Conditions: Volunteers Healthy
Keywords: safety pharmacokinetics
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 32
Healthy volunteers: yes

Brief summary:
Study BTI-101 is a Phase 1, randomized, double-blind, placebo-controlled, dose escalation, parallel design study to evaluate the safety, tolerability, and pharmacokinetics of IV rhu-pGSN or saline placebo administered as 5 doses each of 6, 12, 18, or 24 mg/kg of body weight. Each of 4 dosing cohorts will include 8 subjects randomized 3:1 rhu-pGSN:placebo (6 rhu-pGSN subjects:2 placebo subjects). Subjects will be healthy adult volunteers 18-55 years of age.

Detailed description:
Doses will be administered at 0 hours (Day 1), 12 hours (Day 1), 36 hours (Day 2), 60 hours (Day 3), and 84 hours (Day 4). Subjects will be kept in-house until after the last blood sample is taken on Day 5. Subjects will return for follow-up 7 days after the initiation of therapy (Day 8) and on Day 28 for the End-of-Study (EOS) Visit. After each cohort has completed the Day 8 visit, review of the safety results (including labs) will be conducted (and unblinded where appropriate) before the initiation of the next higher dose cohort.

To assess safety and tolerability, subjects will undergo physical examinations (including vital sign measurements), adverse event (AE) assessments, concomitant medication assessments, and safety laboratory testing. Blood samples will be collected for analysis of pGSN levels and antibodies against pGSN.

Arms:
arm 1: Treated with 5 doses of rhu-pGSN arm 2: Treated with 5 doses of saline

Interventions: intervention 1: Recombinant human plasma gelsolin intervention 2: placebo
Intervention descriptions: intervention 1: intravenous administration of either 6, 12, 18, or 24 mg/kg at time 0, 12, 36, 60 and 84 hours intervention 2: intravenous administration of saline control at time 0, 12, 36, 60 and 84 hours

Protocol document:
Prot_SAP_000.pdf: 
BioAegis Therapeutics, Inc. 
 
Clinical Study Protocol 
rhu-pGSN 
 
BTI-101 
Version 1.1 
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Confidential 
 
A PHASE 1, SINGLE-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED, MULTIPLE ASCENDING DOSE ESCALATION, PARALLEL DESIGN 
STUDY FOR THE EVALUATION OF THE SAFETY, TOLERABILITY, AND 
PHARMACOKINETICS OF RECOMBINANT HUMAN PLASMA GELSOLIN (rhu-pGSN) 
FOLLOWING INTRAVENOUS ADMINISTRATION TO HEALTHY VOLUNTEERS 
 
Protocol Number: 
BTI-101 
Investigational Product: 
rhu-pGSN 
IND Number: 
163130 
EUDRA CT Number 
N/A 
Development Phase: 
Phase 1 
Indication Studied: 
Healthy volunteers 
Sponsor Name and Address: 
BioAegis Therapeutics, Inc. (BTI) 
Responsible Medical Officer: 
Mark J. DiNubile, MD FIDSA 
Compliance Statement: 
This study will be conducted in accordance with the 
ethical principles that have their origin in the 
Declaration of Helsinki, clinical research guidelines 
established by the Code of Federal Regulations (Title 
21, CFR Parts 50, 56, and 312), and ICH GCP 
Guidelines. Essential study documents will be archived 
in accordance with applicable regulations. 
Protocol Date: 
10 January 2023 
Version: 
1.1  
 


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PROTOCOL APPROVAL SIGNATURE PAGE 
 
Protocol: 
BTI-101 
Title: 
A phase 1, single-center, randomized, double-blind, placebo-controlled, 
multiple ascending dose escalation, parallel design study for the evaluation 
of the safety, tolerability, and pharmacokinetics of recombinant human 
plasma gelsolin (rhu-pGSN) following intravenous administration to healthy 
volunteers 
Date: 
10 January 2023 
 
Amendment: 
 
N/A 
 
 
 
 
Reviewed and Approved by: 
 
 
 
 
January 10, 2023 
Mark J. DiNubile, MD  
Chief Medical Officer 
BioAegis Therapeutics, Inc. 
 Date 
 
 
 
 


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PROTOCOL ACCEPTANCE FORM 
 
Protocol: 
BTI-101 
Title: 
A phase 1, single-center, randomized, double-blind, placebo-controlled, 
multiple ascending dose escalation, parallel design study for the evaluation 
of the safety, tolerability, and pharmacokinetics of recombinant human 
plasma gelsolin (rhu-pGSN) following intravenous administration to healthy 
volunteers 
Date: 
10 January 2023 
 
Amendment: 
 
N/A 
 
 
I have carefully read the BTI-101 protocol and agree that it contains all of the necessary 
information required to conduct this study. I agree to conduct this study as described and 
according to the Declaration of Helsinki, ICH Guidelines for GCP, and all applicable regulatory 
requirements. 
 
 
 
  
Investigator’s Signature 
 Date 
 
 
 
  
Name (printed) 
  
 


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1. 
SYNOPSIS  
Name of Sponsor/Company: 
BioAegis Therapeutics Inc. 
Name of Investigational Product: 
Recombinant Human Plasma Gelsolin (rhu-pGSN) 
Name of Active Ingredient: 
rhu-pGSN 
Title of Study:  
A phase 1, single-center, randomized, double-blind, placebo-controlled, multiple ascending dose 
escalation, parallel design study for the evaluation of the safety, tolerability, and pharmacokinetics of 
recombinant human plasma gelsolin (rhu-pGSN) following intravenous administration to healthy 
volunteers 
Study Center(s): 1 site  
Studied Period (Years):  
Estimated date first subject enrolled: FEB 2023 
Estimated date last subject completed: FEB 2023 
Phase of development:  
1 
Objectives:  
Primary 
• 
To evaluate the safety and tolerability of 4 sequentially ascending doses of rhu-pGSN at 
6 mg/kg, 12 mg/kg, 18 mg/kg, and 24 mg/kg of actual body weight administered by intravenous 
(IV) infusion for 5 doses at 0, 12, 36, 60, and 84 hours to healthy subjects  
Secondary 
•  To characterize the pharmacokinetic (PK) profile of rhu-pGSN following administration of 
multiple (5) doses of rhu-pGSN to healthy subjects assigned to 4 dose levels (6, 12, 18, or 
24 mg/kg) 
• 
To investigate the development of anti-pGSN antibodies following administration of multiple (5) 
doses of rhu-pGSN administered to healthy subjects assigned to 4 dose levels (6, 12, 18, or 
24 mg/kg) 
Study Design:  
Study BTI-101 is a Phase 1, randomized, double-blind, placebo-controlled, dose escalation, parallel 
design study to evaluate the safety, tolerability, and PK of IV rhu-pGSN or saline placebo administered 
as 5 doses each of 6, 12, 18, or 24 mg/kg of body weight. Each of 4 dosing cohorts will include 
8 subjects randomized 3:1 rhu-pGSN:placebo (6 rhu-pGSN subjects:2 placebo subjects). Subjects will 
be healthy adults 18-50 years of age. 
Doses will be administered at 0 hours (Day 1), 12 hours (Day 1), 36 hours (Day 2), 60 hours (Day 3), 
and 84 hours (Day 4). Subjects will be kept in-house until after the last blood sample is taken on Day 5. 
Subjects will return for follow-up 7 days after the initiation of therapy (Day 7) and on Day 28 for the 
End-of-Study (EOS) Visit. After each cohort has completed the Day 7 visit, review of the safety results 
(including labs) will be conducted (and unblinded where appropriate) before the initiation of the next 
higher dose cohort.  
To assess safety and tolerability, subjects will undergo physical examinations (including vital sign 
measurements), adverse event (AE) assessments, concomitant medication assessments, and safety 
laboratory testing. Blood samples will be collected for analysis of pGSN levels and antibodies against 
pGSN. 


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Number of Subjects (Enrolled):  
A total of 32 (6 rhu-pGSN and 2 placebo recipients per dose cohort × 4 dosing levels) 
Inclusion Criteria:  
1. Healthy male or female adults 18 to 50 years of age without chronic or active acute medical 
conditions 
2. Informed consent obtained from subject  
3. Weight <100 kg and body mass index (BMI) <25 kg/m2 
4. Willingness during the course of the study, starting at screening and for at least 3 months after 
their final study treatment: 
a) Female subjects of childbearing potential must agree to use 2 medically accepted/Food 
and Drug Association (FDA)-approved birth control methods 
b) Male subjects with a partner who might become pregnant must agree to use reliable forms 
of contraception (i.e., condom, vasectomy, abstinence), and an acceptable method of birth 
control must be used by the partner 
c) All subjects must agree not to donate sperm or eggs 
Exclusion Criteria: 
1. Pregnant or lactating women 
2. Acute illness during the month prior to screening 
3. Circumstances that may require any medications (including prescription medication, over-
the-counter medication, vitamins, or supplements) during the conduct of the study other than 
acetaminophen 
4. Hospitalization during the year prior to screening 
5. History of cancer or treatment with systemic chemotherapy or radiation therapy at any time 
6. Transplantation of hematopoietic or solid organs   
7. History of diabetes mellitus; myocardial infarction, angina, or other cardiovascular disease; 
stroke or cerebrovascular disease; chronic obstructive pulmonary disease (COPD) or asthma; 
deep vein thrombosis (DVT)/pulmonary embolism (PE); liver or kidney disease; psychiatric 
condition; or active or chronic infection  
8. Receipt of blood products during the year prior to screening 
9. Chronic mechanical ventilation or dialysis 
10. Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis 
results as judged by the Investigator 
11. Any clinically significant abnormalities of vital signs or physical examination findings as 
judged by the Investigator 
12. Positive results for recreational drugs during screening 
13. Any other condition deemed by the Investigator as possibly interfering with the conduct of 
the study 
Investigational Product, Dosage, and Mode of Administration:  
rhu-pGSN dissolved in sterile water infused IV at a rate of ≤20 mL per minute through a standard 
0.20 µ filter at a dose of 6 mg/kg, 12 mg/kg, 18 mg/kg, or 24 mg/kg. Each dose level is administered at 
5 time points: 0, 12 (Day 1), 36 (Day 2), 60 (Day 3), and 84 hours (Day 4). 


