Clinical trial NCT04171115
Conditions: Healthy
Keywords: botulinum toxin botulism
Sponsor: Resilience Government Services, Inc.
Start date: 2020-06-01; Completion date: 2023-04-05
Enrollment: 40 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
A Phase 1, randomized, double-blind, placebo-controlled dose escalation trial of four dose cohorts of 10 subjects (1: 10mg, 2: 25mg, 3: 50mg, 4: 100mg).

Detailed description:
A Phase 1, randomized, double-blind, placebo-controlled dose escalation trial of four dose cohorts of 10 subjects (1: 10mg, 2: 25mg, 3: 50mg, 4: 100mg). Dose escalation will not occur until safety data through Day 8 is reviewed by the Safety Review Committee (SRC). The study will consist of a twenty-eight day screening period, 12-hour clinic stay, and 120-day (Cohorts 1-3) or 180-day (Cohort 4) outpatient follow-up. The primary objective of this study is to assess the safety and tolerability of escalating doses of G03-52-01 administered intramuscularly (IM) in healthy adult subjects. The secondary objectives are to evaluate the pharmacokinetics (PK) and immunogenicity of escalating IM doses of G03-52-01.

Arms: arm 1: 8 subjects randomized to 10 mg of G03-52-01 and 2 subjects randomized to placebo arm 2: 8 subjects randomized to 25 mg of G03-52-01 and 2 subjects randomized to placebo arm 3: 8 subjects randomized to 50 mg of G03-52-01 and 2 subjects randomized to placebo arm 4: 8 subjects randomized to 100 mg of G03-52-01 and 2 subjects randomized to placebo
Interventions: intervention 1: G03-52-01 intervention 2: Placebo
Intervention descriptions: intervention 1: G03-52-01 administered intramuscularly intervention 2: Placebo administered intramuscularly

Protocol documents:
Prot_000.pdf: 
Ology Bioservices, Inc. 
 
Proprietary 
 
A Phase 1, Randomized, Double-Blind, Dose Escalation Study to Evaluate the 
Safety and Pharmacokinetics of a Single IM Dose of G03-52-01 vs Placebo in 
Adult Subjects. 
 
Ology Bioservices Protocol Number:  G03-52-01.001 
 
IND Sponsor: Ology Bioservices, Inc. 
 
Principal Investigator: Cassandra Key, MD  
Medical Monitor: Uma Arumugam, MD 
 
 
 
Version 3.0 
September 7, 2021 
 


Protocol: G03-52-01.001 
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STATEMENT OF COMPLIANCE 
The study will be carried out in accordance with Good Clinical Practices (GCP) as required by 
the following: 
• United States Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46; 21 CFR Part 50, 21 CFR Part 54, 21 CFR Part 56, and 21 CFR Part 
312); 
• International Conference on Harmonization (ICH) E6; 62 Federal Register 25691 
(1997); 
• Department of Defense (DOD) Clinical Terms of Award, as applicable. 
• Applicable Laws and Regulations 
Compliance with these standards provides public assurance that the rights, safety and well-being 
of study subjects are protected, consistent with the principles that have their origin in the 
Declaration of Helsinki. 
All key personnel (all individuals responsible for the design and conduct of this study) have 
completed Human Subjects Protection Training. 


Protocol: 003-52-01.00 I 
Signature Page 
Version 3.0 
September 7, 2021 
The signature below constitutes the approval of this protocol and the attachments and provides 
the necessary assurances that this trial will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable United States of America (US) federal regulations and 
ICH guidelines. 
Site Investigator: Cassandra Key, MD I Principal Investigator 
Signature: 
Date: 
Sponsor: 
John Abernethy, MD I Medical Director 
Signature: 
Date: 
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Protocol: G03-52-01.001 
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TABLE OF CONTENTS 
STATEMENT OF COMPLIANCE .................................................................................................2 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF ABBREVIATIONS ..........................................................................................................9 
SUMMARY OF CHANGES FOR VERSION 3.0 ........................................................................13 
SUMMARY OF CHANGES FOR VERSION 2.0 ........................................................................28 
PROTOCOL SUMMARY .............................................................................................................32 
1. 
KEY ROLES ..............................................................................................................37 
2. 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ...................37 
2.1. 
Background Information .............................................................................................39 
2.1.1. 
Introduction .................................................................................................................39 
2.1.2. 
Currently Available Treatments .................................................................................39 
2.1.3. 
G03-52-01 Development ............................................................................................40 
2.1.4. 
Public Readiness and Emergency Preparedness Act ..................................................41 
2.2. 
Rationale For Use of G03-52-01 ................................................................................42 
2.3. 
Potential Risks and Benefits .......................................................................................43 
2.3.1. 
Potential Risks ............................................................................................................43 
2.3.2. 
Known Potential Benefits ...........................................................................................44 
3. 
OBJECTIVES .............................................................................................................44 
3.1. 
Study Objectives .........................................................................................................44 
3.2. 
Study Outcome Measures ...........................................................................................45 
3.2.1. 
Primary Endpoints ......................................................................................................45 
3.2.2. 
Secondary Endpoints ..................................................................................................45 
4. 
STUDY DESIGN .......................................................................................................45 
4.1.1 Subject Inclusion Criteria .....................................................................................................47 
4.1.2 Subject Exclusion Criteria ....................................................................................................48 
4.2 Treatment Assignment Procedures ..........................................................................................50 
4.2.1 Randomization Procedures ...................................................................................................50 
4.2.2 Masking Procedures ..............................................................................................................51 
4.2.3 Reasons for Withdrawal ........................................................................................................51 
4.2.4 Handling of Withdrawals ......................................................................................................52 
4.2.5 Lost to Follow-up ..................................................................................................................52 


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4.2.6 Termination of Study ............................................................................................................52 
5. 
STUDY PRODUCTS .................................................................................................52 
5.1. 
Description of Study Products ....................................................................................52 
5.2. 
Acquisition ..................................................................................................................52 
5.3. 
Formulation, Packaging, and Labeling .......................................................................53 
5.4. 
Product Storage and Stability .....................................................................................53 
5.5. 
Dosage, Preparation and Administration ....................................................................53 
5.6. 
Accountability Procedures for the Study Products .....................................................54 
5.7. 
Assessment of Subject Compliance with Study Product ............................................54 
5.8. 
Concomitant Medications ...........................................................................................54 
6. 
STUDY PROCEDURES ............................................................................................55 
6.1. 
Medical History ..........................................................................................................55 
6.2. 
Physical Examination .................................................................................................55 
6.3. 
Vital Signs ..................................................................................................................56 
6.4. 
Electrocardiogram .......................................................................................................56 
6.5. 
Laboratory Evaluations ...............................................................................................56 
6.5.1. 
Screening Laboratory Tests ........................................................................................56 
6.5.1.1. 
Viral Serology Testing ................................................................................................56 
6.5.2. 
Safety Laboratory Tests ..............................................................................................57 
6.5.3. 
Hypersensitivity Panel ................................................................................................58 
6.6. 
Special Assays or Procedures .....................................................................................58 
6.6.1. 
Pharmacokinetic Assay ...............................................................................................58 
6.6.2. 
Anti-Drug Antibody Assay .........................................................................................58 
6.6.3. 
Future Use ...................................................................................................................58 
6.6.4. 
Specimen Preparation, Handling, and Shipping .........................................................58 
7. 
STUDY SCHEDULE .................................................................................................61 
7.1. 
Visit 1: Screening (Day -28 to Day -3) .......................................................................61 
7.2. 
Visit 2: Baseline (Day 0) ............................................................................................62 
7.3. 
Visit 3: Out-patient Follow-up (24 hours/Day 1) .......................................................63 
7.4. 
Visit 4: Out-patient follow-up Visit (48 hours/Day 2) ...............................................63 
7.5. 
Visit 5: Out-patient Follow-up (72 hours) Cohorts 1-3 ..............................................64 
7.6. 
Visit 6: Out-patient Follow-up (Day 4) ......................................................................64 


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7.7. 
Visit 7: Out-patient Follow-up (Day 8± 1) .................................................................64 
7.8. 
Visit 8: Out-patient Follow-up (Day 15± 1) ...............................................................65 
7.9. 
Visit 9: Out-patient Follow-up (Day 30 ± 1) ..............................................................65 
7.10. 
Visit 10: Out-patient Follow-up (Day 45± 3) .............................................................66 
7.11. 
Visit 11: Out-patient Follow-up (Day 60 ± 3) ............................................................66 
7.12. 
Visit 12: Out-patient Follow-up (Day 90±3) ..............................................................67 
7.13. 
Visit 13: Final Visit / Early Termination Visit for Cohorts 1-3 (Day 120±3)  / 
Cohort 4 (Day 120±3) .................................................................................................67 
7.14. 
Visit 14: Final Visit/ Early Termination for Subjects in Cohort 4  (Day 
180±3) .........................................................................................................................68 
7.15. 
Unscheduled Visit .......................................................................................................68 
8. 
ASSESSMENT OF SAFETY .....................................................................................69 
8.1. 
Specification of Safety Parameters .............................................................................69 
8.2. 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters ...................................................................................................................70 
8.2.1. 
Adverse Events ...........................................................................................................70 
8.2.2. 
Relationship to Study Product ....................................................................................70 
8.3. 
Reporting Procedures ..................................................................................................71 
8.3.1. 
Adverse Events: ..........................................................................................................71 
8.3.2. 
Serious Adverse Events ..............................................................................................71 
8.3.3. 
Regulatory Reporting ..................................................................................................72 
8.3.4. 
Reporting of Pregnancy ..............................................................................................73 
8.4. 
Type and Duration of Follow-up of Subjects after Adverse Events ...........................73 
8.5. 
Halting Rules ..............................................................................................................73 
8.5.1. 
Halting Criteria for the Study .....................................................................................73 
8.5.2. 
Dose Escalation Halting Criteria ................................................................................73 
8.5.3. 
Evaluation of Dose Escalation ....................................................................................74 
8.6. 
Safety Oversight .........................................................................................................74 
8.6.1. 
Independent Safety Monitor (ISM) ............................................................................74 
8.6.2. 
ICON Medical Monitor ..............................................................................................74 
8.6.3. 
Ology Bioservices Medical Monitor ..........................................................................74 
8.6.4. 
Safety Review Committee (SRC) ...............................................................................74 
9. 
CLINICAL MONITORING .......................................................................................75 


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9.1. 
Site Monitoring Plan ...................................................................................................75 
10. 
STATISTICAL CONSIDERATIONS .......................................................................75 
10.1. 
Sample Size Considerations .......................................................................................75 
10.2. 
Planned Interim Analyses ...........................................................................................76 
10.3. 
Final Analysis Plan .....................................................................................................76 
10.3.1. 
Analysis Populations ..................................................................................................76 
10.3.2. 
Demographics and Baseline Characteristics ...............................................................76 
10.3.3. 
Safety Analysis Plan ...................................................................................................76 
10.3.3.1. 
Adverse and Serious Adverse Events .........................................................................76 
10.3.3.2. 
Additional Safety Analyses ........................................................................................77 
10.3.4. 
PK Analysis Plan ........................................................................................................77 
10.3.5. 
Immunogenicity ..........................................................................................................77 
10.3.6. 
Missing values and outliers ........................................................................................78 
11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS ...............................................................................................79 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................79 
13. 
ETHICS/PROTECTION OF HUMAN SUBJECTS ..................................................80 
13.1. 
Ethical Standard ..........................................................................................................80 
13.2. 
Institutional Review Board .........................................................................................80 
13.3. 
Informed Consent Process ..........................................................................................80 
13.3.1. 
Informed Consent .......................................................................................................80 
13.4. 
Exclusion of Women, Minorities, and Children (Special Populations) ......................81 
13.5. 
Subject Confidentiality ...............................................................................................82 
13.6. 
Study Discontinuation ................................................................................................82 
13.7. 
Future Use of Stored Specimens .................................................................................82 
14. 
DATA HANDLING AND RECORD KEEPING ......................................................82 
14.1. 
Data Management Responsibilities ............................................................................83 
14.2. 
Data Capture Methods ................................................................................................83 
14.3. 
Types of Data ..............................................................................................................83 
14.4. 
Timing/Reports ...........................................................................................................83 
14.5. 
Study Records Retention ............................................................................................83 
14.6. 
Protocol Deviations ....................................................................................................84 


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15. 
PUBLICATION POLICY ..........................................................................................84 
16. 
LITERATURE REFERENCES..................................................................................85 
 
  
 
 
 


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LIST OF ABBREVIATIONS 
ADA 
Anti-Drug Antibody 
AE 
Adverse Event/Adverse Experience 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area Under the Curve 
BMI 
Body Mass Index 
BoNT 
Botulinum Neurotoxin 
BP 
Blood Pressure 
Bpm 
Beats per Minute 
BUN 
Blood Urea Nitrogen 
CAR 
Clinical Agents Repository 
CBC 
Complete Blood Count 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CHO 
Chinese hamster ovary 
Cmax 
Maximum Plasma Titer/Concentration 
CPM  
Clinical Project Manager 
CROMS 
Clinical Research Operations and Management Support 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DMP 
Data Management Plan 
DOD 
Department of Defense 
eCRF 
Electronic Case Report Form 
ECG  
Electrocardiogram 
EDC 
Electronic Data Capture 
ECLA 
Electrochemiluminescence Assay 
ELISA 
Enzyme-Linked Immunosorbent Assay 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act 


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FESAP 
Federal Experts Advisory Panel 
FWA 
Federal Wide Assurance 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
Gm 
Gram 
gm/dL 
Grams per Deciliter 
HBAT 
Heptavalent Equine Antitoxin 
HBsAg 
Hepatitis B Surface Antigen 
HCG 
Human Chorionic Gonadotropic Hormone 
HCV 
Hepatitis C Virus 
HED 
Human Equivalent Dose 
HEENT 
Head, Eyes, Ears, Nose and Throat 
HIV 
Human Immunodeficiency Virus 
HR 
Heart Rate 
Hr/hr 
Hour 
HRPO 
Human Research Protections Office 
HRSA 
Health Resources and Services Administration 
ICH 
International Conference on Harmonisation 
IDES 
Internet Data Entry System 
IEC 
Independent or Institutional Ethics Committee 
IgG 
Immunoglobulin G 
IHC 
Immunohistochemistry 
IM 
Intramuscular 
IND 
Investigational New Drug  
IP 
Intraperitoneal  
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ITT 
Intention-To-Treat 
IUDs 
Intrauterine Contraceptive Device 
IV 
Intravenous 


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KG 
Kilogram 
LLN 
Lower Limit of Normal 
mAbs/mAb 
Monoclonal Antibodies 
MedDRA 
Medical Dictionary for Regulatory Activities 
mEq/L 
Milliequivalent per Liter 
Mg/mg 
Milligram/milligram 
mg/dl 
Milligram per Deciliter 
Ml/mL 
Milliliter 
Mm/mm 
Millimeter 
mmHg 
Millimeters of Mercury 
MNA 
Battelle Mouse Neutralization Assay 
MOP 
Manual of Procedures 
MPA 
Mouse Potency Assay 
MRSD 
Maximum Recommended Starting Dose 
N 
Number  
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
NLM 
National Library of Medicine 
NOAEL 
No-Observed-Adverse-Effect-Level 
NSAIDS 
Nonsteriodal Anti-Inflammatory Drugs 
OHRP 
Office for Human Research Protections 
OTC 
Over the Counter 
PE 
Physical Examination 
PI 
Principal Investigator 
PK 
Pharmacokinetic(s) 
PR 
PR Interval-Standard ECG Terminology 
PREP 
Public Readiness and Emergency Preparedness 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
PVG 
Pharmacovigilance Group 


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PVSS 
Pharmacovigilance Safety System 
RBC/HPF 
Red Blood Cells per High-Power Field 
SAE 
Serious Adverse Event 
SRC 
Safety Review Committee 
SOP 
Standard Operating Procedure 
Tmax 
Time to Maximum Concentration 
TTD 
Time to Death 
µg 
Microgram 
ULN 
Upper Limit of Normal 
WBC 
White Blood Count 
 
 
 


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SUMMARY OF CHANGES FOR VERSION 3.0 
 
Version 2.0 
Version 3.0 
Reason for change 
Page 17: Protocol Summary 
Population = 30 
Study Duration = 8 months 
Protocol Summary 
Population = 40 
Study Duration = 10 months 
Additional Cohort added with 
extended follow-up period. 
Page 17: Protocol Summary, 
Subject Participation 
Subjects in all cohorts will 
participate approximately 150 
days (up to 28-day screening, 
12-hour inpatient stay, up to 
120 days outpatient follow-up) 
 
 
Protocol Summary, 
Subject Participation 
Subjects in cohorts 1-3 will 
participate approximately 150 
days (up to 28-day screening, 
12-hour inpatient stay, up to 
120 days outpatient follow-up) 
Subjects in cohorts 4 will 
participate approximately 210 
days (up to a 28-day screening, 
12-hour inpatient stay, up to 
180-day outpatient follow-up) 
Additional Cohort added with 
extended follow-up period. 
Page 17-18: Protocol 
Summary, 
Study Outcome Measures 
Secondary Endpoints: 
 
Pharmacokinetic samples will 
be tested by MNA at pre-dose 
and on Days 4, 30, 60, 90, and 
120  
The assessment of Cmax, 
Tmax, half-life (α and β), 
MRT and AUC(0-t) for each of 
the monoclonal antibodies of 
G03-52-01 as measured by a 
validated 
electrochemiluminescence 
assay (ECLA) or an enzyme-
linked immunosorbent assay 
(ELISA).  
Protocol Summary, 
Study Outcome Measures 
Secondary Endpoints: 
 
Pharmacokinetic samples will 
be tested by MNA at pre-dose 
and on Days 4, 30, 60, 90, and 
120 for cohorts 1-3.   
Pharmacokinetic samples will 
be tested by MNA at pre-dose 
and on Days 4, 30, 45, 60, 90, 
and 120 for cohort 4. 
The assessment of Cmax, 
Tmax, half-life (α and β), MRT 
and AUC(0-t) for each of the 
monoclonal antibodies of G03-
52-01 as measured by a 
validated 
electrochemiluminescence 
Additional Cohort added with 
extended follow-up period. 


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Pharmacokinetic samples will 
be tested by ECLA or ELISA 
at pre-dose, 2, 4, 8, 24, 48, and 
72 hours post injection, and on 
Days 4, 8, 15, 30, 45, 60, 90, 
and 120  
Samples collected to evaluate 
presence of anti-drug 
antibodies (ADA) collected for 
all cohorts. 
Samples will be tested for 
ADA at pre-dose and on Days 
15, 30, 45, 60, 90, and 120  
assay (ECLA) or an enzyme-
linked immunosorbent assay 
(ELISA).  
 
Pharmacokinetic samples will 
be tested by ECLA or ELISA at 
pre-dose, 2, 4, 8, 24, 48, and 72 
hours post injection, and on 
Days 4, 8, 15, 30, 45, 60, 90, 
and 120 for cohorts 1-3.   
 
Pharmacokinetic samples will 
be tested by ECLA or ELISA at 
pre-dose, 6 hours post dose, 
and on Days 1, 2, 4, 8, 15, 30, 
45, 60, 90, 120, and 180 for 
cohort 4.  
 
Samples collected to evaluate 
presence of anti-drug 
antibodies (ADA) collected for 
all cohorts. 
 
Samples will be tested for ADA 
at pre-dose and on Days 15, 30, 
45, 60, 90, and 120 for cohorts 
1-3.   
Samples will be tested for ADA 
at pre-dose and on Days 45, 60, 
90, 120 and 180 for cohort 4.  
Page 18: Protocol Summary, 
Estimated Time to Complete 
Enrollment:   
Approximately 3 months 
Protocol Summary, 
Estimated Time to Complete 
Enrollment:   
Approximately 5 months 
 
 


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Page 18: Protocol Summary, 
Description of Study Design: 
A Phase 1, randomized, 
double-blind, placebo-
controlled dose escalation trial 
of three dose cohorts of 10 
subjects: (A: 10mg, B: 25mg, 
C: 50mg) 
 
 
 
 
 
 
 
 
 
 
Protocol Summary, Description 
of Study Design: 
A Phase 1, randomized, double-
blind, placebo-controlled dose 
escalation trial of four dose 
cohorts as outlined below: 
• Cohort 1: 10 mg IM 
injection (8 active, 2 
placebo) 
• Cohort 2: 25 mg IM 
injection (8 active, 2 
placebo) 
• Cohort 3: 50 mg IM 
injection (8 active, 2 
placebo) 
• Cohort 4: 100mg IM 
injection (8 active, 2 
placebo) 
 
Added cohort 4 
Page 18-19: Protocol 
Summary, Description of 
Study Design 
 
Dose escalation will not occur 
until safety data through Day 8 
is reviewed by the Safety 
Review Committee (SRC) 
composed of the Principal 
Investigator (PI), Ology 
Bioservices Medical Monitor, 
and the DOD Medical 
Monitor. Objective dose-
escalation criteria and safety 
evaluations will be utilized. 
Protocol Summary, Description 
of Study Design 
 
Dose escalation will not occur 
until safety data through Day 8 
is reviewed by the Safety 
Review Committee (SRC) 
composed of the Principal 
Investigator (PI), Ology 
Bioservices Medical Monitor, 
and the ICON Medical 
Monitor. Objective dose-
escalation criteria and safety 
evaluations will be utilized. A 
SRC meeting will be held at 
any time during the course of 
the study if halting criteria are 
met or safety concerns arise.   
Revise to include which 
Medical Monitors will attend 
the SRC and when the SRC 
meetings will occur. 
Page 19: Protocol Summary, 
Description of Study Design 
The study will consist of a 
twenty-eight-day screening 
period and 12-hour clinic stay.  
Follow-up visits will occur at 
24 hours, 48 hours, and 72 
Protocol Summary, Description 
of Study Design 
 
The study will consist of a 
twenty-eight-day screening 
period and 12-hour clinic stay.  
Follow-up visits will occur at 
Additional follow-up visits for 
cohort 4 added 


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hours post dose and on Days 4, 
8, 15, 30, 45, 60, 90, and 120 
for all cohorts. 
24 hours, 48 hours, and 72 
hours post dose and on Days 4, 
8, 15, 30, 45, 60, 90, and 120 
for cohorts 1-3.  Follow-up visits 
for subjects in cohort 4 will 
occur on Days 1, 2, 4, 8, 15, 30, 
45, 60, 90, 120, 150 and 180. 
 
Page 19: Protocol Summary, 
Description of Study Design 
Subjects will be screened for 
Human Immunodeficiency 
Virus (HIV), Hepatitis B 
surface antigen (HBsAg), and 
antibody to Hepatitis C virus 
(HCV), drugs and alcohol.  
Safety parameters include 
physical examination, 12-lead 
Electrocardiogram (ECG), 
vital signs, and clinical 
laboratory values to include: 
Complete Blood Count (CBC) 
with differential, 
comprehensive metabolic 
panel, and urine dipstick for 
blood, glucose and protein. 
Page 33: Protocol Summary, 
Description of Study Design 
 
Subjects will be screened for 
Human Immunodeficiency 
Virus (HIV), Hepatitis B 
surface antigen (HBsAg), and 
antibody to Hepatitis C virus 
(HCV), drugs and alcohol.  
Safety parameters include 
physical examination, 12-lead 
Electrocardiogram (ECG), vital 
signs, and clinical laboratory 
values to include: Complete 
Blood Count (CBC) with 
differential, comprehensive 
metabolic panel, and urine 
dipstick for protein, blood, and 
glucose with reflex microscopy.  
 
Added reflex microscopy 
Page 19: Protocol Summary, 
Description of Study Design 
 
Pharmacokinetic (PK) samples 
will be drawn at pre-dose, 2, 4, 
8, 24, 48, and 72 hours post 
dose and on days 4, 8, 15, 30, 
45, 60, 90, and 120.  PK 
samples will be tested by the 
Battelle Mouse Neutralization 
Assay (MNA) for serotypes A 
and B at pre-dose and on days 
4, 30, 90, and 120 for all 
Protocol Summary, Description 
of Study Design 
 
Cohorts 1-3:  Pharmacokinetic 
(PK) samples will be drawn at 
pre-dose, 2, 4, 8, 24, and 48, 
and 72 hours post dose and on 
days 4, 8, 15, 30, 45, 60, 90, 
and 120.  PK samples will be 
tested by the Battelle Mouse 
Neutralization Assay (MNA) 
for serotypes A and B at pre-
dose and on days 4, 30, 60, 90, 
and 120.  PK samples will be 
Additional Cohort added with 
extended follow-up period. 


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cohorts.  PK samples will be 
tested by ECLA or ELISA at 
pre-dose, 2, 4, 8, 24, 48, and 
72 hours post dose and on days 
4, 8, 15, 30, 45, 60, 90, and 
120 for all cohorts.  Samples 
will be tested for anti-drug 
antibodies (ADA) at pre-dose 
and days 15, 30, 45, 60, 90, 
and 120.  A Safety Review 
Committee (SRC) meeting will 
be held if halting criteria are 
met or safety concerns arise. 
tested by ECLA or ELISA at 
pre-dose, 2, 4, 8, 24, 48, and 72 
hours post dose and on days 4, 
8, 15, 30, 45, 60, 90, and 120.  
Samples will be tested for anti-
drug antibodies (ADA) at pre-
dose and days 15, 30, 45, 60, 
90, and 120. Cohort 4:  
Pharmacokinetic (PK) samples 
will be drawn at pre-dose, 
6hours post dose, and on days 
1, 2, 4, 8, 15, 30, 45, 60, 90, 
120, and 180.  PK samples will 
be tested by the Battelle Mouse 
Neutralization Assay (MNA) 
for serotypes A and B at pre-
dose, and on days 4, 30, 45, 60, 
90, and 120. PK samples will 
be tested by ECLA or ELISA at 
pre-dose, 6 hours post-dose and 
on days 1, 2, 4, 8, 15, 30, 45, 
60, 90, 120, and 180.  Samples 
will be tested for anti-drug 
antibodies (ADA) at pre-dose 
and days 45, 60, 90, 120, and 
180. 
Page 20: Schematic of Study 
Design 
 
Schematic of Study Design 
Added cohort 4 to chart design 
Revised to show addition of 
Cohort 4  
Section 1 Key Roles: 
Ology Bioservices Medical 
Monitor 
John.abernethy@ologybio.com 
Section 1 Key Roles:  
 Ology Bioservices Medical 
Monitor 
John.abernethy@resilience.com 
Update contact information 
Page 25, Section 2.2 Rationale 
for Use of G03-52-01  
Doses will escalate to 25 mg 
and then to 50 mg provided 
there are no safety concerns. 
Section 2.2 Rationale for Use 
of G03-52-01  
Doses will escalate to 25 mg 
and then to 50 mg provided 
there are no safety concerns. 
Added rationale for escalation 
to 100 mg dose  


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The nonclinical IND-enabling 
toxicology studies were 
designed to support this 
clinical design with 
intramuscular route of 
administration. 
The nonclinical IND-enabling 
toxicology studies were 
designed to support this clinical 
design with intramuscular route 
of administration.  Based on 
data received from the Day 60 
blinded interim safety and PK 
analysis, it was determined to 
escalate to 100 mg single dose. 
Page 29, Section 3.2.2 
Secondary endpoints 
The pharmacokinetic 
assessment of Cmax, Tmax 
and AUC(0-t) as measured by 
the validated Battelle Mouse 
Neutralization Assay (MNA) 
for serotypes A and B 
Pharmacokinetic samples will 
be tested by MNA at pre-dose 
and on Days 4, 30, 60, 90, and 
120  
 
 
 
The assessment of Cmax, 
Tmax, half-life (α and β), 
MRT, and AUC(0-t) for each 
of the monoclonal antibodies 
of G03-52-01 as measured by a 
validated 
electrochemiluminescence 
assay (ECLA) or validated 
enzyme-linked immunosorbent 
assay (ELISA). 
Pharmacokinetic samples will 
be tested by ECLA or ELISA 
at pre-dose, 2, 4, 8, 24, 48, and 
72 hours post injection, and on 
Section 3.2.2 Secondary 
endpoints 
The pharmacokinetic 
assessment of Cmax, Tmax and 
AUC(0-t) as measured by the 
validated Battelle Mouse 
Neutralization Assay (MNA) 
for serotypes A and B 
Pharmacokinetic samples will 
be tested by MNA at pre-dose 
and on Days 4, 30, 60, 90, and 
120 for Cohorts 1-3.  
Pharmacokinetic samples will 
be tested by MNA at pre-does 
and on Days 4, 30, 45, 60, 90, 
and 120 for cohort 4.  
The assessment of Cmax, 
Tmax, half-life (α and β), 
MRT, and AUC(0-t) for each of 
the monoclonal antibodies of 
G03-52-01 as measured by a 
validated 
electrochemiluminescence 
assay (ECLA) or validated 
enzyme-linked immunosorbent 
assay (ELISA).  
Pharmacokinetic samples will 
be tested by ECLA or ELISA at 
pre-dose, 2, 4, 8, 24, 48, and 72 
hours post injection, and on 
Details for addition of Cohort 4 


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Days 4, 8, 15, 30, 45, 60, 90, 
and 120  
 
 
 
 
 
Samples will be tested to 
evaluate presence of anti-drug 
antibodies (ADA) collected for 
all cohorts. 
Samples will be tested for 
ADA at pre-dose, 15, 30, 45, 
60, 90, and 120  
Days 4, 8, 15, 30, 45, 60, 90, 
and 120 for Cohorts 1-3.   
Pharmacokinetic samples will 
be tested by ECLA or ELISA at 
pre-dose, 6 hours post-dose, 
and on Days 1, 2, 4, 8, 15, 30, 
45, 60, 90, 120, and 180 for 
cohort 4.  
Samples will be tested to 
evaluate presence of anti-drug 
antibodies (ADA) collected for 
all cohorts. 
Samples will be tested for ADA 
at pre-dose, 15, 30, 45, 60, 90, 
and 120 for cohorts 1-3.  
Samples will be tested for ADA 
at pre-dose and on Days 45, 60, 
90, 120, and 180 for Cohort 4.  
Page 29, Section 4 Study 
Design 
This is a first-in-human study 
consisting of three cohorts of 
ten subjects each.  Each 
subject will receive a single IM 
injection of G03-52-01 or 
placebo.   
 
