twice due to a screening failure result as defined 
above. 
8.2 
Immunogenicity Assessments 
8.2.1 
Immunogenicity Evaluations 
Measurement of anti-Lassa virus antibodies measured by ELISA at Day 1, 8, 29, 36, and 61. 
Measurement of anti-rabies virus antibodies measured by ELISA and RFFIT at Day 1, 8, 29, 36, 
and 61. 
See Appendix 2 for venipuncture volumes. 
8.2.2 
Exploratory Assessments 
• Measurement of anti-Lassa virus antibodies measured by ELISA at Day 121 and 394. 
• Measurement of anti-rabies virus antibodies measured by ELISA and RFFIT measured 
by ELISA at Day 121 and 394. 
In addition to the exploratory assessments, participants will consent to retention of unused serum 
specimens and to collection of additional blood specimens (including human peripheral blood 
mononuclear cells [PBMCs]) for storage and potential future use research. 
See Appendix 2 for venipuncture volumes. 
8.3 
Safety and Other Assessments 
Study procedures, timelines, and acceptable time windows are specified in Section 1.2. A study 
clinician licensed to make medical diagnoses and listed on the 1572 will be responsible for all 
trial-related medical decisions. 
Specimens for clinical screening and safety laboratory evaluations will be transported from the 
clinic sites to the respective site’s certified clinical laboratories or on-site certified laboratories 
for analysis. Specimens for immunology will be transported for processing, storage, transport 

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and/or analysis to CVD research laboratories. 
Ongoing Abstinence and Contraceptive Counseling 
Participants of childbearing potential in a heterosexual relationship should be counseled to use 
highly effective contraception through Day 61. 
Physical Examination 
A physical exam will be conducted at screening (Day -60 to -1) by a licensed study clinician. A 
targeted physical exam will be performed at in-person visits (Days 1, 8, 29, 36, 61, 121, and 394) 
at the investigator’s discretion. 
Vital Signs 
Vital signs will be assessed at screening (Day -60 to -1) and at in-person visits (Days 1, 8, 29, 36, 
61, 121, and 394). Vital signs will include pulse, systolic blood pressure, diastolic blood 
pressure, and oral temperature. On vaccination days (Day 1 and Day 29), vital signs are 
performed prior to vaccination and again at 30 minutes post vaccination. 
Audiometry 
As described in Section 7.1.5, tablet audiometry will be performed by study staff at screening 
(Day -60 to -1), Day 22, Day 61, Day 394, and at the investigator’s discretion. Abnormal tests 
will be confirmed by formal diagnostic sound booth audiometry and otologist evaluation within 2 
business days. 
Clinical Laboratory Evaluations 
• Serology at screening: HIV 1 and 2 antibody, Hepatitis B surface antigen, Hepatitis C 
antibody, rabies neutralization 
• Hematology (at screening and Days 8, 36, and 61 and any unscheduled visit or early 
termination visit at the investigator’s discretion): white blood cells WBC, hemoglobin, 
and platelets 
• Chemistry studies (at screening and Days 8, 36, and 61 and any unscheduled visit or early 
termination visit at the investigator’s discretion): ALT, TBILI, creatinine 
• Serum Beta hCG pregnancy test for participants of childbearing potential at screening 
• Urine pregnancy test will be performed for all participants of childbearing potential 
within the 24 hours prior to study product administration (Days 1 and 29) 
8.3.1 
Scheduled Phone Visits for Safety Assessment 
Safety assessment visits by phone are conducted three days after each study vaccination (Days 3 
and 31). During these visits, participants will be asked whether there has been any change in 
their medical history, and their concomitant medications will be reviewed. The paper Diary Card 
will be reviewed for potential AEs, and participants will be reminded to complete it daily 

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through 7 days post-vaccination. Participant training on the use of the paper Diary Card, the 
thermometer, and the ruler will be reinforced. Participants will also be reminded to contact the 
study personnel for safety concerns or other questions, and they will be directed to contact phone 
numbers in the paper Diary Card. Solicited AEs, unsolicited AEs, MAAEs, NOCMCs, PIMMCs, 
SAEs, and changes in hearing (potentially SNHL) will be assessed. Participants will be reminded 
of their scheduled in-person appointments for Days 8 and 36. If there are concerns about an 
ongoing AE by either the study staff member or the participant, an in-person unscheduled visit 
can be scheduled for further assessment. 
8.3.2 
Procedures to be Followed in the Event of Abnormal Laboratory Test Values or 
Abnormal Clinical Findings 
The PI or designated clinician licensed to make medical diagnoses and listed on Form FDA 1572 
is responsible for recording all AE/SAEs that are observed or reported during this study, 
regardless of relationship to the study product. AE/SAEs, abnormal laboratory test values or 
abnormal clinical findings will be collected, assessed, documented, reported, and followed 
appropriately, using a local laboratory as necessary. In determining eligibility, refer to Section 
5.1 and Section 5.2. 
8.3.3 
Unscheduled Visit 
If the investigator deems the reaction warrants further evaluation or intervention, the investigator 
will give further instructions on the proper course of action, including a return to the clinic for 
immediate evaluation at an unscheduled visit if appropriate. The study will preferentially 
conduct an unscheduled visit in-person, but a visit by phone is acceptable when necessary. 
8.3.4 
Early Termination Visit 
Should the participant withdraw or be withdrawn or terminated from this trial, the study team 
will request a final in-person visit for an evaluation, to include a review of changes in medical 
history, concomitant medications, review for potential AEs (including MAAEs, NOCMCs, 
PIMMCs, AESIs, SAEs) and possible targeted physical examination, tablet audiometry, vital 
signs, and laboratory evaluations, and blood collection for study immunology assays at the 
discretion of the investigator. Depending upon the time of the early termination visit, the 
participant will receive abstinence and contraceptive counseling. 
8.4 
Adverse Events and Serious Adverse Events 
8.4.1 
Definition of Adverse Events (AE) 
Adverse event means any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related (21 CFR 312.32 (a)). An 
AE can therefore be any unfavorable and unintended sign (including an increase in grade in an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of 

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medicinal (investigational) product. Clinical laboratory AEs are defined as laboratory 
abnormalities with a grade level increase in clinical laboratory values per protocol toxicity tables. 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the severity of any pre-existing 
medical condition increases, it should be recorded as an AE. 
Adverse events can be further divided into solicited AEs and unsolicited AEs. Solicited AEs are 
those for which the study team will specifically query the participant whether they occurred. 
Unsolicited AEs are those events that the participant reports occurring without being queried 
about the specific event. All AEs will be assessed for severity and relationship to study 
intervention. 
All AEs, solicited and unsolicited, will be captured on the appropriate data collection form. 
Information to be collected for AEs includes event description, date of onset, assessment of 
severity, relationship to study product and alternate etiology (assessed only by those with the 
training and authority to make a diagnosis and listed on the Form FDA 1572 as an investigator), 
date of resolution, seriousness and outcome. AEs occurring during the trial collection and 
reporting period will be documented appropriately regardless of relationship. 
Laboratory test abnormalities are documented on the laboratory form and not recorded as a 
separate AE eCRF but the relationship, clinical significance, and grade will be noted on the 
laboratory form. 
AEs will be followed through resolution. 
8.4.1.1 Solicited Adverse Events 
Each participant will be given a 7-day paper Diary Card, a thermometer, and a measuring device. 
Participant will use the diary to record their highest temperature, local and systemic symptoms, 
and any new concomitant medications daily for 7 days after each product administration. 
Subjects will be provided training on paper Diary Card completion and proper usage of the 
thermometer to measure temperature and the ruler to measure injection site symptoms. 
Completion of paper Diary Card training will be noted in the source documents. The paper Diary 
Card will be transcribed into the study database and stored in the subject file for monitoring 
purposes.  
Solicited AEs will be collected through the 7-day paper Diary Cards and will include anticipated 
local and systemic AEs for which consistent collection of information is desired. This may 
include: 
• Common and expected events according to the available knowledge about the product 
• Specific events of concern that should be ascertained on every participant 

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• Solicited AEs as noted in protocol toxicity tables, as well as measured temperature and 
size of certain local reactogenicity events will be collected from each participant on Days 
1-7 via the paper Diary Cards. 
The participant paper Diary Card will be reviewed by a clinician for accuracy and completeness 
at follow-up visits. Study clinicians will review the paper Diary Card entries and severity 
assessments with the participants. The severity grading scale will be reviewed, and the 
participants will be asked to confirm that that their recorded symptom severity accurately aligned 
with the severity grading scale. Participants will be given the opportunity to revise their 
symptoms if they believe that they errored in their self-assessment of severity. Clinicians will 
follow any solicited symptoms that are ongoing after 7 days until they have resolved. 
Participants using a paper Diary Card will be encouraged to contact the clinic as soon as possible 
for any moderate or severe side effects that they experience in the 7 days post product 
administration. A study clinician may contact the participant by phone if any moderate or severe 
side effect is reported. Study clinician mobile phone and back-up phone numbers will be 
provided in the event the participant has questions or concerns after clinic hours. 
8.4.1.2 Unsolicited Events 
All AEs spontaneously reported by the participant and/or in response to an open question from 
study personnel or revealed by observation, physical examination or other diagnostic procedures 
must be recorded in the source document. All reported unsolicited AEs are graded in accordance 
with the protocol toxicity tables. 
8.4.1.3 Special Reporting of Adverse Events 
Not applicable 
8.4.2 
Definition of Serious Adverse Events 
An AE or suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or IND sponsor, it results in any of the following outcomes (21 CFR 312.32 (a)): 
• death 
• a life-threatening adverse event 
• inpatient hospitalization or prolongation of existing hospitalization 
• a persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, or 
• a congenital anomaly/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 patient or participant and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. Examples of such medical events include 