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Duration of Treatment:  
5 doses over 4 days (84 hours) 
Duration of Subject Participation:  
Subject screening: up to 6 weeks. Study treatment: 4 days. Safety follow-up: through 28 days post-first 
dose. Maximum duration: 10 weeks. 
Reference Therapy, Dosage, and Mode of Administration:  
Placebo will be dosed at a weight-based volume of 0.025 mL/mg × dose in mg/kg × weight in kg of 
0.9% saline solution via IV push (matching the volume of rhu-pGSN for a subject of that size) injected 
at ≤20 mL/minute though a standard 0.2 μ filter. Placebo will be administered on the same schedule as 
the active drug. 
Endpoints/Outcomes: 
Primary 
• 
Incidence and severity of clinical and laboratory AEs regardless of causality graded according 
to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials 
Secondary 
• 
PK for IV rhu-pGSN including, but not limited to: Cmax, Tmax, T1/2, AUC0-8, and additionally 
after Dose #5, AUC0-24, and AUCinf (levels measured on Day 1 within 30 minutes predose, and 
at 15 minutes and 1, 2, 4, 8, and 12 hours after Dose #1 and on Days 4 and 5 within 30 minutes 
predose, and at 15 minutes and 1, 2, 4, 8, 12, and 24 hours after Dose #5)  
• 
Presence of anti-rhu-pGSN antibodies at Day 28 
Safety Review: 
The safety data will be reviewed by a Safety Review Committee (SRC) comprised of at least 1 expert 
clinician, the Medical Monitor at the contract research organization, and the Sponsor’s Chief Medical 
Officer.  All AEs occurring during this healthy-volunteer study will be presumed to be related to study 
drug unless occurring before the study therapy is initiated pending review by the SRC. 
Adverse events (AEs) will be categorized as “serious” according to the judgement of the site 
investigator and then reviewed and adjudicated by the SRC.  The “severity” of an AE will be graded 
according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials.  An individual patient will be discontinued permanently from study 
treatment if they experience any serious adverse event (SAE) or a severity Grade 3 or greater AE 
(including infusion reactions).  Further study treatment and enrollment will be paused pending review 
by the SRC if there are two Grade 3 AEs, one Grade 4 AE, or one SAE.  The study will only be 
resumed if the SRC unanimously judges the AEs as unrelated to study treatment and procedures after 
consultation with regulatory and outside experts as needed. 
The SRC will review safety data (including lab tests) through the Day 7 visit for each dosing arm to 
determine if it is safe to initiate the next cohort according to the safety criteria for stopping doses in the 
full protocol. 
Statistical Methods and Sample Size Rationale for Power Calculations: 
For each dosing group, 8 subjects will be randomized in a 3:1 ratio to receive an equal volume of 
rhu-pGSN or saline placebo during the treatment period. Baseline characteristics, safety, PK, and 
development of anti-drug antibodies (ADAs) results will be summarized via summary statistics 


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separately for each rhu-pGSN dose level; data for all placebo subjects will be pooled. Additional details 
will be provided in a separate Statistical Analysis Plan (SAP). 
Sample Size and Power Calculations 
Prior studies of rhu-pGSN evaluated 3 doses of rhu-pGSN in subjects hospitalized with community-
acquired pneumonia or coronavirus 2019 (COVID-19). To expand our understanding of possible rhu-
pGSN toxicities in the absence of underlying disease, 24 healthy subjects will be administered 5 doses 
of rhu-pGSN at 6, 12, 18, and 24 mg/kg of body weight (6 subjects per dose group) and 8 healthy 
subjects (2 subjects per dose group) will be given the same volume on a weight basis of a visually 
indistinguishable 0.9% saline placebo to provide additional data to inform the safety and tolerability of 
rhu-pGSN.  
The table below presents the minimum sample size such that there is a 90% probability of observing at 
least 1 AE of a certain type if the TRUE underlying AE incidence is as specified. 
Minimum Sample Size Calculations 
Sample Size 
TRUE underlying AE rate 
6 (each rhu-pGSN dose level) 
32% 
8 (pooled placebo) 
25% 
12 
18% 
18  
13% 
24 (pooled rhu-pGSN doses) 
10% 
With each sample size presented in the table above, if zero AEs of a certain type (e.g., serious adverse 
events [SAEs]) are observed, one could be "90% confident" that the TRUE underlying incidence for 
that AE is at most the percentage indicated above. Thus with 24 healthy subjects, if no SAEs are 
observed, the probability is 90% that the true underlying incidence of SAEs in healthy subjects 
administered 5 doses of rhu-pGSN at 6, 12, 18, or 24 mg/kg of body weight is at most 10%. 
No data will be excluded from the summary statistics and analyses, and missing data will not be 
imputed. All subjects given at least part of 1 dose of study drug will be included in the intention-to-
treat analysis (full analysis set). As a sensitivity analysis, a per-protocol analysis set excluding subjects 
who missed doses and/or randomly discontinued the study before the primary Day 7 Visit will be 
analyzed. The expectation is that all analysis sets will be almost identical. 
Descriptive summaries of the incidence of all AEs, drug-related AEs, SAEs, drug-related SAEs, AEs 
leading to discontinuation, and deaths will be provided. All AEs and drug-related AEs will be 
summarized by counts and proportions of subjects having an AE, each AE type, and an AE of each 
System Organ Class. Serious AEs will be summarized similarly. AEs leading to discontinuation of 
treatment or the study will be summarized. All reasons for any early discontinuations will be 
summarized. 
Laboratory data will be summarized in relation to normal range values via counts and percentages of 
subjects below, within, and above the respective normal range, and by summary statistics (N, mean, 
median, standard deviation, minimum, maximum, 90% confidence intervals, etc.) for baseline, each 
observed time point, and change from baseline at each observed time point for continuous lab 
endpoints. 


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Demographics and medical history characteristics will be summarized via counts and percentages of 
subjects for categorical variables, and by N, mean and standard deviation or median and interquartile 
range, as appropriate for the distribution of continuous variables. 
Cmax, Tmax, T1/2, AUC0-8h, AUC0-12, and additionally after Dose #5, AUC0-24, and AUCinf will be 
calculated from the pGSN levels measured for Doses #1 and #5. Since the assay measures endogenous 
pGSN levels as well as exogenous recombinant pGSN, PK parameters will be calculated for values 
above baseline by subtracting predose pGSN level from each observed concentration. Tables and 
graphs will be provided. 
Antibodies against rhu-pGSN will be assayed from frozen specimens to determine whether the 
investigational product induces an antibody response in recipients. The frequency of anti-pGSN 
antibodies with 95% confidence intervals will be provided for Day 1 (predose) and Day 28. If any 
subjects had antibodies at Day 1, the presence or absence of antibodies at Days 1 and 28 will be 
summarized in a 2 × 2 table (Day 1 vs. Day 28). 


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TABLE OF CONTENTS 
PROTOCOL ACCEPTANCE FORM .............................................................................................3 
1. 
SYNOPSIS ...................................................................................................................4 
TABLE OF CONTENTS .................................................................................................................9 
LIST OF TABLES .........................................................................................................................12 
2. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................13 
3. 
INTRODUCTION ......................................................................................................15 
3.1. 
Background .................................................................................................................15 
3.2. 
Current Treatment of ALI/ARDS ...............................................................................15 
3.3. 
Plasma Gelsolin ..........................................................................................................15 
3.4. 
Preclinical and Clinical Experience ............................................................................16 
3.4.1. 
Preclinical Experience ................................................................................................16 
3.4.2. 
Clinical Experience .....................................................................................................16 
3.5. 
Rationale for Study and Starting Dose .......................................................................19 
4. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................21 
4.1. 
Objectives ...................................................................................................................21 
4.1.1. 
Primary Objective .......................................................................................................21 
4.1.2. 
Secondary Objectives .................................................................................................21 
4.2. 
Endpoints ....................................................................................................................21 
4.2.1. 
Primary Endpoint ........................................................................................................21 
4.2.2. 
Secondary Endpoints ..................................................................................................21 
5. 
INVESTIGATIONAL PLAN .....................................................................................22 
5.1. 
Overall Study Design ..................................................................................................22 
5.2. 
Safety Review Committee ..........................................................................................22 
5.3. 
Safety Criteria for Stopping Doses .............................................................................22 
5.3.1. 
Management of rhu-pGSN Infusion-Related Reactions .............................................23 
5.4. 
Duration of Subject Participation ...............................................................................23 
5.5. 
End of Study Definition ..............................................................................................23 
5.6. 
Criteria for Treatment Discontinuation ......................................................................23 
5.7. 
Criteria for Study Pausing or Termination .................................................................24 
6. 
STUDY POPULATION .............................................................................................25 
6.1. 
Number of Subjects ....................................................................................................25 


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6.2. 
Subject Inclusion Criteria ...........................................................................................25 
6.3. 
Subject Exclusion Criteria ..........................................................................................25 
6.4. 
Subjects or Partners of Subjects of Reproductive Potential .......................................26 
6.5. 
Waivers of Inclusion/Exclusion Criteria ....................................................................26 
7. 
DESCRIPTION OF STUDY TREATMENT .............................................................27 
7.1. 
Description of Study Drug ..........................................................................................27 
7.2. 
Description of Placebo ................................................................................................27 
7.3. 
Preparation of Study Drug for Administration ...........................................................28 
7.4. 
Study Drug Administration.........................................................................................28 
7.5. 
Subject Monitoring During rhu-pGSN Infusion .........................................................28 
7.6. 
Shipment of Study Drug .............................................................................................28 
7.7. 
Receipt and Storage of Study Drug ............................................................................29 
7.8. 
Accountability, Handling, and Disposal of Study Drug .............................................29 
7.9. 
Concomitant Medications ...........................................................................................29 
7.10. 
Treatment Compliance ................................................................................................29 
7.11. 
Randomization and Blinding ......................................................................................30 
7.11.1. 
Unblinding ..................................................................................................................30 
8. 
STUDY ASSESSMENTS ..........................................................................................31 
8.1. 
Safety Assessments .....................................................................................................34 
8.1.1. 
Pregnancy Test ............................................................................................................34 
8.1.2. 
Demographic/Medical History ...................................................................................34 
8.1.3. 
Vital Signs ..................................................................................................................34 
8.1.4. 
Physical Examination .................................................................................................34 
8.1.5. 
Laboratory Assessments .............................................................................................34 
8.2. 
Measurement of pGSN Levels and Pharmacokinetic Assessments ...........................35 
9. 
ADVERSE EVENT MANAGEMENT ......................................................................36 
9.1. 
Definition of Adverse Events .....................................................................................36 
9.1.1. 
Adverse Event (AE) ....................................................................................................36 
9.1.2. 
Serious Adverse Event (SAE) ....................................................................................36 
9.2. 
Clarifications to Serious Adverse Event Reporting ....................................................36 
9.3. 
Assessment of Causality .............................................................................................36 
9.4. 
Assessment of Severity ...............................................................................................36 
9.5. 
Pregnancy or Drug Exposure during Pregnancy ........................................................37 


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9.6. 
Laboratory Abnormalities ...........................................................................................37 
9.7. 
Reporting Adverse Events ..........................................................................................37 
10. 
STATISTICS ..............................................................................................................39 
10.1. 
General Overview .......................................................................................................39 
10.1.1. 
Method of Assigning Subjects to Treatment Groups .................................................39 
10.1.2. 
Data Collection and Analysis .....................................................................................39 
10.2. 
Sample Size and Power Calculations .........................................................................39 
10.3. 
Analysis Populations ..................................................................................................39 
10.4. 
Criteria for Evaluation and Statistical Methods ..........................................................40 
10.4.1. 
Safety ..........................................................................................................................40 
10.4.2. 
Baseline Characteristics ..............................................................................................40 
10.4.3. 
Pharmacokinetics and Immunogenicity ......................................................................40 
11. 
DATA RECORDING, RETENTION AND MONITORING ....................................41 
11.1. 
Case Report Forms .....................................................................................................41 
11.2. 
Records Retention .......................................................................................................41 
11.3. 
Data Monitoring ..........................................................................................................41 
11.4. 
Quality Control and Quality Assurance ......................................................................42 
12. 
REGULATORY, ETHICAL AND LEGAL OBLIGATIONS ..................................43 
12.1. 
Good Clinical Practice ................................................................................................43 
12.2. 
Independent Ethics Committee Approval ...................................................................43 
12.3. 
Regulatory Authority Approval ..................................................................................43 
12.4. 
Other Required Approvals ..........................................................................................43 
12.5. 
Informed Consent .......................................................................................................43 
12.6. 
Subject Confidentiality ...............................................................................................44 
12.7. 
Disclosure of Information ...........................................................................................44 
13. 
LIST OF REFERENCES ............................................................................................45 
 


