Clinical trial NCT04732468
Conditions: Covid19
Sponsor: ImmunityBio, Inc.
Start date: 2021-02-24; Completion date: 2023-01-09
Enrollment: 28 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a phase 1b, open-label study in adult healthy subjects. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity the combination of hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) and to select an optimal combination dose for future studies.

Detailed description:

Arms: arm 1: For subjects in cohort 1, hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-SFusion+N-ETSD (Oral capsule) were administered on day 1 (prime) and hAd5-S-Fusion+N-ETSD (Suspension for injection) again on day 22 (boost). arm 2: For subjects in cohort 2, hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-SFusion+N-ETSD (Oral capsule) were administered on day 1 (prime) and hAd5-S-Fusion+N-ETSD (Oral capsule) on day 22 (boost). arm 3: For subjects in cohort 3, hAd5-S-Fusion+N-ETSD (Oral capsule) were administered on days 1 (prime) and on day 22 (boost). arm 4: For subjects in cohort 4, hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) were administered on day 1 (prime) and hAd5-SFusion+N-ETSD (Oral capsule) will be administered on days 15 (boost) and 22 (boost).
Interventions: intervention 1: hAd5-S-Fusion+N-ETSD (Suspension for injection) intervention 2: hAd5-SFusion+ N-ETSD (Oral capsule)
Intervention descriptions: intervention 1: The hAd5-S-Fusion+N-ETSD Vaccine is a human adenovirus serotype 5 (hAd5) vector with E1/E2b/E3 deletions expressing SARS-CoV-2 viral antigen spike fusion protein and nucleocapsid with an enhanced T-cell stimulation domain. intervention 2: The hAd5-S-Fusion+N-ETSD Vaccine is a human adenovirus serotype 5 (hAd5) vector with E1/E2b/E3 deletions expressing SARS-CoV-2 viral antigen spike fusion protein and nucleocapsid with an enhanced T-cell stimulation domain.

Protocol documents:
Prot_SAP_000.pdf: 
hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
1 
TITLE PAGE  
PHASE 1b OPEN-LABEL STUDY OF THE SAFETY, 
REACTOGENICITY, AND IMMUNOGENICITY OF 
SUBCUTANEOUSLY AND ORALLY ADMINISTERED 
PROPHYLACTIC VACCINATION WITH 2ND 
GENERATION E1/E2B/E3-DELETED ADENOVIRAL-
COVID-19 IN NORMAL HEALTHY VOLUNTEERS 
 
Study Number: 
COVID-4.005 
IND Sponsor: 
ImmunityBio, Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Sponsor Contact:  
(For medical questions/emergencies) 
Lennie Sender, MD 
Medical Monitor 
ImmunityBio, Inc 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: lennie.sender@nantkwest.com 
Cell Phone: 714-615-2350 
 
Protocol Version 
Date 
Version 1 
22 December 2020 
 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
2 
STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization (ICH) Guideline for GCP (E6 [R2]) and in 
accordance with United States (US) Code of Federal Regulations (CFR) applicable to clinical 
studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general 
ethical principles outlined in the Declaration of Helsinki. The study will receive approval from 
an Institutional Review Board (IRB) prior to commencement. The Principal Investigator will 
assure that no deviation from, or changes to the protocol will take place without prior agreement 
from the sponsor and documented approval from the IRB, except where necessary to eliminate 
an immediate hazard(s) to the trial participants.  
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.  
 
 
Signed: _____________________________________ Date: ______________ 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
3 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
ImmunityBio, Inc.  
Name of Investigational Products:  
1. hAd5-S-Fusion+N-ETSD (Suspension for injection) 
2. hAd5-S-Fusion+N-ETSD (Oral capsule) 
Name of Active Ingredients: 
1. hAd5-S-Fusion+N-ETSD 
2. hAd5-S-Fusion+N-ETSD 
Title of Study:  
Phase 1b Open-Label Study of the Safety, Reactogenicity, and Immunogenicity of Subcutaneously and 
Orally Administered Prophylactic Vaccination with 2nd Generation E1/E2B/E3-Deleted 
Adenoviral-COVID-19 in Normal Healthy Volunteers 
Study Number: 
COVID-4.005 
Study Phase: 
Phase 1b 
Rationale and Purpose: In December 2019, numerous pneumonia cases originating at a wholesale 
seafood market in Wuhan in the Hubei province of China were reported. The disease, which has 
subsequently become known as coronavirus disease 2019 (COVID-19), was found to be caused by a 
previously unknown coronavirus since named severe acute respiratory syndrome coronavirus 2 (SARS-
CoV-2). The global pandemic that followed the initial outbreak has already resulted in approximately 
75 million infections and over 1 million deaths as of December 2020, as well as significant economic 
damage due to shutdown of whole sectors in an effort to contain the virus. The United States (US) 
alone has reported more than 16 million infections and over 300,000 deaths. The virus continues to 
circulate in the human global population requiring continued preventive measures like social distancing 
and closing of nonessential businesses in the US and throughout the world. Identification of therapies 
for treating COVID-19 disease and vaccines for preventing the disease will be essential to reducing 
morbidity and mortality and returning to social and economic normalcy. 
To address the urgent need for a vaccine, we have rapidly repurposed our 2nd generation oncology 
adenovirus type 5 (hAd5) platform into vaccines containing SARS-CoV-2 spike (S) and nucleocapsid 
(N) antigens. Our 2nd generation hAd5 platform has demonstrated safety and efficacy in 150 patients in 
13 clinical trials including at the National Cancer Institute. To avoid the adenovirus (Ad) immunization 
barrier for first generation Ad5 [E1-, E3-] vectors, our 2nd-generation hAd5 vector has two additional 
deletions in the E2b region, removing the DNA polymerase and the preterminal protein genes (E1-, 
E2b-, E3-). Deletion of the E2b region confers advantageous immune properties on our novel hAd5 
vectors, eliciting potent immune responses to inserted antigens while minimizing the immune 
responses to Ad5 proteins. Thus, the hAd5 [E1-, E2b-, E3-] vector overcomes limitations of early 
generation vectors, as it permits the immunization of people who have been previously exposed to 
Ad5. We believe that hAd5 [E1-, E2b-, E3-] vectors are superior to Ad5 [E1-, E3-] vectors in 
immunogenicity and safety and are the best platform to develop a COVID-19 vaccine in a rapid and 
efficient manner. 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
4 
To date, vaccine strategies in development all involve developing immunogenicity against S protein. 
However, recent evidence from Grifoni et al in patients who recovered from COVID-19 demonstrates 
Th1 immunity generated against N protein. A second report by Grifoni et al. further confirmed that in 
the predictive bioinformatics model, T and B cell epitopes were highest for both S and N. Our hAd5 
vector with E1/E2b/E3 deletions has been engineered to express optimized forms of SARS-CoV-2 S 
and N proteins, known collectively as the hAd5-COVID-19-Product Series (PS). The first candidate in 
the hAd5-COVID-19-PS to be investigated in a clinical trial is hAd5-S-Fusion+N-ETSD (Suspension 
for injection), which is currently being assessed in an ongoing phase 1b clinical trial (QUILT-4.001; 
NCT04591717). The current trial is designed to investigate the safety and immunogenicity of hAd5-S-
Fusion+N-ETSD (Oral capsule) in combination with hAd5-S-Fusion+N-ETSD (Suspension for 
injection) in healthy volunteers. 
hAd5-S-Fusion+N-ETSD encodes for an optimized S protein (S-Fusion) to enhance stability and cell 
surface expression of RBD; and N protein with an enhanced T-cell stimulation domain (N-ETSD) to 
enhance cell-mediated immunity. In vitro experiments showed that hAd5-S-Fusion+N-ETSD 
demonstrates enhanced expression and exposure of the S protein receptor binding domain (RBD) 
relative to S alone. In an in vivo mouse model, hAd5-S-Fusion+N-ETSD was shown to stimulate 
antibody production and cell-mediated immunity following vaccination. IgG isotyping analysis 
demonstrated that hAd5-S-Fusion+N-ETSD induced Th1 response. Sera from mice vaccinated with 
hAd5-S-Fusion+N-ETSD demonstrated robust neutralizing activity when tested in vitro in a live virus 
neutralization assay and in a surrogate neutralization assay probing RBD binding to receptor. 
Furthermore, on the basis of the recent clinical data from patients recovered from COVID-19 reported 
by Grifoni et al, as well as the corroborating preclinical data that the N protein induces long lasting 
CD4+ and Th1 cell-mediated immunity, it is our hypothesis that this combination of S-Fusion+N-ETSD 
could provide long-lasting immunity beyond short term neutralizing antibodies.  
Moreover, analyses of nonclinical studies in Sprague Dawley (SD) rats have shown that oral 
administration of hAd5-S-Fusion+N-ETSD results in no remarkable changes in clinical signs, 
hematology, clinical pathology, or urinalysis. Similarly, studies in non-human primates (NHPs) have 
shown that SC injection of hAd5-S-Fusion+N-ETSD followed by oral administration of enteric-coated 
capsules in rhesus macaques did not result in any treatment-related toxicities post a single SC injection 
or 7 days after an oral boost. Preliminary analysis of results from these studies have shown that all 
vaccinated NHP generated anti-S IgG and following SARS-CoV-2 challenge, viral replication was 
inhibited in all vaccinated NHP from day 1 post-challenge with complete protection in both nasal 
passages and lung. Furthermore, replicating SARS-CoV-2 dropped immediately and was undetectable 
as soon 3 days post-challenge in some NHP. In contrast, placebo-controlled animals demonstrated 
ongoing viral replication. 
Together, these data suggest that the hAd5-S-Fusion+N-ETSD (Suspension for injection) is well 
tolerated when administered to human subjects SC; that there is little evidence of toxicity associated 
with the oral formulation of hAd5-S-Fusion+N-ETSD in either rodents or NHP; and further, that the 
combination holds promise in stimulating SARS-CoV-2-specific antibody production and rapid viral 
clearance. Advantages of the oral vaccine formulation are 1) that it offers ease of administration and 
the potential to increase patient compliance with scheduled vaccinations and 2) that it incorporates the 
gastrointestinal tract into the antigen sampling mechanism and therefore, the resultant immunity, which 
may result in the production of mucosal immunity and protection from invasion of epithelial tissues by 
SARS-CoV-2 virus. 
Thus, the current study will investigate the safety, reactogenicity, and immunogenicity of the 
combination of SC and oral formulations of hAd5-S-Fusion+N-ETSD and identify an optimal dose for 
future clinical studies. 
 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
5 
Study Objectives 
Study Endpoints 
Primary 
Safety: To determine the safety and reactogenicity 
of the combination of hAd5-S-Fusion+N-ETSD 
(Suspension for injection) and hAd5-S-Fusion+N-
ETSD (Oral capsule). 
• 
Incidence of medically-attended adverse 
events (MAAEs) and serious adverse events 
(SAEs) through 1 week post final vaccine 
administration 
• 
Incidence and severity of solicited local 
reactogenicity AEs through 1 week post final 
vaccine administration 
• 
Incidence and severity of solicited systemic 
reactogenicity AEs through 1 week post final 
vaccine administration 
• 
Incidence and severity of unsolicited AEs 
through 1 week post final vaccine 
administration 
• 
Incidence of MAAEs and SAEs through 
30 days and 6 months post final vaccine 
administration 
• 
Incidence and severity of unsolicited AEs 
through 30 days post final vaccine 
administration 
• 
Incidence of abnormal changes of laboratory 
safety examinations  
• 
Changes in vital signs 
Secondary 
Immunogenicity: To determine immunogenicity 
of the combination of hAd5-S-Fusion+N-ETSD 
(Suspension for injection) and hAd5-S-Fusion+N-
ETSD (Oral capsule) as determined by changes in 
humoral and cellular response. 
Humoral Immunogenicity (Timing per Schedule of 
Events): 
• 
GMFR in IgG titer 
• 
GMT of S-specific, RBD-specific, and 
N-specific antibodies against 2019 novel 
coronavirus tested by ELISA in serum 
• 
Percentage of subjects who seroconverted (as 
defined as 4-fold change in antibody titer 
relative to baseline) 
• 
GMFR in neutralizing antibody 
• 
GMT of neutralizing antibody 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
6 
• 
Seroconversion rate of neutralizing antibody 
(as defined as 4-fold change in antibody titer 
relative to baseline) 
Cellular Immunogenicity (Timing per Schedule of 
Events): 
• 
CD8+ T-Cell activity against SARS-CoV-2 
S protein, RBD, and N protein measured by 
ELISPOT assay 
• 
CD4+ T-Cell activity against SARS-CoV-2 
S protein, RBD, and N protein measured by 
standard immune assay 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
7 
Study Design: 
This is a phase 1b, open-label study in adult healthy subjects. This clinical trial is designed to assess 
the safety, reactogenicity, and immunogenicity the combination of hAd5-S-Fusion+N-ETSD 
(Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) and to select an optimal 
combination dose for future studies. 
The study will be divided into 2 stages. Up to 40 healthy subjects will be enrolled to evaluate the 
safety, reactogenicity, and immunogenicity of four different treatment regimes. In this evaluation stage, 
subjects will be divided into 4 dosing cohorts with dosing schedule, mode of administration, and 
dosage as follows:  
Cohort 
Number of 
Subjects 
Dosing  
Schedule 
Mode of 
Administration 
Dosage 
1 
10 
Day 1 
SC 
1 × 1011 VP/dose 
Oral (PO) 
1 × 1010 infectious units (IU)/dose 
Day 22 
SC 
1 × 1011 VP/dose 
2 
10 
Day 1 
SC 
1 × 1011 VP/dose 
PO 
1 × 1010 IU/dose 
Day 22 
PO 
1 × 1010 IU/dose 
3 
10 
Day 1 
PO 
1 × 1010 IU/dose 
Day 22 
PO 
1 × 1010 IU/dose 
4 
10 
Day 1 
SC 
1 × 1011 VP/dose 
PO 
1 × 1010 IU/dose 
Day 15 
PO 
1 × 1010 IU/dose 
Day 22 
PO 
1 × 1010 IU/dose 
PO (oral) doses are ± 0.5 log. 
For subjects in cohorts 1 and 2, hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-
Fusion+N-ETSD (Oral capsule) will be administered on day 1 (prime). Subjects in cohort 1 will be 
administered hAd5-S-Fusion+N-ETSD (Suspension for injection) again on day 22 (boost) and subjects 
in cohort 2 will be administered hAd5-S-Fusion+N-ETSD (Oral capsule) on day 22 (boost). For 
subjects in cohort 3, hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered on days 1 (prime) 
and on day 22 (boost). For subjects in cohort 4, hAd5-S-Fusion+N-ETSD (Suspension for injection) 
and hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered on day 1 (prime) and hAd5-S-
Fusion+N-ETSD (Oral capsule) will be administered on days 15 (boost) and 22 (boost).  
Up to 25 additional subjects will be enrolled in the expansion stage of the study. Based on safety and 
immunogenicity data gathered from cohorts 1-4, one treatment regimen will be selected for 
administration to subjects in cohort 5.  
In addition to dosing visits described above, all subjects will have follow up study visits for the 
collection of safety, reactogenicity, and/or immunogenicity data. Additional follow up for safety 
information will occur via telephone contact as noted in the Schedule of Events.  