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allergic bronchospasm requiring intensive treatment in an emergency room or at home, 
convulsions that do not result in inpatient hospitalization, etc. 
All SAEs, as with any AE, will be assessed for severity and relationship to study intervention. All 
SAEs will be recorded on the appropriate SAE data collection form and eCRF. 
All SAEs will be followed through resolution by a licensed study clinician (for IND studies, a 
physician listed on the Form FDA 1572 as the Principal Investigator or sub-investigator). 
All SAEs will be reviewed and evaluated by IND sponsor and will be sent to the ISM (periodic 
review unless related), and the IRB/IEC. 
8.4.2.1 Suspected Unexpected Serious Adverse Reactions (SUSAR) 
A SUSAR is any SAE where a causal relationship with the study product is at least reasonably 
possible but is not listed in the Investigator Brochure (IB), Package Insert, and/or Summary of 
Product Characteristics. 
8.4.3 
Classification of an Adverse Event 
The determination of seriousness, severity, and causality will be made by an on-site investigator 
who is qualified (licensed) to diagnose AE information, provide a medical evaluation of AEs, 
and classify AEs based upon medical judgment. This includes but is not limited to physicians, 
physician assistants, and nurse practitioners. 
8.4.3.1 Severity of Event 
All AEs or SAEs will be assessed for severity, according to the FDA Guidance for Industry 
“Toxicity Grading Scales for healthy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials” (Appendix 3, Appendix 4, Appendix 5, and Appendix 6). 
For AEs not included in the protocol defined grading system, the following guidelines will be 
used to describe severity. 
• Mild (Grade 1): Events that are usually transient and may require only minimal or no 
treatment or therapeutic intervention. The event generally does not interfere with the 
participant’s usual activities of daily living. 
• Moderate (Grade 2): Events that are usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research participant. 
• Severe (Grade 3): Events interrupt usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention. Severe events are 
usually incapacitating. 
AEs characterized as intermittent require documentation of onset and duration of each episode. 
The start and stop date of each reported AE will be recorded on the appropriate data collection 

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form and eCRF. Changes in the severity of an AE will be documented to allow an assessment of 
the duration of the event at each level of intensity. 
8.4.3.2 Relationship to Study Intervention 
For each reported adverse reaction, the PI or designee must assess the relationship of the 
event to the study product using the following guideline: 
• Related – The AE is known to occur with the study intervention, there is a reasonable 
possibility that the study intervention caused the AE, or there is a temporal relationship 
between the study intervention and event. Reasonable possibility means that there is 
evidence to suggest a causal relationship between the study intervention and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study 
intervention and event onset, or an alternate etiology has been established. 
8.4.4 
Time Period and Frequency for Event Assessment and Follow-Up 
For this study: 
• Solicited AEs will be collected from vaccination on Day 1 and Day 29 through 7 days, 
and they will be reviewed on Day 8 and Day 36. 
• Non-serious unsolicited AEs will be collected from Day 1 through Day 61. 
• Clinical laboratory AEs will be assessed on Day 8, Day 36, and Day 61. 
• MAAEs, SAEs, NOCMCs, PIMMCs, and the AESI (sensorineural hearing loss) will be 
collected from the Day 1 through the end of the study (Day 394). 
Non-serious unsolicited AEs and clinical laboratory AEs may fall within the allowable time 
window noted in Section 1.2. 
8.4.5 
Adverse Event Reporting 
8.4.5.1 Investigators Reporting of AEs 
Information on all AEs should be recorded on the eCRF. All clearly related signs, symptoms, 
and results of diagnostic procedures performed because of an AE should be grouped together and 
recorded as a single diagnosis. If the AE is a laboratory abnormality that is part of a clinical 
condition or syndrome, it should be recorded as the syndrome or diagnosis rather than the 
individual laboratory abnormality. Each AE will also be described in terms of duration (start 
and stop date), severity, association with the study product, action(s) taken, and outcome. 
8.4.6 
Serious Adverse Event Reporting 
8.4.6.1 Investigators Reporting of SAEs 
Any AE that meets a protocol-defined serious criterion must be submitted immediately (within 
24 hours of site awareness) on an SAE form to the IND sponsor, the SRC, and the ISM. 

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In addition to the SAE form, select SAE data fields must also be entered into the DCC system. 
Please see the protocol-specific MOP for details regarding this procedure. 
Other supporting documentation of the event may be requested by the IND sponsor and should 
be provided as soon as possible. The site will send a copy of the SAE report(s) to the ISM (as 
deemed necessary) when they are provided to the IND sponsor. The IND sponsor will review 
and assess the SAE for regulatory reporting and potential impact on study participant safety and 
protocol conduct. 
At any time after completion of the study, if the PI or appropriate sub-investigator becomes 
aware of an SAE that is suspected to be related to study product, the principal investigator or 
appropriate sub-investigator will report the event to the IND sponsor. 
8.4.6.2 Regulatory Reporting of SAEs 
Following notification from the PI or appropriate sub-investigator, the IND sponsor will report 
any SUSAR in an IND safety report to the FDA. The IND sponsor will report to the FDA any 
unexpected fatal or life-threatening suspected adverse reaction as soon as possible, but in no case 
later than 7 calendar days after the IND sponsor’s initial receipt of the information. If the event is 
not fatal or life-threatening the IND safety report will be submitted within 15 calendar days after 
the IND sponsor determines that the information qualifies for reporting as specified in 21 CFR 
Part 312.32. Relevant follow up information to an IND safety report will be submitted as soon as 
the information is available. Upon request from FDA, the IND sponsor will submit to the FDA 
any additional data or information that the Agency deems necessary, as soon as possible, but in 
no case later than 15 calendar days after receiving the request. SAEs that are not SUSARs will be 
reported to the FDA at least annually in a summary format which includes all SAEs. 
For US-licensed vaccines such as HDCV: Established in 1990, the Vaccine Adverse Event 
Reporting System (VAERS) is a national early warning system to detect possible safety 
problems in US-licensed vaccines. VAERS is co-managed by the Centers for Disease Control 
and Prevention (CDC) and the FDA. VAERS accepts and analyzes reports of AEs (possible side 
effects) after a person has received a vaccination. Anyone can report an AE to VAERS. 
Healthcare professionals are required to report certain AEs and vaccine manufacturers are 
required to report all AEs that come to their attention. 
VAERS is a passive reporting system, meaning it relies on individuals to send in reports of their 
experiences to CDC and FDA. VAERS is not designed to determine if a vaccine caused a health 
problem, but is especially useful for detecting unusual or unexpected patterns of AE reporting 
that might indicate a possible safety problem with a vaccine. This way, VAERS can provide 
CDC and FDA with valuable information that additional work and evaluation is necessary to 
further assess a possible safety concern. 
Link to VAERS https://vaers.hhs.gov/. 

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8.4.7 
Reporting Events to Participants 
Not applicable 
8.4.8 
Adverse Events of Special Interest 
Adverse Events of Special Interest (AESIs) are a pre-defined subset of AEs that may be required 
to be collected at the request of the regulatory agency, industry partner, DMID, or IND sponsor 
and is meant to address a specific safety concern. Any AESI that meets serious criteria must be 
submitted immediately (within 24 hours of site awareness) on an SAE form to the IND sponsor, 
the SRC, and the ISM. 
In this study, new onset SNHL is considered an AESI. The evaluation of SNHL is detailed in 
Section 7.1.5. 
All AESIs are assessed, recorded, and followed as described above. In addition, the AESI will be 
reported on an SAE form to the IND sponsor. 
8.4.9 
Medically-Attended Adverse Events 
For each unsolicited AE experienced, the participant will be asked if he/she had received medical 
attention, defined as hospitalization, an emergency room visit or an otherwise unscheduled visit 
to or from medical personnel for any reason. AEs characterized by such unscheduled medical 
care will be designated as Medically-Attended Adverse Events (MAAEs) and will be reported in 
the DCC system. 
8.4.10 
New-Onset Chronic Medical Conditions 
New-Onset Chronic Medical Conditions (NOCMCs) are defined as any new ICD-10 diagnosis 
(10th revision of the International Statistical Classification of Diseases and Related Health 
Problems) that is applied to the participant during the course of the study, after receipt of the 
study agent, that is expected to continue for at least 3 months and requires continued health care 
intervention. NOCMCs will be reported in the DCC system. 
8.4.11 
Potentially Immune-Mediated Medical Conditions 
PIMMCs constitute a group of AEs that includes diseases which are clearly autoimmune in 
etiology and other inflammatory and/or neurologic disorders which may or may not have 
autoimmune etiologies. A PIMMC is any new ICD-10 diagnosis corresponding to the list of 
relevant diagnoses in Appendix 7 during the course of the study and after receipt of the study 
agent. 
8.4.12 
Reporting of Pregnancy 
Pregnancies occurring in study participants will be reported via DCC system on the Pregnancy 
Report form. If the pregnant participant is agreeable, venous blood samples for safety and 
serological assays will still be collected per protocol; however, large volume blood samples for 

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cellular immunological assays will be discontinued. Efforts will be made to follow all 
pregnancies reported during the course of the study to pregnancy outcome. 
8.5 
Adverse Unanticipated Problems (UP) 
8.5.1 
Definition of Unanticipated Problems (UP) 
The Department of Health and Human Services (DHHS) OHRP considers UP involving risks to 
participants or others to include, in general, any incident, experience, or outcome that meets all 
of the following criteria: 
• Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved research 
protocol and informed consent document; and (b) the characteristics of the participant 
population being studied; 
• Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
• Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
8.5.2 
Unanticipated Problem Reporting 
The investigator will report UPs to the reviewing IRB and to the DCC and the PI. The UP report 
will include the following information: 
• Protocol identifying information: protocol title and number, PI’s name, and the IRB 
project number; 
• A detailed description of the event, incident, experience, or outcome; 
• An explanation of the basis for determining that the event, incident, experience, or 
outcome represents an UP; 
• A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the UP. 
• To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline: 
• UPs that are serious adverse events (SAEs) will be reported to the IRB and to the 
DCC/IND sponsor within 24 hours of the investigator becoming aware of the event. 
• Any other UP will be reported to the IRB and to the DCC/IND sponsor within 2 weeks of 
the investigator becoming aware of the problem. 
8.5.3 
Reporting Unanticipated Problems to Participants 
Not applicable 