Section 4 Study Design 
This is a first-in-human study 
consisting of four cohorts of ten 
subjects each.  Each subject 
will receive a single IM 
injection of G03-52-01 or 
placebo.   
 
Additional cohort added.   
Page 29, Section 4 Study 
Design Table 1 
Cohort A, B, C 
Section 4 Study Design Table 1 
Cohort 1, 2, 3, and 4  
Cohort 4 -  100mg, 10 subjects 
(8 active, 2 placebo) 
 
Additional Cohort added with 
extended follow-up period. 
Page 30, Section 4 Study 
Design: Schedule for Subjects 
Subjects in all cohorts will 
participate in the study for 
Page 45, Section 4 Study 
Design: Schedule for Subjects 
Subjects in Cohorts 1-3 will 
participate in the study for 
Additional Cohort added with 
extended follow-up period. 
 


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approximately 150 days, 
including a 28-day screening 
period, a 12-hour inpatient stay 
and approximately 120-day 
follow-up after study product 
administration.  Subjects will 
remain at the clinic and not be 
eligible for discharge until 8 
hours after the IM injection.  
Last follow up visit scheduled 
at Day 120.   
The end of the study is defined 
as the date of the last visit of 
the last subject in the study. 
 
 
 
 
 
 
 
 
approximately 150 days, 
including a 28-day screening 
period, a 12-hour inpatient stay 
and approximately 120-day 
follow-up after study product 
administration.  Subjects will 
remain at the clinic and not be 
eligible for discharge until 8 
hours after the IM injection.  
Last follow up visit scheduled 
at Day 120.   
Subjects in Cohort 4 will 
participate in the study for 
approximately 210 days, 
including a 28-day screening 
period, a 12-hour inpatient stay 
and approximately 180-day 
follow-up after study product 
administration.  Subjects will 
remain at the clinic and not be 
eligible for discharge until 8 
hours after the IM injection.  
Last follow up visit scheduled 
at Day 180.   
The end of the study is defined 
as the date of the last visit of 
the last subject in the study. 
 
 
 
 
 
 
 
 
 
 
 
Section 5.2 subject Exclusion 
Criteria 
 
Section 5.2 subject Exclusion 
Criteria 
Addition of #24. Subjects with 
NX02 levels present at 
screening will be exclude from 
cohort 4. 
 
Page 34, Section 5.3.1 
Randomization Procedures 
This is a Phase 1 double-
blinded, placebo-controlled 
trial that will randomize 
subjects within three dosing 
Section 5.3.1 Randomization 
Procedures 
This is a Phase 1 double-
blinded, placebo-controlled 
trial that will randomize 
subjects within four dosing 
 
Addition of cohort 4 


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cohorts to either active or 
placebo in an overall 4:1 
ratio.   
cohorts to either active or 
placebo in an overall 4:1 ratio.   
Section 6.2 Acquisition 
ICON Early Phase Services 
Attn: Jane Willman, RPh 
8307 Gault Lane 
San Antonio, TX 78209 
Section 6.2 Acquisition  
ICON Early Phase Services 
Attn: Pharmacist 
8307 Gault Lane 
San Antonio, TX 78209 
Jane Willman no longer at the 
site. 
Page 36, Section 6.3 
Formulation. Packaging, and 
Labeling 
G03-52-01 will be 
administered intramuscularly 
(IM) as a single dose at 
concentrations of 10 mg, 25 
mg, and 50 mg by varying the 
administration volume. 
Page 52, Section 6.3 
Formulation. Packaging, and 
Labeling 
G03-52-01 will be administered 
intramuscularly (IM) as a single 
dose at concentrations of 10 
mg, 25 mg, 50 mg and 100 mg 
by varying the administration 
volume. 
Cohort 4 will receive 100mg 
dose.   
Page 40, Section 7.5.1.3 
Pregnancy Testing 
A urine pregnancy test will be 
repeated on Day 4, Day 45, 
and Day 120 (end of study). 
Page 56, Section 7.5.1.3 
Pregnancy Testing 
A urine pregnancy test will be 
repeated on Day 4, Day 45, and 
end of study (Day 120 or Day 
180, depending on cohort). 
Added cohort 4 with extended 
visit schedule 
Page 42, Section 7.6.2 Anti-
Drug Antibody Assay 
Six-mL samples of blood will 
be drawn on Days 0, 15, 
30,45,60, 90, and 120 for 
determining the presence of 
ADA using a validated ECLA 
that measures total anti-drug 
antibody in serum.   This will 
be done to assess 
immunogenicity. 
Page 57, Section 7.6.2 Anti-
Drug Antibody Assay 
Six-mL samples of blood will 
be drawn pre-dose on Day 0, 
and on Days 15, 30,45,60, 90, 
and 120 for determining the 
presence of ADA using a 
validated ECLA that measures 
total anti-drug antibody in 
serum for Cohorts 1-3.    
Six-mL samples of blood will 
be drawn pre-dose on Day 0 
and on Days 45, 60, 90, 120, 
Additional Cohort added with 
extended follow-up period. 


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and 180 for determining the 
presence of ADA using a 
validated ECLA that measures 
total anti-drug antibody in 
serum for Cohort 4.  This will 
be done to assess 
immunogenicity. 
 
Page 43, Table 2  
 
Page 58, Table 2 
Updated to reflect additional 
visits on day 180 for Cohort 4. 
24hr/Day 1.  48hr/Day2 
PK, MNA and ADA and 
Cumulative totals shown for 
Cohorts 1-3 and 4 separately 
Footnotes revised. 
 
Additional Cohort added with 
extended follow-up period. 
Section 8.2 Visit 2: Baseline 
(Day0)  
• Obtain blood samples 
for 
Baseline serum PK (prior to 
injection and at the completion 
of the injection and 2hr, 4hr, 
and 8 hr post dosing) 
Section 8.2 Visit 2: Baseline 
(Day0) 
• Obtain blood samples 
for 
Baseline serum PK (prior to 
injection and at the 
completion of the 
injection and 2hr, 4hr, 
and 8hr post dosing for 
subjects in Cohorts 1-3. 
Baseline serum PK (prior to 
injection and at 6 hrs 
post-injection for 
subjects in Cohort 4) 
MNA (prior to injection for 
subjects in Cohorts 1-3) 
Added cohort 4 


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MNA (prior to injection and at 
2 hours post injection for 
subjects in Cohort 4) 
ADA (prior to injection for all 
subjects) 
 
Section 8.3 visit 3: Out-patient 
Follow-up (24 hrs) 
• Obtain blood samples for 
the following: 
•  PK measurement 
Section 8.3 visit 3: Out-patient 
Follow-up (24 hrs/Day 1) 
• Obtain blood samples for 
the following: 
o PK measurement at 24 
hours for subjects in 
cohorts 1-3 
PK measurement at 24 hours 
(+/- 2houirs)  for subjects in 
cohort 4 
Added cohort 4 
Section 8.4 Visit 4: Outpatient 
follow-up  Visit (48 hours) 
• Obtain blood samples for 
the following: 
•   PK measurement 
Section 8.4 Visit 4: Outpatient 
follow-up  Visit (48 hours/Day 
2) 
• Obtain blood samples for 
the following: 
o PK measurement at 48 
hours for subjects in 
cohorts 1-3 
o PK measurement 48 
hours (+/- 2 hours) for 
subjects in cohort 4 
Added cohort 4 
Section 8.5 visit 5: Out-patient 
Follow-up (72 hours) 
Section 8.5 visit 5: Out-patient 
Follow-up (72 hours) Cohorts 
1-3 
Specified visit for cohort 3 
Section 8.8 Visit 8: Out-patient 
Follow-up (Day 15 +1) 
• Obtain blood samples 
for the following: 
o Clinical Safety 
Labs 
Section 8.8 Visit 8: Out-patient 
Follow-up (Day 15 +1) 
• Obtain blood samples 
for the following: 
o Clinical Safety 
Labs 
Specified ADA for cohorts 1-3 


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o PK 
measurement  
o ADA  
 
o PK 
measurement  
o ADA (cohorts 1-
3) 
 
Section 8.9 visit 9: Out-patient 
Follow-up (Day30 +1) 
• Obtain blood samples 
for the following: 
o Clinical Safety 
Labs 
o PK 
measurement  
o MNA 
o ADA 
Section 8.9 visit 9: Out-patient 
Follow-up (Day30 +1) 
• Obtain blood samples 
for the following: 
o Clinical Safety 
Labs 
o PK 
measurement  
o MNA 
o ADA (cohorts 1-
3) 
Specified ADA for cohorts 1-3 
Section 8.10  Visit 10: Out-
patient Follow-up (Day 45 +3) 
• Obtain blood samples 
for the following: 
o PK 
measurement 
o ADA 
Section 8.10  Visit 10: Out-
patient Follow-up (Day 45 +3)  
• Obtain blood samples 
for the following: 
o PK 
measurement 
o ADA 
o MNA (cohort 4) 
Specified MNA for cohort 4 
Section 8.13 Visit 13: Final 
Visit/Early Termination Visit 
(Day 120 +3) 
• Obtain blood samples 
for the following: 
o Clinical Safety 
Labs 
o PK 
measurement 
o MNA 
o ADA 
 
Section 8.13 Visit 13: Final 
Visit /Early Termination Visit 
for Cohorts 1-3 (Day 120 +3) / 
Cohorts 4 (Day 120 +3) 
• Obtain blood samples 
for the following: 
o Clinical Safety 
Labs (cohorts 1-
3) 
o PK 
measurement 
o MNA 
o ADA 
 
Specified labs for cohorts 1-3 


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Section 8.14 
Section 8.14 Visit 14: Final 
Visit/Early Termination for 
subjects in Cohorts 4 (Day 180 
+3)  
• Obtain vital signs 
• Review and update 
concomitant 
medications 
• Perform symptom 
directed PE  
• Obtain blood samples 
for the following: 
o Clinical Safety 
Labs 
o PK 
measurement  
o ADA 
• Obtain urine sample for 
dipstick analysis  
• Perform urine 
pregnancy test on 
women of child-bearing 
potential 
• Assessment of AEs and 
SAEs 
• Counsel women of 
child-bearing potential 
on the avoidance of 
pregnancy. Counsel the 
subject not to receive 
any botulinum toxin 
preparation (e.g.  
Botox) for 4 months 
after injection 
Addition of Cohort 4 final visit 
Section 8.14 Unscheduled 
Visit 
Section 8.15 Unscheduled Visit 
Section number update 
Section 9.3.2 Serious Adverse 
Events 
SAE Email Address: 
safety@ologybio.com 
Section 9.3.2 Serious Adverse 
Events  
SAE Email address: 
olo.safety@reilience.com 
Revision to correct SAE email 
address 
Revision to correct Medical 
Monitor 


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The DOD medical monitor and 
clinical project manager will 
be notified of the SAE by 
DOD PVG.   
The DOD medical monitor 
will review and assess the SAE 
for potential impact on study 
subject safety and protocol 
conduct. 
The ICON medical monitor and 
clinical project manager will be 
notified of the SAE by DOD 
PVG.   
The ICON medical monitor 
will review and assess the SAE 
for potential impact on study 
subject safety and protocol 
conduct. 
Page xx, Section 9.6.3 DOD 
Medical Monitor 
The DOD Medical Monitor 
will communicate with the 
Ology Bioservices Medical 
Monitor for any safety related 
questions.  The DOD MM will 
participate in the planned SRC 
meetings and can make a 
recommendation that the SRC 
be convened to review any 
safety concerns.  
Section 9.6.2 ICON Medical 
Monitor 
The ICON Medical Monitor 
will communicate with the 
Ology Bioservices Medical 
Monitor for any safety related 
questions.  The ICON MM will 
participate in the planned SRC 
meetings and can make a 
recommendation that the SRC 
be convened to review any 
safety concerns. 
Revision to correct section 
numbering and Medical Monitor 
Section 9.6.4 Ology 
Bioservices Medical Monitor 
The Ology Bioservices 
Medical Monitor will be the 
main point of contact for the 
ICON MM and the DOD MM, 
including any safety-related 
questions or concerns.  The 
Ology Bioservices MM will 
escalate any medical or safety 
concerns to the DOD MM as 
needed.  
Section 9.6.3 Ology 
Bioservices Medical Monitor 
The Ology Bioservices Medical 
Monitor will be the main point 
of contact for the ICON MM, 
including any safety-related 
questions or concerns.  The 
Ology Bioservices MM will 
escalate any medical or safety 
concerns to the DOD as 
needed. 
Revision to correct section 
numbering and Medical Monitor 
Page xx, Section 9.6.5 Safety 
Review Committee (SRC) 
The SRC will be composed of:  
PI, or designee  
Ology Bioservices Medical 
Monitor  
Section 9.6.4 Safety Review 
Committee (SRC) 
The SRC will be composed of:  
PI, or designee  
Ology Bioservices Medical 
Monitor  
Revision to correct section 
numbering and name of Medical 
Monitor  


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DOD Medical Monitor or 
designee; 
 
The SRC recommendation to 
advance to the next level will 
be documented and provided 
to all the appropriate parties 
(PI, Ology Bioservices and 
DOD) involved with the study. 
ICON Medical Monitor or 
designee; 
 
The SRC recommendation to 
advance to the next level will 
be documented and provided to 
all the appropriate parties (PI, 
Ology Bioservices, ICON, and 
DOD) involved with the study. 
Section 11.2 Planned Interim 
Analyses 
A blinded interim safety and 
PK analysis is planned for this 
study to analyze all PK, ADA, 
and MNA samples through 
Day 60. This will include all 
subject in all cohorts through 
Day 60. Stopping criteria are 
for safety and are defined in 
section 9.5. 
Section 11.2 Planned Interim 
Analyses 
A blinded interim safety and PK 
analysis is planned for this study 
to analyze all PK, ADA, and 
MNA samples for Cohorts 1-3 
through Day 60.  A second 
blinded interim safety analysis is 
planned to analyze all PK, ADA, 
and MNA samples for Cohort 4 
through Day 90.  Stopping criteria 
are for safety and are defined in 
section 9.5. 
 
 
Appendix A: Schedule of 
Events 
Appendix A: Schedule of 
Events 
Addition columns added for 
Study Day 180 
Footnotes updated.  
Additional Cohort added with 
extended follow-up period. 
 
 


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SUMMARY OF CHANGES FOR VERSION 2.0 
 
Version 1.0 
Version 2.0 
Reason for Change 
Page 8:  List of 
Abbreviations 
Page 9:  List of Abbreviations 
Added abbreviation for ELISA, 
HRPO, PVG, and PVSS 
Page 12: Protocol Summary, 
Study Outcome Measures: 
Secondary Endpoint:  
The assessment of Cmax, 
Tmax, half-life (α and β), MRT 
and AUC(0-t) for each of the 
monoclonal antibodies of 
G03-52-01 as measured by a 
validated 
electrochemiluminescence 
assay (ECLA) method.  
 
Pharmacokinetic samples 
will be tested by ECLA at 
pre-dose, 2, 4, 8, 24, 48, and 
72 hours post injection, and 
on Days 4, 8, 15, 30, 45, 60, 
90, and 120. 
 
Page 17: Protocol Summary, 
Study Outcome Measures: 
Secondary Endpoint:  
The assessment of Cmax, Tmax, 
half-life (α and β), MRT and 
AUC(0-t) for each of the 
monoclonal antibodies of G03-
52-01 as measured by a validated 
electrochemiluminescence assay 
(ECLA) or an enzyme-linked 
immunosorbent assay (ELISA).  
 
Pharmacokinetic samples will be 
tested by ECLA or ELISA at 
pre-dose, 2, 4, 8, 24, 48, and 72 
hours post injection, and on Days 
4, 8, 15, 30, 45, 60, 90, and 120. 
 
Added enzyme-linked 
immunosorbent assay (ELISA) 
Page 12: Protocol Summary, 
Description of Study Design: 
PK samples will be tested by 
ECLA at pre-dose, 2, 4, 8, 
24, 48, and 72 hours post 
dose and on days 4, 8, 15, 
30, 45, 60, 90, and 120 for 
all cohorts.   
Page 17: Protocol Summary, 
Description of Study Design: 
PK samples will be tested by 
ECLA or ELISA at pre-dose, 2, 
4, 8, 24, 48, and 72 hours post 
dose and on days 4, 8, 15, 30, 45, 
60, 90, and 120 for all cohorts.   
 
Added ELISA 


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Page 24: Section 4: Study 
Design Table 1 lists the IP as 
Dose of NTM-1634 
Page 28: Section 4: Study 
Design Table 1 corrected name 
of IP to read Dose of G03-52-01 
Revision to correct the name of 
the IP to G03-52-01 
Page 24: Section 3.2.2 
Secondary Endpoint:  
The assessment of Cmax, 
Tmax, half-life (α and β), MRT 
and AUC(0-t) for each of the 
monoclonal antibodies of 
G03-52-01 as measured by a 
validated 
electrochemiluminescence 
assay (ECLA) method.  
 
Pharmacokinetic samples 
will be tested by ECLA at 
pre-dose, 2, 4, 8, 24, 48, and 
72 hours post injection, and 
on Days 4, 8, 15, 30, 45, 60, 
90, and 120. 
Page 29 Section 3.2.2: 
Secondary Endpoint:  
The assessment of Cmax, Tmax, 
half-life (α and β), MRT and 
AUC(0-t) for each of the 
monoclonal antibodies of G03-
52-01 as measured by a validated 
electrochemiluminescence assay 
(ECLA) or an enzyme-linked 
immunosorbent assay (ELISA).  
 
Pharmacokinetic samples will be 
tested by ECLA or ELISA at 
pre-dose, 2, 4, 8, 24, 48, and 72 
hours post injection, and on Days 
4, 8, 15, 30, 45, 60, 90, and 120. 
 
Added ELISA 
Page 36: Section 7.6.1 
Pharmacokinetic Assay 
Serum will be analyzed for 
levels of each of the 
antibodies using a validated 
ECLA.  Five-mL samples of 
blood will be drawn to be 
analyzed for neutralizing 
antibody concentrated using 
the validated Battelle MNA. 
 
Page 41: Section 7.6.1 
Pharmacokinetic Assay 
Six-mL of blood will be drawn 
for the analysis of levels of each 
of the monoclonal antibodies in 
serum using a validated ECLA 
or ELISA.  Ten-mL samples of 
blood will be drawn to be 
analyzed for neutralizing 
antibody concentrated using the 
validated Battelle MNA.  
Added ELISA and revised the 
amount of blood to be drawn for 
analysis. 
Page 37 Section 7.6.2 Anti-
Drug Antibody Assay 
Six-mL samples of blood 
will be drawn on Days 0, 15, 
30,45,60, 90, and 120 for 
determining the presence of 
Page 42 Section 7.6.2 Anti-Drug 
Antibody Assay 
Six-mL samples of blood will be 
drawn on Days 0, 15, 30,45,60, 
90, and 120 for determining the 
presence of ADA using a 
Added that ECLA assay is 
validated 


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ADA using an ECLA assay 
that measures total anti-drug 
antibody in serum.   This 
will be done to assess 
immunogenicity. 
 
validated ECLA that measures 
total anti-drug antibody in 
serum.   This will be done to 
assess immunogenicity. 
 
Page 38 Table 2: Laboratory 
Samples and Estimated Total 
Blood Volume (mL) 
Page 43 Table 2: Laboratory 
Samples and Estimated Total 
Blood Volume (mL) 
Estimated blood volume 
Page 40 Section 8.2 Visit 
2/Baseline  
Page 45 Section 8.2 Visit 2/ 
Baseline:  Added MNA 
Added MNA 
Page 42 Section 8.6 Visit 
6/Day 4 
Page 47 Section 8.6 Visit 6/Day 
4:  Added MNA 
Added MNA 
Page 42 Section 8.8 Visit 
8/Day 15 
Page 47 Section 8.8 Visit 8/Day 
15: Added: 
Counsel women of child-bearing 
potential on the avoidance of 
pregnancy 
Counsel the subject not to 
receive any botulinum toxin 
preparation (e.g.  Botox) for 4 
months after injection 
Added: 
Counsel women of child-bearing 
potential on the avoidance of 
pregnancy 
Counsel the subject not to 
receive any botulinum toxin 
preparation (e.g.  Botox) for 4 
months after injection 
Page 43 Section 8.9 Visit 
9/Day 30 
Page 48 Section 8.9 Visit 9/Day 
30:  Added MNA 
Added MNA 
Page 43 Section 8.11 Visit 
11/Day 60 
Page 49 Section 8.11 Visit 
11/Day 60:  Added MNA 
Added MNA 
Page 44 Section 8.12 Visit 
12/Day 90 
Page 49 Section 8.12 Visit 
12/Day 90:  Added MNA 
Added MNA 
Page 44 Section 8.13 Visit 
13/Day 120 
Page 49 Section 8.13 Visit 
13/Day 120:  Added MNA 
Added MNA 


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Page 47 Section 9.3.2 
Serious Adverse Events:  
ICON Medical Monitor  
SAE Phone: 443-983-1332 
Page 53 Section 9.3.2 Serious 
Adverse Events:  ICON Medical 
Monitor 
SAE Phone: 410-294-2537 
Revision in Medical Monitor 
Phone Number to Report SAE. 
 
Revision captured in 
Administrative Letter to Protocol 
dated March 5, 2020 
N/A 
Page 56 Section 9.6.2 ICON 
Medical Monitor 
Added the ICON Medical 
Monitor and defined the role 
N/A 
Page 56 Section 9.6.3 DOD 
Medical Monitor 
Added the DOD Medical 
Monitor and defined the role 
N/A 
Page 56 Section 9.6.4 Ology Bio 
Medical Monitor 
Added the Ology Bio Medical 
Monitor and defined the role 
Page 63 Appendix A: 
Schedule of Events 
Page 69: Appendix A: Schedule 
of Events 
Added MNA as a line item on 
the Schedule of Events 


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PROTOCOL SUMMARY 
Title: 
 
A Phase 1, Randomized, Double-Blind, Dose Escalation Study to Evaluate the 
Safety and Pharmacokinetics of a Single IM Dose of G03-52-01 vs Placebo in 
Adult Subjects. 
 
 
Phase: 
 
1 
 
Population: 
 
40 healthy male and female subjects between 18-45 years of age 
 
Number of 
Sites: 
 
One 
 
Study 
Duration: 
 
Approximately 10 months. 
 
Subject 
Participation 
Duration 
 
Subjects in Cohorts 1-3 will participate approximately 150 days (up to 28-day 
screening, 12-hour inpatient stay, up to 120 days outpatient follow-up) 
Subjects in Cohort 4 will participate approximately 210 days (up to a 28-day 
screening, up to 12-hour clinic stay, up to 180-day outpatient follow-up) 
Description of 
Agent: 
 
G03-52-01 drug product is a mixture of five human monoclonal IgG1 antibodies 
(NX01, NX11, XB10, XB18, and XB23) and one humanized monoclonal IgG1 
antibody (NX02) which bind to non-overlapping epitopes on BoNT/A/B.   
  
 
 


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Study 
Objectives: 
Primary Objective:   
 
• To assess the safety and tolerability of escalating doses of G03-52-01 
administered intramuscularly (IM) in healthy adult subjects 
 
Secondary Objective: 
 
• To assess the pharmacokinetics (PK) and immunogenicity of escalating 
doses of G03-52-01 administered IM in healthy adult subjects 
 
Study Outcome 
Measures: 
 
Primary Endpoints:   
 
• The occurrence of Serious Adverse Events (SAE) following 
administration of G03-52-01 to the final follow-up visit. 
 
• The occurrence of Adverse Events (AE) from administration of G03-52-
01 to the final follow-up visit. 
 
• The occurrence of changes from baseline in physical examination, vital 
signs and clinical safety laboratory values following administration of 
G03-52-01 to the final follow-up visit. 
 
Secondary Endpoints: 
 
• The pharmacokinetic assessment of Cmax, Tmax and AUC(0-t) as measured 
by the validated Battelle Mouse Neutralization Assay (MNA) for 
serotypes A and B. 
 
o Pharmacokinetic samples will be tested by MNA at pre-dose and 
on Days 4, 30, 60, 90, and 120 for Cohorts 1-3. 
o Pharmacokinetic samples will be tested by MNA at pre-dose, 2-
hour post-dose (for future use), and on Days 4, 30, 45, 60, 90, 
and 120 for Cohort 4. 
 
The assessment of Cmax, Tmax, half-life (α and β), MRT and AUC(0-t) for 
each of the monoclonal antibodies of G03-52-01 as measured by a 
validated electrochemiluminescence assay (ECLA) or an enzyme-linked 
immunosorbent assay (ELISA).  
o Pharmacokinetic samples will be tested by ECLA or ELISA at 
pre-dose, 2, 4, 8, 24, 48, and 72 hours post injection, and on 
Days 4, 8, 15, 30, 45, 60, 90, and 120 for Cohorts 1-3. 
o Pharmacokinetic samples will be tested by ECLA or ELISA at 
pre-dose, 6 hours post dose, and on Days 1, 2, 4, 8, 15, 30, 45, 
60, 90, 120, and 180 for Cohort 4. 
 


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• Samples collected to evaluate presence of anti-drug antibodies (ADA) 
collected for all cohorts. 
 
o Samples will be tested for ADA at pre-dose and on Days 15, 30, 
45, 60, 90, and 120 for Cohorts 1-3. 
o Samples will be tested for ADA at pre-dose and on Days 45, 60, 
90, 120, and 180 for Cohort 4. 
 
 
Estimated Time 
to Complete 
Enrollment: 
 
Approximately 5 months. 
Description of 
Study Design: 
A Phase 1, randomized, double-blind, placebo-controlled dose escalation trial of 
four dose cohorts outlined below:  
• Cohort 1: 10 mg IM injection (8 active, 2 placebo) 
• Cohort 2: 25 mg IM injection (8 active, 2 placebo) 
• Cohort 3: 50 mg IM injection (8 active, 2 placebo) 
• Cohort 4: 100mg IM injection (8 active, 2 placebo) 
 
Dosing for each cohort is as follows: Two sentinel subjects will be administered 
a single IM dose (one G03-52-01, one placebo).  The dosing of the remaining 
eight subjects within that cohort will not be initiated until at least 24 hours have 
passed and no adverse events have occurred that meet halting criteria, and no 
safety signals have occurred that in the opinion of the investigator warrant 
further investigation.   The remaining eight subjects in the cohort will be 
admitted as scheduled without delay. Dose escalation will not occur until safety 
data through Day 8 is reviewed by the Safety Review Committee (SRC) 
composed of the Principal Investigator (PI), Ology Bioservices Medical 
Monitor, and the ICON Medical Monitor. Objective dose-escalation criteria and 
safety evaluations will be utilized. A SRC meeting will be held at any time 
during the course of the study if halting criteria are met or safety concerns arise. 
The study will consist of a twenty-eight-day screening period and up to 12-hour 
clinic stay.  Follow-up visits will occur at 24 hours, 48 hours, and 72 hours post 
dose and on Days 4, 8, 15, 30, 45, 60, 90, and 120 for Cohorts 1-3.  Follow-up 
visits for subjects in Cohort 4 will occur at on Days 1, 2, 4, 8, 15, 30, 45, 60, 90, 
120, and 180. 
Subjects will be screened for Human Immunodeficiency Virus (HIV), Hepatitis 
B surface antigen (HBsAg), and antibody to Hepatitis C virus (HCV), drugs and 
alcohol.  Safety parameters include physical examination, 12-lead 
Electrocardiogram (ECG), vital signs, and clinical laboratory values to include: 


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Complete Blood Count (CBC) with differential, comprehensive metabolic 
panel, and urine dipstick for protein, blood, and glucose with reflex microscopy.   
Cohorts 1-3: Pharmacokinetic (PK) samples will be drawn at pre-dose, 2, 4, 8, 
24, 48, and 72 hours post dose and on days 4, 8, 15, 30, 45, 60, 90, and 120.  PK 
samples will be tested by the Battelle Mouse Neutralization Assay (MNA) for 
serotypes A and B at pre-dose and on days 4, 30, 60, 90, and 120.  PK samples 
will be tested by ECLA or ELISA at pre-dose, 2, 4, 8, 24, 48, and 72 hours post 
dose and on days 4, 8, 15, 30, 45, 60, 90, and 120.  Samples will be tested for 
anti-drug antibodies (ADA) at pre-dose and days 15, 30, 45, 60, 90, and 120.   
Cohort 4:  PK samples will be tested by the Battelle Mouse Neutralization 
Assay (MNA) for serotypes A and B at pre-dose, 2-hours post-dose (future use) 
and on days 4, 30, 45, 60, 90, and 120.  PK samples will be tested by ECLA or 
ELISA at pre-dose, 6 hours post-dose, and on days 1, 2, 4, 8, 15, 30, 45, 60, 90, 
120, and 180.  Samples will be tested for anti-drug antibodies (ADA) at pre-
dose and days 45, 60, 90, 120, and 180. 
A Safety Review Committee (SRC) meeting will be held if halting criteria are 
met or safety concerns arise.     
 