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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................13 
Table 2: 
Summary of Deaths in Study CBC-101 ......................................................................17 
Table 3: 
Investigational Product ...............................................................................................27 
Table 4: 
Schedule of Assessments ............................................................................................32 
Table 5: 
Minimum Sample Size Calculations ..........................................................................39 
 


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2. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
ADA 
anti-drug antibody 
AE 
adverse event 
ALI 
acute lung injury 
ALT 
alanine aminotransferase 
aPTT 
activated partial thromboplastin time 
ARDS 
acute respiratory distress syndrome 
AST 
aspartate aminotransferase 
AUC0-8 
area under the curve from time zero to 8 hours 
AUCinf 
area under the curve from time zero to infinity 
BioAegis or BTI 
BioAegis Therapeutics, Inc. or Sponsor 
BMI 
body mass index 
CAP 
community-acquired pneumonia 
CBC 
complete blood count 
Cmax 
maximum concentration 
COPD 
chronic obstructive pulmonary disease 
COVID-19 
coronavirus 2019 
CPK 
creatine phosphokinase 
eCRF 
electronic case report form 
DSMB 
Data and Safety Monitoring Board 
DVT 
deep vein thrombosis 
EDC 
electronic data capture 
ELISA 
enzyme-linked immunosorbent assay 
EOS 
end-of-study (visit) 
f-actin 
filamentous actin 
FDA 
Food and Drug Association 
g-actin 
globular actin 
GCP 
Good Clinical Practice 
ICF 
informed consent form 


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Abbreviation or Specialist Term 
Explanation 
ICH 
International Council for Harmonization of Technical 
Requirements for Pharmaceuticals for Human Use 
ICU 
intensive care unit 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IRR 
infusion-related reaction 
IUD 
intrauterine device 
IV 
intravenous 
MV 
mechanical ventilation 
NOAEL 
no-observed-adverse-effect level 
NSAIDs 
non-steroidal anti-inflammatory drugs 
NSS 
normal saline solution 
PDF 
portable document format 
PE 
pulmonary embolism 
PI 
Principal Investigator 
The investigator who leads the study conduct at an 
individual study site. Every study site has a principal 
investigator. 
PK 
pharmacokinetics 
PT 
prothrombin time 
rhu-pGSN 
recombinant human plasma gelsolin 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SOC 
standard of care 
SRC 
Safety Review Committee 
SUSAR 
suspected unexpected serious adverse reaction 
T1/2 
terminal half-life 
TEAE 
treatment-emergent adverse event 
Tmax 
time to maximum concentration 
US 
United States 
VP 
vasopressor 
 


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3. 
INTRODUCTION 
3.1. 
Background 
Acute hypoxemic respiratory failure can result from a severe inflammatory process in the lung 
(e.g., viral or bacterial pneumonia or inhalation injury) or distant from the lungs (e.g., intra-
abdominal sepsis or necrotizing pancreatitis). In its advanced form (identified by a partial 
pressure of O2/fraction of inspired O2 [P/F ratio] <300, often <200), bilateral infiltrates develop 
that are not caused by volume overload or heart failure within 1 week of an inciting injury (often 
infection in the lung or a distant site), which culminates in intubation or noninvasive respiratory 
support. Using an expanded Berlin definition, these patients generally satisfy criteria for acute 
respiratory distress syndrome (ARDS) or at least moderate-to-severe acute lung injury (ALI) and 
require intensive care with mechanical or non-invasive ventilation or high-flow oxygen therapy. 
ALI/ARDS appears to be mediated by excessive and injurious inflammation that targets the lung 
whether or not the lung is or was the site of the initial injury. 
3.2. 
Current Treatment of ALI/ARDS 
Other than supportive care and treatment of the precipitating event, no pharmacologic 
interventions aimed directly at the lung injury clearly benefit patients with ALI/ARDS. 
Interrupting or tempering the maladaptive inflammatory process could theoretically lessen 
further organ injury. To this end, glucocorticoids at various doses have been used without 
conclusive results in most circumstances. The evidence in ALI/ARDS associated with 
coronavirus 2019 (COVID-19) pneumonia indicates a role for steroids in severe-critical 
infections. Unfortunately, steroids induce an immunosuppressive state that may complicate 
ongoing infection or exaggerate the risk of nosocomial infection. Thus, there is an unmet need 
for less toxic alternative therapies for the treatment of inflammatory diseases leading to 
ALI/ARDS.  
3.3. 
Plasma Gelsolin  
Plasma gelsolin is a human protein produced and secreted by virtually every cell type, and it 
circulates at high levels in the blood of healthy individuals. At normal levels of 200-300 mg/L, it 
is the fourth most abundant protein in the circulation. 
The therapeutic protein being developed by BioAegis Therapeutics, Inc. (BioAegis or Sponsor) 
is recombinant human plasma gelsolin (rhu-pGSN). It is identical to the complete natural protein 
and is comprised of 755 amino acids. The protein, like the natural protein, is non-glycosylated. 
The protein consists of six repeated domains, which make up three distinct actin binding sites, 
two that bind globular actin (G-actin) and one that binds filamentous actin (F-actin). Domain 1 
plus the first 10 amino acids of domain 2 of gelsolin is the minimal fragment size required for its 
actin severing activity. Rhu-pGSN contains multiple calcium binding sites that regulate its 
activity. It is a highly conserved protein, as far back as drosophila. 
Plasma gelsolin modulates inflammation while at the same time, boosting the body’s ability to 
clear pathogens. It functions through mechanisms quite distinct from anti-inflammatory agents, 
which are antagonists of specific mediators or inhibitors of specific enzymes. Plasma gelsolin 
functions through a pleiotropic mechanism of action, scavenging toxic actin, binding 


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inflammatory mediators and enhancing pathogen clearance. Repletion of pGSN in patients 
developing ALI/ARDS may limit lung injury and improve survival.  
3.4. 
Preclinical and Clinical Experience 
3.4.1. 
Preclinical Experience 
Repeat IV administration of rhu-pGSN to rats at up to 25 or 100 mg/kg/day for 14 and 7 days, 
respectively, and to monkeys at up to 20 mg/kg/day for 14 days revealed no adverse effects on 
body weight, food consumption, clinical signs, ophthalmology parameters, clinical pathology, 
the cardiovascular system (monkeys), organ weights, and macroscopic and microscopic 
pathology. No clinically relevant pathological effects were evident in rats or monkeys following 
administration of rhu-pGSN for 14 days by IV injection. In addition, a study in Sprague Dawley 
rats utilizing the recently manufactured lot of BioAegis drug product administered at 100 mg/kg 
in 5 doses over 72 hours was conducted with no remarkable findings or adverse effects on the 
central nervous system. Thus, the no-observed-adverse-effect levels (NOAELs) for IV 
administration of rhu-pGSN in Sprague Dawley rats are:100 mg/kg/dose with 5 doses over 
3 days, 100 mg/kg/dose daily for 7 days, and 25 mg/kg/dose daily for 14 days. The NOAEL for 
IV administration of rhu-pGSN in cynomolgus monkeys is 20 mg/kg/dose daily for 14 days. 
Test article-related effects observed following repeat aerosol administration (3-25 mg/day) of 
rhu-pGSN under conditions of continuous pulmonary exposure were limited to minimal 
microscopic changes in the lungs of monkeys. The microscopic change is attributed to an 
immunogenic response as evidenced by the detection of antibodies to rhu-pGSN. The antibodies 
appeared to be directed against the human-specific epitopes of intact rhu-pGSN and caused no 
clinical or pathological signs of serum sickness. Thus, the immunogenic reaction to rhu-pGSN in 
monkeys appears to be a species-specific response and, therefore, is not considered to be 
clinically relevant. No eye (0.5 mg) or skin (2.5 mg/site) irritation was noted in rabbits after 
acute exposure to the product.  
In summary, the preclinical profile of rhu-pGSN suggests that this drug will be well tolerated by 
humans and that the risk of respiratory or systemic toxicity is low. 
3.4.2. 
Clinical Experience 
Rhu-pGSN has been previously evaluated in 5 clinical studies. 
Study 96-900 was a Phase 1, double-blind, randomized, controlled, within-subject, dose 
escalation study in 24 healthy volunteers conducted in the United Kingdom. Patients were dosed 
via nebulization up to a maximum dose of 32 mg given twice per day. Adverse events (AEs) 
were minor, and none were consistently attributed to treatment. No formation of antibodies to 
rhu-pGSN was observed.  
Study C96-901 was a randomized, double-blind, placebo-controlled, dose escalating, tolerability 
study of inhaled rhu-pGSN in 21 patients with cystic fibrosis conducted at one clinical site in 
Canada. Rhu-pGSN or placebo was administered via nebulization at 3.0 mg per day (Day 1 and 
2), 10 mg per day (Day 3 and 4) and 25 mg per day (Day 5 to 9). Sixteen patients were 
randomized to rhu-pGSN and five patients to placebo (randomization ratio 3:1). Rhu-pGSN was 
well tolerated and no safety concerns were raised. No patients withdrew from the study. There 