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
8 
Safety will be assessed for all subjects and will include monitoring of vital signs, and incidence and 
severity of AEs. Blood samples will be collected for hematology and chemistry analyses and urine 
samples will be collected for urinalysis. Toxicities will be graded using the Guidance for Industry: 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials (2007). Solicited local and systemic AEs will be collected using diaries for 7 days 
following any dose of vaccine. Solicited local AEs to be assessed include pain, itching, induration, 
swelling, and erythema at the injection site. Solicited systemic AEs to be assessed include chills, fever, 
nausea, vomiting, diarrhea, headache, fatigue, and myalgia. Unsolicited AEs will be recorded in a diary 
from time of first vaccine dose until 30 days after last vaccine dose. Safety visits and telephone calls 
will occur at scheduled times for one year after the last vaccine dose, and will be used to collect 
unsolicited AEs for 30 days post last vaccine dose, all MAAEs and SAEs for 6 months post last 
vaccine dose (related MAAEs and SAEs at any time), as well as any solicited AEs continuing beyond 
the 7-day period after vaccination.  
Immunogenicity analyses will be conducted by collecting serum and peripheral blood mononuclear cell 
(PBMC) samples from individual patients before and after vaccinations to test for humoral- and cell-
mediated immune responses. Neutralizing antibodies will be assessed. Immunogenicity assessments 
will be conducted for 1 year after the last vaccine dose. 
Enrollment (planned):  
Up to 65 subjects will be enrolled in this study. 
Eligibility Criteria:  
Inclusion Criteria: 
1. Healthy adults, age 18 – 55 years, inclusive, at time of enrollment. 
2. Able to understand and provide a signed informed consent that fulfills the relevant Institutional 
Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. 
3. Agrees to the collection of biospecimens (eg, nasopharyngeal [NP] swabs) and venous blood 
per protocol. 
4. Ability to attend required study visits and return for adequate follow-up, as required by this 
protocol.  
5. Ability to swallow a capsule. 
6. Temperature < 38°C. 
7. Negative for SARS-CoV-2 (qPCR or LAMP test) and no known previous COVID-19 exposure 
or disease. 
8. Agreement to practice effective contraception for female subjects of childbearing potential and 
non-sterile males. Female subjects of childbearing potential must agree to use effective 
contraception while on study until at least 1 month after the last dose of vaccine. Non-sterile 
male subjects must agree to use a condom while on study until at least 1 month after the last 
dose of vaccine. Effective contraception includes surgical sterilization (eg, vasectomy, tubal 
ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, 
intrauterine devices (IUDs), oral contraceptives, and abstinence. 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
9 
Exclusion Criteria: 
1. Allergy to any component of the investigational vaccine, or a more severe allergic reaction and 
history of allergies in the past. 
2. Pregnant and nursing women. A negative serum or urine pregnancy test during screening and 
on the day of and prior to each dose must be documented before the vaccine is administered to 
a female subject of childbearing potential. 
3. Live in a nursing home or long-term care facility. 
4. Chronic lung disease including chronic obstructive pulmonary disease (COPD) or moderate to 
severe asthma. 
5. Pulmonary fibrosis. 
6. Current or former smoker. 
7. Bone marrow or organ transplantation. 
8. Obesity (defined as body mass index [BMI] of 30 kg/m2 or higher). 
9. Diabetes. 
10. Chronic kidney disease. 
11. Liver disease. 
12. Sickle cell disease. 
13. Thalassemia. 
14. Doctors, nurses, first responders, and other healthcare workers working in direct contact with 
COVID-19 patients. 
15. Any disease associated with acute fever, or any infection. 
16. Self-reported history of severe acute respiratory syndrome (SARS). 
17. History of hepatitis B or hepatitis C. 
18. HIV or other acquired or hereditary immunodeficiency. 
19. Serious cardiovascular diseases, such as heart failure, coronary artery disease, 
cardiomyopathies, arrhythmia, conduction block, myocardial infarction, pulmonary 
hypertension, severe hypertension without controllable drugs, etc. 
20. Cerebrovascular disease. 
21. Cystic fibrosis. 
22. Neurologic conditions, such as dementia. 
23. Hereditary or acquired angioneurotic edema. 
24. Urticaria in the last 12 months. 
25. No spleen or functional asplenia. 
26. Platelet disorder or other bleeding disorder that may cause injection contraindication. 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
10 
27. Chronic use (more than 14 continuous days) of any medications that may be associated with 
impaired immune responsiveness within 3 months before administration of study vaccine. 
(Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone 
equivalent, allergy injections, immunoglobulin, interferon, immunomodulators. The use of low 
dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted.) 
28. Prior administration of blood products in last 4 months. 
29. Prior administration of other research medicines in last 1 month. 
30. Received or plans to receive an attenuated vaccine within 1 month before or after each study 
vaccination. 
31. Received or plans to receive an inactivated vaccine within 14 days before or after each study 
vaccination. 
32. Current treatment with investigational, authorized, or approved agents for prophylaxis of 
COVID-19. 
33. Have a household contact that has been diagnosed with COVID-19. 
34. Current anti-tuberculosis prophylaxis or therapy. 
35. Currently receiving treatment for cancer or history of cancer in the last five years (except basal 
cell carcinoma of the skin and cervical carcinoma in situ). 
36. According to the judgement of investigator, various medical, psychological, social or other 
conditions that could affect the subjects’ ability to sign informed consent.  
37. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the 
protocol. 
Duration of Treatment:  
In the evaluation stage of the study, subjects in cohorts 1-3 will receive vaccine on days 1 and 22. 
Subjects in cohort 4 will receive vaccine on days 1, 15, and 22. 
In the expansion stage of the study, subjects’ duration of treatment will be determined by the 
corresponding cohort treatment regimen selected from the evaluation stage. 
Duration of Follow-up: 
Subjects who receive vaccine will be followed by a health care professional until either death (by any 
cause) or for 1 year past last administration of hAd5-S-Fusion+N-ETSD (Suspension for injection) or 
hAd5-S-Fusion+N-ETSD (Oral capsule). 
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
11 
Evaluation of Endpoints: 
Safety: Safety endpoints include assessments of treatment-emergent MAAEs, SAEs, reactogenicity 
AEs, unsolicited AEs, safety laboratory tests, and vital signs. Toxicities will be graded using the 
Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled 
in Preventive Vaccine Clinical Trials (2007).  
Immunogenicity: Immunogenicity endpoints will include GMFR in IgG and additional antibody titers 
from baseline, and percentage of subjects who seroconverted defined as a 4-fold change in antibody 
titer from baseline. Neutralizing antibodies will be determined. ImmunityBio will calculate a relative 
IgG/Neutralization titer based on those data. CD8+ T-Cell activity against SARS-CoV-2 S protein, 
RBD, and N protein will be measured by ELISPOT assay and CD4+ T-Cell activity against  
SARS-CoV-2 S protein, RBD, and N protein will be measured by standard immune assays.  
Statistical Methods: 
The purpose of this study is to determine the safety, reactogenicity, and immunogenicity of the 
combination of hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD 
(Oral capsule) and to select an optimal combination dose for future studies. Descriptive statistics will 
be presented for all study endpoints by individual cohort and for all cohorts combined. 
Safety will be assessed by the incidence of treatment-emergent MAAEs, SAEs, and solicited local and 
systemic reactogenicity AEs, and unsolicited AEs for the time period of interest, overall and by grade 
using the Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials (2007). Clinically significant changes in safety 
laboratory tests and vital signs also will be summarized. 
Immunology analyses will be used to provide an assessment of immune responses. Geometric mean 
fold rises (GMFRs) and geometric mean titers (GMTs) and their associated 95% confidence intervals 
(CIs) will be computed by exponentiation of the corresponding log-transformed means and 95% CIs. 
The percentage of subjects who seroconverted (as defined as 4-fold change in antibody titer relative to 
baseline) and 95% Clopper-Pearson CI will be summarized. Neutralizing antibody levels will also be 
summarized. CD8+ and CD4+ T-Cell activity also will be summarized. 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
12 
Figure 1: 
Phase 1b Study Schema 
 
 
 


hAd5-COVID-19-PS  
 
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
89 
Table 10: 
Evaluation Stage (Cohorts 1-4): Schedule of Events 
Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
82 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
 
8 
 
 
9 
10 
11 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
60 
90 
120 
150 
180 
270 
365 
Windows (Days) 
 
± 1 
± 5 
± 14 
± 28 
General Assessments 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 history 
of disease or 
exposureb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Confirm 
contraceptive 
measures 
X 
X 
 
C4 
only 
X 
 
 
 