 
 
 
 


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Schematic of Study Design 
 
Assess Eligibility 
Randomize 
Cohort 1 N=10 
Single IM injection of 10mg G03-52-01  
(8 subjects) or Placebo (2 subjects) 
Dose-Escalation Halting Criteria Not Met 
SRC Agrees to Dose Escalation 
Cohort 2 N=10 
Single IM injection of 25mg G03-52-01 
 (8 subjects) or Placebo (2 subjects) 
Dose-Escalation Halting Criteria Not Met 
SRC Agrees to Dose Escalation 
 Study Halting Criteria Met/Dose Escalation 
Halting Criteria Met/SRC Review 
Study Halting Criteria Met/Dose-Escalation 
Halting Criteria Met/SRC Review 
Safe to Proceed 
Halt Study 
Safe to Proceed 
Halt Study 
Dose-Escalation Halting Criteria Not Met 
SRC Agrees to Dose Escalation 
Study Halting Criteria Met/Dose-Escalation 
Halting Criteria Met/SRC Review 
Safe to Proceed 
Halt Study 
 Cohort 3 N=10 
Single IM injection of 50mg G03-52-01  
(8 subjects) or Placebo (2 subjects) 
Cohort 4 N=10 
Single IM injection of 100mg G03-52-01  
(8 subjects) or Placebo (2 subjects) 
SRC Review Assessment of Final Outcome 
Measures 


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1. 
 KEY ROLES 
Principal Investigator: 
 
Cassandra Key, MD 
Sr. Medical Director, ICON Early Phase Services 
8307 Gault Lane 
San Antonio, TX 78209 
Telephone: 210-283-4572 
Email: cassandra.key@iconplc.com  
Ology Bioservices Medical 
Monitor: 
 
 
 
 
John Abernethy, MD 
Ology Bioservices, Inc. 
13200 NW Nano Court 
Alachua, FL 32615 
Telephone:  352-213-5757 
Email:  john.abernethy@resilience.com  
 
 
CRO Safety and 
Pharmacovigilance Contractor: 
 
 
ICON Pharmacovigilance & Safety Services 
Unit 2, Globeside Business Park 
Marlow 
SL7 1HZ 
United Kingdom 
PV email:  ICON-Safety-CentralReceipt@iconplc.com  
 


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Central Laboratory for Safety 
Testing: 
 
 
 
Back up Laboratory for Safety 
Testing: 
 
 
Research Laboratory for PK and 
ADA Samples: 
ICON Early Phase Services LLC. 
8307 Gault Lane 
San Antonio, TX 78209 
 
Quest Diagnostic Clinical Laboratories Inc. 
4770 Regent Blvd. 
Irving, TX 75063 
 
Ology Bioservices, Inc. 
2601 Challenger Drive, Suite 101 
Alameda, CA 94501 
Research Laboratory for MNA  
Samples:                                                
Battelle 
1425 State Route 142  
West Jefferson, OH 43162 


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2. 
BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
2.1. 
Background Information 
2.1.1. 
  Introduction 
Botulism is caused by absorption of Botulinum Neurotoxin (BoNT) into the blood stream 
following oral ingestion (food-borne botulism), through the growth of C. botulinum in the 
gastrointestinal tract (infant botulism), in wounds contaminated by the organism (wound 
botulism), or through inhalation (inhalation botulism).1 There are 7 BoNT serotypes (A-G)2 
which differ by 35-68% at the amino acid level.  Recent data has been published identifying a 
BoNT/H serotype that appears to be a hybrid of A and F serotype.3 Three of the BoNT serotypes 
(A, B, E) cause up to 99% of the cases of human botulism.4,5 
Botulism is characterized by prolonged paralysis, which is either immediately fatal or requires 
prolonged hospitalization in an Intensive Care Unit and mechanical ventilation.  The onset and 
severity of symptoms depends on the amount of toxin absorbed.  Onset of symptoms typically 
occurs 12-72 hours after ingestion, with a range of up to 8 days.  Recovery from the paralysis 
does not occur until new nerve growth occurs. Mechanical ventilator support is commonly 
needed for 2 to 8 weeks, with some patients requiring support for up to 7 months.6, 7 
The development of approaches to treat or prevent biothreat botulism has been designated a high 
priority area by the National Institute of Allergy and Infectious Diseases (NIAID) [see NIAID 
Biodefense Research Agenda for the Centers for Disease Control and Prevention (CDC) 
Category A Agents].8  In June 2011, the Federal Experts Advisory Panel (FESAP) published 
recommendations concerning the Select Agent Program to address the requirements of Executive 
Order 13546, “Optimizing the Security of Biological Select Agents and Toxins in the United 
States”, published in the Federal Register on July 8th, 2010; the recommendations of the FESAP 
classified Botulinum toxins as “Tier 1” agents.   
2.1.2. 
  Currently Available Treatments 
Equine antitoxin and human botulism immune globulin are currently used to treat adult 9, 10 and 
infant botulism, 11 respectively.  Traditional antitoxins are not readily renewable resources, 
requiring animal or human immunization, plasmapheresis or bleeding, and serum processing for 
each lot.  Moreover, each lot produced will vary in antibody composition, potency, dosing, and 
possibly safety profile. Human botulism immune globulin is produced by plasmapheresing 
laboratory personnel who have been immunized because they are at risk of exposure to BoNT.11  
Although human botulism immune globulin has been shown to be both safe and effective for 
treating infant botulism, scaling of this product for the biothreat drug repository is not feasible.11  
Moreover, the pentavalent toxoid used to produce botulism immune globulin is no longer 
available,12 raising questions concerning the ability to continue to make this product. 
With the previous generation of equine antitoxin there was a 9% incidence of acute or delayed 
hypersensitivity reactions, including serum sickness (3.7%) and anaphylactic shock (1.9%).9 The 
observed side effects are attributable to the residual content of the equine Fc region.  The current 
generation heptavalent equine antitoxin (HBAT) also is produced from horses, but is more 


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thoroughly digested to yield largely Fab and Fab’2 to theoretically reduce the incidence of 
hypersensitivity reactions.13  HBAT has a very short serum half-life (8-34 hours depending on 
serotype) and as a result, an approximately 2% incidence of recurrence of botulism occurs after 
treatment, a phenomenon called BoNT reintoxication.14  HBAT has an approximately 1% 
incidence of anaphylaxis, as reported at the 2011 Interagency Botulism Coordinating Committee 
Meeting by CDC.  Rapid deployment of equine antitoxin also is complicated by the inability to 
use it prophylactically and the need to dilute the product 10-fold and infuse intravenously (IV) 
slowly over hours.  Finally, the potency of equine antitoxins, such as HBAT, can vary 
significantly for sub-serotypes where there is significant sequence difference between the 
immunizing sub-serotype and other sub-serotypes.  
2.1.3. 
  G03-52-01 Development 
G03-52-01 drug product is being investigated for the treatment of botulinum neurotoxin and 
prophylaxis of inhalation botulism from serotypes A and B in adults.  G03-52-01 is a mixture of 
five human IgG1 antibodies and one humanized IgG1 antibody each with distinct specificities 
that are individually expressed in a Chinese hamster ovary (CHO) cell line. Each of the drug 
substance antibodies (anti-BoNT/A NX01, NX02, NX11 and anti-BoNT/B XB10, XB18, XB23) 
used in the manufacture of G03-52-01 binds non-overlapping regions on BoNT/A or BoNT/B. 
While each of the mAbs binds to a distinct epitope on BoNT/A or BoNT/B, none was able to 
sufficiently neutralize BoNT when tested alone in vivo. The in vivo studies showed that the 
highest levels of mAb potency were dependent on the presence of three antibodies.15 The 
protective capacity of G03-52-01 to neutralize toxicity caused by BoNT/A and BoNT/B has been 
verified in mice and in guinea pigs. 
As these drug products are directed at foreign targets not expressed in animals or humans and 
based on the observed lack of cross-reactivity of G03-52-01 in healthy human and animal tissue, 
the focus of the nonclinical safety evaluation of G03-52-01 was to assess potential off-target 
toxicity and to identify any untoward effects due to administration of either drug product.   
A GLP 12-week repeat dose toxicity study was performed to evaluate the safety of G03-52-01 in 
rate when administered by intramuscular injection once weekly for three injections and to 
evaluate toxicity and reversibility of effects after a two-month recovery period.  The study 
consisted of four Main Study/Recovery dose groups (15 rats/sex/group) and four Toxicokinetic 
(TK) dose groups (12 rats/sex/group) Experimental endpoints included moribundity/mortality; 
physical examinations, injection site (Draize) reactogenicity scoring; body weights; food 
consumption; body temperature measurements; clinical pathology parameters (clinical 
chemistry, hematology, and coagulation); serum drug levels/toxicokinetics; organ weights; gross 
pathology at necropsy; and microscopic pathology. IM treatment at doses of 10, 50, or 100 
mg/kg of G03-52-01 against botulinum neurotoxins A and B did not result in any treatment-
related, toxicologically significant, or adverse findings following three injections on Study Days 
1, 8, and 15. Therefore, the No Observed Adverse Effect Level (NOAEL) was 100 mg/kg for this 
study. 


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2.1.4. 
  Public Readiness and Emergency Preparedness Act 
This protocol and the study product tested are covered under the Public Readiness and 
Emergency Preparedness (PREP) act.  The PREP Act provides compensation to participants in 
the event of serious physical injury or death caused by covered drugs and vaccines, and liability 
protection for persons conducting the clinical trial and the manufacturer of the drug or vaccine. 
On October 10, 2008, an amendment was issued to the Declaration for use of the PREP act to 
include countermeasures to treat, identify, or prevent adverse health consequences or death from 
exposure to botulinum toxin. (Federal Register, Volume 73, Number 202, Pages: 61864-61866).  
The study product used in this clinical trial is one such countermeasure.  The PREP act provides 
immunity for covered persons (such as Manufacturers, Distributers, Program planners and other 
qualified persons who prescribe, administer or dispense the study product) from tort liability, 
unless the injury was caused by willful misconduct. 
The PREP Act also authorized a “Covered Countermeasures Process Fund” to provide 
compensation to eligible individuals who suffer specified injuries from administration or use of a 
countermeasure pursuant to the declaration.  Any requests for compensation must be filed within 
one year of administration or use of the countermeasure.  Requests would go to the HRSA 
Preparedness Countermeasures Injury Compensation Program (http://www.hrsa.gov/cicp).  
Compensation may then be available for medical benefits, lost wages and death benefits to 
eligible individuals for specified injuries in accordance with regulations published by the 
Secretary.  Eligibility for compensation and the injuries for which compensation may be 
available are further defined by regulation. 
An individual who suffers a serious physical injury or death from the administration and use of 
the study product must first seek compensation from the Covered Countermeasures Process 
Fund.  A serious physical injury means an injury that is life threatening, results in, or requires 
medical or surgical intervention to prevent, permanent impairment of a body function or 
permanent damage to body structure.  Any compensation will be reduced by public or private 
insurance or worker’s compensation available to the injured individual. 
If no funds have been appropriated to the compensation program, the Secretary does not make a 
final determination on the individual’s request within 240 days, or if the individual decides not to 
accept the compensation, the injured individual or his representative may pursue a tort claim in 
the US District Court for the District of Columbia, but only if the claim involves willful 
misconduct, is pled with particularity required under the PREP Act, verified, and accompanied 
by an affidavit by a physician who did not treat the individual and certified medical records.  
Any award is reduced by any public or private insurance or worker’s compensation available to 
the injured individual.  Awards for non-economic damages, such as pain, suffering, physical 
impairment, mental anguish, and loss of consortium are also limited.  If the individual accepts 
compensation, or if there is no willful misconduct, the individual does not have a tort claim that 
can be filed in a US Federal or a State court. 


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2.2. 
Rationale For Use of G03-52-01  
Based on nonclinical and clinical experience with other anti-BoNT mAbs, use of G03-52-01 for 
the treatment of botulism and prophylaxis of inhalation botulism from serotypes A and B in 
adults may provide the following advantages over the equine antitoxins:   
• An improved safety profile  
 Substantially decreased anaphylaxis and no risk of serum sickness 
 G03-52-01 is directed at foreign targets not expressed in animals or humans 
 Toxicity studies demonstrated a lack of cross-reactivity of G03-52-01 in 
healthy human tissue 
 A similar product targeting BoNT serotype A was well tolerated and no 
safety concerns were observed in a Phase 1 clinical study  
 A similar product targeting BoNT serotype B was well tolerated and no 
safety concerns were observed in a Phase 1 clinical trial 
• A longer half-life 
• The ability to administer repeated doses for prevention and therapy 
• The ability to use small doses via IV and IM administration (permitting flexible 
administration scenarios, including self-administration) 
• The ability to easily and consistently manufacture a large number of doses in 
sufficient quantities for stockpiling 
The proposed starting dose for G03-52-01 dose escalation (10 mg IM) is based on previous 
toxicology and clinical studies of anti-BoNT mAbs that included intravenous dosing. The 10 mg 
IM dose includes 5 mg of anti-BoNT/A mAbs (NX01, NX02, and NX11; similar to NTM-1631, 
formerly XOMA 3AB) and 5 mg of anti-BoNT/B mAbs (XB10, XB18 and XB23; similar to 
NTM-1632, formerly XOMA 3B). 
NTM-1631 and NTM-1632 have undergone Phase 1 clinical testing under protocols very similar 
to Protocol G03-52-001.001. These studies were placebo-controlled, double-blind, dose 
escalation studies to evaluate the safety and tolerability of each drug. Each subject received a 
single intravenous (IV) infusions of study drug or placebo administered over one hour, as an 
inpatient, at one of three dose levels (0.33, 0.165, or 0.033 mg/kg) equating to approximately 25, 
12, or 2.5 mg assuming a 75 kg subject. All three doses of each drug were safe and generally 
well tolerated during and following infusion. No pattern of treatment emergent adverse events 
was seen at any of the doses. None of the three NTM-1631 mAbs induced an antibody response 
or augmentation of preexisting antibodies in the few subjects who had them and similar analysis 
of NTM-1632 antibody response is underway. 
Doses will escalate to 25 mg and then to 50 mg up to 100mg provided there are no safety 
concerns. The nonclinical IND-enabling toxicology studies were designed to support this clinical 
design with intramuscular route of administration. Based on data received from the Day 60 
blinded interim safety and PK analysis, it was determined to escalate to 100mg single dose. 


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2.3. 
Potential Risks and Benefits 
2.3.1. 
  Potential Risks 
The potential risks to the subjects due to participation in the study are those related to 
venipuncture, the IM injection and the administration of G03-52-01 
Venipuncture 
Venipuncture causes transient discomfort and may cause fainting.  Bruising at the site of the 
venipuncture may occur but can be prevented or lessened by applying pressure for several 
minutes. Infection at the site is possible but highly unlikely as aseptic technique must be 
employed. 
IM Injection 
An IM injection may cause some discomfort at the injection site.  Other risks may include pain, 
redness, swelling, or warmth at the injection site.  These risks are minimal. 
G03-52-01 
As G03-52-01 has not been administered to humans, the potential risks are based on adverse 
events associated with NTM-1631and NTM-1632 in the Phase 1 studies, infusion or injection of 
other antibody products, in particular other monoclonal antibody preparations against non-human 
targets, and the possibility of allergic reactions, especially IgE-mediated and serum sickness-like 
reactions. 
Adverse Events with a Similar Product 
A summary of all Adverse Events (AEs) assessed as related on the NTM-1631 clinical protocol 
following administration of NTM-1631 follows: 
NTM-1631 dose level 0.033mg/kg:  
• One female subject experienced a moderate decrease in hemoglobin reported 1-week post 
infusion.  She also had a mild elevation in Alanine Aminotransferase (ALT) 2 weeks post 
infusion. 
• One male subject experienced moderate protein in the urine one-week post infusion and a 
mild elevation in Aspartate Aminotransferase (AST) two months post infusion. 
• One male subject experienced a moderate elevation in blood sugar three days post 
infusion and then again two weeks post infusion. 
NTM-1631 dose level 0.165mg/kg: 
• One female subject experienced a mild increase in neutrophils starting one-month post 
infusion. 
NTM-1631 dose level 0.330mg/kg: 
• No associated AEs were reported in subjects receiving NTM-1631 at this dose. 
No safety signals or trends were identified on this protocol and a placebo subject also had a mild 
increase in AST and ALT three days post infusion.   


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A summary of all AEs assessed as related with the NTM-1632 clinical protocol following 
administration of NTM-1632 is as follows: 
NTM-1632 dose level 0.033mg/kg:  
• One female subject experienced mild throbbing pressure on forehead during infusion 
• One female subject experienced mild lightheadedness during infusion 
NTM-1632 dose level 0.33mg/kg 
• One female subject experienced mild loose stools 1-day post infusion 
Risk Factors Associated with Monoclonal Antibodies 
Injections of mAbs may be associated with injection reactions including: 
anaphylaxis/anaphylactoid type reaction, especially during a first exposure, and when 
administered rapidly.  Fever, chills and rigors, typically occurring within the first two hours 
following injection, characterize these reactions.  Other symptoms sometimes associated with 
injection reactions include nausea, vomiting, rash, pruritus, bronchospasm or other acute 
pulmonary response, angioedema, hypotension, hypertension, cardiac arrhythmias, dizziness, 
dyspnea, headache, and malaise.  
Risk of Immunogenicity 
Antibodies directed against G03-52-01 may develop following injection.  This will be assessed 
by taking blood samples at selected visits throughout the study.  G03-52-01 is a fully humanized 
mAb which based on experience with other humanized or chimeric mAbs, reduces the 
immunogenic potential.   
2.3.2. 
Known Potential Benefits 
This trial has no benefit for the subjects participating in the trial.  The knowledge gained in this 
trial may help society, especially those exposed to, or at risk of being exposed to, the toxins of 
botulism. 
3. 
OBJECTIVES 
3.1. 
Study Objectives 
Primary Objective:   
• To assess the safety and tolerability of escalating doses of G03-52-01 administered IM in 
healthy adult subjects. 
Secondary Objective: 
• To assess the (PK) and immunogenicity of escalating doses of G03-52-01 administered 
IM in healthy adult subjects. 


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3.2. 
Study Outcome Measures 
3.2.1. 
Primary Endpoints 
• The occurrence of Serious Adverse Events following administration of G03-52-01 to the 
final follow-up visit. 
• The occurrence of Adverse Events from administration of G03-52-01 to the final follow-
up visit. 
• The occurrence of changes from baseline in physical examination, vital signs and clinical 
safety laboratory values following administration of G03-52-01 to the final follow-up 
visit. 
3.2.2. 
Secondary Endpoints 
• The pharmacokinetic assessment of Cmax, Tmax and AUC(0-t) as measured by the validated 
Battelle Mouse Neutralization Assay (MNA) for serotypes A and B 
o Pharmacokinetic samples will be tested by MNA at pre-dose and on Days 4, 30, 
60, 90, and 120 for Cohorts 1-3. 
o Pharmacokinetic samples will be tested by MNA at pre-dose, 2-hours post-dose 
(future use), and on Days 4, 30, 45, 60, 90, and 120 for Cohort 4. 
• The assessment of Cmax, Tmax, half-life (α and β), MRT, and AUC(0-t) for each of the 
monoclonal antibodies of G03-52-01 as measured by a validated 
electrochemiluminescence assay (ECLA) or validated enzyme-linked immunosorbent 
assay (ELISA). 
o Pharmacokinetic samples will be tested by ECLA or ELISA at pre-dose, 2, 4, 8, 
24, 48, and 72 hours post injection, and on Days 4, 8, 15, 30, 45, 60, 90, and 120 
for Cohorts 1-3. 
o Pharmacokinetic samples will be tested by ECLA or ELISA at pre-dose, 6 hours 
post-dose, and on Days 1, 2, 4, 8, 15, 30, 45, 60, 90, 120, and 180 for Cohort 4. 
• Samples will be tested to evaluate presence of anti-drug antibodies (ADA) collected for 
all cohorts. 
o Samples will be tested for ADA at pre-dose, 15, 30, 45, 60, 90, and 120 for 
Cohorts 1-3. 
o Samples will be tested for ADA at pre-dose and on Days 45, 60, 90, 120, and 180 
for Cohort 4. 
4. 
STUDY DESIGN 
This is a Phase 1, single-center, placebo-controlled, double-blind, dose-escalation study to 
evaluate the safety and tolerability of G03-52-01 in healthy adults. This is a first-in-human study 
consisting of four Cohorts of ten subjects each.  Each subject will receive a single IM injection of 
G03-52-01 or placebo.   


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Table 1: 
 Cohorts 
Cohort 
Dose of G03-52-01  
Number of Subjects 
1 
10 mg 
10 subjects (8 active, 2 placebo) 
2 
25 mg 
10 subjects (8 active, 2 placebo) 
3 
50 mg 
10 subjects (8 active, 2 placebo) 
4 
100 mg 
10 subjects (8 active, 2 placebo) 
 
Schedule for Subjects 
Subjects in Cohorts 1-3 will participate in the study for approximately 150 days, including a 28-
day screening period, up to12-hour inpatient stay and approximately 120-day follow-up after 
study product administration.  Subjects will remain at the clinic and not be eligible for discharge 
until 8 hours after the IM injection.  Last follow up visit scheduled at Day 120.   
Subjects in Cohort 4 will participate in the study for approximately 210 days, including a 28-day 
screening period, up to a 12-hour clinic stay and approximately 180-day follow-up after study 
product administration.  Subjects will remain at the clinic and not be eligible for discharge until 
approximately 8 hours after the IM injection.  Last follow up visit scheduled at Day 180.   
The end of the study is defined as the date of the last visit of the last subject in the study. 
Schedule for Cohorts 
Since this is a first-in-human study, administration of the study products to subjects in a cohort 
will occur over a period of up to two weeks to allow careful observation of individuals for 
adverse events.  Two sentinel subjects within each cohort will be admitted initially and will be 
administered a single IM injection, and the randomization scheme will be designed to ensure that 
one subject will receive G03-52-01 and the other will receive placebo.  The dosing of the 
remaining eight subjects within that cohort will not be initiated until at least 24 hours have 
passed and no adverse events have occurred that meet halting criteria, and no safety signals have 
occurred that in the opinion of the investigator warrant further investigation.   The remaining 
eight subjects in the cohort will be admitted as scheduled without delay.   An alternate subject 
will be admitted to the unit for each two-subject group. Up to four alternates per cohort will be 
recruited. Dose escalation will not occur until safety data through Day 8 is reviewed by the 
Safety Review Committee (SRC) composed of the Principal Investigator (PI), Ology Bioservices 
Medical Monitor, and the ICON Medical Monitor. 
 
4.1 Study Enrollment and Withdrawal 
Only subjects who meet all of the inclusion and none of the exclusion criteria will be eligible 
for enrollment into this study.  No exemptions are granted on Inclusion/Exclusion Criteria in 
DOD-sponsored studies. 


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Forty healthy male and female subjects, ages 18 to 45 years old, will be enrolled in four cohorts.  
Up to four alternates per cohort will be recruited.  Alternates who meet all eligibility criteria 
may effectively have their check-in at the same time as the lead two subjects and be rolled over 
into the next group within that cohort but will not be dosed until 24 hours after the initial two 
subjects are dosed (Cohorts 1-3).  Alternates not enrolled into a dosing group within a cohort 
are eligible for enrollment into the next group for that cohort. Alternates not enrolled into the 
cohort are eligible for enrollment in subsequent cohorts but would have to undergo re-screening 
with the exception of the viral serology labs listed in section 7.5.1.1 if more than 28 days have 
passed since collection of screening laboratory parameters. 
4.1.1 Subject Inclusion Criteria 
All must be answered yes for the subject to be eligible for study participation 
1. Informed consent understood and signed 
2. Healthy male or healthy, non-pregnant, non-lactating female 
3. Willingness to comply and be available for all protocol procedures   
4. Between 18 and 45 years of age on the day of IM injection 
5. Body Mass Index (BMI) of ≥18.5 and ≤35 kg/m2  
6. If the subject is female and of childbearing potential, she has a negative serum pregnancy 
test at screening and negative urine test within 24 hours prior to IM injection 
• Note: A woman is considered of childbearing potential unless post-menopausal (≥ 
1 year without menses) or surgically sterilized via bilateral oophorectomy, or 
hysterectomy or bilateral tubal ligation or successful Essure placement with 
documented confirmation test at least 3 months after the procedure. 
7. If the subject is female and of childbearing potential, she agrees to practice abstinence from 
sexual intercourse with men or use acceptable contraception during participation in the 
study  
• Note: Acceptable contraception methods are restricted to effective devices 
(Intrauterine Contraceptive Devices)  
8. The hemoglobin, platelet count, white blood cell count and absolute neutrophil count are not 
below the LLN and ≤ULN x 10% 
• Abnormalities in mean corpuscular volume (MCV), mean corpuscular hemoglobin 
(MCH), mean corpuscular hemoglobin concentration (MCHC), red cell 
distribution width (RDW), mean platelet volume (MPV), and nucleated red blood 
cell count (NRBC CT), which are included in a complete blood count with 
differential, will not be exclusions. 
 
9. The urine dipstick results on protein, glucose and blood are negative or trace 
 
• Note: Menstruating females failing inclusion criteria due to a positive blood on 
urine dipstick may be retested following cessation of menses.   


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• Note: When a urine dipstick is more than trace positive for blood (whether a 
menstruating female or other subjects), that subject would not be excluded if the 
urine microscopic exam shows <5 rbcs/hpf. 
 
10. Chemistry screening laboratory tests as outlined in Section 7.5.1.4 are in the normal 
reference range 
• Note: The following exceptions to laboratory normal reference ranges are 
allowed: Creatinine, Blood Urea Nitrogen (BUN), total bilirubin, AST, ALT, 
lipase, amylase, Prothrombin Time (PT), Partial Thromboplastin Time (PTT) 
below the lower limit of normal (LLN); CK less than 400U/L; Glucose, 
potassium, total protein, and alkaline phosphatase with a toxicity grade of 1 is 
allowable; albumin above the upper limit of normal (ULN).  
• 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. 
11. The urine drug screen is negative 
12. Breathalyzer test is negative 
13. Available for follow-up for the duration of the study 
14. Agrees not to participate in vigorous activity 72 hours prior to dosing through day 15 post 
dosing 
4.1.2 Subject Exclusion Criteria 
Subjects meeting any of the following exclusion criteria are not eligible for participation. 
All must be answered no for the subject to be eligible for study participation 
1. History of a chronic medical condition that would either interfere with the accurate 
assessment of the objectives of the study or increase the risk profile of the subject. 
• Note: Chronic medical conditions include but not limited to diabetes; Asthma 
requiring use of medication in the year before screening; Autoimmune disorder 
such as lupus, Wegener’s, rheumatoid arthritis, thyroid disease; Coronary artery 
disease; Chronic hypertension; History of malignancy except low-grade 
(squamous and basal cell) skin cancer thought to be cured; chronic renal, 
hepatic, pulmonary, or endocrine disease (except previous asthma which has 
required no treatment for the past year);  
2. History of severe allergic reaction of any type to medications, bee stings, food, or 
environmental factors or hypersensitivity or reaction to immunoglobulins.   
• Note: Severe allergic reaction is defined as any of the following: anaphylaxis, 
urticaria, or angioedema 
3. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a 
QTc interval >450 milliseconds) 
4. Clinically significant abnormal electrocardiogram at screening.  


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• Note: Clinically significant abnormal ECG results include but not limited to: 
complete left or right bundle branch block; other ventricular conduction block; 
2nd degree or 3rd degree atrioventricular (AV) block; sustained ventricular 
arrhythmia; sustained atrial arrhythmia; two Premature Ventricular Contractions 
in a row; pattern of ST elevation felt consistent with cardiac ischemia; or any 
condition deemed clinically significant by a study investigator 
5. Positive serology results for HIV, HBsAg, or HCV antibodies 
 
6. Febrile illness with temperature ≥38°C within 7 days of dosing 
 
7. Pregnant or breastfeeding 
 
8. Donated blood within 56 days of enrollment 
 
9. Known allergic reactions to any of the study product components present in the formulation 
or in the processing, as listed in the Investigator Brochure  
 
10. Treatment with another investigational drug within 28 days of dosing 
 
11. Treatment with a monoclonal antibody within 3 months of enrollment.  
 
12. Receipt of antibody (e.g. TIG, VZIG, IVIG, IM gamma globulin) or blood transfusion 
within 6 months or within 5 half-lives of the specific product given 
 
13. Active drug or alcohol use or dependence that, in the opinion of the investigator, would 
interfere with adherence to study requirements 
 
14. Use of H1 antihistamines or beta-blockers within 5 days of dosing 
 
15. Use of any prohibited medication within 28 days prior to study entry or planned use during 
the study period 
 
• Note: Prohibited medications include immunosuppressives (except Nonsteroidal 
Anti-Inflammatory Drugs [NSAIDS]); immune modulators; oral corticosteroids 
(topical/intranasal steroids are acceptable); anti-neoplastic agents; any vaccine 
(licensed or investigational). Subjects will be eligible to receive any authorized 
COVID-19 vaccine after they complete Study Day 8 
16. Previous exposure to botulinum toxin, receipt of antibodies against botulinum toxin, or 
previous treatment with equine antitoxin 
 
17. Any previous injection or planned injection within 4 months after enrollment of 
botulinum toxin for cosmetic reasons, spastic dysphonia, torticollis, or any other reason 
 


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18. Any specific condition that in the judgment of the investigator precludes participation 
because it could affect subject safety 
 
19. Plans to enroll or is already enrolled in another clinical trial* that could interfere with 
safety assessment of the investigational product at any time during the study period 
 
• Note: Includes trials that have a study intervention such as a drug, biologic, 
or device 
 
20. Is a study site employee or staff 
• Note: Site employees or staff include the PIs and sub-investigators or staff 
who are supervised by the PI or Sub-Investigators 
 
21.  Systolic blood pressure >140mm Hg or diastolic blood pressure >90 mm Hg 
a.   Grade 1 values may be repeated once if the PI believes a transient condition let 
to the aberrant value and are allowable unless deemed clinically significant by 
the PI. 
 
22. Resting heart rate <50 or >100 beats per minute 
 
23. Oral temperature ≥ 38°C (100.4°F) 
 
24.  Subjects with NX02 antibody levels present at screening will be excluded from Cohort 4. 
4.2 Treatment Assignment Procedures 
4.2.1 Randomization Procedures 
Randomized treatment assignments will be generated by a statistician at ICON PLC.  
Randomization will occur following admittance to the unit and confirmation of eligibility is 
confirmed. 
This is a Phase 1 double-blinded, placebo-controlled trial that will randomize subjects within 
four dosing Cohorts to either active or placebo in an overall 4:1 ratio.  For each dosing cohort, 
the first two subjects will be randomized in a 1:1 fashion to active and placebo to ensure that one 
of the first two subjects receives active treatment and the other control.  An alternate subject will 
be admitted to the unit for each two-subject group.  If one of the first two subjects is not 
randomized for any reason, then the alternate subject will receive the next consecutive 
randomization number. The product assignment of the remaining eight subjects in each cohort 
will be a simple random sample to ensure the 4:1 ratio for the dosing cohort.  The randomization 
list will be generated by the unblinded study biostatistician and transferred to the unblinded study 
pharmacist prior to start of the study.   
If 2 or more subjects withdraw, are lost to follow up or terminate prior to Day 8, those subjects 
need to be replaced to ensure that data for at least 7 subjects is available for review. 