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9. STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
There are no hypothesis tests pre-specified for this Phase I study, although some inferential 
statistics such as 95% confidence levels will be calculated to supplement the descriptive statistics 
provided for outcome measures. Any potential hypothesis testing will be considered exploratory 
and will be detailed in a separate statistical analysis plan (SAP). Details about planned tables, 
figures, and data listings will be presented in a separate SAP. 
9.2 
Sample Size Determination 
The sample size is chosen without the intention that group differences will be detected with a 
sufficient power but is consistent with FDA guidance. A sample size of 55 is selected, with 15 
persons in each of the three dose groups (Treatment Groups A, B, and C) for 
LASSARAB+aPHAD-SE and 10 persons in the HDCV control group (Treatment Group D). 
Table 4 indicates the probability of observing one or more safety events for a single group (N=10 
or 15) and for all enrolled subjects (N=55). 
Table 4. Probability to Detect One or More Safety Events 
Number of Subjects 
Event rate 
10 
15 
55 
10% -- Very Common 
0.651 
0.794 
0.997 
1% -- Common 
0.096 
0.140 
0.425 
0.1% -- Uncommon 
0.010 
0.015 
0.054 
0.01% -- Rare 
0.001 
0.001 
0.005 
9.3 
Populations for Analyses 
• The Intent-to-Treat (ITT) population will consist of all randomized participants who are 
vaccinated. 
• The Modified Intention-to-Treat (mITT) population will include participants in the ITT 
population with the following exclusions of data: 
o Data from participants determined to be ineligible at baseline 
o Data from any visit that occurs out of window as defined in the Schedule of 
Activities 
o Data from all visits subsequent to major protocol deviations, as defined in the 
SAP, that could affect the validity of later data, such as: 
• 
Receipt of immunosuppression or any medications that may be associated 
with impaired responsiveness 
• 
Receipt of any non-study investigational drug/investigational 
vaccine/licensed vaccine as defined in the exclusion criteria 
o Data are available for a particular analysis. 

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The ITT population will be used for all analyses of AEs and reactogenicity. Immunogenicity 
analyses will be done in the mITT population. 
9.4 
Statistical Analyses 
The primary clinical database for this study will consist of safety data including solicited 
reactogenicity events, unsolicited events, and abnormal laboratory values, as well as 
baseline/demographic data. There are two planned analyses. A first analysis (Interim Analysis) 
will occur after Day 61. After all participants have completed Day 61,  fields from instruments 
needed for the interim analysis will be cleaned and there will be a database freeze to ensure data 
integrity.  After the freeze, a snapshot of the data will be downloaded and used for the interim 
analysis. This database freeze will include fields from the following instruments: Demographics, 
Inclusion/Exclusion Criteria, Vaccine Administration, Reactogenicity Assessment, Laboratory 
Results and Adverse Events. After clinical database through Day 61 freeze and receipt of 
secondary endpoint immunogenicity data, a set of topline tables will be generated by the study 
statistician, including summaries of clinical safety and secondary immunogenicity data by 
treatment group. The topline report will be made available to the study team for planning 
subsequent trials and may be presented in a public forum or used for publication in collaboration 
with the PI. These analyses will be considered final and will be included in the CSR. Once the 
last participant has completed the final visit, the remaining clinical database (Day 61 through the 
end of the study) will be cleaned, monitored, and locked. At the time of database lock, access 
will be restricted to read-only to prevent further modification.  
The CSR, comprised of the final analyses of safety and available immunological data, will be 
subsequently completed. The final CSR will be completed when all primary and secondary 
safety, clinical, and immunological endpoint data are available. Any available data from the 
exploratory endpoints at the time of compilation of the final CSR may also be included. 
Additional exploratory endpoint data may be included in an addendum to the CSR, publication of 
manuscript(s), or other report. 
A formal SAP, which will elaborate on the analyses described here and describe any changes to 
the planned analyses, will be developed and finalized before performing any of these analyses 
(with the exception of SRC/ISM reviews of descriptive safety analyses). 
In addition to the descriptive analyses of study data for SRC/ISM review, an interim analysis is 
planned for the ongoing study to allow for an early assessment of the immunogenicity of the 
study vaccine and to aid in decision-making regarding future studies after Day 61 is completed 
for all participants. This analysis would not affect the conduct of this trial via early stopping. 
Additional details on the planned interim analysis are given in Section 9.4.5. 
9.4.1 
General Approach 

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The non-missing sample size, mean, standard deviation, and the minimum, median, interquartile 
range, and maximum will be summarized as a descriptive analysis for all continuous variables. 
Categorical variables will be descriptively summarized by frequencies and percentages of 
observed levels, based on the observed data. Titers will be summarized with geometric means 
(GMTs), first across technical replicates to compute one value for each individual sample (where 
applicable) and then applied again across participants within the same group. 
In general, summaries will be presented by treatment group and compared across groups using 
ANOVA F-test or Kruskal-Wallis H test for continuous variables and chi-square test or Fisher’s 
exact test for categorical variables. All tables will be annotated with the total sample size 
relevant to that table, including any missing observations. The analysis sample for each exhibit 
will be clearly indicated. 95% confidence intervals will be computed for binary variables, where 
applicable. 
Safety Analysis 
The primary objective of the study is to assess the safety of a single dose of the study 
vaccination, as determined by the incidence of solicited reactogenicity events, unsolicited serious 
and non-serious AEs, SAEs, MAAEs, NOCMCs, PIMMCs, the AESI, and clinical laboratory 
AEs. 
Safety objectives will be assessed in the ITT population. All summaries will be provided by 
treatment actually received. Solicited local and systemic reactogenicity events will be 
summarized via the number and percentage of participants reporting each event, and any 
solicited reactogenicity event, through 7 days post-vaccination. These will be tabulated by 
severity and any severity. 95% confidence intervals (CIs) for the probability of each event 
occurring collectively across any severity level post-vaccination will be computed for each 
group. Severity will be determined as described in Section 8.4.3.1. 
Non-serious unsolicited AEs through Day 61 will be summarized by the Medical Dictionary for 
Regulatory Activities (MedDRA) system organ class (SOC), MedDRA preferred term and 
severity at the end of the study in the final CSR. SAEs, MAAEs, NOCMCs, PIMMCs, and 
AESIs reported through the end of the study (one year after the second study vaccination) will be 
summarized similarly. Clinical laboratory AEs are defined as a grade level increase in clinical 
laboratory values (per protocol toxicity tables) and will be summarized separately. For 
unsolicited events, summaries regarding relationship to study vaccine will also be provided, as 
described in Section 8.4.3.2. AE rates will be compared among the treatment groups as well as 
between the control group and the three study treatment groups combined. 
AEs and abnormal clinical laboratory results, including clinical laboratory AEs, will be presented 
in data listings. 
9.4.2 
Secondary Immunogenicity Analysis 

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The secondary objectives of the study are the following: 
1) To assess the serum antibody response of LASSARAB+aPHAD-SE vaccine as compared 
to licensed HDCV control. These responses will be assessed via Lassa- glycoprotein 
complex (GPC) antigen antibodies measured by ELISA at Day 1, 8, 29, 36, and 61 per 
treatment group. 
2) To assess the antibody response of LASSARAB+aPHAD-SE vaccine as compared to 
licensed HDCV control as measured by rabies GP antigen antibodies as measured by IgG 
ELISA and RFFIT test at Days 1, 8, 29, 36, and 61 per treatment group. 
9.4.3 
Exploratory Immunogenicity Analyses 
Exploratory objectives of the study include: 
• To assess the serum antibody response of LASSARAB+aPHAD-SE vaccine as compared 
to licensed HDCV control. These responses will be assessed via Lassa- glycoprotein 
complex (GPC) antigen antibodies measured by ELISA at Days 121 and 394 per 
treatment group. 
• To assess the antibody response of LASSARAB+aPHAD-SE vaccine as compared to 
licensed HDCV control as measured by rabies GP antigen antibodies as measured by IgG 
ELISA and RFFIT test at Days 121 and 394per treatment group. 
For each analysis, the GMT and corresponding 95% confidence intervals will be presented for 
applicable endpoints by treatment group and study day. For post-baseline time points, the 
geometric mean fold rise (GMFR) from baseline and corresponding 95% confidence intervals 
will be presented by treatment group. Seroconversion is defined as > 4 fold rise in antibody titer 
at any time point as compared to baseline with the minimum titer for seroconversion defined as 
four times the lower limit of quantification (LLOQ). The LLOQ for the assay will be determined 
as part of assay qualification. When an antibody titer at baseline is below LLOQ, it will be 
assigned a value 50% of the LLOQ to enable the calculation of fold rise. Details of the 
immunogenicity analyses will be included in the SAP. 
9.4.4 
Baseline Descriptive Statistics 
Baseline and demographic characteristics will be summarized by treatment group, with summary 
statistics for all enrolled participants as described in Section 9.4.1. These characteristics will 
include age, sex, ethnicity, and race. 
9.4.5 
Planned Interim and Early Analyses 
9.4.5.1 Interim Safety Analyses 
Two groups will review safety for this study: The SRC and the ISM. They are described in detail 
in Section 10.1.6. 
9.4.5.2 Interim Immunogenicity 

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As described in Section 9.4, an interim analysis focused primarily on immunogenicity will be 
conducted while the study is ongoing. 
9.4.6 
Sub-Group Analyses 
There are no planned sub-group analyses for this study due to small sample sizes. 
9.4.7 
Tabulation of Individual Participant Data 
Safety data, reactogenicity data, and immunogenicity data will be presented in listings at the end 
of study in the final CSR, as described in Section 9.4.1. 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 
Regulatory, Ethical, and Study Oversight Considerations 
Each institution engaged in this research will hold a current Federalwide Assurance (FWA) 
issued by the OHRP for federally funded research. 
The investigator will submit applicable information to the IRB/IEC on which it relies for the 
review, to conduct the review in accordance with 45 CFR 46, ICH E6(R2) GCP, and as 
applicable, 21 CFR 56 (Institutional Review Boards) and 21 CFR 50 (Protection of Human 
Subjects), other federal, state, and local regulations. The IRB/IEC must be registered with OHRP 
as applicable to the research. IND sponsor must receive the documentation that verifies 
IRB/IEC-approval for this protocol, associated informed consent documents, and upon request 
any recruitment material and handouts or surveys intended for the participants, prior to the 
recruitment and enrollment of participants. 
Any amendments to the protocol or consent materials will be approved by the IRB/IEC before 
they are implemented. IRB/IEC review and approval will occur at least annually throughout the 
enrollment and follow-up of participants. The investigator will notify the IRB/IEC of deviations 
from the protocol and reportable SAEs, as applicable to the IRB/IEC policy. 
10.1.1 
Informed Consent Process  
Informed consent is a process that is initiated prior to an individual agreeing to participate in a 
trial and continuing throughout the individual’s trial participation. Before any study procedures 
are performed, informed consent will be obtained and documented. Participants will receive a 
concise and focused presentation of key information about the clinical trial, verbally and with a 
written consent form. The key information about the purpose of the study, the procedures and 
experimental aspects of the study, study interventions/products, probability for random 
assignment to treatment groups, risks and discomforts, the expected duration of the participant’s 
participation in the trial, any expected benefits to the participant, and alternative treatments and 
procedures that may be available to the participant. The explanation will be organized and 
presented in lay terminology and language that facilitates understanding why one might or might 

