A Phase 1, Open-Label, Randomized Study to Evaluate Safety and Pharmacokinetics of Anti-SARS-CoV-2 Immunoglobulin (Human) Investigational Product (COVID-HIG) Administered Through Intramuscular, Subcutaneous or Intravenous Routes as a Single Dose Regimen to SARS-CoV-2 Uninfected Adults
Phase: PHASE1
Conditions: SARS-CoV-2 Infection
Sponsor: Emergent BioSolutions

Anti-SARS-CoV-2 Immunoglobulin Intravenous (Human) (NP-028), abbreviated as COVID-HIG 
EBS-CVH-006, Version 3.0, 18 Feb 2022 
 
 
Emergent BioSolutions 
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CLINICAL STUDY PROTOCOL 
A Phase 1, Open-Label, Randomized Study to Evaluate Safety and 
Pharmacokinetics of Anti-SARS-CoV-2 Immunoglobulin (Human) 
Investigational Product (COVID-HIG) Administered through 
Intramuscular, Subcutaneous or Intravenous Routes as a Single Dose 
Regimen to SARS-CoV-2 Uninfected Adults 
EBS-CVH-006 
Version 3.0  
18 Feb 2022 
Funding Source: The United States Department of Defense 
Study Sponsor: Emergent BioSolutions Canada Inc.  
 
 
CONFIDENTIAL 
This document is a confidential communication of the Sponsor. Acceptance of this document 
constitutes an agreement by the recipient that no unpublished information contained within 
will be published or disclosed without prior written approval, except that this document may 
be disclosed to the appropriate Ethics Committee and Regulatory Authority under the 
condition that they keep it confidential. 
 
Number: CLIN040217  Version: 3.0                    Effective Date: 18 Feb 2022

Anti-SARS-CoV-2 Immunoglobulin Intravenous (Human) (NP-028), abbreviated as COVID-HIG 
EBS-CVH-006, Version 3.0, 18 Feb 2022 
 
 
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DOCUMENT HISTORY 
Version 
Date 
Description of Change 
Brief Rationale 
1.0 
12 Oct 2021 
n/a 
Initial version of the protocol 
2.0 
23 Nov 2021 
Substitution for a comparable 
antibody assay for screening, 
simplified randomization 
scheme, and administrative 
changes 
Modified due to logistical 
challenges and to improve clarity.  
3.0 
18 Feb 2022 
Decreased study follow-up to 
56 days post-dosing (Day 57) 
and stopped enrollment at 23 
of 36 subjects enrolled. 
Primary endpoints were 
updated to remove pseudoviral 
neutralization assay testing 
and some administrative 
changes were made. 
Study follow-up period was 
decreased, and enrollment was 
stopped due to the impact of the 
COVID-19 pandemic and 
logistical difficulties of enrolling 
and retaining SARS-CoV-2 
negative participants. The 
pseudoviral neutralization assay 
was eliminated due to assay 
limitations related to low 
sensitivity. Other minor changes 
were made to improve clarity. 
 
  Version: 3.0                    Effective Date: 18 Feb 2022

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EBS-CVH-006, Version 3.0, 18 Feb 2022 
 
 
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SPONSOR SIGNATORY 
 
Signatory: 
See electronic signature page 
  
 
 
 
 
 
 
Date (dd/mmm/yyyy) 
 
KEY STUDY CONTACT INFORMATION 
 
Sponsor’s Medical Monitor: 
 
 
 
  
 
Immediately Reportable Adverse Events: 
Emergent Global Pharmacovigilance 
Email: productsafety@ebsi.com  
 
 
 
 
For all other contact information please refer to study contact list. 
  Version: 3.0                    Effective Date: 18 Feb 2022

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INVESTIGATOR SIGNATORY 
Compliance Statement: This study is to be conducted in accordance with the ethical 
principles that originate from the Declaration of Helsinki and that are consistent with 
International Council for Harmonization of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) Good Clinical Practice (GCP) guidelines and regulatory requirements, as 
applicable. 
 
EBS_CVH-006, Version 3.0: 
A Phase 1, Open-Label, Randomized Study to Evaluate 
Safety and Pharmacokinetics of Anti-SARS-CoV-2 
Immunoglobulin (Human) Investigational Product 
(COVID-HIG) Administered through Intramuscular, 
Subcutaneous or Intravenous Routes as a Single Dose 
Regimen to SARS-CoV-2 Uninfected Adults 
 
 
QPS Holdings, LLC (Phase I units) 
 
 Newark, DE 19711, USA  
 
My signature below verifies that I have read and agree to this protocol. I am aware of my 
responsibilities as a Principal Investigator (PI) under the current ICH GCP Guidelines, the 
Declaration of Helsinki, and applicable laws and regulations of the country of the 
investigational site for which I am responsible. I agree to conduct the study according to 
these regulations. 
I have read this protocol in its entirety and agree to conduct this study accordingly. Any 
changes in procedure will only be made if necessary, to protect the safety, rights and welfare 
of study subjects. 
I agree to conduct in person and/or to supervise staff assigned to specific study 
responsibilities. I will ensure that all staff who assist me in the conduct of the study have 
access to the protocol and all pertinent information. I will ensure that all assigned staff are 
trained and qualified and are fully informed of their responsibilities regarding the conduct of 
the study. 
I agree to abide by the terms of the confidentiality disclosure agreement and/or contract with 
the Sponsor and/or its representatives. 
Miami Site Principal 
Investigator: 
 
 
 
 
Principal Investigator Name (print) 
Title (print) 
 
 
  
 
 
 
Principal Investigator Signature 
 Date dd/mmm/yyyy) 
  Version: 3.0                    Effective Date: 18 Feb 2022

Anti-SARS-CoV-2 Immunoglobulin Intravenous (Human) (NP-028), abbreviated as COVID-HIG 
EBS-CVH-006, Version 3.0, 18 Feb 2022 
 
 
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INVESTIGATOR SIGNATORY 
Compliance Statement: This study is to be conducted in accordance with the ethical 
principles that originate from the Declaration of Helsinki and that are consistent with 
International Council for Harmonization of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) Good Clinical Practice (GCP) guidelines and regulatory requirements, as 
applicable. 
 
EBS_CVH-006, Version 3.0: 
A Phase 1, Open-Label, Randomized Study to Evaluate 
Safety and Pharmacokinetics of Anti-SARS-CoV-2 
Immunoglobulin (Human) Investigational Product 
(COVID-HIG) Administered through Intramuscular, 
Subcutaneous or Intravenous Routes as a Single Dose 
Regimen to SARS-CoV-2 Uninfected Adults 
 
 
QPS Holdings, LLC (Phase I units) 
 
 Newark, DE 19711, USA  
 
My signature below verifies that I have read and agree to this protocol. I am aware of my 
responsibilities as a Principal Investigator (PI) under the current ICH GCP Guidelines, the 
Declaration of Helsinki, and applicable laws and regulations of the country of the 
investigational site for which I am responsible. I agree to conduct the study according to 
these regulations. 
I have read this protocol in its entirety and agree to conduct this study accordingly. Any 
changes in procedure will only be made if necessary, to protect the safety, rights and welfare 
of study subjects. 
I agree to conduct in person and/or to supervise staff assigned to specific study 
responsibilities. I will ensure that all staff who assist me in the conduct of the study have 
access to the protocol and all pertinent information. I will ensure that all assigned staff are 
trained and qualified and are fully informed of their responsibilities regarding the conduct of 
the study. 
I agree to abide by the terms of the confidentiality disclosure agreement and/or contract with 
the Sponsor and/or its representatives. 
Springfield Site 
Principal Investigator: 
 
 
 
 
Principal Investigator Name (print) 
Title (print) 
 
 
  
 
 
 
Principal Investigator Signature 
 Date dd/mmm/yyyy) 
 
 
  Version: 3.0                    Effective Date: 18 Feb 2022

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EBS-CVH-006, Version 3.0, 18 Feb 2022 
 
 
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PROTOCOL SYNOPSIS 
 
Name of Sponsor/Company:   
Emergent BioSolutions Canada Inc. (Emergent) 
  
Winnipeg, MB, R3T 5Y3, CANADA 
Name of Investigational Product:  COVID-HIG 
Name of Active Ingredient(s):  Anti-SARS-CoV-2 Immunoglobulin Injection (Human) 
[COVID HIG] is a purified liquid immunoglobulin G (IgG) preparation 
Protocol No.: EBS-CVH-006 
Title of Study: A Phase 1, Open-Label, Randomized Study to Evaluate Safety and 
Pharmacokinetics of Anti-SARS-CoV-2 Immunoglobulin (Human) Investigational Product 
(COVID-HIG) Administered through Intramuscular, Subcutaneous, or Intravenous Routes 
as a Single Dose Regimen to SARS-CoV-2 Uninfected Adults  
Study Center(s): two sites in the United States (US)  
Study Duration for Each Subject: 56 days 
Estimated Study Duration: 3.5 months 
Estimated Enrollment Period: 1.5 months 
Anticipated Start Date: Q4 (December) 2021 
Estimated End Date: Q1 2022 
Phase of Development: Phase 1 
Primary Objectives:  
• To evaluate safety of COVID-HIG administered intramuscularly (IM) or 
subcutaneously (SC) as a single dose  
• To evaluate pharmacokinetics (PK) of COVID-HIG administered IM or SC as a 
single dose  
Secondary Objectives: 
• To compare PK of COVID-HIG IM to COVID-HIG IV  
• To compare PK of COVID-HIG SC to COVID-HIG IV  
• To compare PK of COVID-HIG SC to COVID-HIG IM 
Exploratory Objectives 
• To evaluate the effects of COVID-HIG in participants that become Severe Acute 
Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) positive 
 
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Methodology 
Study Design:  
This will be a Phase 1, two-center, open-label, randomized study to evaluate one dose level 
of COVID-HIG administered IM or SC for safety and PK in healthy adults compared to 
COVID-HIG administered intravenously (IV). Up to 36 adult participants will be targeted 
to be enrolled in the study. The study has been truncated to 23 randomized participants due 
to the impact of high circulating SARS-CoV-2 omicron cases on enrollment and 
participant retention. The sample size with 7-8 participants per study arm will allow for 
assessment of the primary safety and PK objectives. 
Table 1 
Study Design 
Group 
Study Arm 
No. of Participants 
Dosing Schedule – Day 1 
Intramuscular 
1 
Up to 12 
≈250,000 AU COVID-HIG1 
Subcutaneous 
2 
Up to 12 
≈250,000 AU COVID-HIG1 
Intravenous 
3 
Up to 12 
≈250,000 AU COVID-HIG1  
1Exact dose volumes (mL) was determined based on potency of COVID-HIG clinical lot as defined in Alliance Units 
(AU) using the wild-type neutralization assay (Clinical lot potency: 29,282 AU/mL, 8.5 mL volume; target protein 
concentration: 100 mg/mL). 
 
Up to thirty-six participants will be enrolled and assigned equally to one of three study 
arms to receive a single IM, SC, or IV dose of COVID-HIG, respectively (see the table 
above). Randomization will be separate for Cohort 1 (12 subjects) and Cohort 2 (up to 24 
subjects), but both randomization ratios will be 1:1:1 for each administration route. 
Subjects will be stratified based on their SARS-CoV-2 detectable antibody status (>LLOQ, 
but ≤80 AU/mL on the Diasorin LIAISON SARS-CoV-2 S1/S2 IgG assay) and 
undetectable antibody (≤LLOQ) at screening. 
Enrollment into the study will be staggered, wherein no more than three participants will 
be randomized and dosed on the first day with at least one hour between dosing of each 
participant. On the second day, up to two more subjects will be randomized and dosed. 
The remaining participants will be randomized and dosed, with no more than 5 participants 
dosed per day. Safety data will be reviewed by a Safety Monitoring Committee (SMC) 
(consisting of at least three independent external members) after all 12 participants in 
Cohort 1 have completed at least 72 hours of safety follow-up. An overall decision by the 
SMC will be made whether to proceed with full randomization (1:1:1) and dosing of the 
remaining study participants (Cohort 2, up to n=24).  
Participants will be admitted to the inpatient unit one day prior to dosing (Day -1), and 
following dosing on Day 1, each participant will stay overnight in the inpatient unit for 
close observation and PK sample collection. Each dosed participant will be discharged 
from the inpatient unit once all assessments at the 24 hours post-dosing timepoint (i.e., 
Day 2) are completed. Participants will be followed for safety and PK up to 56 days post-
dosing (Day 57; see Table 2 for Schedule of Events). Follow-up visits to collect required 
samples and/or safety assessments can occur in-clinic or at-home as indicated in Table 2. 
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Study enrollment and administration of study treatments may be paused by the PI or 
medical monitor for safety review by the SMC if any of the following occur after study 
product administration and during the enrollment period: 
• One or more serious adverse event(s) [SAE(s)].  
• Three or more of the same Grade 3 adverse events (AEs)  
• Three or more Grade 2 hypersensitivity AEs  
Adverse event severity will be graded according to the DAIDS Severity Grading Scale 
(Appendix I). 
If any participants become positive for SARS-CoV-2 during the study follow-up period, 
they will be assessed using an Ordinal Outcome Scale (Appendix II) until symptom 
resolution and will be followed until they complete their last scheduled follow-up visit (via 
telemedicine). Participants who test positive for SARS-CoV-2 will be excluded from PK 
analyses. As such, all subsequent visits should be done via telemedicine following SARS-
CoV-2 positive status (except the Day 57 or the withdrawal visit), unless an in-person visit 
is deemed clinically necessary by the PI. Any in-person visits should be scheduled in a 
manner that reduces the risk of SARS-CoV-2 transmission, according to local rules and 
regulations. As the Day 57 or withdrawal visit necessitates in-person safety assessments, 
this visit should proceed in-person, if possible. If a participant tests positive for SARS-
CoV-2 immediately prior to or at the in-person Day 57 visit, reasonable efforts will be 
made to collect as many of the required samples from the Day 57 visit in a manner that 
reduces the risk of SARS-CoV-2 transmission, according to local rules and regulations. 
Number of Subjects (Planned): Up to 36 participants (truncated at 23 participants 
randomized) 
Study Population: Healthy adult (18-59 years of age) non-pregnant females and males, 
without clinical symptoms of Coronavirus Disease 2019 (COVID-19) and without 
evidence of SARS-CoV-2 infection (negative RT-PCR result for SARS-CoV-2 RNA) at 
screening. 
Criteria for Study Participation 
Inclusion Criteria:  
1. 
Able and willing to provide written informed consent (voluntarily signed by the 
participant) prior to performing study procedures. 
2. 
Females and males 18-59 years of age.  
3. 
Have a body mass index (BMI) less than or equal to 35.0 kg/m2. 
4. 
Healthy, based on medical history (no chronic disease, no chronic therapy, no 
ongoing acute condition within four weeks prior to dosing), normal physical 
examination (no clinically significant findings in the opinion of the investigator), 
and screening laboratory assessments (no clinically significant findings in the 
opinion of the investigator).  
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5. 
No clinical symptoms suspicious for COVID-19 infection, as well as SARS-CoV-2 
IgM antibody negative and no laboratory evidence of current SARS-CoV-2 
infection (i.e., RT-PCR negative for SARS-CoV-2) at Screening. 
6. 
Females must not be pregnant, or trying to become pregnant as demonstrated by 
either of the following A or B:  
A. Not of childbearing potential: surgically sterile (at least six weeks post bilateral 
salpingectomy, bilateral oophorectomy, or hysterectomy); or post-menopausal 
(history of ≥12 consecutive months without menses prior to randomization in the 
absence of other pathologic or physiologic causes and confirmed by follicle 
stimulating hormone [FSH] level ≥40 mIU/mL); OR 
B. Women of childbearing potential (WOCBP) who are not planning to be pregnant 
during the study period and who meet all of criteria i–iii: 
i. 
Negative serum pregnancy test at the Screening Visit. 
ii. 
Negative urine pregnancy test on Day 1 (a positive test will result in 
discontinuation from intervention). 
iii. 
Using one of the following highly effective methods of contraception 
during the study:  
• Combined estrogen and progestogen, or progestogen-only hormonal 
contraception associated with inhibition of ovulation (e.g., implants, 
pills, patches) initiated ≥30 days prior to Study Day 1. 
• Intrauterine device (IUD) or hormone releasing intrauterine system 
(IUS) inserted ≥30 days prior to Study Day 1. 
7. 
Participant understands and agrees to comply with planned study procedures. 
Exclusion Criteria:  
1. 
Use of any investigational product within 30 days or SARS-CoV-2 monoclonal 
antibodies and COVID-19 convalescent plasma within 90 days prior to Screening 
or anticipated receipt during the study follow-up period, or participant plans to 
participate in another clinical study during the study period.   
2. 
Receipt of 1 or 2 doses COVID-19 vaccine within 60 days prior to screening or 
anticipated receipt during the study follow-up period. 
3. 
SARS-CoV-2 IgG antibody levels >80 AU/mL as determined by the Diasorin 
LIAISON SARS-CoV-2 S1/S2 IgG antibody assay. 
4. 
Screening clinical laboratory test result greater than the laboratory's upper limit of 
normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase 
(AST), random glucose, total and/or direct bilirubin, blood urea nitrogen (BUN), or 
creatinine. Other serum chemistry parameters that are not within the reference 
range will not be considered exclusionary unless deemed clinically significant by 
the principal investigator. 
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5. 
Positive laboratory evidence of current infection with human immunodeficiency 
virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV). Note: Positive 
anti-HCV antibody result along with a negative HCV PCR would NOT be 
exclusionary. 
6. 
History of allergy or hypersensitivity to blood or plasma products or to COVID-
HIG excipients (proline, PS80). 
7. 
History of allergy to latex or rubber. 
8. 
History of hemolytic anemia. 
9. 
History of IgA deficiency. 
10. Receipt of any blood product within the past 12 months. 
11. Plasma donation within 7 days or blood loss/donation (>450 mL) within 56 days of 
dosing. 
12. History of known congenital or acquired immunodeficiency or receipt of 
immunosuppressive therapy (e.g., prednisone or equivalent for more than two 
consecutive weeks within the past three months). 
13. History of thrombosis or hypercoagulable state with increased risk of thrombosis. 
14. Receipt of a live vaccine within 30 days prior to screening or anticipated receipt of 
a live vaccine during the study period. 
15. Currently pregnant, breastfeeding, or planning to become pregnant during the 
study. 
16. History of, or suspected substance abuse problem (including alcohol). 
17. Any planned elective surgery or procedure during the follow-up period that impacts 
study compliance. 
18. Other condition which may place participant at increased risk due to participation 
in the study or may impact study compliance as determined by the investigator. 
19. An opinion of the investigator (or designee) that it would not be in the best interest 
of the individual to participate in the study. 
 
