COVID-19 Subcutaneously and Orally Administered Supplemental Vaccine Boost to Enhance T Cell Protection in Those Who Have Already Received EUA S-Based Vaccines

Study Overview
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Brief Summary
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This is a phase 1/2 study in adult healthy subjects that have previously been vaccinated with an FDA-authorized vaccine against COVID-19. This clinical trial is designed to assess the safety, efficacy, reactogenicity, and immunogenicity of hAd5-S-Fusion+N-ETSD formulated for subcutaneous and oral (capsule) administration.

Official Title
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Phase 1/2 Study of the Safety, Reactogenicity, and Immunogenicity of a Subcutaneously- and Orally- Administered Supplemental Spike & Nucleocapsid-targeted COVID-19 Vaccine to Enhance T Cell Based Immunogenicity in Participants Who Have Already Received Prime + Boost Vaccines Authorized For Emergency Use

Conditions
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Covid19

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 years, inclusive, at time of enrollment, that have previously received an FDA-authorized COVID-19 vaccine (both prime and boost) ≥14 days and ≤ 6 months before 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, NP swabs and/or saliva sample) 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. 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, IUDs, oral contraceptives, and abstinence. Exclusion Criteria: Persistent grade ≥ 2 AEs related to previous COVID-19 vaccination at the time of enrollment. 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. Chronic lung disease including chronic obstructive pulmonary disease (COPD) or moderate to severe asthma. Pulmonary fibrosis. Bone marrow or organ transplantation. Extreme obesity (defined as BMI of 35 kg/m2 or higher). Diabetes. Chronic kidney disease. Liver disease. Sickle cell disease. Thalassemia. Any disease associated with acute fever, or any infection. Self-reported history of 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. 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. 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: 80 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: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Open label 2 Cohort Phase 1 Study leading to Randomized Phase 2 Study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Cohort 1: hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous<br>Cohort 1 (n=20): hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous on Day 1 | Biological: hAd5-S-Fusion+N-ETSD vaccine<br>* hAd5-S-Fusion+N-ETSD is a human adenovirus serotype 5 (hAd5) vector with E1/E2b/E3 deletions expressing SARS-CoV-2 viral antigen S fusion protein and N with an enhanced T-cell stimulation domain.<br>|
| Experimental: Experimental: Cohort 2: hAd5-S-Fusion+N-ETSD Subcutaneous and Oral<br>Cohort 2 (n=20): hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous and 1 × 10e10 IU/dose Oral on Day 1 | Biological: hAd5-S-Fusion+N-ETSD vaccine<br>* hAd5-S-Fusion+N-ETSD is a human adenovirus serotype 5 (hAd5) vector with E1/E2b/E3 deletions expressing SARS-CoV-2 viral antigen S fusion protein and N 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 |
| --- | --- | --- |
| Phase 1 Safety: Incidence of MAAEs and SAEs | Incidence of MAAEs and SAEs through 1 week post final vaccine administration | through 1 week post final vaccine administration | 
| Phase 1 Safety: Incidence and severity of solicited local reactogenicity AEs | Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration | through 1 week post final vaccine administration | 
| Phase 1 Safety: Incidence and severity of solicited systemic reactogenicity AEs | Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration | through 1 week post final vaccine administration | 
| Phase 1 Safety: Incidence and severity of unsolicited AEs | Incidence and severity of unsolicited AEs through 1 week post final vaccine administration | through 1 week post final vaccine administration | 
| Phase 1 Safety: Incidence of MAAEs and SAEs | Incidence of MAAEs and SAEs through 30 days | through 30 days | 