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not want to participate. 
Participants will receive an explanation as to whether any compensation and any medical 
treatments are available if injury occurs, and, if so, what they consist of, or where further 
information may be obtained. Participants will be informed of the anticipated financial expenses, 
if any, to the participant for participating in the trial, as well as any anticipated prorated 
payments, if any, to the participant for participating in the trial. They will be informed of whom 
to contact (e.g., the investigator) for answers to any questions relating to the research project. 
Information will also include the foreseeable circumstances and/or reasons under which the 
participant’s participation in the trial may be terminated. The participants will be informed that 
participation is voluntary and that they are free to withdraw from the study for any reason at any 
time without penalty or loss of benefits to which the participant is otherwise entitled. 
Participants will be informed that records identifying the participant will be kept confidential, 
and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly 
available and, if the results of the trial are published, the participant’s identity will remain 
confidential. Participants will be informed whether private information collected from this 
research and/or specimens will be used for additional research, even if identifiers are removed. 
Participants will be informed that the monitor(s), auditors(s), IRB, NIAID, and regulatory 
authority(ies) will be granted direct access to the participant’s original medical records for 
verification of clinical trial procedures and/or data without violating the confidentiality of the 
participant, to the extent permitted by the applicable laws and regulations, and that, by signing a 
written informed consent form, the participant is authorizing such access. 
Participants will be allowed sufficient time to consider participation in this research trial and have 
the opportunity to discuss this trial with their family, friends or legally authorized representative, 
or think about it prior to agreeing to participate. 
Informed consent forms will be IRB-approved and participants will be asked to read and review 
the consent form. Participants must sign the ICF prior to starting any study procedures for this 
trial. Once signed, a copy of the ICF will be given to the participant(s) for their records. New 
information will be communicated by the PI to participants who consent to participate in this 
trial in accordance with IRB requirements. The informed consent document will be updated, and 
participants will be re-consented per IRB requirements, if necessary. 
10.1.1.1 
Requirements for Permission by Parents/Guardians and Assent by Children 
(in case of a minor) 
Not applicable 
10.1.1.2 
Other Informed Consent Procedures 
Not applicable 

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10.1.2 
Study Termination and Closure 
Section 7.1 describes the temporary halting of the study. 
This study may be prematurely terminated if there is sufficient reasonable cause, including but 
not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Halting criteria met and it is deemed unsafe to proceed with further dosing 
• Insufficient compliance with protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Decision by regulatory authorities 
If the study is prematurely terminated, the PI will promptly inform study participants, the IRB 
and regulatory authorities as applicable. Study participants will be contacted, as applicable, and 
be informed of changes to the study visit schedule. The PI will assure appropriate follow-up for 
the participants, as necessary. 
The IND sponsor will notify regulatory authorities as applicable. 
10.1.3 
Confidentiality and Privacy 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, the 
IND sponsor and their agents. This confidentiality is extended to cover clinical information 
relating to participants, test results of biological samples and all other information generated 
during participation in the study. No identifiable information concerning participants in the study 
will be released to any unauthorized third party. When a participant’s hepatitis B, hepatitis C, or 
HIV screening result is positive, the result will be reported to the Maryland Department of 
Health. The test results will be kept confidential to the extent permissible under the law. 
Participant confidentiality will be maintained when study results are published or discussed in 
conferences. 
The study monitor, other authorized representatives of the IND sponsor, representatives of the 
IRB, and/or regulatory agencies may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, medical records (office, clinic, or 
hospital) and pharmacy records for the participants in this study. The clinical study site will 
permit access to such records. 
All source records including electronic data will be stored in secured systems in accordance with 
institutional polices and federal regulations. 
All study data and research specimens that leave the site (including electronic transmission of 
data) will be identified by a coded number that is linked to a participant through a code key 
maintained at the clinical site. The code key, including names or readily identifiable information 
is kept confidential and will not be transmitted off site. 

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As this research is funded by the NIH, it is covered by NIH policy which effectively issues the 
research a Certificate of Confidentiality (COC). By this policy, researchers cannot be forced to 
disclose or provide, in any Federal, State, or local civil, criminal, administrative, legislative, or 
other proceeding, the name of such individual or any such information, document, or 
biospecimen that contains identifiable, sensitive information about the individual and that was 
created or compiled for purposes of the research, unless such disclosure or use is made with the 
consent of the individual to whom the information, document, or biospecimen pertains. 
The Certificate cannot be used to resist a demand for information from personnel of the US 
Government that is used for auditing or evaluation of federally funded projects, like this study, or 
for information that must be released in order to meet the requirements of the FDA. 
A Certificate of Confidentiality does not prevent the participant from voluntarily releasing 
information about themselves or their involvement in this research. If any person or agency 
obtains a written consent to receive research information, then the researchers may not use the 
Certificate to withhold that information. 
The Certificate of Confidentiality does not prevent the researchers from reporting without the 
participant’s consent, information that would identify the participant as a participant in the 
research project regarding matters that must be legally reported including child and elder abuse, 
sexual abuse, or wanting to harm themselves or others. 
The release of individual private information or specimens for other research will only occur if 
consent was obtained from the individual to whom the information, document, or biospecimen 
pertains, or for the purposes of other research that the release is in compliance with applicable 
Federal regulations governing the protection of human subjects in research. 
10.1.4 
Future Use of Stored Specimens and Data 
Secondary Human Subject Research is the re-use of identifiable data or identifiable 
biospecimens that were collected from some other ‘‘primary’’ or ‘‘initial’’ activity, such as the 
data and samples collected in this protocol. This section will detail the samples and data 
available for secondary research. Any use of the sample or data, however, will be presented in a 
separate protocol and require separate IRB approval.  
10.1.4.1 
Samples for Secondary Research 
To participate in this study, eligible participants must consent to the storage and use of leftover 
and extra samples and associated data for the purpose of future research. Some extra specimens 
will be collected specifically for the purposes of secondary research. Samples designated for 
secondary research use may be used in additional assessments that may include but are not 
limited to, evaluation of antibody responses, functional antibody assays, evaluation of cellular 
immune response, and evaluation of the innate immune response. These specimens might be 
used in new or different immunological laboratory tests, to provide information for the 

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development of new vaccines or therapeutics, or for the study of Lassa virus or other infections. 
Specimens will be coded. Any future testing laboratory will not have access to the code, and 
therefore will not be able to identify study participants. Diagnostic genetic testing on these 
samples will not be performed. The specifics of this secondary research testing will be in a 
separate protocol and will be reviewed by an IRB. Samples will not be sold for commercial 
profit. Although the results of any future research may be patentable or have commercial profit, 
participants will have no legal or financial interest in any commercial development resulting 
from any future research. 
Risks are associated with the additional volume of blood collected, such as anemia. Risks for 
loss of privacy and confidentiality are described below. Hence, the following types of samples 
will be stored and used for secondary research: 
• Residual biological specimens - Any leftover primary research sample after laboratory 
testing is completed per protocol. 
• Repository research sample - Samples will be collected with the participant’s consent in 
this protocol with the intent to store for additional research (i.e., samples collected 
beyond those needed for primary research including whole blood for isolation of 
peripheral blood mononuclear cells) and will be used in future studies. 
Samples will be stored indefinitely at an IND sponsor-designated storage facility. 
Secondary research with coded samples and data may occur; however, participant confidentiality 
will be maintained as described for this protocol. An IRB review of the secondary research using 
coded specimens is required. Residual/Repository Research Samples, upon written request and 
approval from IND sponsor and any approvals required by the site, may be shared for secondary 
research with investigators at the participating site, with researchers at other institutions, or 
company-designated research laboratories. The samples will not be sold or used directly for 
production of any commercial product. Reports from secondary research will not be kept in the 
participants’ health records or shared with participants, unless required by law. The participant’s 
decision for secondary research can be changed at any time by notifying the study doctors or 
nurses in writing. If the participant changes his/her decision, the samples will be destroyed if the 
samples have not been used for research or released for a specific research project. 
10.1.4.2 
Data Sharing for Secondary Research 
Data from this study may be used for secondary research. All of the individual participant data 
collected during the trial will be made available after deidentification. The Statistical Analysis 
Plan and Analytic Code will also be made available. This data will be available immediately 
following publication, with no end date. The data will be made available to researchers who 
provide a methodologically sound proposal. The data will be available for any purpose outlined 
in the approved proposal. Proposals should be directed to the IND sponsor. To gain access, data 
requestors will need to sign a data access agreement. 