X 
 
 
 
 
 
 
 
Physical exam: 
height, weightc 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
X 
Vital signsd 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
X 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


hAd5-COVID-19-PS  
 
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
90 
Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
82 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
 
8 
 
 
9 
10 
11 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
60 
90 
120 
150 
180 
270 
365 
Subject training on 
AE diaries 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Issue diaries for 
solicited and 
unsolicited AEs 
 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
 
Review and collect 
solicited AE diary  
 
 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
Review and collect 
unsolicited AE diary  
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
In office AE 
collectione 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
 
X 
X 
X 
Telephone safety 
follow up 
 
 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
 
 
Vaccine Administration 
Cohort 1  
 
Xf 
 
 
Xg 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
Xf 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Cohort 3 
 
Xh 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Cohort 4 
 
Xf 
 
Xh 
Xh 
 
 
 
 
 
 
 
 
 
 
 


hAd5-COVID-19-PS  
 
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Clinical Trial Protocol: COVID-4.005 
 
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Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
82 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
 
8 
 
 
9 
10 
11 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
60 
90 
120 
150 
180 
270 
365 
Laboratory Assessments 
Chemistry panela,i 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
 
 
Hematologya,j 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
 
 
Urinalysisa,k  
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
 
 
Collect 
biospecimens for 
SARS-CoV-2 
testinga 
X 
X 
 
C4 
only 
X 
 
 
 
 X 
 
X 
 
 
X 
X 
X 
Collect whole blood 
for immunogenicityl 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
 
X 
X 
X 
Pregnancy testa,m 
X 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: C4, cohort 4 
a Day 1 chemistry, hematology, and urinalysis assessments do not need to be repeated if screening assessments were performed within 1 week prior to the start of 
treatment. Day 1 biospecimen collection for SARS-CoV-2 testing does not need to be repeated if screening assessments were performed within 48 hours prior 
to the start of treatment. Day 1 pregnancy testing does not need to be repeated if screening assessments were performed within 48 hours prior to the start of 
treatment. 
b Potential exposure to SARS-CoV-2, symptoms of COVID-19, or outside testing results for SARS-CoV-2 infection will be collected at every study follow up 
visit and phone call. 


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Clinical Trial Protocol: COVID-4.005 
 
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c Full physical examination will be performed at screening and symptom-directed (targeted) physical examination at all other time points if indicated. Height 
required at baseline/screening visit only.  
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Temperature will be documented at each visit and 
subsequently if clinically indicated. 
e In office AE collection will continue to occur for 1 year, but only applicable AEs will be collected (see Section 7.2). 
f Both hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered. 
g hAd5-S-Fusion+N-ETSD (Suspension for injection) will be administered only. 
h hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered only. 
i See Table 9 for additional details on laboratory assessments. Blood draws for lab assessments should occur prior to vaccine administration. 
j Hematology to include CBC with differential (5 part) as outlined in Table 9. Blood draws for lab assessments should occur prior to vaccine administration. 
k Urinalysis testing will include at a minimum protein, glucose, and presence of red blood cells. Sample collection should occur prior to vaccine administration. 
l Immunogenicity testing includes measures of antibody response and cell-mediated immunity against target antigens, as well as hAd5 serostatus for determining 
baseline hAd5 immunity and monitoring for anti-vector immune responses. Sample collection should occur prior to vaccine administration. A lab manual will 
be provided to the sites with detailed guidance for serum and PBMC preparation, storage, and shipping. 
m Serum or urine pregnancy tests for females of childbearing potential at baseline/screening and each visit where study drug is administered. Day 1 pregnancy 
testing does not need to be repeated if screening assessment was performed within 48 hours prior to the start of treatment. 


hAd5-COVID-19-PS  
 
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
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Table 11: 
Escalation Stage (Cohort 5): Schedule of Events 
The schedule below shows assessments for each of the evaluation stage cohorts 1-4. Based on safety and immunogenicity data 
gathered from cohorts 1-4, one treatment regimen will be selected for administration to subjects in cohort 5; only the corresponding 
assessments will apply in this escalation stage. 
Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
82 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
 
8 
 
 
9 
10 
11 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
60 
90 
120 
150 
180 
270 
365 
Windows (Days) 
 
± 1 
± 5 
± 14 
± 28 
General Assessments 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 history 
of disease or 
exposureb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Confirm 
contraceptive 
measures 
X 
X 
 
C4 
only 
X 
 
 
 
X 
 
 
 
 
 
 
 
Physical exam: 
height, weightc 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
X 


hAd5-COVID-19-PS  
 
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Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
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Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
82 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
 
8 
 
 
9 
10 
11 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
60 
90 
120 
150 
180 
270 
365 
Vital signsd 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
X 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Subject training on 
AE diaries 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Issue diaries for 
solicited and 
unsolicited AEs 
 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
 
Review and collect 
solicited AE diary  
 
 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
Review and collect 
unsolicited AE diary  
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
In office AE 
collectione 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
 
X 
X 
X 
Telephone safety 
follow up 
 
 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
 
 
Vaccine Administration 
Cohort 1  
 
Xf 
 
 
Xg 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
Xf 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 


hAd5-COVID-19-PS  
 
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
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Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
82 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
 
8 
 
 
9 
10 
11 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
60 
90 
120 
150 
180 
270 
365 
Cohort 3 
 
Xh 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Cohort 4 
 
Xf 
 
Xh 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Laboratory Assessments 
Collect 
biospecimens for 
SARS-CoV-2 
testinga 
X 
X 
 
C4 
only 
X 
 
 
 
 X 
 
X 
 
 
X 
X 
X 
Collect whole blood 
for immunogenicityi 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
 
X 
X 
X 
Pregnancy testa,j 
X 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: C4, cohort 4 
a Day 1 chemistry, hematology, and urinalysis assessments do not need to be repeated if screening assessments were performed within 1 week prior to the start of 
treatment. Day 1 biospecimen collection for SARS-CoV-2 testing does not need to be repeated if screening assessments were performed within 48 hours prior 
to the start of treatment. Day 1 pregnancy testing does not need to be repeated if screening assessments were performed within 48 hours prior to the start of 
treatment. 
b Potential exposure to SARS-CoV-2, symptoms of COVID-19, or outside testing results for SARS-CoV-2 infection will be collected at every study follow up 
visit and phone call. 
c Full physical examination will be performed at screening and symptom-directed (targeted) physical examination at all other time points if indicated. Height 
required at baseline/screening visit only.  
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Temperature will be documented at each visit and 
subsequently if clinically indicated. 
e In office AE collection will continue to occur for 1 year, but only applicable AEs will be collected (see Section 7.2). 
f Both hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered. 


hAd5-COVID-19-PS  
 
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 
 
Confidential and Proprietary 
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g hAd5-S-Fusion+N-ETSD (Suspension for injection) will be administered only. 
h hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered only. 
i Immunogenicity testing includes measures of antibody response and cell-mediated immunity against target antigens, as well as hAd5 serostatus for determining 
baseline hAd5 immunity and monitoring for anti-vector immune responses. Sample collection should occur prior to vaccine administration. A lab manual will 
be provided to the sites with detailed guidance for serum and PBMC preparation, storage, and shipping. 
j Serum or urine pregnancy tests for females of childbearing potential at baseline/screening and each visit where study drug is administered. Day 1 pregnancy 
testing does not need to be repeated if screening assessment was performed within 48 hours prior to the start of treatment. 


hAd5-COVJD-19-PS 
Clinical Trial Protocol: COVJD-4.005 
JmrmmityBio, Inc. 
APPENDIX 4. SPONSOR Sf GNA TURE 
Study Title: 
Phase I b Open-Label Study of the Safety, Rea.ctogenicity, and 
lmmuoogenicity ofSubcutaneou.sly and Orally Administered 
Prophylactic Vaccmation with 2"" Generation E l/E2B/E3-
Deleted Adenoviral-COVID-19 in Normal Healthy Volunteers 
Study Number: 
COVID-4.005 
Version Number: 
I 
Final Date: 
22 December 2020 
This clinical trial protocol was subject to critical review and bas been approved by lmmunityBio. 
The following personnel contributed to writing and/or approving this protocol: 
Signed: 
Lennie Sender, MD 
Medical Monitor 
lmmunityBio, lnc 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: lennie.sender@nantkwest.com 
Cell Phone: 714-615-2350 
Confidential and Proprietary 
158 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 Amendment 1 
 
Confidential and Proprietary 
1 
TITLE PAGE  
PHASE 1b OPEN-LABEL STUDY OF THE SAFETY, 
REACTOGENICITY, AND IMMUNOGENICITY OF 
SUBCUTANEOUSLY AND ORALLY ADMINISTERED 
PROPHYLACTIC VACCINATION WITH 2ND 
GENERATION E1/E2B/E3-DELETED ADENOVIRAL-
COVID-19 IN NORMAL HEALTHY VOLUNTEERS 
 
Study Number: 
COVID-4.005 
IND Sponsor: 
ImmunityBio, Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Sponsor Contact:  
(For medical questions/emergencies) 
Lennie Sender, MD 
Medical Monitor 
ImmunityBio, Inc 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: lennie.sender@nantkwest.com 
Cell Phone: 714-615-2350 
 
Protocol Version 
Date 
Version 1 
22 December 2020 
Version 2 
21 January 2021 
 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 Amendment 1 
 
Confidential and Proprietary 
2 
STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization (ICH) Guideline for GCP (E6 [R2]) and in 
accordance with United States (US) Code of Federal Regulations (CFR) applicable to clinical 
studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general 
ethical principles outlined in the Declaration of Helsinki. The study will receive approval from 
an Institutional Review Board (IRB) prior to commencement. The Principal Investigator will 
assure that no deviation from, or changes to the protocol will take place without prior agreement 
from the sponsor and documented approval from the IRB, except where necessary to eliminate 
an immediate hazard(s) to the trial participants.  
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.  
 
 
Signed: _____________________________________ Date: ______________ 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 Amendment 1 
 
Confidential and Proprietary 
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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
ImmunityBio, Inc.  
Name of Investigational Products:  
1. hAd5-S-Fusion+N-ETSD (Suspension for injection) 
2. hAd5-S-Fusion+N-ETSD (Oral capsule) 
Name of Active Ingredients: 
1. hAd5-S-Fusion+N-ETSD 
2. hAd5-S-Fusion+N-ETSD 
Title of Study:  
Phase 1b Open-Label Study of the Safety, Reactogenicity, and Immunogenicity of Subcutaneously and 
Orally Administered Prophylactic Vaccination with 2nd Generation E1/E2B/E3-Deleted 
Adenoviral-COVID-19 in Normal Healthy Volunteers 
Study Number: 
COVID-4.005 
Study Phase: 
Phase 1b 
Rationale and Purpose: In December 2019, numerous pneumonia cases originating at a wholesale 
seafood market in Wuhan in the Hubei province of China were reported. The disease, which has 
subsequently become known as coronavirus disease 2019 (COVID-19), was found to be caused by a 
previously unknown coronavirus since named severe acute respiratory syndrome coronavirus 2 (SARS-
CoV-2). The global pandemic that followed the initial outbreak has already resulted in approximately 
75 million infections and over 1 million deaths as of December 2020, as well as significant economic 
damage due to shutdown of whole sectors in an effort to contain the virus. The United States (US) 
alone has reported more than 16 million infections and over 300,000 deaths. The virus continues to 
circulate in the human global population requiring continued preventive measures like social distancing 
and closing of nonessential businesses in the US and throughout the world. Identification of therapies 
for treating COVID-19 disease and vaccines for preventing the disease will be essential to reducing 
morbidity and mortality and returning to social and economic normalcy. 
To address the urgent need for a vaccine, we have rapidly repurposed our 2nd generation oncology 
adenovirus type 5 (hAd5) platform into vaccines containing SARS-CoV-2 spike (S) and nucleocapsid 
(N) antigens. Our 2nd generation hAd5 platform has demonstrated safety and efficacy in 150 patients in 
13 clinical trials including at the National Cancer Institute. To avoid the adenovirus (Ad) immunization 
barrier for first generation Ad5 [E1-, E3-] vectors, our 2nd-generation hAd5 vector has two additional 
deletions in the E2b region, removing the DNA polymerase and the preterminal protein genes (E1-, 
E2b-, E3-). Deletion of the E2b region confers advantageous immune properties on our novel hAd5 
vectors, eliciting potent immune responses to inserted antigens while minimizing the immune 
responses to Ad5 proteins. Thus, the hAd5 [E1-, E2b-, E3-] vector overcomes limitations of early 
generation vectors, as it permits the immunization of people who have been previously exposed to 
Ad5. We believe that hAd5 [E1-, E2b-, E3-] vectors are superior to Ad5 [E1-, E3-] vectors in 
immunogenicity and safety and are the best platform to develop a COVID-19 vaccine in a rapid and 
efficient manner. 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 Amendment 1 
 