Investigational Product (IP), Dosage and Mode of Administration: COVID-HIG is a 
purified liquid IgG preparation containing antibodies (including neutralizing antibodies) to 
SARS-CoV-2. COVID-HIG is intended for IM, SC or IV administration. COVID-HIG 
product contains a target of 100 mg/mL protein and is formulated with 250 mM proline 
and polysorbate 80 (0.03% w/w) target pH 5.8 COVID-HIG potency against SARS-CoV-2 
will be expressed in AU/mL as assessed using the NIAID neutralization assay.  
Reference Therapy, Dosage and Mode of Administration:  
There is no reference product for this study.  
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Study Endpoints/Outcome Measure(s)  
Primary:  
The following primary safety endpoints will be evaluated:  
• Adverse events within 72 hours post-dosing.  
• Adverse events leading to discontinuation or temporary suspension of study treatment 
administration 
• Adverse events and serious adverse events up to 56 days post-administration of a 
single dose. 
The following primary COVID-HIG PK endpoints (based on PK sample test results by an 
immunobinding IgG assay) will be evaluated: 
• AUC0-inf: AUC0-last plus the additional area extrapolated to infinity after dosing. 
• AUC0-last: area under the concentration-time curve from time 0 to the last quantifiable 
concentration after dosing. 
• Cmax: maximum observed concentration after dosing. 
• Tmax: time at which Cmax occurs after dosing. 
• C28d: observed or estimated concentration at 28 days after dosing. 
Secondary: 
The following additional COVID-HIG PK endpoints (based on PK sample test results by 
an immunobinding IgG assay) will be calculated, when data permit: 
• AUC0-inf ratios (bioavailability) will be compared between routes for comparable dose 
levels (COVID-HIG SC to IV; IM to IV; and SC to IM). 
• AUC0-14d after dosing. 
• AUC0-28d after dosing. 
• λz: terminal elimination rate constant after dosing. 
• T1/2: apparent terminal elimination half-life after dosing. 
• CL: systemic clearance after dosing. 
• VZ: volume of distribution after dosing. 
Exploratory: 
• COVID-19 disease severity among SARS-CoV-2 positive participants as assessed by 
an Ordinal Outcomes scale (Appendix II).  
Procedures and Assessments:  
For a tabular summary of visits/assessments refer to Table 2 Schedule of Events at the end 
of the synopsis. 
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Screening: in-clinic visit; within 14 days prior to randomization. 
• Informed consent. 
• Eligibility assessment. 
• Demography (age, sex, race/ethnicity, height, body weight, BMI).  
• Perform rapid SARS-CoV-2 IgM/IgG antibody test and SARS-CoV-2 antigen 
test prior to collecting other samples. Only proceed further with screening if 
negative for SARS-CoV-2 IgM and antigen. 
• Nasopharyngeal (NP) swab sample for SARS-CoV-2 RT-PCR test. 
• Medical history and ongoing medications. 
• Complete physical exam (to include assessment of general appearance, and the 
following body systems: head-neck, respiratory, cardiovascular, 
gastrointestinal, dermatological, lymphatic/hematological, musculoskeletal, 
neurological, metabolic/endocrine). 
• For WOCBP: assess contraception use (>30 days prior to dosing) and instruct 
on use of contraception from the time of Screening through end of study (up to 
Day 57). 
• Vital signs (resting ≥10 minutes) including body temperature, blood pressure 
(seated), pulse, SpO2 (pulse oximetry) and respiratory rate.  
• Safety laboratory assessments: 
• Chem 7 panel [sodium (Na+), potassium (K+), chloride (Cl-), bicarbonate 
(HCO3-), BUN, creatinine, glucose], total and direct bilirubin, ALT, AST, 
LDH. 
• Complete blood count (CBC) (red blood cells, white blood cells, 
hemoglobin, hematocrit) with differential (neutrophils, eosinophils, 
basophils, monocytes, lymphocytes).  
• Urinalysis. 
• Viral marker testing [Human immunodeficiency virus 1/2 (HIV 1/2) antibody, 
HBV surface antigen, HCV antibody]. 
• Urine drug screening (e.g., amphetamines, barbiturates, benzodiazepines, 
cannabinoids, cocaine opioids) 
• Serum sample for the Diasorin LIAISON SARS-CoV-2 S1/S2 IgG antibody 
test. 
• Serum pregnancy test for WOCBP and follicle stimulating hormone (FSH) 
testing for post-menopausal women. 
• Provide counselling to participants on precautions/measures to prevent 
contracting SARS-CoV-2 infection. 
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• Assess for any COVID-19 symptoms or SARS-CoV-2 exposure. 
• Monitor/assess AEs related to study procedures. 
Pre-Dosing – Day -1: in-clinic overnight stay 
• If required, update medical history and ongoing medications. 
• Inquire if the participant has had a suspected or confirmed exposure to SARS-
CoV-2 or developed COVID-19 symptoms in the period of Screening visit to 
Day 1. 
• Perform rapid SARS-CoV-2 IgM/IgG antibody test. 
• If WOCBP, perform urine pregnancy test (UPT). 
• If WOCBP, confirm use of contraceptives. 
• Alcohol breath test 
• Confirm eligibility. 
• Collect serum sample for SARS-CoV-2 antibody PK assessment. 
• Collect NP swab sample for SARS-CoV-2 RT-PCR test. 
• Targeted physical exam, if clinically indicated.  
• Assess for any COVID-19 symptoms or SARS-CoV-2 exposure. 
• Monitor/assess AEs related to study procedures. 
Dosing – Day 1: in-clinic overnight visit. 
• Collect pre-dose serum sample (within 2 hours prior to dosing) for SARS-CoV-
2 antibody PK assessment. 
• Vital signs (resting ≥10 minutes) [body temperature, blood pressure (seated), 
pulse, SpO2 (pulse oximetry) and respiratory rate]; within 2 hours prior to 
dosing. 
• Randomize. 
• Administer randomized study treatment.  
• Monitor/assess AEs before, during injection and post-administration in the 
clinic overnight.  
• Vital signs (resting ≥10 minutes) [body temperature, blood pressure (seated), 
pulse, SpO2 (pulse oximetry) and respiratory rate] at 30 minutes (±5 mins) and 
1 hour (±10 mins) post-administration. 
• Serum samples for post-dosing assessment of SARS-CoV-2 antibodies for PK 
at 1 hr ±10min, 2 hrs ±15min, 4 hrs ±15min, 8 hrs ±30min, and 12 hrs ±30min 
(from end of infusion/injection).  
• Targeted physical exam, if clinically indicated. 
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• Record any concomitant medications (if applicable). 
Post-Dosing Assessments (Days 2-57)*: 
Day 2 (1±0.5 days) – in-clinic discharge visit  
Day 3 (2±0.5 days), Day 4 (3±0.5 days), Day 6 (5±0.5 days), Day 8 (7±1 day), Day 15 
(14±2 days), Day 29 (28±2 days), Day 43 (42±3 days): – visit can be conducted in-
clinic or as home healthcare/telemedicine follow-up.  
If randomized to IV group (Arm 3), omit visits on Day 3 and Day 6.  
* Visits are indicated as calendar days, while the time post-dosing and the visit windows 
are indicated in the brackets. 
Perform the following in-clinic or via telemedicine follow-up: 
• Assessment of AEs and concomitant medications.   
• Targeted physical exam, if clinically indicated. Based on the investigator’s 
assessment of adverse events/concomitant medication during telemedicine 
follow-up, an unscheduled visit (in-clinic) can be arranged to conduct a 
targeted physical exam. The investigator can also refer the subject to their 
healthcare provider or urgent care if more immediate medical attention is 
required.  
• If WOCBP, confirm use of contraceptives.  
• Provide counseling to participants on precautions/measures to prevent 
contracting SARS-CoV-2 infection. 
• Only if participant becomes positive for SARS-CoV-2 at any time post-dosing 
during the study period: assess clinical status based on an Ordinal Outcome 
Scale (Appendix II). Perform assessments via telemedicine if possible.  
In-clinic staff or home healthcare attendant to perform the following: 
• Serum sample for SARS-CoV-2 antibody PK assessment. 
• Blood sample for safety laboratory assessments (chem 7 panel, total and direct 
bilirubin, ALT, AST, LDH, CBC) at Day 2 and Day 4 only. At other follow-
ups, collect sample only if clinically indicated (as per investigator’s discretion 
during in-clinic or home healthcare/telemedicine follow-up). 
• Sample for urinalysis at Day 2 and Day 4 only. At other follow-ups, collect 
sample only if clinically indicated (as per investigator’s discretion during in-
clinic or home healthcare/telemedicine follow-up).  
• Vital signs (resting ≥10 minutes) [body temperature, blood pressure (seated), 
pulse, SpO2 (pulse oximetry) and respiratory rate] at Day 2 and Day 4 only. At 
other follow-ups perform only if clinically indicated (as per investigator/sub-
investigator’s assessment of the participant in-clinic or during the home 
healthcare/telemedicine follow-up). 
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• NP swab sample for SARS-CoV-2 RT-PCR test on Day 8, Day 15 Day 29, and 
Day 43. At other follow-ups perform only if clinically indicated (as per 
investigator/sub-investigator’s assessment of the participant in-clinic or during 
the home healthcare/telemedicine follow-up). 
Day 57 (±3 days)*: visit can be conducted in-clinic or as home healthcare follow-up. 
* Visit window is based in relation to Day 1 visit. 
Perform the following in-clinic or via telemedicine follow-up:  
• Assessment of AEs and concomitant medications.   
• Targeted physical exam, if clinically indicated. 
• If WOCBP, confirm use of contraceptives.   
• Provide counseling to participants on precautions/measures to prevent 
contracting SARS-CoV-2 infection. 
• Only if participant becomes positive for SARS-CoV-2: assess clinical status 
based on an Ordinal Outcome Scale (Appendix II). Perform assessments via 
telemedicine if possible.  
In-clinic staff or home healthcare attendant to perform the following: 
• Serum sample for SARS-CoV-2 antibody PK assessment.  
• Safety laboratory assessments (e.g., ALT, AST, LDH, CBC, urinalysis), if 
clinically indicated. 
• Blood sample for viral marker testing (HIV 1/2 antibody, HBV surface antigen, 
HCV antibody). 
• Vital signs (resting ≥10 minutes) [body temperature, blood pressure (seated), 
pulse, SpO2 (pulse oximetry) and respiratory rate]. Note: perform only if 
clinically indicated (as per investigator’s discretion). 
• Nasopharyngeal swab sample for SARS-CoV-2 RT-PCR test. 
If any participants become positive for SARS-CoV-2 at any point during the study follow-
up period, all subsequent visits should be done via telemedicine (except for the Day 57 or 
the withdrawal visit), unless an in-person visit is deemed clinically necessary by the PI. As 
the Day 57 or withdrawal visit necessitates in-person safety assessments, this visit should 
proceed in-person, if possible. In-person visits should be performed after the infectious 
period has passed to reduce the risk of transmission and should follow local rules and 
regulations. If a participant tests positive for SARS-CoV-2 immediately prior to or at the 
in-person Day 57 visit, reasonable efforts will be made to collect as many of the required 
samples from the Day 57 visit in a manner that reduces the risk of SARS-CoV-2 
transmission, according to local rules and regulations. 
Withdrawal Visit (WV): visit can be conducted in-clinic or as home healthcare follow-
up. 
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Perform if withdrawal occurs at any time during the follow-up period, but outside of 
scheduled visits / visit windows. 
Perform the following in-clinic or via telemedicine follow-up: 
• Assessment of AEs and concomitant medications.   
• Targeted physical exam, if clinically indicated. 
• If WOCBP, confirm use of contraceptives. 
• Provide counseling to participants on precautions/measures to prevent 
contracting SARS-CoV-2 infection. 
• Only if participant becomes positive for SARS-CoV-2: assess clinical status 
based on an Ordinal Outcome Scale (Appendix II). Perform assessments via 
telemedicine if possible.  
In-clinic staff or home healthcare attendant to perform the following: 
• Serum sample for SARS-CoV-2 antibody PK assessment.  
• Safety laboratory assessments (e.g., ALT, AST, LDH, CBC, urinalysis), if 
clinically indicated. 
• Blood sample for viral marker testing (HIV 1/2 antibody, HBV surface antigen, 
HCV antibody). 
• Vital signs (resting ≥10 minutes) [body temperature, blood pressure (seated), 
pulse, SpO2 (pulse oximetry) and respiratory rate]. Note: perform only if 
clinically indicated (as per investigator’s discretion). 
• Nasopharyngeal swab sample for SARS-CoV-2 RT-PCR, if clinically indicated 
(as per investigator/sub-investigator’s assessment). 
Unscheduled Visit(s): in-clinic or telemedicine/home healthcare follow-up. 
Participants can be evaluated during an unscheduled visit if the investigator deems it 
necessary to further follow-up on participant’s safety. The following may be performed at 
an unscheduled visit at investigator’s discretion. 
Perform the following in-clinic, at-home, or via telemedicine follow-up. If telemedicine 
follow-up requires sample collection or in-person assessments, an in-clinic or at-home 
follow-up should be scheduled: 
• Assessment of AEs and concomitant medications.   
• Targeted physical exam, if clinically indicated. 
• Nasopharyngeal swab samples for SARS-CoV-2 RT-PCR test (as per 
investigator’s discretion assessing COVID-19 symptoms/exposure). 
• Safety laboratory assessments: (e.g., ALT, AST, LDH, CBC, urinalysis), if 
clinically indicated. 
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• Vital signs (resting ≥10 minutes) [body temperature, blood pressure (seated), 
pulse, SpO2 (pulse oximetry) and respiratory rate]. Note: perform only if 
clinically indicated (as per investigator’s discretion). 
• If WOCBP, confirm use of contraceptives.  
• If WOCBP and only if clinically indicated, perform serum pregnancy test. 
• Provide counseling to participants on precautions/measures to prevent 
contracting SARS-CoV-2 infection. 
• Only if participant becomes positive for SARS-CoV-2: assess clinical status 
based on an Ordinal Outcome Scale (Appendix II). Perform assessments via 
telemedicine if possible.  
Statistical Methods 
Sample Size Considerations: There was no formal sample size calculation for this Phase 
1 study. However, based on previous experience with hyperimmune globulin products 
manufactured by Emergent (see Section 1.3.1) in Phase 1 clinical studies, Emergent deems 
the number of participants planned to receive study treatments in the study  is sufficient to 
descriptively assess COVID-HIG safety and PK administered IM, SC, and IV. Even with 
the truncation to 23 randomized participants due to the COVID-19 pandemic case surge, 7-
8 participants per study arm should be sufficient to meet study objectives, similar to the 
previous PK study EBS-CVH-003 with 7-8 participants per arm. 
Analysis Populations:  
The following analysis populations will be evaluated in the study: 
• Safety Population: All randomized participants who receive any amount of 
COVID-HIG IM, COVID-HIG SC or COVID-HIG IV, analyzed according to 
the actual study treatment arm. 
• PK Population: All participants who are randomized and received COVID-HIG 
IM, COVID-HIG SC or COVID-HIG IV according to the protocol and with 
evaluable PK data (i.e., no major protocol deviations affecting PK sampling 
and results including COVID-19 infection, adequate number of PK sample test 
results), analyzed according to actual study treatment arm.  
• SARS-CoV-2 Positive Population: Any randomized participant (whether or not 
dosed with COVID-HIG) who tests positive for SARS-CoV-2 during the study 
period and for whom data are available, analyzed according to randomized 
study treatment arm. 
Considerations for Endpoints: 
In general, continuous endpoints will be summarized by descriptive statistics including 
number of participants, mean, standard deviation (SD), median, minimum, and maximum. 
Logarithmic transformation will be used when appropriate; coefficient of variation (CV), 
geometric mean, and geometric CV will also be summarized. Categorical endpoints will be 
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summarized by the total number of participants, frequencies, and percentages. 
Non-compartmental methods will be used for estimating PK parameters. 
Bioavailability will be compared between administration routes, if data permit. An analysis 
of variance (ANOVA) model will be used with AUC0-inf as the dependent variable and 
administration route as the fixed effect. The adjusted least square means will be used to 
estimate ratios of AUC0-inf IM / AUC0-inf IV * 100%, AUC0-inf SC / AUC0-inf IV * 100%, and 
AUC0-inf IM / AUC0-inf SC * 100% along with corresponding two-sided 90% confidence 
intervals (CIs) calculated based on the ANOVA. The width of the 90% CIs will be 
examined relative to the standard of [80%, 125%] for comparative bioavailability.  
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SCHEDULE OF EVENTS 
Table 2 
Schedule of Events  
 
In-clinic 
In-clinic overnight stay 
In-clinic or home healthcare/telemedicine visit 
 
Screening 
Day -1 
Day 
1 
Day 
2 
Day 
3* 
Day 
4 
Day 
6* 
Day 
8 
Day 
15 
Day 
29 
Day 
43 
Day 
57 
Withdrawal 
Visit (WV) 
Unsched-
uled 
Visit Window (days in relation to Day 1) 
≤14 days 
≤1 day 
 
1±0.5 
2±0.5 
3±0.5 
5±0.5 
7±1 
14±2 
28±2 
42±3 
56±3 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
X 
X2 
 
 
 
 
 
 
 
 
 
 
 
 
Demography (age, sex, race/ethnicity, 
height, body weight, BMI) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history & ongoing medications1 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Targeted physical exam 
 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
Randomization and dosing 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Vital signs4 
X 
 
X5 
X 
X13 
X 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
Safety laboratory tests6 
X 
 
 
X 
X13 
X 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
Urinalysis7 
X 
 
 
X 
X13 
X 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
X13 
Serum pregnancy test, if WOCBP 
X8 
 
 
 
 
 
 
 
 
 
 
 
 
X13 
Urine pregnancy test, if WOCBP 
 
X8 
 
 
 
 
 
 
 
 
 
 
 
 
FSH test, if postmenopausal female 
X8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine drug screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alcohol breath test 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Viral markers (HBV surface Ag, HCV Ab, 
HIV 1/2 Ab)9 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
NP sample for SARS-CoV-2 RT-PCR 
X 
X 
 
X13 
X13 
X13 
X13 
X 
X 
X 
X 
X 
X13 
X13 
Rapid SARS-CoV-2 IgM/IgG test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Rapid SARS-CoV-2 antigen test  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum sample for Diasorin LIAISON  
SARS-CoV-2 S1/S2 IgG assay 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum sample for SARS-CoV-2 Ab PK 
 
X 
X10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
AEs & concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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Confirm use of contraceptives (if 
appropriate) 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Counselling on precautions to prevent 
SARS-CoV-2 infection and assess COVID-
19 symptoms/exposure.11 
X 
X12 
 
X12 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
* Visits on Day 3 and Day 6 are not necessary for the IV arm (Arm 3) 
 
1 Medical history information will be collected from participants at the Screening Visit and confirmed (and updated, if required) at the Day -1 Visit and will include 
(but not be limited to) demographic information (date of birth, race, ethnicity, and sex of participant), current and past medical conditions, prior and concomitant 
medications.  
2 Review and confirm eligibility. 
3 A complete physical examination will be performed on participants during the Screening Visit. The examination should include, general appearance, eyes-ears-nose-
throat, head-neck, lungs-chest, heart, abdomen, musculoskeletal, lymph nodes, skin, extremities, and neurological assessment. A targeted physical exam may be 
performed on participants at additional time points if indicated by AE or SAE reporting.  
4 Vital signs collected from participants will include blood pressure, heart rate, SpO2 (pulse oximetry), respiratory rate, and temperature. Vital signs must be taken after 
≥10 minutes resting. Vital signs can be repeated twice if grade 3 or higher to verify the severity. Body weight, height for BMI calculations will be obtained at 
Screening Visit. 
5 Collect resting vital signs within 2 hours prior to dosing and at 30±5 mins and 1 hour±10 mins postdosing (from end of infusion/injection). 
6 Clinical chemistry assessments will include the Chem 7 panel [Na+, K+, Cl-, HCO3-, BUN, creatinine, glucose], total and direct bilirubin, ALT, AST, LDH, and 
CBC with differential. 
7 Urinalysis will include appearance and color, specific gravity, protein, glucose, pH, occult blood. Initial analysis will be by dipstick, with further testing and 
microscopic examination only if clinically indicated. 
8 Serum pregnancy tests will be performed at Screening for all females of childbearing potential. Urine pregnancy tests will be performed on Day -1 visit for all females 
of childbearing potential. Pregnancy tests are not required for female participants who are postmenopausal ≥12 months, or surgically sterilized. Follicle stimulating 
hormone levels will be evaluated for females who are postmenopausal for ≥12 months. 
9 Viral markers include: HBsAg, HCV antibody, HIV-1/2. HCV RNA will be performed in HCV antibody positive individuals only.  
10 Collect serum PK samples at pre-dose (within 2 hrs prior to dosing) and postdose (from end of infusion/injection) at 1 hr ±10min, 2 hrs ±15min, 4 hrs ±15min, and 8 
hrs±30min, and 12 hrs ±30min.  
11 If COVID-19 symptoms are present or high-risk exposure has occurred based on investigator’s discretion, an NP sample can be collected for SARS-CoV-2 RT-PCR. 
If participant tests positive for SARS-CoV-2 prior to dosing, they are no longer eligible to be enrolled.   
12 At Day -1 visit, participants will be assessed for COVID-19 symptoms/exposure only. At Day 2 visit, prior to discharge, participants will be counselled on 
precautions/measures to prevent SARS-CoV-2 infection. 
13 Assessment to be performed only if clinically indicated (as per investigator’s discretion during in-clinic, home healthcare or telemedicine follow-up). 
 
 
 
  
 