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10.1.5 
Key Roles and Study Governance 
The IND sponsor of this study is Dr. Wilbur Chen of CVD, UMB. Decisions related to the study 
will be made by the protocol team, which includes the PI, DMID (the Funding organization), and 
the IND sponsor. The PI is listed on the cover page. Other study team members and roles are 
listed in the protocol-specific MOP. 
10.1.6 
Safety Oversight 
This clinical study will use both a Safety Review Committee (SRC) and an Independent Safety 
Monitor (ISM). The SRC will consist of the PI, a DMID Representative, and the IND sponsor 
Representative. The SRC will evaluate safety data after the first study vaccination for each of the 
Cohorts 1-3 to assess safety of sentinel subgroup participants, provide sentinel subgroup safety 
data for ISM for concurrence of SRC safety findings, and will notify the IND sponsor 
Representative of intent to proceed if no study halting criteria are met (Appendix 1). Ad hoc 
reviews may also be called for by the investigators, IND sponsor, the SRC, or the ISM. 
Decisions are dependent on the failure to meet halting criteria when the required follow-up data 
are available. The SRC deliberations may occur by teleconference, videoconference, or email. 
The SRC will review all available blinded safety data needed for dose escalation decisions. The 
SRC will determine whether halting criteria may have been met and seek ISM review. If the ISM 
agrees that halting criteria were not met, they will provide the SRC with a recommendation to 
proceed with dose escalation. If the ISM determines that halting criteria have been met, the study 
will be halted for further review by the ISM. 
The ISM will be an objective, medically qualified physician-scientist who is not involved with 
the conduct of the study. The ISM will be separate and independent of study personnel 
participating in this trial and should not have scientific, financial, or other conflicts of interest 
related to this trial. The primary responsibility of the ISM is to monitor participant safety. The 
ISM considers study-specific data as well as relevant background information about the disease, 
test agent, and target population under study. During scheduled reviews after sentinel subgroup 
vaccinations as well as at any time during the study when the unblinded SRC identifies that 
halting criteria may have been met, the ISM will evaluate the data and recommend 
appropriateness of further dosing. If the unblinded SRC determines that halting criteria were not 
met, the ISM will be provided relevant study safety data for review and potential concurrence.  
Any member of the SRC may request an ISM review at any time. The ISM will have the option 
to be unblinded to treatment group as needed and will have as a resource an unblinded 
statistician to aid in analyses of data. The decision to advance to the next dosing cohort will be 
documented and provided to the SRC. The ISM will be empowered to suspend (halt) the study, 
recommend amendments to the protocol, and/or to request further information for their review. If 
the ISM determines that the study data have met the criteria necessary to continue from a sentinel 
subgroup to expanded subgroup cohort or to begin a subsequent cohort, the ISM will notify the 

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SRC of the determination. 
If the SRC or any of its members is unable to determine that the criteria necessary to continue to 
an expanded subgroup cohort or to begin a subsequent cohort have been met, or if halting criteria 
have been met, the ISM will be asked to review the data for independent assessment. Any SRC 
member can request an ISM review at any time. 
Procedures for the SRC and ISM reviews will be detailed in the SRC Charter. See Appendix 1 
for Sentinel Subgroup Halting Criteria, Individual Halting Criteria, and General Study Halting 
Criteria. Further information about safety assessments is in Section 8.3. 
10.1.7 
Clinical Monitoring 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants 
are protected, that the reported trial data are accurate, complete, and verifiable. Clinical 
Monitoring also ensures conduct of the trial is in compliance with the currently approved 
protocol/amendment(s), International Council for Harmonisation, Good Clinical Practice, and 
with applicable regulatory requirement(s) and IND sponsor requirements. 
Monitoring for this study will be performed by a representative of the IND sponsor. Details of 
clinical site monitoring are documented in a Clinical Monitoring Plan (CMP). The CMP 
describes in detail who will conduct the monitoring, at what frequency monitoring will be done, 
at what level of detail monitoring will be performed, and the distribution of monitoring reports. 
Monitoring visits will include, but are not limited to, review of regulatory files, accountability 
records, eCRFs, informed consent forms, medical and laboratory reports, site study intervention 
storage records, training records, and protocol and GCP compliance. Site monitors will have 
access to each participating site, study personnel, and all study documentation according to the 
site monitoring plan. Study monitors will meet with site principal investigators to discuss any 
problems and outstanding issues, and they will document site visit findings and discussions. 
10.1.8 
Quality Assurance and Quality Control 
To ensure the reliability of study data, each site will develop a Clinical Quality Management Plan 
(CQMP). The CQMP will describe: 
• Routine internal quality control (QC) and quality assurance (QA) activities 
o For the purposes of measuring, documenting and reporting study conduct, 
protocol adherence, human subjects’ protections, and reliability of the protocol- 
driven data collected; 
• A process for addressing in a timely manner any data quality issues (i.e., collecting, 
recording and reporting data), systemic issues (i.e., protocol conduct, non-compliance, 
human subject protections), and implementation of Corrective and Preventive Actions 
(CAPA) procedures. 
The PI will implement QC procedures beginning with the data entry system and generate data QC 

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checks that will be run on the database. Any missing data or data anomalies will be 
communicated to the PI and clinical team for prompt clarification and resolution. 
10.1.9 
Data Handling and Record Keeping 
10.1.9.1 
Data Collection and Management Responsibilities 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported. 
The site will maintain appropriate medical and research records in compliance with ICH E6, 
Section 4.9 and regulatory and institutional requirements for the protection of confidentiality of 
participants. The site will permit authorized representatives of the DMID and its designees, the 
IND sponsor and its designees, and appropriate regulatory agencies to examine (and when 
required by applicable law, to copy) clinical records for the purposes of quality assurance 
reviews, audits, and evaluation of the study safety and progress. These representatives will be 
permitted access to all source data and source documents, which include, but are not limited to, 
hospital records, clinical and office charts, laboratory notes, memoranda, participants’ paper 
Diary Cards or evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified after verification as being accurate and 
complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, and 
participant files and records kept at the pharmacy, at the laboratories, and medico-technical 
departments involved in the clinical trial. 
This study uses direct data entry for the participating clinic site and the eCRFs serve as the 
source documents for data collected. Data will be entered electronically over the Internet by site 
study staff into REDCap, developed and maintained by the SDCC. 
Participants will use a paper Diary Card. Participants will enter data into the paper Diary Card 
and review them with clinic staff during scheduled postvaccination phone calls (Days 3 and 31). 
Participants will also be asked to bring their paper Diary Card to postvaccination clinic appoints 
(Days 8 and 36) to review with study staff. The paper Diary Card is not considered source data. 
After clinic staff review and save the paper Diary Cards, the data will be entered into REDCap as 
source. 
Clinical (including, but not limited to, AE/SAEs, concomitant medications, medical history, vital 
signs, ECG data, physical assessments, and clinical laboratory values) will be entered into eCRFs 
via a 21 CFR Part 11-compliant internet data entry system provided by the SDCC. The data 
system includes password protection and internal quality checks, such as automatic range checks, 
to identify data that appear inconsistent, incomplete, or inaccurate. 
Site staff who are delegated the responsibility by the study PI will be the data originators for 
clinical data entered directly into the eCRF. A list of all authorized data originators, including site 
staff, will be included on the Study Personnel/Signature Responsibility List. 

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Data collection is the responsibility of the study personnel at the participating clinical study site 
under the supervision of the principal investigator. The investigator is responsible for ensuring 
the accuracy, completeness, legibility, and timeliness of the data reported. During the study, the 
principal investigator must maintain complete and accurate documentation for the study. The 
data coordinating center for this study will be responsible for data management, quality review, 
analysis, and reporting of the study data. 
The IND sponsor is responsible for review of data collection tools and processes, and review of 
data and reports. 
Adverse events will be coded according to the MedDRA dictionary Version 26.1. 
At the end of the study, a copy of all datasets including annotated case report forms and data 
dictionary will be provided to the IND sponsor. 
10.1.9.2 
Study Record Retention 
Study related records, including the regulatory file, study product accountability records, consent 
forms, participant source documents and electronic records should be maintained for a period of 
2 years following the date a marketing application is approved for the investigational product for 
the indication for which it is being investigated; or, if no application is to be filed or if the 
application is not approved for such indication, until 2 years after the investigation is 
discontinued and FDA is notified. These documents should be retained for a longer period, 
however, if required by local policies or regulations. No records will be destroyed without the 
written consent of the IND sponsor. Consent forms with specimen retention linked to identifiable 
specimens will be maintained for as long as the specimens remain in identifiable format, and a 
minimum of three years after use of the identifiable specimens in nonexempt human participant 
research. 
10.1.9.3 
Source Records 
Source data are all information in original records (and certified copies of original records) of 
clinical findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data should be attributable, legible, 
contemporaneous, original, accurate, and complete (ALCOA-C). Each participating site will 
maintain appropriate medical and research records for this trial, in compliance with ICH GCP 
E6(R2), regulatory, and institutional requirements. For this trial, the electronic medical record is 
considered source data. Data recorded in the eCRF derived from source documents should be 
consistent with the data recorded on the source documents. Interview of participants is sufficient 
for obtaining medical history. Solicitation of medical records from the participant’s primary care 
provider is not required. 
10.1.10 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, any process that is 

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noted in the protocol and refers to details in the MOP, or GCP requirements. The noncompliance 
may be either on the part of the participant, the investigator, or the study site staff. Following a 
deviation(s), corrective actions should be developed by the site and implemented promptly. All 
individual protocol deviations will be addressed in participant study records. 
It is the responsibility of the principal investigator and personnel to use continuous vigilance to 
identify and report deviations within five working days of identification of the protocol 
deviation, or within five working days of the scheduled protocol-required activity. All deviations 
must be promptly reported to the IND sponsor per the protocol deviation reporting procedures. 
Protocol deviations must be sent to the local IRB/IEC per their guidelines. The principal 
investigator and personnel are responsible for knowing and adhering to their IRB requirements. 
A completed copy of the Protocol Deviation Form must be maintained in the Regulatory File, as 
well as in the participant's chart if the deviation is participant specific. 
10.1.11 Publication and Data Sharing Policy 
Following completion of the study, results of this research will be published in a scientific 
journal. Data will be available immediately following publication, with no end date, with data 
sharing at the discretion of the IND sponsor. Publication may occur prior to completion of a final 
CSR for the entire trial. 
10.1.12 Human Data Sharing Plan 
This study will be conducted in accordance with the following publication and data sharing 
policies and regulations: 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has 
access to the published results of NIH funded research. It requires scientists to submit final peer- 
reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central 
upon acceptance for publication. 
10.1.13 Genomic Data Sharing Plan 
Not applicable 
10.1.14 Publication 
Following completion of the study, the PI is expected to publish the results of this research in a 
scientific journal. This study will adhere to the following publication and data sharing policies 
and regulations. This study will comply with the NIH Public Access Policy, which ensures that 
the public has access to the published results of NIH-funded research. As such, the final peer-
reviewed journal manuscripts will be accessible to the public on PubMed Central no later than 12 
months after publication. 
10.1.15 Conflict of Interest Policy 

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The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed 
and managed. Furthermore, persons who have a perceived conflict of interest will be required to 
have such conflicts managed in a way that is appropriate to their participation in the design and 
conduct of this trial. The study will follow DMID policies and procedures for all study group 
members to disclose all conflicts of interest. 
10.2 
Additional Considerations 
10.2.1 
Research Related Injuries 
If it is determined by the PI that an injury occurred to a participant as a direct result of the tests 
or treatments that are done for this study, then referrals to appropriate health care facilities will 
be provided to the participant. Study personnel will try to reduce, control, and treat any 
complications from this study. Immediate medical treatment may be provided by the 
participating site. No financial compensation will be provided by the NIAID, NIH, or the federal 
government to the participant, for any injury suffered due to participation in this trial. 
 