Confidential and Proprietary 
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To date, vaccine strategies in development all involve developing immunogenicity against S protein. 
However, recent evidence from Grifoni et al in patients who recovered from COVID-19 demonstrates 
Th1 immunity generated against N protein. A second report by Grifoni et al. further confirmed that in 
the predictive bioinformatics model, T and B cell epitopes were highest for both S and N. Our hAd5 
vector with E1/E2b/E3 deletions has been engineered to express optimized forms of SARS-CoV-2 S 
and N proteins, known collectively as the hAd5-COVID-19-Product Series (PS). The first candidate in 
the hAd5-COVID-19-PS to be investigated in a clinical trial is hAd5-S-Fusion+N-ETSD (Suspension 
for injection), which is currently being assessed in an ongoing phase 1b clinical trial (QUILT-4.001; 
NCT04591717). The current trial is designed to investigate the safety and immunogenicity of hAd5-S-
Fusion+N-ETSD (Oral capsule) in combination with hAd5-S-Fusion+N-ETSD (Suspension for 
injection) in healthy volunteers. 
hAd5-S-Fusion+N-ETSD encodes for an optimized S protein (S-Fusion) to enhance stability and cell 
surface expression of RBD; and N protein with an enhanced T-cell stimulation domain (N-ETSD) to 
enhance cell-mediated immunity. In vitro experiments showed that hAd5-S-Fusion+N-ETSD 
demonstrates enhanced expression and exposure of the S protein receptor binding domain (RBD) 
relative to S alone. In an in vivo mouse model, hAd5-S-Fusion+N-ETSD was shown to stimulate 
antibody production and cell-mediated immunity following vaccination. IgG isotyping analysis 
demonstrated that hAd5-S-Fusion+N-ETSD induced Th1 response. Sera from mice vaccinated with 
hAd5-S-Fusion+N-ETSD demonstrated robust neutralizing activity when tested in vitro in a live virus 
neutralization assay and in a surrogate neutralization assay probing RBD binding to receptor. 
Furthermore, on the basis of the recent clinical data from patients recovered from COVID-19 reported 
by Grifoni et al, as well as the corroborating preclinical data that the N protein induces long lasting 
CD4+ and Th1 cell-mediated immunity, it is our hypothesis that this combination of S-Fusion+N-ETSD 
could provide long-lasting immunity beyond short term neutralizing antibodies.  
Moreover, analyses of nonclinical studies in Sprague Dawley (SD) rats have shown that oral 
administration of hAd5-S-Fusion+N-ETSD results in no remarkable changes in clinical signs, 
hematology, clinical pathology, or urinalysis. Similarly, studies in non-human primates (NHPs) have 
shown that SC injection of hAd5-S-Fusion+N-ETSD followed by oral administration of enteric-coated 
capsules in rhesus macaques did not result in any treatment-related toxicities post a single SC injection 
or 7 days after an oral boost. Preliminary analysis of results from these studies have shown that all 
vaccinated NHP generated anti-S IgG and following SARS-CoV-2 challenge, viral replication was 
inhibited in all vaccinated NHP from day 1 post-challenge with complete protection in both nasal 
passages and lung. Furthermore, replicating SARS-CoV-2 dropped immediately and was undetectable 
as soon 3 days post-challenge in some NHP. In contrast, placebo-controlled animals demonstrated 
ongoing viral replication. 
Together, these data suggest that the hAd5-S-Fusion+N-ETSD (Suspension for injection) is well 
tolerated when administered to human subjects SC; that there is little evidence of toxicity associated 
with the oral formulation of hAd5-S-Fusion+N-ETSD in either rodents or NHP; and further, that the 
combination holds promise in stimulating SARS-CoV-2-specific antibody production and rapid viral 
clearance. Advantages of the oral vaccine formulation are 1) that it offers ease of administration and 
the potential to increase patient compliance with scheduled vaccinations and 2) that it incorporates the 
gastrointestinal tract into the antigen sampling mechanism and therefore, the resultant immunity, which 
may result in the production of mucosal immunity and protection from invasion of epithelial tissues by 
SARS-CoV-2 virus. 
Thus, the current study will investigate the safety, reactogenicity, and immunogenicity of the 
combination of SC and oral formulations of hAd5-S-Fusion+N-ETSD and identify an optimal dose for 
future clinical studies. 
 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 Amendment 1 
 
Confidential and Proprietary 
5 
Study Objectives 
Study Endpoints 
Primary 
Safety: To determine the safety and reactogenicity 
of the combination of hAd5-S-Fusion+N-ETSD 
(Suspension for injection) and hAd5-S-Fusion+N-
ETSD (Oral capsule). 
• 
Incidence of medically-attended adverse 
events (MAAEs) and serious adverse events 
(SAEs) through 1 week post final vaccine 
administration 
• 
Incidence and severity of solicited local 
reactogenicity AEs through 1 week post final 
vaccine administration 
• 
Incidence and severity of solicited systemic 
reactogenicity AEs through 1 week post final 
vaccine administration 
• 
Incidence and severity of unsolicited AEs 
through 1 week post final vaccine 
administration 
• 
Incidence of MAAEs and SAEs through 
30 days and 6 months post final vaccine 
administration 
• 
Incidence and severity of unsolicited AEs 
through 30 days post final vaccine 
administration 
• 
Incidence of abnormal changes of laboratory 
safety examinations  
• 
Changes in vital signs 
Secondary 
Immunogenicity: To determine immunogenicity 
of the combination of hAd5-S-Fusion+N-ETSD 
(Suspension for injection) and hAd5-S-Fusion+N-
ETSD (Oral capsule) as determined by changes in 
humoral and cellular response. 
Humoral Immunogenicity (Timing per Schedule of 
Events): 
• 
GMFR in IgG titer 
• 
GMT of S-specific, RBD-specific, and 
N-specific antibodies against 2019 novel 
coronavirus tested by ELISA in serum 
• 
Percentage of subjects who seroconverted (as 
defined as 4-fold change in antibody titer 
relative to baseline) 
• 
GMFR in neutralizing antibody 
• 
GMT of neutralizing antibody 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 Amendment 1 
 
Confidential and Proprietary 
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• 
Seroconversion rate of neutralizing antibody 
(as defined as 4-fold change in antibody titer 
relative to baseline) 
Cellular Immunogenicity (Timing per Schedule of 
Events): 
• 
CD8+ T-Cell activity against SARS-CoV-2 
S protein, RBD, and N protein measured by 
ELISPOT assay 
• 
CD4+ T-Cell activity against SARS-CoV-2 
S protein, RBD, and N protein measured by 
standard immune assay 


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 Amendment 1 
 
Confidential and Proprietary 
7 
Study Design: 
This is a phase 1b, open-label study in adult healthy subjects. This clinical trial is designed to assess 
the safety, reactogenicity, and immunogenicity the combination of hAd5-S-Fusion+N-ETSD 
(Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) and to select an optimal 
combination dose for future studies. 
The study will be divided into 2 stages. Up to 40 healthy subjects will be enrolled to evaluate the 
safety, reactogenicity, and immunogenicity of four different treatment regimens. In this evaluation 
stage, subjects will be divided into 4 dosing cohorts with dosing schedule, mode of administration, and 
dosage as follows:  
Cohort 
Number of 
Subjects 
Dosing  
Schedule 
Mode of 
Administration 
Dosage 
1 
10 
Day 1 
SC 
1 × 1011 VP/dose 
Oral (PO) 
1 × 1010 infectious units (IU)/dose 
Day 22 
SC 
1 × 1011 VP/dose 
2 
10 
Day 1 
SC 
1 × 1011 VP/dose 
PO 
1 × 1010 IU/dose 
Day 22 
PO 
1 × 1010 IU/dose 
3 
10 
Day 1 
PO 
1 × 1010 IU/dose 
Day 22 
PO 
1 × 1010 IU/dose 
4 
10 
Day 1 
SC 
1 × 1011 VP/dose 
PO 
1 × 1010 IU/dose 
Day 15 
PO 
1 × 1010 IU/dose 
Day 22 
PO 
1 × 1010 IU/dose 
PO (oral) doses are ± 0.5 log. 
For subjects in cohorts 1 and 2, hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-
Fusion+N-ETSD (Oral capsule) will be administered on day 1 (prime). Subjects in cohort 1 will be 
administered hAd5-S-Fusion+N-ETSD (Suspension for injection) again on day 22 (boost) and subjects 
in cohort 2 will be administered hAd5-S-Fusion+N-ETSD (Oral capsule) on day 22 (boost). For 
subjects in cohort 3, hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered on days 1 (prime) 
and on day 22 (boost). For subjects in cohort 4, hAd5-S-Fusion+N-ETSD (Suspension for injection) 
and hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered on day 1 (prime) and hAd5-S-
Fusion+N-ETSD (Oral capsule) will be administered on days 15 (boost) and 22 (boost).  
Enrollment of the first 6 subjects will be staggered, with no more than 3 subjects enrolled per day for 
the first 2 days. On each of these days, vaccinations will occur at ≥ 3 hour intervals. Safety for these 6 
subjects will be assessed by telephone follow up 24 and 48 hours after receiving the priming 
vaccination. The ImmunityBio Safety Review Committee (SRC) will conduct a review of 48 hour 
safety data on the first 6 subjects; vaccination of additional subjects will proceed if no safety concerns 
are identified.  


hAd5-COVID-19-PS  
ImmunityBio, Inc. 
Clinical Trial Protocol: COVID-4.005 Amendment 1 
 
Confidential and Proprietary 
8 
Up to 25 additional subjects will be enrolled in the expansion stage of the study. Based on safety and 
immunogenicity data gathered from cohorts 1-4, one treatment regimen will be selected for 
administration to subjects in cohort 5.  
In addition to dosing visits described above, all subjects will have follow up study visits for the 
collection of safety, reactogenicity, and/or immunogenicity data. Additional follow up for safety 
information will occur via telephone contact as noted in the Schedule of Events.  
Safety will be assessed for all subjects and will include monitoring of vital signs, and incidence and 
severity of AEs. Blood samples will be collected for hematology and chemistry analyses and urine 
samples will be collected for urinalysis. Toxicities will be graded using the Guidance for Industry: 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials (2007). Solicited local and systemic AEs will be collected using diaries for 7 days 
following any dose of vaccine. Solicited local AEs to be assessed include pain, itching, induration, 
swelling, and erythema at the injection site. Solicited systemic AEs to be assessed include chills, fever, 
nausea, vomiting, diarrhea, headache, fatigue, and myalgia. Unsolicited AEs will be recorded in a diary 
from time of first vaccine dose until 30 days after last vaccine dose. Safety visits and telephone calls 
will occur at scheduled times for one year after the last vaccine dose, and will be used to collect 
unsolicited AEs for 30 days post last vaccine dose, all MAAEs and SAEs for 6 months post last 
vaccine dose (related MAAEs and SAEs at any time), as well as any solicited AEs continuing beyond 
the 7-day period after vaccination.  
Immunogenicity analyses will be conducted by collecting serum and peripheral blood mononuclear cell 
(PBMC) samples from individual patients before and after vaccinations to test for humoral- and cell-
mediated immune responses. Neutralizing antibodies will be assessed. Immunogenicity assessments 
will be conducted for 1 year after the last vaccine dose. 
Enrollment (planned):  
Up to 65 subjects will be enrolled in this study. 
Eligibility Criteria:  
Inclusion Criteria: 
1. Healthy adults, age 18 – 55 years, inclusive, at time of enrollment. 
2. Able to understand and provide a signed informed consent that fulfills the relevant Institutional 
Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. 
3. Agrees to the collection of biospecimens (eg, nasopharyngeal [NP] swabs) and venous blood 
per protocol. 
4. Ability to attend required study visits and return for adequate follow-up, as required by this 
protocol.  
5. Ability to swallow a capsule. 
6. Temperature < 38°C. 
7. Negative for SARS-CoV-2 (qPCR or LAMP test) and no known previous COVID-19 exposure 
or disease. 
8. Agreement to practice effective contraception for female subjects of childbearing potential and 
non-sterile males. Female subjects of childbearing potential must agree to use effective 
contraception while on study until at least 1 month after the last dose of vaccine. Non-sterile 