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TABLE OF CONTENTS 
DOCUMENT HISTORY ........................................................................................................2 
SPONSOR SIGNATORY .......................................................................................................3 
KEY STUDY CONTACT INFORMATION.........................................................................3 
INVESTIGATOR SIGNATORY ...........................................................................................4 
INVESTIGATOR SIGNATORY ...........................................................................................5 
PROTOCOL SYNOPSIS ........................................................................................................6 
SCHEDULE OF EVENTS ....................................................................................................19 
1 
BACKGROUND INFORMATION ............................................................................29 
1.1 
Name and Description of Investigational Product(s) ........................................29 
1.1.1 
Indication ............................................................................................................29 
1.1.2 
Description of Investigational Product ...............................................................29 
1.2 
Summary of Findings from Nonclinical and Clinical Studies .........................29 
1.3 
Summary of Known and Potential Risks and Benefits.....................................31 
1.3.1 
Risks Related to Study Intervention ...................................................................31 
1.3.2 
Risks Related to the Study ..................................................................................34 
1.3.3 
Benefits ...............................................................................................................34 
1.4 
Population to be Studied .....................................................................................34 
1.5 
Literature and Data Relevant to the Trial .........................................................35 
1.5.1 
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and 
Coronavirus Disease 2019 (COVID-19) .............................................................35 
1.5.2 
Natural History of COVID-19 ............................................................................35 
1.5.3 
Current Standard of Care for the Treatment and Prevention of COVID-19 .......36 
1.6 
Hypothesis .............................................................................................................36 
2 
STUDY OBJECTIVES AND PURPOSE ...................................................................36 
2.1 
Study Purpose.......................................................................................................36 
2.1.1 
Dose Rationale ....................................................................................................37 
2.2 
Study Objectives...................................................................................................38 
2.2.1 
Primary Objective(s) ...........................................................................................38 
2.2.2 
Secondary Objective(s) .......................................................................................38 
2.2.3 
Exploratory Objective .........................................................................................38 
3 
STUDY DESIGN ...........................................................................................................38 
3.1 
Study Description .................................................................................................38 
3.1.1 
Schematic Diagram of Study Design, Procedures, and Stages ...........................40 
3.1.2 
Study Center(s) ...................................................................................................40 
3.2 
Study Endpoints ...................................................................................................41 
3.2.1 
Pharmacokinetic Endpoints ................................................................................41 
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3.2.2 
Exploratory Endpoints ........................................................................................41 
3.2.3 
Safety Endpoints .................................................................................................41 
3.3 
Measures Taken to Minimize/Avoid Bias ..........................................................42 
3.3.1 
Masking/Blinding Procedures .............................................................................42 
3.3.2 
Treatment Assignment/Randomization ..............................................................42 
3.4 
Description of Stopping Rules.............................................................................42 
3.5 
Accountability Procedures ..................................................................................43 
3.6 
Maintenance of Study Intervention Randomization ........................................43 
3.7 
Data Directly Recorded on the Case Report Form ...........................................43 
3.8 
End of Study .........................................................................................................43 
3.8.1 
Terminating the Study.........................................................................................43 
3.8.2 
Terminating the Study at an Individual Investigational Site ..............................43 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS .............................................44 
4.1 
Subject Inclusion Criteria ...................................................................................44 
4.2 
Subject Exclusion Criteria ..................................................................................45 
4.3 
Subject Withdrawal Criteria ..............................................................................46 
4.3.1 
Withdrawal of Consent .......................................................................................46 
4.3.2 
Discontinuation of Intervention ..........................................................................46 
4.3.3 
Subject Withdrawal Criteria ...............................................................................46 
4.3.4 
Subject Replacement ...........................................................................................47 
5 
STUDY INTERVENTION ...........................................................................................47 
5.1 
Investigational Product(s) ...................................................................................47 
5.1.1 
Packaging and Labeling ......................................................................................48 
5.1.2 
Storage Conditions ..............................................................................................48 
5.1.3 
Preparation ..........................................................................................................48 
5.1.4 
Investigational Product Administration ..............................................................49 
5.1.5 
Investigational Product Accountability ...............................................................50 
5.2 
Prior and Concomitant Medications ..................................................................51 
5.2.1 
Prohibited and/or Restricted Medications ...........................................................51 
5.3 
Rescue Medications ..............................................................................................52 
5.4 
Procedures for Monitoring Subject Compliance ..............................................52 
6 
STUDY PROCEDURES AND ASSESSMENTS PER VISIT ..................................52 
6.1 
Screening ...............................................................................................................52 
6.2 
Re-Screening .........................................................................................................53 
6.3 
Pre-dosing (Day -1) – In-patient overnight assessment ....................................53 
6.4 
Baseline (Visit 1, Day 1) Assessments – Randomization and Dosing ..............54 
6.5 
Investigational Product Administration (Visit 1, Day 1) ..................................55 
6.5.1 
Acute Observation After Investigational Product Administration......................55 
6.6 
Scheduled Study Visits ........................................................................................55 
6.7 
Unscheduled Visits ...............................................................................................56 
6.8 
End of Study Visit (Visit 10, Day 57)..................................................................57 
6.9 
Early Withdrawal/Termination Visit .................................................................58 
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7 
ASSESSMENT OF PHARMACOKINETICS ...........................................................59 
7.1 
Description of Study Assessments ......................................................................59 
7.1.1 
Efficacy Outcomes ..............................................................................................59 
7.1.2 
Pharmacokinetic Samples ...................................................................................59 
7.1.3 
Nasopharyngeal Samples ....................................................................................59 
7.1.4 
Non-standard Safety Outcomes ..........................................................................60 
7.2 
Specification of the Outcome Measures .............................................................60 
7.3 
Methods and Timing for Assessing and Recording of Outcome Measures ....60 
8 
SAFETY ASSESSMENTS AND REPORTING ........................................................60 
8.1 
Definitions .............................................................................................................61 
8.1.1 
Adverse Event .....................................................................................................61 
8.1.2 
Serious Adverse Event ........................................................................................61 
8.1.3 
Adverse Drug Reaction .......................................................................................62 
8.1.4 
Suspected Unexpected Serious Adverse Reaction ..............................................62 
8.1.5 
Adverse Events of Special Interest .....................................................................62 
8.1.6 
Solicited Adverse Event(s) .................................................................................62 
8.1.7 
Unsolicited Adverse Event .................................................................................62 
8.1.8 
Severity of Adverse Events .................................................................................62 
8.1.9 
Causality of Adverse Events ...............................................................................63 
8.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters ............................................................................................................63 
8.2.1 
Solicited Adverse Events ....................................................................................64 
8.2.2 
Safety Laboratory Tests ......................................................................................64 
8.3 
Reporting Requirements for Immediately Reportable Events ........................65 
8.3.1 
Principal Investigator’s Reporting Requirements ...............................................65 
8.3.2 
Emergent’s Reporting Requirements ..................................................................66 
8.4 
Follow-up of Adverse Events ..............................................................................67 
8.4.1 
Follow-up of Nonserious Adverse Events ..........................................................67 
8.4.2 
Follow-up of Serious Adverse Events ................................................................67 
8.4.3 
Follow-up of Pregnancies ...................................................................................68 
8.4.4 
Unanticipated Problems ......................................................................................68 
8.5 
Safety Data Monitoring .......................................................................................69 
9 
STATISTICAL CONSIDERATIONS ........................................................................69 
9.1 
Sample Size Rationale..........................................................................................69 
9.2 
Statistical Methods ...............................................................................................69 
9.3 
Handling of Missing Data ....................................................................................70 
9.4 
Planned Analyses .................................................................................................70 
9.4.1 
Analyses of Disposition, Demographic and Baseline Characteristics ................70 
9.4.2 
Pharmacokinetic Analyses ..................................................................................70 
9.4.3 
Safety Analyses ...................................................................................................71 
9.4.4 
Subgroup Analyses .............................................................................................72 
9.4.5 
Planned Interim Analyses and Criteria for Study Termination ..........................72 
9.5 
Analysis Populations ............................................................................................72 
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10 
DATA HANDLING AND RECORD KEEPING .......................................................73 
10.1 
Source Documents and Access ............................................................................73 
10.2 
Data Management ................................................................................................73 
10.3 
Data Collection and Discrepancy Management ................................................73 
10.4 
Laboratory Data...................................................................................................74 
10.5 
File Management at the Investigational Site .....................................................74 
10.6 
Records Retention at the Investigational Site ...................................................74 
10.7 
Deviations from the Protocol ..............................................................................74 
11 
QUALITY CONTROL AND ASSURANCE..............................................................75 
11.1 
Monitoring ............................................................................................................75 
11.2 
Auditing ................................................................................................................75 
12 
ETHICS AND RESPONSIBILITY .............................................................................75 
12.1 
Informed Consent/Assent ....................................................................................76 
12.2 
Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC)/Research Ethics Board (REB) ..................................................................76 
12.3 
Compensation for Injury .....................................................................................77 
12.4 
Documentation Required Prior to Study Initiation ..........................................77 
12.5 
Subject Confidentiality ........................................................................................78 
12.6 
Future Use of Stored Samples .............................................................................78 
13 
ADMINISTRATIVE AND LEGAL REQUIREMENTS ..........................................78 
13.1 
Sponsorship ..........................................................................................................78 
13.2 
Protocol Amendments .........................................................................................78 
13.3 
Clinical Study Registration .................................................................................79 
13.4 
Publication Policy.................................................................................................79 
14 
REFERENCES ..............................................................................................................80 
15 
APPENDICES ...............................................................................................................87 
APPENDIX 
APPENDIX I 
GRADING OF ADVERSE EVENTS .................................................87 
APPENDIX II 
ORDINAL OUTCOME CATEGORIES AND CRITERIA .............88 
APPENDIX III 
GRADING OF VITAL SIGNS ............................................................89 
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LIST OF TABLES 
Table 1 
Study Design .........................................................................................................7 
Table 2 
Schedule of Events..............................................................................................19 
Table 3 
Risk Assessment for COVID-HIG .....................................................................32 
Table 4 
Study Design .......................................................................................................39 
Table 5 
Generic AE Grading Scale ..................................................................................63 
LIST OF FIGURES 
Figure 1 
Schematic of Study Design and Procedures. ......................................................40 
Figure 2 
Reporting Periods for Adverse Events................................................................64 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ADE 
Antibody-dependent enhancement 
AE 
Adverse event 
AESI 
Adverse events of special interest 
ALT 
Alanine aminotransferase 
AMS 
Aseptic meningitis syndrome 
ANOVA 
Analysis of variance 
anti-HCV 
antigen (HBsAg), Hepatitis C virus antibody 
AST 
Aspartate aminotransferase 
AU 
Alliance units 
BARDA 
Biomedical Advanced Research and Development Authority 
BMI 
Body mass index 
BUN 
Blood urea nitrogen 
CBC 
Complete blood count 
CCP 
COVID-19 convalescent plasma 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
Cl- 
Chloride 
CNJ-016® 
Vaccinia immune globulin intravenous (Human) 
COVID-19 
Coronavirus disease 2019 
COVID-HIG 
Anti-SARS-CoV-2 Immunoglobulin Injection (Human) 
CRO 
Contract research organization 
CRF 
Case Report Form 
CSF 
Cerebrospinal fluid 
CV 
Coefficient of variation 
DAIDS 
Division of Acquired Immunodeficiency Syndrome (AIDS) 
DMC 
Data Monitoring Committee 
DMP 
Data management plan 
DoD 
Department of Defense 
EAP 
Expanded access program 
EC 
Ethics committee 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
Emergent 
Emergent BioSolutions Canada Inc. 
FDA 
US Food and Drug Administration 
GCP 
Good clinical practices 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B Virus 
HC03- 
Bicarbonate 
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HCV 
Hepatitis C Virus 
HepaGam B® 
Hepatitis B immune globulin (human) 
HIV 
Human immunodeficiency virus 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International conference on harmonization 
ICU 
Intensive care unit 
ID 
Identification  
IEC 
Independent ethics committee 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G (gamma globulin) 
IgM 
Immunoglobulin M 
IGIV 
Immunoglobulin intravenous 
IM 
intramuscular 
IP 
Investigational product 
IPD 
Important protocol deviation 
IRB 
Institutional review board 
ITT 
Intent-to-Treat Set 
IUD 
Intrauterine device 
IUS 
Intrauterine system 
IV 
Intravenous  
K+ 
Potassium 
KM 
Kaplan-Meier 
LDH 
Lactate dehydrogenase 
LLOQ 
Lower limit of quantitation 
LSLV 
Last subject last visit 
mAb 
Monoclonal antibody 
MM 
Medical monitor 
Na+ 
Sodium 
NHP 
Non-human primate 
NIAID 
National Institute of Allergy and Infectious Diseases 
NP 
Nasopharyngeal  
NP-028 
Anti-SARS-CoV-2 Immunoglobulin Intravenous (Human) 
OHRP 
Office for Human Research Protection 
OR 
Odds ratios 
PD 
Protocol deviation 
PE 
Physical exam 
PEP 
Postexposure prophylaxis 
PI 
Principal investigator 
PK 
Pharmacokinetics 
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ppm 
Parts per million 
PS80 
Polysorbate 80 
PV 
Pharmacovigilance 
REB 
Research ethics board 
RTSM 
Randomization and trial supply management 
RT-PCR 
Reverse transcriptase polymerase chain reaction 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SC 
subcutaneous 
SD 
Standard deviation 
SMC 
Safety Monitoring Committee 
SOC 
Standard of Care 
SOC 
System Organ Class 
SS 
Safety Set 
SUSAR 
Suspected Unexpected Serious Adverse Reaction  
TEAE 
Treatment emergent adverse event 
TnBP 
Tri-n-butyl phosphate 
TNF-α 
Tumor necrosis factor alpha 
TRALI 
Transfusion-related acute lung injury 
TX-100 
Triton X-100 (octyl phenylpolyethylene glycol ether) 
ULN 
Upper limit of normal 
UPT 
Urine pregnancy test 
US 
United States of America 
USG 
United States Government 
VARIZIG® 
Varicella zoster immune globulin intravenous (human) 
VIGIV 
Vaccinia immune globulin intravenous (human) 
WinRho® SDF 
Rho (D) immune globulin intravenous (human) 
WHO 
World Health Organization 
WOCBP 
Women of childbearing potential 
 
 
 
 
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1 
BACKGROUND INFORMATION 
1.1 
Name and Description of Investigational Product(s) 
1.1.1 Indication 
COVID-HIG is being developed for treatment of COVID-19 caused by the SARS-CoV-2 virus 
to be administered as a single dose following diagnosis. 
1.1.2 Description of Investigational Product 
Anti-SARS-CoV-2 Immunoglobulin Injection (Human), also referred to as COVID-HIG (code 
name: NP-028), is a hyperimmune product that consists of purified IgG fraction of human 
plasma containing antibodies (including neutralizing antibodies) to SARS CoV-2. COVID-HIG 
is intended as a passive immunization therapy (i.e., passive transfer of antibodies) that would 
provide suitable levels of SARS-CoV-2 antibodies for binding and neutralization of SARS-CoV-
2 preventing viral cellular entry and potentially augmenting the immune response.  
COVID-HIG is prepared from pooled plasma collected at US Food and Drug Administration 
(FDA) licensed and/or registered plasma and/or blood collection centers and Health Canada 
licensed/US FDA licensed and/or registered plasma collection centers from healthy, adult donors 
who have elevated levels of SARS-CoV-2 antibodies. 
COVID-HIG (85-115 mg/mL protein) is provided as a sterile liquid for IV, SC, or IM 
administration.  
For IP details, refer to Section 5.1 and the most current version of the Investigator’s Brochure 
(IB). 
1.2 
Summary of Findings from Nonclinical and Clinical Studies 
Animal studies in a variety of species have shown that both polyclonal and monoclonal (mAb) 
antibodies administered intravenously are efficacious against SARS-CoV-2. Passive transfer of 
COVID-19 convalescent serum reduced lung virus load in both non-human primates (NHP) and 
hamsters when administered one day post-infection, with complete protection (sterile immunity) 
when treated one day before infection (1, 2). Several mAbs showed a protective effect by 
reducing the duration and/or degree of body weight loss, tissue virus load and lung pathology 
when given within a window of one day before or one day post-infection in adenovirus 
transduced mice, NHPs and hamsters (3, 4, 5, 6, 7, 8, 9). Evidence to date demonstrates that 
administration of antibodies in NHP and hamsters infected with a human SARS-CoV-2, 
significantly reduces the virus replication in the respiratory system and prevents the development 
of lung pathology.  
Preclinical studies demonstrated the efficacy of COVID-HIG in hamsters and adenovirus 
transduced ACE2 expressing mice when administered in a post-exposure prophylaxis setting. 
COVID-HIG in these models reduced the lung viral burden and reduced the duration and/or 
degree of infection related transient body weight loss.  
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In human clinical trials in recently tested SARS-CoV-2 positive patients, mAb treatments 
showed a reduction in viral load in upper respiratory samples, with the greatest effect seen in 
patients treated earlier in disease course (10, 11). These data suggest that antibody therapeutics 
have the potential to impact SARS-CoV-2 viral replication which may result in reduced disease 
severity. 
COVID-19 convalescent plasma rapidly became an intervention for hospitalized patients after 
initial reports from open label treatment studies (12, 13) supported use under an expanded access 
program (EAP) in the US. Data emerging from the EAP and other published studies have 
demonstrated the safety and suggested the benefit of passive immunotherapy with COVID-19 
convalescent plasma (CCP) (14, 15, 16, 17) which supported emergency use authorization 
(EUA) for CCP in hospitalized COVID-19 patients (18). Contrary to EAP experience, 
randomized controlled studies in India and Argentina have failed to demonstrate efficacy of CCP 
in patients hospitalized with COVID-19 (19, 20). Limitations to CCP include the 1:1 donor to 
recipient treatment and a lack of consistent neutralizing potency from unit to unit. Despite 
limitations, analyses of over 3000 patients treated with CCP in the US, has shown a mortality 
benefit for treatment with CCP with high neutralizing antibody titers in comparison to low titer 
CCP as well as benefit with intervention earlier in disease course prior to the need for 
mechanical ventilation (21). These data speak both to the importance of a threshold of antibody 
levels and to the timing of intervention prior to a hyperinflammatory state. Selection of high titer 
CCP combined with early intervention has also been supported by a randomized placebo-
controlled trial of high titer CCP in older adults treated within 72 hours of symptom onset mild 
COVID-19 (22). Despite stopping early due to a decrease in the regional COVID-19 incidence in 
Argentina, this study showed a 48% reduction in the incidence of severe COVID-19 in patients 
infused with high titer CCP.  
Neutralizing mAbs and antibody cocktails have also demonstrated the benefit of early treatment 
in the prevention of COVID-19 disease progression. The combination of casirivimab and 
imdevimab (REGN-CoV2) and sotrovimab (VIR-7831) have received EUA for the treatment of 
mild to moderate COVID-19 in patients at high risk of disease progression (23, 24), with REGN-
CoV2 recently being granted EUA for post-exposure prophylaxis as well (23). Although 
bamlanivimab plus etesevimab has received an EUA for treatment as well (10), there are 
concerns about its efficacy against certain neutralization-escaping variants (25). Both REGN-
COV2 and sotrovimab similarly demonstrated a decrease in hospitalizations with antibody 
treatment in ambulatory patients (11, 26) yet have maintained resilience against emerging 
variants (27). These studies also demonstrated the benefit of early antibody seroconversion, as 
outpatients who were seropositive at baseline had lower viral load and a trend for faster 
alleviation of symptoms than seronegative patients (28). In line with this, the RECOVERY trial 
observed a survival benefit only in hospitalized severe COVID-19 patients that were 
seronegative at baseline (29). Additional studies are underway in hospitalized patients with 
COVID-19; however, mAbs may be associated with worse clinical outcomes when administered 
to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. 
Thus, evidence currently suggests that mAb use provides benefit primarily in seronegative 
patients, which typically represents those early in disease course or certain hospitalized patients.    
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Currently three clinical trials with Emergent’s COVID-HIG product are ongoing. Emergent has 
partnered with the US Government (USG) to advance this program by working closely with 
Biomedical Advanced Research and Development Authority (BARDA) and National Institute of 
Allergy and Infectious Diseases (NIAID) for participation in randomized controlled trials with 
COVID-HIG for treatment of hospitalized COVID-19 patients [INSIGHT 013] and high-risk 
outpatients [INSIGHT 012]. The INSIGHT 013 trial [NCT04546581] was an international, 
multi-center, adaptive, randomized, double-blind, placebo-controlled trial of the safety, 
tolerability, and efficacy of a single dose infusion (up to 400 mL) of Anti-Coronavirus 
Hyperimmune Intravenous Immunoglobulin (hIVIG) for the treatment of adult recently 
hospitalized COVID-19 patients (N=593). Participants received one of four hIVIG products 
(from different manufacturers) or placebo in addition to standard of care (SOC). Although the 
trial did not meet the primary efficacy endpoint to provide clinical benefit when compared to 
SOC plus placebo, there were no significant safety issues reported with Emergent’s COVID-HIG 
product (n=80).   
INSIGHT 012 [NCT04910269] is an international, multi-center, randomized, double-blind, 
placebo-controlled trial of the safety, tolerability and efficacy of hIVIG in high-risk adult 
outpatients in early stages of COVID-19. Participants will receive one of two hIVIG products 
(from two different manufacturers) or placebo in addition to SOC. The primary efficacy endpoint 
is an ordinal outcome (ranging from death to asymptomatic COVID-19) based on the 
participant’s clinical status at Day 7. As of 06Aug2021, recruitment has been initiated.   
EBS-CVH-003, funded by the US Department of Defense (DoD) was a Phase 1 double-blind, 
randomized, placebo-controlled study conducted by Emergent in healthy adults to assess the 
safety and pharmacokinetics of three dose levels of COVID-HIG IV [NCT04661839]. Study 
enrollment (n=28) has been completed with all participants being followed up to study 
completion. Thus far, one SAE has occurred not related to study treatment.  
1.3 
Summary of Known and Potential Risks and Benefits 
1.3.1 Risks Related to Study Intervention 
The overall safety profile of COVID-HIG is anticipated to be comparable to other commercially 
available human hyperimmune products, including those hyperimmune products manufactured 
by Emergent (VARIZIG®, HepaGam B®, ANTHRASIL®, WinRho® SDF, CNJ-016®-VIGIV) 
(30, 31, 32, 33, 34). The most common types of adverse reactions to hyperimmune products are 
local injection reactions (e.g., pain, redness, swelling) and non-anaphylactic infusion reactions, 
such as back or abdominal pain, nausea and vomiting during longer IVIG infusions. Usually 
there is no dyspnea or other clinically significant changes in vital signs. Fever, headache, chills, 
rash, fatigue may begin during the injection and continue for several hours. More severe 
reactions of this type may require treatment with corticosteroids or acetaminophen and persist for 
several hours after the injection. These may be treated symptomatically. The incidence of 
adverse reactions associated with IM/SC/IV administration of immunoglobulin products is 
reported by the manufacturers to be typically in the range of 1 to 15% (30, 31, 32, 33, 34, 35, 36, 
37, 38, 39). Infrequent events associated with IV immunoglobulin treatment have also been 
reported (mostly in individuals with risk factors for developing these events), such as 
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hypersensitivity reactions, renal failure, aseptic meningitis syndrome (AMS), hemolysis, 
transfusion-related acute lung injury (TRALI) and thrombotic events (40). Potential risk of 
antibody-dependent enhancement (ADE) in COVID-19 patients following treatment with 
antibody-based therapies has not been clinically observed (e.g., in COVID-19 patients after 
transfusion of convalescent COVID-19 plasma) (15). 
The risk assessment for COVID-HIG and mitigation strategies for EBS-CVH-006 are 
summarized in Table 3. 
Table 3 
Risk Assessment for COVID-HIG 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Potential for injection-related 
local (e.g., pain, redness, 
tenderness or swelling) and 
systemic (back or abdominal 
pain, nausea and vomiting, 
fever, headache, myalgia, 
chills, rash, or fatigue) 
reactions.  
These are common adverse reactions 
seen with other human hyperimmune 
products (VARIZIG, HepaGam B, 
ANTHRASIL, WinRho SDF, CNJ-
016-VIGIV, BIVIGAM®, 
GAMMAPLEX®, Privigen®, 
GAMUNEX®-C, Hizentra®) (30, 31, 
32, 33, 34, 35, 36, 37, 38, 39). 
The IM dose will be administered to the 
thigh muscle and will be split between 
both thigh muscles to mitigate 
discomfort. All study participants will 
stay overnight in the inpatient unit for 
close observation for approximately 24 
hours post injection. Injection stopping 
rules and study stopping rules are 
provided (Pharmacy Manual and Sections 
3.4).  
Potential for hypersensitivity 
reactions within six hours after 
the injection. 
Hypersensitivity reactions are rare. 
Severe immediate hypersensitivity 
reactions to plasma-derived products 
occur in individuals with IgA 
deficiency or hypersensitivity to 
human globulin.  
Participants will be monitored overnight 
after injection in a setting with 
appropriate equipment, medication and 
personnel trained in the management of 
hypersensitivity, anaphylaxis, and shock. 
Participants at risk of hypersensitivity 
reactions are excluded from the study. 
Potential for renal 
dysfunction/acute renal failure.  
Renal dysfunction has been associated 
with HIG products containing sucrose 
as a stabilizer.  
COVID-HIG does not contain sucrose. 
Serum blood urea nitrogen and creatinine 
will be monitored at Screening and at Day 
2 and Day 4 post-administration.  
Potential for hematologic 
complications such as 
hemolytic anemia and 
thrombotic complications.   
Rare thrombotic events have been 
associated with presence of activated 
factor XI resulting in elevated 
procoagulant activity in some 
immunoglobulin products.  
High doses (>1–2 g/kg) are associated 
with an increased risk of hemolysis.  
COVID-HIG has been tested for 
procoagulant activity and has met the 
product release specification. The 
COVID-HIG doses being administered 
are well below 1 g/kg.  
Hemoglobin will be monitored at 
Screening and at Day 2 and Day 4 post-
administration.   
Participants with pre-existing thrombotic 
or procoagulant disorders are excluded 
from the study. 
Potential for AMS or TRALI 
AMS and TRALI rarely occurs in 
association with high doses (1–2 g/kg) 
of IGIV therapy. AMS begins within 
several hours to two days following 
The COVID-HIG doses being 
administered are well below 1 g/day. 
Participants will be monitored overnight 
after injection, with safety tests at Days 2 
and 4 post injection. 
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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
IGIV treatment, while TRALI occurs 
one to six hours post infusion. 
Potential for transmission of 
infectious diseases 
Human plasma is used in the 
manufacture of COVID-HIG. Plasma 
is collected in accordance with 
regulatory requirements and donors 
are screened to assess the risk of 
exposure. Plasma donations are tested 
for HIV 1/2, HCV, and Hepatitis B.  
Manufacturing processes include viral 
filtration and inactivation steps with 
quality control testing to eliminate risk of 
viral infection from COVID-HIG. Viral 
markers for Hepatitis B, Hepatitis C, and 
HIV 1/2 will be obtained from 
participants at Screening to document 
baseline status and at End of Study visit. 
Additional follow-up tests will be 
performed only if clinically indicated. 
Potential for immunologic 
interference with live 
attenuated virus vaccine or the 
COVID-19 vaccine 
Antibody therapies may impair the 
efficacy of live attenuated virus 
vaccines such as measles, mumps, 
rubella, and varicella.  
Concomitant administration of 
antibody therapies and the COVID-19 
vaccine could theoretically result in 
immunologic interference.  
The use of live virus vaccination before 
or after COVID-HIG should follow 
current recommendations.  
COVID-19 vaccination must occur at 
least 60 days prior to screening to be 
eligible. COVID-19 vaccination after the 
study should be deferred for 90 days post-
administration as per current ACIP 
recommendations post-administration of 
passive antibody therapies (41)414141 
 