 

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10.3 
Abbreviations 
Abbreviation 
Definition 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
ALT 
Alanine Aminotransferase 
BMI 
Body Mass Index 
BP 
Blood Pressure 
CAPA 
Corrective and Preventative Actions 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CSR 
Clinical Study Report 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DMID 
Division of Microbiology and Infectious Diseases 
eCRF 
Electronic Case Report Forms 
ELISA 
Enzyme Linked Immunosorbent Assay 
ER 
Emergency Room 
FDA 
United States Food and Drug Administration 
FWA 
Federal Wide Assurance 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMFR 
Geometric Mean Fold Rise 
GMP 
Good Manufacturing Practices 
GMT 
Geometric Mean Titer 
HBV 
Hepatitis B 
HCG 
Human Chorionic Gonadotropin 
HCV 
Hepatitis C 
HDCV 
Human Diploid Cell Vaccine 
HIV 
Human Immunodeficiency Virus 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent or Institutional Ethics Committee 
IM 
Intramuscular 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ITT 
Intention-To-Treat 
LLOQ 
Lower Limit of Quantification 
MAAE 
Medically-Attended Adverse Events 
MedDRA 
Medical Dictionary for Regulatory Activities 

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MOP 
Manual of Procedures 
N 
Number (typically refers to participants) 
NOCMC 
New-Onset Chronic Medical Conditions 
NHP 
Nonhuman Primate 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
NOCMC 
New-Onset Chronic Medical Conditions 
NHP 
Nonhuman Primate 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
NOCMC 
New-Onset Chronic Medical Conditions 
OHRP 
Office for Human Research Protections 
PBMC 
Peripheral Blood Mononuclear Cell 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PII 
Personally Identifiable Information 
PIMMC 
Potentially Immune-Mediated Medical Condition 
QA 
Quality Assurance 
QC 
Quality Control 
RFFIT 
Rapid Fluorescent Foci Inhibition Test 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SRC 
Safety Review Committee 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TBILI 
Total Bilirubin 
UP 
Unanticipated Problem 
US 
United States 
USP 
US Pharmacopeia 
VAERS 
Vaccine Adverse Event Reporting System 
VTEU 
Vaccine Treatment and Evaluation Unit 
WBC 
White Blood Cells 
WHO 
World Health Organization 
TBILI 
Total Bilirubin 
UP 
Unanticipated Problem 
US 
United States 
USP 
US Pharmacopeia 
VAERS 
Vaccine Adverse Event Reporting System 
VTEU 
Vaccine Treatment and Evaluation Unit 
WBC 
White Blood Cells 
WHO 
World Health Organization 
 
 

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11. PROTOCOL AMENDMENT HISTORY 
Version 
Date 
Description of Change  
Brief Rationale 
2.0 
30 July 
2024 
N/A 
Original version submitted to IRB 
3.0 
23 
October 
2024 
Individual halting criteria added to the protocol 
Administrative 
The e-Memory Aid has been removed and replaced with a 
paper Diary Card 
Change made to address FDA concerns 
about the use of digital health 
technologies for collecting solicited AE 
data 
Added: “Seroconversion is defined as >4-fold rise in 
antibody titer...SAP.” 
Endpoint clarification 
Clarified that safety analysis will summarize outcomes by 
treatment received 
Endpoint clarification 
Rabies assay normal value changed to <0.148 IU/mL 
Change of rabies serology laboratory 
resulting in different normal cutoff 
Removed footnote and updated remaining footnote 
numbers 
Administrative 
Updated institutional name to “University of Maryland, 
Baltimore” 
Administrative 
Removed Objectives and Endpoints from this section; 
directed readers to Section 1.2 
Administrative 
Removed Inclusion and Exclusion Criteria from this 
section; directed readers to Section 1.2 
Administrative 
Added: “Study product will be administered within four 
hours of its preparation.” 
Administrative 
Extended the screening period to 60 days 
To accommodate turn-around time for 
screening rabies serology lab test 
Procedures may be performed up to 60 days prior to 
enrollment 
Administrative 
Expanded statement noting that study procedures, 
timelines, and acceptable time windows are in Section 1.2 
Administrative 
Removed reference to MOP, as protocol 
inclusion/exclusion criteria are sufficient 
Administrative 
Added: “The study will preferentially conduct an 
unscheduled visit in-person, but a phone visit is acceptable 
when necessary.” 
Administrative 
Clarified that SRC and ISM activities are detailed in the 
SRC Charter 
Administrative 
Updated list of abbreviations 
Better defines abbreviations used in the 
protocol 
Removed Section 10.4 (Protocol Amendment History) 
Administrative 
Harmonized blood draw timepoints and use 
Administrative 
4.0 
04 
December 
2024 
Clarified in Synopsis, Section 4, Section 6.1.1, and 
Section 6.2.2 that Treatment Group C receives two 
1400rU injections... 
Administrative 
Corrected Treatment Group C antigen dose in Section 
6.2.2 
Administrative 
Updated Section 6.2.7 to note that vaccine administrators 
will be unblinded but will not participate in endpoint 
assessments 
Administrative 
Added unblinding procedures for emergency cases in 
Section 6.3 
Administrative 
Edited Appendix 2 blood volume table due to change in 
safety lab volume from 8mL to 12mL 
Administrative 

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5.0 
21 
February 
2025 
Changed inclusion criterion #9 RFFIT threshold from 
<0.148 IU/mL to <0.5 IU/mL 
Updated to international reference 
value for seroprotection 
Corrected punctuation errors in exploratory objectives 
Administrative 
Changed exclusion criterion #8 rescreening window from 
28 to 60 days to harmonize document 
Administrative 
Edited Appendix 3 - WBC severity grading scale 
Clarified FDA grading scale for WBC 
increase; added WBC decrease per 
FDA guidance 
Edited Appendix C - WBC and platelet count grading 
scale 
Corrected values to align with reported 
units; previous values were off by a 
factor of 1000 
6.0 
13 June 
2025 
Synopsis and Section 4.1 clarified interim analysis plans, 
including database freeze 
Administrative 
Synopsis, Section 4.1, and Section 9.4 corrected error 
from version 4.0 to clarify that vaccine administrators will 
not be blinded 
Error correction 
Added Protocol Amendment History section 
Administrative 
Schedule of Activities updated to include activities to be 
undertaken by enrolled participants who do not receive 
Vaccination #2 
Administrative 
Throughout punctuation, formatting, and changes for 
sense 
Administrative 
 
 
 
 

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12. REFERENCES 
1. Centers for Disease Control and Prevention. Lassa Fever Accessed 3/23/24, 
https://www.cdc.gov/vhf/lassa/pdf/lassa-factsheet-508.pdf 
2. Centers for Disease Control and Prevention. Lassa Fever. Accessed 3/23/24, 
https://www.cdc.gov/vhf/lassa/index.html 
3. Purushotham J, Lambe T, Gilbert SC. Vaccine platforms for the prevention of Lassa fever. 
Immunol Lett. Nov 2019;215:1-11. doi:10.1016/j.imlet.2019.03.008  
4. Kurup D, Fisher CR, Scher G, et al. Tetravalent Rabies-Vectored Filovirus and Lassa Fever 
Vaccine Induces Long-term Immunity in Nonhuman Primates. J Infect Dis. Sep 17 
2021;224(6):995-1004. doi:10.1093/infdis/jiab014 
5. Mateo M, Reynard S, Journeaux A, et al. A single-shot Lassa vaccine induces long-term 
immunity and protects cynomolgus monkeys against heterologous strains. Sci Transl Med. 
Jun 9 2021;13(597)doi:10.1126/scitranslmed.abf6348 
6. Abreu-Mota T, Hagen KR, Cooper K, et al. Non-neutralizing antibodies elicited by 
recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever. Nat 
Commun. Oct 11 2018;9(1):4223. doi:10.1038/s41467-018-06741-w 
7. World Health Organization. WHO target product profile for Lassa virus Vaccine. Lassa 
fever R&D https://www.who.int/teams/blueprint/lassa-fever. 2017 
8. Blaney JE, Wirblich C, Papaneri AB, et al. Inactivated or live-attenuated bivalent vaccines 
that confer protection against rabies and Ebola viruses. J Virol. Oct 2011;85(20):10605-16. 
doi:10.1128/jvi.00558-11 
9. Kurup D, Malherbe DC, Wirblich C, et al. Inactivated rabies virus vectored SARS-CoV-2 
vaccine prevents disease in a Syrian hamster model. PLoS Pathog. Mar 
2021;17(3):e1009383. doi:10.1371/journal.ppat.1009383 
10. Tschismarov R, Van Damme P, Germain C, et al. Immunogenicity, safety, and tolerability 
of a recombinant measles-vectored Lassa fever vaccine: a randomised, placebo- controlled, 
first-in-human trial. Lancet. Apr 15 2023;401(10384):1267-1276. doi:10.1016/s0140- 
6736(23)00048-x 
11. Wu CJ, Chou HW, Liou CJ, Shen JJ, Wang LC, Kuo ML. Prophylactic vaccination with 
adjuvant monophosphoryl lipid a prevents Th2-mediated murine asthmatic responses. J 
Asthma. May 2013;50(4):327-33. doi:10.3109/02770903.2013.769268 
12. Chen C, Zhang C, Li R, et al. Monophosphoryl-Lipid A (MPLA) is an Efficacious 
Adjuvant for Inactivated Rabies Vaccines. Viruses. Dec 3 
2019;11(12)doi:10.3390/v11121118 
13. Casella CR, Mitchell TC. Putting endotoxin to work for us: monophosphoryl lipid A as a 
safe and effective vaccine adjuvant. Cell Mol Life Sci. Oct 2008;65(20):3231-40. 
doi:10.1007/s00018-008-8228-6 
14. Coler RN, Bertholet S, Moutaftsi M, et al. Development and characterization of synthetic 
glucopyranosyl lipid adjuvant system as a vaccine adjuvant. PLoS One. Jan 26 
2011;6(1):e16333. doi:10.1371/journal.pone.0016333 
15. Coler RN, Baldwin SL, Shaverdian N, et al. A synthetic adjuvant to enhance and expand 
immune responses to influenza vaccines. PLoS One. Oct 27 2010;5(10):e13677. 
doi:10.1371/journal.pone.0013677 
16. Coler RN, Day TA, Ellis R, et al. The TLR-4 agonist adjuvant, GLA-SE, improves 
magnitude and quality of immune responses elicited by the ID93 tuberculosis vaccine: 
first-in- human trial. NPJ Vaccines. 2018;3:34. doi:10.1038/s41541-018-0057-5 