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was no negative effect on pulmonary function. There were no serious adverse events (SAEs), and 
no AEs were considered likely or definitely related to treatment.  
Study CBC-101 was a randomized, double-blind, placebo-controlled, ascending dose, infusion 
trial of the PK of rhu-pGSN in patients with decreased natural gelsolin levels. This Phase 1b/2a 
study was conducted in Hong Kong and enrolled patients admitted to the intensive care unit 
(ICU). Twenty-eight patients were enrolled; 21 patients received rhu-pGSN and 7 received 
placebo. The 4 cohorts were treated with ascending doses of rhu-pGSN via IV infusion 
according to the following scheme: 
Cohort 1: Single infusion of 3 mg/kg rhu-pGSN (10 patients) or placebo (3 patients) 
Cohort 2: Single infusion of 6 mg/kg rhu-pGSN (3 patients) or placebo (2 patients) 
Cohort 3: Daily infusion of 6 mg/kg rhu-pGSN for 3 days (6 patients) or placebo (2 patients) 
Cohort 4: Daily infusion of 6 mg/kg rhu-pGSN for 3 days (2 patients with severe multiple organ 
failure) 
The dose escalation over the successive cohorts was supervised by an independent data and 
safety monitoring board (DSMB). The DSMB had to document the safety profile of the drug 
before allowing the study to proceed to a higher dose and/or exposure. No safety concerns 
associated with rhu-pGSN were raised by the DSMB. Seven patients died during the 3-month 
observation period (Table 2); none of the deaths were assessed as related to study treatment. No 
patient who received placebo died. The incidence of death in the rhu-pGSN-treated patients 
(7/21; 33%) is within the limits of expectation for patients admitted in ICU with similar 
diagnoses. However, the incidence of death was lower than expected in the placebo group, most 
probably due to imbalances in multiple baseline clinical prognostic factors in favor of the 
placebo group when compared to the rhu-pGSN group. 
Table 2: 
Summary of Deaths in Study CBC-101 
Subject Cohort 
Age 
pGSN 
mU/mL 
Admission diagnosis1 
VP 
MV 
Day of 
admission 
relative to 
infusion2 
Day of 
death3 
G004 
1 
84 
921 
Fecal peritonitis, 
emergency 
rectosigmoidectomy, 
renal insufficiency 
Yes Yes 
-10 
5 
G006 
1 
69 
1892 
Pneumonia with 
hepatitis 
No 
Yes 
-10 
3 
G012 
1 
79 
524 
Sigmoid perforation, 
emergency 
rectosigmoidectomy 
No 
No 
-6 
26 
G015 
2 
79 
1161 
Pneumonia, COPD 
Yes Yes 
-15 
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Subject Cohort 
Age 
pGSN 
mU/mL 
Admission diagnosis1 
VP 
MV 
Day of 
admission 
relative to 
infusion2 
Day of 
death3 
G017 
2 
78 
963 
Peritonitis with terminal 
cholangiocarcinoma 
No 
No 
-10 
16 
G018 
2 
85 
1128 
Pneumonia with renal 
insufficiency 
Yes Yes 
-10 
66 
G401 
4 
83 
780 
Pneumonia with renal 
insufficiency 
Yes Yes 
-4 
7 
COPD=chronic obstructive pulmonary disease; ICU=intensive care unit; MV=mechanical ventilation; 
pGSN=plasma gelsolin; VP=vasopressor. 
1 Diagnosis established at ICU admission 
2 Represents the day of hospitalization (irrespective of ICU or not) relative to day of infusion 
3 Day of death relative to first infusion 
 
Study BTI-201 was a Phase 1b/2a, double-blind, placebo-controlled, single and multiple 
ascending dose escalation study to evaluate the safety, PK, and pharmacodynamics of rhu-pGSN 
added to standard of care (SOC) in non-ICU patients hospitalized for mild community-acquired 
pneumonia (CAP). Eligible subjects were randomized 3:1 to receive adjunctive IV rhu-pGSN or 
placebo. Thirty-three subjects were treated: 8 received a single dose of rhu-pGSN 6 mg/kg, and 
25 received a daily rhu-pGSN dose of 6, 12, or 24 mg/kg over 3 consecutive days (Tannous et 
al., 2020). 
Overall, AEs were mild in both treatment groups irrespective of dose. AEs were reported more 
frequently in the lowest rhu-pGSN dose cohorts and the less frequently in the highest rhu-pGSN 
dose cohorts. Treatment-emergent adverse events (TEAEs) that were reported in more than 
1 subject in the rhu-pGSN groups were: nausea (11.1% rhu-pGSN; 0% placebo) and blood 
pressure increased (11.1% rhu-pGSN; 0% placebo). No infusion-related reactions (IRRs) were 
reported. Of the subjects treated with rhu-pGSN, no subject experienced a TEAE assessed as 
drug-related, and no subject discontinued due to a TEAE. 
Two subjects experienced SAEs: 1 SAE was reported in 1 subject who received a single dose of 
rhu-pGSN, and 2 SAEs were reported in 1 subject who received placebo in the multiple 
ascending dose phase. One subject who received a single dose of rhu-pGSN had an SAE of 
pneumonia (Grade 5, not related) after being withdrawn from the study; and 1 subject who 
received placebo had SAEs of pneumonia (Grade 4, not related) and pulmonary embolism 
(Grade 5, not related).  
Pharmacokinetic analyses showed that the median rhu-pGSN half-life exceeded 17 hours with all 
dosing regimens. Overall, rhu-pGSN was well tolerated in patients admitted to non-ICU beds 
with CAP. 
Study BTI-202 was a Phase 2 randomized, double-blind, placebo-controlled study to evaluate 
the efficacy and safety of rhu-pGSN added to SOC for the treatment of subjects hospitalized with 
severe COVID-19 pneumonia (NCT04358406) (DiNubile et al., 2022). The study was conducted 


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in Spain and Romania. Sixty-four subjects with severe COVID-19 pneumonia were randomized 
1:1 to receive rhu-pGSN or placebo intravenously in addition to SOC. Standard of care was left 
to the judgment of the caregivers without restrictions. Three doses of rhu-pGSN 12 mg/kg based 
on actual body weight were administered at 0, 12, and 36 hours. Of the 61 treated subjects, 
54 completed the study, 4 died, and 3 were lost to follow-up. No subject discontinued due to an 
AE. The primary efficacy endpoint, the proportion of subjects alive without respiratory, 
hemodynamic, or renal support on Day 14, did not differ between treatment arms: 25 of 30 rhu-
pGSN recipients (83.3%) and 27 of 31 placebo recipients (87.1%). Adverse events occurred with 
similar frequencies in both treatment groups. Most AEs were mild to moderate in severity and 
related to COVID-19 pneumonia. Serious adverse events were numerically fewer in the rhu-
pGSN group than placebo group and all were assessed as unrelated to study drug. No pattern of 
AEs was discernable in either treatment arm. Two subjects in each group died during the 90-day 
study, but no deaths were attributable to study drug.   
3.5. 
Rationale for Study and Starting Dose 
Given that pGSN is a naturally occurring plasma protein, the risk of drug toxicity related to rhu-
pGSN infusion is expected to be low. In healthy primates dosed for 14 days, drug levels were 
similar to those obtained in human patients with pneumonia after administration of 12 mg/kg 
without evident toxicities. The doses given to humans have reached 24 mg/kg for 3 consecutive 
days. No distinctive safety signal was seen in the 2 small BioAegis studies to date; in fact, SAEs 
were numerically fewer in rhu-pGSN recipients compared to saline-placebo control subjects. 
However, in Study CBC-101 evaluating sick patients in the ICU administered a previous 
formulation of rhu-pGSN, 7 of 21 rhu-pGSN and 0 of 7 placebo recipients died (Table 2). None 
of the deaths were judged to be related to study drug and were all attributed to the serious 
underlying conditions of the participants. A post-hoc analysis indicated the rhu-pGSN group had 
higher acuity scores than the placebo group. All but one subject who died in Study CBC-101 
were in the single-dose rhu-pGSN dosing groups.  
Efficacy has only been demonstrated in animal models. It is anticipated that in sick patients, 
pGSN levels would be lower than normal at presentation and that rhu-pGSN administered IV 
would be consumed more rapidly than in healthy subjects. As such, efficacy in sick patients may 
require doses higher than used in the earlier clinical trials. Based on the previous human 
experience, 3 daily doses of 6, 12, and 24 mg/kg of rhu-pGSN were well tolerated in patients 
with CAP. An accelerated dosing schedule where rhu-pGSN was administered to patients 
hospitalized with COVID-19 pneumonia as 12 mg/kg at time 0, 12, and 36 hours was also 
generally well tolerated. 
Before treating a larger number of critically ill patients to establish proof of concept in subjects 
with ALI/ARDS, the Sponsor aims to study the safety, tolerability, and PK of IV rhu-pGSN 
administered to healthy subjects. The current study is designed to primarily evaluate the safety 
and tolerability of sequential ascending doses of rhu-pGSN at 6, 12, 18, and 24 mg/kg of body 
weight, each given 5 times at 0, 12, 36, 60, and 84 hours. 
A risk analysis of the immunogenicity potential of rhu-pGSN has been conducted. Overall, the 
risk assessment based upon product, process, and subject factors indicates a low potential for 
generation of an immune response. Anti-pGSN antibodies could in theory be clinically 


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meaningful. In the current study, specimens will be collected for ADA measurements at the first 
and last study visit. 


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4. 
STUDY OBJECTIVES AND ENDPOINTS 
4.1. 
Objectives 
4.1.1. 
Primary Objective 
• To evaluate the safety and tolerability of 4 sequentially ascending doses of rhu-pGSN 
at 6 mg/kg, 12 mg/kg, 18 mg/kg, and 24 mg/kg of actual body weight administered by 
intravenous (IV) infusion for 5 doses at 0, 12, 36, 60, and 84 hours to healthy subjects 
4.1.2. 
Secondary Objectives 
•  To characterize the pharmacokinetic (PK) profile of rhu-pGSN following 
administration of multiple (5) doses of rhu-pGSN to healthy subjects assigned to 4 
dose levels (6, 12, 18, or 24 mg/kg) 
• To investigate the development of anti-pGSN antibodies following administration of 
multiple (5) doses of rhu-pGSN administered to healthy subjects assigned to 4 dose 
levels (6, 12, 18, or 24 mg/kg) 
4.2. 
Endpoints 
4.2.1. 
Primary Endpoint 
• Incidence and severity of AEs regardless of causality graded according to the 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials 
4.2.2. 
Secondary Endpoints 
• PK for IV rhu-pGSN including, but not limited to: Cmax, Tmax, T1/2, AUC0-8, and 
additionally after Dose #5, AUC0-24, and AUCinf (levels measured on Day 1 within 
30 minutes predose, and at 15 minutes and 1, 2, 4, 8, and 12 hours after Dose #1 and 
on Days 4 and 5 within 30 minutes predose, and at 15 minutes and 1, 2, 4, 8, 12, and 
24 hours after Dose #5) 
• Presence of anti-rhu-pGSN antibodies at Day 28 
 


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5. 
INVESTIGATIONAL PLAN 
5.1. 
Overall Study Design 
Study BTI-101 is a Phase 1, randomized, double-blind, placebo-controlled, dose escalation, 
parallel design study to evaluate the safety, tolerability, and PK of IV rhu-pGSN or saline 
placebo administered as 5 doses each of 6, 12, 18, or 24 mg/kg of body weight. Each of 4 dosing 
cohorts will include 8 subjects randomized 3:1 rhu-pGSN:placebo (6 rhu-pGSN 
subjects:2 placebo subjects). Subjects will be healthy adults 18-50 years of age. 
Doses will be administered at 0 hours (Day 1), 12 hours (Day 1), 36 hours (Day 2), 60 hours 
(Day 3), and 84 hours (Day 4). Subjects will be kept in-house until after the last blood sample is 
taken on Day 5. Subjects will return for follow-up 7 days after the initiation of therapy (Day 7) 
and on Day 28 for the End-of-Study (EOS) Visit. After each cohort has completed the Day 7 
visit, review of the safety results (including labs) will be conducted (and unblinded where 
appropriate) before the initiation of the next higher dose cohort.  
To assess safety and tolerability, subjects will undergo physical examinations (including vital 
sign measurements), AE assessments, concomitant medication assessments, and safety 
laboratory testing. Blood samples will be collected for analysis of pGSN levels and antibodies 
against pGSN. See Table 4 for a schedule of all study events. 
5.2. 
Safety Review Committee 
The safety data will be reviewed by a Safety Review Committee (SRC) comprised of at least 
1 expert clinician, the Medical Monitor at the contract research organization, and the Sponsor’s 
Chief Medical Officer. 
Adverse events (AEs) will be categorized as “serious” according to the judgement of the site 
investigator as to whether the definition of SAE (section 9.1.2)  is met and then reviewed and 
adjudicated by the SRC.  The “severity” of an AE will be graded according to the Toxicity 
Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials.  An individual patient will be discontinued permanently from study treatment if 
they experience any serious adverse event (SAE) or a severity Grade 3 or greater AE (including 
infusion reactions).  Further study treatment and enrollment will be paused pending review by 
the SRC if there are two Grade 3 AEs, one Grade 4 AE, or one SAE.  The study will only be 
resumed if the SRC unanimously judges the AEs as unrelated to study treatment and procedures 
after consultation with regulatory and outside experts as needed. 
The SRC will review safety data (including lab tests) through the Day 7 visit for each dosing arm 
to determine if it is safe to initiate the next cohort according to the safety criteria for stopping 
doses (Section 5.3).  
5.3. 
Safety Criteria for Stopping Doses 
Dosing of rhu-pGSN may be stopped during the study at the discretion of the SRC.  All AEs 
occurring during this healthy-volunteer study will be presumed to be related to study drug unless 
occurring before the study therapy is initiated pending review by the SRC.   