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male subjects must agree to use a condom while on study until at least 1 month after the last 
dose of vaccine. Effective contraception includes surgical sterilization (eg, vasectomy, tubal 
ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, 
intrauterine devices (IUDs), oral contraceptives, and abstinence. 
Exclusion Criteria: 
1. Allergy to any component of the investigational vaccine, or a more severe allergic reaction and 
history of allergies in the past. 
2. Pregnant and nursing women. A negative serum or urine pregnancy test during screening and 
on the day of and prior to each dose must be documented before the vaccine is administered to 
a female subject of childbearing potential. 
3. Live in a nursing home or long-term care facility. 
4. Chronic lung disease including chronic obstructive pulmonary disease (COPD) or moderate to 
severe asthma. 
5. Pulmonary fibrosis. 
6. Current or former smoker. 
7. Bone marrow or organ transplantation. 
8. Obesity (defined as body mass index [BMI] of 30 kg/m2 or higher). 
9. Diabetes. 
10. Chronic kidney disease. 
11. Liver disease. 
12. Sickle cell disease. 
13. Thalassemia. 
14. Doctors, nurses, first responders, and other healthcare workers working in direct contact with 
COVID-19 patients. 
15. Any disease associated with acute fever, or any infection. 
16. Self-reported history of severe acute respiratory syndrome (SARS). 
17. History of hepatitis B or hepatitis C. 
18. HIV or other acquired or hereditary immunodeficiency. 
19. Serious cardiovascular diseases, such as heart failure, coronary artery disease, 
cardiomyopathies, arrhythmia, conduction block, myocardial infarction, pulmonary 
hypertension, severe hypertension without controllable drugs, etc. 
20. Cerebrovascular disease. 
21. Cystic fibrosis. 
22. Neurologic conditions, such as dementia. 
23. Hereditary or acquired angioneurotic edema. 


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24. Urticaria in the last 12 months. 
25. No spleen or functional asplenia. 
26. Platelet disorder or other bleeding disorder that may cause injection contraindication. 
27. Chronic use (more than 14 continuous days) of any medications that may be associated with 
impaired immune responsiveness within 3 months before administration of study vaccine. 
(Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone 
equivalent, allergy injections, immunoglobulin, interferon, immunomodulators. The use of low 
dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted.) 
28. Prior administration of blood products in last 4 months. 
29. Prior administration of other research medicines in last 1 month. 
30. Received or plans to receive an attenuated vaccine within 1 month before or after each study 
vaccination. 
31. Received or plans to receive an inactivated vaccine within 14 days before or after each study 
vaccination. 
32. Current treatment with investigational, authorized, or approved agents for prophylaxis of 
COVID-19. 
33. Have a household contact that has been diagnosed with COVID-19. 
34. Current anti-tuberculosis prophylaxis or therapy. 
35. Currently receiving treatment for cancer or history of cancer in the last five years (except basal 
cell carcinoma of the skin and cervical carcinoma in situ). 
36. According to the judgement of investigator, various medical, psychological, social or other 
conditions that could affect the subjects’ ability to sign informed consent.  
37. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the 
protocol. 
Duration of Treatment:  
In the evaluation stage of the study, subjects in cohorts 1-3 will receive vaccine on days 1 and 22. 
Subjects in cohort 4 will receive vaccine on days 1, 15, and 22. 
In the expansion stage of the study, subjects’ duration of treatment will be determined by the 
corresponding cohort treatment regimen selected from the evaluation stage. 
Duration of Follow-up: 
Subjects who receive vaccine will be followed by a health care professional until either death (by any 
cause) or for 1 year past last administration of hAd5-S-Fusion+N-ETSD (Suspension for injection) or 
hAd5-S-Fusion+N-ETSD (Oral capsule). 
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable 


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Evaluation of Endpoints: 
Safety: Safety endpoints include assessments of treatment-emergent MAAEs, SAEs, reactogenicity 
AEs, unsolicited AEs, safety laboratory tests, and vital signs. Toxicities will be graded using the 
Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled 
in Preventive Vaccine Clinical Trials (2007).  
Immunogenicity: Immunogenicity endpoints will include GMFR in IgG and additional antibody titers 
from baseline, and percentage of subjects who seroconverted defined as a 4-fold change in antibody 
titer from baseline. Neutralizing antibodies will be determined. ImmunityBio will calculate a relative 
IgG/Neutralization titer based on those data. CD8+ T-Cell activity against SARS-CoV-2 S protein, 
RBD, and N protein will be measured by ELISPOT assay and CD4+ T-Cell activity against  
SARS-CoV-2 S protein, RBD, and N protein will be measured by standard immune assays.  
Statistical Methods: 
The purpose of this study is to determine the safety, reactogenicity, and immunogenicity of the 
combination of hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD 
(Oral capsule) and to select an optimal combination dose for future studies. Descriptive statistics will 
be presented for all study endpoints by individual cohort and for all cohorts combined. 
Safety will be assessed by the incidence of treatment-emergent MAAEs, SAEs, and solicited local and 
systemic reactogenicity AEs, and unsolicited AEs for the time period of interest, overall and by grade 
using the Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials (2007). Clinically significant changes in safety 
laboratory tests and vital signs also will be summarized. 
Immunology analyses will be used to provide an assessment of immune responses. Geometric mean 
fold rises (GMFRs) and geometric mean titers (GMTs) and their associated 95% confidence intervals 
(CIs) will be computed by exponentiation of the corresponding log-transformed means and 95% CIs. 
The percentage of subjects who seroconverted (as defined as 4-fold change in antibody titer relative to 
baseline) and 95% Clopper-Pearson CI will be summarized. Neutralizing antibody levels will also be 
summarized. CD8+ and CD4+ T-Cell activity also will be summarized. 


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Figure 1: 
Phase 1b Study Schema 
 
 
 


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Table 10: 
Evaluation Stage (Cohorts 1-4): Schedule of Events 
Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
82 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
 
8 
 
 
9 
10 
11 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
60 
90 
120 
150 
180 
270 
365 
Windows (Days) 
 
± 1 
± 5 
± 14 
± 28 
General Assessments 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 history 
of disease or 
exposureb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Confirm 
contraceptive 
measures 
X 
X 
 
C4 
only 
X 
 
 
 
X 
 
 
 
 
 
 
 
Physical exam: 
height, weightc 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
X 
Vital signsd 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
X 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
82 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
 
8 
 
 
9 
10 
11 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
60 
90 
120 
150 
180 
270 
365 
Subject training on 
AE diaries 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Issue diaries for 
solicited and 
unsolicited AEs 
 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
 
Review and collect 
solicited AE diary  
 
 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
Review and collect 
unsolicited AE diary  
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
In office AE 
collectione 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
 
X 
X 
X 
Telephone safety 
follow up 
 
 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
 
 
Vaccine Administration 
Cohort 1  
 
Xf 
 
 
Xg 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
Xf 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Cohort 3 
 
Xh 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Cohort 4 
 
Xf 
 
Xh 
Xh 
 
 
 
 
 
 
 
 
 
 
 


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Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
82 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
 
8 
 
 
9 
10 
11 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
60 
90 
120 
150 
180 
270 
365 
Laboratory Assessments 
Chemistry panela,i 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
 
 
Hematologya,j 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
 
 
Urinalysisa,k  
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
 
 
Collect 
biospecimens for 
SARS-CoV-2 
testinga 
X 
X 
 
C4 
only 
X 
 
 
 
 X 
 
X 
 
 
X 
X 
X 
Collect whole blood 
for immunogenicityl 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
 
X 
X 
X 
Pregnancy testm 
X 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: C4, cohort 4 
a Day 1 chemistry, hematology, and urinalysis assessments do not need to be repeated if screening assessments were performed within 1 week prior to the start of 
treatment. Day 1 biospecimen collection for SARS-CoV-2 testing does not need to be repeated if screening assessments were performed within 48 hours prior 
to the start of treatment.  
b Potential exposure to SARS-CoV-2, symptoms of COVID-19, or outside testing results for SARS-CoV-2 infection will be collected at every study follow up 
visit and phone call. 
c Full physical examination will be performed at screening and symptom-directed (targeted) physical examination at all other time points if indicated. Height 
required at baseline/screening visit only.  


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d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Temperature will be documented at each visit and 
subsequently if clinically indicated. 
e Safety for the first 6 subjects enrolled will be assessed by telephone follow up 24 and 48 hours after receiving the priming vaccination. The ImmunityBio SRC 
will conduct a review of 48 hour safety data on the first 6 subjects; vaccination of additional subjects will proceed if no safety concerns are identified.  In office 
AE collection will continue to occur for 1 year, but only applicable AEs will be collected (see Section 7.2). 
f Both hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered. 
g hAd5-S-Fusion+N-ETSD (Suspension for injection) will be administered only. 
h hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered only. 
i See Table 9 for additional details on laboratory assessments. Blood draws for lab assessments should occur prior to vaccine administration. 
j Hematology to include CBC with differential (5 part) as outlined in Table 9. Blood draws for lab assessments should occur prior to vaccine administration. 
k Urinalysis testing will include at a minimum protein, glucose, and presence of red blood cells. Sample collection should occur prior to vaccine administration. 
l Immunogenicity testing includes measures of antibody response and cell-mediated immunity against target antigens, as well as hAd5 serostatus for determining 
baseline hAd5 immunity and monitoring for anti-vector immune responses. Sample collection should occur prior to vaccine administration. A lab manual will 
be provided to the sites with detailed guidance for serum and PBMC preparation, storage, and shipping. 
m Serum or urine pregnancy tests for females of childbearing potential at baseline/screening and each visit where study drug is administered.  