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If 2 or more subjects withdraw, are lost to follow up or terminate prior to Day 60 or are not 
compliant with all PK draws through Day 15, they may be replaced.   
If more than 2 subjects withdraw, are lost to follow up or terminate following the Day 8 SRC 
review of safety data, the site will attempt to replace those subjects in that dose group at the time 
of the next planned cohort. 
4.2.2 Masking Procedures 
The study staff participating in the administration of study product and assessment of the 
subjects will not be aware of the contents of the IM vial.  The G03-52-01 and placebo will look 
identical, so the study staff and the subject will not be able to determine whether placebo or G03-
52-001 is being injected. 
The Investigator may unblind a subject’s treatment assignment only in the case on an emergency 
or SAE, when knowledge of the study treatment is essential to the appropriate clinical 
management or welfare of the subject.  Whenever possible, the Investigator should first discuss 
the options with the Ology Bioservices Medical Monitor or appropriately designated Ology 
Bioservices personnel before unblinding the subject’s treatment assignment.  If this is 
impractical, the Investigator must notify Ology Bioservices as soon as possible but without 
revealing the subject’s treatment assignment.  The date and reason for unblinding must be 
recorded on the SAE form.  
4.2.3 Reasons for Withdrawal 
A subject may withdraw from the study at any time for any reason, without any consequence.  
A study subject will be discontinued from participation in the study if any of the following 
reasons occur prior to dosing: 
• Development of any exclusion criteria;  
• Request by the subject to terminate participation; 
• Requirement for prohibited concomitant medication or treatment; 
A subject may be removed from the study for the following reasons post dosing; however, 
whenever possible the subject should be followed for safety per protocol: 
• Failure to adhere to the protocol requirements 
• Lost to follow-up; 
• Request of primary care provider; 
• At the request of the Institutional Review Board (IRB)/Ethics committee, Food and 
Drug Administration (FDA), or DOD; 
• The subject’s well-being based on the opinion of the investigator;  
• The occurrence of a Serious Adverse Event (SAE) or (AE warranting withdrawal). 


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4.2.4 Handling of Withdrawals  
Subjects who are withdrawn prior to dosing may be replaced. Following dosing, one subject per 
cohort may withdraw prior to the completion of Visit 11 (Day 60) or was noncompliant with all 
PK draws through Visit 6 (Day 4) without being replaced.  Should more than one subject from the 
same cohort voluntarily withdraw from the study who did not meet the above criteria, those 
subjects may be replaced. Subjects who withdraw or are withdrawn from the study who received 
any amount of the study product will be encouraged to continue follow-up (with subjects’ consent) 
for safety.   Subjects withdrawing will be asked to complete a final termination visit if they do not 
wish to be followed per protocol. 
4.2.5 Lost to Follow-up 
In the case of subjects who fail to appear for a follow-up assessment, extensive effort (i.e., three 
documented contact attempts via phone calls, e-mail, etc., made on separate occasions and 
followed by a certified letter) will be made to locate or recall them, or at least to determine their 
health status.  These efforts will be documented in the subjects’ records. 
4.2.6 Termination of Study  
Although the study Sponsor has every intention of completing the study, it reserves the right to 
terminate the study at any time for clinical or administrative reasons. 
5. 
STUDY PRODUCTS 
5.1. 
Description of Study Products 
G03-52-01 drug product is a mixture of five human monoclonal IgG1 antibodies and one 
humanized monoclonal IgG1 antibody, which bind to non-overlapping epitopes on BoNT/A/B.  
Each of the component antibodies, NX01, NX02, NX11, XB10, XB18, and XB23, is separately 
produced in CHO cell lines.  Each mAb comprising G03-52-01 has distinct human variable 
regions that bind to BoNT/A/B.  No subtypes of BoNT/A or BoNT/B have been described. 
Placebo is 0.9% Sodium Chloride Injection, USP is a sterile, nonpyrogenic, isotonic solution of 
sodium chloride and water for injection.   
5.2. 
Acquisition 
The G03-52-01 will be supplied by Ology Bioservices, Inc. Study product will be shipped to the 
following address: 
 
ICON Early Phase Services 
Attn:  Pharmacist 
8307 Gault Lane 
San Antonio, TX 78209 


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The normal saline for injection will be supplied by ICON. 
5.3. 
Formulation, Packaging, and Labeling 
G03-52-01 
G03-52-01 is a mixture of five human IgG1 antibodies and one humanized IgG1 antibody 
lyophilized in a single use vial to 55 mg per vial.  When reconstituted with water for injection 
(WFI), the drug product is a clear, colorless, sterile aqueous solution in a pH 6 buffered vehicle 
without preservatives.   
Cohorts 1-3: The drug product will be supplied in 2-mL, pyrogen-free, Type 1 glass vials fitted 
with Teflon-coated butyl rubber stoppers and flip-up aluminum seals.   
Cohort 4: The drug product is supplied in a 3mL/13mm glass serum/lyophilized vial fitted with a 
13-mm FluroTec™-coated stopper and flip-up aluminum seal. 
G03-52-01 will be administered intramuscularly (IM) as a single dose at concentrations of 10 
mg, 25 mg, 50 mg, and 100 mg by varying the administration volume. 
 
Placebo (Normal Saline, 0.9% Sodium Chloride, USP) 
0.9% Sodium Chloride Injection, USP is a sterile, nonpyrogenic, isotonic solution of sodium 
chloride and water for injection.  Each mL contains sodium chloride 9 mg and contains no 
preservatives, bacteriostatic, antimicrobial agent, or added buffer.  The solution is clear in 
appearance with a pH range of 4.5 to 7.0.    
5.4. 
Product Storage and Stability 
G03-52-01 
G03-52-01 drug product will be shipped refrigerated at 2-8°C (36-46°F) and should be stored 
refrigerated at 2-8°C (36-46°F) until time of preparation.  If a vial is removed from refrigeration 
it must be used within 8 hours.  If not used, it must be quarantined and maintained for study 
product accountability as per Section 6.6. G03-52-01 should be protected from direct sunlight. 
G03-52-01 is not light sensitive under normal shipping and storage conditions.  The product 
should be used within 30 minutes upon reconstitution.  Avoid vigorous shaking or agitation. 
 
Placebo (Normal Saline, 0.9% Sodium Chloride, USP) 
Store at 20ºC to 25ºC (68°F to 77ºF) [See USP Controlled Room Temperature; excursions 
between 15°C and 30°C (59°F and 86°F) are permitted].  Protect from freezing. 
5.5. 
Dosage, Preparation and Administration 
The unblinded site Research Pharmacist will prepare the study drug on the same day as 
administration.  Prior to using any of the parenteral products, inspect for discoloration or 


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particulate matter before use.  Any product that fails inspection should be quarantined at 2-8°C 
for inspection by the Sponsor. Preparation of the product will be performed using aseptic 
technique under a sterile environment (e.g., Biologic Safety Cabinet or laminar flow hood). 
Based on the subject assigned cohort randomization, the appropriate G03-52-01 dose will be 
calculated, and the appropriate number of vials will be removed from storage to prepare the 
injection.  Vials containing G03-52-01 should not be vigorously shaken. Water for injection will 
be used to reconstitute the G03-52-01 for IM injection.  Any unused portion left in the vial 
should be retained for study product accountability as per Section 6.6. The placebo will be a 
normal saline injection without the addition of G03-52-01.  The product should be used within 
30 minutes upon reconstitution. 
The subjects will be admitted to the Phase 1 unit the day of the planned injection.  Verification 
that the subject still meets all inclusion criteria and does not have any exclusion criteria must be 
made prior to randomization. The unblinded site Research Pharmacist will prepare the injection 
as described and the injection must be completed within 30 minutes after preparation.  G03-52-
01 or Placebo should be administered as a single IM injection to the central, thickest portion of 
the deltoid.   
5.6. 
Accountability Procedures for the Study Products 
The Site Principal Investigator is responsible for the distribution and disposition of study product 
(both G03-52-01 and placebo) and has ultimate responsibility for accountability.  The site 
Principal Investigator may delegate this responsibility to the unblinded site Research Pharmacist.  
If delegated, the site Research Pharmacist will be responsible for maintaining complete records 
and documentation of study product receipt, accountability, dispensation, temperature 
monitoring, and storage conditions, and final disposition of the study product.   
All study products, whether administered or not, must be documented on the appropriate study 
product accountability record or dispensing log. Used and unused G03-52-01 vials and placebo 
vials will be retained until monitored and released for disposition as per requirements.       
Upon completion of the study and after the final monitoring visit, any remaining unused study 
product will either be returned or destroyed appropriately at the clinical site as per sponsor 
requirements and instructions, or in accordance with disposition plans. 
5.7. 
Assessment of Subject Compliance with Study Product  
Because each dose of G03-52-01 will be administered by site personnel, subject compliance is 
not anticipated to be an issue. 
5.8. 
Concomitant Medications 
Concomitant medication information will be recorded at Screening for the prior 28 days.  At 
each subsequent study visit each new concomitant medication and changes to existing 
medications will be recorded.   Subjects will be required not to utilize non-study medication or 
herbal supplements during the study except those deemed necessary by the site PI or sub 
investigator.  Any drug (e.g., over-the-counter herbal supplement, vitamins or prescription) used 


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by the subject during the course of the trial will be recorded in the subject’s source documents 
and on the appropriate eCRF. 
Subjects will be instructed to refrain from the receipt of any of the following during study 
participation unless medically indicated and deemed immediately necessary by their private 
physician: 
• Blood or blood products, 
• Any antibody (e.g. TIG, VZIG, IVIG, IM gamma globulin) 
• Any vaccines (licensed or investigational)  
*Subjects will be eligible to receive any authorized COVID-19 vaccine after they 
complete Study Day 8 
• Monoclonal antibody 
• Botulinum toxin 
• H1 antihistamines 
• Beta-blockers 
• Immunosuppressives (except NSAIDS) 
• Immune modulators 
• Oral corticosteroids (topical/intranasal steroids are acceptable) 
• Anti-neoplastic agents 
6. 
STUDY PROCEDURES  
6.1. 
Medical History 
Medical history will be obtained by direct interview.  Subjects will be queried regarding a history 
of significant medical disorders of the head, eyes, ears, nose, throat (HEENT), mouth, 
cardiovascular system, lungs, gastrointestinal tract, liver, pancreas, kidney, urologic, nervous 
system, blood, lymph glands, endocrine system, musculoskeletal system, skin, and 
genital/reproductive tract.  A history of any allergies, cancer, immunodeficiency, psychiatric 
illness, substance abuse, and autoimmune disease will be solicited. The medical history will 
include current and past medical diagnoses, hospitalizations and major surgical procedures. 
Demographic information (date of birth, gender, race, ethnicity) will be obtained as part of the 
medical history assessment.  The medical history will be obtained at screening and updated upon 
admittance to the unit on Day 0. 
6.2. 
Physical Examination 
An abbreviated physical examination (PE) will be conducted at the screening visit and Day 0.  
Height and weight will be obtained at screening.  An abbreviated PE is distinguished from a 
complete PE as all body system assessments are not required (e.g., pelvic, rectal, etc.).  On Day 


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0, the PE will focus assessment for the presence of the following in order to detect signs of a 
hypersensitivity reaction:  
o General appearance including alertness and any difficulty breathing.   
o  HEENT (confirm no swelling of lips/tongue/uvula) 
o Chest (confirm no stridor or wheezing) 
o Heart (assess regularity of rhythm) 
o Skin (confirm no hives, examine for any eruptions) 
o Joints (confirm no swelling, warmth, or tenderness) 
A symptom- directed PE will be performed at all other in-clinic study visits.  Refer to the MOP 
for further details.  Any new findings on examination post dosing or worsening of existing 
conditions are to be reported as AEs.   
6.3. 
Vital Signs 
Vital sign assessments including systolic and diastolic blood pressure (BP) [measured after 
sitting for at least 10 minutes], heart rate (HR), and oral temperature will be performed at each 
in-clinic study visit.  Vital signs that are thought to be aberrant due to an error in measurement 
may be repeated. During screening and follow-up, a measurement that is a Grade 1 (as 
referenced in Appendix B Toxicity Grading) may be repeated once if the PI believes a transient 
condition led to the aberrant value.   
Vital signs obtained at screening will serve as baseline values for the subject.  Grade 1 values are 
allowable unless deemed clinically significant by the study investigator. 
6.4. 
Electrocardiogram 
A 12-lead ECG will be performed at screening and reviewed by the study PI or a co-Investigator 
to assess the cardiac status of a subject for eligibility for enrollment. ECGs will be performed 
after the subject rests quietly in a supine position for at least 10 minutes. To be eligible for 
participation, the QT interval should be ≤450ms, and there must be no clinically significant ECG 
abnormalities according to the study investigators and may be repeated once.     
6.5. 
Laboratory Evaluations 
Venipuncture schedule and volumes are displayed in Table 2.  
6.5.1. 
 Screening Laboratory Tests 
6.5.1.1. 
Viral Serology Testing 
Subjects will be screened for HIV, HBsAg, and antibody to HCV.  These tests must be negative 
for eligibility into the study. In cases where a false positive result is suspected, confirmatory 
testing may be performed (e.g., Polymerase Chain Reaction).   
 


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  7.5.1.2    Drug Screen 
A urine toxicology screen will be performed to detect for the presence of the following: cocaine 
(and metabolite), barbiturates, benzodiazepines, opiates, THC, methamphetamine/amphetamine, 
methadone and PCP. The results must be negative for eligibility into the study.  A breathalyzer 
test will also be performed and results must be negative for eligibility into the study. 
 
 7.5.1.3 Pregnancy Testing 
For women of child-bearing potential, a serum pregnancy test will be done at screening and must 
be negative.  A urine pregnancy test will be done at Visit 2 (Day 0), which must be reported as 
negative before dosing. A urine pregnancy test will be repeated on Day 4, Day 45, and end of 
study (Day 120 or Day 180 (Cohort 4 only).  
 
7.5.1.4 Screening Laboratory Tests 
• Hematology: hemoglobin, WBC with differential, absolute neutrophil count and platelet 
count. MCV, MCH, MCHC, RDW, MPV, which are included in a complete blood count 
with differential, will not be graded. 
• Chemistry:  serum creatinine, BUN, calcium, total bilirubin, direct bilirubin, indirect 
bilirubin, alkaline phosphatase, PT, PTT, INR, ALT, AST, sodium, potassium, and total 
CK.  
• Urinalysis: dipstick: Urine protein, blood and glucose must be negative or trace. 
Menstruating females failing with a positive blood on urine dipstick may be retested 
following cessation of menses.  If dipstick is abnormal, a complete urinalysis with 
microscopic will be performed.  When a urine dipstick is more than trace positive for 
blood (whether a menstruating female or other subject), that subject would not be 
excluded if the urine microscopic exam shows <5 RBC/HPF.  
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.   Laboratory values will be entered in 
the Clinical Labs eCRF. 
6.5.2. 
 Safety Laboratory Tests 
The following laboratory tests will be done at screening and end of study.  Subjects should be 
fasting.  This means no food or drink (other than water) for at least eight hours prior to sampling. 
Safety labs with a Grade 1 value (Appendix B) will not exclude a subject from participation but 
will serve as their baseline value.   
• Hematology: hemoglobin, WBC with differential, absolute neutrophil count and platelet 
count. MCV, MCH, MCHC, RDW, MPV, which are included in a complete blood count 
with differential, will not be graded. 


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• Chemistry:  serum creatinine, BUN, calcium, total bilirubin, direct bilirubin, indirect 
bilirubin, alkaline phosphatase, PT, PTT, INR, ALT, AST, sodium, potassium, and total 
CK.  
• Urinalysis: dipstick: Urine protein, blood and glucose must be negative or trace. 
Menstruating females failing with a positive blood on urine dipstick may be retested 
following cessation of menses. 
6.5.3. 
Hypersensitivity Panel 
A hypersensitivity panel includes cytokine and complement panels, IgE and tryptase. This 14 mL 
sample will be drawn on Day 0 prior to dosing. The sample will be processed only if the subject 
has a hypersensitivity reaction. If a subject develops anaphylaxis or anaphylactoid reaction, an 
additional 14 mL sample will be drawn during the event and another will be drawn after the 
event.  Refer to the Manual of Procedures for further details. 
6.6. 
Special Assays or Procedures 
6.6.1. 
  Pharmacokinetic Assay 
Six-mL of blood will be drawn for the analysis of levels of each of the monoclonal antibodies in 
serum using a validated ECLA or ELISA.  Three ten-mL samples of blood will be drawn to be 
analyzed for neutralizing antibody concentrated using the validated Battelle MNA.  
6.6.2. 
 Anti-Drug Antibody Assay 
Six-mL samples of blood will be drawn pre-dose on Day 0, and on Days 15, 30, 45, 60, 90, and 
120 for determining the presence of ADA using a validated ECLA that measures total anti-drug 
antibody in serum for Cohorts 1-3.   This will be done to assess immunogenicity. 
Six-mL samples of blood will be drawn pre-dose on Day 0 and on Days 45, 60, 90, 120, and 180 
for determining the presence of ADA using a validated ECLA that measures total anti-drug 
antibody in serum for Cohort 4.  This will be done to assess immunogenicity. 
6.6.3. 
 Future Use  
Five-mL samples of blood will be drawn for subjects who consent to have samples stored for 
future use.  These samples will be collected at Day 0, 8 and 30 for all cohorts and 2 hours post 
dose for cohort 4. 
This blood sample may be used in new or different laboratory tests, to provide information for 
the development of new drug products, or for the studies of botulism or other infections. 
6.6.4. 
Specimen Preparation, Handling, and Shipping 
Details regarding the specimen preparation, handling, storage, and shipping are described in the 
MOP. 
 


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Table 2: Laboratory Samples and Estimated Total Blood Volume (mL)  
 
Study Visit 
 
01 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
Total 
Cohorts 
1-3 
Total 
for 
Cohort 
4 
Day 
-28 
to 
 -3 
Baseline 
24  hr 
 
48 hr/ 
 
72 hr 
 
4 
 
8 
±1 
15 
±1 
30 
±1 
45 
±3 
60 
±3 
90 
±3 
120 
±3 
180 
±3 
 
 
Dosing 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, HBV,HCV 
Serum β-HCG 
 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 
 
4 
 
Screening Labs 
 
9 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9 
 
9 
 
Safety Labs 
 
 
9 
 
 
 
 
 
9 
 
9 
 
9 
 
 
 
 
9e 
 
9 
 
45 
 
45 
PKa  (cohorts 1-3) 
 
 
 
24a 
 
 
     6 
 
6 
 
6 
 
6 
 
6 
 
6 
 
6 
 
6 
 
6 
 
 
6 
 
 
6 
 
6 
 
90 
 
 
PKa  (cohorts 4) 
 
12 
6 
6 
 
6 
6 
6 
6 
6 
6 
6 
6 
6 
 
78 
MNA (cohorts 1-3) 
 
30 
 
 
 
30 
 
 
30 
 
30 
30 
30 
 
180 
 
MNA (cohorts 4) 
 
30 
 
 
 
30 
 
 
30 
30 
30 
30 
30 
 
 
210 
ADA (cohorts 1-3) 
 
 
6 
 
 
 
 
 
 
6 
 
6 
 
6 
 
6 
 
6 
 
6 
 
 
 
42 
 
 
ADA (cohorts 4) 
 
6 
 
 
 
 
 
 
 
6 
6 
6 
6 
6 
 
36 
Future Usec 
 
 
5 
 
 
 
 
 
 
5 
 
 
5 
 
 
 
 
 
 
15 
 
15 
Hypersensitivity 
panel 
 
 
 
14b 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
14 
 
14 
Total Volume/ 
Visit (cohorts 1-3) 
 
13 
 
88 
 
6 
 
6 
 
6 
 
36 
 
20 
 
21 
 
56 
 
12 
 
42 
 
42 
 
51 
 
51 
 
399e 
 
 
Total Volume/ 
Visit (cohort 4) 
 
13 
 
76 
 
6 
 
6 
 
 
 
36 
 
20 
 
15 
 
50 
 
42 
 
42 
 
   42 
 
42 
 
27 
 
 
417 
Cumulative Totald 
Cohorts 1-3 
 
13 
 
101 
 
107 
 
 
113 
 
119 
 
155 
 
175 
 
196 
 
252 
 
264 
 
306 
 
348 
 
399e 
 
 
 
 
 


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Cumulative Total 
Cohorts 4 
 
13 
 
89 
 
95 
 
101 
 
101 
 
137 
 
157 
 
172 
 
222 
 
264 
 
306 
 
   348 
 
390 
 
417 
 
 
 
a PK serum samples taken prior to injection and 2hr, 4hr, 8hr, 24hr, 48hr, 72hr post-dose, and on days 4, 8, 15, 30, 45, 60, 90, and 120 for cohorts 1-3;  PK serum samples taken prior to 
injection and 6-hr post-dose, and on days 1, 2, 4, 8, 15, 30, 45, 60, 90, 120 and 180 for Cohort 4. 
b If a subject develops anaphylaxis or anaphylactoid reaction, an additional 14ml will be drawn during the event and after the event.  In this instance an additional 28 ml may be 
drawn from a subject than is reflected in the table totals. 
c For subjects consenting to future use 
d Total estimated volume drawn will vary slightly depending on future use consent and need for additional draws for the occurrence of hypersensitivity  
e Subjects in Cohorts 1-3 only 
 


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7. 
STUDY SCHEDULE 
The Schedule of Events is included as Appendix A. 
7.1. 
Visit 1: Screening (Day -28 to Day -3) 
After providing written informed consent, each subject will be assigned a Subject ID number and 
undergo an eligibility assessment.  The following will be done during the screening period 
(within 28 days prior to administration of study product).  Results of screening tests and 
procedures will be evaluated by the investigator to determine eligibility prior to enrollment and 
randomization.  The following procedures will be performed. 
• Record demographics including age, gender, race and ethnicity.  Obtain contact 
information. 
• Obtain medical history.  The medical history will include the following: 
 current medical diagnoses 
 past medical diagnoses 
 hospitalizations 
 major surgical procedures  
 blood transfusions or immunoglobulin within the last 6 months 
 live vaccines within the last 28 days 
 killed vaccines within the last 28 days 
 *Subjects will be eligible to receive any authorized COVID-19 vaccine after they 
complete Study Day 8 
 
 blood donation within the last 56 days 
 allergic reactions 
 drug and/or alcohol use or dependence 
 receipt of investigational drug within the last 28 days 
 Receipt of monoclonal antibody in the past  
 Exposure to botulinum toxin in the past 4 months 
• Review concomitant medication history, including all medications taken within the 
last 28 days 
• Review current use of contraceptive methods and recent menstrual history (female 
subjects only) 


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• Perform abbreviated PE by licensed clinician listed on the Form FDA 1572 [examples 
include Medical Doctor, Nurse Practitioner and Physician’s Assistant] 
• Obtain height and weight and calculate BMI 
• Take vital signs (systolic and diastolic blood pressure, pulse rate, and oral 
temperature)  
• Obtain fasting blood samples for viral serology, clinical laboratory screening tests 
• Obtain blood sample for serum pregnancy test for women of child bearing potential 
• Obtain blood to assess NX02 antibody levels (Cohort 4 subjects only) 
• Obtain urine sample for dipstick urinalysis and urine toxicology 
• Obtain 12-lead ECG 
• Perform Breathalyzer test for recent alcohol use 
• Counsel on the avoidance of pregnancy for women of child-bearing potential 
• Counsel on the avoidance of botulinum toxin, vaccines and drugs listed in section 6.8. 
7.2. 
Visit 2: Baseline (Day 0) 
Subjects meeting inclusion/exclusion criteria will be admitted to the clinical unit the day of the 
injection and the following procedures will be performed prior to study drug administration: 
• Review inclusion/exclusion criteria to ensure the subject remains eligible for enrollment 
• Update medical history 
• Review and update concomitant medications 
• Perform abbreviated physical examination  
• Obtain vital signs 
• Perform Breathalyzer test to detect recent alcohol use 
• For women, a urine hCG test will be done.  The results must be confirmed to be negative 
before dosing 
• Obtain urine sample for toxicology 
• Obtain blood samples for 
o Baseline serum PK (prior to injection and at the completion of the 
injection and 2hr, 4hr, and 8 hr post dosing for subjects in Cohorts 1-3)  
o Baseline serum PK (prior to injection and at 6 hours post-injection for 
subjects in Cohort 4) 
o Serum sample to store for future use samples (for subjects who consent) 
o MNA (prior to injection for subjects in Cohorts 1-3) 


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o MNA (prior to injection and at 2 hours post-injection (optional) for 
subjects in Cohort 4)  
o ADA (prior to injection for all subjects) 
o Hypersensitivity panel 
o Clinical Safety Labs 
• Randomize the subject and obtain study product from the pharmacy 
• Perform IM Administration of study product 
• Assessment of AEs and SAEs after administration of study product 
• The subject is eligible for discharge after all assessments have been performed, including 
the 8-hour post injection blood draw and there are no signs of anaphylaxis. 
7.3. 
Visit 3: Out-patient Follow-up (24 hours/Day 1) 
• Obtain vital signs  
• Review and update concomitant medications 
• Perform symptom directed PE  
• Obtain blood samples for the following: 
o PK measurement at 24 hours (+/- 2 hours)   
• Counsel women of child-bearing potential on the avoidance of pregnancy 
• Counsel the subject not to receive any botulinum toxin preparation (e.g., Botox) for 4 
months after injection.   
• Assessment of AEs and SAEs  
7.4. 
Visit 4: Out-patient follow-up Visit (48 hours/Day 2) 
• Obtain vital signs  
• Review and update concomitant medications 
• Perform symptom directed PE  
• Obtain blood samples for the following: 
• PK measurement at 48 hours (+/- 2 hours)  Counsel women of child-bearing potential on 
the avoidance of pregnancy 
• Counsel the subject not to receive any botulinum toxin preparation (e.g., Botox) for 4 
months after injection   
• Assessment of AEs and SAEs  


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7.5. 
Visit 5: Out-patient Follow-up (72 hours) Cohorts 1-3 
• Obtain vital signs  
• Review and update concomitant medications 
• Perform symptom directed PE  
• Obtain blood samples for the following: 
o PK measurement at 72 hours (+/- 2 hours)   
• Counsel women of child-bearing potential on the avoidance of pregnancy 
• Counsel the subject not to receive any botulinum toxin preparation (e.g., Botox) for 4 
months after injection.   
• Assessment of AEs and SAEs  
7.6. 
Visit 6: Out-patient Follow-up (Day 4) 
• Obtain vital signs  
• Review and update concomitant medications 
• Perform symptom directed PE  
• Obtain blood samples for the following: 
o PK measurement  
o MNA   
• Obtain urine sample urine HCG for women of child bearing potential 
• Counsel women of child-bearing potential on the avoidance of pregnancy 
• Counsel the subject not to receive any botulinum toxin preparation (e.g., Botox) for 4 
months after injection.   
• Assessment of AEs and SAEs 
7.7. 
Visit 7: Out-patient Follow-up (Day 8± 1) 
• Obtain vital signs  
• Review and update concomitant medications 
• Perform symptom directed PE  
• Obtain blood samples for the following: 
o Clinical Safety Labs 
o PK measurement  
o Serum sample to store for future use (if subject gave consent) 
• Counsel women of child-bearing potential on the avoidance of pregnancy 


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• Counsel the subject not to receive any botulinum toxin preparation (e.g.  Botox) for 4 
months after injection 
• Assessment of AEs and SAEs 
 
7.8. 
Visit 8: Out-patient Follow-up (Day 15± 1) 
• Obtain vital signs  
• Review and update concomitant medications 
• Perform symptom directed PE  
• Obtain blood samples for the following: 
o Clinical Safety Labs 
o PK measurement  
o ADA (Cohorts 1-3 only) 
• Assessment of AEs and SAEs 
• Counsel women of child-bearing potential on the avoidance of pregnancy 
• Counsel the subject not to receive any botulinum toxin preparation (e.g.  Botox) for 4 
months after injection 
• Assessment of COVID-19 vaccination status 
7.9. 
Visit 9: Out-patient Follow-up (Day 30 ± 1) 
• Obtain vital signs  
• Review and update concomitant medications 
• Perform symptom directed PE  
• Obtain blood samples for the following: 
o Clinical Safety Labs 
o PK measurement  
o MNA 
o ADA (Cohorts 1-3 only) 
o Serum sample to store for future use (if subject gave consent) 
• Assessment of AEs and SAEs 
• Counsel women of child-bearing potential on the avoidance of pregnancy 
• Counsel the subject not to receive any botulinum toxin preparation (e.g.  Botox) for 4 
months after injection 


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• Assessment of COVID-19 vaccination status.  
 
7.10. 
Visit 10: Out-patient Follow-up (Day 45± 3) 
• Obtain vital signs 
• Review and update concomitant medications 
• Perform symptom directed PE  
• Obtain blood samples for the following: 
o PK measurement  
o ADA 
o MNA (Cohort 4 only) 
• Perform urine pregnancy test on women of child-bearing potential 
• Assessment of AEs and SAEs 
• Counsel women of child-bearing potential on the avoidance of pregnancy 
• Counsel the subject not to receive any botulinum toxin preparation (e.g.  Botox) for 4 
months after injection 
• Assessment of COVID-19 vaccination status.  
 