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An individual patient will be discontinued permanently from study treatment if they experience 
any serious adverse event (SAE) or a severity Grade 3 or greater AE (including infusion-related 
reactions) regardless of causality.   
Further study treatment and enrollment will be paused pending review by the SRC if any patient 
dies or there are two Grade 3 AEs, one Grade 4 AE, or one SAE.  The study will only be 
resumed if the SRC unanimously judges the death or AEs as unrelated to study treatment and 
procedures after consultation with regulatory and outside experts as needed. 
5.3.1. 
Management of rhu-pGSN Infusion-Related Reactions 
In general, doses should only be temporarily interrupted for Grade 1 or 2 AEs, but treatment to 
control symptoms should be provided, if applicable.  The infusion can be restarted at a slower 
rate once symptoms have dissipated,  If symptoms recur, the infusion will be permanently 
discontinued. If a subject develops a Grade 3-4 IRR: 
• The infusion should be stopped immediately, and the infusion tubing should be 
disconnected from the subject. 
• The subject should receive appropriate treatment with an antihistamine and/or 
acetaminophen (paracetamol) and/or methylprednisolone (or equivalent) and, if 
necessary, further medications (i.e., epinephrine, bronchodilator). 
• The subject may not receive further infusions of study therapy. 
5.4. 
Duration of Subject Participation 
The duration of subject participation includes screening for up to 6 weeks, study treatment for 
4 days, and safety follow-up through 28 days post-first dose for a maximum duration of subject 
participation of 10 weeks. 
5.5. 
End of Study Definition 
End of study (EOS) will be defined as the date the last subject completes the EOS Visit. The 
Sponsor will notify all applicable regulatory agencies in accordance with local requirements 
when the study has ended. 
5.6. 
Criteria for Treatment Discontinuation 
Subjects are free to discontinue their participation in the study at any time and without prejudice 
to further treatment. The Investigator must withdraw any subject from the study if that subject 
requests to be withdrawn, or if it is determined that continuing in the study would result in a 
significant safety risk to the subject. 
The subject's participation in this study may be discontinued for the following reasons: 
• Any SAE 
• Grade 3 AEs or Grade 4 AE 
• Subject withdrew consent 
• Subject is unwilling or unable to continue the study or is lost to follow up 
• Subject is non-compliant with study procedures/study protocol 


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• Investigator decides that withdrawal from the study is in the best interest of the subject 
• Any clinically significant change in subject’s medical condition (at the discretion of the 
Investigator) 
• Sponsor decision to end the study 
If a subject withdraws from the study prematurely, assessments scheduled for the EOS Visit 
should be performed as soon as possible. If a subject refuses further assessment, the subject 
should be contacted for safety evaluations (AE/concomitant medications/potential pregnancy) 
approximately 28 days after study withdrawal. 
If such withdrawal occurs, or if the subject refuses to participate in the EOS Visit, the 
Investigator must determine the primary reason for a subject’s withdrawal from the study and 
record the information on the electronic case report form (eCRF). If the reason for withdrawal is 
an AE, monitoring should continue until the outcome is evident. The specific event or test 
result(s) must be recorded in the eCRF. At the discretion of the Sponsor, subjects may also be 
removed from the study (Section 5.4). 
It should be clearly documented in the source data whether a subject withdrew his/her consent 
and will not enter the follow-up phase, or if a subject withdrew his/her consent for study drug 
treatment but will continue further participation in the study. 
5.7. 
Criteria for Study Pausing or Termination 
The Sponsor reserves the right to discontinue the study at any time for any reason. Such reasons 
may be any of, but not limited to, the following:  
• Occurrence of AEs unknown to date in respect to their nature, severity, and duration, 
or the unexpected incidence of known AEs  
• Any SAE pending review by the Safety Review Committee (SRC) 
• Two Grade 3 or one Grade 4 AE pending review by the Safety Review Committee 
(SRC) 
• Any death pending review by the Safety Review Committee (SRC) 
• Medical or ethical reasons affecting the continued performance of the study 
If the study is prematurely terminated, the Investigator is to promptly inform the study subjects 
and Independent Ethics Committee (IEC) and should ensure appropriate follow up for the 
subjects. All procedures and requirements pertaining to the archiving of study documents should 
be followed. All other study materials (e.g., study drug, etc.) must be destroyed or returned to the 
Sponsor. 


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6. 
STUDY POPULATION 
6.1. 
Number of Subjects 
A total of 32 (6 rhu-pGSN and 2 placebo recipients per dose cohort x 4 dosing levels). 
6.2. 
Subject Inclusion Criteria 
1. Healthy male or female adults 18 to 50 years of age without chronic or active acute 
medical conditions 
2. Informed consent obtained from subject  
3. Weight <100 kg and body mass index (BMI) <25 kg/m2 
4. Willingness during the course of the study, starting at screening and for at least 3 months 
after their final study treatment: 
a) Female subjects of childbearing potential must agree to use 2 medically 
accepted/Food and Drug Association (FDA)-approved birth control methods 
b) Male subjects with a partner who might become pregnant must agree to use 
reliable forms of contraception (i.e., condom, vasectomy, abstinence), or an 
acceptable method of birth control must be used by the partner 
c) All subjects must agree not to donate sperm or eggs 
6.3. 
Subject Exclusion Criteria 
1. Pregnant or lactating women 
2. Acute illness during the month prior to screening 
3. Circumstances that may require any medications (including prescription medication, 
over-the-counter medication, vitamins, or supplements) during the conduct of the study 
other than acetaminophen 
4. Hospitalization during the year prior to screening 
5. History of cancer or treatment with systemic chemotherapy or radiation therapy at any 
time 
6. Transplantation of hematopoietic or solid organs   
7. History of diabetes mellitus; myocardial infarction, angina, or other cardiovascular 
disease; stroke or cerebrovascular disease; chronic obstructive pulmonary disease 
(COPD) or asthma; deep vein thrombosis (DVT)/pulmonary embolism (PE); liver or 
kidney disease; psychiatric condition; or active or chronic infection  
8. Receipt of blood products during the year prior to screening 
9. Chronic mechanical ventilation or dialysis 
10. Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis 
results as judged by the Investigator 


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11. Any clinically significant abnormalities of vital signs or physical examination findings as 
judged by the Investigator 
12. Positive results for recreational drugs during screening 
13. Any other condition deemed by the Investigator as possibly interfering with the conduct 
of the study 
6.4. 
Subjects or Partners of Subjects of Reproductive Potential 
Pregnancy is an exclusion criterion and women of childbearing potential must not be considering 
getting pregnant during the study. Unless they have had a hysterectomy, female subjects must 
have a negative serum or urine pregnancy test within 36 hours prior to start of study drug. A 
serum or urine pregnancy test will be performed at the EOS Visit. A total of 2 acceptable 
methods of birth control must be used per couple. 
Women of childbearing potential must practice 2 acceptable methods of birth control starting at 
screening and continuing at least 3 months after the last study treatment. Acceptable methods of 
birth control in this study include true sexual abstinence (i.e., completely refraining from 
heterosexual intercourse throughout the study), hormonal methods (e.g., “the pill,” hormone 
injections, implants), barrier methods (e.g., condom or diaphragm), intrauterine device (IUD or 
“coil”), or sex exclusively with a sterilized partner. An accepted birth control method used by the 
male partner can count as one of the 2 acceptable methods of birth control for the woman. 
Male subjects with a partner who might become pregnant must use reliable forms of 
contraception (i.e., condom, vasectomy, abstinence) during the study starting at screening and for 
at least 3 months after the last study treatment, and an acceptable method of birth control must be 
used by the female partner (i.e., oral contraceptive, IUD, hormonal implants, contraceptive 
injection, or a double-barrier method). 
Subjects will be instructed to notify the Investigator if pregnancy is discovered either during or 
within 3 months of the last dose of study drug.  
6.5. 
Waivers of Inclusion/Exclusion Criteria 
No waivers of these inclusion or exclusion criteria (Section 6.2 and Section 6.3) will be granted 
by the Investigator and/or the Sponsor or its designee for any subject enrolling into the study.  
 


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7. 
DESCRIPTION OF STUDY TREATMENT  
7.1. 
Description of Study Drug 
Rhu-pGSN drug product is provided as lyophilized powder containing rhu-pGSN plus 
excipients. It is provided in 10-mL glass vials to be reconstituted to a volume of 5.3 mL with 
4.9 mL of sterile water yielding a final concentration of 40 mg/mL of rhu-pGSN, 2% glycine, 
4% trehalose, 0.5% arginine, and 0.1% poloxamer 188 in a 10-mM phosphate buffer, pH 7 
(Table 3). 
Rhu-pGSN is administered via IV push ≤20 mL/minute. A total of 5 doses of rhu-pGSN will be 
administered to participating subjects at 0, 12, 36, 60, and 84 hours (Dose 1 is administered at 
time 0; a window of ±2 hours will be allowed around dosing times for the 2nd and 3rd doses, and 
±4 hours for the last 2 doses).  
Table 3: 
Investigational Product 
 
Investigational Product 
Product Name: 
rhu-pGSN 
Dosage Form: 
Powder for solution filled as a 5.3 mL fill in 10 mL glass vials  
Unit Dose 
rhu-pGSN reconstituted to a volume of 5.3 mL with 4.9 mL 
of sterile water 
Route of Administration 
Intravenous 
Physical Description 
Lyophilized powder  
Storage Conditions 
2 to 8 °C 
Manufacturer 
Drug Product: Lyophilization Services of New England, Inc., 
25 Commerce Drive, Bedford, NH 03110, USA 
Vials containing rhu-pGSN study drug will be labeled according to national regulations for 
investigational products. 
7.2. 
Description of Placebo 
Placebo will be dosed at a weight-based volume of 0.025 mL/mg × dose in mg/kg × weight in kg 
of 0.9% saline solution via IV push (matching the volume of rhu-pGSN for a subject of that size) 
injected at ≤20 mL/minute though a standard 0.2 μ filter at 0, 12, 36, 60, and 84 hours (Dose 1 is 
administered at time 0; a window of ±2 hours will be allowed around dosing times for the 2nd and 
3rd doses, and ±4 hours for the last 2 doses). The placebo requires no special manipulation.  