The active ingredient of COVID-HIG is human IgG, which is a normal constituent of the human 
body and therefore it is not expected to be toxic to humans. A no-observed-adverse-effect level 
of 2000 mg/kg total protein was determined for product manufactured on the same platform and 
formulated identically to COVID-HIG administered IV to rats in a Good Laboratory Practice 
compliant single dose acute toxicology study conducted by Emergent (42). At the proposed 
COVID-HIG doses (~2-10 mg/kg) for this study, exposure levels of excipients (proline, PS80) 
and residuals (TnBP, TX-100) are well below maximum tolerated doses in animals; hence, these 
substances are not expected to pose any clinically significant health risks to study participants 
(refer to the most current version of the IB for more details). 
The available clinical safety and efficacy data from immune based therapies such as 
convalescent plasma and mAbs that have been granted EUA support early intervention to 
prevent serious outcomes associated with COVID-19. Preclinical efficacy data with COVID-
HIG, related preclinical safety data with product manufactured on the same platform as COVID-
HIG and safety data from ongoing COVID-HIG studies (INSIGHT 013 and EBS-CVH-003) in 
180 participants to date support the further development of COVID-HIG as a COVID-19 
therapeutic.
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1.3.2 Risks Related to the Study 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Participants may have in-
clinic visits which could 
involve attendance at 
healthcare facilities during 
the global SARS-CoV-2 
pandemic.  
There is a potential for increased 
exposure/transmission of SARS-CoV-2.  
Participants will have the 
opportunity to have a home visit 
for vital signs and collection of 
study specimens followed by a 
telemedicine appointment with 
the investigator if required. 
Participants will be counseled on 
precautions for reducing 
transmission of COVID-19.  
Participants will undergo 
nasopharyngeal swab 
testing.  
There is a potential for discomfort, risk of 
gagging during the test. Participants may have a 
minor nosebleed afterwards. Rarely cerebrospinal 
fluid (CSF) leak has been reported following 
COVID-19 testing (43). 
Only appropriately qualified 
personnel will obtain the NP 
swab. Individuals at risk for 
serious complications following 
nasopharyngeal swab testing 
(e.g., CSF leak) are excluded 
from participation in the study 
(healthy participants only).  
Blood draws will be 
performed during the study.  
There is a risk of bleeding, bruising, hematoma 
formation and infection at the venipuncture site.  
Only appropriately qualified 
personnel will obtain the blood 
draw.  
Unauthorized exposure or 
release of confidential 
information.  
As with any procedure that collects protected 
personal identifiable information, there is a risk 
of inappropriate exposure to unauthorized 
individuals or unapproved use of information.  
Only approved personnel will be 
able to access participant 
information. Participant data and 
samples will only be used as 
consented by the participant. 
Procedures and safeguards to 
maintain integrity of confidential 
information are outlined in 
Section 12.  
1.3.3 Benefits 
There are no proven benefits of the study intervention that participants in this study should 
expect. Clinical data derived from participants in this study will contribute to the development of 
COVID-HIG for treatment of COVID-19.  
1.4 
Population to be Studied 
COVID-HIG will be evaluated in healthy non-pregnant female and male adults 18–59 years of 
age.  
Refer to Section 3.1 for Study Description and Section 4 for Subject Inclusion and Exclusion 
criteria.  
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1.5 
Literature and Data Relevant to the Trial 
1.5.1 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and 
Coronavirus Disease 2019 (COVID-19) 
The COVID-19 pandemic caused by SARS-CoV-2 has resulted in significant worldwide 
increase in hospitalizations for pneumonia with multiorgan failure (44). Due to the spread of 
SARS-CoV-2, first identified in December 2019, causing a sudden increase in COVID-19 cases 
throughout the world, a pandemic was declared by World Health Organization (WHO) in March 
2020. As of early August 2021, >200 million COVID-19 cases and >4.2 million COVID-19 
attributed deaths have been reported to the WHO. In the US and Canada, COVID-19 cases 
continue to rise prompting public health authorities to continue active monitoring and focus on 
containment of the outbreak to prevent further spread (45).   
1.5.2 Natural History of COVID-19  
The incubation period for SARS-CoV-2 is approximately four to five days (range: two to seven 
days) (46, 47), and most individuals who develop symptoms (~98%) will do so within 11.5 days 
post-infection (46). Acute manifestations of COVID-19 include the following signs and 
symptoms: fever, cough, shortness of breath, fatigue, myalgia, nausea/vomiting or diarrhea, 
headache, rhinorrhea, anosmia, and ageusia. (48). 
Many COVID-19 patients present with mild disease (approximately 80%). Although mild, 
symptomatic COVID-19 often resolves five to seven days (and up to 14 days) after symptom 
onset, there is growing recognition of the occurrence of postinfectious sequelae lasting for 
months in individuals, including young, physically fit individuals who initially experienced mild 
acute illness (49). Fatigue, dyspnea, cough, arthralgia, and chest pain are among the most 
commonly reported. Based on current available evidence, postinfectious sequelae may also 
include serious outcomes: cardiac (myocardial inflammation, ventricular dysfunction), 
respiratory (pulmonary function abnormalities), renal (acute kidney injury), dermatologic (rash, 
alopecia), neurologic (altered cognition, memory impairment, olfactory and gustatory 
dysfunction, sleep dysregulation), and psychiatric (depression and changes in mood).  
Approximately 20% of patients will progress to more severe COVID-19 characterized by 
worsening dyspnea and hypoxia, severe pneumonia with >50% lung involvement on imaging. 
The median time from symptom onset to hospitalization is seven days; range: three to nine days 
post-symptom onset (50). Five percent of patients progress to critical COVID-19 manifested as 
acute respiratory distress syndrome, septic shock and/or multiorgan system dysfunction (47, 51, 
52, 53). Cardiac, neurologic, hepatic, renal and hematologic complications may occur (54). 
Mortality in hospitalized COVID-19 patients ranges from 15% to 40% (55).  
Reports of reinfection and vaccine breakthrough infections have become more frequent with 
emerging novel variants, but still remain relatively infrequent, with vaccination post-infection 
yielding a greater than two-fold reduction in reinfection risk (56).  
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1.5.3 Current Standard of Care for the Treatment and Prevention of COVID-19 
General methods to prevent COVID-19 based on current guidance are to wear a mask in public 
settings, practice social distancing and avoid crowds and poorly ventilated indoor spaces (57). In 
December 2020, regulatory agencies in both the US and Canada authorized emergency use of the 
Moderna® and Pfizer-BioNTech® vaccines for pre-exposure prophylaxis of COVID-19 (58, 59, 
60, 61). Although these vaccines are widely available in the U.S. and Canada, as of mid-July 
2021, less than 60% of each country’s population has been fully vaccinated (62). With emerging 
variants of increased transmissibility and severity (63), COVID-19 remains an urgent public 
health threat.   
Individuals with mild to moderate COVID-19 disease not requiring supplemental oxygen are 
currently provided with symptomatic treatment if needed and instructed to follow public health 
protocols for self-isolation and return to the hospital if symptoms worsen. Several SARS-CoV-2 
mAb (casirivimab plus imdevimab, bamlanivimab plus etesevimab or sotrovimab) are available 
under EUA for outpatients who are at high risk of disease progression and as post-exposure 
prophylaxis in high risk individuals (casirivimab plus imdevimab and bamlanivimab plus 
etesevimab) (64, 65, 66). The current standard of care for hospitalized patients with severe 
disease requiring supplemental oxygen includes dexamethasone with or without remdesivir in 
addition to supportive care. Current NIH treatment guidelines (updated 15Sep2021) recommend 
these mAbs for a broad range of high-risk patients ≥12 years of age that are likely to progress to 
more severe disease, however they are not considered SOC for all that test positive for SARS-
CoV-2 (67).   
1.6 
Hypothesis 
No statistically-powered hypothesis is tested in this Phase 1 study. It is hypothesized that 
COVID-HIG in all three routes of administration (IM, SC, and IV) is well-tolerated and that 
concentrations of SARS-CoV-2 antibodies will be measurable over time, with derived PK 
parameters in line with immunoglobulin product class kinetics.   
2 
STUDY OBJECTIVES AND PURPOSE 
2.1 
Study Purpose 
This study is designed to evaluate safety and PK of COVID-HIG administered as IM, SC, or IV 
routes as a single dose in healthy adults. 
Like other human immunoglobulin products, the hyperimmune products manufactured by 
Emergent (see Section 1.3.1) have been studied in several healthy adult volunteers and clinical 
studies with patients; the safety profile of these hyperimmune products is consistent with other 
commercial hyperimmune products and the PK profile is typically similar to the PK of licensed 
hyperimmune products, with a half-life of approximately 24 to 30 days after IV administration.  
Results from this clinical study will provide safety information on intramuscularly and 
subcutaneously administered COVID-HIG, as well as PK parameters such as peak COVID-HIG 
plasma levels, trough titers of SARS-CoV-2 antibodies, and COVID-HIG half-life in healthy 
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adults; the safety data and PK parameters from this study (along with data available from other 
ongoing or planned clinical studies with COVID-HIG) will be used for dose optimization/dose 
selection for the proposed COVID-HIG indications (treatment of COVID-19; post-exposure 
prophylaxis of COVID-19). 
2.1.1 Dose Rationale 
The proposed dose for this clinical study (approximately 8–16 mg/kg based on an estimated 
participant weight of 50–100 kg) is within the dose levels tested in clinical studies of other 
licensed hyperimmune products and is expected to display similar safety and PK profile to those 
products. The selected dose for this clinical study is ≈250,000 Alliance Units (AU), based on 
COVID-HIG product lot potency of 29,282 AU/mL in the wild-type neutralization assay 
(performed at the NIAID analytical laboratory), resulting in a dose volume of 8.5 mL. The 
COVID-HIG lot potency is derived using an internal standard that has been established in the 
NIAID sponsored treatment study INSIGHT-013 (clinical lot potency of COVID-HIG is 29,282 
AU/mL). The selected dose is based on antibody titer data available from treatment studies with 
COVID-19 convalescent plasma (CCP) and SARS-CoV-2 antibody-based therapeutics and 
vaccine trials as well as emerging literature on protective antibody levels (17, 21, 22, 68, 69, 70). 
The proposed dose potency is within the range of COVID-HIG doses that have been used for 
treatment of hospitalized COVID-19 patients (INSIGHT-013; NCT04546581) and for early 
treatment of high-risk COVID-19 patients (INSIGHT-012; NCT04910269).  
As part of Emergent’s manufacturing process for COVID-HIG, identification and screening of 
convalescent plasma donors is performed to select plasma as source material for manufacturing 
of COVID-HIG from COVID-19 convalescent donors that have been vaccinated against 
COVID-19. Plasma screening is primarily with an in-house immunobinding assay to SARS-
CoV-2 Spike protein, however several assays including viral (wild type and pseudovirus) 
neutralization and external binding assays including the Ortho VITROS and the Diasorin 
LIAISON SARS-CoV-2 S1/S2 IgG immunoassays, have been assessed for correlation. This 
experience has identified a range of neutralizing titers in non-vaccinated convalescent donors, 
which are typically around 20-50 AU/mL (data on file). Plasma testing data generated by 
Emergent allow a high-level comparison of COVID-HIG neutralizing antibody potency to that of 
CCP used in therapeutic clinical trials. COVID-19 convalescent plasma treatment in hospitalized 
patients from the US National registry demonstrated that higher titers of binding and neutralizing 
antibodies were associated with decreased 30-day mortality (21). Extrapolating based on our 
calculations of COVID-HIG and high-titer CCP potency, COVID-HIG is estimated to be at least 
60 times as potent as high titer CCP based on the Ortho VITROS assay. Informal comparison of 
COVID-HIG potency to the high titer CCP in an early treatment study in elderly patients 
Argentina (22), suggest that COVID-HIG contains approximately 100-fold higher neutralizing 
antibody levels than CCP. Thus, a dose of 250 mL high titer CCP in the aforementioned study 
that was associated with a reduction in incidence of severe disease, is expected to be equivalent 
to approximately 2.5 mL of COVID-HIG.  
Vaccine studies also provide an early estimate of antibodies levels that correlate with protection, 
especially as vaccine studies include results comparing convalescent plasma control samples 
with samples from vaccinated subjects (69, 70). Antibody levels achieved post-vaccination after 
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two doses of vaccine are toward the higher high end of the CCP neutralizing antibody range and 
remain relatively stable for at least 6 months following vaccination.  
Based on cumulative considerations presented above, the selected dose of ≈250,000 AU is 
expected to provide substantially higher antibody levels than high titer CCP that was used 
therapeutically in most clinical trials. Although this study will be performed in healthy, 
uninfected adults for safety and PK analyses, this dose level will inform future dose 
optimization/dose selection for future COVID-HIG studies.  
2.2 
Study Objectives 
2.2.1 Primary Objective(s) 
The following primary objectives will be evaluated: 
• To evaluate safety of COVID-HIG administered IM or SC as a single dose  
• To evaluate PK of COVID-HIG administered IM or SC as a single dose  
2.2.2 Secondary Objective(s) 
The following secondary objectives will be evaluated:  
• To compare PK of COVID-HIG IM to COVID-HIG IV  
• To compare PK of COVID-HIG SC to COVID-HIG IV  
• To compare PK of COVID-HIG SC to COVID-HIG IM 
2.2.3 Exploratory Objective 
The following exploratory objective will be evaluated:  
• To evaluate the effects of COVID-HIG in participants that become Severe Acute 
Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) positive. 
3 
STUDY DESIGN 
3.1 
Study Description 
This will be a Phase 1, two-center, open-label, randomized study to evaluate one dose level of 
COVID-HIG administered IM, SC, or IV for safety and PK in healthy adults. Up to 36 adult 
participants will be targeted to be enrolled in the study. The study has been truncated to 23 
randomized participants due to the impact of high circulating SARS-CoV-2 omicron cases on 
enrollment and participant retention. The sample size with 7-8 participants per study arm will 
allow for assessment of the primary safety and PK objectives. 
Subjects that provide written informed consent and meet eligibility criteria will be stratified 
based on their SARS-CoV-2 detectable antibody status (>LLOQ, but ≤80 AU/mL on the 
Diasorin LIAISON SARS-CoV-2 S1/S2 IgG antibody assay) and undetectable antibody 
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(≤LLOQ) at screening, and randomized in two cohorts. If the proportion of subjects in one 
stratum is high, that stratum may be closed to allow for enrollment in the other stratum.  
Table 4 
Study Design  
Group 
Study Arm 
No. of Participants 
Dosing Schedule – Day 1 
Intramuscular 
1 
Up to 12 
≈250,000 AU COVID-HIG IM1 
Subcutaneous 
2 
Up to 12 
≈250,000 AU COVID-HIG SC1 
Intravenous 
3 
Up to 12 
≈250,000 AU COVID-HIG IV1  
1Exact dose volumes was determined based on the potency of the COVID-HIG clinical lot as defined in Alliance 
Units (AU) through the wild-type neutralization assay (Clinical lot potency: 29,282 AU/mL, 8.5 mL volume; target 
protein concentration: 100 mg/mL). 
 
Up to thirty-six participants will be enrolled and assigned equally to one of three study arms to 
receive a single IM, SC, or IV dose of COVID-HIG, respectively (see the table above). Cohort 1 
will consist of 12 subjects; Cohort 2 will comprise up to 24 subjects. 
Enrollment into the study will be staggered, wherein no more than three participants will be 
randomized and dosed on the first day with at least one hour between dosing of each participant. 
On the second day, up to two more subjects will be randomized and dosed. The remaining 
participants will be randomized and dosed, with no more than 5 participants dosed per day. 
Safety data will be reviewed by an SMC (consisting of at least three independent external 
members) after all 12 participants in Cohort 1 have completed at least 72 hours of safety follow-
up. An overall decision by the SMC will be made whether to proceed with full randomization 
(1:1:1) and dosing of the remaining study participants (Cohort 2, up to n=24).   
Participants will be admitted to the inpatient unit one day prior to dosing (Day -1), and following 
dosing on Day 1, each participant will stay overnight in the inpatient unit for close observation 
and PK sample collection. Each dosed participant will be discharged from the inpatient unit once 
all assessments at 24 hours post-dosing timepoint (i.e., Day 2) are completed. Participants will be 
followed for safety and PK up to 56 days post-dosing (Day 57; see Table 2 for Schedule of 
Events). Follow-up visits to collect required samples and/or safety assessments can occur in-
clinic or at-home as indicated in Table 2. 
Study enrollment and administration of study treatments may be paused by the PI or medical 
monitor for safety review if any of the following occur after study product administration and 
during the enrollment period: 
• One or more SAE(s)  
• Three or more of the same AEs classified as Grade 3 severity  
• Three or more hypersensitivity AEs classified as Grade 2 
AE severity will be graded according to the DAIDS Severity Grading Scale (Appendix I). 
Participants will be followed for 56 days post-dose.  
If any participants become positive for SARS-CoV-2 during the study follow-up period, they 
will be assessed using an Ordinal Outcome Scale (Appendix II) until symptom resolution and 
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will be followed until they complete their last scheduled follow-up visit (via telemedicine). 
Participants who test positive for SARS-CoV-2 will be excluded from PK analyses. As such, all 
subsequent visits should be done via telemedicine following SARS-CoV-2 positive status 
(except the Day 57 or the withdrawal visit), unless an in-person visit is deemed clinically 
necessary by the PI. Any in-person visits should be scheduled in a manner that reduces the risks 
of SARS-CoV-2 transmission, according to local rules and regulations. As the Day 57 or 
withdrawal visit necessitates in-person safety assessments, this visit should proceed in-person, if 
possible. If a participant tests positive for SARS-CoV-2 immediately prior to or at the in-person 
Day 57 visit, reasonable efforts will be made to collect as many of the required samples from the 
Day 57 visit in a manner that reduces the risk of SARS-CoV-2 transmission, according to local 
rules and regulations. 
For details on schedule of events, refer to Table 2 Schedule of Events. 
3.1.1 Schematic Diagram of Study Design, Procedures, and Stages 
Figure 1 
Schematic of Study Design and Procedures. 
 