7.11. 
Visit 11: Out-patient Follow-up (Day 60 ± 3) 
• Obtain vital signs  
• Review and update concomitant medications 
• Perform symptom directed PE  
• Obtain blood samples for the following: 
o PK measurement  
o MNA 
o ADA 
• Assessment of AEs and SAEs 
• Counsel women of child-bearing potential on the avoidance of pregnancy 
• Counsel the subject not to receive any botulinum toxin preparation (e.g.  Botox) for 4 
months after injection 
• Assessment of COVID-19 vaccination status.  
 


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7.12. 
Visit 12: Out-patient Follow-up (Day 90±3) 
• Obtain vital signs  
• Review and update concomitant medications 
• Perform symptom directed PE  
• Obtain blood samples for the following: 
o PK measurement  
o MNA 
o ADA 
• Assessment of AEs and SAEs 
• Counsel women of child-bearing potential on the avoidance of pregnancy 
• Counsel the subject not to receive any botulinum toxin preparation (e.g.  Botox) for 4 
months after injection 
• Assessment of COVID-19 vaccination status.  
 
7.13. 
Visit 13: Final Visit / Early Termination Visit for Cohorts 1-3 (Day 
120±3)  / Cohort 4 (Day 120±3) 
• Obtain vital signs  
• Review and update concomitant medications 
• Perform symptom directed PE  
• Obtain blood samples for the following: 
o Clinical Safety labs (Cohorts 1-3 Only) 
o PK measurement  
o MNA 
o ADA 
• Obtain urine sample for dipstick analysis  
• Perform urine pregnancy test on women of child-bearing potential 
• Assessment of AEs and SAEs 
• Counsel women of child-bearing potential on the avoidance of pregnancy 
• Counsel the subject not to receive any botulinum toxin preparation (e.g.  Botox) for 4 
months after injection 
• Assessment of COVID-19 vaccination status.  


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7.14. 
Visit 14: Final Visit/ Early Termination for Subjects in Cohort 4  
(Day 180±3) 
• Obtain vital signs  
• Review and update concomitant medications 
• Perform symptom directed PE  
• Obtain blood samples for the following: 
o Clinical Safety Labs  
o PK measurement  
o ADA 
• Obtain urine sample for dipstick analysis  
• Perform urine pregnancy test on women of child-bearing potential 
• Assessment of AEs and SAEs 
• Counsel women of child-bearing potential on the avoidance of pregnancy 
• Counsel the subject not to receive any botulinum toxin preparation (e.g.  Botox) for 4 
months after injection 
• Assessment of COVID-19 vaccination status.  
 
 
7.15. 
Unscheduled Visit 
A subject may return to the clinic for an unscheduled visit at any time.  The following activities 
at a minimum should be performed:  
• Obtain vital signs  
• Perform symptom directed PE as appropriate 
• Review and update concomitant medications 
• Assessment of AEs and SAEs 
• Assessment of COVID-19 vaccination status.  
 


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8. 
ASSESSMENT OF SAFETY 
Regulatory requirements including the FDA regulations and ICH Guidelines for GCP set forth 
safety monitoring and reporting responsibilities of sponsors and investigators to ensure the safety 
and protection of human subjects participating in clinical trials.   
Responsibilities 
Investigators participating in this clinical trial are responsible for and will: 
• evaluate subject safety including assessment of AEs for seriousness, severity, and 
causality; 
• notify the sponsor (Ology Bioservices) of SAEs immediately; 
• provide detailed written reports, including necessary documentation requested by the 
sponsor or IRB/Independent Ethics Committee (IEC), promptly following immediate 
initial reports, and; 
• Inform the IRB/IEC of AEs as required by applicable regulatory requirements. 
8.1. 
Specification of Safety Parameters 
Definitions 
Adverse events 
ICH E6(R2) defines an AE as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily have 
a causal relationship with this treatment.  An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of medicinal (investigational) product, whether or not related to the 
medicinal (investigational) product.   
FDA defines an AE as any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. 
 
Serious Adverse Events 
An SAE is any untoward medical occurrence that at any dose: 
• Results in death, 
• Is life-threatening*,  
• Requires inpatient hospitalization or prolongation of existing hospitalization, 
• Congenital anomaly/birth defect; 
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
*Life-threatening adverse event.  An adverse event is considered “life-threatening” if, 
in the view of either the investigator or sponsor, its occurrence places the patient or 


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subject at immediate risk of death.  It does not include an adverse event, had it 
occurred in a more severe form, might have caused death. 
Unexpected 
An adverse reaction, the nature or severity of which is not consistent with the applicable product 
information (e.g. Investigator’s Brochure for an unapproved investigational product or package 
insert/summary of product characteristics for an approved product). 
8.2. 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters 
8.2.1. 
Adverse Events 
Any medical condition that is present at the time that the subject is screened should be 
considered as baseline and not reported as an AE.  However, if the condition increases in severity 
or frequency at any time during the study, it should be recorded as an AE. 
All AEs must be graded for severity and relationship to study product based on the Investigator’s 
assessment. 
Severity of adverse events will be graded as follows based on the Investigator’s assessment 
unless otherwise specified in Appendix B.: 
Mild:  Events require minimal or no treatment and do not interfere with the subject’s daily 
activities. 
Moderate:  Events result in a low level of inconvenience or concern with therapeutic measures. 
Moderate events may cause some interference with functioning. 
Severe:  Events interrupt a subject’s usual daily activity and may require systemic drug therapy 
or other treatment.  Severe events are usually incapacitating. 
8.2.2. 
Relationship to Study Product 
AEs and SAEs must be assessed by the investigator to determine relationship to study product.  
All AEs must have their relationship to study product assessed using the following terms.  In a 
clinical trial the study product must always be suspect.   
• Definitely Related:  There is a definite probability that the study product caused the 
adverse event. 
• Possibly Related:  There is a reasonable possibility that the study product caused the 
adverse event.  Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study product and the adverse event 
• Not Related: There is not a reasonable possibility that the administration of the study 
product caused the event 
To help assess, the following factors may be considered: 
• Temporal relationship of the event to the administration of study product; 


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• Whether an alternative etiology has been identified; 
• Biological plausibility; 
• Existing therapy and/or concomitant medications. 
8.3. 
Reporting Procedures 
8.3.1. 
 Adverse Events: 
AEs not meeting the criteria for “SAEs,” will be captured on the appropriate case report form.  
Information to be collected for AEs includes event description, time of onset, investigator 
assessment of severity, relationship to study product, date of resolution of the event, seriousness, 
and outcome. 
All AEs will be followed until resolved or considered stable by the investigator.  
8.3.2. 
Serious Adverse Events 
The following procedures will apply to all serious adverse events: 
• 
The Principal Investigator will report any SAE to ICON PVSS within 24 hours of 
awareness. 
• 
ICON PVSS will perform an initial check of the SAE for missing elements and then inform 
the ICON MM, and the ISM. 
• 
ICON PVSS will record the information on the appropriate serious adverse event report 
form and send to DOD  PVG and to Ology Bioservices 
• 
Each SAE will be reviewed and followed to resolution or stability by a study physician 
• SAEs will be collected on each subject until his/her last study visit. 
 
Any AE that meets a protocol-defined serious criterion must be submitted immediately 
(within 24 hours of site awareness) on an SAE form to Ology Bioservices at the following 
address: 
 
ICON PVSS 
ICON plc PVSS 
 
3rd Floor Marlow International, Parkway, Marlow, 
 
Buckinghamshire, SL7 1YL, United Kingdom 
 
SAE Email Address: ICON-Safety-
CentralReceipt@iconplc.com  
 
ICON Medical Monitor:                                            Uma Arumugam, MD  
                                                                                                                                 ICON Early Phase Services 


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820 West Diamond Ave., Suite 100 
       
Gaithersburg, MD 20878, USA 
       
SAE Phone:  410-294-2537 
       
SAE Email Address:  uma.arumugam@iconplc.com  
 
ICON PVSS will send AE/SAE information to Ology Bioservices, Inc. 
Ology Bioservices 
Ology Bioservices, Inc. 
 
13200 NW Nano Court  
 
Alachua, FL 32615, USA 
 
 SAE Hotline: 352-213-5757  
 
SAE Fax Number:  888-551-1691 
 
SAE Email Address: olo.safety@resilience.com 
 
Other supporting documentation of the event may be requested by Ology Bioservices and should 
be provided as soon as possible.  
ICON plc PVSS will send SAEs with the ICON Drug Safety Physician assessment of causality, 
expectedness, and any impact on the benefit-risk ratio of the IMP to Ology Bioservices and DOD 
PVG.  The ICON medical monitor and clinical project manager will be notified of the SAE by 
DOD PVG.  The ICON medical monitor will review and assess the SAE for potential impact on 
study subject safety and protocol conduct.   
At any time after completion of the study, if the investigator becomes aware of an SAE that is 
suspected to be related to study product, the investigator will report the event to ICON PVSS. 
8.3.3. 
Regulatory Reporting  
Following notification from the investigator, Ology Bioservices, the IND sponsor, will report 
any suspected adverse reaction that is both serious and unexpected to the FDA.  Ology 
Bioservices will report an adverse event as a suspected adverse reaction only if there is evidence 
to suggest a causal relationship between the drug and the AE.  Ology Bioservices will notify 
FDA and all participating investigators (i.e., all investigators to whom the sponsor is providing 
drug under its INDs or under any investigator’s IND) in an IND safety report of potential serious 
risks from clinical trials or any other source, as soon as possible, but in no case later than 15 
calendar days after the sponsor determines that the information qualifies for reporting as 
specified in 21 CFR Part 312.32. Ology Bioservices will also notify FDA of any unexpected fatal 
or life-threatening suspected adverse reaction as soon as possible but in no case later than 7 
calendar days after the sponsor’s initial receipt of the information. Relevant follow up 
information to an IND safety report will be submitted as soon as the information is available.  
Upon request from FDA, Ology Bioservices will submit to FDA any additional data or 


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information that the agency deems necessary, as soon as possible, but in no case later than 15 
calendar days after receiving the request. 
All SAEs designated as “not related” to study product(s), will be reported to the FDA at least 
annually in a summary format. 
8.3.4. 
 Reporting of Pregnancy 
Pregnancies that occur during the study period will be reported to the Sponsor on the Pregnancy 
Report form within five days of site awareness. 
Efforts will be made to follow all pregnancies occurring prior to 56 days post product 
administration through to outcome, as described in the Safety Management Plan (e.g. delivery, 
spontaneous abortion or therapeutic abortion). 
8.4. 
Type and Duration of Follow-up of Subjects after Adverse Events 
AEs will be followed until resolution or stability even if this extends beyond the study-reporting 
period.  Resolution of an AE is defined as the return to pretreatment status or stabilization of the 
condition with the expectation that it will remain chronic. 
Follow-up procedures, evaluations, and outcomes will be recorded on the subject's case report 
forms. 
8.5. 
Halting Rules 
8.5.1. 
Halting Criteria for the Study 
Study dosing can be halted at any time if medically indicated.  Study dosing must be stopped, and 
a review of available safety data will be conducted by the SRC if any of the following occur: 
1. Death of a dosed subject following injection and prior to the subject’s last visit that was 
not the result of trauma or accident, and possibly related to study product. 
2. Occurrence of a life-threatening allergic/hypersensitivity reaction (anaphylaxis) in any 
subject, manifested by bronchospasm with or without urticaria or angioedema or 
requiring hemodynamic support with pressor medications or mechanical ventilation.  
3.  One subject with an SAE. 
4. Two or more subjects with a Grade 3 AE in the same organ class (systemic toxicity, 
clinical laboratory tests or vital signs) regardless of relatedness to study drug.  An 
exception to this includes scenarios where there are obvious and acceptable physiological 
explanations for a Grade 3 abnormality (e.g., Grade 3 hematuria in a menstruating 
female). 
8.5.2. 
Dose Escalation Halting Criteria 
If any of the following criteria are met, escalation to the next planned dose cohort will not 
proceed until all available study data have been reviewed by the SRC.  


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- 
More than 25% of the subjects in the cohort experience an AE, grade 2 or above in 
the same organ class 
- 
A specific AE increases in severity from one cohort to the next AND the number of 
subjects reporting that AE (at the higher severity level) in the cohort is the same or 
greater. An exception would be headaches going from a grade 1 to a grade 2. 
8.5.3. 
Evaluation of Dose Escalation 
The SRC must agree unanimously on the following criteria prior to dose escalation: 
• A review of all available unmonitored and uncoded safety data from at least 7 
subjects per cohort to Day 8, at a minimum, demonstrate that study halting criteria 
as outlined in Section 9.5.2 have not been met. 
• A review of all available unmonitored and uncoded safety data from at least 7 
subjects per cohort to Day 8, at a minimum, demonstrate that no safety signals of 
any nature were observed. 
8.6. 
Safety Oversight  
8.6.1. 
Independent Safety Monitor (ISM) 
The ISM is a physician with relevant expertise whose primary responsibility is to provide 
independent safety monitoring in a timely fashion.  The ISM will review SAEs and other AEs as 
needed and provide an independent assessment.   
8.6.2. 
ICON Medical Monitor 
The ICON Medical Monitor (MM) is the clinical site’s primary point of contact for eligibility or 
safety related questions.  The ICON MM is responsible for liaising with Ology Bioservices 
Medical Monitor to ensure that all medical concerns are communicated and will provide any 
potential pertinent medical communication update to the project team as needed.  Can make a 
recommendation that the SRC be convened to review any safety concerns.  
The ICON Medical Monitor will communicate with the Ology Bioservices Medical Monitor for 
any safety related questions.  The ICON MM will participate in the planned SRC meetings and 
can make a recommendation that the SRC be convened to review any safety concerns. 
8.6.3. 
Ology Bioservices Medical Monitor  
The Ology Bioservices Medical Monitor will be the main point of contact for the ICON MM 
including any safety-related questions or concerns.  The Ology Bioservices MM will escalate any 
medical or safety concerns to the DOD as needed. The Ology Bioservices MM will participate in 
the planned SRC meetings and can make a recommendation that the SRC be convened to review 
any safety concerns.  
8.6.4. 
Safety Review Committee (SRC) 
The SRC will be composed of:  


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• PI, or designee  
• Ology Bioservices Medical Monitor  
• ICON Medical Monitor or designee; 
Objective dose-escalation criteria and safety evaluations will be utilized.  For Cohorts 1, 2, and 3 
the SRC will evaluate unmonitored and uncoded safety and tolerability data for at least 7 
subjects out to Day 8 to determine whether dose escalation can occur.  If none of the events 
described in 9.5.1 Study Halting Criteria or in 9.5.2 Dose Escalation Halting Criteria are 
observed, dose escalation will proceed.  Should any of the study halting criteria or dose 
escalation halting criteria be met, the SRC will meet to evaluate the data and recommend 
appropriateness of further dosing.  The SRC recommendation to advance to the next level will be 
documented and provided to all the appropriate parties (PI, Ology Bioservices, ICON and DOD) 
involved with the study. 
If 2 or more subjects withdraw prior to Day 8, those subjects need to be replaced to ensure that 
data for at least 7 subjects is available for review. 
If 2 or more subjects withdraw prior to Day 60 or are not compliant with all PK draws through 
Day 15, they may be replaced.   
If more than 2 subjects withdraw following the Day 8 SRC review of safety data, the site will 
attempt to replace those subjects in that dose group at the time of the next planned cohort. 
9. 
CLINICAL MONITORING 
9.1. 
Site Monitoring Plan 
Site monitoring is conducted to ensure that the human subject protection, study and laboratory 
procedures, study intervention administration, and data collection processes are of high quality 
and meet sponsor, GCP/ICH and, when appropriate, regulatory guidelines.  Site visits may be 
conducted by an authorized representative of ICON or other regulatory agencies to inspect study 
data, subjects’ medical records, and eCRFs in accordance with ICH guidelines, GCP and the 
respective local and national government regulations and guidelines. 
The investigator will permit authorized representatives of ICON and the respective local and 
national health authorities to inspect facilities and records relevant to this study, if needed. 
A separate monitoring plan, to be developed by ICON, will describe protocol-specific items to be 
monitored. 
10. 
STATISTICAL CONSIDERATIONS 
10.1. 
Sample Size Considerations 
This is a Phase 1 study first in humans with four dosing Cohorts and no formal sample size 
calculations based on testing a statistical hypothesis were constructed. Four dosing groups of ten 
each with eight participants assigned the active group and two assigned to the control group are 


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practical and provide sufficient information for a total sample size of 40 for a Phase 1 trial 
primarily designed to assess safety.  If ten subjects are studied, then the probability of at least 
one subject experiencing an event of toxicity can range from 0.728 to 0.996 assuming true event 
rates between 0.15 and 0.5 Additionally, if no events are observed in a cohort of six dosed 
subjects receiving G03-52-01 the upper bound of an exact 95% confidence interval for the true 
proportion is 0.46   
10.2. 
Planned Interim Analyses  
A blinded interim safety and PK analysis is planned for this study to analyze all PK, ADA, and 
MNA samples for Cohorts 1-3 through Day 60 and Day 120.  A second blinded interim safety 
analysis is planned to analyze all PK, ADA, and MNA samples for Cohort 4 through Day 90.  
Stopping criteria are for safety and are defined in section 9.5. 
10.3. 
Final Analysis Plan 
The ICH Guidance Document E9 (Statistical Principles for Clinical Trials) will be followed for 
all statistical content.  For categorical data, summaries of frequencies and percentages will be 
presented.  Summaries for continuous data will include minimum, lower quartile, median, mean, 
standard deviation, upper quartile, and maximum 
10.3.1. 
Analysis Populations 
All subjects who received study product will be included in the safety population and analyzed 
as treated. The PK analysis population will consist of all subjects who complete G03-52-01 
injection and have sufficient evaluable PK samples for the estimation of PK parameters. 
10.3.2. 
Demographics and Baseline Characteristics 
Subject demographics and baseline characteristics will be summarized by dose cohort and 
control group.   
10.3.3. 
 Safety Analysis Plan 
10.3.3.1. Adverse and Serious Adverse Events 
AEs will be coded using Medical Dictionary for Regulatory Activities® (MedDRA). All AEs that 
occur after the initiation of study medication will be summarized using frequency counts and 
percentages. Summaries will be presented by dose cohort and control group. The following 
summaries will be presented for AEs and SAEs:  
• Overall (i.e., regardless of severity or relationship to treatment) 
• By severity grade (mild, moderate, or severe) 
• By relationship to study medication 
• By MedDRA level hierarchy (system organ class and preferred term) 
Unless otherwise specified, at each level of subject summarization in reporting the incidence of 
the AEs, a subject will be counted once if the subject reported one or more events. If more than 


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one occurrence of an event is reported, the event of the worst severity or the worst-case 
relationship assessment will be summarized.  
10.3.3.2. Additional Safety Analyses 
Vital signs, physical examinations, and clinical laboratory values, including change from 
baseline, will be summarized by dose cohort and control group. 
Descriptive summary statistics for laboratory data at admission (baseline value) and each 
applicable post-injection visit, including change from the baseline value, will be calculated. 
Descriptive summary statistics for vital signs at screening (baseline value) and each applicable 
post-injection visit, including change from the baseline value, will be calculated. Shift tables, 
showing individual subject changes from baseline will be presented for laboratory parameters 
using toxicity grading (Appendix B). Subjects with Graded values of vital sign and laboratory 
parameters will be identified in listings.  
10.3.4. 
  PK Analysis Plan 
PK parameters will be estimated for each of the six monoclonal antibodies separately using 
noncompartmental methods in WinNonlin or a similar software package. Parameters will be 
estimated by dose cohort. Summary statistics will include the mean, median, coefficient of 
variation, and range. When evaluable, estimated PK parameters will include: 
• AUC(0-t): Area under the concentration time-curve to the last concentration above the lower 
limit of quantitation 
• Cmax: Maximum observed concentration 
• Tmax: Time of maximum observed concentration 
• Kel: Elimination rate constant 
• AUC(0-∞): Area under the concentration time-curve extrapolated to infinity 
• t1/2: Terminal elimination half-life 
• CL: Total clearance 
• Vz: Volume of distribution 
Additionally, multi-compartmental models will be considered based on inspection of 
concentration-time curves. If models are fit, base models will assume first-order elimination 
from the central compartment, and models will be parameterized in terms of clearance, volume 
of distribution and inter-compartmental rates. Standard objective goodness of fit measures will 
be used to determine the final model. 
10.3.5. 
Immunogenicity 
Immunogenicity will be measured by the development of antibody titers.  The presence of ADA 
will be measured over the course of the post-injection period. 


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10.3.6. 
 Missing values and outliers 
All attempts will be made to collect all data per protocol.  No imputation will be performed for 
missing values. Outliers identified during the PK analysis will be discussed in the analysis report. 


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11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
The site will maintain appropriate medical and research records for this trial, in compliance with 
ICH E6(R2) GCP, Section 4.9, and regulatory and institutional requirements for the protection of 
confidentiality of subjects.  As part of participating in a DOD-affiliated, or manufacturer-
sponsored study, the site will permit authorized representatives of the sponsor(s), DOD, and 
regulatory agencies to review (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. 
Forms for use as source documents will be derived from the electronic CRFs and will be 
provided by ICON.  Additional source data are all information, original records of clinical 
findings, observations, or other activities in a clinical trial necessary for the reconstruction and 
evaluation of the trial.  Examples of these original documents and data records include, but are 
not limited to, hospital records, clinical and office charts, laboratory notes, memoranda, 
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 subject files and records kept at the pharmacy, 
laboratories, and medico-technical departments involved in the clinical trial.  If data is recorded 
directly into the eCRF with no paper source, then that data should be listed as being a direct 
electronic data entry with no paper source available. 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Following a written DOD-accepted site quality management plan, the investigational site is 
responsible for conducting routine quality assurance and quality control activities to internally 
monitor study progress and protocol compliance.  The PI will provide direct access to all trial-
related sites, source data/documents, and reports for the purpose of monitoring and auditing by 
the sponsor, and inspection by local and regulatory authorities. The PI will ensure all study 
personnel are appropriately trained and applicable documentations are maintained on site.  
Clinical monitors will verify that the clinical trial is conducted, and data are generated, 
documented (recorded), and reported in compliance with the protocol, GCP, and the applicable 
regulatory requirements.  Clinical monitoring reports will be submitted to Ology Bioservices. 
ICON will implement quality control procedures beginning with the data entry system and 
generate data quality control checks that will be run on the database. Any missing data or data 
anomalies will be communicated to the site(s) for clarification and resolution. 
 
 
 
 
 
 
 


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13. 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
13.1. 
Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with principles of the 
Belmont Report:  Ethical Principles and Guidelines for the Protection of Human Subjects of 
Research of the National Commission for the Protection of Human Subjects of Biomedical and 
Behavioral Research (April 18, 1979) and codified in 45 CFR 46, 21 CFR 50 and 56, and ICH 
E6(R2); 62 Federal Regulations 25691 (1997), if applicable.  The investigator’s Institution will 
hold a current Federal Wide Assurance (FWA) issued by the Office of Human Research 
Protection for federally funded research. 
13.2. 
Institutional Review Board 
The site will provide for the review and approval of this protocol and the associated informed 
consent documents, by an appropriate ethics review committee or IRB listed on the FWA.  Any 
amendments to the protocol or consent materials must also be approved before they are placed 
into use unless change is for the safety of the subject.  Only those IRB members who are 
independent of the investigators and the sponsor should provide an opinion on study related 
matters.  Verification of IRB approval of the protocol and the written informed consent will be 
transmitted by the investigator or designee prior to the shipment of study product.  No deviations 
from or changes to the protocol will be initiated without prior approval of an appropriate 
amendment unless change is for the safety of the subject. 
13.3. 
Informed Consent Process 
13.3.1. 
  Informed Consent 
The written consent document will embody the elements of informed consent as described in the 
Declaration of Helsinki and will adhere to the ICH Harmonized Tripartite Guideline for Good 
Clinical Practice.  Informed consent should be implemented before any protocol-specified 
procedures or interventions are carried out.  Informed consent will be obtained in accordance 
with 21 CFR 50.25 and 45 CFR 46.  Information should be presented both orally and in written 
form. 
An investigator or designee will describe the protocol to potential subjects face-to-face.  The 
Subject Information and Consent Form may be read to the subjects, but, in any event, the 
investigator shall give the subjects ample opportunity to inquire about details of the study and 
ask any questions before the signing and dating the consent form. 
Study staff must inform subjects that the trial involves research, and explain the purpose of the 
trial, those aspects of the trial that are experimental, any expected benefits, all possible risks 
(including a statement that the particular treatment or procedure may involve risks to the subject 
or to the embryo or fetus, if the subject is or may become pregnant, that are currently 
unforeseeable), the expected duration of the subject’s participation in the trial, the procedures of 


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the research study, including all invasive procedures, and the probability for random assignment 
to treatment groups.  Subjects will be informed that they will be notified in a timely manner if 
information becomes available that may be relevant to their willingness to continue participation 
in the trial.  They must also be informed of alternative procedures that may be available, and the 
important potential benefits and risks of these available alternative procedures.  Subjects must 
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.  
Subjects must be informed of the anticipated financial expenses, if any, to the subject for 
participating in the trial, as well as any anticipated prorated payments, if any, to the subject for 
participating in the trial.  They must 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 subject’s participation in the trial may 
be terminated.  The subjects must 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 subject is otherwise entitled. 
Neither the investigator, nor the trial staff, should coerce or unduly influence a subject to 
participate or continue to participate in the trial.  The extent of the confidentiality of the subjects’ 
records must be defined, and subjects must be informed that applicable data protection 
legislation will be followed.  Subjects must be informed that the monitor(s), auditors(s), IRB, 
DOD, Ology Bioservices, and regulatory authority(ies) will be granted direct access to the 
subject’s original medical records for verification of clinical trial procedures and/or data without 
violating the confidentiality of the subject, to the extent permitted by the applicable laws and 
regulations, and that, by signing a written informed consent form, the subject is authorizing such 
access.  Subjects must be informed that records identifying the subject 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 subject’s identity will remain 
confidential. 
Consent forms must be in a language fully comprehensible to the prospective subjects.  Informed 
consent shall be documented by the use of a written consent form approved by the IRB and 
signed and dated by the subject and the person who conducted the informed consent discussion.  
The signature confirms that the consent is based on information that has been provided and all 
questions have been answered to the prospective participant’s satisfaction.  Each subject’s signed 
informed consent form must be kept on file by the investigator for possible inspection by 
Regulatory Authorities and/or the sponsor and Regulatory Compliance persons.  The subject 
should receive a copy of the signed and dated written informed consent form and any other 
written information provided to the subjects and should receive copies of any signed and dated 
consent form updates and any amendments to the written information provided to subjects. 
13.4. 
Exclusion of Women, Minorities, and Children (Special Populations) 
Children are excluded for safety reasons. 


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13.5. 
Subject Confidentiality 
Subject confidentiality is held strictly in trust by the participating investigators, their staff, and 
the sponsor and their agents.  This confidentiality is extended to cover testing of biological 
samples in addition to the clinical information relating to participating subjects. 
The study protocol, documentation, data, and all other information generated will be held in 
strict confidence.  No information concerning the study, or the data will be released to any 
unauthorized third party without prior written approval from the sponsor. 
The study monitor or other authorized representatives of the sponsor 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 subjects in this study.  The 
clinical study site will permit access to such records. 
13.6. 
Study Discontinuation 
Ology Bioservices has the right to terminate this study or the site’s participation at any time.  
Reasons for terminating the study may include, but are not limited to, the following: 
• Incidence or severity of adverse events indicates a potential health hazard; 
• Data recording is inaccurate or incomplete; 
• Investigator does not adhere to the protocol or applicable regulatory guidelines in 
conducting the study. 
13.7. 
Future Use of Stored Specimens 
Samples will be collected as outlined in the protocol.  Subjects will be given a choice during the 
informed consent process to have their residual linked samples stored indefinitely for future 
research, have their residual samples de-linked from any subject information and stored 
indefinitely, or have their residual linked samples destroyed at completion of the study.  The use 
of long-term stored linked samples will be conducted under the restrictions regarding 
confidentiality, as outlined in the preceding paragraphs. 
Only coded specimens will be sent to the sponsor with the code identifiers maintained by the 
principal investigator.  Any future research studies will utilize only the residual long-term stored 
specimens from subjects consenting to future use.  
14. 
DATA HANDLING AND RECORD KEEPING 
The investigator is responsible to ensure the accuracy, completeness, legibility, and timeliness of 
the data reported.  All data collection forms should be completed in a neat, legible manner to 
ensure accurate interpretation of data.  Black ink is required to ensure clarity of reproduced 
copies.  When making changes or corrections, cross out the original entry with a single line, and 
initial and date the change.  Do not erase, overwrite, or use correction fluid or tape on the 
original. 