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7.3. 
Preparation of Study Drug for Administration 
The Investigator or designee will be responsible for administering the appropriate dose of IV 
rhu-pGSN to subjects. rhu-pGSN must be stored refrigerated at 2 to 8 °C in its original package 
in an appropriate storage facility accessible only to the pharmacist(s), the Investigator, or a duly 
designated person. 
The unblinded pharmacist will determine the dose (mg) of rhu-pGSN, calculate the volume of 
rhu-pGSN solution needed, and reconstitute lyophilized study drug with sterile water. 
The individual rhu-pGSN infusion will be prepared under aseptic conditions and administered at 
the study site according to the directions of the Sponsor, which will be provided in a Pharmacy 
Manual. Any powder remaining in the vial must be discarded. After dilution for infusion, 
administration of rhu-pGSN should be initiated as soon as possible but no later than 6 hours. 
Maximum allowed storage times and conditions will be detailed in the Pharmacy Manual. 
7.4. 
Study Drug Administration 
rhu-pGSN is administered via IV push ≤20 mL/minute. A total of 5 doses of rhu-pGSN will be 
administered to participating subjects at 0, 12, 36, 60, and 84 hours. Dose 1 is time 0; a window 
of ±2 hours will be allowed around dosing times for the 2nd and 3rd doses, and ±4 hours for the 
last 2 doses. 
Subjects are to be monitored for administration site reactions during an infusion and for 1 hour 
after its completion. Infusion site reactions will be recorded as AEs using the appropriate coding 
terms on the eCRF. 
7.5. 
Subject Monitoring During rhu-pGSN Infusion 
Vital signs should be measured as outlined in Section 8.1.3. All supportive measures consistent 
with optimal patient care will be provided throughout the study according to institution 
standards. 
Precautions for anaphylaxis should be observed during rhu-pGSN administration. Emergency 
resuscitation equipment and medications should be readily available. Additional supportive 
measures should also be available and may include, but are not limited to, epinephrine, 
antihistamines, corticosteroids, IV fluids, vasopressors, oxygen, bronchodilators, 
diphenhydramine, and acetaminophen (paracetamol). 
7.6. 
Shipment of Study Drug 
Prior to study treatment, study medications will be supplied to the clinical trial site's pharmacy 
by the Sponsor or its designee. 
Shipment of study drug supplies for the study will be accompanied by a shipment form 
describing the contents of the shipment, drug information, and other appropriate documentation. 
The shipment form will assist in maintaining current and accurate inventory records. 


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7.7. 
Receipt and Storage of Study Drug 
All study supplies should arrive at the pharmacy in sufficient quantity and in time to enable 
dosing as scheduled. The Investigator must ensure the acknowledgement of receipt of the clinical 
trial material (i.e., study drug and placebo) at the site, including that the material was received in 
good condition.  
The Sponsor or its designee must notify the Investigator/study staff prior to dispatch of drug 
supplies, with the anticipated date of their arrival, addressed to the site’s pharmacy. 
The investigational drug will be stored in the pharmacy, refrigerated at 2 to 8 ºC. The Sponsor 
should be notified for any deviation from the storage conditions. 
7.8. 
Accountability, Handling, and Disposal of Study Drug 
The study site must maintain accurate records documenting dates and amount of study drug 
received. The trial site's pharmacy will be responsible for ensuring the supervision of the storage 
and allocation of these supplies. When a shipment is received, the pharmacist will verify the 
quantities received and the accompanying documentation and will provide acknowledgment of 
receipt. 
Accountability logs will be provided to assist the pharmacist in maintaining current and accurate 
inventory records covering receipt, dispensing, and disposition of the study drug. An unblinded 
study monitor will examine inventory during the study. Accountability records must be readily 
available and may be subject to inspection by regulatory authorities or independent auditors at 
any time.  
Drug administration will be recorded in source documents and in the eCRFs.  
At the end of the study, delivery records of study drug will be reconciled with used / unused 
supplies. A disposition form will be completed to verify that all used, unused or partially used 
supplies have been returned or destroyed following appropriate accountability review by the 
monitor. One copy of all accountability records and the disposition form will be retained by the 
Investigator for the study files. 
7.9. 
Concomitant Medications 
Medications (i.e., prescriptions, over-the-counter medications, vitamins, or supplements) taken in 
the 6 weeks prior to study enrollment should be recorded and include the generic name (if 
possible). If known, document the start/stop date of each medication in the subject's file and in 
the eCRF. 
During the study, no medications except acetaminophen are permitted. 
7.10. 
Treatment Compliance 
The study drug will be administered by personnel at the study site to ensure compliance. 


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7.11. 
Randomization and Blinding 
Following screening, subjects qualified for study entry will be randomized to receive rhu-pGSN 
or placebo during the treatment period. All eligible subjects will be assigned a randomization 
number.  
The investigational site team and the subject will be kept blinded to the treatment allocation of 
each participant. Only the designated pharmacist(s) will be unblinded to the treatment allocation. 
The unblinded pharmacist will randomly assign a treatment allocation. 
7.11.1. 
Unblinding 
There is no antidote for rhu-pGSN. Unblinding should only be performed if knowledge of the 
treatment assignment will change the planned management of a medical condition. If possible, 
prior to unblinding, the need to unblind should be discussed with the Medical Monitor and 
Sponsor’s Chief Medical Officer; however, this should not delay unblinding if the Investigator 
believes it is necessary. Each case of unblinding will be documented and documentation will be 
stored separately by the unblinded pharmacist.  
Subjects that are unblinded may be withdrawn from the study. The decision to withdraw a 
subject from the study because of unblinding should be discussed with the Sponsor. If the subject 
is withdrawn, the Investigator or designee must record the date and reason for withdrawal on the 
appropriate eCRF for that subject.  
 


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8. 
STUDY ASSESSMENTS 
The procedures and assessments that will be conducted during this study are described in this 
section and summarized in the Schedule of Assessments (Table 4). Detailed instructions 
regarding all laboratory procedures, including collection and handling of samples, will be 
included in the study Laboratory Manual provided by the Sponsor or its designee. 
Written informed consent must be granted by each subject prior to the initiation of any study 
procedure or assessment. 
Study visits will occur daily for 5 days (inpatient), at 7 ± 1 day after Dose #1 (outpatient), and at 
28 ± 3 days after Dose #1 (outpatient). Subjects will be kept in-house until after the last blood 
sample is taken on Day 5 and asked to return on Days 7 and 28. 


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Table 4: 
Schedule of Assessments 
 
Outpatient 
Inpatient 
Inpatient 
Inpatient 
Inpatient 
Discharge 
Outpatient 
Outpatient 
Visit 
Screening 
Baseline/ 
Randomization
/Treatment  
Treatment/Follow-Up Days 
EOS Visit 
Day 
-6 weeks to 0 
1 
2 
3  
4 
5 
7 ±1 
28 ± 3 
Informed consent 
X 
 
 
 
 
 
 
 
Eligibility assessment 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Blood or urine 
pregnancy testa 
Xb 
 
 
 
 
 
 
X 
Physical exam (incl. 
height and weight) 
X 
 
 
 
 
 
 
 
Vital signsc 
X 
X 
X 
X 
X 
X 
X 
 
Blood/urine for 
safety laboratory 
analysesd 
Xb 
 
 
 
 
 
X 
X 
Adverse eventse 
 
X 
X 
X 
X 
X 
X 
X 
Review of 
Systems/Symptomse 
X 
X 
X 
X 
X 
X 
X 
X 
Study drug 
administrationf 
 
X/X 
(0 and 
12 hours) 
X 
(36 hours) 
X 
(60 hours) 
X 
(84 hours) 
 
 
 
Blood sampling for 
pGSN levelsg 
 
X 
(Dose #1) 
 
 
X 
(Dose #5) 
X 
(24 hours after 
Dose #5) 
X 
X 


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Outpatient 
Inpatient 
Inpatient 
Inpatient 
Inpatient 
Discharge 
Outpatient 
Outpatient 
Visit 
Screening 
Baseline/ 
Randomization
/Treatment  
Treatment/Follow-Up Days 
EOS Visit 
Day 
-6 weeks to 0 
1 
2 
3  
4 
5 
7 ±1 
28 ± 3 
Anti-rhu-pGSN 
antibody sampling  
 
X 
 
 
 
 
 
X 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AEs=adverse events; ALT=alanine aminotransferase; aPTT=activated partial thromboplastin time; AST=aspartate 
aminotransferase; CBC=complete blood count; CPK=creatine phosphokinase; EOS=end of study; PK=pharmacokinetic; PT=prothrombin time  
a Perform a serum or urine pregnancy test for female subjects unless they have had a hysterectomy. 
b If performed more than 36 hours before initiation of study drug, the test must be repeated within this time frame. 
c Record blood pressure, oral temperature, respiration rate, and heart rate. To be measured during infusions at the following time points: pre-
infusion, every 15 minutes after the start of infusion, at the end of infusion, and 30 minutes after the end of infusion. 
d Safety labs include collection of blood for a CBC, PT, aPTT, creatinine, bilirubin, alkaline phosphatase, CPK, AST, and ALT levels and 
collection of urine for drug screening (e.g., amphetamines, benzodiazepines, cannabinoids, cocaine, and opiates) and urinalysis (dipstick: glucose, 
protein, red blood cells, white blood cells). 
e Subjects will be interviewed to assess any possible AEs daily for 5 days, at 7 ± 1 day after Dose #1, and at 28 ± 3 days after Dose #1 (EOS Visit). 
Interviews can be done in person or by phone as mutually agreed by the Investigator and subject, but the EOS Visit should be done in person if 
possible so blood specimens can be collected.   
f Study drug will be administered by IV infusion at time 0 (Day 1), 12 hours (Day 1), 36 hours (Day 2), 60 hours (Day 3), and 84 hours (Day 4). 
Dose 1 will be at time 0, and a window of ±2 hours will be allowed around dosing times for the 2nd and 3rd doses, and ±4 hours for the last 2 doses. 
Subjects are to be monitored for administration site reactions during an infusion and for 1 hour after its completion.  
g Approximately 5 mL volume of blood will be drawn for measurement of pGSN levels on Day 1 within 30 minutes predose, and at 15 minutes 
and 1, 2, 4, 8, and 12 hours after Dose #1 and on Days 4 and 5 within 30 minutes predose, and at 15 minutes and 1, 2, 4, 8, 12, and 24 hours after 
Dose #5. Plasma will be obtained after centrifugation and promptly frozen at -20°C for assay in the central lab. A window of ±15 minutes will be 
allowed around the scheduled times except for the samples collected at 15 minutes postdose which have a window of ±5 minutes. A single sample 
will be collected anytime on Days 7 and 28. 
 


