COVID-19 Oral and Subcutaneous Vaccination Using a 2nd Generation (E1/E2B/E3-Deleted) Adenovirus Platform in Healthy Volunteers in USA

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 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.

Official Title
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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

Conditions
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Covid19

Intervention / Treatment
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* Biological: hAd5-S-Fusion+N-ETSD (Suspension for injection)
* Drug: hAd5-SFusion+ N-ETSD (Oral capsule)


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. Ability to swallow a capsule. 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. Current or former 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, authorized, or approved 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- hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-SFusion+ N-ETSD (Oral capsule)<br>For subjects in cohort 1, hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-SFusion+N-ETSD (Oral capsule) will be administered on day 1 (prime) and hAd5-S-Fusion+N-ETSD (Suspension for injection) again on day 22 (boost). | Biological: hAd5-S-Fusion+N-ETSD (Suspension for injection)<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>Drug: hAd5-SFusion+ N-ETSD (Oral capsule)<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- hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-SFusion+ N-ETSD (Oral capsule)<br>For subjects in cohort 2, hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-SFusion+N-ETSD (Oral capsule) will be administered on day 1 (prime) and hAd5-S-Fusion+N-ETSD (Oral capsule) on day 22 (boost). | Biological: hAd5-S-Fusion+N-ETSD (Suspension for injection)<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>Drug: hAd5-SFusion+ N-ETSD (Oral capsule)<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 3 - hAd5-S-Fusion+N-ETSD (Oral capsule)<br>For subjects in cohort 3, hAd5-S-Fusion+N-ETSD (Oral capsule) will be administered on days 1 (prime) and on day 22 (boost). | Drug: hAd5-SFusion+ N-ETSD (Oral capsule)<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 4 - hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule)<br>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-SFusion+N-ETSD (Oral capsule) will be administered on days 15 (boost) and 22 (boost). | Biological: hAd5-S-Fusion+N-ETSD (Suspension for injection)<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>Drug: hAd5-SFusion+ N-ETSD (Oral capsule)<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 medically-attended adverse events (MAAEs) and serious adverse events (SAEs) through 1 week post final vaccine administration | 1 week post final vaccine administration | 
| 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 post final vaccine administration | 
| 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 post final vaccine administration | 
| Incidence and severity of unsolicited AEs | Incidence and severity of unsolicited AEs through 1 week post final vaccine administration | 1 week post final vaccine administration | 
| Incidence of MAAEs and SAEs | Incidence of MAAEs and SAEs through 30 days post final vaccine administration | 30 days post final vaccine | 
| Incidence of MAAEs and SAEs | Incidence of MAAEs and SAEs through 6 months post final vaccine | 6 months post final vaccine | 
| Incidence and severity of unsolicited AEs | Incidence and severity of unsolicited AEs through 30 days post final vaccine administration | 30 days post final vaccine administration | 
| Incidence of changes of laboratory safety examinations | Incidence of abnormal changes of laboratory safety examinations | Day 387 | 
| Vital Sign - Temperature | Changes in vital signs from Grades 1-4: Temperature - measured in (°C) or (°F) | Day 387 | 
| Vital Sign - Heart rate | Changes in vital signs from Grades 1-4: Heart rate - measured by how many heart beats per minute | Day 387 | 
| Vital Sign - Blood Pressure | Changes in vital signs from Grades 1-4: Systolic/Diastolic - measured in mm Hg | Day 387 | 
| Vital Sign - Respiratory Rate | Changes in vital signs from Grades 1-4: Respiratory Rate - measured in how many breaths per minute | Day 387 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMFR in IgG titer | Geometric mean fold rise (GMFR) in IgG titer | Day 387 | 
| GMT of S-specific, RBD-specific, and N-specific antibodies | Geometric mean titer (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, in the absence of evidence of incident natural infection | Day 387 | 
| GMT of neutralizing antibody | GMT in neutralizing antibody, in the absence of evidence of incident natural infection | 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 |