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Copies of the electronic CRF (eCRF) will be provided for use as source documents and 
maintained for recording data for each subject enrolled in the study.  Data reported in the eCRF 
derived from source documents should be consistent with the source documents or the 
discrepancies should be explained. 
Ology Bioservices and/or its designee will provide guidance to investigators on making 
corrections to the data collection forms/source documents and eCRFs. 
14.1. 
Data Management Responsibilities 
All source documents and laboratory reports must be reviewed by the clinical team and data 
entry staff, who will ensure that they are accurate and complete.  Adverse Events must be 
graded, assessed for severity and causality, and reviewed by the site Principal Investigator or 
designee. 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site Principal Investigator.  During the study, the investigator must maintain complete and 
accurate documentation for the study. 
ICON will serve as the Statistical and DCC for this study, and will be responsible for data 
management, quality review, analysis, and reporting of the study data. 
14.2. 
Data Capture Methods 
Clinical data (including AEs, concomitant medications, and reactogenicity data) and clinical 
laboratory data will be entered into a 21CFR11-compliant Internet Data Entry System provided 
by ICON.  The data system includes password protection and internal quality checks, such as 
automatic range checks, to identify data that appear inconsistent, incomplete, or inaccurate.  
Clinical data will be entered directly from the source documents. 
14.3. 
Types of Data 
Data for this study will include clinical safety assessments, safety laboratory assessments, 
immunology and PK. 
14.4. 
Timing/Reports 
A final report will be prepared following the availability of all the safety and immunogenicity 
data. 
14.5. 
Study Records Retention 
Study files (except for future use consent forms) must be maintained for a minimum of two years 
after the last approval of a marketing application in an ICH region and until there are no pending 
or contemplated marketing applications in and ICH region or at least 2 years have elapsed since 
the formal discontinuation of clinical development of the investigational product.  These 
documents should be retained for a longer period, however, if required by local regulations. No 
records will be destroyed without the written consent of the sponsor, if applicable.  It is the 


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responsibility of the sponsor to inform the investigator when these documents no longer need to 
be retained.  Consent forms for future use will be maintained as long as the sample exists. 
14.6. 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or protocol-
specific MOP requirements.  The noncompliance may be either on the part of the subject, the 
investigator, or the study site staff.  As a result of deviations, corrective actions are to be 
developed by the site and implemented promptly. 
These practices are consistent with ICH E6(R2): 
4.5 
Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3 
5.1 
 Quality Assurance and Quality Control, Section 5.1.1 
5.20  Noncompliance, Sections 5.20.1, and 5.20.2. 
It is the responsibility of the site PI/study staff 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 ICON/Ology Bioservices. 
All protocol deviations, as defined above, must be addressed in study subject source documents.  
A completed copy of the Protocol Deviation Form must be maintained in the Regulatory File, as 
well as in the subject's source document.  Protocol deviations must be sent to the local IRB/IEC 
per their guidelines.  The site PI/study staff is responsible for knowing and adhering to their IRB 
requirements. 
15. 
PUBLICATION POLICY 
All manuscripts resulting from this trial will be reviewed by representatives from the sites, DOD 
and the product manufacturer.  Each institution will have at least thirty days to review the 
publication prior to submission. 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted 
a trials-registration policy as a condition for publication.  This policy requires that all clinical 
trials be registered in a public trials registry such as ClinicalTrials.gov, which is sponsored by the 
National Library of Medicine (NLM).  Other biomedical journals are considering adopting 
similar policies.  This trial will be registered in NLM in accordance with the new NLM 
requirements under the Food and Drug Administration Amendments Act (FDAAA). 
*Journal Citation : 
De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, et al. Clinical trial 
registration: a statement from the International Committee of Medical Journal Editors. N Engl J 
Med. 2004;351:1250-1. 


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16. 
LITERATURE REFERENCES 
1. Werner SB, Passaro D, McGee J, Schechter R and Vugia DJ. Wound botulism in 
California, 1951-1998: recent epidemic in heroin injectors. Clin Infect Dis  
2000;31(4):1018-24. 
 
2. Lacy DB and Stevens RC. Sequence homology and structural analysis of the clostridial 
neurotoxins. J Mol Biol  1999;291(5):1091-104. 
 
3. Barash JR and Arnon SS.  A novel strain of clostridium botulinum that produces type b 
and type h botulinum toxins. J Infect Dis. 2014;209(2):183-91. 
 
4. Arnon SS, Schechter R, Inglesby TV, et al. Botulinum toxin as a biological weapon: 
medical and public health management. JAMA  2001;285(8):1059-70. 
 
5. CDC. Botulism in the United States, 1899-1996. Handbook for epidemiologists, 
clinicians, and laboratory workers. Atlanta, GA, Centers for Disease Control and 
Prevention 1998. 
 
6. Hughes JM, Blumenthal JR, Merson MH, Lombard GL, Dowell VR, Jr. and Gangarosa 
EJ. Clinical features of types A and B food-borne botulism. Ann Intern Med  
1981;95(4):442-5. 
 
7. Seals JE, Snyder JD, Edell TA, et al. Restaurant-associated type A botulism: transmission 
by potato salad. Am J Epidemiol 1981;113(4):436-44. 
 
8. NIAID. NIAID Biodefense research agenda for CDC category A agents. NIAID. 
Washington, D.C., U.S. Department of Health and Human Services.  2002. 
 
9. Black RE and Gunn RA. Hypersensitivity reactions associated with botulinal antitoxin. 
American Journal of the Medical Sciences  1980;69:567-70. 
 
10. Hibbs RG, Weber JT, Corwin A, et al. Experience with the use of an investigational 
F(ab')2 heptavalent botulism immune globulin of equine origin during an outbreak of 
type E botulism in Egypt. Clin Infect Dis  1996;23(2):337-40. 
 
11. Arnon SS, Schechter R, Maslanka SE, Jewell NP and Hatheway CL. Human botulism 
immune globulin for the treatment of infant botulism. N Engl J Med  2006;354:462-71. 
 


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12. CDC. Notice of CDC's discontinuation of investigational pentavalent (ABCDE) 
botulinum toxoid vaccine for workers at risk for occupational exposure to botulinum 
toxins. Morbidity and Mortality Weekly Report  2011;60(42):1454-5. 
 
13. CDC. Investigational heptavalent botulinum antitoxin (HBAT) to replace licensed 
botulinum antitoxin AB and investigational botulinum antitoxin E Morbidity and 
Mortality Weekly Report  2010;59(10):299. 
 
14. Fagan RP, Neil KP, Sasich R, et al. Initial recovery and rebound of type f intestinal 
colonization botulism after administration of investigational heptavalent botulinum 
antitoxin. Clin Infect Dis  2011;53(9):e125-8. 
15. Nowakowski A, Wang C, Powers DB, et al. Potent neutralization of botulinum 
neurotoxin by recombinant oligoclonal antibody. Proc Natl Acad Sci U S A 
2002;99(17):11346-50. 


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APPENDICES


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APPENDIX A: SCHEDULE OF EVENTS 
Study Visit 
Screening1 
 
01 
Baseline 
 
02 
 
 
03 
 
 
04 
 
 
05 
Cohort 
1-3 
Only  
 
 
06 
 
 
07 
 
 
08 
 
 
 
09 
 
 
10 
 
 
11 
 
 
12 
 
 
13 / 
Early 
Term 
14 
Cohort 
4 Only 
Study Day (Window) 
-28 to -3 
0 
24 hr 
48 
hr 
72 hr 
4 
8±1 
15±1 
30±1 
45±3 
60±3 
90±3 
120±3 
180±3 
Review Inc/ ExcI Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Review Medical History 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Review Contraception/menses 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Perform Abbreviated PE3 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Perform Symptom-Directed PE13 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Obtain Vital Signs4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Obtain Screening Labs5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Obtain Clinical Safety Labs,6 
 
X 
 
 
 
 
X 
X 
X 
 
 
 
X,18 
X 
Serum β-HCG 
X7 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X18 
X 
Urine Dipstick8  
X 
X 
 
 
 
 
 
 
 
 
 
 
X18 
X 
Urine Toxicology 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Breathalyzer test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Immunogenicity (ADA)14 
 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Hypersensitivity Panel15 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Viral Serology10 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK samples11 
 
X 
  X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MNA 
 
X16 
 
 
 
X 
 
 
X 
X17 
X 
X 
X 
 
Concomitant Medications2 
X 
X 
  X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Administration 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Future Use Sample12 
 
X 
 
 
 
 
X 
 
X 
 
 
 
  
 


Protocol: G03-52-01.001 
                   Version 3.0 
 
September 7, 2021 
 ______________________________________________________________________________________________________  
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Study Visit 
Screening1 
 
01 
Baseline 
 
02 
 
 
03 
 
 
04 
 
 
05 
Cohort 
1-3 
Only  
 
 
06 
 
 
07 
 
 
08 
 
 
 
09 
 
 
10 
 
 
11 
 
 
12 
 
 
13 / 
Early 
Term 
14 
Cohort 
4 Only 
Study Day (Window) 
-28 to -3 
0 
24 hr 
48 
hr 
72 hr 
4 
8±1 
15±1 
30±1 
45±3 
60±3 
90±3 
120±3 
180±3 
Counsel on the avoidance of 
pregnancy 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Counsel on avoidance of 
botulinum toxin and vaccines 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE Review  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SAE Review 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1. 
Screening will be completed within 28 days prior to administration of study drug and may require more than one visit. 
2. 
Concomitant medications including all of the following: prescription drugs, over-the –counter drugs, herbs, vitamins, nutritional supplements, illicit and recreational substance use, birth 
control information. 
3. 
PE includes height and weight at screening.     
4. 
Vital Signs to include sitting diastolic and systolic blood pressure, heart rate, and oral temperature. Vital signs will be checked just before injection and every visit. 
5. 
Subjects should be fasting for Screening Laboratory Tests that will include hemoglobin, WBC with differential, absolute neutrophil count and platelet count. MCV, MCH, MCHC, RDW, 
MPV, which are included in a complete blood count with differential, will not be graded, serum creatinine, BUN, calcium, total bilirubin, direct bilirubin, indirect bilirubin, alkaline 
phosphatase, PT, PTT, INR, ALT, AST, sodium, potassium, and total CK.  Subjects in cohort 4 only will have NX02 levels drawn at screening 
6. 
Subjects should be fasting for Clinical Safety Laboratory Tests that will include hemoglobin, WBC with differential, absolute neutrophil count and platelet count. MCV, MCH, MCHC, 
RDW, MPV, which are included in a complete blood count with differential, will not be graded, serum creatinine, BUN, calcium, total bilirubin, direct bilirubin, indirect bilirubin, alkaline 
phosphatase, PT, PTT, INR, ALT, AST, sodium, potassium, and total CK.  
7. 
A serum pregnancy test will be obtained for all women of reproductive capacity.  Results must be confirmed as negative before study product is dosed.   
8. 
A urine dipstick will be done to evaluate for presence of protein, glucose or blood in urine. If dipstick is abnormal, a complete urinalysis with microscopic will be performed. 
9. 
A 12-lead ECG will be done during screening. 
10. Viral Serology includes HIV, HBsAg and antibody to HCV. 
11. Subjects in Cohorts 1-3 will have PK samples taken at the following times: pre-dose, 2, 4, 8, 24, 48, and 72 hours post injection and on days 4, 8, 15, 30, 45, 60, 90, and 120. .   Subjects in 
Cohort 4 will have PK samples taken at pre-dose, 6 hours post-dose, and on days 1, 2, 4, 8, 15, 30, 45, 60, 90, 120, and 180. 
12. Serum from subjects who give consent will be stored for future use.  On Days 0, 8, and 30. 
13. The subject will be under direct observation during at least the initial 30 minutes of the injection.  A physical examination will be performed at approximately 30 minutes after starting the 
injection and again in response to subject symptoms which will include the following: General appearance including alertness and any difficulty breathing, HEENT, Chest, Heart, Skin and 
Joints. 
14. Draw prior to dosing at baseline for all Cohorts. Subjects in Cohorts 4 will not have ADA blood draws on Day 15 or Day 30. Cohort 4 will have ADA drawn on follow- up Days 45, 60, 90, 120 and 
180. 
        15. The Hypersensitivity Panel  includes cytokine and complement panels, IgE, and tryptase.  Draw 14ml prior to dosing. If a subject develops anaphylaxis or anaphylactoid reaction, an additional 
14 mL sample will be drawn during the event and another will be drawn after the event. 
16. MNA: To be drawn pre-dose for All Cohorts.  Cohort 4 subjects will also have a 2-hour post dose optional  (+/- 10 minutes) draw.  
18. Cohorts 1-3 only. 


Protocol: G03-52-01.001 
                   Version 3.0 
 
September 7, 2021 
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APPENDIX B: TOXICITY GRADING 
Clinical Adverse Events 
VITAL SIGNS 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
Grade 3 
Fever - °C 
  
 
38.0-38.4 
  
 
38.5-38.9 
  
 
>38.9 
  
 
Tachycardia - bpm 
101-115 
116-130 
>130 or ventricular 
dysrhythmias 
Bradycardia – bpm 
• 
Baseline ≥60 
OR, if 
                Baseline <60 
•   50-54  
OR, if Baseline 
<60,  
•   45-50 
•    45-49  
OR, if baseline <60,  
•         40-44 
•   <45  
OR, if baseline <60 
•     <40 
Hypertension (systolic) - mmHg 
141-150 
151-160 
>160 
Hypertension (diastolic) - mmHg 
91-95 
96-100 
>100 
Hypotension (systolic) - mmHg 
85-89 
80-84 
<80 
Tachypnea – breaths per min 
23-25 
26-30 
>30 
CARDIOVASCULAR 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Arrhythmia 
   
Asymptomatic; transient signs; 
no medical intervention required  
Recurrent/persistent; 
symptomatic medical 
intervention required  
Hemorrhage, Blood Loss  
Estimated blood 
loss ≤100 mL  
Estimated blood loss >100 mL; 
no transfusion required 
Transfusion required 
QTc (Fridericia’s correction)1 
 
 
Asymptomatic, 
QTc interval 
450-479 msec  
Asymptomatic; QTc interval 480 
to 499 msec OR Increase in 
interval 30-59 msec above 
baseline 
Asymptomatic; QTc 
interval ≥ 500 msec OR 
Increase in interval ≥ 60 
msec above baseline 
PR Interval (prolonged)1 
PR interval 
0.21-0.25 sec 
PR interval >0.25 
Type II 2nd degree AV 
block OR Ventricular 
pause >3.0 sec 
RESPIRATORY    
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Cough 
Transient; no 
treatment  
Persistent cough  
Interferes with daily 
activities 
Bronchospasm, Acute 
Transient; no 
treatment; 
FEV1 71-80% 
of predicted 
peak flow  
Requires medical intervention; 
normalizes with bronchodilator; 
FEV1 60-70% of predicted peak 
flow  
No normalization with 
bronchodilator; FEV1 
<60% of predicted peak 
flow 
Dyspnea   
Does not 
interfere with 
usual and social 
activities 
Interferes with usual and social 
activities; no treatment 
Prevents daily and 
usual social activity OR 
requires treatment 
GASTROINTESTINAL   
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
                                                 
1Inclusion dependent upon protocol requirements. 


Protocol: G03-52-01.001 
                   Version 3.0 
 
September 7, 2021 
 ______________________________________________________________________________________________________  
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Nausea  
No interference 
with activity 
Some interference with activity 
Prevents daily activities 
Vomiting  
No interference 
with activity 
OR 1-2 
episodes/24 
hours 
Some interference with activity 
OR >2 episodes/24 hours 
Prevents daily activity 
OR requires IV 
hydration OR requires 
medical intervention 
Diarrhea  
2-3 loose or 
watery stools or 
<400 g/24 hours 
4-5 loose or watery stools or 
400-800 g/24 hours 
≥6 loose or watery 
stools or >800g/24 
hours OR requires IV 
hydration OR requires 
medical intervention 
REACTOGENICITY 
 
 
 
LOCAL REACTIONS 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Pain – experienced without 
touching the injection site 
(spontaneous discomfort) 
Does not 
interfere with 
activity 
Repeated use of non-narcotic 
pain reliever >24 hours OR 
interferes with activity 
Any use of narcotic 
pain reliever OR 
prevents daily activity 
Tenderness – hurts only when 
injection site is touched, or the 
arm is moved 
Discomfort only 
to touch 
Discomfort with movement 
Significant discomfort 
at rest 
Pruritus (Itching) 
Does not 
interfere with 
daily activity 
Interferes with daily activity 
Prevents daily activity 
Ecchymosis (Bruising)* 
Does not 
interfere with 
daily activity 
Interferes with daily activity 
Prevents daily activity 
Erythema (Redness)* 
Does not 
interfere with 
daily activity 
Interferes with daily activity  
Prevents daily activity 
Induration 
(Hardness)/Swelling* 
Does not 
interfere with 
daily activity 
Interferes with daily activity  
Prevents daily activity 
Nodule 
Does not 
interfere with 
daily activity 
Interferes with daily activity  
Prevents daily activity 
Ulcer 
Does not 
interfere with 
daily activity 
Interferes with daily activity  
Prevents daily activity 
Ecchymosis (Bruising)* 
25 mm – 
50 mm 
51 mm – 100 mm 
>100 mm 
Erythema (Redness)* 
25 mm – 
50 mm 
51 mm – 100 mm 
>100 mm 
Induration 
(Hardness)/Swelling* 
25 mm – 
50 mm 
51 mm – 100 mm 
>100 mm 
Nodule 
25 mm – 
50 mm 
51 mm – 100 mm 
>100 mm 
Ulcer 
1 mm – 50 mm 
51 mm – 100 mm 
>100 mm 
SYSTEMIC REACTIONS 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Allergic Reaction  
Pruritus without 
rash  
Localized urticaria OR requires 
oral therapy 
Generalized urticaria; 
angioedema OR 


Protocol: G03-52-01.001 
                   Version 3.0 
 
September 7, 2021 
 ______________________________________________________________________________________________________  
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anaphylaxis OR 
requires epinephrine 
Headache  
No interference 
with activity 
Repeated use of non-narcotic 
pain reliever >24 hours OR some 
interference with activity 
Significant; any use of 
narcotic pain reliever 
OR prevents daily 
activity OR requires 
triptans  
Fatigue  
No interference 
with activity 
Some interference with activity 
Significant; prevents 
daily activity 
Myalgia 
No interference 
with activity 
Some interference with activity 
Significant; prevents 
daily activity 
All Other conditions 
Mild  
(Grade 1) 
Moderate  
(Grade 2) 
Severe  
(Grade 3)  
Illness or clinical AE (as 
defined according to applicable 
regulations) 
No interference 
with activity 
Some interference with activity 
not requiring medical 
intervention 
Prevents daily activity 
and requires medical 
intervention 
*Will not be used as halting criteria 
 
 


Protocol: G03-52-01.001 
                   Version 3.0 
 
September 7, 2021 
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Ology Bioservices, Inc. 
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Laboratory and Vital Signs Reference Ranges, Eligibility Ranges, and Toxicity Grading 
Laboratory Adverse Events* 
Mild 
Moderate  
Severe 
ICON Normal Lab 
Values 
(Grade 1) 
(Grade 2) 
(Grade 3) 
Blood, Serum, or Plasma 
Sodium (hyponatremia) – mEq/L 
131-132 
129-130 
<129 
133 – 143 
Sodium (hypernatremia) – 
mEq/L 
144 – 145 
146 – 147 
>147 
133 – 143 
Potassium (hyperkalemia) – 
mEq/L 
5.2 – 5.4 
5.5 – 5.6 
>5.6 
3.5 - 5.1 
Potassium (hypokalemia) – 
mEq/L 
3.2-3.4 
3.0 – 3.1 
<3.0 
3.5 - 5.1 
Glucose (hypoglycemia) – 
mg/dL 
65 – 69 
55 – 64 
<55 
70 – 105 
Glucose (hyperglycemia) – 
mg/dL Fasting 
106 – 125 
126 – 200 
>200 
70 – 105 
Blood Urea Nitrogen – mg/dL 
21-26 
27 – 31 
> 31 
6 – 20 
Creatinine (Male) – mg/dL 
1.3 – 2.0 
2.1-2.3 
>2.3 
0.7-1.2 
Creatinine (Female) – mg/dL 
1.0 – 1.7 
1.8 – 2.0 
>2.0 
0.5 - 0.9 
Calcium (hypocalcemia) – 
mg/dL 
8 - <LLN 
7.5 – 7.9 
<7.5 
8.7 - 10.3 
Calcium (hypercalcemia) – 
mg/dL 
ULN - 10.8  
10.9 – 11.4 
>11.4 
8.7 - 10.3 
CK-U/L  
309-1000 
1001-1500 
>1500 
39-308 
Albumin (hypoalbuminemia) – 
g/dL 
2.8 – 3.4 
2.5 – 2.7 
< 2.5 
3.5 - 5.2 
AST – U/L (Male) 
40-97 
98-195 
>195 
<40  
 
AST – U/L (Female) 
32-77 
78-155 
>155 
<32  
ALT – U/L (Male) 
41-100 
101-200 
>200 
<41  
 
ALT – U/L (Female) 
33-80 
81-160 
>160 
<33 
Alkaline phosphatase – IU/L 
(Male) 
131-260 
261-390 
>390 
40-130  
 
Alkaline phosphatase – IU/L 
(Female) 
106-210 
211-315 
>315 
35-105 
Total Bilirubin (serum) – mg/dL 
1.3-1.5 
1.6-1.9 
>1.9 
0 - 1.2 
Direct Bilirubin – mg/dL 
NA 
NA 
NA 
0.0-0.2 
Chloride –mEq/L 
(hypochloremia) 
NA 
NA 
NA 
 
96-108 
Chloride –mEq/L 
(hyperchloremia) 
NA 
NA 
NA 
96-108 
CO2 –mEq/L  (hypo) 
NA 
NA 
NA 
20- 30 
CO2 –mEq/L (hyper) 
NA 
NA 
NA 
20- 30 
Total Protein – g/dL 
5.5 - 5.9 
5.0 - 5.4 
<5.0 
6.0 - 8.0 
Phosphorus- mg/dl  (hypo) 
2.3-2.4 
2.1-2.2 
<2.0 
2.5 – 4.5 
Phosphorus-mg/dl  (hyper) 
NA 
NA 
NA 
2.5 – 4.5 
Total Cholesterol-mg/dl 
NA 
NA 
NA 
<201 
Triglycerides-mg/dl 
NA 
NA 
NA 
<151 
HDL – mg/dl 
NA 
NA 
NA 
>65 F      >55 M 


Protocol: G03-52-01.001 
                   Version 3.0 
 
September 7, 2021 
 ______________________________________________________________________________________________________  
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94 
Proprietary 
 
 
Laboratory Adverse Events* 
Mild 
Moderate  
Severe 
ICON Normal Lab 
Values 
(Grade 1) 
(Grade 2) 
(Grade 3) 
LDL Direct – mg/dl 
NA 
NA 
NA 
<130 
Hemoglobin (Male) – g/dL 
11.2 - 12.2 
10.0 – 11.1 
<10.0 
12.3-17.3 
Hemoglobin (Female) – g/dL 
9.8 - 10.8 
8.5 - 9.7 
<8.5 
10.9 - 14.6 
WBC Increase – cell/mm3 
10,001– 15,000 
15,001 – 20,000 
> 20,000 
4,000-10,000 
WBC Increase – cell/mm3 
(African America Males) 
9,001 – 14, 000 
14,001 – 19, 000 
>19,000 
4,000-10,000 
WBC Increase – cell/mm3 
(African American Females) 
11,001 – 15,000 
15,001 – 20,000 
>20,000 
4,000-10,000 
WBC Decrease – cell/mm3 
2,500– 3,999 
1,500 – 2,499 
< 1,500 
4,000-10,000 
WBC Decrease – cell/mm3 
(African American Males) 
2,200 – 2,499 
1,200 – 2,199 
<1,200 
4,000-10,000 
WBC Decrease – cell/mm3 
(African American Females) 
2,200 – 2,499 
1,500 – 2,199 
<1,500 
4,000-10,000 
Neutrophils Decrease – cell/mm3 
1,300 – 1,699 
1,000 – 1,299 
< 1,000 
1,700-7,000 
Neutrophils Decrease – cell/mm3 
(African American Males) 
1,000 – 1,299 
800 - 999 
<800 
1,700-7,000 
Neutrophils Decrease – cell/mm3 
(African American Females) 
1,100 – 1,299 
1,000 – 1,099 
<1,000 
1,700-7,000 
Platelets Decreased – 10^3/mm3 
120 – 149 
100 – 119 
<100 
150-400 
Hematocrit (Male) - % 
33.0 -36.1 
29.8 - 32.9 
< 29.8 
36.2-51.1 
Hematocrit (Female) - %  
29.5 - 32.6 
26.0 – 29.4 
< 26.0 
32.7 - 43.5 
RBC (Male) – x 106/uL   
3.9 - 4.1 
3.4 - 3.8 
< 3.4 
4.2-5.8 
RBC (Female) – x 106/uL   
3.5 - 3.7 
3.0 - 3.4 
< 3.0 
3.8 - 5.8 
Lymphocytes - cell/mm3 
decrease 
600- 799 
500 – 599 
< 500 
800 - 3600 
Monocytes – cell/mm3     
increase 
1001-2000 
2001-3000 
>3000 
100 - 1000 
Eosinophils - cell/mm3     
increase 
871 - 950 
951 - 1700 
>1700 
60- 870 
Basophils - cell/mm3       increase 
101 - 300 
301 - 800 
> 800 
10-100 
PT (prothrombin time) – seconds 
11.1-12.1 
12.2-13.2 
>13.2 
9.1 - 11.0 
PT INR (Prothrombin INR) 
1.2-1.4 
1.5-1.9 
2.0 or higher 
.9-1.1 
PTT (partial thromboplastin 
time) –seconds 
34.1-40.8 
40.9-47.6 
>47.6 
22 - 34 
Urine 
Protein 
1+ 
2+ 
>2+ 
Neg. 
Glucose 
1+ 
2+ 
>2+ 
Neg. 
Blood (microscopic) - red blood 
cells per high power field 
(rbc/hpf)** 
5-10* 
11-50* 
>50 and/or 
gross blood** 
<5* 
 
 
 
 

SAP_001.pdf: 
 
Ology Bioservices, Inc. 
Protocol. No. G03-52-01.001 
ICON Project No. 3426/0009 
Statistical Analysis Plan Final 2.0 
24 Aug 2022 
 
 
CONFIDENTIAL 
  
Page 1 of 42 
 
STATISTICAL ANALYSIS PLAN 
 
 
 
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, DOSE ESCALATION 
STUDY TO EVALUATE THE SAFETY AND PHARMACOKINETICS OF 
A SINGLE IM DOSE OF G03-52-01 VS PLACEBO IN ADULT SUBJECTS. 
 
 
 
 
 
SAP Version 2.0 
FINAL 
Date: 24 Aug 2022 
 
for 
 
Protocol No. G03-52-01.001 
 
 
 
Submitted to: 
Ology Bioservices, Inc. 
13200 NW Nano Court 
Alachua, FL 32615 
 
 
 
Prepared by: 
ICON Early Phase Services, LLC 
8307 Gault Lane  
San Antonio, TX 78209 
 
 
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Protocol. No. G03-52-01.001
ICON Project No. 3426/0009
Statistical Analysis Plan Final 2.0
24 Aug 2022
CONFIDENTIAL
Page 2 of 42
SIGNATURES
ICON Early Phase Services, LLC Signature Page
ICON Author:
Shuchi Joshi, M.Sc.
Principal Biostatistician, BioStats
Date
ICON Reviewers:
Ganesh Munuswamy, M.Sc., MA
Manager, Stat Programming, IEP SAS Programming
Date
Laurie Reynolds, PhD
Senior PK Scientist , IEP Pharmacokinetics
Date
Uma Arumugam, MD
Medical Director, Clinical Research & Development, IEP 
Clinical - R&D
Date
DocUUID : b56f7427-c03e-4ee9-b0f1-1c50cc62ddcf
e0ddc4f6-173f-436a-9e21-5abf1441f0b8
Shuchi Joshi
30 Aug 2022 04:39:21 PDT (-07:00)
REASON: I approve this document as author.
d76df923-b741-4eb3-8c04-561fecf38f81
Uma Arumugam
30 Aug 2022 06:18:05 PDT (-07:00)
REASON: I approve this document
3ae89d69-8d9e-4922-815b-1809d52f30aa
Ganesh Munuswamy
30 Aug 2022 07:43:33 PDT (-07:00)
REASON: I approve this document


Ology Bioservices, Inc.
Protocol. No. G03-52-01.001
ICON Project No. 3426/0009
Statistical Analysis Plan Final 2.0
24 Aug 2022
CONFIDENTIAL
Page 3 of 42
ICON Approvals:
Colm Farrell, PhD 
Sr Director, Pharmacokinetics, IEP Pharmacokinetics
Date
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b5383b1b-f645-4a48-be75-b3ed19d2aac8
Colm Farrell
31 Aug 2022 03:35:56 PDT (-07:00)
REASON: I approve this document


Ology Bioservices, Inc.
Protocol. No. G03-52-01.001
ICON Project No. 3426/0009
Statistical Analysis Plan Final 2.0
24 Aug 2022
CONFIDENTIAL
Page 4 of 42
CLIENT SIGNATURE PAGE
Client Approvals:
Wael El-Amin, MD
Senior Director, Medical Affairs
Ology Bioservices, Inc.
Date
Angie Kimbler, CCRP
Sr. Manager, Regulatory & Clinical Operations
Ology Bioservices, Inc.
Date
DocUUID : b56f7427-c03e-4ee9-b0f1-1c50cc62ddcf
a1bd9fb3-22f9-48de-8319-5df19a9d0e18
Angie Kimbler
30 Aug 2022 06:01:15 PDT (-07:00)
REASON: I have reviewed this document and have no comments that require addressing.
923f4c9f-38d8-4efe-bc13-b37c69d8e727
Wael El-Amin
30 Aug 2022 06:24:56 PDT (-07:00)
REASON: I approve this document


 
Ology Bioservices, Inc. 
Protocol. No. G03-52-01.001 
ICON Project No. 3426/0009 
Statistical Analysis Plan Final 2.0 
24 Aug 2022 
 
 
CONFIDENTIAL 
  
Page 5 of 42 
REVISION HISTORY 
Version 
Number 
Effective Date 
Changes since previous version 
Final 1.0  
05-Jun-2020 
Original version, Not Applicable 
Final 1.1 
28-Jul-2020 
1. Section 2. Introduction: Changed the version of the 
protocol from 1.0 to 2.0 
2. Section 5. Changes in the conduct of the study or planned 
analysis: Changed the version of the protocol from 1.0 to 
2.0 and removed the below explanation provided in SAP 
version 1.0 
“1) As per protocol, each of the monoclonal antibodies of G03-
52-01 will be measured by ECLA. However, they can be 
measured by ECLA or ELISA validated method. 
2) t1/2 (α and β) and MRT will not be analyzed for antibodies, 
only t1/2 will be determined. “ 
Final 2.0 
24-Aug-2022 
1. Section 2: Reference to latest protocol version 3.0 dated 
07 Sept 2021 
2. Section 2.2.2: Secondary endpoints are updated  
3. Section 3.1: Number of cohorts, dose of study drug, 
follow-up visits for cohort 4, and SRC section are updated  
4. Figure 3-1: Study schematic is updated  
5. Table 3-2: Schedule of Events Cohort 4 and follow up 
visits are updated  
6. Section 3.2: Study population is updated for Cohort 4 and 
total of 40 subjects  
7. Section 3.5: Sample size is updated for 40  
8. Section 3.6: Dose of 100 mg is added for Cohort 4 
9. Section 3.10: Visits are added for cohort 4  
10. Section 3.12: Visits are added for cohort 4  
11. Section 5: Reference to latest protocol version 3.0 dated 
07 Sept 2021  
12. Section 7.22.1: MedDRA Version is updated  
13. Section 7.23: Interim analysis of Cohort 4 is updated  
14. The cohorts A, B, C, D are referred as cohorts 1, 2, 3, 4 in 
line with the protocol  
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Ology Bioservices, Inc. 
Protocol. No. G03-52-01.001 
ICON Project No. 3426/0009 
Statistical Analysis Plan Final 2.0 
24 Aug 2022 
 