 
3.1.2 Study Center(s) 
This study will be conducted at two centers in the US. 
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3.2 
Study Endpoints 
3.2.1 Pharmacokinetic Endpoints 
3.2.1.1 
Primary Pharmacokinetic Endpoints 
The following primary PK endpoints (based on PK sample test results of an immunobinding IgG 
assay) will be evaluated in healthy adults belonging to both strata, detectable SARS-CoV-2 
antibody and undetectable antibody (≤LLOQ) at screening: 
• AUC0-inf: AUC0-last plus the additional area extrapolated to infinity after dosing. 
• AUC0-last: area under the concentration-time curve from time 0 to the last quantifiable 
concentration after dosing. 
• Cmax: maximum observed concentration after dosing. 
• Tmax: time at which Cmax occurs after dosing. 
• C28d: observed or estimated concentration at 28 days after dosing. 
3.2.1.2 
Secondary Pharmacokinetic Endpoints 
The following additional COVID-HIG PK endpoints (based on PK sample test results by an 
immunobinding IgG assay) will be calculated when data permit: 
• AUC0-inf ratios (bioavailability) will be compared between routes for comparable dose 
levels (COVID-HIG SC to IV; IM to IV; and SC to IM). 
• AUC0-14d after dosing. 
• AUC0-28d after dosing. 
• λz: terminal elimination rate constant after dosing. 
• T1/2: apparent terminal elimination half-life after dosing. 
• CL: systemic clearance after dosing. 
• VZ: volume of distribution after dosing. 
3.2.2 Exploratory Endpoints 
Descriptive analyses of COVID-19 disease severity among SARS-CoV-2 positive subjects as 
assessed by an Ordinal Outcomes scale (Appendix II).  
3.2.3 Safety Endpoints 
3.2.3.1 
Primary Safety Endpoints 
The following primary safety endpoints will be evaluated:  
• AEs within 72 hours post-dosing. 
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• AEs and SAEs in healthy adults up to 56 days post- administration of a single COVID-
HIG dose. 
3.3 
Measures Taken to Minimize/Avoid Bias 
3.3.1 Masking/Blinding Procedures 
As this is an open label study, no masking/blinding procedures are necessary.  
3.3.2 Treatment Assignment/Randomization 
Enrollment into the study will be staggered. In the sentinel Cohort 1 a total of 12 participants will 
be randomized 1:1:1 to each study arm. As part of the sentinel cohort, the first three participants 
will be randomized and dosed on the first day with at least one hour between dosing of each 
participant. Another nine participants will then be randomized and dosed at least 24 hours after 
the first three participants have been dosed, with no more than 5 participants dosed per day in 
this set. Following randomization/dosing of the first four participants in each of the three arms 
(Cohort 1, n=12), safety data will be reviewed by the SMC once these 12 participants have 
completed at least 72 hours of safety follow-up. An overall decision by the SMC will be made 
whether to proceed with full randomization (1:1:1) and dosing of the remaining study 
participants (Cohort 2, up to n=24). Due to the impact of the COVID-19 pandemic surge in cases 
affecting enrollment and participant retention, the study has been truncated to 23 participants 
randomized, with 7-8 participants per study arm. 
Subjects will be stratified based on their SARS-CoV-2 detectable antibody status (>LLOQ, but 
≤80 AU/mL on the Diasorin LIAISON SARS-CoV-2 S1/S2 IgG antibody assay) and 
undetectable antibody (≤LLOQ) at screening. If the proportion of subjects in one stratum is high, 
that stratum may be closed to allow for enrollment in the other stratum. 
Randomization lists will be generated by a Randomization and Trial Supply Management 
(RTSM) system vendor. Details on the randomization procedures will be provided in the 
Pharmacy Manual. Sites will not be permitted to view the randomization list, and subjects will be 
assigned to treatment arm according to their stratum and randomization order. 
3.4 
Description of Stopping Rules 
As described in Section 3.3.2, the SMC will evaluate safety data for sentinel participants to 
determine if the study can proceed to enroll remaining participants. The following related safety 
stopping rules apply throughout the entire study and will be managed by the SMC: 
Study enrollment and IP administration will be temporarily held by the Sponsor if any of the 
following occur, pending further evaluation: 
• One or more SAE(s).  
• Three or more of the same AEs classified as grade 3 severity. 
• Three or more hypersensitivity AEs classified as grade 2 severity. 
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These events will be reviewed by the SMC and a recommendation will be made regarding IP 
administration, continuation of study, or study termination. The procedures for SMC notification 
and review of AEs will be outlined in the SMC Charter. 
3.5 
Accountability Procedures 
The investigator (or designee) is responsible for maintaining accurate inventory records of the 
investigational product.   
Refer to Section 5.1.5 for Investigational Product Accountability. 
3.6 
Maintenance of Study Intervention Randomization 
As this study will be open label, there are no procedures for breaking randomization codes. Refer 
to Section 3.3.2 for Treatment Assignment/Randomization. 
3.7 
Data Directly Recorded on the Case Report Form 
There are no planned data to be recorded directly on the eCRF that would be considered source 
data.  
Refer to Section 9.3. 
3.8 
End of Study 
End of study is defined as the last subject’s last visit (LSLV). An individual participant is 
considered to have completed the study after completing the last study visit, Day 57 and all AEs 
have been followed to resolution or diagnosis. The study could be terminated early if stopping 
rules are triggered and the SMC or Emergent determines the study should be stopped.  
3.8.1 Terminating the Study 
The Sponsor reserves the right to stop or terminate the study at any time for clinical or 
administrative reasons.  
Any decision to voluntarily suspend or terminate a clinical study will be carefully reviewed and 
fully justified. The Sponsor will notify the applicable regulatory authority country regulatory 
agency of any suspension or termination, along with justification for terminating the study. 
The PI must notify the IRB/IEC/REB in writing of the study’s completion or early termination.  
The Sponsor must receive a copy of the notification letter from the IRB/IEC/REB indicating 
receipt of the completion or early termination letter. 
3.8.2 Terminating the Study at an Individual Investigational Site 
An investigational site may be terminated from the study at the discretion of the Sponsor or 
IRB/IEC/REB for reasons such as non-compliance, lack of recruitment, fraud or blacklisting by 
the regulatory authorities, etc.  
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The Sponsor may decide to replace a terminated investigational site.  
4 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
Subject Inclusion Criteria 
All participants must meet all the following inclusion criteria in order to be enrolled into the 
study: 
1. 
Able and willing to provide written informed consent (voluntarily signed by the 
participant) prior to performing study procedures. 
2. 
Females and males 18–59 years of age.  
3. 
Have a BMI less than or equal to 35.0 kg/m2. 
4. 
Healthy, based on medical history (no chronic disease, no chronic therapy, no ongoing 
acute condition within four weeks prior to dosing), normal physical examination (no 
clinically significant findings in the opinion of the investigator), and screening laboratory 
assessments (no clinically significant findings in the opinion of the investigator).  
5. 
No clinical symptoms suspicious for COVID-19 infection, as well as SARS-CoV-2 IgM 
antibody negative and no laboratory evidence of current SARS-CoV-2 infection (i.e., RT-
PCR negative for SARS-CoV-2) at Screening. 
6. 
Females must not be pregnant, or trying to become pregnant as demonstrated by either of 
the following A or B:  
A. Not of childbearing potential: surgically sterile (at least six weeks post bilateral 
salpingectomy, bilateral oophorectomy, or hysterectomy); or post-menopausal 
(history of ≥12 consecutive months without menses prior to randomization in the 
absence of other pathologic or physiologic causes and confirmed by follicle FSH 
level ≥40 mIU/mL); OR 
B. Women of childbearing potential who are not planning to be pregnant during the 
study period and who meet all of criteria i–iii: 
i. 
Negative serum pregnancy test at the Screening Visit. 
ii. 
Negative urine pregnancy test on Day 1 (a positive test will result in 
discontinuation from intervention). 
iii. 
Using one of the following highly effective methods of contraception during 
the study:  
• Combined estrogen and progestogen, or progestogen-only hormonal 
contraception associated with inhibition of ovulation (e.g., implants, pills, 
patches) initiated ≥30 days prior to Study Day 1. 
• Intrauterine device or hormone releasing IUS inserted ≥30 days prior to 
Study Day 1. 
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7. 
Participant understands and agrees to comply with planned study procedures. 
4.2 
Subject Exclusion Criteria 
Participants who meet any of the following criteria cannot be enrolled: 
1. 
Use of any investigational product within 30 days or SARS-CoV-2 monoclonal 
antibodies and COVID-19 convalescent plasma within 90 days prior to Screening or 
anticipated receipt during the study follow-up period, or participant plans to participate in 
another clinical study during the study period.   
2. 
Receipt of 1 or 2 doses COVID-19 vaccine within 60 days prior to screening or 
anticipated receipt during the study follow-up period. 
3. 
SARS-CoV-2 IgG antibody levels >80 AU/mL as determined by the Diasorin LIAISON 
SARS-CoV-2 S1/S2 IgG antibody assay. 
4. 
Screening clinical laboratory test result greater than the laboratory's ULN for ALT, AST, 
random glucose, total and/or direct bilirubin, BUN, or creatinine. Other serum chemistry 
parameters that are not within the reference range will not be considered exclusionary 
unless deemed clinically significant by the PI. 
5. 
Positive laboratory evidence of current infection with HIV, HCV, or HBV. Note: Positive 
anti-HCV antibody result along with a negative HCV PCR would NOT be exclusionary. 
6. 
History of allergy or hypersensitivity to blood or plasma products or to COVID-HIG 
excipients (proline, PS80). 
7. 
History of allergy to latex or rubber. 
8. 
History of hemolytic anemia. 
9. 
History of IgA deficiency. 
10. Receipt of any blood product within the past 12 months. 
11. Plasma donation within 7 days or blood loss/donation (>450 mL) within 56 days of 
dosing. 
12. History of known congenital or acquired immunodeficiency or receipt of 
immunosuppressive therapy (e.g., prednisone or equivalent for more than two 
consecutive weeks within the past three months). 
13. History of thrombosis or hypercoagulable state with increased risk of thrombosis. 
14. Receipt of a live vaccine within 30 days prior to screening or anticipated receipt of a live 
vaccine during the study period. 
15. Currently pregnant, breastfeeding, or planning to become pregnant during the study. 
16. History of, or suspected substance abuse problem (including alcohol). 
17. Any planned elective surgery or procedure during the follow-up period that impacts study 
compliance. 
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18. Other condition which may place participant at increased risk due to participation in the 
study or may impact study compliance as determined by the investigator. 
19. An opinion of the investigator (or designee) that it would not be in the best interest of the 
individual to participate in the study. 
4.3 
Subject Withdrawal Criteria 
4.3.1 Withdrawal of Consent 
All participants are free to withdraw from participation in this study at any time, for any reason. 
The PI will request (but cannot require) such participants to provide the reason(s) for withdrawal 
of consent.  
Outreach will be made to ensure that participants who withdraw from the study during the active 
treatment or follow-up period will complete all safety and available assessments for the Early 
Withdrawal visit as outlined in this protocol. The PI should inform the participant that these 
assessments are for their own well-being and, if possible, for study purposes. Additional 
information regarding ongoing adverse events may be provided as a follow-up report.  
The participant must first agree to the collection of early withdrawal and safety assessments prior 
to the assessments, and this agreement must be documented in the source documents.  
Safety follow-up for adverse events should occur for all participants. 
4.3.2 Discontinuation of Intervention 
If applicable based on randomized route of administration, the injection(s) can be stopped if 
Grade 2 or higher or serious AE (anaphylaxis or hypersensitivity reaction) are observed. All 
participants should still be followed-up for the duration of the study for safety. Refer to Section 
5.1.4 for further information related to AEs and administration of IP.  
4.3.3 Subject Withdrawal Criteria 
The PI may withdraw a participant from further IP administration or participation in the study, at 
their discretion, if medically necessary or for reasons of noncompliance. The reason for 
withdrawal of any participant must be clearly documented on the study source documents and 
the appropriate electronic Case Report Form (eCRF). The PI is encouraged to consult the 
Sponsor prior to the withdrawal of any participant, except in the event of a medical emergency.  
The PI (and/or the Sponsor) may withdraw a participant from further IP administration or 
participation in the study for any of, but not limited to, the following reasons: 
• Lost to Follow-up 
• Lost to follow-up determination requires documentation of at least 3 unsuccessful 
attempts to contact participants.  
• Adverse Event 
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• Protocol Deviation 
• Pregnancy 
• Physician (i.e., PI) Decision 
• Withdrawal by Subject 
• Participant contracts COVID-19 
• Participant receives prohibited COVID-19 vaccination 
• Other 
Safety follow-up for adverse events should occur for all participants.  
Reasons for withdrawal of individual participants from the study prior to final protocol required 
visit and/or final safety follow-up are to be recorded on the CRF and subject source documents. 
A participant who is withdrawn from the study will not be re-entered into the study for any 
reason. 
4.3.4 Subject Replacement   
Participants who are discontinued or withdraw consent prior to baseline/randomization after 
signing consent will be replaced. Participants withdrawn from the study or who withdraw 
consent after randomization will not be replaced, regardless of whether they have been dosed. 
The study sample size determination has included consideration for some participants to be lost 
to follow-up or withdraw consent.  
5 
STUDY INTERVENTION 
5.1 
Investigational Product(s) 
Anti-SARS-CoV-2 Immunoglobulin Injection (Human), also referred to as COVID-HIG, is a 
hyperimmune product that consists of purified IgG fraction of human plasma containing 
antibodies (including neutralizing antibodies) to SARS CoV-2. The product is a clear to slightly 
opalescent and colorless or pale, yellow liquid essentially free of foreign particles. The final 
sterile liquid product contains 85-115 mg/mL of human plasma proteins (target 100 mg/mL), of 
which at least 90% is human IgG. COVID-HIG is formulated with 250 mM proline and 0.03% 
(w/w) PS80 and has a pH between 5.5 and 6.0 (target pH 5.8). The final product contains no 
preservatives. 
The potency of the final product is determined by a validated immunoassay that measures 
concentration of binding SARS-CoV-2 antibodies (with SARS-CoV-2 trimeric S protein as the 
antigen) in relation to a reference standard; the final drug product is also characterized by a wild-
type SARS-CoV-2 neutralization assay (refer to the most current version of the IB). 
COVID-HIG will be administered as a single ≈250,000 AU dose through an IM, SC, or IV route 
of administration. Based on a calculated potency of 29,282 AU/mL as assessed using a wildtype 
neutralization assay, this will equate to an 8.5 mL (~850 mg, based on a target protein 
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concentration of 100 mg/mL) dose that may be split across several sites, depending on route of 
administration.  
For additional information, refer to the IB and Pharmacy Manual for dose preparation 
instructions. 
5.1.1 Packaging and Labeling 
The final COVID-HIG product will be supplied in 6 mL Type 1 glass vials sealed with 20 mm 
siliconized bromobutyl rubber stoppers, aluminum seals, and plastic flip-off caps. The 
extractable volume per vial is 5.0 mL. Each vial is intended for single use. The vials will be 
provided in shelf cartons (35 vials per shelf carton). 
Anti-SARS-CoV-2 Immunoglobulin Injection (Human) [COVID-HIG] vial and shelf carton 
labels will include information to comply with local regulations for the country in which the 
study is conducted, in the appropriate language(s). 
For dispensing labels for secondary receptacles, see Section 5.1.3 Preparation. 
For more information, please refer to the most current version of the IB for COVID-HIG. 
5.1.2 Storage Conditions 
Anti-SARS-CoV-2 Immunoglobulin Injection (Human) [COVID-HIG] will be shipped to the 
sites at a temperature of 2–8°C (35–46°F). During shipment, the temperature will be monitored 
to ensure the required temperature conditions are maintained. The site pharmacist or designate 
will be responsible for checking the number of vials and the condition of the vials received and 
entering this information into the drug accountability records, reporting the condition to 
Emergent or designate. The site pharmacist or designate will be responsible for confirming the 
requisite storage temperature was maintained during the shipment and completing the relevant 
documentation, if applicable. (See Pharmacy Manual for details). COVID-HIG will be released 
for use by the site only after the temperature monitor results are reviewed and written 
authorization has been issued to the investigator/designate by Emergent/designate. Temperature 
excursions during shipment must be reported to Emergent/designate as per instructions provided 
in the Pharmacy Manual. 
Once at the site, COVID-HIG vials must be stored at 2–8C (35–46F) in a secured area until 
used for dose preparation by the assigned pharmacy staff. The temperature in the storage area 
should be monitored with properly calibrated instruments and recorded on a temperature log. 
Temperature excursions must be reported to Emergent or designate as per instructions provided 
in the Pharmacy Manual. 
For further information, refer to the COVID-HIG IB and the Pharmacy Manual. 
5.1.3 Preparation 
The site must maintain documentation of a clear written formalized procedure for study drug 
preparation activities (including any sample labels and documentation to be completed), and 
documented training and delegation of the activity to appropriate study staff. 
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The pharmacy staff assigned to this study will prepare COVID-HIG as follows: 
Visually inspect the vials to ensure the product is free from particulate matter and discoloration 
prior to dose preparation and administration. The solution should be clear or slightly opalescent 
and colorless or pale yellow. Do not use solutions that are cloudy or have particulates.  DO 
NOT SHAKE VIALS; AVOID FOAMING. 
Prepare COVID-HIG at the required dosage as per Pharmacy Manual instructions. In general, 
perform the following:  
• Remove the protective caps from the product vials. 
• Wipe the exposed central portion of the rubber stopper with an isopropyl alcohol swab. 
• Withdraw the vial content using standard aseptic techniques and transfer the content into 
an appropriately sized receptacle.  
Once punctured, use the vial contents to prepare the dose promptly. COVID-HIG contains no 
preservative. Vials are for single use only. Do not reuse or save vial(s) for future use.  
Retain used and empty vials for drug accountability as per instructions in the Pharmacy Manual. 
The label on final dispensed dose will capture at a minimum: participant identification (ID), 
expiry date of the prepared dose (i.e., <24 hours after dose preparation), the investigator’s name, 
protocol code (EBS-CVH-006) and caution statement “For investigational use only”.  
Record date of the injection, start/stop times (where applicable) and the total volume 
administered. For further details, refer to the Pharmacy Manual. 
5.1.4 Investigational Product Administration 
Investigational product is to be administered only under the direct supervision of the PI or 
qualified investigational site personnel. An acute observation period after IP administration will 
occur (Section 6.5.1) where the participant will be monitored by study staff for signs of an acute 
adverse reaction after administration. 
Participants will be monitored in-clinic closely during injection and overnight in-clinic. A 
detailed safety follow-up for participants will occur one day and three days post-dose (Days 2 
and 4). 
If AEs occur during or immediately after the injection, such as grade 1 (mild) events of flushing, 
headache, chills, fatigue, nausea, slight changes in pulse rate or blood pressure, slow the rate of 
injection until symptoms subside or until dose is completely administered (at discretion of the 
investigator). If the recipient experiences grade 2 (moderate) or higher AEs such as chest pain, 
difficulty breathing, vomiting, arthralgia, or severe headache, unresponsive to slowing or 
stopping the injection, halt the injection and wait until symptoms subside to determine whether 
to resume injection.  
Depending on the route of administration, the participant may receive multiple injections of 
COVID-HIG to achieve the full dose in the study arm. Stop the injection if serious AEs develop 
(e.g., anaphylaxis, severe hypersensitivity reactions) and administer appropriate medical 
management. Do not complete the injection.  
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For additional details regarding administration of COVID-HIG please see the IB and Pharmacy 
Manual. 
5.1.4.1 
Intramuscular Administration 
COVID-HIG should be warmed to room temperature before use. The dose can be split into 
multiple injections to be administered slowly in both thigh muscles to reduce discomfort. All 
injections should be administered over approximately two minutes or as directed by the PI. 
Additional details will be provided in the Pharmacy Manual.     
Date, time and locations of injections of COVID-HIG will be documented in the source 
documents and captured in eCRF. 
5.1.4.2 
Subcutaneous Administration 
COVID-HIG should be warmed to room temperature before use. The dose can be split into 
multiple injections with a maximum of 3 mL per injection. Each injection should be 
administered slowly at a different injection site in the abdomen (except for 2 inches (5 cm) 
around the navel), thigh or back of the upper arm. The waistline should be avoided. It is 
recommended to use different quadrants of the abdomen or upper thighs or back of upper arms to 
space apart each dose. All injections should be administered over approximately two minutes or 
as directed by the PI. Additional details will be provided in the Pharmacy Manual. 
Date, time and locations of injections of COVID-HIG will be documented in the source 
documents and captured in eCRF. 
5.1.4.3 
Intravenous Administration 
COVID-HIG should be warmed to room temperature before use. Administer COVID-HIG by IV 
infusion through a dedicated IV line as a bolus IV injection. Administer the prepared dose slowly 
over five minutes at a rate of 1.7 mL/min or as directed by the PI. Additional details will be 
provided in the Pharmacy Manual. 
Date and time of COVID-HIG administration will be documented in the source documents and 
captured in eCRF.  
5.1.5 Investigational Product Accountability 
The investigator is responsible for maintaining accurate inventory records of COVID-HIG bulk 
product. The pharmacist or pharmacy staff designee will inventory all COVID-HIG shipments 
upon receipt, acknowledge possession by signing all required documentation, and returning these 
to the sponsor. The investigator must ensure that all drug supplies are kept in a secure location in 
the site pharmacy in accordance with recommended storage conditions. A site pharmacist or a 
designated individual not involved in study treatment administration/study assessments will 
maintain a current inventory and ongoing record of test material supplies using the Drug 
Accountability Form provided by the sponsor.  This inventory record for the COVID-HIG will 
include: 
• Protocol name, number, and sponsor 
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• Product name and description 
• Study site and investigator name 
• Product lot number and date of manufacture and/or Use-by/Expiry/Re-test date 
• Number of vials dispensed, date and time of dispensing, and study participant for whom 
product was dispensed 
• Product balance 
• Name and title of qualified individual dispensing product. 
These records will be reviewed by representatives contracted out by the sponsor and may be 
reviewed by regulatory agencies. 
5.1.5.1 
Investigational Product Resupply 
Resupply of IP may be requested through the study monitor. 
5.1.5.2 
Used or Partially Used Investigational Product 
At the end of the study or upon request of Emergent, all unused, partially used, or empty vials 
will be returned to Emergent or destroyed at the site with a record of disposition maintained, as 
directed by Emergent. 
5.2 
Prior and Concomitant Medications 
Participants should not take prescription medications at the time of enrollment (with the 
exception of hormonal contraceptives for WOCBP). Participants must abstain from alcoholic 
beverages for at least 48 hours prior to baseline assessments. 
The use of concomitant medication that the investigator considers unnecessary will be 
discouraged. No pre-infusion pre-medication will be permitted. Medications to treat minor 
ailments (headache, nausea, etc.) will be allowed at the discretion of the investigator. Study 
participants will be questioned about all concomitant medications during in-clinic follow-up 
visits including all herbal preparations and non-prescription medications that they are 
consuming. This information will be recorded on the appropriate source documents and captured 
in the eCRF.  
Concomitant medications taken in relation to adverse events and/or COVID-19 will be noted.  
5.2.1 Prohibited and/or Restricted Medications 
Prescription medications (with the exception of hormonal contraceptives for females) and certain 
concomitant medications are prohibited and/or restricted for at least 30 days before Day 1 and 
during the study. Over-the-counter drugs, supplements, vitamins, and herbal preparations will be 
assessed and documented in medical history. 
Elective blood-or plasma-derived products/plasma exchange procedures during the study are not 
allowed. If these are required for medical emergency reasons; the use of these types of 
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products/procedures and the reason for such use will be recorded by the investigator (or 
designate) in the source documents and captured in the eCRF. 
Participants must be advised to abstain from alcoholic beverages for at least 48 hours prior to 
screening assessments. The following are prohibited/restricted medications: 
• Any commercially available live vaccine is prohibited from at least 30 days prior to 
dosing and through to the end of the study follow-up (Day 57).  
• Any COVID-19 vaccination dose is prohibited at least 60 days prior to Screening and 
through to the end of the study follow-up (Day 57).  
The use of medications considered prohibited is not allowed. Medications to treat minor ailments 
(headache, nausea, etc.) are allowed at the discretion of the investigator. Study participants will 
be questioned about all concomitant medications including all herbal preparations and non-
prescription medications. All concomitant medication will be recorded on the CRF, including 
whether the medication is taken in relation to an adverse event.  
The Medical Monitor (MM) should be consulted for any questions about prohibited or restricted 