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8.1. 
Safety Assessments 
Prior to screening, all subjects must provide informed consent for study participation, per 
Section 12.5. The following assessments will be performed according to the time points in the 
Schedule of Assessments (Table 4). 
8.1.1. 
Pregnancy Test 
Unless they have had a hysterectomy, female subjects are required to have a negative serum or 
urine pregnancy test at screening to participate in the study. If the screening test is performed 
more than 36 hours before initiation of study drug, the test must be repeated within this time 
frame.   
8.1.2. 
Demographic/Medical History 
A review of demographic parameters, including age, gender, race, and ethnicity will be 
performed at screening.  
Past and present medical history will be recorded. Any ongoing condition or signs and symptoms 
observed prior to the initiation of study treatment should be recorded as medical history.  
8.1.3. 
Vital Signs 
Vital signs will include blood pressure, oral temperature, respiration rate, and heart rate, as well 
as pulse oximetry. Vitals signs will be measured during infusions at the following time points: 
pre-infusion, every 15 minutes after the start of infusion, at the end of infusion, and 30 minutes 
after the end of infusion. Significant findings noticed after the start of study drug that meet the 
definition of an AE must be recorded in the eCRF. 
8.1.4. 
Physical Examination 
All physical examinations, including measurement of body height and weight for calculation of 
BMI, will be performed by a study physician or designee. Height need only be measured at the 
screening examination. The initial body weight measured at enrollment will be used to calculate 
rhu-pGSN dosing for all doses (so that an individual subject will always receive the same dose). 
The physical examination includes skin, head, ears, eyes, nose, throat, heart, lungs, abdomen, 
and neurologic system. Additional examination may be performed as found relevant by the 
Investigator. 
8.1.5. 
Laboratory Assessments 
Where indicated, handling and shipping clinical laboratory samples to a central laboratory will 
be outlined in the Laboratory Manual. If a laboratory screening assessment is performed more 
than 36 hours before initiation of study drug, the test must be repeated within this time frame.   
Blood will be collected at the time points specified in Table 4 for safety laboratory evaluations 
including complete blood count [CBC], prothrombin time (PT), activated partial thromboplastin 
time (aPTT), creatinine, bilirubin, alkaline phosphatase, creatine phosphokinase [CPK], aspartate 
aminotransferase [AST], and alanine aminotransferase [ALT] levels.  


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In addition, urine will be collected at the time points specified in Table 4 for drug screening (e.g., 
amphetamines, benzodiazepines, cannabinoids, cocaine, and opiates) and urinalysis (dipstick: 
glucose, protein, red blood cells, white blood cells). 
Abnormal laboratory test results considered clinically significant by the Investigator or that 
require treatment should be reported as AEs in the eCRF.  
8.2. 
Measurement of pGSN Levels and Pharmacokinetic Assessments 
As indicated in Table 4, approximately 5 mL volume of blood will be drawn for measurement of 
pGSN levels on Day 1 within 30 minutes predose, and at 15 minutes and 1, 2, 4, 8, and 12 hours 
after Dose #1 and on Days 4 and 5 within 30 minutes predose, and at 15 minutes postdose, and 1, 
2, 4, 8, 12, and 24 hours after Dose #5. A window of ±15 minutes will be allowed around the 
scheduled times except for the samples collected at 15 minutes postdose which have a window of 
±5 minutes. A single sample will be collected anytime on Days 7 and 28. 
Plasma will be obtained after centrifugation and promptly frozen at -20°C for assay in the central 
lab for analysis of pGSN concentrations. The concentration-time data will be used for the 
determination of PK parameters: maximum concentration (Cmax), time to maximum 
concentration (Tmax), terminal half-life (T1/2), area under the curve from time zero to 8 hours 
(AUC0-8), area under the curve from time zero to 12 hours (AUC0-12), and additionally after 
Dose #5, area under the curve from time zero to 24 hours (AUC0-24) and time zero to infinity 
(AUCinf). 


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9. 
ADVERSE EVENT MANAGEMENT 
9.1. 
Definition of Adverse Events 
9.1.1. 
Adverse Event (AE) 
An AE is the development of an undesirable medical condition or the worsening of a pre-existing 
medical condition following or during exposure to a pharmaceutical product, whether or not 
considered causally related to the product.  
9.1.2. 
Serious Adverse Event (SAE) 
A serious adverse event (SAE) is an AE occurring during any study phase (i.e., baseline, 
treatment, or follow-up), and at any dose of the investigational product, comparator, or placebo, 
that fulfills one or more of the following: 
• Results in death 
• It is immediately life-threatening 
• It requires in-patient hospitalization or prolongation of existing hospitalization 
• It results in persistent or significant disability or incapacity 
• Results in a congenital abnormality or birth defect 
• It is an important medical event that may jeopardize the subject or may require medical 
intervention to prevent one of the outcomes listed above. 
All SAEs that occur after a subject has signed the consent form, including before or during 
treatment and within 28 days following the cessation of treatment, whether or not judged to be 
related to the study, must be recorded on forms provided by the Sponsor. 
9.2. 
Clarifications to Serious Adverse Event Reporting 
Death is an outcome of an SAE and not an SAE in itself. When death is an outcome, report the 
event(s) resulting in death as the SAE term (e.g., “pulmonary embolism”). If the cause of death is 
unknown, report “Death, unknown cause” as the SAE term. 
9.3. 
Assessment of Causality 
All AEs occurring during this healthy-volunteer study will be presumed to be related to study 
drug unless occurring before the study therapy is initiated pending review by the SRC.  AEs in 
the placebo group, although possibly related to a study procedure, cannot be related to rhu-pGSN 
unless the subject was mistakenly given the wrong treatment. 
9.4. 
Assessment of Severity 
The severity rating of an AE refers to its intensity. The severity of each AE will be graded 
according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled 
in Preventive Vaccine Clinical Trials (https://www.fda.gov/regulatory-information/search-fda-


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guidancedocuments/toxicity-grading-scale-healthy-adult-and-adolescent-volunteers-
enrolledpreventive-vaccine-clinical).  
It is important to distinguish between serious and severe AEs. Severity is a measure of intensity 
whereas seriousness is defined by the criteria under Section 9.1.2. An AE of severe intensity may 
not be considered serious. 
9.5. 
Pregnancy or Drug Exposure during Pregnancy 
If a subject becomes pregnant during the study, administration of study drug is to be 
discontinued immediately. 
Pregnancies must be reported within 24 hours of the Investigator’s knowledge using the 
Sponsor’s pregnancy form.  
Pregnancy in itself is not regarded as an AE or SAE unless there is a suspicion that an 
investigational product may have interfered with the effectiveness of a contraceptive medication. 
The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth or 
congenital abnormality) must be followed up and documented even if the subject was 
discontinued from the study. 
All reports of congenital abnormalities/birth defects are SAEs. Spontaneous miscarriages should 
also be reported and handled as SAEs. Elective abortions without complications should not be 
handled as AEs. 
9.6. 
Laboratory Abnormalities 
The severity of each laboratory AE will be  graded according to the Toxicity Grading Scale for 
Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 
(https://www.fda.gov/regulatory-information/search-fda-guidancedocuments/toxicity-grading-
scale-healthy-adult-and-adolescent-volunteers-enrolledpreventive-vaccine-clinical). 
To the extent possible, all laboratory abnormalities observed during the course of the study will 
be included under a reported AE term describing a clinical syndrome (e.g., elevated blood urea 
nitrogen and creatinine in the setting of an AE of “renal failure”). In these cases (e.g., an AE of 
renal failure), the laboratory abnormality itself (e.g., elevated creatinine) does not need to be 
recorded as an AE.  
If a laboratory abnormality cannot be reported as a clinical syndrome, AND if the laboratory 
abnormality results in a therapeutic intervention (i.e., concomitant medication or therapy), or is 
judged by the Investigator to be of other clinical relevance, then the laboratory abnormality 
should be reported as an AE.  
Subjects experiencing AEs or clinically significant laboratory abnormalities will be assessed and 
appropriate evaluations performed until all parameters have returned to baseline levels or are 
consistent with the subject’s then-current physical condition.  
9.7. 
Reporting Adverse Events 
All AEs, serious and nonserious, will be fully documented on the appropriate eCRF. For each 
AE, the Investigator must provide its duration (start and end dates or ongoing), intensity, 


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assessment of causality and whether specific action or therapy was required. All AEs occurring 
during this healthy-volunteer study will be presumed to be related to study drug unless occurring 
before the study therapy is initiated pending review by the SRC. 
All AEs that occur from the signing of the informed consent form (ICF) until the first dose of 
study drug should be recorded on the AE eCRF page only if the event was related to a study 
procedure. All other AEs/findings prior to the first dose of study drug should be recorded as 
medical history on the applicable eCRF page. All AEs occurring from the first dose of study 
drug until 28 days after the last dose of study drug must be recorded on the AE eCRF. 
All SAEs and Grade 4 AEs must be reported to the Sponsor within 24 hours of the Investigator’s 
knowledge. All AEs occurring during this healthy-volunteer study will be presumed to be related 
to study drug unless occurring before the study therapy is initiated pending review by the SRC. 
This reporting should be done by faxing/emailing the completed SAE Report Form to the 
number provided on the SAE Report Form. After the EOS Visit, only new treatment-related 
SAEs need to be captured on the AE eCRF and reported to the Sponsor.  
Investigators must follow subjects with AEs/SAEs until the event has resolved, the condition has 
stabilized, withdrawal of consent, the subject is lost to follow up or death OR until the EOS 
Visit, whichever occurs first. New and ongoing treatment-related SAEs should be followed 
beyond the EOS Visit. If the subject dies, this should be captured as the outcome of the AE 
unless no link between the AE and the subject death can be established, in which case the AE 
will be marked as ongoing and the death will be reported as a separate event. 
If a subject is lost to follow up, this should be captured accordingly within the AE eCRF and on 
the follow up SAE report.  
The Sponsor or designee is responsible for notifying the relevant regulatory authorities of 
applicable suspected unexpected serious adverse reactions (SUSARs) as individual notifications 
or through periodic line listings. It is the Principal Investigator’s responsibility to notify the 
Institutional Review Board (IRB) or IEC of all SAEs that occur at his or her site. Investigators 
will also be notified of all unexpected, serious, and drug-related events (7/15 Day Safety 
Reports) that occur during the clinical trial. Each site is responsible for notifying its IRB or IEC 
of these additional SAEs. 