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17. Laupeze B, Herve C, Di Pasquale A, Tavares Da Silva F. Adjuvant Systems for vaccines: 
13 years of post-licensure experience in diverse populations have progressed the way 
adjuvanted vaccine safety is investigated and understood. Vaccine. Sep 10 
2019;37(38):5670-5680. doi:10.1016/j.vaccine.2019.07.098 
18. Phan T, Devine C, Laursen ED, et al. Squalene Emulsion Manufacturing Process Scale- Up 
for Enhanced Global Pandemic Response. Pharmaceuticals (Basel). Jul 28 
2020;13(8)doi:10.3390/ph13080168  
19. Beck Z, Matyas GR, Jalah R, Rao M, Polonis VR, Alving CR. Differential immune 
responses to HIV-1 envelope protein induced by liposomal adjuvant formulations 
containing monophosphoryl lipid A with or without QS21. Vaccine. Oct 13 
2015;33(42):5578-5587. doi:10.1016/j.vaccine.2015.09.001 
20. Alving CR, Peachman KK, Matyas GR, Rao M, Beck Z. Army Liposome Formulation 
(ALF) family of vaccine adjuvants. Expert Rev Vaccines. Mar 2020;19(3):279-292. 
doi:10.1080/14760584.2020.1745636 
21. Plc CI. 699800 | MPLA (PHAD®). Accessed 4/25/24, 
https://avantilipids.com/product/699800 
22. Plc CI. 699852 | 3D-PHAD®. Accessed 4/25/24, https://avantilipids.com/product/699852 
23. Carol Liu YC, Ibekwe T, Kelso JM, et al. Sensorineural hearing loss (SNHL) as an adverse 
event following immunization (AEFI): Case definition & guidelines for data collection, 
analysis, and presentation of immunization safety data. Vaccine. Jun 19 2020;38(30):4717-
4731. doi:10.1016/j.vaccine.2020.05.019 
24. Centers for Disease Control and Prevention. Rabies Information for Specific Groups. 
Accessed 3/23/2024, 
https://www.cdc.gov/rabies/specific_groups/hcp/adverse_reaction.html 
 
 
 

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13. APPENDICES 
Appendix 1. Sentinel Subgroup Halting Criteria, Individual Halting Criteria, and General 
Study Halting Criteria 
Sentinel Subgroup Halting Criteria 
Enrollment and study interventions/administration of study products will be halted for ISM 
review/recommendation if any of the following are reported during the 7-day observation period 
of sentinel subgroup participants after the first vaccination of Cohorts 1, 2, and 3: 
1. Any participant experiences ulceration, abscess, or necrosis at the vaccination site that is 
considered related to study product administration. 
2. Any participant experiences laryngospasm, bronchospasm or anaphylaxis within 24 hours 
after administration of study product that is considered related to study product. 
3. Any participant experiences generalized urticaria (defined as occurring at more than two 
body parts) within 72 hours after administration of study product that is considered related 
to study product. 
4. Any participant experiences an SAE after administration of study product that is 
considered related to study product. 
5. Any participant experiences acute weakness of limbs and/or cranial nerve innervated 
muscles (description of potential signal of GBS) after administration of study product. 
6. Any participant experiences a grade 3 vaccination site or systemic solicited adverse event 
(excluding measured grades of erythema and induration alone). 
Individual Halting Criteria 
The study intervention will be discontinued in an individual if: 
1. The participant experiences a hypersensitivity reaction considered related to study product. 
2. The participant experiences ulceration, abscess, or necrosis at the vaccination site that is 
considered related to study product administration.  
3. The participant experiences laryngospasm, bronchospasm or anaphylaxis within 24 hours 
after administration of study product that is considered related to study product.  
4. The participant experiences generalized urticaria (defined as occurring at more than two 
body parts) within 72 hours after administration of study product that is considered related 
to study product.  
5. The participant experiences an SAE after administration of study product that is considered 
related to study product.  
6. The participant experiences a grade 3 or greater adverse event (including laboratory tests) 
considered related to study product. 
7. The participant becomes pregnant.  
8. If the participant met an exclusion criterion for participation in the study (either newly 
developed or not previously recognized) that precludes further study participation. 
9. The participant develops a PIMMC or AESI after administration of study product. 
10. If any clinical adverse event (AE), laboratory abnormality, or other medical condition or 
situation occurs such that continued participation in the study would not be in the best 
interest of the participant. 
11. Medical disease or condition, or new clinical finding(s) for which continued participation, 
in the opinion of the investigator might compromise the safety of the participant, interfere 

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with the participant's successful completion of this study, or interfere with the evaluation of 
responses. 
General Study Halting Criteria 
Enrollment and study interventions/administration of study products in this trial will be halted for 
ISM review/recommendation if any of the following are reported during the trial: 
1. Any participant experiences an SAE after administration of study product that is 
considered related to study product. 
2. Any participant experiences ulceration, abscess or necrosis at the vaccination site that is 
considered related to study product administration. 
3. Any participant experience laryngospasm, bronchospasm, or anaphylaxis within 24 hours 
after administration of study product that is considered related to study product. 
4. Two or more participants experience an allergic reaction such as generalized urticaria 
(defined as occurring at two or more body parts) after administration of vaccine that is 
considered related to vaccine. 
5. Two or more participants experience the same Grade 3 laboratory adverse event that is 
considered related to study product. 
6. Two (2) or more participants experience a Grade 3 AE (unsolicited) related to vaccine 
administration, in the same or similar Preferred Terms based on the Medical Dictionary for 
Regulatory Activities (MedDRA) coding. 
7. Any participant experiences acute weakness of limbs and/or cranial nerve innervated 
muscles (description of potential signal of GBS) after administration of study product. 
8. Any participant develops a PIMMC or AESI after administration of study product. 
9. Two (2) participants or more experience a grade 3 vaccination site or systemic solicited 
adverse event. 
 

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Appendix 2. Schedule of Blood Draws and Volumes 
Procedures1 
Screening  
Study Visit 0 
Day -60 to Day -1 
Vaccination #1 
Study Visit 1 
Day 1 
Study Visit 2 
Day 3 (±1) 
Study Visit 3 
Day 8 (±3) 
Study 
Visit 4 
Day 22 
(±7) 
Vaccination #2 
Study Visit 5 
Day 29 (±3) 
Study Visit 6 
Day 31 (±3) 
Study Visit 7 
Day 36 (±3) 
Study Visit 8 
Day 61 (±3) 
Study Visit 9 
Day 121 (±14) 
Study Visit 10 
Day 210 (±14) 
Study Visit 11 
Day 394 (±14) 
Unscheduled Visit2 
Early Termination 
Visit2 
Type of Visit 
Clinic 
Clinic 
Phon
e 
Clinic Clinic Clinic 
Phon
e 
Clinic Clinic Clinic 
Phon
e 
Clinic 
Clinic 
Clinic 
Clinical 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Hematology/Chemistries 
8 
 
 
12 
 
 
 
12 
12 
 
 
 
12 
12 
• HIV, HCV, HbsAg, 
Serum Pregnancy Test 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Rabies neutralization 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total clinical blood volume 
(scheduled) 
16 
 
 
12 
 
 
 
12 
12 
 
 
 
12 
12 
Immunology 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• IgG ELISA 
 
15 
 
15 
 
15 
 
15 
15 
15 
 
15 
15 
15 
• PBMC 
 
80 
 
50 
 
50 
 
50 
50 
50 
 
50 
50 
50 
Total immunology blood 
volume 
 
95 
 
65 
 
65 
 
65 
65 
65 
 
65 
65 
65 
Total visit volume 
16 
95 
N/A 
77 
N/A 
65 
N/A 
77 
77 
65 
N/A 
65 
77 
77 
Cumulative volume3 
16 
111 
111 
188 
188 
253 
253 
330 
407 
472 
472 
537 
 
 
1. Volumes are in milliliters (mL), are approximate, and may be adjusted to meet the clinical site’s requirements. 
2. Blood draws at the investigator discretion.  
3. Total scheduled blood volume is approximately 537mL per participant over the 13-month trial participation. 
 