medication usage.  
5.3 
Rescue Medications 
Not applicable. 
5.4 
Procedures for Monitoring Subject Compliance 
Participants will be monitored for study compliance through solicited responses to questions 
regarding any changes to concomitant medications and vaccinations at each visit. Counselling 
regarding preventing SARS-CoV-2 infection and contraceptive use (if WOCBP) will occur at 
each visit to help ensure the participant remains eligible for study participation.     
6 
STUDY PROCEDURES AND ASSESSMENTS PER VISIT 
6.1 
Screening 
Screening period is within 14 days prior to Day 1.  
Eligible participants will first undergo informed consent counseling. Once informed consent has 
been obtained, participants will undergo a screening visit to ascertain their eligibility in this 
study. The Screening visit assessments will include: 
• Written informed consent. 
• Collection of demography information (date of birth, sex, race/ethnicity, height, body weight, 
BMI).  
• Review of inclusion/exclusion criteria. 
• Medical history and ongoing medications.  
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• Perform rapid SARS-CoV-2 IgM/IgG antibody test and SARS-CoV-2 antigen test prior to 
collecting other samples. Only proceed further with screening assessments if negative for 
SARS-CoV-2 IgM and antigen. 
• Complete physical examination: to include assessment of general appearance, and the 
following body systems: head-neck, respiratory, cardiovascular, gastrointestinal, 
dermatological, lymphatic/hematological, musculoskeletal, neurological, 
metabolic/endocrine.  
• For WOCBP: assess contraception use (>30 days prior to dosing) and instruct on use of 
contraception from the time of Screening through end of study (up to Day 57).  
• Serum pregnancy test for WOCBP and FSH testing for post-menopausal women. 
• Vital signs (resting ≥10 minutes) include body temperature, pulse, respiratory rate, sitting 
blood pressure, and SpO2 (pulse oximetry).  
• Local safety laboratory assessments:  
• Chem 7 panel [Na+, K+, Cl−, HCO3−, BUN, creatinine, glucose], total and direct 
bilirubin, ALT, AST, LDH.  
• CBC (red blood cells, white blood cells, hemoglobin, hematocrit) with differential 
(neutrophils, eosinophils, basophils, monocytes, lymphocytes).  
• Urinalysis. 
• Viral marker testing [Human immunodeficiency virus 1/2 (HIV 1/2) antibody, HBV surface 
antigen, HCV antibody]. 
• Urine drug screening (e.g., amphetamines, barbiturates, benzodiazepines, cannabinoids, 
cocaine opioids). 
• Nasopharyngeal swab sample for SARS-CoV-2 RT-PCR test.  
• Serum sample for the Diasorin LIAISON SARS-CoV-2 S1/S2 IgG antibody test. 
• Provide counselling to participants on precautions/measures to prevent contracting SARS-
CoV-2 infection. 
• Assess for any COVID-19 symptoms or SARS-CoV-2 exposure. 
• Monitor/assess AEs related to study procedures. 
6.2 
Re-Screening 
Participants may be re-screened once at the discretion of the investigator in consultation with the 
sponsor’s MM. Re-screened participants outside the screening period will be assigned a new 
subject identification number.   
6.3 
Pre-dosing (Day -1) – In-patient overnight assessment 
• If required, update medical history and ongoing medications. 
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• Inquire if the participant has had a suspected or confirmed exposure to SARS-CoV-2 or 
developed COVID-19 symptoms in the period of Screening visit to Day 1. 
• Perform rapid SARS-CoV-2 IgM/IgG antibody test. 
• If WOCBP, perform UPT. 
• If WOCBP, confirm use of contraceptives. 
• Alcohol breath test. 
• Confirm eligibility. 
• Collect pre-dose serum sample for SARS-CoV-2 baseline antibody PK assessment. 
• Collect NP swab sample for SARS-CoV-2 RT-PCR test. 
• Targeted physical exam, if clinically indicated. 
• Monitor/assess AEs related to study procedures. 
6.4 
Baseline (Visit 1, Day 1) Assessments – Randomization and Dosing 
Perform the following assessments on Day 1 as an in-clinic overnight visit: 
• Collect pre-dose serum sample (within 2 hours prior to dosing) for SARS-CoV-2 baseline 
antibody PK assessment. 
• Vital signs (resting ≥10 minutes) [body temperature, blood pressure (seated), pulse, SpO2 
(pulse oximetry) and respiratory rate]; within 2 hours prior to dosing. 
• Randomize. Stratification will be based on the Diasorin LIAISON SARS-CoV-2 S1/S2 IgG 
antibody status (positive/negative) from screening visit.  
• Administer randomized study treatment.  
• Monitor/assess AEs before, during and post-administration of the injection in the clinic 
overnight.  
• Vital signs (resting ≥10 minutes) [body temperature, blood pressure (seated), pulse, SpO2 
(pulse oximetry) and respiratory rate] at 30 minutes (±5 mins) and 1 hour (±10 mins) post-
administration (from end of infusion/injection). 
• Serum samples for post-dosing assessment of SARS-CoV-2 antibodies for PK at 1 hr 
±10min, 2 hrs ±15min, 4 hrs ±15min, 8 hrs ±30min, and 12 hrs ±30min (from end of 
infusion/injection).  
• Targeted physical exam, if clinically indicated. 
• Provide counseling to participants on precautions/measures to prevent contracting SARS-
CoV-2 infection. 
• Record any concomitant medications (if applicable). 
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6.5 
Investigational Product Administration (Visit 1, Day 1) 
The participant must receive COVID-HIG on the Day 1 visit which much occur within 14 days 
after screening. Participants will be randomized to receive a single dose of ≈250,000 AU of 
COVID-HIG as either an IM, SC, or IV infusion following confirmation of eligibility and 
collection of samples outlined in Section 6.3.   
COVID-HIG is to be administered only under the direct supervision of the PI or a qualified sub-
investigator identified on the Form FDA 1572.  Under no circumstances will the PI allow 
COVID-HIG to be used other than as specified in the protocol. 
Refer to Section 5.1.4 for details on Investigational Product Administration.  
6.5.1 Acute Observation After Investigational Product Administration 
The participant will be monitored by study staff for signs of an acute adverse reaction overnight 
in-clinic. Vital signs (resting ≥10 minutes) will be assessed at 30 minutes (±5 mins) and 1 hour 
(±10 mins) after administration. 
6.6 
Scheduled Study Visits 
Day 2, 3, 4, 6, 8, 15, 29, 43 
Visits are conducted as in-clinic or telemedicine/home healthcare follow-ups.  
Visit windows are as follows (in relation to Day 1):  
Day 2: (1±0.5 days), Day 3: (2±0.5 days), Day 4: (3±0.5 days), Day 6: (5±0.5 days), Day 8: (7±1 
day), Day 15: (14±2 days), Day 29: (28±2 days), Day 43: (42±3 days).  
*Visits are indicated as calendar days, while the time post-dosing and the visit windows are 
indicated in the brackets.  
If randomized to IV group (Arm 3), omit visits on Day 3 and Day 6.  
Perform the following in-clinic or via telemedicine follow-up: 
• Assessment of AEs and concomitant medications (in-clinic or telemedicine).  
• Targeted physical exam, if clinically indicated. Based on the investigator’s assessment of 
AEs/concomitant medication during telemedicine follow-up, an unscheduled visit (in-clinic) 
can be arranged to conduct a targeted physical exam. The investigator can also refer the 
subject to their healthcare provider or urgent care if more immediate medical attention is 
required.  
• If WOCBP, confirm use of contraceptives.  
• Provide counseling to participants on precautions/measures to prevent contracting SARS-
CoV-2 infection. 
• Only if participant becomes positive for SARS-CoV-2 at any time post-dosing during the 
study period: assess clinical status based on an Ordinal Outcome scale (Appendix II). 
Perform assessments via telemedicine if possible.  
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In-clinic staff or home healthcare attendant to perform the following: 
• Serum sample for SARS-CoV-2 antibody PK assessment. 
• Blood sample for safety laboratory assessments (chem 7 panel, total and direct bilirubin, 
ALT, AST, LDH, CBC) at Day 2 and Day 4 only. At other follow-ups, collect sample only if 
clinically indicated (as per investigator’s discretion). 
• Sample for urinalysis at Day 2 and Day 4 only. At other follow-ups, collect sample only if 
clinically indicated (as per investigator’s discretion).  
• Vital signs (resting ≥10 minutes) [body temperature, blood pressure (seated), pulse, SpO2 
(pulse oximetry) and respiratory rate] at Day 2 and Day 4 only. At other follow-ups perform 
only if clinically indicated (as per investigator/sub-investigator’s assessment). 
• NP swab sample for SARS-CoV-2 RT-PCR test on Day 8, Day 15 Day 29, and Day 43. At 
other follow-ups perform only if clinically indicated (as per investigator/sub-investigator’s 
assessment). 
If any participants become positive for SARS-CoV-2 at any point during the study follow-up 
period, all subsequent visits should be done via telemedicine (except for the Day 57 or the 
withdrawal visit), unless an in-person visit is deemed clinically necessary by the PI. 
6.7 
Unscheduled Visits 
Visit is conducted in-clinic or as telephone/home healthcare follow-up. 
Participants can be evaluated during an unscheduled visit if the investigator deems it necessary to 
further follow-up on participant’s safety. 
Any unscheduled visit(s) must be recorded on the Unscheduled Visit eCRF.  
The following may be performed at an unscheduled visit at investigator’s discretion in-clinic or 
via telemedicine follow-up. If telemedicine follow-up requires sample collection or in-person 
assessments, an in-clinic or at-home follow-up should be scheduled: 
• Assessment of AEs and concomitant medications.   
• Targeted physical exam, if clinically indicated. 
• Nasopharyngeal swab samples for SARS-CoV-2 RT-PCR test (as per investigator’s 
discretion assessing COVID-19 symptoms/exposure). 
• Safety laboratory assessments: 
• Blood sample for Chem 7 panel, total and direct bilirubin, ALT, AST, LDH, CBC with 
differential) if clinically indicated (as per investigator’s discretion during in-clinic or 
telemedicine follow-up).  
• Sample for urinalysis if clinically indicated (as per investigator’s discretion during in-
clinic or telemedicine follow-up). 
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• Vital signs (resting ≥10 minutes) [body temperature, blood pressure (seated), pulse, SpO2 
(pulse oximetry) and respiratory rate]. Note: perform only if clinically indicated (as per 
investigator’s discretion). 
• If WOCBP, confirm use of contraceptives. 
• If WOCBP and only if clinically indicated, perform serum pregnancy test. 
• Provide counseling to participants on precautions/measures to prevent contracting SARS-
CoV-2 infection. 
• Only if participant becomes positive for SARS-CoV-2 at any time post-dosing during the 
study period: assess clinical status based on an Ordinal Outcome Scale (Appendix II). 
Perform assessments via telemedicine if possible.  
Participants may be referred for emergency medical care (i.e., to emergency room, for 
hospitalization), if clinically indicated. Participants will inform the site of any emergency 
medical care (either by phone call or at the next in-clinic visit). Any healthcare emergency 
encounter will be documented in the source documents and captured in the eCRF. 
6.8 
End of Study Visit (Visit 10, Day 57) 
Visit is conducted in-clinic or as telemedicine/home healthcare follow-up. 
Visit window for Day 57: 56±3 days (in relation to Day 1 visit). 
Perform the following in-clinic or via telemedicine follow-up: 
• Assessment of AEs and concomitant medications.   
• Targeted physical exam, if clinically indicated. 
• If WOCBP, confirm use of contraceptives.  
• Provide counseling to participants on precautions/measures to prevent contracting SARS-
CoV-2 infection. 
• Only if participant becomes positive for SARS-CoV-2: assess clinical status based on an 
Ordinal Outcome Scale (Appendix II). Perform assessments via telemedicine if possible.  
In-clinic staff or home healthcare attendant to perform the following:  
• Serum sample for SARS-CoV-2 antibody PK assessment.  
• Safety laboratory assessments: 
• Blood sample for Chem 7 panel, total and direct bilirubin, ALT, AST, LDH, CBC with 
differential) if clinically indicated (as per investigator’s discretion during in-clinic or 
telemedicine follow-up).  
• Sample for urinalysis if clinically indicated (as per investigator’s discretion during in-
clinic or telemedicine follow-up). 
• Blood sample for viral marker testing (HIV 1/2 antibody, HBV surface antigen, HCV 
antibody). 
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• Vital signs (resting ≥10 minutes) [body temperature, blood pressure (seated), pulse, SpO2 
(pulse oximetry) and respiratory rate]. Note: perform only if clinically indicated (as per 
investigator’s discretion). 
• Nasopharyngeal swab sample for SARS-CoV-2 RT-PCR test. 
If a subject tests positive for SARS-CoV-2 during the study: As the Day 57 visit necessitates an 
in-person safety assessment (viral marker testing), this visit should proceed in-person, if 
possible. In-person visits should be performed after the infectious period has passed to reduce 
risk of transmission and should follow local rules and regulations. If a participant tests positive 
for SARS-CoV-2 immediately prior to or at the in-person Day 57 visit, reasonable efforts will be 
made to collect as many of the required samples from the Day 57 visit in a manner that reduces 
the risk of SARS-CoV-2 transmission, according to local rules and regulations. 
6.9 
Early Withdrawal/Termination Visit 
Early withdrawal visit procedures will be performed for participants who received study 
treatment and who withdrew from the study prior to Day 57. Collect as much of the safety data 
as possible. If a subject tests positive for SARS-CoV-2 during the study and a subject withdraws 
prior to Day 57, collect as much safety data as possible while reducing the risk of transmission 
and following local rules and regulations.  
If the participant withdrew consent, the PI must get participant agreement to perform the early 
withdrawal assessments and document this agreement in the source documents.  
Perform the following in-clinic or via telemedicine follow-up: 
• Assessment of AEs and concomitant medications.   
• Targeted physical exam, if clinically indicated. 
• If WOCBP, confirm use of contraceptives.  
• Provide counseling to participants on precautions/measures to prevent contracting SARS-
CoV-2 infection. 
• Only if participant becomes positive for SARS-CoV-2: assess clinical status based on an 
Ordinal Outcome Scale (Appendix II). Perform assessments via telemedicine if possible.  
In-clinic staff or home healthcare attendant to perform the following: 
• Serum sample for SARS-CoV-2 antibody PK assessment.  
• Safety laboratory assessments: 
• Blood sample for Chem 7 panel, total and direct bilirubin, ALT, AST, LDH, CBC with 
differential) if clinically indicated (as per investigator’s discretion during in-clinic or 
telemedicine follow-up).  
• Sample for urinalysis if clinically indicated (as per investigator’s discretion during in-
clinic or telemedicine follow-up). 
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• Blood sample for viral marker testing (HIV 1/2 antibody, HBV surface antigen, HCV 
antibody). 
• Vital signs (resting ≥10 minutes) [body temperature, blood pressure (seated), pulse, SpO2 
(pulse oximetry) and respiratory rate]. Note: perform only if clinically indicated (as per 
investigator’s discretion). 
• Nasopharyngeal swab sample for SARS-CoV-2 RT-PCR, if clinically indicated (as per 
investigator/sub-investigator’s assessment). 
7 
ASSESSMENT OF PHARMACOKINETICS  
In this study, only pharmacokinetic assessments will be performed to evaluate study objectives. 
The assessments described below will be used to derive serum concentrations of SARS-CoV-2 
antibodies (by testing PK samples with a validated immunobinding IgG assay) that will be used 
to calculate the PK parameters.   
7.1 
Description of Study Assessments 
Assessments that will be performed according to standard practices as scheduled in the Schedule 
of Events are not described further in this section. The visit time points of these procedures and 
assessments can be found in the Schedule of Events (Table 2).  
Specific procedures related to collection, processing, storage, and shipment of the samples are 
provided in the Laboratory Manual. For the timing of sample collection refer to the Schedule of 
Events (Table 2). 
7.1.1 Efficacy Outcomes 
Not applicable. 
7.1.2 Pharmacokinetic Samples 
Serum samples will be collected as described for all participants for PK analyses as described in 
Section 7.3. For duration of sample retention see Section 12.6.   
All serum samples must be taken as closely as possible to the specified times in relation to the 
start of IP administration (visit windows provided in Section 6). 
Refer to the Laboratory Manual for information regarding samples to be collected and tests to be 
completed.  
7.1.3 Nasopharyngeal Samples 
Nasopharyngeal swabs will be used to collect samples from the nasopharynx to measure if the 
participant is infected with SARS-CoV-2. Nasopharyngeal swab samples for SARS-CoV-2 RT-
PCR test will be collected at Screening, Day -1, Day 8, Day 15, Day 29, Day 43, Day 57, and as 
clinically indicated (as per investigator/sub-investigator’s assessment of the participant in-clinic 
or during the telemedicine follow-up) and tested by the Phase 1 unit. 
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7.1.4 Non-standard Safety Outcomes 
There are no non-standard safety outcomes.  
7.2 
Specification of the Outcome Measures 
Blood will be drawn to collect serum to measure SARS-CoV-2 antibodies and for safety 
laboratory assessments.  
Refer to the Laboratory Manual for information regarding samples to be collected and tests to be 
completed. 
7.3 
Methods and Timing for Assessing and Recording of Outcome Measures  
Pharmacokinetic parameters of COVID-HIG administered IM, SC, or IV as a single dose will be 
determined in healthy adults (see Section 9.4.2). The samples drawn at the time points described 
below will be used to derive serum concentrations of SARS-CoV-2 antibodies (by testing PK 
samples with a validated immunobinding IgG assay) that will be used to calculate the PK 
parameters. The immunobinding IgG assay will be performed at the facility outlined in the EBS-
CVH-006 Laboratory Manual.  
Analysis of PK will include PK sample test results (from samples collected by assigned site 
staff) from pre-dose on Day 1 and post-dose timepoints at Day 1: 1 hour (±10 mins), 2 hour (±15 
mins), 4 hour (±15 mins), 8 hour (±30 mins) and 12 hour (±30 mins) post-infusion. In addition, 
the following post-dose timepoints will be included (brackets indicate days after injection on 
Day 1): Day 2 (1±0.5 days), Day 3 (2±0.5 days), Day 4 (3±0.5 days), Day 6: (5±0.5 days), Day 8 
(7±1 day), Day 15 (14±2 days), Day 29 (28±2 days), Day 43 (42±3 days), and Day 57 (56±3 
days). The IV arm (Arm 3) will not have data for post dose samples on Day 3 or Day 6 as these 
will not be collected. 
8 
SAFETY ASSESSMENTS AND REPORTING 
The safety of COVID-HIG will be assessed by collection of AEs, laboratory test results (blood 
chemistry and hematology, urinalysis), concomitant medications, vital signs, and physical exam 
results. 
The occurrence of AEs will be monitored throughout all phases of the study and will cover all 
participating subjects. Any medical history changes that occur after screening but before dosing 
will be captured as an AE. Any AE that occurs after screening but before dosing will be 
documented in the source documents and captured in EDC if subject is randomized. Capture of 
treatment emergent adverse events (TEAEs) starts from the time of COVID-HIG administration 
and until the end of study period (up to Day 57 visit). Unanticipated problems related to study 
procedures may be collected following enrollment.  
Adverse events are to be elicited by the investigator (or designate) by asking the participant non-
leading questions. The association of the AE to COVID-HIG is to be judged by the investigator 
as related or unrelated (see Section 8.1.9 below). 
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8.1 
Definitions 
8.1.1 Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and that does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. 
Notes:  
• A diagnosis should be captured as an adverse event term and signs and symptoms should 
be captured only in the absence of a unifying diagnosis. If a diagnosis is ultimately made, 
it should replace the previous report based on signs and symptoms.  
• In the event that there are multiple diagnoses, then all diagnoses should be captured.  
• The worsening of an existing sign, symptom or disease is also considered to be an AE.  
• An abnormal laboratory finding deemed by the PI (or designee) as not clinically 
significant will not be captured as an AE, but an abnormal laboratory finding that 
worsens after dosing with the investigational product, from not clinically significant to 
clinically significant, is considered an AE.  
• Surgical procedures are not AEs. They are the action taken to treat a medical condition. 
Interventions that were planned prior to study entry for medical conditions that started 
prior to study entry but did not worsen during the clinical study are not reported as AEs. 
8.1.2 Serious Adverse Event 
An SAE is any untoward medical occurrence that: results in death, is life threatening, requires 
inpatient hospitalization or prolongation of existing hospitalization, results in persistent or 
significant disability/incapacity or substantial disruption of the ability to conduct normal life 
functions, or is a congenital anomaly/birth defect. 
Important medical events which may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, they 
may jeopardize the patient or subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 
Notes:  
• Death is an outcome and not an event. The condition leading to death is the event. If no 
other information regarding the cause of death is available, the event will be considered 
“Unspecified Adverse Event”.  
• Overnight stays at hospital/clinic that occurs during a trial for social reasons (e.g., 
transportation difficulties, respite care) is not considered to be a hospitalization event. 
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8.1.3 Adverse Drug Reaction 
A response to a medicinal product which is noxious and unintended [DIR 2001/83/EC Art 
1(11)]1. Response in this context means that a causal relationship between a medicinal product 
and an AE is at least a reasonable possibility (see Annex IV, ICH-E2A Guideline).   
8.1.4 Suspected Unexpected Serious Adverse Reaction 
Suspected Unexpected Serious Adverse Reaction (SUSAR) is the term used to refer to an AE 
that occurs in a clinical trial subject, which is assessed by the Sponsor and or PI as being 
unexpected, serious and as having a reasonable possibility of a causal relationship with the IP.   
8.1.5 Adverse Events of Special Interest 
Adverse events of special interest (AESIs) are AEs (serious or non-serious) that are of scientific 
and medical concern specifically related to the sponsor’s product or program for which ongoing 
monitoring and rapid communication by the investigator to the sponsor may be appropriate. Such 
events may require further investigation in order to characterize and understand them. In this 
study, there are no AESIs.  
8.1.6 Solicited Adverse Event(s)   
A solicited adverse event (solicited AE) is a protocol-specified AE about which the PI (or 
designee) proactively asks the subjects during a protocol-specified time period. There are no 
solicited adverse events in this study.  
8.1.7 Unsolicited Adverse Event 
An unsolicited adverse event (unsolicited AE) is an AE that is spontaneously reported by the 
subject or discovered by the PI. Any newly reported/identified AE following dosing or an 
increase in the severity/frequency of a previously reported condition prior to dosing regardless of 
causal relationship with investigational product or procedure is considered an 
unsolicited/spontaneous event. 
8.1.8 Severity of Adverse Events 
All AEs (clinical and laboratory abnormalities) irrespective of relationship to study treatment, 
including those that are not of a serious nature and those that are expected, will be documented 
by the investigators (or designate) in the source documents and appropriately recorded on AE 
eCRF. All AEs will be examined by the investigator or sub-investigator(s) for assessment of AE 
severity using the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events 
(see Appendix I). For AEs that are not included in the DAIDS AE Grading Table, use the 
following generic scale is: 
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Table 5 
Generic AE Grading Scale 
Grade 1  
(mild) 
Mild symptoms causing no or minimal interference with usual social & functional activities 
with intervention not indicated 
Grade 2 
(moderate) 
Moderate symptoms causing greater than minimal interference with usual social & functional 
activities with intervention indicated 
Grade 3 
(severe) 
Severe symptoms causing inability to perform usual social & functional activities with 
intervention or hospitalization indicated 
Grade 4 
(potentially life-
threatening)  
Potentially life-threatening symptoms causing inability to perform basic self-care functions 
with intervention indicated to prevent permanent impairment, persistent disability 
Grade 5 (death) 
Death 
8.1.9 Causality of Adverse Events  
The PI is responsible for the assessment of the causality of an adverse event and the Sponsor’s 
MM will also assess SAE causality, independent of the PI.    
The following guidelines are provided for this assessment. 
• Unrelated: No relationship between the investigational product and the reported event 
• Possibly related: The event follows a reasonable temporal sequence from the time of 
administration of investigational product and/or follows a known response pattern to the 
investigational product but could also have been produced by other factors. 
• Probably related: A reasonable temporal sequence of the event with administration of IP 
exists and based on the known response to the investigational product, known or previously 
reported adverse reactions to the IP or similar products, or in the PI’s (or designee) clinical 
judgment the association of the event with the IP seems likely. 
• Definitely related: A clinical event, including laboratory test abnormality, occurring in a 
plausible time relationship to IP administration, and which cannot be explained by concurrent 
disease or other drugs or chemicals (e.g., injection site pain, anaphylaxis, TRALI). The 
response to withdrawal of the IP (DECHALLENGE) should be clinically plausible. The 
event must be definitive pharmacologically or phenomenologically, using a satisfactory 
RECHALLENGE procedure if necessary. 
When possible, de-challenge and re-challenge should be considered to assess the causality of the 
relationship between the AE and the IP. 
If the relationship between the AE and the IP is determined to be “possible” or “probable,” the 
event will be considered to be “related” to the investigational product, otherwise it will be 
considered “not related” for reporting purposes. 
8.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters 
All events that occur following screening until immediately before the first dose of IP on Day 1, 
will be recorded as an AE for randomized participants. Adverse event reporting is required for 
any new observation presenting after the first dose of IP or for a deterioration of baseline 
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condition (e.g., increased severity/frequency). Adverse events following first dose of IP will be 
considered TEAEs. Refer to Figure 1 below for timing of safety monitoring in this study. 
Occurrence of AEs will be monitored until the end of the study (Day 57) and will cover all 
participants. Study participants will be provided with a 24-hour telephone number to contact 
study personnel in case of an untoward reaction. Adverse events reported spontaneously by the 
participant and/or in response to an open question from the PI (or designee) or revealed by 
observation (e.g., during physical exam or from a clinical test result) will be recorded by the PI 
(or designee) on the AE eCRF if they occurred during the study period, regardless of causal 
association with the IP.  
Figure 2 
Reporting Periods for Adverse Events 
 