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10. 
STATISTICS 
10.1. 
General Overview 
10.1.1. 
Method of Assigning Subjects to Treatment Groups 
For each dosing group, 8 subjects will be randomized in a 3:1 ratio to receive an equal volume of 
rhu-pGSN or saline placebo during the treatment period. See Section 7.11 for details regarding 
randomization. 
10.1.2. 
Data Collection and Analysis 
Baseline characteristics, safety, PK, and development of ADAs will be summarized via summary 
statistics separately for each rhu-pGSN dose level; data for all placebo subjects will be pooled. 
Additional details will be provided in a separate Statistical Analysis Plan (SAP). 
10.2. 
Sample Size and Power Calculations 
Prior studies of rhu-pGSN evaluated 3 doses of rhu-pGSN in subjects hospitalized with CAP or 
COVID-19. To expand our understanding of possible rhu-pGSN toxicities in the absence of 
underlying disease, 24 healthy subjects will be administered 5 doses of rhu-pGSN at 6, 12, 18, 
and 24 mg/kg of body weight (6 subjects per dose group) and 8 healthy subjects (2 subjects per 
dose group) will be given the same volume on a weight basis of a visually indistinguishable 
0.9% saline placebo to provide additional data to inform the safety and tolerability of rhu-pGSN.  
Table 5 presents the minimum sample size such that there is a 90% probability of observing at 
least 1 AE of a certain type if the TRUE underlying AE incidence is as specified. 
Table 5: 
Minimum Sample Size Calculations 
Sample Size 
TRUE Underlying AE Rate 
6 (each rhu-pGSN dose level) 
32% 
8 (pooled placebo) 
25% 
12 
18% 
18  
13% 
24 (pooled rhu-pGSN doses) 
10% 
With each sample size presented in Table 5, if zero AEs of a certain type (e.g., SAEs) are 
observed, one could be "90% confident" that the TRUE underlying incidence for that AE is at 
most the percentage indicated in Table 5. Thus with 24 healthy subjects, if no SAEs are 
observed, the probability is 90% that the true underlying incidence of SAEs in healthy subjects 
administered 5 doses of rhu-pGSN at 6, 12, 18, or 24 mg/kg of body weight is at most 10%. 
10.3. 
Analysis Populations  
No data will be excluded from the summary statistics and analyses, and missing data will not be 
imputed. All subjects given at least part of 1 dose of study drug will be included in the intention-
to- treat analysis (full analysis set). As a sensitivity analysis, a per-protocol analysis set 
excluding subjects who missed doses and/or randomly discontinued the study before the primary 
Day 7 Visit will be analyzed. The expectation is that all analysis sets will be almost identical. 


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10.4. 
Criteria for Evaluation and Statistical Methods 
10.4.1. 
Safety 
Descriptive summaries of the incidence of all AEs, drug-related AEs, SAEs, drug-related SAEs, 
AEs leading to discontinuation, and deaths will be provided. All AEs and drug-related AEs will 
be summarized by counts and proportions of subjects having an AE, each AE type, and an AE of 
each System Organ Class. Serious AEs will be summarized similarly. AEs leading to 
discontinuation of treatment or the study will be summarized. All reasons for any early 
discontinuations will be summarized. 
Laboratory data will be summarized in relation to normal range values via counts and 
percentages of subjects below, within, and above the respective normal range, and by summary 
statistics (N, mean, median, standard deviation, minimum, maximum, 90% confidence intervals, 
etc.) for baseline, each observed time point, and change from baseline at each observed time 
point for continuous lab endpoints. 
10.4.2. 
Baseline Characteristics  
Demographics and medical history characteristics will be summarized via counts and 
percentages of subjects for categorical variables, and by N, mean and standard deviation or 
median and interquartile range, as appropriate for the distribution of continuous variables. 
10.4.3. 
Pharmacokinetics and Immunogenicity 
Cmax, Tmax, T1/2, AUC0-8, AUC0-12, and additionally after Dose #5, AUC0-24 and AUCinf will be 
calculated from the pGSN levels measured for Doses #1 and #5. Since the assay measures 
endogenous pGSN levels as well as exogenous recombinant pGSN, PK parameters will be 
calculated for values above baseline by subtracting predose pGSN level from each observed 
concentration. Tables and graphs will be provided. 
Antibodies against rhu-pGSN will be assayed from frozen specimens to determine whether the 
investigational product induces an antibody response in recipients. The frequency of anti-pGSN 
antibodies with 95% confidence intervals will be provided for Day 1 (predose) and Day 28. If 
any subjects had antibodies at Day 1, the presence or absence of antibodies at Days 1 and 28 will 
be summarized in a 2 × 2 table (Day 1 vs. Day 28). 


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11. 
DATA RECORDING, RETENTION AND MONITORING 
11.1. 
Case Report Forms 
Data will be collected using an electronic data capture (EDC) system at the clinical site. The 
Investigator or designee will record data specified in the protocol using eCRFs. Changes or 
corrections to eCRFs will be made by the Investigator or an authorized member of the study staff 
according to the policies and procedures at the site and the eCRF completion guidelines. 
It is the responsibility of the Investigator to ensure eCRFs are complete and accurate. Following 
review and approval, the Investigator or designee will electronically sign and date the pages. 
This signature certifies that the Investigator has thoroughly reviewed and confirmed all data on 
the eCRF. Regardless of whether this responsibility has been delegated, the Investigator is 
personally responsible for the accuracy and completeness of all data included in the eCRF. 
The Sponsor or designee will provide a portable document format (PDF) file of the eCRFs to the 
site for archiving after all data have been monitored and reconciled. 
11.2. 
Records Retention 
Per Good Clinical Practice (GCP) guidelines regarding records retention, study documents are to 
be retained at the site until at least 2 years after the last approval of a marketing application in an 
International Council for Harmonization of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) region or at least 2 years have elapsed since the formal discontinuation of 
clinical development of study drug. The Sponsor will notify the site of the date when study 
documentation may be destroyed. 
11.3. 
Data Monitoring 
This study will be closely monitored by representatives of the Sponsor throughout its duration. 
Monitoring will include personal visits with the Investigator and study staff as well as 
appropriate communications by telephone, fax, mail, email or use of the EDC system, if 
applicable. It is the responsibility of the monitor to inspect eCRFs at regular intervals throughout 
the study to verify the completeness, accuracy and consistency of the data and to confirm 
adherence to the study protocol and to GCP guidelines. The Investigator agrees to cooperate with 
the monitor to ensure that any problems detected during the course of this study are resolved 
promptly. The Investigator and site will permit study-related monitoring, audits, IEC review and 
regulatory inspection, including direct access to source documents. 
It is understood that study monitors and any other personnel authorized by the Sponsor and/or 
Sponsor representatives may contact and visit the Investigator and will be permitted to inspect all 
study records (including eCRFs and other pertinent data) on request, provided that subject 
confidentiality is maintained and that the inspection is conducted in accordance with local 
regulations. 
Every effort will be made to maintain the anonymity and confidentiality of subjects during this 
study. However, because of the experimental nature of this treatment, the Investigator agrees to 
allow representatives of the Sponsor as well as authorized representatives of regulatory 
authorities to inspect the facilities used in the conduct of this study and to inspect, for purposes 
of verification, the hospital or clinic records of all subjects enrolled in the study. 


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11.4. 
Quality Control and Quality Assurance 
The study site may be audited by a quality assurance representative of the Sponsor or its 
designee for the purpose of monitoring any aspect of the study. The Investigator agrees to allow 
the monitor and/or auditor to inspect the drug storage area, study drug stocks, drug accountability 
records, patient charts and study source documents, and other records relative to study conduct.   
The Investigator should contact the Sponsor or designee immediately if contacted by a regulatory 
agency about an inspection.  


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12. 
REGULATORY, ETHICAL AND LEGAL OBLIGATIONS 
12.1. 
Good Clinical Practice 
The study will be performed in accordance with the protocol, guidelines for GCP established by 
the ICH, and applicable local regulatory requirements and laws. 
12.2. 
Independent Ethics Committee Approval 
The Investigator must inform and obtain approval from the IEC for the conduct of the study at 
named sites, the protocol, informed consent documents and any other written information that 
will be provided to the subjects and any advertisements that will be used. Written approval must 
be obtained prior to recruitment of subjects into the study and shipment of study drug. 
The Investigator is responsible for informing the IEC of any amendment to the protocol in 
accordance with local requirements. Amendments may be implemented only after a copy of the 
approval letter from the IEC has been transmitted to the Sponsor. Amendments that are intended 
to eliminate an apparent immediate hazard to subjects may be implemented prior to receiving 
Sponsor or IEC approval. However, in this case, approval must be obtained as soon as possible 
after implementation. 
Per GCP guidelines, the Investigator will be responsible for ensuring that an annual update is 
provided to the IEC to facilitate continuing review of the study and that the IEC is informed 
about the end of the study. Copies of the update, subsequent approvals and final letter must be 
sent to the Sponsor. 
12.3. 
Regulatory Authority Approval 
The study will be performed in accordance with regional regulatory requirements and will also 
meet all of the requirements of ICH GCP guidance. Amendments to the protocol will be 
submitted to the appropriate regulatory agency/agencies prior to implementation in accordance 
with applicable regulations. 
12.4. 
Other Required Approvals 
In addition to IEC and regulatory authority approval, all other required approvals (e.g. approval 
from the local research and development board or scientific committee) will be obtained prior to 
recruitment of subjects into the study and shipment of study drug. 
12.5. 
Informed Consent 
It is the responsibility of the Investigator (or designee) to obtain written informed consent from 
each subject after adequate explanation of the aims, methods and potential hazards of the study 
and before any study procedures are initiated. The subject should be given the opportunity to ask 
questions and allowed time to consider the information provided. Each subject should be given a 
copy of the informed consent document and associated materials. The original copy of the signed 
and dated informed consent document must be retained at the site and is subject to inspection by 
representatives of the Sponsor or regulatory authorities; the subject should be given a copy of the 
signed ICF. 


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Substantial changes to the study protocol may necessitate modifications to the informed consent 
document. If an amended informed consent document is issued during a subject’s participation in 
the study, the subject is required to provide written informed consent using the updated consent 
form prior to continuing with study-related activities. 
Subjects unable or unwilling to provide written informed consent will not be enrolled in the 
study. 
12.6. 
Subject Confidentiality 
The Investigator must ensure that subjects’ privacy is maintained. On the eCRF or other 
documents submitted to the Sponsor, subjects will be identified by a subject number or a subject 
number and initials only. Documents that are not submitted to the Sponsor (e.g., signed informed 
consent documents) should be kept in a strictly confidential file by the Principal Investigator. 
The Investigator shall permit authorized representatives of the Sponsor, regulatory authorities 
and IECs to review the portion of the subject’s medical record that is directly related to the study. 
As part of the required content of informed consent documents, the subject must be informed that 
his/her records will be reviewed in this manner. 
12.7. 
Disclosure of Information 
Information concerning the study, patent applications, processes, scientific data or other pertinent 
information is confidential and remains the property of the Sponsor. The Principal Investigator 
may use this information for the purposes of the study only. 
It is understood by the Principal Investigator that the Sponsor will use information obtained in 
this clinical study in connection with the clinical development program, and therefore may 
disclose it as required to other clinical Investigators and to regulatory authorities. In order to 
allow the use of the information derived from this clinical study, the Principal Investigator 
understands that he/she has an obligation to provide complete test results and all data obtained 
during this study to the Sponsor. 
Verbal or written discussion of results prior to study completion and full reporting should only 
be undertaken with written consent from the Sponsor. 


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13. 
LIST OF REFERENCES 
DiNubile MJ, Parra S, Castro-Salomo A, and Levinson, SL. Adjunctive recombinant human 
plasma gelsolin for severe coronavirus disease 2019 pneumonia. Open Forum Infect Dis 2022; 
9(8):ofac357. doi: 10.1093/fid/ofac357. eCollection 2022 Aug. 
Tannous A, Levinson SL, Bolognese J, et al. Safety and pharmacokinetics of recombinant human 
plasma gelsolin in patients hospitalized for non-severe community-acquired pneumonia. 
Antimicrob Agents Chemother 2020;64 (10). https://doi.org/10.1128/AAC.00579-20.