 
CONFIDENTIAL 
  
Page 6 of 42 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ADA  
Anti-Drug Antibody 
AE 
Adverse Event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area Under the Curve 
BLQ 
Below Limit of Quantification 
CK 
Cytokine 
CV 
Coefficient of Variation 
Cmax  
Maximum Plasma Titer/Concentration 
CSR 
Clinical study report  
DMP  
Data Management Plan 
eCRF  
Electronic Case Report Form  
ECG   
Electrocardiogram 
ECLA 
Electrochemiluminescence Assay 
ELISA 
Enzyme-linked Immune Sorbent Assay 
GCP 
Good Clinical Practice 
HBsAg 
Hepatitis B Surface Antigen 
HCG  
Human Chorionic Gonadotropic Hormone 
HCV 
Hepatitis C Virus 
HEENT 
Head, Eyes, Ears, Nose and Throat  
HIV 
Human Immunodeficiency Virus 
ICH 
International Council for Harmonization 
Ig 
Immunoglobulin 
IM 
Intramuscular 
INR 
International Normalized Ratio 
MCH 
Mean Corpuscular Hemoglobin 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MNA 
Battelle Mouse Neutralization Assay 
MPV 
Mean Platelet Volume 
MOP 
Manual of Procedures 
MRT 
Mean Residence Time 
N/n 
Number 
PE  
Physical Examination 
PI 
Principal Investigator 
PK 
Pharmacokinetic(s) 
PT 
Preferred Term 
PTT 
Partial Thromboplastin Time 
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RDW 
Red Blood Cell Distribution Width 
SAE  
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
SRC  
Safety Review Committee  
TEAE 
Treatment-emergent Adverse Event 
Tmax 
Time to Maximum Concentration 
WBC 
White Blood Count 
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TABLE OF CONTENTS 
SIGNATURES ................................................................................................................................ 2 
CLIENT SIGNATURE PAGE ....................................................................................................... 4 
REVISION HISTORY.................................................................................................................... 5 
LIST OF ABBREVIATIONS ......................................................................................................... 6 
1. 
INTRODUCTION ................................................................................................................. 11 
2. 
STUDY OBJECTIVES AND ENDPOINTS ........................................................................ 12 
2.1 
Objectives ....................................................................................................................... 12 
2.1.1 
Primary Objective ................................................................................................... 12 
2.1.2 
Secondary Objective ............................................................................................... 12 
2.1.3 
Exploratory Objective ............................................................................................. 12 
2.2 
Endpoints ........................................................................................................................ 12 
2.2.1 
Primary Endpoints .................................................................................................. 12 
2.2.2 
Secondary Endpoints .............................................................................................. 12 
2.2.3 
Exploratory Endpoint .............................................................................................. 13 
3. 
STUDY DESIGN .................................................................................................................. 14 
3.1 
General ........................................................................................................................... 14 
3.2 
Study Population ............................................................................................................ 19 
3.3 
Evaluations at Screening and Check-in .......................................................................... 19 
3.4 
Randomization and Treatment Assignments.................................................................. 19 
3.5 
Determination of Sample Size........................................................................................ 19 
3.6 
Study Drug Administration ............................................................................................ 20 
3.7 
Concomitant Medications .............................................................................................. 20 
3.8 
Drug Administration and Compliance ........................................................................... 20 
3.9 
Evaluation of Efficacy .................................................................................................... 21 
3.10 Evaluation Pharmacokinetic and Sampling Schedule .................................................... 21 
3.11 Evaluation of Pharmacodynamics and Sampling Schedule ........................................... 21 
3.12 Evaluation of Immunogenicity and Sampling Schedule ................................................ 21 
3.13 Evaluation of Other Parameters and Sampling Schedule............................................... 21 
3.14 Evaluation of Treatment Safety...................................................................................... 21 
3.15 Adverse Events ............................................................................................................... 21 
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3.16 Clinical Laboratory Assessments ................................................................................... 22 
3.17 Vital Signs ...................................................................................................................... 23 
3.18 Electrocardiograms......................................................................................................... 23 
3.19 Physical Examinations ................................................................................................... 24 
3.20 Other Safety Assessments .............................................................................................. 24 
3.20.1 
Hypersensitivity Panel ................................................................................................ 24 
3.21 Protocol Deviation Reporting......................................................................................... 24 
3.22 Medical and Surgical History ......................................................................................... 24 
4. 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSIS .............. 26 
5. 
QUALITY CONTROL AND QUALITY ASSURANCE METHODS FOR DATA 
ANALYSIS ................................................................................................................................... 27 
6. 
PHARMACOKINETIC AND IMMUNOGENICITY ASSESSMENTS ............................. 28 
6.1 
Pharmacokinetic Assessment ......................................................................................... 28 
6.1.1 
Treatment of Outliers .............................................................................................. 29 
6.1.2 
Non-Quantifiable Concentrations ........................................................................... 29 
6.2 
Immunogenicity ............................................................................................................. 29 
7. 
STATISTICAL METHODS.................................................................................................. 30 
7.1 
General ........................................................................................................................... 30 
7.2 
Handling of Dropouts or Missing Data .......................................................................... 30 
7.2.1 
Handling of missing/ incomplete dates for AE ....................................................... 31 
7.3 
Multiple Comparisons and Multiplicity ......................................................................... 31 
7.4 
Adjustments for covariates ............................................................................................. 31 
7.5 
Multicenter Studies ........................................................................................................ 31 
7.6 
Examination of Subgroups ............................................................................................. 31 
7.7 
Coding Dictionaries........................................................................................................ 31 
7.8 
Analysis Populations ...................................................................................................... 32 
7.8.1 
Safety Population .................................................................................................... 32 
7.8.2 
Pharmacokinetic Analysis Population .................................................................... 32 
7.9 
Subject Accountability ................................................................................................... 32 
7.10 Protocol Deviations ........................................................................................................ 32 
7.11 Subject Demographics and Baseline Characteristics ..................................................... 32 
7.12 Medical and Surgical History ......................................................................................... 32 
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7.13 Other Baseline Characteristics ....................................................................................... 33 
7.14 Prior and Concomitant Medications ............................................................................... 33 
7.15 Measurements of Treatment Compliance ...................................................................... 33 
7.16 Physical Examinations ................................................................................................... 33 
7.17 Pharmacokinetic Analysis .............................................................................................. 33 
7.18 Pharmacodynamic Analysis ........................................................................................... 33 
7.19 Efficacy Analyses ........................................................................................................... 33 
7.20 Biomarker Analysis ........................................................................................................ 34 
7.21 Immunogenicity Analysis .............................................................................................. 34 
7.22 Safety Analyses .............................................................................................................. 34 
7.22.1 
Adverse Events ....................................................................................................... 34 
7.22.2 
Clinical Laboratory Assessments ............................................................................ 35 
7.22.3 
Vital Signs ............................................................................................................... 36 
7.22.4 
Electrocardiograms ................................................................................................. 36 
7.22.5 
Physical Examinations ............................................................................................ 36 
7.22.6 
Prior and Concomitant Medications ....................................................................... 36 
7.22.7 
Other Observations Related to Safety ..................................................................... 36 
7.23 Planned Interim Analysis ............................................................................................... 36 
7.24 Statistical Software ......................................................................................................... 37 
7.25 General Conventions for Tables, Listings and Figures .................................................. 38 
8. 
LIST OF TABLES, FIGURES, AND LISTINGS ................................................................ 39 
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1. 
INTRODUCTION 
This statistical analysis plan (SAP) is consistent with the statistical methods section of the final 
study protocol (Version 3.0, dated 07 Sept 2021) and includes additional detail of 
pharmacokinetic (PK), immunogenicity, safety and tolerability summaries to be included in the 
clinical study report (CSR). 
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2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1 
Objectives 
The following are the study objectives 
2.1.1 Primary Objective 
x To assess the safety and tolerability of escalating doses of G03-52-01 administered 
intramuscularly (IM) in healthy adult subjects. 
2.1.2 Secondary Objective 
x To assess the PK and immunogenicity of escalating doses of G03-52-01 administered IM 
in healthy adult subjects. 
2.1.3 Exploratory Objective 
Not Applicable 
2.2 
Endpoints 
The following are the study endpoints 
2.2.1 Primary Endpoints 
x The occurrence of Serious Adverse Events (SAE) following administration of G03-52-01 
to the final follow-up visit. 
x The occurrence of Adverse Events (AE) from administration of G03-52-01 to the final 
follow-up visit. 
x The occurrence of changes from baseline in physical examination, vital signs and clinical 
safety laboratory values following administration of G03-52-01 to the final follow-up 
visit.  
2.2.2 Secondary Endpoints 
x The pharmacokinetic assessment of Cmax, Tmax and AUC(0-t) as measured by the validated 
Battelle Mouse Neutralization Assay (MNA) for serotypes A and B 
 
o Pharmacokinetic samples will be tested by MNA at pre-dose and on Days 4, 30, 
60, 90, and 120 for Cohorts 1-3. 
o Pharmacokinetic samples will be tested by MNA at pre-dose, 2-hour post-dose 
(for future use), and on Days 4, 30, 45, 60, 90, and 120 for Cohort 4. 
 
x The assessment of Cmax, Tmax, half-life (α and β), MRT and AUC(0-t) for each of the 
monoclonal 
antibodies 
of 
G03-52-01 
as 
measured 
by 
a 
validated 
electrochemiluminescence assay (ECLA) or enzyme-linked immunosorbent assay 
(ELISA) method. 
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o PK samples will be tested by ECLA or ELISA at pre-dose, and at 2, 4, 8, 24, 48, 
and 72 hours post injection, and on Days 4, 8, 15, 30, 45, 60, 90, and 120 for 
Cohorts 1-3. 
o Pharmacokinetic samples will be tested by ECLA or ELISA at pre-dose, 6 hours 
post dose, and on Days 1, 2, 4, 8, 15, 30, 45, 60, 90, 120, and 180 for Cohort 4. 
 
x Samples will be tested to evaluate presence of anti-drug antibodies (ADA) collected for 
all cohorts. 
 
o Samples will be tested for ADA at pre-dose and on Days 15, 30, 45, 60, 90, and 
120 for Cohorts 1-3. 
o Samples will be tested for ADA at pre-dose and on Days 45, 60, 90, 120, and 180 
for Cohort 4. 
2.2.3 Exploratory Endpoint 
Not Applicable 
 
 
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3. 
STUDY DESIGN 
3.1 General 
A Phase 1, randomized, double-blind, placebo-controlled dose escalation trial of four dose 
cohorts of 10 subjects (1: 10 mg, 2: 25 mg, 3: 50 mg and 4: 100 mg). Dosing for each cohort is 
as follows: Two sentinel subjects will be administered a single IM dose (one G03-52-01, one 
placebo).  The dosing of the remaining eight subjects within that cohort will not be initiated until 
at least 24 hours have passed and no AEs have occurred that meet halting criteria, and no safety 
signals have occurred that in the opinion of the investigator warrant further investigation. The 
remaining eight subjects in the cohort will be admitted as scheduled without delay. Dose 
escalation will not occur until safety data through Day 8 is reviewed by the Safety Review 
Committee (SRC) composed of the Principal Investigator (PI), Ology Bioservices Medical Lead, 
and the ICON Medical Monitor. Objective dose-escalation criteria and safety evaluations will be 
utilized. The study will consist of a twenty-eight-day screening period and 12-hour clinic stay. 
Follow-up visits will occur at 24 hours, 48 hours, and 72 hours post dose and on Days 4, 8, 15, 
30, 45, 60, 90, and 120 for Cohort 1-3. Follow-up visits for subjects in Cohort 4 will occur at on 
Days 1, 2, 4, 8, 15, 30, 45, 60, 90, 120, and 180. An SRC meeting will be held if halting criteria 
are met or safety concerns arise.      
 
Table 3-1: Cohorts 
 
Cohort 
Dose of G03-52-01 
Number of Subjects 
1 
10 mg 
10 subjects (8 active, 2 placebo) 
2 
25 mg 
10 subjects (8 active, 2 placebo) 
3 
50 mg 
10 subjects (8 active, 2 placebo) 
4 
100 mg 
10 subjects (8 active, 2 placebo) 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Figure 3-1:  
Study Schematic 
 
 
Note: Sentinel dosing will occur within each cohort. 
Assess Eligibility 
Randomize 
Cohort 1 N=10 
Single IM injection of 10mg G03-52-01  
(8 subjects) or Placebo (2 subjects) 
Dose-Escalation Halting Criteria Not Met 
SRC Agrees to Dose Escalation 
Cohort 2 N=10 
Single IM injection of 25mg G03-52-01 
 (8 subjects) or Placebo (2 subjects) 
Dose-Escalation Halting Criteria Not Met 
SRC Agrees to Dose Escalation 
 Study Halting Criteria Met/Dose Escalation 
Halting Criteria Met/SRC Review 
Study Halting Criteria Met/Dose-Escalation 
Halting Criteria Met/SRC Review 
Safe to Proceed 
Halt Study 
Safe to Proceed 
Halt Study 
Dose-Escalation Halting Criteria Not Met 
SRC Agrees to Dose Escalation 
Study Halting Criteria Met/Dose-Escalation 
Halting Criteria Met/SRC Review 
Safe to Proceed 
Halt Study 
 Cohort 3 N=10 
Single IM injection of 50mg G03-52-01  
(8 subjects) or Placebo (2 subjects) 
Cohort 4 N=10 
Single IM injection of 100mg G03-52-01  
(8 subjects) or Placebo (2 subjects) 
SRC Review Assessment of Final Outcome 
Measures 
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Table 3-2: Schedule of Events 
Study Visit 
Screening1 
01 
Baseline 
02 
 
03 
 
04 
 
05 
Cohort 
1-3 
Only  
 
06 
 
07 
 
08 
 
 
09 
 
10 
 
11 
 
12 
 
13 / 
Early 
Term 
 
14 
Cohort 
4 Only 
Study Day (Window) 
-28 to -3 
0 
24 hr 
48 
hr 
72 hr 
4 
8±1 
15±1 
30±1 
45±3 
60±3 
90±3 
120±3 
180±3 
Review Inc/ ExcI Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Review Medical History 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Review Contraception/menses 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Perform Abbreviated PE3 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Perform Symptom-Directed PE13 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Obtain Vital Signs4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Obtain Screening Labs5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Obtain Clinical Safety Labs,6 
 
X 
 
 
 
 
X 
X 
X 
 
 
 
X,18 
X 
Serum β-HCG 
X7 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X18 
X 
Urine Dipstick8  
X 
X 
 
 
 
 
 
 
 
 
 
 
X18 
X 
Urine Toxicology 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Breathalyzer test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Immunogenicity (ADA)14 
 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
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Study Visit 
Screening1 
01 
Baseline 
02 
 
03 
 
04 
 
05 
Cohort 
1-3 
Only  
 
06 
 
07 
 
08 
 
 
09 
 
10 
 
11 
 
12 
 
13 / 
Early 
Term 
 
14 
Cohort 
4 Only 
Study Day (Window) 
-28 to -3 
0 
24 hr 
48 
hr 
72 hr 
4 
8±1 
15±1 
30±1 
45±3 
60±3 
90±3 
120±3 
180±3 
Hypersensitivity Panel15 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Viral Serology10 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK samples11 
 
X 
  X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MNA 
 
X16 
 
 
 
X 
 
 
X 
X17 
X 
X 
X 
 
Concomitant Medications2 
X 
X 
  X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Administration 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Future Use Sample12 
 
X 
 
 
 
 
X 
 
X 
 
 
 
  
 
Counsel on the avoidance of 
pregnancy 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Counsel on avoidance of 
botulinum toxin and vaccines 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE Review  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SAE Review 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1. 
Screening will be completed within 28 days prior to administration of study drug and may require more than one visit. 
2. 
Concomitant medications including all of the following: prescription drugs, over-the –counter drugs, herbs, vitamins, nutritional supplements, illicit and recreational substance use, birth 
control information. 
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3. 
PE includes height and weight at screening.     
4. 
Vital Signs to include sitting diastolic and systolic blood pressure, heart rate, and oral temperature. Vital signs will be checked just before injection and every visit. 
5. 
Subjects should be fasting for Screening Laboratory Tests that will include hemoglobin, WBC with differential, absolute neutrophil count and platelet count. MCV, MCH, MCHC, 
RDW, MPV, which are included in a complete blood count with differential, will not be graded, serum creatinine, BUN, calcium, total bilirubin, direct bilirubin, indirect bilirubin, 
alkaline phosphatase, PT, PTT, INR, ALT, AST, sodium, potassium, and total CK.  Subjects in cohort 4 only will have NX02 levels drawn at screening 
6. 
Subjects should be fasting for Clinical Safety Laboratory Tests that will include hemoglobin, WBC with differential, absolute neutrophil count and platelet count. MCV, MCH, MCHC, 
RDW, MPV, which are included in a complete blood count with differential, will not be graded, serum creatinine, BUN, calcium, total bilirubin, direct bilirubin, indirect bilirubin, 
alkaline phosphatase, PT, PTT, INR, ALT, AST, sodium, potassium, and total CK.  
7. 
A serum pregnancy test will be obtained for all women of reproductive capacity.  Results must be confirmed as negative before study product is dosed.   
8. 
A urine dipstick will be done to evaluate for presence of protein, glucose or blood in urine. If dipstick is abnormal, a complete urinalysis with microscopic will be performed. 
9. 
A 12-lead ECG will be done during screening. 
10. Viral Serology includes HIV, HBsAg and antibody to HCV. 
11. Subjects in Cohorts 1-3 will have PK samples taken at the following times: pre-dose, 2, 4, 8, 24, 48, and 72 hours post injection and on days 4, 8, 15, 30, 45, 60, 90, and 120. Subjects in 
Cohort 4 will have PK samples taken at pre-dose, 6 hours post-dose, and on days 1, 2, 4, 8, 15, 30, 45, 60, 90, 120, and 180. 
12. Serum from subjects who give consent will be stored for future use.  On Days 0, 8, and 30. 
13. The subject will be under direct observation during at least the initial 30 minutes of the injection.  A physical examination will be performed at approximately 30 minutes after starting 
the injection and again in response to subject symptoms which will include the following: General appearance including alertness and any difficulty breathing, HEENT, Chest, Heart, 
Skin and Joints. 
14. Draw prior to dosing at baseline for all Cohorts. Subjects in Cohorts 4 will not have ADA blood draws on Day 15 or Day 30. Cohort 4 will have ADA drawn on follow- up Days 45, 60, 
90, 120 and 180. 
15. The Hypersensitivity Panel  includes cytokine and complement panels, IgE, and tryptase.  Draw 14ml prior to dosing. If a subject develops anaphylaxis or anaphylactoid reaction, an 
additional 14 mL sample will be drawn during the event and another will be drawn after the event. 
16. MNA: To be drawn pre-dose for All Cohorts.  Cohort 4 subjects will also have a 2-hour post dose optional (+/- 10 minutes) draw.  
17. MNA at Day 45 for Cohort 4 only. 
18. Cohorts 1-3 only. 
 
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3.2 
Study Population 
Forty healthy male and female subjects, ages 18 to 45 years old and BMI of ≥18.5 and 
≤35 kg/m2, will be enrolled in four cohorts. Up to four alternates per cohort will be recruited.   
 
3.3 
Evaluations at Screening and Check-in 
The screening period will be a maximum of 28 days and there will be a 12-hour inpatient stay. 
Subjects meeting inclusion/exclusion criteria will be admitted to the clinical unit the day of the 
injection and the procedures as per Table 3-2 will be performed prior to study drug 
administration. 
 
3.4 
Randomization and Treatment Assignments 
Eligible subjects will be randomly assigned to study drug G03-52-01 within four dosing cohorts 
to either active or placebo in an overall 4:1 ratio. For each dosing cohort, the first two subjects 
will be randomized in a 1:1 fashion to active and placebo to ensure that one of the first two 
subjects receives active treatment and the other control. An alternate subject will be admitted to 
the unit for each two-subject group.  If one of the first two subjects is not randomized for any 
reason, then the alternate subject will receive the next consecutive randomization number. The 
product assignment of the remaining eight subjects in each cohort will be a simple random 
sample to ensure the 4:1 ratio for the dosing cohort.   
 
Randomized treatment assignments will be generated by a statistician at ICON PLC. 
Randomization will occur following admittance to the unit and confirmation of eligibility is 
confirmed. The randomization list will be generated by the unblinded study biostatistician and 
transferred to the unblinded study pharmacist prior to start of the study.   
 
If 2 or more subjects withdraw, are lost to follow up or terminate prior to Day 8, those subjects 
need to be replaced to ensure that data for at least 7 subjects is available for review.  
 
If 2 or more subjects withdraw, are lost to follow up or terminate prior to Day 60 or are not 
compliant with all PK draws through Day 15, they may be replaced.    
 
If more than 2 subjects withdraw, are lost to follow up or terminate following the Day 8 SRC 
review of safety data, the site will attempt to replace those subjects in that dose group at the time 
of the next planned cohort. 
 
The detailed randomization scheme and distribution list will be described in the randomization 
plan.  
 
3.5 
Determination of Sample Size 
This is a Phase 1 study first in humans with four dosing cohorts and no formal sample size 
calculations based on testing a statistical hypothesis were constructed. Four dosing groups of ten, 
each with eight participants assigned the active group and two assigned to the control group, are 
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practical and provide sufficient information for a total sample size of 40 for a Phase 1 trial 
primarily designed to assess safety. 
 
If ten subjects are studied, then the probability of at least one subject experiencing an event of 
toxicity can range from 0.728 to 0.996 assuming true event rates between 0.15 and 0.5 
Additionally, if no events are observed in a cohort of six dosed subjects receiving G03-52-01 the 
upper bound of an exact 95% confidence interval for the true proportion is 0.46. 
 
3.6 
Study Drug Administration 
G03-52-01 will be administered IM as a single dose at concentrations of 10 mg, 25 mg, 50 mg, 
and 100 mg by varying the administration volume. Placebo will be 0.9% Sodium Chloride 
Injection, USP is a sterile, non-pyrogenic, isotonic solution of sodium chloride and water for 
injection. 
 
G03-52-01 and placebo should be administered as a single IM injection to the central, thickest 
portion of the deltoid and the injection must be completed within 30 minutes after preparation. 
 
3.7 
Concomitant Medications 
Concomitant medication information will be recorded at Screening for the prior 28 days. At each 
subsequent study visit each new concomitant medication and changes to existing medications 
will be recorded. Subjects will be required not to utilize non-study medication or herbal 
supplements during the study except those deemed necessary by the site PI or sub investigator. 
Any drug (e.g., over-the-counter herbal supplement, vitamins or prescription) use by the subject 
during the course of the trial will be recorded in the subject’s source documents and on the 
appropriate eCRF.  
 
Subjects will be instructed to refrain from the receipt of any of the medication/ product as per 
Section 5.8 of the protocol during study participation unless medically indicated and deemed 
immediately necessary by their private physician.  
 
3.8 
Drug Administration and Compliance 
G03-52-01 and placebo should be administered as a single IM injection to the central, thickest 
portion of the deltoid. Water for injection will be used to reconstitute the G03-52-01 for IM 
injection. The placebo will be normal saline without the addition of G03-52-01. The product 
should be used within 30 minutes upon reconstitution. 
 
Complete records and documentation of study product receipt, accountability, dispensation, 
temperature monitoring, and storage conditions, and final disposition of the study product will be 
maintained. All study products, whether administered or not, must be documented on the 
appropriate study product accountability record or dispensing log.  
 
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3.9 
Evaluation of Efficacy 
Not Applicable 
 
3.10 
Evaluation Pharmacokinetic and Sampling Schedule 
Six-mL samples of blood for PK samples will be drawn at the following times: pre-dose, and at 
2, 4, 8, 24, 48, and 72 hours post dose and on Days 4, 8, 15, 30, 45, 60, 90, and 120 for cohorts 
1-3 & pre-dose, at 6 hours post-dose, and on days 1, 2, 4, 8, 15, 30, 45, 60, 90, 120 and 180 for 
cohort 4. Serum will be analyzed for levels of each of the monoclonal antibodies using a 
validated ECLA or ELISA. All PK samples will be tested by ECLA or ELISA. 
 
Three 10-mL samples of blood will be drawn to be analyzed for neutralizing antibody 
concentrated using the validated Battelle MNA. PK samples will be tested by the Battelle MNA 
for serotypes A and B at pre-dose and on Days 4, 30, 60, 90, and 120 for cohorts 1-3 & at pre-
dose, and on days 4, 30, 45, 60, 90 and 120 for cohort 4. 
 
PK samples will be collected as described in Table 3-2. 
 
3.11 
Evaluation of Pharmacodynamics and Sampling Schedule 
Not Applicable 
 
3.12 
Evaluation of Immunogenicity and Sampling Schedule 
Six-mL samples of blood will be drawn at pre-dose, on Days 15, 30, 45, 60, 90, and 120 for 
determining the presence of ADA using a validated ECLA that measures of total anti-drug 
antibody in serum for Cohorts 1-3.  
 
Six-mL samples of blood will be drawn pre-dose and on Days 45, 60, 90, 120, and 180 for 
determining the presence of ADA using a validated ECLA that measures total anti-drug antibody 
in serum for Cohort 4.  This will be done to assess immunogenicity.  
 
Immunogenicity samples will be collected as described in Table 3-2. 
 
3.13 
Evaluation of Other Parameters and Sampling Schedule 
Not Applicable 
 
3.14 
Evaluation of Treatment Safety 
Study products safety will be assessed as per sections 3.15 to 3.21. 
3.15 
Adverse Events 
An AE is defined as any untoward medical occurrence in a subject administered a 
pharmaceutical product during the course of a clinical investigation. An AE can therefore be any 
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unfavorable and unintended sign, symptom, or disease temporally associated with the use of a 
study drug, whether or not thought to be related to the study drug. 
 
A treatment-emergent AE (TEAE) is defined as any event not present before exposure to study 
drug or any event already present that worsens in either intensity or frequency after exposure to 
study drug. 
 
An SAE is any untoward medical occurrence that at any dose: 
 
• Results in death, 
• Is life-threatening*,  
• Requires inpatient hospitalization or prolongation of existing hospitalization, 
• Congenital anomaly/birth defect; 
• Persistent or significant incapacity or substantial disruption of the ability to conduct  
  normal life functions  
 
*Life-threatening adverse event. An adverse event is considered “life-threatening” if, in the 
view of either the investigator or sponsor, its occurrence places the patient or subject at 
immediate risk of death. It does not include an adverse event, had it occurred in a more severe 
form, might have caused death. 
 
Subjects will be monitored throughout the study for AEs, from the time informed consent is 
obtained through End of Study (EOS). Any medical condition that is present at the time the 
subject is screened should be considered as baseline and not reported as an AE. However, if the 
condition increases in severity or frequency at any time during the study, it should be recorded as 
an AE. 
 
All AEs must be graded for severity and relationship to study product based on the Investigator’s 
assessment. AEs will be followed until resolution or stability even if this extends beyond the 
study-reporting period. Resolution of an AE is defined as the return to pretreatment status or 
stabilization of the condition with the expectation that it will remain chronic. Follow-up 
procedures, evaluations, and outcomes will be recorded on the subject's case report forms. 
 
The following details will be collected: description of the AE, onset date, action taken with study 
drug (dose not changed, dose reduced, drug interruption, drug withdrawn, dose increased and not 
applicable), date of resolution, outcome (recovered/resolved, not recovered/not resolved, 
recovered/resolved with sequelae, recovering/resolving, fatal and unknown), severity (mild, 
moderate, severe), seriousness (yes, no), causality/relationship to study drug (not related, 
possibly related and definitely related), additional treatment required.  
 
Reactogenicity (Other conditions, local and systemic reactions) will also be collected. 
 
3.16 
Clinical Laboratory Assessments 
The following laboratory tests will be done at screening and end of study. Subjects should be 
fasting, which means no food or drink (other than water) for at least eight hours prior to 
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sampling. Safety labs with a Grade 1 value will not exclude a subject from participation but will 
serve as their baseline value.    
 
Table 3-3: Laboratory Evaluations 
Category 
Evaluation items 
Hematology 
Hemoglobin, WBC with differential, absolute neutrophil count and 
platelet count. MCV, MCH, MCHC, RDW, MPV. 
Chemistry 
Serum creatinine, BUN, calcium, total bilirubin, direct bilirubin, indirect 
bilirubin, alkaline phosphatase, PT, PTT, INR, ALT, AST, sodium, 
potassium, and total CK.   
Urinalysis 
Dipstick: Urine protein, blood and glucose. Menstruating females failing 
with a positive blood on urine dipstick may be retested following 
cessation of menses. 
Other tests 
Viral Serology Tests (HIV, HBsAg and antibody to HCV), Urine 
toxicology (cocaine (and metabolite), barbiturates, benzodiazepines, 
opiates, THC, methamphetamine/amphetamine, methadone and PCP), 
Urine pregnancy test, Serum β-hCG test 
Immunogenicity samples will be collected as described in Table 3-2. 
 