Protocol 23-0015 
CVD LASSARAB+aPHAD-SE 
Version 5.0 
21 February 2025 
 
DMID/NIAID/NIH 
Confidential 
Page 75 of 79 
 
Appendix 3: Grading Scale for Clinical Laboratory Values 
 
Grade for Abnormal Results 
Parameter 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Creatinine (mg/dL) 
1.5 – 1.7 
1.8 – 2.0 
2.1 – 2.5 
> 2.5 or requires 
dialysis 
Total bilirubin 
(mg/dL) 
1.1 – 1.5 x ULN* 
1.1 – 1.25 x ULN** 
1.6 – 2.0 x ULN* 
1.26 – 1.5 x ULN** 
2.0 – 3.0 x ULN* 
1.51 – 1.75 x 
ULN** 
> 3.0 x ULN* 
> 1.75 x ULN** 
ALT (SGPT) (U/L) 
1.1 – 2.5 x ULN 
2.6 – 5.0 x ULN 
5.1 – 10 x ULN 
> 10 x ULN 
WBC Increase- 
(K/µL, K/mm3 or 
109/L) 
10.800 – 15.000 
 
15.001 – 20.000 
 
20.001 – 25. 000 
 
> 25.000 
 
WBC Decrease-  
(K/µL, K/mm3 or 
109/L) 
2.500 – 3.500 
 
1.500 – 2.499 
 
1.000 – 1.499 
 
< 1.000 
 
Hemoglobin (g/dL) 
M: 12.5 – 13.5 
F: 11.0 – 12.0 
M: 10.5 – 12.4 
F: 9.5 – 10.9 
M: 8.5 – 10.4 
F: 8.0 – 9.4 
M: < 8.5  
F: < 8.0 
Platelet count (K/µL, 
K/mm3 or 109/L) 
125.000 – 140.000 
100.000 – 124.000 
25.000 – 99.000 
< 25.000 
Note: ULN=upper limit of normal; LLN=lower limit of normal.  
1 FDA Guidance for Industry Toxicity Grading Scale for Healthy Adults Enrolled in Preventive Vaccine Clinical 
Trials, 2007. 
* Tox grading for total bilirubin when liver transaminases are normal.  
** Tox grading for total bilirubin when accompanied by increased transaminases. 
 
 
 
 

Protocol 23-0015 
CVD LASSARAB+aPHAD-SE 
Version 6.0 
13 June 2025 
 
DMID/NIAID/NIH 
Confidential 
Page 76 of 79 
 
Appendix 4: Grading Scale for Local Injection Site Reactions 
Local Reaction to 
Injectable Product 
Grade 1 (Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Potentially Life 
Threatening 
(Grade 4) 
Pain 
Does not interfere 
with activity 
Repeated use of 
nonnarcotic 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 
Note: Local injection site reaction grading should not be confused with general AE grading. 
* 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. 
 
 
 
 

Protocol 23-0015 
CVD LASSARAB+aPHAD-SE 
Version 6.0 
13 June 2025 
 
DMID/NIAID/NIH 
Confidential 
Page 77 of 79 
 
Appendix 5: Grading Scale for Determining the Severity of Abnormal Vital Signs 
Vital Signs* 
Mild  
(Grade 1) 
Moderate 
(Grade 2) 
Severe  
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Fever: oral (˚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 – bpm 
101 – 115 
116 – 130 
> 130 
ER visit or hospitalization 
for arrhythmia 
Bradycardia*** – bpm 
50 – 54 
45 – 49 
< 45 
ER visit or hospitalization 
for arrhythmia 
Hypertension (systolic) 
mm Hg 
141 – 150 
151 – 155 
> 155 
ER visit or hospitalization 
for malignant hypertension 
Hypertension (diastolic) 
mm Hg 
91 – 95 
96 – 100 
> 100 
ER visit or hospitalization 
for malignant hypertension 
Hypotension (systolic) 
mm Hg 
85 – 89 
80 – 84 
< 80 
ER visit or hospitalization 
for hypotensive shock 
Respiratory Rate– 
breaths per minute  
17 – 20  
21 – 25  
> 25  
Intubation 
* Participants should be at rest for at least 5 minutes prior to vital sign measurements 
** Oral temperature; no recent hot or cold beverages or smoking. Note: A fever can be considered not related to the 
study product if an alternative etiology can be documented and it is confirmed to be not related to the study product 
by the Independent Safety Monitor at the site. 
*** When resting heart rate is between 60-100 beats per minute. Use clinical judgment when characterizing 
bradycardia among some healthy participant populations, for example conditioned athletes. 
 
 
 
 
 

Protocol 23-0015 
CVD LASSARAB+aPHAD-SE 
Version 6.0 
13 June 2025 
 
DMID/NIAID/NIH 
Confidential 
Page 78 of 79 
 
Appendix 6: Grading Scale for Determining the Severity of Clinical AEs 
Systemic 
(General) 
Mild  
(Grade 1) 
Moderate  
(Grade 2) 
Severe  
(Grade 3)  
Potentially Life 
Threatening 
(Grade 4) 
Headache 
Does not interfere 
with activity 
Repeated use of 
non-narcotic pain 
reliever >24 hours 
or interferes with 
activity 
Significant; any use 
of narcotic pain 
reliever or prevents 
daily activity 
ER visit or 
hospitalization  
Fatigue 
Does not interfere 
with activity 
Interferes with 
activity 
Significant; 
prevents daily 
activity 
ER visit or 
hospitalization  
Myalgia 
(generalized 
muscle pain) 
Does not interfere 
with activity 
Interferes with 
activity 
Significant; 
prevents daily 
activity 
ER visit or 
hospitalization  
Arthralgia (joint 
pain) 
Does not interfere 
with activity 
Interferes with 
activity 
Prevents daily 
activity 
ER visit or 
hospitalization  
Chills 
Does not interfere 
with activity 
Interferes with 
activity 
Prevents daily 
activity 
ER visit or 
hospitalization  
Anorexia (loss of 
appetite) 
Does not interfere 
with activity 
Interferes with 
activity 
Prevents daily 
activity 
ER visit or 
hospitalization  
Nausea/Vomiting 
Does not interfere 
with activity or 1 – 
2 episode in 24 
hours 
Interferes with 
activity or >2 
episodes in 24 
hours 
Prevents daily 
activity or requires 
outpatient IV 
hydration 
ER visit or 
hospitalization  
Diarrhea 
2-3 loose stools or 
< 400 grams/24 h  
4-5 stools or 400-
800 grams/24 hours 
6 or more watery 
stools or >800 
grams/24 hours or 
requires outpatient 
IV hydration 
ER visit or 
hospitalization  
 
 
 
 

Protocol 23-0015 
CVD LASSARAB+aPHAD-SE 
Version 6.0 
13 June 2025 
 
DMID/NIAID/NIH 
Confidential 
Page 79 of 79 
 
Appendix 7: List of PIMMCs 
This list is provided by U.S. FDA/CBER and is participant to periodic update. Any updates will be implemented via 
a Note to File. The investigator should exercise their clinical judgement as to whether other diseases or conditions 
that do not appear on this list are autoimmune or autoinflammatory in nature and should be reported as a PIMMC. 
Gastrointestinal disorders 
Liver disorders 
Metabolic diseases 
• Celiac disease 
• Crohn’s disease 
• Ulcerative colitis 
• Ulcerative proctitis 
• Autoimmune cholangitis 
• Autoimmune hepatitis 
• Primary biliary cirrhosis 
• Primary sclerosing cholangitis 
• Addison’s disease 
• Autoimmune thyroiditis 
(including Hashimoto 
thyroiditis) 
• Diabetes mellitus type I 
• Grave’s or Basedow’s 
disease 
Neuroinflammatory disorders 
Musculoskeletal disorders 
Skin disorders 
• Acute disseminated encephalomyelitis, 
including site specific variants (e.g., non-
infectious encephalitis, encephalomyelitis, 
myelitis, radiculomyelitis) 
• Cranial nerve disorders, included 
paralyses/paresis (e.g., Bell’s palsy) 
• Guillain-Barré syndrome, including Miller 
Fisher syndrome and other variants 
• Immune-mediated peripheral neuropathies and 
plexopathies, including chronic inflammatory 
demyelinating polyneuropathy, multifocal 
motor neuropathy and polyneuropathies 
associated with monoclonal gammopathy 
• Multiple sclerosis 
• Myasthenia gravis, including Eaton-Lambert 
syndrome 
• Narcolepsy 
• Optic neuritis 
• Transverse myelitis 
• Antisynthetase syndrome 
• Dermatomyositis 
• Juvenile chronic arthritis (including 
Still’s disease) 
• Mixed connective tissue disorder 
• Polymyalgia rheumatic 
• Polymyositis 
• Psoriatic arthropathy 
• Relapsing polychondritis 
• Rheumatoid arthritis 
• Scleroderma, including diffuse 
systemic form and CREST syndrome 
• Spondyloarthritis, including 
ankylosing spondylitis, reactive 
arthritis (Reiter’s Syndrome) and 
undifferentiated spondyloarthritis 
• Systemic lupus erythematosus 
• Systemic sclerosis 
• Alopecia areata 
• Autoimmune bullous skin 
diseases, including 
pemphigus, pemphigoid and 
dermatitis herpetiformis 
• Cutaneous lupus 
erythematosus 
• Erythema nodosum 
• Morphoea 
• Lichen planus 
• Psoriasis 
• Rosacea 
• Sweet’s syndrome 
• Vitiligo 
Vasculitides 
Others 
• Large vessels vasculitis including: giant cell 
arteritis such as Takayasu’s arteritis and 
temporal arteritis 
• Medium sized and/or small vessels vasculitis 
including: polyarteritis nodosa, Kawasaki’s 
disease, microscopic polyangiitis, Wegener’s 
granulomatosis, Churg-Strauss syndrome 
(allergic granulomatous angiitis), Buerger’s 
disease thromboangiitis obliterans, necrotizing 
vasculitis and anti-neutrophil cytoplasmic 
antibody (ANCA) positive vasculitis (type 
unspecified), Henoch-Schonlein purpura, 
Behcet’s syndrome, leukocytoclastic vasculitis 
• Antiphospholipid syndrome 
• Autoimmune hemolytic anemia 
• Autoimmune glomerulonephritis (including IgA nephropathy, 
glomerulonephritis rapidly progressive, membranous 
glomerulonephritis, membranoproliferative glomerulonephritis, and 
mesangioproliferative glomerulonephritis) 
• Autoimmune myocarditis/cardiomyopathy 
• Autoimmune thrombocytopenia 
• Goodpasture syndrome 
• Idiopathic pulmonary fibrosis 
• Pernicious anemia 
• Raynaud’s phenomenon 
• Sarcoidosis 
• Sjögren’s syndrome 
• Stevens-Johnson syndrome 
• Uveitis