8.2.1 Solicited Adverse Events 
There are no solicited adverse events in this study. 
8.2.2 Safety Laboratory Tests 
It is the responsibility of the PI or designee to review the results of all screening and safety 
laboratory tests (including unscheduled lab tests) as they become available, initially for the 
assessment of study eligibility (screening laboratory test results, if not otherwise specified in the 
inclusion/exclusion criteria, should be within the central laboratory’s reference ranges, or, if 
outside such ranges, be assessed by the investigator as not clinically significant) and 
subsequently for the continuous safety monitoring of participants. 
The following standard safety laboratory tests will be performed in the study: 
• Blood chemistry: glucose, sodium, potassium, bicarbonate, chloride, BUN, creatinine, 
ALT, AST, LDH, bilirubin (direct, total). 
• Blood hematology (CBC, with differential): red blood cells, white blood cells, 
hemoglobin, hematocrit, with differential (neutrophils, eosinophils, basophils, 
monocytes, lymphocytes). 
• Urinalysis: appearance, bilirubin, color, glucose, ketones, leukocyte esterase, nitrite, 
occult blood, pH, protein, specific gravity, urobilinogen, microscopic examination (only 
if protein, nitrite, leukocyte esterase, or occult blood results are positive). 
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For each abnormal laboratory test result, the PI or designee needs to ascertain if this is a 
clinically significant change from baseline for that individual. This determination, however, does 
not necessarily need to be made the first time an abnormal value is observed. The PI or designee 
may repeat the laboratory test and/or request additional tests to verify the results of the original 
laboratory tests. The PI (or designee) will inform the MM of any unscheduled clinical laboratory 
testing, including but not limited to confirmatory testing of laboratory samples, with the 
exception that notification is not required for confirmatory testing for pregnancy, HCV, and HIV. 
Safety laboratory tests will be done at Screening, Day 2, and Day 4 visits, and can be done at any 
other visit if clinically warranted based on PI (or designee) discretion. The PI or designee may 
request the participant return to the clinic for an unscheduled visit for an assessment of clinical 
status. The decision to redraw laboratory tests will be made by the PI (with notification to the 
MM) and/or MM and will be based on the type and severity of the laboratory abnormality and 
the clinical status of the participant. If the original (retested sample) or repeat laboratory value is 
Grade 3 or higher, this will be considered an AE and will be recorded by the PI on the AE eCRF. 
Any other clinical laboratory abnormalities must also be reported as AEs if considered by the PI 
or designee to be a clinically significant change from baseline. 
Refer to Table 2 (Schedule of Events) for timing of the safety laboratory tests and Appendix I for 
toxicity grading to determine which abnormal labs should be evaluated as AEs (Grade 3 or 
higher). If the lab analyte does not have toxicity grading criteria specified in Appendix I, then the 
PI or designee will use the grading criteria for “illness or clinical AE” in Appendix I to assign the 
AE toxicity grading. If an abnormal laboratory test result is a sign of a disease or syndrome, the 
disease or syndrome will be recorded as the AE/SAE and not the abnormal laboratory result.    
8.2.2.1 
Drug Screen 
Urine drug screening (e.g., amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine 
opioids) will be performed at Screening visit.  
8.2.2.2 
Alcohol Screen 
An alcohol breath test will be performed on Day -1 in-clinic visit.    
8.2.2.3 
Viral Testing 
A blood sample will be collected for viral marker testing (HIV 1/2, HbsAg, HCV antibody, and 
HCV RNA only if positive for HCV antibody) to be performed at Screening visit and at the end 
of study visit (Day 57 or Early Withdrawal Visit). Viral marker testing may be performed at an 
unscheduled visit, as applicable. 
8.3 
Reporting Requirements for Immediately Reportable Events 
8.3.1 Principal Investigator’s Reporting Requirements 
The investigator will report all SAEs and confirmed pregnancies to Emergent within the 
electronic data capture within 24 hours of the investigator’s knowledge of occurrence. The SAE 
report should include a medical summary of the SAE. 
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An email notification will be sent to EBCI pharmacovigilance (PV) team through Medidata 
RAVE to: productsafety@ebsi.com.  
Applicable events must be entered into the validated EDC system. In the event of a system 
failure, paper forms may be used as a back-up method for reporting and sent via email to the 
following address: 
The appropriate forms will be completed and sent by email to the following address:  
Global Pharmacovigilance Department 
Emergent BioSolutions Canada Inc. 
Medical Monitor Phone: 1 (204) 230-6804 
Email: productsafety@ebsi.com 
Toll free fax: 1-800-768-2281 
 