3.17 
Vital Signs 
Vital sign assessments including systolic and diastolic blood pressure (BP) [measured after 
sitting for at least 10 minutes], heart rate (HR), and oral temperature will be performed at each 
in-clinic study visit. Vital signs that are thought to be aberrant due to an error in measurement 
may be repeated. During screening and follow-up, a measurement that is a Grade 1 may be 
repeated once if the PI believes a transient condition led to the aberrant value.    
 
Vital signs obtained at screening will serve as baseline values for the subject. Grade 1 values are 
allowable unless deemed clinically significant by the study investigator. 
 
3.18 
Electrocardiograms 
A 12-lead ECG will be performed at screening and reviewed by the study PI or a co-Investigator 
to assess the cardiac status of a subject for eligibility for enrollment. ECGs will be performed 
after the subject rests quietly in a supine position for at least 10 minutes. To be eligible for 
participation, the QTc interval should be ≤450ms, and there must be no clinically significant 
ECG abnormalities according to the study investigators and may be repeated once. ECG will be 
recorded at Screening visit. 
 
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3.19 
Physical Examinations 
An abbreviated physical examination (PE) will be conducted at the screening visit and Day 0. 
Height and weight will be obtained at screening. An abbreviated PE is distinguished from a 
complete PE as all body system assessments are not required (e.g., pelvic, rectal, etc.).   
 
On Day 0, the PE will focus assessment for the presence of the following in order to detect signs 
of a hypersensitivity reaction:   
x General appearance including alertness and any difficulty breathing.   
x HEENT (confirm no swelling of lips/tongue/uvula) 
x Chest (confirm no stridor or wheezing) 
x Heart (assess regularity of rhythm) 
x Skin (confirm no hives, examine for any eruptions) 
x Joints (confirm no swelling, warmth, or tenderness) 
 
A symptom- directed PE will be performed at all other in-clinic study visits. Any new findings 
on examination post dosing or worsening of existing conditions are to be reported as AEs.    
 
3.20 
Other Safety Assessments 
3.20.1 Hypersensitivity Panel 
A hypersensitivity panel includes cytokine and complement panels, IgE and tryptase. This 14 mL 
sample will be drawn on Day 0 prior to dosing. The sample will be processed only if the subject 
has a hypersensitivity reaction. If a subject develops anaphylaxis or anaphylactoid reaction, an 
additional 14 mL sample will be drawn during the event and another will be drawn after the 
event.   
 
3.21 
Protocol Deviation Reporting 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or protocol-
specific MOP requirements.  The noncompliance may be either on the part of the subject, the 
investigator, or the study site staff.  As a result of deviations, corrective actions are to be 
developed by the site and implemented promptly. All protocol deviations must be addressed in 
study subject source documents. 
 
3.22 
Medical and Surgical History 
Medical history will be obtained by direct interview.  Subjects will be queried regarding a history 
of significant medical disorders of the head, eyes, ears, nose, throat (HEENT), mouth, 
cardiovascular system, lungs, gastrointestinal tract, liver, pancreas, kidney, urologic, nervous 
system, blood, lymph glands, endocrine system, musculoskeletal system, skin, and 
genital/reproductive tract.  A history of any allergies, cancer, immunodeficiency, psychiatric 
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illness, substance abuse, and autoimmune disease will be solicited. The medical history will 
include current and past medical diagnoses, hospitalizations and major surgical procedures. The 
medical history will be obtained at screening and updated upon admittance to the unit on Day 0. 
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4. 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSIS 
All analyses specified in this SAP are consistent with the final study protocol (Version 3.0, dated 
7 Sept 2021). 
Any changes in the analysis provided or any additional analysis performed will be documented 
in CSR.   
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5. 
QUALITY CONTROL AND QUALITY ASSURANCE METHODS FOR DATA 
ANALYSIS 
Case report forms will be monitored and collected by ICON. All monitored CRFs will be sent to 
the Data Management group at ICON and processed according to the ICON Study Specific 
Procedure Data Management Plan (DMP). The DMP describes CRF data processing, edit 
checks, data query management, medical dictionary coding, SAE reconciliation, data transfers, 
and data quality review through database lock or any necessary reopening of the database. After 
database lock, the data will be retrieved from the database using SAS®. 
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6. 
PHARMACOKINETIC AND IMMUNOGENICITY ASSESSMENTS 
6.1 
Pharmacokinetic Assessment 
Pharmacokinetic parameters for serum concentrations for each monoclonal antibody (NX01, 
NX02, NX11, XB10, XB18, and XB23) and serotypes (A and B) will be estimated separately 
using non-compartmental analysis (Phoenix™ WinNonlin®, version 8.0 or later; Certara L.P., 
Princeton, New Jersey, USA) and actual sample collection timeponts. 
PK parameters will include, samples analysed using MNA method for Serotypes A and B: 
Parameter 
Definition 
AUC(0-t) 
Area under the concentration time-curve to the last concentration above the 
lower limit of quantitation 
Cmax 
Maximum observed concentration 
Tmax 
Time of maximum observed concentration  
 
PK parameters will include, samples analysed using ECLA or ELISA method for each of the 
monoclonal antibodies of G03-52-01: 
Parameter 
Definition 
AUC(0-∞) 
Area under the concentration time-curve extrapolated to infinity 
AUC(0-t) 
Area under the concentration time-curve to the last concentration above the 
lower limit of quantitation 
CL/F 
Apparent oral clearance of drug following extravascular administration (total 
clearance) 
Cmax 
Maximum observed concentration 
Kel 
Elimination rate constant  
t1/2 
Terminal elimination half-life   
Tmax 
Time of maximum observed concentration  
Vz/F 
Volume of distribution during terminal phase following extravascular 
administration 
 
AUC will be computed using the log-linear trapezoidal rule. The value of AUC%extrap should 
be less than or equal to 20% for the AUC(0-∞) to be considered well estimated. If this proportion 
is >20%, then the values of AUC(0-∞) will be treated with caution. When AUC(0-∞) is calculated 
and tabulated, the AUC%extrap will also be tabulated. Where AUC%extrap >20%, AUC(0-∞) and 
all related parameters (i.e. CL/F and Vz/F) will be presented but excluded from the calculation of 
summary statistics. All values excluded from the summaries should be flagged in the individual 
listings with an explanation for the exclusion. 
 
The apparent terminal phase rate-constant (Kel) will be estimated by log-linear regression of the 
concentration-time data associated with this phase. The decision as to which data points describe 
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the terminal phase will be reached by inspecting the semi-logarithmic plot of the data, only 
considering concentrations at time points beyond Tmax. A minimum of three data points will be 
used for the estimation of Kel preferably covering a time span of at least 2 times t1/2. Ideally, the 
adjusted r2 value associated with the estimated Kel will be ≥0.80. Poorly estimated Kel (i.e. if 
estimated over a time time span less than 2 times t1/2 or adjusted R2 <0.80), the corresponding t1/2 
and other parameters derived using Kel (i.e. AUC(0-∞), CL/F, Vz/F, and t1/2) will be flagged in the 
report and excluded from deriving PK parameters dependent on Kel. 
 
In addition, population PK models will be developed for each of the monoclonal antibodies of 
G03-52-01 using nonlinear mixed-effect modelling. A separate Modelling & Simulation 
Analysis Plan will describe this analysis and the results will be reported separately to the CSR. 
6.1.1 Treatment of Outliers 
Individual concentration-time points, if considered anomalous, may be excluded from the 
analysis at the discretion of the pharmacokinetics following a review of the available 
documentation. Any such exclusion will be discussed with the sponsor and clearly outlined in the 
study report. 
Entire individual study drug profiles for a subject may be excluded following review of the 
available documentation and discussion with the sponsor. However, results of analysis with and 
without the excluded profiles may be presented in the study report. Any such exclusion will be 
clearly listed in the study report along with justification for exclusion. 
Any anomalous concentration values observed at predose will be identified and discussed in the 
CSR. Pharmacokinetic parameters will be computed if the predose concentration value is not 
greater than 5% of Cmax for a given patient. If the predose concentration value is greater than 5% 
of the subsequent Cmax, concentration and the PK parameter data for the given subject will be 
listed but excluded from the PK summaries and statistical analysis. The analysis may be repeated 
with and without these subjects as deemed appropriate. 
6.1.2 Non-Quantifiable Concentrations 
All concentration values reported as no results (not collected or not determined) values will be 
treated as missing. For the calculation of concentration summaries, all concentrations below the 
quantifiable limit (BLQ) will be treated as zero. For the purpose of calculating summary 
statistics and plotting mean and individual concentration time profiles, BLQ values will be 
treated as zero prior to the first measurable concentration. After the first measurable 
concentration, subsequent BLQ values will be treated as missing. Descriptive statistics at any 
point will only be calculated if at least 2/3 of the individual data were measured and were 
quantifiable. 
 
6.2  Immunogenicity 
Immunogenicity will be assessed by the development of antibody titers. The presence of ADA 
will be evaluated over the course of the post-injection period. 
 
  
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7. 
STATISTICAL METHODS 
7.1 
General 
 
The statistical analysis will be conducted following the principles specified in the International 
Council for Harmonization (ICH) Topic E9 Statistical Principles for Clinical Trials 
(CPMP/ICH/363/96). 
All statistical analyses will be performed using the statistical software SAS GRID Linux/SAS 
Studio and any exceptions will be detailed in the CSR. 
All results collected in the database will be presented in listings. Both observed values and 
change-from-baseline values for each subject will be given where applicable. All continuous data 
will be listed with the same precision as presented in the database. Cohort, Subject ID, treatment 
and visit will be used to sort data listings. 
Unless otherwise noted, continuous variables will be summarized using number of non-missing 
observations (n), arithmetic mean (mean), standard deviation (SD), median, minimum, 
maximum, lower quartile and upper quartile; categorical variables will be summarized using the 
frequency count and the percentage of subjects in each category. 
In the data listings, study day relative to the study product dosing date for each cohort may be 
presented. Study day relative to dose will be calculated as: event date – study product dose date 
(+ 1 if event date ≥ dose date). 
All subjects who received placebo in each of the cohorts will be combined and presented along 
with the other dose levels until specified otherwise. 
Baseline will be the latest available measurement prior to the study product dose date in each 
cohort. 
7.2 
Handling of Dropouts or Missing Data 
All attempts will be made to collect all data per protocol. No imputation will be performed for 
missing values.  
 
If the character result is reported for quantitative laboratory parameter then for summary and 
analysis it will be changed as follows into numerical value –  
a) 
If less than ‘<’ sign is used then the value will be reduced by 1 point from the last 
precision digit  
b) 
If greater than ‘>’ sign is used then 1 point will be added to the last precision digit. 
 
Eg: if the lab parameter is reported to 2 decimal precision, <40.01 then for summary and analysis 
it will be treated as 40.00, if lab parameter is reported as whole number >40 then it will be 
considered as 41 and if the parameter is reported with 1 decimal precision <40.1 then it will be 
considered as 40.0. 
 
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7.2.1 Handling of missing/ incomplete dates for AE 
Imputation rules for missing or partial AE start date are defined below: 
If only Day of AE start date is missing:  
If the start date has month and year but day is missing, the first day of the month will be imputed 
x If this date is earlier than the first dose date, then the first dose date will be used instead. 
x If this date is later than the stop date (possibly imputed), then the stop date will be used 
instead. 
If Day and Month of AE start date are missing: 
If the start date has year, but day and month are missing, the 1st of January will be imputed 
x If this date is earlier than the first dose date, then the first dose date will be used instead. 
x If this date is later than the stop date (possibly imputed), then the stop date will be used 
instead. 
If Year of AE start date is missing: 
If the year of AE start is missing or AE start date is completely missing, then imputation will not 
be done.  
 
If the AE end date (full or partial) is before the first dose date, then the AE should be considered 
as a pre-treatment AE. Otherwise, the AE will be considered as TEAE. 
 
Missing dates for Concomitant medication will be imputed similarly as described above for AE. 
 
7.3 
Multiple Comparisons and Multiplicity 
Not Applicable 
 
7.4 
Adjustments for covariates 
Not Applicable 
 
7.5 
Multicenter Studies 
This is a single-center study. 
 
7.6 
Examination of Subgroups 
There is no planned subgroup analysis. 
 
7.7 
Coding Dictionaries 
Medical history and AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) version 23.0 or later. Medical procedures, prior and concomitant medications will 
not be coded. 
 
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7.8 
Analysis Populations 
7.8.1 Safety Population 
All subjects who received study product will be included in the safety population and analyzed 
as treated. 
7.8.2 Pharmacokinetic Analysis Population 
The PK analysis population will consist of all subjects who received G03-52-01 injection and 
have sufficient evaluable PK samples for the reliable estimation of PK parameters for at least one 
of the monoclonal antibodies or serotypes A and B. 
 
7.9 
Subject Accountability 
Summaries of analysis populations and subject disposition will be presented by each G03-52-01 
cohort, Placebo (pooled across all cohorts) and overall will contain the following information: 
x Number of subjects who are enrolled 
x Number and percent of subjects who are randomized 
x Number and percent of subjects who are dosed 
x Number and percent of subjects who completed the study 
x Number and percent of subjects who discontinued early and reason for early 
discontinuation 
x Number and percent of subjects in the Safety and PK Analysis Population 
This summary will be based on Enrolled Subjects. 
Subject disposition and analysis populations, eligibility criteria satisfaction and consent 
information will be presented in listings. 
 
7.10 
Protocol Deviations 
All protocol deviations captured will be listed by subject. These will be summarized by dose 
cohort and control group.  
 
7.11 
Subject Demographics and Baseline Characteristics 
Subject demographics and baseline characteristics such as age, sex, race, ethnicity, height, 
weight, and Body Mass Index (BMI) will be summarized by dose cohort and control group. 
Individual subject demographics and baseline characteristics will be presented in listings. 
Demographics will be summarized for the Safety Population. 
 
7.12 
Medical and Surgical History 
Medical history will be coded using the MedDRA, Version 23.0 or later and listed. 
 
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7.13 
Other Baseline Characteristics 
Not Applicable 
 
7.14 
Prior and Concomitant Medications 
All concomitant procedures, prior and concomitant medications will be listed by subject.  
 
7.15 
Measurements of Treatment Compliance 
As this is a single dose injection study, treatment compliance will not be separately summarized. 
It will be presented as part of drug administration listing.  
 
7.16 
Physical Examinations 
All physical examination results will be presented in a subject listing. 
 
7.17 
Pharmacokinetic Analysis 
PK parameters will be summarized by dose levels using descriptive statistics for each 
monoclonal antibodies (NX01, NX02, NX11, XB10, XB18, and XB23) and serotypes (A and B), 
separately. PK Analysis Population will be used for all listings, concentration summary, PK 
parameter summary and graphical presentation.  
 
The individual sampling and subject concentration-time will be listed and displayed graphically 
on linear and semi-log scales. The concentrations will be summarized descriptively by nominal 
time point in tabular and graphical formats (linear and semi-log scales) for each monoclonal 
antibodies (NX01, NX02, NX11, XB10, XB18, and XB23) and serotypes (A and B), separately. 
Summary statistics (n, mean, SD, coefficient of variation [CV%], median, minimum, maximum, 
geometric mean and geometric CV%) will be calculated for each time point. Geometric CV% 
will be calculated as the square root of the exponentiated SD of the natural log transformed data 
(SQRT(exp(sln2)-1), where appropriate. 
 
Pharmacokinetic parameters for each monoclonal antibodies (NX01, NX02, NX11, XB10, 
XB18, and XB23) and serotypes (A and B) will be listed and summarized descriptively, 
including n, arithmetic mean, SD, minimum, median, maximum, CV(%), geometric mean, 
geometric CV%. For Tmax, only n, minimum, median, and maximum will be reported. 
 
7.18 
Pharmacodynamic Analysis 
Not Applicable 
 
7.19 
Efficacy Analyses 
Not Applicable 
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7.20 
Biomarker Analysis 
Not Applicable 
 
7.21 
Immunogenicity Analysis 
Antidrug antibodies titers will be summarized by dose levels using descriptive statistics for each 
monoclonal antibodies (NX01, NX02, NX11, XB10, XB18, and XB23), separately. PK Analysis 
Population will be used for all listings, summary tables and graphical presentation.  
 
The frequency and percentage of positive immunogenicity response will be summarized by dose 
levels. Anti-drug antibody status will be listed by subject over time, and percentage of subjects 
determined to be positive or negative summarized by dose levels at each available time point.  
7.22 
Safety Analyses 
All Safety analyses will be performed using the Safety Population. 
Tables will be presented by dose levels. All subjects who received placebo in each of the cohorts 
will be combined and presented along with the other dose levels. 
Unscheduled visits data for all safety variables (vitals, ECG and clinical laboratory) will be listed 
only and will not be summarized. 
7.22.1 Adverse Events 
All AEs will be classified by Primary System Organ Class (SOC) and Preferred Term (PT) 
according to the MedDRA, Version 23 or later. Only treatment-emergent AEs (TEAEs) will be 
included, ie, AEs that begin or worsen after dose of study drug has been received. 
The following AE summaries will be presented (where applicable the number of patients (%) and 
number of events will be summarized) by dose cohort and control group:  
• 
Overall summary of TEAEs  
• 
TEAEs by SOC and PT  
• 
TEAEs by maximum severity  
• 
TEAEs by closest relationship 
 
The overall incidence of TEAEs (number and percentage of subjects) as well as the number of 
events will be summarized by study drug; severity of TEAE; SAE; relation to study drug of 
TEAE and SAE; TEAEs leading to study or study drug discontinuation; and TEAEs leading to 
death will be tabulated for each study drug. 
Study drug related AEs are those which were determined by the investigator to be study drug-
related. The incidence of study drug related AEs (as recorded in the CRF) will be summarized 
using descriptive statistics by SOC and PT, categorized by severity and relationship to study 
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drug as recorded in CRF. The frequency of treatment emergent AEs (AE burden) will be 
summarized using descriptive statistics by SOC and PT.  
For the incidence at the subject level by SOC and PT, if a subject experience more than 1 event 
within the same SOC and PT, only 1 occurrence will be included in the incidence. Although all 
the occurrences will be included in the counting of events. 
For the incidence at the subject level by SOC, PT, and severity, if a subject experience more than 
1 event within the same SOC and PT, only the most severe occurrence will be included in the 
incidence. Although all the occurrences will be included in the counting of events. 
For the incidence at the subject level by SOC, PT, and relationship to study drug; if a subject 
experience more than 1 event within the same SOC and PT, only the most closely related 
occurrence will be included in the incidence. Although all the occurrences will be included in the 
counting of events. 
Relative day of AE onset = AE onset date – date of dosing of study product + 1 
Treatment Related AEs are those AEs which can be categorized under the relation “POSSIBLY 
RELATED” and/or “DEFINITELY RELATED”.  
All AE data will be listed for all patients. Both the Investigator’s verbatim terms and the 
MedDRA preferred terms will be listed for each patient. AEs listings will also include start and 
end date, relationship to study drug, severity, action taken for the AEs and if the AE is serious.  
Any SAEs, AEs with outcome of death, or AEs resulting in discontinuation of study or study 
drug will be listed separately. 
AEs recorded as Reactogenicity will be listed by each subject and summarized by dose level and 
control group similarly as described above. Summaries will be provided for severity and closest 
relationship. 
7.22.2 Clinical Laboratory Assessments 
Safety Population will be used to present summaries and listings. Clinical laboratory data will be 
listed and summarized using System International (SI) units. 
 
Laboratory data will be listed by subject at each time point. Clinical laboratory values that are 
out of normal ranges will be presented in a separate listing. 
 
Observed and change from baseline of continuous clinical laboratory values (serum chemistry, 
coagulation panel, hematology, and urinalysis) for each parameter will be summarized by dose 
cohort and control group at each scheduled nominal time point. Categorical Urinalysis will be 
presented in the listing. 
 
The number and percentage of subjects with shift from baseline based on the laboratory normal 
ranges will be tabulated.  
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For female subjects, urine/ serum pregnancy test results will be presented in the individual 
subject data listings for each visit.  
 
7.22.3 Vital Signs 
Vital signs data will be listed by subject at each nominal time point. Observed and change from 
baseline vital signs values will be summarized by dose cohort and control group at each nominal 
timepoint. 
7.22.4 Electrocardiograms 
ECG data will only be listed. 
7.22.5 Physical Examinations 
Physical examination findings will be listed individually for each nominal timepoint. Shift from 
baseline and table describing finding as normal/abnormal will be presented for each nominal 
timepoint. 
7.22.6 Prior and Concomitant Medications 
All prior and concomitant medications will be listed. A separate listing will be provided for 
concomitant procedures.    
7.22.7 Other Observations Related to Safety 
Hypersensitivity panel data if available will be listed. Reactogenicity data will be listed and 
summarized as described in Section 7.22.1. 
7.23 
Planned Interim Analysis 
A blinded interim safety and PK analysis is planned for this study to analyze all PK, ADA, and 
MNA samples for Cohorts 1-3 through Day 60 and Day 120. This will include all subjects in all 
cohorts through Day 60 and Day 120. A second blinded interim safety analysis is planned to 
analyze all PK, ADA, and MNA samples for Cohort 4 through Day 90. Stopping criteria are for 
safety and are defined in Section 9.5 of the protocol. 
 
The ICON PK scientist will be unblinded to the treatment assignment for that particular cohort to 
facilitate a more detailed assessment of the PK and ADA data, which may include individual 
patient demographic and safety data. The ICON PK scientist will provide a summary of the PK 
and ADA analysis, including individual patient data, but will not include the unique patient 
number to ensure the Investigators and Sponsor remain blinded or any other individual data that 
may unblind. 
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7.24 
Statistical Software 
PK parameters will be calculated using Phoenix™ WinNonlin®, version 8.0 or later. All data 
listings, summaries, and statistical analyses will be generated using SAS GRID Linux/SAS 
Studio. 
 
 
 
 
 
 
 
 
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7.25 
General Conventions for Tables, Listings and Figures  
Tables and listings will be presented in landscape mode with minimum of 3/4” bound edge 
margin and 3/8” other margins on 8.5” x 11” paper. 
Times new roman font size of no less than 8 point will be used for tables and listings. 
A source line will be included on the bottom of each page of all tables and listings. It will contain 
the SAS code program name and the run date and time. 
Each variable is recorded to a specific number of decimal places. If the raw data is presented 
with varying precision, then the least precise value will be considered as the data precision. 
For summary tables, unless otherwise specified, the number of decimal places provided in the 
tables and listings will be based on the accuracy of the least accurate value in the raw data as 
follows: 
n 
integer 
Arithmetic mean 
1 decimal place more than the least accurate number in the raw data 
SD 
2 decimal place more than the least accurate number in the raw data 
CV(%) 
2 decimal places 
Geometric mean 
1 decimal place more than the least accurate number in the raw data 
Geometric CV 
2 decimal places 
Median 
1 decimal place more than the least accurate number in the raw data 
Minimum 
same number of decimal places as raw data 
Maximum 
same number of decimal places as raw data 
Percentage 
1 decimal place 
 
 
 
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8. 
LIST OF TABLES, FIGURES, AND LISTINGS 
 
Table/Figure 
Number 
Table/Figure Name 
Section 14.1 
Demographic and Subject Characteristics Data Summaries 
Table 14.1.1 
Summary of Subject Enrollment and Disposition (All Subjects) 
Table 14.1.2 
Summary of Analysis Populations  
Table 14.1.3 
Summary of Demographic and Baseline Characteristics (Safety Population) 
Section 14.2 
Pharmacokinetic and Immunogenicity Data Summaries 
Section 14.2.1 
Pharmacokinetic Data Summaries 
Table 14.2.1.1 
Summary of Pharmacokinetic Concentrations (PK Analysis Population) 
Note: separate for each monoclonal antibody and serotype 
Table 14.2.1.2 
Summary of Pharmacokinetic Parameters (PK Analysis Population) 
Note: separate for each monoclonal antibody and serotype 
Figure 14.2.1.1 
Plot of Mean (SD) Serum Concentration-Time Profile (PK Analysis 
Population) 
Note: separate for each monoclonal antibody and serotype 
Section 14.2.2 
Immunogenicity Data Summaries 
Table 14.2.2.1 
Summary of Anti-drug Antibody Titers (PK Analysis Population) 
Note: separate for each monoclonal antibody and serotype 
Table 14.2.2.2 
Summary of Anti-drug Antibody status (PK Analysis Population) 
Note: separate for each monoclonal antibody and serotype 
Section 14.3 
Safety Data Summaries 
Section 14.3.1 
Displays of Adverse Events 
Table 14.3.1.1 
Overall Summary of Treatment-Emergent Adverse Events (Safety 
Population) 
Table 14.3.1.2 
Summary of Treatment-Emergent Adverse Events by System Organ Class 
and Preferred Term (Safety Population) 
Table 14.3.1.3 
Summary of Treatment-Emergent Adverse Events by System Organ Class, 
Preferred Term, and Maximum Reported Severity Grade (Safety Population) 
Table 14.3.1.4 
Summary of Treatment-Emergent Adverse Events by System Organ Class, 
Preferred Term, and Closest Relationship to Study Drug (Safety Population) 
Table 14.3.1.5 
Overall Summary of Reactogenic Adverse Events (Safety Population) 
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Table 14.3.1.6 
Summary of Reactogenic Adverse Events by System Organ Class, Preferred 
Term, and Maximum Reported Severity Grade (Safety Population) 
Table 14.3.1.7 
Summary of Reactogenic Adverse Events by System Organ Class, Preferred 
Term, and Closest Relationship to Study Drug (Safety Population) 
Section 14.3.2 
Listings of Deaths, Other Serious and Certain Significant Adverse 
Events 
Table 14.3.2.1 
Subject Listing of Deaths (Safety Population) 
Table 14.3.2.2 
Subject Listing of Serious Adverse Events (Safety Population)  
Table 14.3.2.3 
Subject Listing of Adverse Events Leading to Study Discontinuation (Safety 
Population) 
Section 14.3.4 
Abnormal Laboratory Value Listing 
Table 14.3.4.1 
Individual Subjects with Abnormal Clinical Laboratory Values (Safety 
Population) 
Note: Please provide reference to Listing 16.2.8.3 
Section 14.3.5 
Additional Safety Data Summaries 
Table 14.3.5.1 
Absolute and Change from Baseline of Clinical Laboratory Results by 
Category and Test (Safety Population) 
Note: please include only continuous tests 
Table 14.3.5.2 
Shift from Baseline in Clinical Laboratory Results (Safety Population) 
Table 14.3.5.3 
Absolute and Change from Baseline for Vital Signs (Safety Population) 
Table 14.3.5.4 
Shift from Baseline in Physical Examination (Safety Population) 
 
 
Listing Number 
Listing Name 
Section 16.2.1 
Discontinued Subjects 
Listing 16.2.1 
Subject Disposition (Enrolled Subjects) 
Section 16.2.2 
Protocol Deviations 
Listing 16.2.2 
Protocol Deviations (Safety Population) 
Section 16.2.3 
Subjects Excluded from Analysis 
Listing 16.2.3 
Analysis Sets 
Section 16.2.4 
Demographic Data 
Listing 16.2.4.1 
Demographics and Baseline Characteristics (Safety Population) 
Note: Including Screening Height and Weight 
Listing 16.2.4.2 
Screening Outcome (All Subjects) 
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Listing 16.2.4.3 
Eligibility Criteria Satisfaction (Enrolled Subjects) 
Listing 16.2.4.4 
Consent Information (Safety Population) 
Listing 16.2.4.5 
Medical and Surgical History (Safety Population) 
Listing 16.2.4.6 
Prior and Concomitant Medications (Safety Population) 
Listing 16.2.4.7 
Concomitant Procedures (Safety Population) 
Section 16.2.5 
Compliance and/or Drug Concentration Data 
Listing 16.2.5.1 
Study Drug Dosing Record and Compliance (Safety Population) 
Listing 16.2.5.2 
Individual Serum Concentrations (PK Analysis Population) 
Note: separate for each monoclonal antibody and serotype 
Figure 16.2.5.1.1 
Overlay of Individual Serum Concentration-Time Profiles (PK Analysis 
Population) 
Note: separate for each monoclonal antibody and serotype 
Figure 16.2.5.1.2 
Plots of Individual Serum Concentration-Time Profiles (PK Analysis 
Population) 
Note: separate for each monoclonal antibody and serotype 
Section 16.2.6 
Individual Pharmacokinetic and Immunogenicity Data 
Section 16.2.6.1 
Individual Pharmacokinetic Response Data 
Listing 16.2.6.1 
Individual Pharmacokinetic Parameters (PK Analysis Population) 
Note: separate for each monoclonal antibody and serotype 
Section 16.2.6.2 
Individual Immunogenicity Data 
Listing 16.2.6.2 
Individual Anti-drug Antibody Titer (PK Analysis Population) 
Note: separate for each monoclonal antibody and serotype 
Section 16.2.7 
Adverse Event Listings 
Listing 16.2.7.1 
All Adverse Events (Safety Population) 
Listing 16.2.7.2 
Verbatim to Preferred Term Mapping of All Adverse Events 
Listing 16.2.7.3 
Reactogenic Adverse Events (Safety Population) 
Listing 16.2.7.4 
Hypersensitivity Panel (Safety Population) 
Section 16.2.8 
Individual Laboratory Measurements by Subject 
Listing 16.2.8.1 
Normal Ranges for Laboratory Data 
Listing 16.2.8.2 
Clinical Laboratory Data by Category (Safety Population) 
Listing 16.2.8.3 
Abnormal Laboratory Results by Category (Safety Population) 
Listing 16.2.8.4 
Serology Test (Safety Population) 
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Listing 16.2.8.5 
Pregnancy Test (Safety Population) 
Listing 16.2.8.6 
Vital Signs (Safety Population) 
Listing 16.2.8.7 
Electrocardiogram Results (Safety Population) 
Listing 16.2.8.8 
Physical Examination Findings (Safety Population) 
Listing 16.2.8.9 
Abnormal Physical Examination Findings (Safety Population) 
Listing 16.2.8.10 
Future Use Sample (Safety Population) 
Listing 16.2.8.11 
Comments (Safety Population) 
 
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