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Table 11: 
Escalation Stage (Cohort 5): Schedule of Events 
The schedule below shows assessments for each of the evaluation stage cohorts 1-4. Based on safety and immunogenicity data 
gathered from cohorts 1-4, one treatment regimen will be selected for administration to subjects in cohort 5; only the corresponding 
assessments will apply in this escalation stage. 
Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
82 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
 
8 
 
 
9 
10 
11 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
60 
90 
120 
150 
180 
270 
365 
Windows (Days) 
 
± 1 
± 5 
± 14 
± 28 
General Assessments 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 history 
of disease or 
exposureb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Confirm 
contraceptive 
measures 
X 
X 
 
C4 
only 
X 
 
 
 
X 
 
 
 
 
 
 
 
Physical exam: 
height, weightc 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
X 


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Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
82 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
 
8 
 
 
9 
10 
11 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
60 
90 
120 
150 
180 
270 
365 
Vital signsd 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
X 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Subject training on 
AE diaries 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Issue diaries for 
solicited and 
unsolicited AEs 
 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
 
Review and collect 
solicited AE diary  
 
 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
Review and collect 
unsolicited AE diary  
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
In office AE 
collectione 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
 
X 
X 
X 
Telephone safety 
follow up 
 
 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
 
 
Vaccine Administration 
Cohort 1  
 
Xf 
 
 
Xg 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
Xf 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 


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Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
82 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
 
8 
 
 
9 
10 
11 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
60 
90 
120 
150 
180 
270 
365 
Cohort 3 
 
Xh 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Cohort 4 
 
Xf 
 
Xh 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Laboratory Assessments 
Collect 
biospecimens for 
SARS-CoV-2 
testinga 
X 
X 
 
C4 
only 
X 
 
 
 
 X 
 
X 
 
 
X 
X 
X 
Collect whole blood 
for immunogenicityi 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
 
X 
X 
X 
Pregnancy testj 
X 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: C4, cohort 4 
a Day 1 chemistry, hematology, and urinalysis assessments do not need to be repeated if screening assessments were performed within 1 week prior to the start of 
treatment. Day 1 biospecimen collection for SARS-CoV-2 testing does not need to be repeated if screening assessments were performed within 48 hours prior 
to the start of treatment.  
b Potential exposure to SARS-CoV-2, symptoms of COVID-19, or outside testing results for SARS-CoV-2 infection will be collected at every study follow up 
visit and phone call. 
c Full physical examination will be performed at screening and symptom-directed (targeted) physical examination at all other time points if indicated. Height 
required at baseline/screening visit only.  
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Temperature will be documented at each visit and 
subsequently if clinically indicated. 
e In office AE collection will continue to occur for 1 year, but only applicable AEs will be collected (see Section 7.2). 
f Both hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered. 
g hAd5-S-Fusion+N-ETSD (Suspension for injection) will be administered only. 


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h hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered only. 
i Immunogenicity testing includes measures of antibody response and cell-mediated immunity against target antigens, as well as hAd5 serostatus for determining 
baseline hAd5 immunity and monitoring for anti-vector immune responses. Sample collection should occur prior to vaccine administration. A lab manual will 
be provided to the sites with detailed guidance for serum and PBMC preparation, storage, and shipping. 
j Serum or urine pregnancy tests for females of childbearing potential at baseline/screening and each visit where study drug is administered.  


hAdS-COVID-19-PS 
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Clinical Trial Protocol: COVID-4.005 Amendment I 
APPENDIX 4. SPONSOR SIGNATURE 
Study Title: 
Phase lb Open-Label Study of the Safety, Reactogenicity, and 
lmmunogenicity of Subcutaneously and Orally Administered 
Prophylactic Vaccination with 2"d Generation El/E2B/E3-
Deleted Adenoviral-COVID-19 in Normal Healthy Volunteers 
Study Number: 
COVID-4.005 
Version Number: 
2 
Final Date: 
21January2021 
This clinical trial protocol was subject to critical review and has been approved by lmrnunityBio. 
The following personnel contributed to writing and/or approving this protocol: 
Signed: 
Lennie Sender, MD 
Medical Monitor 
ImmunityBio, Inc 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: lennie.sender@nantkwest.com 
Cell Phone: 714-615-2350 
Confidential and Proprietary 
Date: _I -_2_1-_2_0_2._J_ 
158 


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TITLE PAGE
PHASE 1b OPEN-LABEL STUDY OF THE SAFETY, 
REACTOGENICITY, AND IMMUNOGENICITY OF 
SUBCUTANEOUSLY-, INTRAMUSCULARLY-, AND 
ORALLY-ADMINISTERED PROPHYLACTIC 
VACCINATION WITH 2ND GENERATION E1/E2B/E3-
DELETED ADENOVIRAL-COVID-19 IN NORMAL 
HEALTHY VOLUNTEERS 
Study Number: 
COVID-4.005 
IND Sponsor: 
ImmunityBio, Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Sponsor Contact:  
(For medical questions/emergencies) 
Lennie Sender, MD 
Medical Monitor 
ImmunityBio, Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: lennie.sender@immunitybio.com 
Cell Phone: 714-615-2350 
Protocol Version 
Date 
Version 1 
22 December 2020 
Version 2 
21 January 2021 
Version 3 
31 March 2021 
1


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STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization (ICH) Guideline for GCP (E6 [R2]) and in 
accordance with United States (US) Code of Federal Regulations (CFR) applicable to clinical 
studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general 
ethical principles outlined in the Declaration of Helsinki. The study will receive approval from 
an Institutional Review Board (IRB) prior to commencement. The Principal Investigator will 
assure that no deviation from, or changes to the protocol will take place without prior agreement 
from the sponsor and documented approval from the IRB, except where necessary to eliminate 
an immediate hazard(s) to the trial participants.  
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.  
 
 
Signed: _____________________________________ Date: ______________ 
2


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Clinical Trial Protocol: COVID-4.005 Amendment 2 
 
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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
ImmunityBio, Inc.  
Name of Investigational Products:  
1. hAd5-S-Fusion+N-ETSD (Suspension for injection and sublingual administration); hereafter 
referred to as hAd5-S-Fusion+N-ETSD (Suspension for injection) 
2. hAd5-S-Fusion+N-ETSD (Oral capsule) 
Name of Active Ingredients: 
1. hAd5-S-Fusion+N-ETSD 
2. hAd5-S-Fusion+N-ETSD 
Title of Study:  
Phase 1b Open-Label Study of the Safety, Reactogenicity, and Immunogenicity of Subcutaneously-, 
Intramuscularly-, and Orally-Administered Prophylactic Vaccination with 2nd Generation E1/E2B/E3-
Deleted Adenoviral-COVID-19 in Normal Healthy Volunteers 
Study Number: 
COVID-4.005 
Study Phase: 
Phase 1b 
Rationale and Purpose: In December 2019, numerous pneumonia cases originating at a wholesale 
seafood market in Wuhan in the Hubei province of China were reported. The disease, which has 
subsequently become known as coronavirus disease 2019 (COVID-19), was found to be caused by a 
previously unknown coronavirus since named severe acute respiratory syndrome coronavirus 2 (SARS-
CoV-2). The global pandemic that followed the initial outbreak has resulted in significant morbidity 
and mortality in the US and throughout the world. The virus continues to circulate in the human global 
population requiring continued preventive measures like social distancing and closing of nonessential 
businesses in the US and throughout the world. Identification of therapies for treating COVID-19 
disease and vaccines for preventing the disease will be essential to reducing morbidity and mortality 
and returning to social and economic normalcy. 
To address the urgent need for a vaccine, we have rapidly repurposed our 2nd generation oncology 
adenovirus type 5 (hAd5) platform into vaccines containing SARS-CoV-2 spike (S) and nucleocapsid 
(N) antigens. Our 2nd generation hAd5 platform has demonstrated safety and efficacy in 150 patients in 
13 clinical trials including at the National Cancer Institute. To avoid the adenovirus (Ad) immunization 
barrier for first generation Ad5 [E1-, E3-] vectors, our 2nd-generation hAd5 vector has two additional 
deletions in the E2b region, removing the DNA polymerase and the preterminal protein genes (E1-, 
E2b-, E3-). Deletion of the E2b region confers advantageous immune properties on our novel hAd5 
vectors, eliciting potent immune responses to inserted antigens while minimizing the immune 
responses to Ad5 proteins. Thus, the hAd5 [E1-, E2b-, E3-] vector overcomes limitations of early 
generation vectors, as it permits the immunization of people who have been previously exposed to 
Ad5. We believe that hAd5 [E1-, E2b-, E3-] vectors are superior to Ad5 [E1-, E3-] vectors in 
immunogenicity and safety and are the best platform to develop a COVID-19 vaccine in a rapid and 
efficient manner. 
3


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Clinical Trial Protocol: COVID-4.005 Amendment 2 
 
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To date, vaccine strategies in development all involve developing immunogenicity against S protein. 
However, recent evidence from Grifoni et al in patients who recovered from COVID-19 demonstrates 
Th1 immunity generated against N protein. A second report by Grifoni et al. further confirmed that in 
the predictive bioinformatics model, T and B cell epitopes were highest for both S and N. Our hAd5 
vector with E1/E2b/E3 deletions has been engineered to express optimized forms of SARS-CoV-2 S 
and N proteins, known collectively as the hAd5-COVID-19-Product Series (PS). The first candidate in 
the hAd5-COVID-19-PS to be investigated in a clinical trial is hAd5-S-Fusion+N-ETSD (Suspension 
for injection), which is currently being assessed in an ongoing phase 1b clinical trial (QUILT-4.001; 
NCT04591717). The current trial is designed to investigate the safety and immunogenicity of hAd5-S-
Fusion+N-ETSD (Oral capsule) in combination with hAd5-S-Fusion+N-ETSD (Suspension for 
injection) in healthy volunteers. 
hAd5-S-Fusion+N-ETSD encodes for an optimized S protein (S-Fusion) to enhance stability and cell 
surface expression of RBD; and N protein with an enhanced T-cell stimulation domain (N-ETSD) to 
enhance cell-mediated immunity. In vitro experiments showed that hAd5-S-Fusion+N-ETSD 
demonstrates enhanced expression and exposure of the S protein receptor binding domain (RBD) 
relative to S alone. In an in vivo mouse model, hAd5-S-Fusion+N-ETSD was shown to stimulate 
antibody production and cell-mediated immunity following vaccination. IgG isotyping analysis 
demonstrated that hAd5-S-Fusion+N-ETSD induced Th1 response. Sera from mice vaccinated with 
hAd5-S-Fusion+N-ETSD demonstrated robust neutralizing activity when tested in vitro in a live virus 
neutralization assay and in a surrogate neutralization assay probing RBD binding to receptor. 
Furthermore, on the basis of the recent clinical data from patients recovered from COVID-19 reported 
by Grifoni et al, as well as the corroborating preclinical data that the N protein induces long lasting 
CD4+ and Th1 cell-mediated immunity, it is our hypothesis that this combination of S-Fusion+N-ETSD 
could provide long-lasting immunity beyond short term neutralizing antibodies.  
Moreover, analyses of nonclinical studies in Sprague Dawley (SD) rats have shown that oral 
administration of hAd5-S-Fusion+N-ETSD results in no remarkable changes in clinical signs, 
hematology, clinical pathology, or urinalysis. Similarly, studies in non-human primates (NHPs) have 
shown that SC injection of hAd5-S-Fusion+N-ETSD followed by oral administration of enteric-coated 
capsules in rhesus macaques did not result in any treatment-related toxicities post a single SC injection 
or 7 days after an oral boost. Preliminary analysis of results from these studies have shown that all 
vaccinated NHP generated anti-S IgG and following SARS-CoV-2 challenge, viral replication was 
inhibited in all vaccinated NHP from day 1 post-challenge with complete protection in both nasal 
passages and lung. Furthermore, replicating SARS-CoV-2 dropped immediately and was undetectable 
as soon 3 days post-challenge in some NHP. In contrast, placebo-controlled animals demonstrated 
ongoing viral replication. 
Together, these data suggest that the hAd5-S-Fusion+N-ETSD (Suspension for injection) is well 
tolerated when administered to human subjects SC; that there is little evidence of toxicity associated 
with the oral formulation of hAd5-S-Fusion+N-ETSD in either rodents or NHP; and further, that the 
combination holds promise in stimulating SARS-CoV-2-specific antibody production and rapid viral 
clearance. Advantages of the oral vaccine formulation are 1) that it offers ease of administration and 
the potential to increase patient compliance with scheduled vaccinations and 2) that it incorporates the 
gastrointestinal tract into the antigen sampling mechanism and therefore, the resultant immunity, which 
may result in the production of mucosal immunity and protection from invasion of epithelial tissues by 
SARS-CoV-2 virus. Intramuscular (IM) administration of hAd5-based COVID-19 vaccines has not 
been explored in clinical trials, but hAd5 [E1-] vectors have been administered IM in human clinical 
trials and currently authorized vaccines have utilized this route of administration with proven 
effectiveness. Moreover, one vaccine authorized by FDA, Janssen Ad26.COV2.S, employs an 
adenovirus vector and is administered IM. Therefore, we have included IM administration of hAd5-S-
4


