COVID-19 Vaccination Using a 2nd Generation (E1/E2B/E3-Deleted) Adenoviral-COVID-19 in Normal Healthy Volunteers

Study Overview
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Brief Summary
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This is a phase 1b, open-label study in adult healthy subjects. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of the hAd5-S-Fusion+N-ETSD vaccine and select a dose for future studies.

Official Title
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Phase 1b Open-Label Study of the Safety, Reactogenicity, and Immunogenicity of Prophylactic Vaccination With 2nd Generation (E1/E2B/E3-Deleted) Adenoviral-COVID-19 in Normal Healthy Volunteers

Conditions
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COVID-19

Intervention / Treatment
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* Biological: hAd5-S-Fusion+N-ETSD vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults, age 18 - 55 years, inclusive, at time of enrollment. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. Agrees to the collection of biospecimens (eg, nasopharyngeal [NP] swabs) and venous blood per protocol. Ability to attend required study visits and return for adequate follow-up, as required by this protocol. Temperature < 38°C. Negative for SARS-CoV-2 (qPCR or LAMP test) and no known previous COVID-19 exposure or disease. 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: Allergy to any component of the investigational vaccine, or a more severe allergic reaction and history of allergies in the past. 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. Live in a nursing home or long-term care facility. Chronic lung disease including chronic obstructive pulmonary disease (COPD) or moderate to severe asthma. Pulmonary fibrosis. Active smoker. Bone marrow or organ transplantation. Obesity (defined as body mass index [BMI] of 30 kg/m2 or higher). Diabetes. Chronic kidney disease. Liver disease. Sickle cell disease. Thalassemia. Doctors, nurses, first responders, and other healthcare workers working in direct contact with COVID-19 patients. Any disease associated with acute fever, or any infection. Self-reported history of severe acute respiratory syndrome (SARS). History of hepatitis B or hepatitis C. HIV or other acquired or hereditary immunodeficiency. Serious cardiovascular diseases, such as heart failure, coronary artery disease, cardiomyopathies, arrhythmia, conduction block, myocardial infarction, pulmonary hypertension, severe hypertension without controllable drugs, etc. Cerebrovascular disease. Cystic fibrosis. Neurologic conditions, such as dementia. Hereditary or acquired angioneurotic edema. Urticaria in the last 12 months. No spleen or functional asplenia. Platelet disorder or other bleeding disorder that may cause injection contraindication. 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.) Prior administration of blood products in last 4 months. Prior administration of other research medicines in last 1 month. Received or plans to receive an attenuated vaccine within 1 month before or after each study vaccination. Received or plans to receive an inactivated vaccine within 14 days before or after each study vaccination. Current treatment with investigational agents for prophylaxis of COVID-19. Have a household contact that has been diagnosed with COVID-19. Current anti-tuberculosis prophylaxis or therapy. 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). According to the judgement of investigator, various medical, psychological, social or other conditions that could affect the subjects ability to sign informed consent. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 0.5 mL of hAd5-S-Fusion+N-ETSD SC<br>0.5 mL of hAd5-S-Fusion+N-ETSD SC (5 × 10e10 VP/dose) on days 1 and 22 | Biological: hAd5-S-Fusion+N-ETSD vaccine<br>* 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.<br>|
| Experimental: Cohort 2: 1.0 mL of hAd5-S-Fusion+N-ETSD SC<br>Cohort 2: 1.0 mL of hAd5-S-Fusion+N-ETSD SC (1 × 10e11 VP/dose) on days 1 and 22 | Biological: hAd5-S-Fusion+N-ETSD vaccine<br>* 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.<br>|