For SAEs, the Serious Adverse Event Form will be completed (abbreviated hereafter SAE 
Form). The SAE Report Form is NOT the same as the AE eCRF. Subject identifiers (e.g., name, 
address, telephone number, social security number, medical record number, or 
hospital/laboratory number) must be redacted from the source documentation.  
All SAEs that are unexpected (e.g., adverse drug reactions) must be reported to the 
IRB/IEC/REB by the PI (or designee) as required by ICH GCP E6. 
If a participant becomes pregnant during a study, Emergent will be notified. All pregnancies 
where conception occurred after first exposure to the IP through the End of Study visit are to be 
followed to outcome (e.g., delivery, spontaneous/elective/therapeutic abortion) and up to 28 days 
post-birth, including after the study is completed and even if the participant is withdrawn from 
the study. If a pregnancy results in an abnormal outcome that the reporting health care 
professional considers might be due to the IP, then the guidelines for expedited reporting of 
SUSARs should be followed. 
Any pregnancy that occurs during study participation must be reported on a clinical study 
pregnancy form in the EDC. To ensure participant safety, each pregnancy must be reported to 
Emergent within 24 hours of learning of its occurrence. The pregnancy must be followed up to 
determine outcome (including premature termination) and status of mother and child up to 28 
days post-birth. Pregnancy complications and elective terminations for medical reasons must be 
reported as an AE or SAE. Spontaneous abortions must be reported as a SAE. 
Any SAE occurring in association with a pregnancy brought to the investigator’s attention during 
or after the participant has completed the study and considered by the investigator as possibly, 
probably, or related to the study treatment, must be promptly reported to Emergent 
The PI is responsible to notify their IRB/IEC/REB according to their policy. 
8.3.2 Emergent’s Reporting Requirements 
As specified in 21 CFR 312.32, SUSARs will be reported by Emergent to the FDA and to all 
participating investigators in an individual case safety report as soon as possible, no later than 15 
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calendar days after Emergent becomes aware of the suspected adverse reaction (21 CRF 312.32). 
In addition, any unexpected fatal or life-threatening suspected adverse reaction will be reported 
to the FDA as soon as possible, but in no case later than seven calendar days after Emergent’s 
initial receipt of the information (21CRF 312.32).  
8.4 
Follow-up of Adverse Events 
All AEs/SAEs will be followed until resolution, stabilization, or up to 30 days after the last study 
follow-up. 
8.4.1 Follow-up of Nonserious Adverse Events 
The status of ongoing, previously reported AEs will be subject to active follow-up. Participants 
will be interviewed at each study visit to determine if any previously on-going AEs are resolved. 
Nonserious AEs that are identified on the last scheduled visit must be recorded on the AE eCRF 
with the current status noted. All nonserious events that are ongoing at this time will be recorded 
as “Not Recovered/Not Resolved” on the AE eCRF. 
8.4.2 Follow-up of Serious Adverse Events  
This study requires that participants be monitored for SAEs up to Day 57. From Study Day 1, 
confirmed SAEs will be recorded on the AE eCRF. The status of ongoing SAEs will be assessed 
at each clinic visit and at each quarterly safety phone contact to determine any new information 
and to update the resolution status in the AE eCRF. 
The PI will provide or arrange appropriate care for participants for whom SAEs are experienced.  
All SAEs will be followed by the PI until at least one of the following conditions is met:  
• The SAE is resolved or stable if expected to remain chronic. 
• The participant is referred to a specialist or other physician for treatment and follow-up. The 
PI (or designee) will follow the participant’s condition even if the participant is seen by 
another physician, to obtain information about the diagnosis and outcome and any treatments 
and medications administered for the event. 
The following will be considered acceptable reasons for discontinuation of follow-up of ongoing 
SAEs: 
• Participant withdraws consent. 
• Participant is referred to appropriate long-term medical care. 
• Participant is considered lost to follow-up. 
It is expected that the investigational site will obtain supporting medical records from 
appropriate physicians and record this information on the SAE Form and AE eCRF. The site 
must report SAEs to Emergent (study MM and Global PV Department) within 24 hours of 
knowledge of the SAE and the SAE Report Form must be completed and provided to Emergent’s 
study MM and to Global PV Department within 72 hours (productsafety@ebsi.com). Additional 
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information received related to any SAE must be forwarded within 24 hours of awareness to the 
Emergent Global PV Department (productsafety@ebsi.com). 
8.4.3 Follow-up of Pregnancies 
Any pregnancy, where conception occurred after first exposure to the IP through the End of 
Study visit of a female participant must be reported to the Sponsor within 24 hours of learning of 
its occurrence. Such pregnancies must be reported using a clinical study pregnancy form. All 
pregnancies are to be followed to outcome and status of mother and child (e.g., delivery, 
spontaneous/elective/therapeutic abortion), including up to when the infant is 28 days old. Any 
events following study closeout will be captured in the safety database.      
If a pregnancy results in an abnormal outcome that the reporting health care professional 
considers might be due to the IP, then the guidelines for expedited reporting of serious, 
unexpected adverse drug reactions should be followed.  
Pregnancy complications and elective terminations for medical reasons must be reported as an 
AE or SAE. 
Spontaneous abortions/miscarriage must be reported as an SAE. 
8.4.4 Unanticipated Problems  
For investigational sites in the US, as outlined by the Office for Human Research Protection 
(OHRP), unanticipated problems must be reported to the IRB/IEC/REB according to the 
requirements of 45 CFR Part 46. Unanticipated problems are considered to include any incident, 
experience, or outcome that meets ALL the following criteria: 
• Unexpected (in terms of nature, severity, or frequency) given: 
• Procedures that are described in the study-related documents, such as the IRB/IEC/REB 
approved research protocol and informed consent document. 
• The characteristics of the subject population being entered into the study. 
• Related or possibly related to participation in the study which means there is a reasonable 
possibility that the incident, experience, or outcome may have been caused by the sample 
collection. 
• Suggests that the study places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
An incidence, experience, or outcome that meets the three criteria above generally will warrant 
consideration of substantive changes in the study or informed consent process/document or other 
corrective actions in order to protect the safety, welfare, or rights of participants or others.  
The PI should promptly notify the IRB/IEC/REB when an unanticipated problem involving risks 
to participants or others is identified. Also, the PI should notify the Sponsor of unanticipated 
problem(s). 
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8.5 
Safety Data Monitoring 
An independent SMC will provide on-going review of safety data during the study. In fulfilling 
these responsibilities, the SMC may make recommendations concerning continuation and/or 
stopping of the study as it relates to safety and risk to the participant population as outlined in the 
SMC Charter. 
Study enrollment and IP administration may be temporarily paused at the discretion of the PI or 
MM for safety review by the SMC if any of the following AEs occur after administration of 
COVID-HIG:  
• ≥ one SAE regardless of relatedness to IP 
• ≥ three of the same AEs classified as Grade 3 severity  
• ≥ three Grade 2 hypersensitivity AEs   
These events will be reviewed by the SMC. The procedures for SMC notification and review of 
safety data will be outlined in the SMC Charter. 
9 
STATISTICAL CONSIDERATIONS 
This section is a summary of the planned statistical analyses and justification of sample size. The 
details are described in the study Statistical Analysis Plan (SAP). 
Tables will be displayed by administration route columns. Data from both study sites and both 
cohorts will be pooled. 
9.1 
Sample Size Rationale 
There was no formal sample size calculation for this Phase 1 study. However, based on previous 
experience with hyperimmune globulin products manufactured by Emergent (30, 31, 32, 33, 34) 
in Phase 1 clinical studies with healthy adults, Emergent deems the number of participants 
planned to receive treatment in the study [N=up to 36; n=up to 12 per each treatment arm] is 
sufficient to descriptively assess COVID-HIG safety and PK of a single dose in healthy adults. 
Even with the truncation to 23 randomized participants due to high circulating SARS-CoV-2 
omicron cases, 7-8 participants per study arm should be sufficient to meet study objectives, 
similar to the previous PK study EBS-CVH-003 with 7-8 participants per arm. 
9.2 
Statistical Methods 
In general, continuous endpoints will be summarized by descriptive statistics including number of 
participants, mean, standard deviation (SD), median, minimum, and maximum. Logarithmic 
transformation will be used when appropriate, CV, geometric mean, and geometric CV will also be 
summarized. Categorical endpoints will be summarized by the total number of participants, 
frequencies, and percentages. 
See Section 9.4.2 for statistical methods for PK analyses. 
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9.3 
Handling of Missing Data 
When calculating summary statistics, including geometric mean and 90% CIs and PK 
parameters, PK (SARS-CoV-2 antibody) concentrations below the assay’s lower limit of 
quantitation (LLOQ) will be imputed as half of the LLOQ value. If the lower bound of the CIs is 
below the LLOQ, it will be replaced by “<LLOQ” in the output. Unless otherwise specified, no 
imputation will be made for missing data and complete data analysis will be used. Imputation 
rules for partial or missing dates will be described in the study SAP. 
9.4 
Planned Analyses 
9.4.1 Analyses of Disposition, Demographic and Baseline Characteristics 
Participant disposition, including early termination reasons, will be provided for all randomized 
participants by administration route. Demographic and baseline characteristics including age, 
sex, race, ethnicity, and BMI will be tabulated by administration route for all randomized 
participants and the safety and PK populations. 
Medical history will be coded to System Organ Class (SOC) and Preferred Term (PT) using the 
MedDRA dictionary and summarized by administration route for the safety population. Protocol 
deviations (PDs) will be categorized as important or not important and evaluated for exclusion of 
data from PK analyses. Protocol deviations will be presented by administration route for the 
safety population. 
Physical examination data will be listed by participant. 
9.4.2 Pharmacokinetic Analyses 
Pharmacokinetic parameters will be estimated using standard non-compartmental methods (i.e., 
log-linear trapezoidal method). Subjects will be stratified based on their SARS-CoV-2 detectable 
antibody status (>LLOQ, but ≤80 AU/mL on the Diasorin LIAISON SARS-CoV-2 S1/S2 IgG 
assay) and undetectable antibody (≤LLOQ) at screening, with analyses done by antibody status 
(if possible) and overall per each arm. Actual times and not nominal times will be used in the 
analysis; concentrations at nominal time points may be imputed using linear interpolation. 
Participants with elevated baseline levels of SARS-CoV-2 antibodies or participants with 
inadequate number of PK time points (e.g., no pre-dose sample, or no measurable post-dose 
sample) may be excluded from the PK analysis. Outliers will be examined for possible exclusion 
from analysis, such as spiking antibody levels during the study attributed to active infection. 
Baseline subtraction may be employed, if necessary and where possible, using the mean of 
individual subject’s pre-dose antibody titers. For partial AUCs through a given time point, the 
partial AUC will be set to missing unless an actual time point occurs within ±10% of the nominal 
timepoint for a given profile. 
Bioavailability will be compared between administration routes, if data permit. An ANOVA 
model will be used with AUC0-inf as the dependent variable and administration route as the fixed 
effect. The adjusted least square means will be used to estimate ratios of AUC0-inf IM / AUC0-inf IV 
* 100%, AUC0-inf SC / AUC0-inf IV * 100%, and AUC0-inf IM / AUC0-inf SC * 100% along with 
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corresponding two-sided 90% CIs calculated based on the ANOVA. The width of the 90% CIs 
will be examined relative to the standard of [80%, 125%] for comparative bioavailability. If the 
area extrapolated from the time of the last measured concentration to infinity is greater than 40% 
of the total AUC for a subject profile, then the observation will be excluded from bioavailability 
analyses. No adjustment for multiplicity will be applied, and no formal hypothesis testing will be 
performed.  
Any anomalous concentration values observed prior to the first dose will be identified. Such 
values less than 5% of the observed Cmax for the affected PK profile will be set to 0 (zero) for the 
calculation of PK parameters. The original concentration values will be used in statistical 
summaries. If the pre-dose value is greater than 5% of Cmax, the affected PK profile will be 
excluded from statistical summaries and analysis. Similarly, PK concentrations for the affected 
profile will be excluded from statistical summaries. 
Pharmacokinetic analyses will be performed separately for each administration route for the PK 
population, using the results of the binding IgG antibody assay (see Section 0). Comparative 
bioavailability will be presented between administration routes (IM to IV; SC to IV; and IM to 
SC), if data permit. Derived PK parameters, including both primary and secondary PK endpoints, 
will be tabulated by administration route for the PK population. Binding IgG SARS-CoV-2 
antibody serum concentrations versus time curves will be summarized and plotted by 
administration route for the PK population. 
9.4.3 Safety Analyses 
9.4.3.1 
Study Medication Exposure 
Participant exposure to study medication (amount administered and administration per protocol 
yes/no) will be tabulated for the safety population by administration route and by baseline 
antibody level. 
9.4.3.2 
Adverse Events and Serious Adverse Events 
Treatment-emergent adverse events are defined as AEs that present after the initiation of study IP 
or any AEs already present that worsen in either intensity or frequency following treatment. The 
incidences of TEAEs and SAEs will be summarized by administration route for the PK 
population using the MedDRA coded terms for SOC and PT and by event severity. 
9.4.3.3 
Clinical Laboratory Test Results 
Hematology and clinical chemistry laboratory test results and change from baseline to Day 2 and 
Day 4 will be summarized by time point and administration route for the safety population. The 
clinical significance of any abnormality will be assessed by the investigator. Abnormal 
laboratory results will be graded with severity grade 1 to 4 (grade 1=mild, through grade 
4=potentially life-threatening) according to the DAIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events (Appendix I). Values within the normal range as well as out of 
range laboratory values not meeting criteria for severity of at least grade 1 will be considered 
grade 0. Shift tables of laboratory abnormalities (Low, Normal, High) and/or severity grade (0, 
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1-2, ≥3) will be provided for selected laboratory parameters summarized by time point and 
administration route for the safety population. 
Results for urinalysis, pregnancy tests, and viral markers will be listed by participant.  
9.4.3.4 
Vital Signs Test Results 
Vital signs test results (including temperature, blood pressure, pulse, pulse oximetry, and 
respiratory rate) and change from baseline to Day 1 post-dose (from end of injection/infusion) 
time points, Day 2, and Day 4 will be summarized by time point and administration route for the 
safety population. The clinical significance of any abnormality will be assessed by the 
investigator, any abnormal vital signs results will be graded per Appendix III. Vital signs can be 
repeated twice if grade 3 or higher to verify the severity. Values within the normal range as well 
as out of range vital signs values not meeting criteria for severity of at least grade 1 will be 
considered grade 0. Shift tables of vital signs severity grade (0, 1-2, ≥3) may be provided for 
selected parameters summarized by time point and administration route for the safety population. 
9.4.3.5 
Nasopharyngeal Swab Results 
Nasopharyngeal swabs at Days 8, 15, 29, 43, and 57 will be analyzed for SARS-CoV-2 by RT-
PCR and results will be reported by time point and administration route for the safety population. 
In addition, the frequency and percentage of participants testing positive for COVID-19 will be 
reported for the safety population. The maximum COVID-19 symptom severity per participant 
using an Ordinal Outcome grading scale (Appendix II) will be tabulated for the SARS-CoV-2 
positive population. 
9.4.4 Subgroup Analyses 
No subgroup analyses are planned for this phase 1 study. 
9.4.5 Planned Interim Analyses and Criteria for Study Termination 
No interim analysis is planned for the study. 
The SMC will review safety data after the first 12 participants have completed at least 72 hours 
of safety follow-up. Stopping rules are provided in Section 3.4 and will be explained futher in the 
SMC Charter. 
9.5 
Analysis Populations 
Analysis will be based on the following study populations: 
Safety Population: All randomized participants who receive any amount of COVID-HIG IM, 
COVID-HIG SC, or COVID-HIG IV, analyzed according to the actual study treatment arm. 
PK Population: All participants who are randomized and received COVID-HIG IM, COVID-
HIG SC, or COVID-HIG IV according to the protocol and with evaluable PK data (i.e., no major 
protocol deviations affecting PK sampling and results including COVID-19 infection, adequate 
number of PK sample test results), analyzed according to actual study treatment arm. 
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SARS-CoV-2 Positive Population: Any randomized participant (whether or not dosed with 
COVID-HIG) who tests positive for SARS-CoV-2 during the study period and for whom data 
are available, analyzed according to randomized study treatment arm. This population is used for 
the COVID-19 symptom severity exploratory endpoint. 
10 DATA HANDLING AND RECORD KEEPING 
10.1 
Source Documents and Access 
Source data are all information, original records of clinical findings, and observations in a 
clinical trial necessary for the reconstruction and evaluation of the trial. The source 
documentation requirements described below apply to all source documentation and study 
records in any form, including those maintained in the Institution’s Electronic Health Record 
system, if applicable. 
The PI/Institution will maintain adequate and accurate source documents and study records that 
include all pertinent information related to subjects’ participation in the study, including details 
but not limited to signed and dated notes on consenting, eligibility, medical history, study 
assessments, IP administration, AEs, concomitant medications, participant follow-up 
information, and other relevant observations. 
Source data should be attributable, legible, contemporaneous, original, accurate, and complete. 
Changes to source data should be traceable, should not obscure the original entry and should be 
explained if necessary (e.g., via an audit trail). 
The PI/Institution shall permit study-related monitoring, audits, IRB/IEC/REB review, and 
regulatory inspection(s), providing direct access to source data/documents.  
Records from the study that identify the participant will be confidential except that they may be 
given to and inspected by the Sponsor (or designee), the IRB/IEC/REB, the FDA, other 
government agencies as appropriate, and will not otherwise be released except as required by 
law. Refer to Section 12.5 Subject Confidentiality. All information provided to the PI by the 
Sponsor is to be considered confidential unless otherwise stated. 
10.2 
Data Management 
A validated, EDC system will be used during the study. Data management activities to be 
performed for the study will be described in detail in the Data Management Plan (DMP). 
10.3 
Data Collection and Discrepancy Management 
This study will employ eCRFs provided by Emergent. Certain clinical information requested in 
this protocol will be recorded on these eCRFs. The PI is responsible for the adequacy and 
accuracy of all data entered on the eCRFs. The PI is also responsible for signing all eCRFs, after 
which they will be locked by the Sponsor to prevent further data entry or modification. 
For further information on eCRFs, please refer to the CRF Completion Guidelines. Details on 
data handling will be described in the DMP. 
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10.4 
Laboratory Data 
This study will employ electronic transfers of external laboratory data generated from clinical 
specimens collected by the PI. The PI is responsible for the adequacy and accuracy of data 
associated with collection of these specimens. Emergent will ensure the adequacy and accuracy 
of the data generated by external laboratories. 
10.5 
File Management at the Investigational Site 
The PI will ensure that the essential study documents are maintained in accordance with the ICH 
GCP Guidelines and as required by applicable local and federal regulations. The PI/Institution 
will take measures to prevent accidental or premature destruction of these documents. 
10.6 
Records Retention at the Investigational Site 
Per ICH guidelines, study documents will be retained for one of the following periods: 
• A period of at least two years after the date of the last approval of a marketing application in 
an ICH region until there are no pending or contemplated marketing applications. 
• A period of at least two years after Emergent has notified the regulatory authority(ies) that 
clinical investigation with this product is discontinued. 
The investigator must arrange for the retention of the subject identification codes for at least 25 
years after the completion or discontinuation of the study (Revised Canadian CTA Regulations, 
September 2001). Subject files and other source data must be securely stored and kept for the 
maximum time permitted by the hospital, institution, or private practice but not less than 25 
years after completion or termination of the study. Archival data may be held on microfiche or 
electronic record, provided that a backup exists, and that hard copy can be obtained from it if 
required. If source documents are to be destroyed as per hospital or local regulatory policy, the 
investigator is requested to contact Emergent. 
The PI must not dispose of any records relevant to this study without either (1) written 
permission from Emergent or (2) provision of an opportunity for Emergent to collect such 
records. The PI will be responsible to maintain adequate and accurate electronic or hard copy 
source documents of all observations and data generated during this study, including any data 
queries received from Emergent (or designee). Such documentation is subject to inspection by 
Emergent (or its designee(s)) and relevant regulatory agencies. If the PI withdraws from the 
study (e.g., due to relocation or retirement), all study-related records will be transferred to a 
mutually agreed upon designee within Emergent’s specified timeframe. Notice of such transfer 
will be given to Emergent in writing. 
10.7 
Deviations from the Protocol 
The PI agrees to conduct the clinical study in compliance with the protocol agreed to by the 
Sponsor and approved by the investigational site’s IRB/IEC/REB. 
A PD is any minor or major change, divergence, or departure from the study design or 
procedures defined in the protocol. 
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The PI or investigational site staff may not deviate from the protocol, except, in rare 
circumstances, as necessary to eliminate immediate hazards to study participants. In such event, 
both Emergent and IRB/IEC/REB will be immediately notified.  
The occurrence of PDs will be routinely monitored for evaluation of PI compliance with the 
protocol, GCP, and regulatory requirements. Emergent will review all PDs on an ongoing basis 
and will be responsible for determining if the deviation should be categorized as an Important 
Protocol Deviations (IPDs). Important PDs may require additional documentation as requested 
by Emergent. 
Continued PDs despite re-education of investigational site personnel, or persistent protocol 
deviations that are reportable to regulatory agencies may result in discontinued shipment of IP 
and termination of further enrollment at the investigational site, or termination of the 
investigational site from the study. 
11 QUALITY CONTROL AND ASSURANCE 
11.1 
Monitoring 
The assigned clinical study monitor will verify eCRF entries against source documentation at 
regular intervals throughout the study to verify adherence to the protocol; completeness, 
accuracy, and consistency of the data; and adherence to ICH GCP Guidelines and local and 
federal regulations applicable to the conduct of the clinical study. The PI must make source 
documentation accessible to the study monitor as needed to verify the information in the eCRF. 
The PI agrees to meet with the study monitor at regular intervals to discuss study progress and 
ensure that any problems detected in the course of data monitoring are resolved appropriately. 
11.2 
Auditing 
The Sponsor’s Clinical Quality Assurance Department (or designee) may conduct investigational 
site audits before study initiation, during the study, or after study completion. Audits will 
include, but are not limited to, review of source documents, verification of eCRF against source 
documents and review of essential documents to ensure compliance with protocol and applicable 
local and federal regulations. The PI agrees to participate in site audits and assist in the prompt 
resolution of any issues found during audits. 
In the event the PI is contacted by a regulatory agency in relation to this study, the PI and 
investigational site staff must be available to respond to reasonable requests and inspection 
queries made during the inspection process. The PI must provide the Sponsor with copies of all 
correspondence that may affect the review of the current study (e.g., Form FDA 483, 
inspectional observations, warning letters). The Sponsor will provide any needed assistance in 
responding to regulatory inspections. 
12 ETHICS AND RESPONSIBILITY 
This study must be conducted in accordance with the ethical principles described in the current 
Declaration of Helsinki, and in compliance with the protocol, current ICH GCP Guidelines, and 
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applicable local and federal regulations, and all other applicable local laws. Each investigational 
site will seek approval by an IRB/IEC/REB according to regional requirements. The 
IRB/IEC/REB will evaluate the ethical, scientific, and medical appropriateness of the study. 
Further, in collecting and handling subject data and completing eCRFs, the PI and investigational 
site staff will take measures to ensure adequate care in protecting subject privacy. To this end, a 
subject ID number will be used to identify each subject. 
12.1 
Informed Consent/Assent  
Informed consent/assent is a process that is initiated prior to the participant agreeing to 
participate in the study and continues throughout their study participation.  
Emergent (or the designee) will generate and provide a master Informed Consent Form (ICF) 
template to each investigational site for development of a site-specific ICF.  
All site-specific ICFs must be in compliance with ICH GCP Guidelines, local regulatory 
requirements, and legal requirements and must be approved by the Sponsor (or designee) and the 
IRB/IEC/REB. Emergent (or the designee) will advise the investigational site of required 
changes to the master ICF template during the course of the study. 
The participant will be asked to read and review the document. The PI will explain the research 
study to the participant and answer any questions that may arise. A verbal explanation will be 
provided in terms suited to the participant’s comprehension of the purposes, procedures, and 
potential risks of the study and of their rights as research participants. Participants will have the 
opportunity to carefully review the written consent form and ask questions prior to signing. The 
participants should have the opportunity to discuss the study with their family or think about it 
prior to agreeing to participate. The participant will sign the informed consent/assent document 
prior to any procedures being done specifically for the study. Participants must be informed that 
participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the informed consent/assent document will be given to the participants for 
their records. The informed consent/assent process will be conducted and documented in the 
source document (including the date), and the form signed, before the participant undergoes any 
study-specific procedures. The rights and welfare of the participants will be protected by 
emphasizing to them that the quality of their medical care will not be adversely affected if they 
decline to participate in this study. 
12.2 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC)/Research 
Ethics Board (REB) 
Before the start of the study, the protocol, the IB, proposed ICF(s), subject compensation (if 
any), Sponsor-approved study materials and advertisements, and any other written information to 
be provided to the participant, and applicable amendments, will be submitted to a properly 
constituted IRB/IEC/REB for review. Emergent must receive a copy of the written approval from 
the IRB/IEC/REB for all of the above applicable documents prior to recruitment of participants 
and shipment of COVID-HIG.  
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The PI (or designee) is responsible for informing, and obtaining appropriate approval from, the 
IRB/IEC/REB of any amendment to the protocol or ICF in accordance with local requirements.  
The PI (or designee) is also responsible for providing the IRB/IEC/REB with reports of any 
reportable serious adverse drug reactions from any other study conducted with the IP, if required 
by the IRB/IEC/REB. Emergent will provide this information to the PI. 
Initial IRB/IEC/REB approval, and all materials approved by the IRB/IEC/REB for the study 
including the ICF and recruitment materials, must be maintained by the PI and made available 
for inspection.  
All correspondence between the PI and the IRB/IEC/REB will be available for review by 
Emergent, contract research organization (CRO) personnel, and applicable regulatory 
authority(ies). 
12.3 
Compensation for Injury 
Emergent will adhere to local regulations and guidelines regarding clinical study compensation 
to participants whose health is adversely affected by taking part in the study. Compensation for 
injury will be described in the ICF. 
12.4 
Documentation Required Prior to Study Initiation  
The PI (or designee) is responsible for forwarding the following documents to the Sponsor for 
review prior to study initiation: 
• Signed protocol signature page, form FDA 1572 (or equivalent, depending on applicable 
local and federal regulations), financial disclosure form (principal and sub-investigators), 
Clinical Study Agreement, and any other required regulatory documents. 
• Copy of IRB/IEC/REB-approved informed consent form and assent form (as applicable). 
• Copy of the written IRB/IEC/REB approval for the following documents: protocol, 
Investigator’s Brochure, informed consent and assent form(s), participant compensation (if 
any), any study materials and advertising, and any other written information or tools 
(including diaries and/or memory aids) to be provided to the participant. 
• Current signed and dated Curriculum Vitae and a copy of medical license (if applicable) of 
the principal and sub-investigator, and other investigational site personnel as required by the 
Sponsor. 
• Written statement that the IRB/IEC/REB is properly constituted and operates according to 
ICH GCP Guidelines and applicable local and federal regulations. Investigators participating 
in this study, if IRB/IEC/REB members, should state in writing that they have abstained from 
voting in regard to this protocol.  
• Laboratory normal ranges and documentation of laboratory certification. 
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12.5 
Subject Confidentiality 
The PI must ensure the anonymity of each participant is maintained at all times. Participants 
should only be identified by their Subject Study ID number on the CRF or on any other study 
documents provided to the Sponsor (or designee(s)). Biospecimens should only be identified by 
sample numbers/codes as specified in the Laboratory Manual. Any documents that identify the 
participant should be kept in strict confidence by the investigational site.  
Based on ICH GCP Guidelines and regulatory requirements, the PI is required to allow 
authorized personnel of Emergent (or its designee), the IRB/IEC/REB, and members of the 
appropriate regulatory authority(ies) to review participant’s files that are related to 
EBS-CVH-006. Participants must be informed that their records may be reviewed by the 
Sponsor, its designee(s), the IRB/IEC/REB and the appropriate regulatory authority(ies) through 
direct access to the participant’s original medical records. 
Redacted copies of participant medical records that are related to EBS-CVH-006 may be 
collected by Emergent for the purposes of adverse event follow up and reporting, and/or 
monitoring. Redacted copies of medical records may be transferred via encrypted email (AES or 
triple DES); via secure fax line; or uploaded to a secure, encrypted password-protected 
environment hosted by a third-party service provider to which only assigned site personnel and 
monitors have access, with a list of users maintained for the duration of the study and audit trails 
available on all activities.  
Copies of redacted medical records related to monitoring will be permanently destroyed at study 
closure. 
12.6 
Future Use of Stored Samples 
Stored specimens (e.g., PK samples) will be identified by subject ID/sample numbers/codes for 
future testing. Participants will be asked to consent to the future use of the samples as part of the 
informed consent process. Samples may be retained until at least two years after the last approval 
of a marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or until at least two years have elapsed since the formal 
discontinuation of clinical development. 
13 ADMINISTRATIVE AND LEGAL REQUIREMENTS 
13.1 
Sponsorship 
This clinical study is sponsored by Emergent BioSolutions Canada Inc., 155 Innovation Drive, 
Winnipeg, Manitoba, Canada, who is the manufacturer of COVID-HIG. 
13.2 
Protocol Amendments 
Protocol amendments will only be made by the Sponsor. In general, any change to the protocol 
must be made in the form of a formal amendment to the protocol and must be approved in 
writing by the PI, the Sponsor, and the IRB/IEC/REB prior to implementation. The PI must 
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receive written IRB/IEC/REB approval for all protocol amendments prior to implementing 
protocol amendments at the investigational site; copies of IRB/IEC/REB correspondence 
including approval/disapproval letters from the IRB/IEC/REB must be provided to the Sponsor. 
However, a protocol change intended to eliminate an apparent immediate hazard to participants 
will be implemented immediately, followed by IRB/IEC/REB notification within five working 
days. The Sponsor will submit protocol amendments to the applicable regulatory authority(ies). 
Administrative amendments are defined as having no effect on the safety or physical or mental 
integrity of participants, the conduct or management of the study, the scientific value of the study 
or the quality or safety of IP used in the study.  
13.3 
Clinical Study Registration 
The Sponsor is responsible for clinical trial registration and reporting to Clinicaltrials.gov and 
other registries in accordance with applicable regulations. 
13.4 
Publication Policy 
Following the completion of the study, the data may be considered for reporting at a scientific 
meeting or for publication in a scientific journal. In these cases, the Sponsor will be responsible 
for these activities and may work with the PI to determine how the manuscript is written and 
edited, the number and order of authors, the publication to which it will be submitted and other 
related issues. The Sponsor has final approval authority over all such issues.  
Any proposed publication will be participant to review conditions and timelines agreed between 
the Sponsor and the investigational site PI and detailed in the agreements with these parties prior 
to the start of the study. The Sponsor will also post the results of the clinical study on 
ClinicalTrials.gov (or other applicable registries) in a period no greater than 12 months from the 
completion of the study (if applicable as per FDAAA 801 requirements), defined as the time the 
final participant was examined or received an intervention for purposes of final collection of data 
for the primary outcome. 
Data are the property of the Sponsor and cannot be published without prior authorization from 
the Sponsor, but data and publication thereof will not be unduly withheld. 
All publication rights are delineated in the Clinical Trial Agreement. 
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15 APPENDICES 
APPENDIX I 
GRADING OF ADVERSE EVENTS 
The severity of adverse events will be graded according to the U.S. Department of Health 
and Human Services, National Institutes of Health, National Institute of Allergy and 
Infectious Diseases, Division of AIDS. Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1. [July 2017]. 
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APPENDIX III GRADING OF VITAL SIGNS 
Use the following criteria to grade vital signs. Vital signs can be repeated twice if grade 3 or 
higher to verify the severity. 
Grading Scale* 
Grade 1  
(mild) 
Grade 2 
(moderate) 
Grade 3  
(severe) 
Grade 4 
(potentially life-
threatening) 
Temperature  
(C)  
(F) 
 
38.0-38.4 
100.4-101.1 
 
38.5-38.9 
101.2-102.0 
 
39.0-40.0 
102.1-104.0 
 
>40.0 
>104 
Tachycardia 
(beats/min) 
101-115 
116-130 
>130 
ER visit or 
hospitalization for 
arrhythmia 
Bradycardia 
(beats/min) 
50-54 
45-49 
<45 
ER visit or 
hospitalization for 
arrhythmia 
Hypertension 
systolic (mmHg) 
141-150 
151-155 
>155 
ER visit or 
hospitalization for 
malignant 
hypertension 
Hypertension 
diastolic (mmHg) 
91-95 
96-100 
>100 
ER visit or 
hospitalization for 
malignant 
hypertension 
Hypotension 
systolic (mmHg) 
85-89 
80-84 
<80 
ER visit or 
hospitalization for 
hypotensive shock 
Respiratory Rate 
(breaths/min) 
17-20 
21-25 
>25 
Intubation 
SPO2 (%) 
92 - <95 
90 - <92 
85 - <90 
<85 or 
ER visit or 
hospitalization for 
hypoxia 
* Taken from Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials {CBER, 2007}, except SPO2. 
 
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