hAd5-COVID-19-PS  
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Confidential and Proprietary 
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Fusion+N-ETSD in the current study to allow the comparison of safety and immunogenicity to SC 
administration. 
Thus, the current study will investigate the safety, reactogenicity, and immunogenicity of the 
combination of SC/IM and oral formulations of hAd5-S-Fusion+N-ETSD and identify an optimal dose 
for future clinical studies. 
Study Objectives 
Study Endpoints 
Primary 
Safety:  
To determine the safety and reactogenicity of the 
combination of hAd5-S-Fusion+N-ETSD 
(Suspension for injection) and hAd5-S-Fusion+N-
ETSD (Oral capsule). 
• 
Incidence of medically-attended adverse 
events (MAAEs) and serious adverse events 
(SAEs) through 1 week post final vaccine 
administration 
• 
Incidence and severity of solicited local 
reactogenicity AEs through 1 week post final 
vaccine administration 
• 
Incidence and severity of solicited systemic 
reactogenicity AEs through 1 week post final 
vaccine administration 
• 
Incidence and severity of unsolicited AEs 
through 1 week post final vaccine 
administration 
• 
Incidence of MAAEs and SAEs through 
30 days and 6 months post final vaccine 
administration 
• 
Incidence and severity of unsolicited AEs 
through 30 days post final vaccine 
administration 
• 
Incidence of abnormal changes of laboratory 
safety examinations  
• 
Changes in vital signs 
Secondary 
Immunogenicity: To determine immunogenicity 
of the combination of hAd5-S-Fusion+N-ETSD 
(Suspension for injection) and hAd5-S-Fusion+N-
ETSD (Oral capsule) as determined by changes in 
humoral and cellular response. 
Humoral Immunogenicity (Timing per Schedule of 
Events): 
• 
GMFR in IgG titer 
• 
GMT of S-specific, RBD-specific, and 
N-specific antibodies against 2019 novel 
coronavirus tested by ELISA in serum 
5


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• 
Percentage of subjects who seroconverted (as 
defined as 4-fold change in antibody titer 
relative to baseline) 
• 
GMFR in neutralizing antibody 
• 
GMT of neutralizing antibody 
• 
Seroconversion rate of neutralizing antibody 
(as defined as 4-fold change in antibody titer 
relative to baseline) 
Cellular Immunogenicity (Timing per Schedule of 
Events): 
• 
CD8+ T-Cell activity against SARS-CoV-2 
S protein and N protein measured by 
ELISPOT assay 
• 
CD4+ T-Cell activity against SARS-CoV-2 
S protein and N protein measured by standard 
immune assay 
6


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Study Design: 
This is a phase 1b, open-label study in adult healthy subjects. This clinical trial is designed to assess 
the safety, reactogenicity, and immunogenicity the combination of hAd5-S-Fusion+N-ETSD 
(Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) and to select an optimal 
combination dose for future studies. 
The study will be divided into 2 stages. Up to 50 healthy subjects will be enrolled to evaluate the 
safety, reactogenicity, and immunogenicity of 5 different treatment regimens. In this evaluation stage, 
subjects will be divided into 5 dosing cohorts with dosing schedule, mode of administration, and 
dosage as follows:  
Cohort 
Number of 
Subjects 
Dosing  
Schedule 
Mode of 
Administration 
Dosage 
1 
10 
Day 1 
SC 
1 × 1011 VP/dose (4 × 109 infectious 
units [IU]/dose) 
Oral (PO) 
1 × 1010 IU/dose 
Day 22 
SC 
1 × 1011 VP/dose (4 × 109 IU/dose) 
2 
10 
Day 1 
SC 
1 × 1011 VP/dose (4 × 109 IU/dose) 
PO 
1 × 1010 IU/dose 
Day 22 
PO 
1 × 1010 IU/dose 
3 
10 
Day 1 
PO 
1 × 1010 IU/dose 
Day 22 
PO 
1 × 1010 IU/dose 
4 
10 
Day 1 
SC 
1 × 1011 VP/dose (4 × 109 IU/dose) 
PO 
1 × 1010 IU/dose 
Day 15 
PO 
1 × 1010 IU/dose 
Day 22 
PO 
1 × 1010 IU/dose 
5 
10 
Day 1 
Intramuscular 
(IM) 
1 × 1011 VP/dose (4 × 109 IU/dose) 
PO 
1 × 1010 IU/dose 
Day 22 
PO 
1 × 1010 IU/dose 
PO (oral) doses are ± 0.5 log. 
Number of IU in this table and throughout protocol was calculated in accordance with Certificate of Analysis 
(COA) for lot number CO5028002.  
 
For subjects in cohorts 1 and 2, hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-
Fusion+N-ETSD (Oral capsule) will be administered on day 1 (prime). Subjects in cohort 1 will be 
administered hAd5-S-Fusion+N-ETSD (Suspension for injection) again on day 22 (boost) and subjects 
in cohort 2 will be administered hAd5-S-Fusion+N-ETSD (Oral capsule) on day 22 (boost). For 
subjects in cohort 3, hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered on days 1 (prime) 
and on day 22 (boost). For subjects in cohort 4, hAd5-S-Fusion+N-ETSD (Suspension for injection) 
and hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered on day 1 (prime) and hAd5-S-
Fusion+N-ETSD (Oral capsule) will be administered on days 15 (boost) and 22 (boost). For subjects in 
cohort 5, hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral 
7


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capsule) will be administered on day 1 (prime) and hAd5-S-Fusion+N-ETSD (Oral capsule) will be 
administered on day 22 (boost). Subjects in cohorts 1, 2, and 4 will be administered hAd5-S-Fusion+N-
ETSD (Suspension for injection) via SC injection and subjects in cohort 5 will be administered hAd5-
S-Fusion+N-ETSD (Suspension for injection) via IM injection. 
Enrollment of the first 6 subjects will be staggered, with no more than 3 subjects enrolled per day for 
the first 2 days. On each of these days, vaccinations will occur at ≥ 3 hour intervals. Safety for these 6 
subjects will be assessed by telephone follow up 24 and 48 hours after receiving the priming 
vaccination. The ImmunityBio Safety Review Committee (SRC) will conduct a review of 48 hour 
safety data on the first 6 subjects; vaccination of additional subjects will proceed if no safety concerns 
are identified.  
Up to 25 additional subjects will be enrolled in the expansion stage of the study. Based on safety and 
immunogenicity data gathered from cohorts 1–5, one treatment regimen will be selected for 
administration to subjects in cohort 6.  
In addition to dosing visits described above, all subjects will have follow up study visits for the 
collection of safety, reactogenicity, and/or immunogenicity data. Additional follow up for safety 
information will occur via telephone contact as noted in the Schedule of Events.  
Safety will be assessed for all subjects and will include monitoring of vital signs, and incidence and 
severity of AEs. Blood samples will be collected for hematology and chemistry analyses and urine 
samples will be collected for urinalysis. Toxicities will be graded using the Guidance for Industry: 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials (2007). Solicited local and systemic AEs will be collected using diaries for 7 days 
following any dose of vaccine. Solicited local AEs to be assessed following both SC and IM 
administration include pain, itching, induration, swelling, and erythema at the injection site. Bleeding, 
bruising, and tingling/numbness will also be assessed following IM administration. Solicited systemic 
AEs to be assessed include chills, fever, nausea, vomiting, diarrhea, headache, fatigue, myalgia, and 
abdominal pain/discomfort. Unsolicited AEs will be recorded in a diary from time of first vaccine dose 
until 30 days after last vaccine dose. Safety visits and telephone calls will occur at scheduled times for 
one year after the last vaccine dose, and will be used to collect unsolicited AEs for 30 days post last 
vaccine dose, all MAAEs and SAEs for 6 months post last vaccine dose (related MAAEs and SAEs at 
any time), as well as any solicited AEs continuing beyond the 7-day period after vaccination.  
Immunogenicity analyses will be conducted by collecting serum and peripheral blood mononuclear cell 
(PBMC) samples from individual patients before and after vaccinations to test for humoral- and 
cell-mediated immune responses. Neutralizing antibodies will be assessed. Immunogenicity 
assessments will be conducted for 1 year after the last vaccine dose. 
Enrollment (planned):  
Up to 75 subjects will be enrolled in this study. 
Eligibility Criteria:  
Inclusion Criteria: 
1. Healthy adults, age 18 – 55 years, inclusive, at time of enrollment. 
2. Able to understand and provide a signed informed consent that fulfills the relevant Institutional 
Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. 
3. Agrees to the collection of biospecimens (eg, nasopharyngeal [NP] swabs and saliva) and 
venous blood per protocol. 
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4. Ability to attend required study visits and return for adequate follow-up, as required by this 
protocol.  
5. Ability to swallow a capsule. 
6. Temperature < 38°C. 
7. Negative for SARS-CoV-2 (qPCR or LAMP test).  
8. Agreement to practice effective contraception for female subjects of childbearing potential and 
non-sterile males. Female subjects of childbearing potential must agree to use effective 
contraception while on study until at least 1 month after the last dose of vaccine. Non-sterile 
male subjects must agree to use a condom while on study until at least 1 month after the last 
dose of vaccine. Effective contraception includes surgical sterilization (eg, vasectomy, tubal 
ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, 
intrauterine devices (IUDs), oral contraceptives, and abstinence. 
Exclusion Criteria: 
1. Allergy to any component of the investigational vaccine, or a more severe allergic reaction and 
history of allergies in the past. 
2. Pregnant and nursing women. A negative serum or urine pregnancy test during screening and 
on the day of and prior to each dose must be documented before the vaccine is administered to 
a female subject of childbearing potential. 
3. Live in a nursing home or long-term care facility. 
4. Chronic lung disease including chronic obstructive pulmonary disease (COPD) or moderate to 
severe asthma. 
5. Pulmonary fibrosis. 
6. Bone marrow or organ transplantation. 
7. Obesity (defined as body mass index [BMI] of 30 kg/m2 or higher). 
8. Diabetes. 
9. Chronic kidney disease. 
10. Liver disease. 
11. Sickle cell disease. 
12. Thalassemia. 
13. Doctors, nurses, first responders, and other healthcare workers working in direct contact with 
COVID-19 patients. 
14. Any disease associated with acute fever, or any infection. 
15. Self-reported history of severe acute respiratory syndrome (SARS). 
16. History of hepatitis B or hepatitis C. 
17. HIV or other acquired or hereditary immunodeficiency. 
9