| Experimental: Cohort 3a: 1.0 mL of hAd5-S-Fusion+N-ETSD SC and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually<br>Cohort 3a: 1.0 mL of hAd5-S-Fusion+N-ETSD SC (1 × 10e11 VP/dose) and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on day 1; 1.0 mL of hAd5-S-Fusion+N-ETSD SC (1 × 10e11 VP/dose) and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on day 22 | Biological: hAd5-S-Fusion+N-ETSD vaccine<br>* 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.<br>|
| Experimental: Cohort 3b: 1.0 mL of hAd5-S-Fusion+N-ETSD SC and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually<br>Cohort 3b: 1.0 mL of hAd5-S-Fusion+N-ETSD SC (1 × 10e11 VP/dose) and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on day 1; no vaccine on day 22 | Biological: hAd5-S-Fusion+N-ETSD vaccine<br>* 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.<br>|
| Experimental: Cohort 3c: 1.0 mL of hAd5-S-Fusion+N-ETSD SC and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually<br>Cohort 3c: 1.0 mL of hAd5-S-Fusion+N-ETSD SC (1 × 10e11 VP/dose) and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on day 1; 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on day 22 | Biological: hAd5-S-Fusion+N-ETSD vaccine<br>* 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.<br>|
| Experimental: Cohort 3d: 1.0 mL of hAd5-S-Fusion+N-ETSD SC and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually<br>Cohort 3d: 1.0 mL of hAd5-S-Fusion+N-ETSD SC (1 × 10e11 VP/dose) and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on day 1; 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on days 15 and 29 | Biological: hAd5-S-Fusion+N-ETSD vaccine<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of MAAEs and SAEs | Incidence of MAAEs and SAEs through 1 week post final vaccine administration | 1 week | 
| Incidence and severity of solicited local reactogenicity AEs | Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration | 1 week | 
| Incidence and severity of solicited systemic reactogenicity AEs | Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration | 1 week | 
| Incidence and severity of unsolicited AEs | Incidence and severity of unsolicited AEs through 1 week post final vaccine administration | 1 week | 
| Incidence of MAAEs and SAEs | Incidence of MAAEs and SAEs through 30 days and 6 months post final vaccine administration | 30 days to 6 months | 
| Incidence and severity of unsolicited AEs | Incidence and severity of unsolicited AEs through 30 days post final vaccine administration | 30 days | 
| Incidence of abnormal changes of laboratory safety examinations | Incidence of abnormal changes of laboratory safety examinations | 30 days | 
| Vital Signs - Fever | Changes in vital signs from Grades 1-4: - Fever - measured in (°C) or (°F) | 30 days | 
| Vital Signs - Tachycardia | Changes in vital signs from Grades 1-4: - Tachycardia - measured in beats per minute | 30 Days | 
| Vital Signs - Bradycardia | Changes in vital signs from Grades 1-4: - Bradycardia - measured in how many beats per minute | 30 Days | 
| Vital Signs - Hypertension | Changes in vital signs from Grades 1-4: - Hypertension (systolic/diastolic) - measured in mm Hg | 30 Days | 
| Vital Signs - Hypotension | Changes in vital signs from Grades 1-4: - Hypotension (systolic) - measured in mm Hg | 30 Days | 
| Vital Signs - Respiratory Rate | Changes in vital signs from Grades 1-4: - Respiratory Rate - measured in how many breaths per minute | 30 Days | 
| GMFR in IgG titer | GMFR in IgG titer | Day 387 | 
| GMT of S-specific, RBD-specific, and N-specific antibodies against 2019 novel coronavirus | GMT of S-specific, RBD-specific, and N-specific antibodies against 2019 novel coronavirus tested by ELISA in serum | Day 387 | 
| Percentage of subjects who seroconverted | Percentage of subjects who seroconverted (as defined as 4-fold change in antibody titer relative to baseline) | Day 387 | 
| GMFR in neutralizing antibody | GMFR in neutralizing antibody | Day 387 | 
| GMT | GMT of neutralizing antibody | Day 387 | 
| Seroconversion rate of neutralizing antibody | Seroconversion rate of neutralizing antibody (as defined as 4-fold change in antibody titer relative to baseline) | Day 387 | 
| CD8+ T-Cell activity against SARS-CoV-2 S protein, RBD, and N protein | CD8+ T-Cell activity against SARS-CoV-2 S protein, RBD, and N protein measured by ELISPOT assay | Day 387 | 
| CD4+ T-Cell activity against SARS-CoV-2 S protein, RBD, and N protein | CD4+ T-Cell activity against SARS-CoV-2 S protein, RBD, and N protein measured by standard immune assay | Day 387 |