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18. Serious cardiovascular diseases, such as heart failure, coronary artery disease, 
cardiomyopathies, arrhythmia, conduction block, myocardial infarction, pulmonary 
hypertension, severe hypertension without controllable drugs, etc. 
19. Cerebrovascular disease. 
20. Cystic fibrosis. 
21. Neurologic conditions, such as dementia. 
22. Hereditary or acquired angioneurotic edema. 
23. Urticaria in the last 12 months. 
24. No spleen or functional asplenia. 
25. Platelet disorder or other bleeding disorder that may cause injection contraindication. 
26. Chronic use (more than 14 continuous days) of any medications that may be associated with 
impaired immune responsiveness within 3 months before administration of study vaccine. 
(Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone 
equivalent, allergy injections, immunoglobulin, interferon, immunomodulators. The use of low 
dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted.) 
27. Prior administration of blood products in last 4 months. 
28. Prior administration of other research medicines in last 1 month. 
29. Received or plans to receive an attenuated vaccine within 1 month before or after each study 
vaccination. 
30. Received or plans to receive an inactivated vaccine within 14 days before or after each study 
vaccination. 
31. Current treatment with investigational, authorized, or approved agents for prophylaxis of 
COVID-19. 
32. Have a household contact that has been diagnosed with COVID-19. 
33. Current anti-tuberculosis prophylaxis or therapy. 
34. Currently receiving treatment for cancer or history of cancer in the last five years (except basal 
cell carcinoma of the skin and cervical carcinoma in situ). 
35. According to the judgement of investigator, various medical, psychological, social or other 
conditions that could affect the subjects’ ability to sign informed consent.  
36. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the 
protocol. 
Duration of Treatment:  
In the evaluation stage of the study, subjects in cohorts 1, 2, 3, and 5 will receive vaccine on days 1 and 
22. Subjects in cohort 4 will receive vaccine on days 1, 15, and 22. 
In the expansion stage of the study, subjects’ duration of treatment will be determined by the 
corresponding cohort treatment regimen selected from the evaluation stage. 
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Duration of Follow-up: 
Subjects who receive vaccine will be followed by a health care professional until either death (by any 
cause) or for 1 year past last administration of hAd5-S-Fusion+N-ETSD (Suspension for injection) or 
hAd5-S-Fusion+N-ETSD (Oral capsule). 
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable 
Evaluation of Endpoints: 
Safety: Safety endpoints include assessments of treatment-emergent MAAEs, SAEs, reactogenicity 
AEs, unsolicited AEs, safety laboratory tests, and vital signs. Toxicities will be graded using the 
Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled 
in Preventive Vaccine Clinical Trials (2007).  
Immunogenicity: Immunogenicity endpoints will include GMFR in IgG and additional antibody titers 
from baseline, and percentage of subjects who seroconverted defined as a 4-fold change in antibody 
titer from baseline. Neutralizing antibodies will be determined. ImmunityBio will calculate a relative 
IgG/Neutralization titer based on those data. CD8+ T-Cell activity against SARS-CoV-2 S protein and 
N protein will be measured by ELISPOT assay and CD4+ T-Cell activity against  
SARS-CoV-2 S protein and N protein will be measured by standard immune assays.  
Statistical Methods: 
The purpose of this study is to determine the safety, reactogenicity, and immunogenicity of the 
combination of hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD 
(Oral capsule) and to select an optimal combination dose for future studies. Descriptive statistics will 
be presented for all study endpoints by individual cohort and for all cohorts combined. 
Safety will be assessed by the incidence of treatment-emergent MAAEs, SAEs, and solicited local and 
systemic reactogenicity AEs, and unsolicited AEs for the time period of interest, overall and by grade 
using the Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials (2007). Clinically significant changes in safety 
laboratory tests and vital signs also will be summarized. 
Immunology analyses will be used to provide an assessment of immune responses. Geometric mean 
fold rises (GMFRs) and geometric mean titers (GMTs) and their associated 95% confidence intervals 
(CIs) will be computed by exponentiation of the corresponding log-transformed means and 95% CIs. 
The percentage of subjects who seroconverted (as defined as 4-fold change in antibody titer relative to 
baseline) and 95% Clopper-Pearson CI will be summarized. Neutralizing antibody levels will also be 
summarized. CD8+ and CD4+ T-Cell activity also will be summarized. 
11


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Figure 1: 
Phase 1b Study Schema 
 
 
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Table 10: 
Evaluation Stage (Cohorts 1‒5): Schedule of Events 
Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
73 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
8 
9 
 
 
10 
11 
12 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
51 
90 
120 
150 
180 
270 
365 
Windows (Days) 
 
± 1 
± 5 
± 14 
± 28 
General Assessments 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 history 
of disease or 
exposureb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Confirm 
contraceptive 
measures 
X 
X 
 
C4 
only 
X 
 
 
 
X 
 
 
 
 
 
 
 
Physical exam: 
height, weightc 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
X 
Vital signsd 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
X 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
73 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
8 
9 
 
 
10 
11 
12 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
51 
90 
120 
150 
180 
270 
365 
Subject training on 
AE diaries 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Issue diaries for 
solicited and 
unsolicited AEs 
 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
 
Review and collect 
solicited AE diary  
 
 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
Review and collect 
unsolicited AE diary  
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
In office AE 
collectione 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
X 
X 
X 
Telephone safety 
follow upe 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
 
 
 
Vaccine Administration 
Cohort 1  
 
Xf 
 
 
Xg 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
Xf 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Cohort 3 
 
Xh 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Cohort 4 
 
Xf 
 
Xh 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Cohort 5 
 
Xf 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
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Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
73 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
8 
9 
 
 
10 
11 
12 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
51 
90 
120 
150 
180 
270 
365 
Laboratory Assessments 
Chemistry panela,i 
X 
X 
X 
C4 
only 
X 
 
 
 
X 
 
X 
 
 
X 
 
 
Hematologya,j 
X 
X 
X 
C4 
only 
X 
 
 
 
X 
 
X 
 
 
X 
 
 
Urinalysisa,k  
X 
X 
X 
C4 
only 
X 
 
 
 
X 
 
X 
 
 
X 
 
 
Collect 
biospecimens for 
SARS-CoV-2 
testinga 
X 
X 
 
C4 
only 
X 
 
 
 
 X 
 
X 
 
 
X 
X 
X 
Collect whole 
blood/saliva for 
immunogenicityl 
 
X 
 
C4 
only 
X 
 
X 
 
X 
X 
X 
 
 
X 
X 
X 
Pregnancy testm 
X 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: C4, cohort 4 
a Day 1 chemistry, hematology, and urinalysis assessments do not need to be repeated if screening assessments were performed within 1 week prior to the start of 
treatment. Day 1 biospecimen collection for SARS-CoV-2 testing does not need to be repeated if screening assessments were performed within 72 hours prior 
to the start of treatment.  
b Potential exposure to SARS-CoV-2, symptoms of COVID-19, or outside testing results for SARS-CoV-2 infection will be collected at every study follow up 
visit and phone call. 
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c Full physical examination will be performed at screening and symptom-directed (targeted) physical examination at all other time points if indicated. Height 
required at baseline/screening visit only.  
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed. Temperature will be documented upon collection of vital signs and 
subsequently if clinically indicated. Day 1 collection of vital signs does not need to be repeated if screening assessments were performed within 72 hours prior 
to the start of treatment. 
e Safety for the first 6 subjects enrolled will be assessed by telephone follow up 24 and 48 hours after receiving the priming vaccination. The ImmunityBio SRC 
will conduct a review of 48-hour safety data on the first 6 subjects; vaccination of additional subjects will proceed if no safety concerns are identified.  In office 
AE collection will continue to occur for 1 year, but only applicable AEs will be collected (see Section 7.2). 
f Both hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered. hAd5-S-Fusion+N-ETSD 
(Suspension for injection) will be administered either SC (subjects in cohorts 1, 2, and 4) or IM (subjects in cohort 5). 
g hAd5-S-Fusion+N-ETSD (Suspension for injection) will be administered SC only. 
h hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered only. 
i See Table 9 for additional details on laboratory assessments. Blood draws for lab assessments should occur prior to vaccine administration. 
j Hematology to include CBC with differential (5 part) as outlined in Table 9. Blood draws for lab assessments should occur prior to vaccine administration. 
k Urinalysis testing will include at a minimum protein, glucose, and presence of red blood cells. Sample collection should occur prior to vaccine administration. 
l Immunogenicity testing includes measures of antibody response and cell-mediated immunity against target antigens, as well as hAd5 serostatus for determining 
baseline hAd5 immunity and monitoring for antivector immune responses. Sample collection should occur prior to vaccine administration. A lab manual will 
be provided to the sites with detailed guidance for saliva collection, serum and PBMC preparation, storage, and shipping. Saliva and blood will be collected on 
all days indicated except days 10 (cohort 4 only) and 22, on which only blood will be collected. 
m Serum or urine pregnancy tests for females of childbearing potential at baseline/screening and at each visit where study drug is administered. 
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Table 11: 
Escalation Stage (Cohort 6): Schedule of Events 
The schedule below shows assessments for each of the evaluation stage cohorts 1‒5. Based on safety and immunogenicity data 
gathered from cohorts 1‒5, one treatment regimen will be selected for administration to subjects in cohort 6; only the corresponding 
assessments will apply in this escalation stage. 
Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
73 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
8 
9 
 
 
10 
11 
12 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
51 
90 
120 
150 
180 
270 
365 
Windows (Days) 
 
± 1 
± 5 
± 14 
± 28 
General Assessments 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 history 
of disease or 
exposureb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Confirm 
contraceptive 
measures 
X 
X 
 
C4 
only 
X 
 
 
 
X 
 
 
 
 
 
 
 
Physical exam: 
height, weightc 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
X 
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Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
73 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
8 
9 
 
 
10 
11 
12 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
51 
90 
120 
150 
180 
270 
365 
Vital signsd 
X 
X 
X 
C4 
only 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
X 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Subject training on 
AE diaries 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Issue diaries for 
solicited and 
unsolicited AEs 
 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
 
Review and collect 
solicited AE diary  
 
 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
Review and collect 
unsolicited AE diary  
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
In office AE 
collectione 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
X 
X 
X 
Telephone safety 
follow up 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
 
 
 
Vaccine Administration 
Cohort 1  
 
Xf 
 
 
Xg 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
Xf 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
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Study Period 
Baseline/ 
Screeninga 
Vaccine Administration and Initial 
Follow Up 
Extended Follow Up 
EOS 
Study Day 
-14 to -1 
1 
8 
15 
22 
29 
36 
43 
52 
73 
112 
142 
172 
202 
292 
387 
Clinical visit 
number 
Screening 
1 
2 
3 
4 
5 
6 
 
7 
8 
9 
 
 
10 
11 
12 
Days post 1st dose 
 
 
7 
14 
21 
 
 
 
 
 
 
 
 
 
 
 
Days post final dose 
 
 
 
 
 
7 
14 
21 
30 
51 
90 
120 
150 
180 
270 
365 
Cohort 3 
 
Xh 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Cohort 4 
 
Xf 
 
Xh 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Cohort 5 
 
Xf 
 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Laboratory Assessments 
Collect 
biospecimens for 
SARS-CoV-2 
testinga 
X 
X 
 
C4 
only 
X 
 
 
 
 X 
 
X 
 
 
X 
X 
X 
Collect whole 
blood/saliva for 
immunogenicityi 
 
X 
 
C4 
only 
X 
 
X 
 
X 
X 
X 
 
 
X 
X 
X 
Pregnancy testj 
X 
X 
 
C4 
only 
X 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: C4, cohort 4 
a Day 1 biospecimen collection for SARS-CoV-2 testing does not need to be repeated if screening assessments were performed within 72 hours prior to the start 
of treatment.  
b Potential exposure to SARS-CoV-2, symptoms of COVID-19, or outside testing results for SARS-CoV-2 infection will be collected at every study follow up 
visit and phone call. 
c Full physical examination will be performed at screening and symptom-directed (targeted) physical examination at all other time points if indicated. Height 
required at baseline/screening visit only.  
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed. Temperature will be documented upon collection of vital signs and 
subsequently if clinically indicated. Day 1 collection of vital signs does not need to be repeated if screening assessments were performed within 72 hours prior 
to the start of treatment. 
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e In office AE collection will continue to occur for 1 year, but only applicable AEs will be collected (see Section 7.2). 
f Both hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered. hAd5-S-Fusion+N-ETSD 
(Suspension for injection) will be administered either SC (subjects in cohorts 1, 2, and 4) or IM (subjects in cohort 5). 
g hAd5-S-Fusion+N-ETSD (Suspension for injection) will be administered SC only. 
h hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered only. 
i Immunogenicity testing includes measures of antibody response and cell-mediated immunity against target antigens, as well as hAd5 serostatus for determining 
baseline hAd5 immunity and monitoring for anti-vector immune responses. Sample collection should occur prior to vaccine administration. A lab manual will 
be provided to the sites with detailed guidance for saliva collection, serum and PBMC preparation, storage, and shipping. Saliva and blood will be collected on 
all days indicated except days 10 (cohort 4 only) and 22, on which only blood will be collected. 
j Serum or urine pregnancy tests for females of childbearing potential at baseline/screening and each visit where study drug is administered. 
95