| Phase 1 Safety: Incidence of MAAEs and SAEs | Incidence of MAAEs and SAEs at 6 months post final vaccine administration | 6 months post final vaccine administration | 
| Phase 1 Safety: Incidence and severity of unsolicited AEs | Incidence and severity of unsolicited AEs through 30 days post final vaccine administration | through 30 days post final vaccine administration | 
| Phase 1 Safety: Incidence of changes of laboratory safety examinations | Incidence of abnormal changes of laboratory safety examinations | Day 365 | 
| Phase 1 Safety: Vital Sign - Temperature | Changes in vital signs from Grades 1-4: measured in (°C) or (°F) | Day 365 | 
| Phase 1 Safety: Vital Sign - Heart Rate | Changes in vital signs from Grades 1-4: measured by how many heart beats per minute | Day 365 | 
| Phase 1 Safety: Vital Sign - Blood Pressure | Changes in vital signs from Grades 1-4: systolic/diastolic - measured in mm Hg | Day 365 | 
| Phase 1 Safety: Vital Sign - Respiratory Rate | Changes in vital signs from Grades 1-4: measured in how many breaths per minute | Day 365 | 
| Phase 2 Efficacy: Percent of subjects that show an increase in N-reactive T cells | Percent of subjects that show an increase in N-reactive T cells as assayed by N-Tiferon assay (≥ 25 pg/mL increase in cytokine concentration from baseline) | from baseline to Day 365 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 Humoral Immunogenicity: GMT of S-specific and N-specific antibodies | GMT of S-specific and N-specific antibodies against 2019 novel coronavirus | Day 365 | 
| Phase 1 Humoral Immunogenicity: GMT of neutralizing antibody | GMT of neutralizing antibody | Day 365 | 
| Phase 1 Mucosal Immunogenicity: GMT of IgA antibody levels | GMT of IgA antibody levels | Day 365 | 
| Phase 1 Cellular Immunogenicity: T cell activity | T cell activity against SARS-CoV-2 S protein and N protein. T cell activity against SARS-CoV-2 S protein and N protein. ImmunityBio has developed a rapid assay (N-Tiferon) to detect SARS-CoV-2-specific T cell responses directly in whole blood from participants in QUILT-4.001 vaccinated with hAd5 S-Fusion+N-ETSD targeting the S and N antigens of SARS-CoV-2. This assay detected interferon-γ (IFN-γ)-secreting S- and N-specific T cells directly in whole blood post-vaccination. | Day 365 | 
| Phase 2 Efficacy: Incidence and severity of COVID-19 ≥14 days after vaccination | Incidence and severity of COVID-19 ≥14 days after vaccination in subjects with no evidence of past SARS-CoV-2 infection. It applies to ≥3 for injection site reaction, fever, and other AEs. It also includes signs and symptoms of hypersensitivity which may include red rash (excluding site of injection), swollen throat or swollen areas of the body, wheezing, fainting, chest tightness, difficulty breathing, hoarse voice, difficulty swallowing, vomiting, diarrhea, and stomach cramping. | ≥14 days after vaccination | 
| Phase 2 Efficacy: Mean SARS-CoV-2 viral load | Mean SARS-CoV-2 viral load for subjects with confirmed COVID-19 ≥14 days after vaccination | Day 365 | 
| Phase 2 Efficacy: Humoral Immunogenicity - GMT of S-specific and N-specific antibodies | GMT of S-specific and N-specific antibodies against 2019 novel coronavirus | Day 365 | 
| Phase 2 Efficacy: Humoral Immunogenicity - GMT of neutralizing antibody | GMT of neutralizing antibody | Day 365 | 
| Phase 2 Efficacy: Mucosal Immunogenicity - GMT of IgA antibody levels | GMT of IgA antibody levels | Day 365 | 
| Phase 2 Efficacy: Cellular Immunogenicity - T cell activity | T cell activity against SARS-CoV-2 S protein and N protein measured | Day 365 | 
| Phase 2 Safety: Incidence of MAAEs and SAEs | Incidence of MAAEs and SAEs through 1 week post final vaccine administration | through 1 week post final vaccine administration | 
| Phase 2 Safety: Incidence and severity of solicited local reactogenicity AEs | Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration | through 1 week post final vaccine administration | 
| Phase 2 Safety: Incidence and severity of solicited systemic reactogenicity AEs | Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration | through 1 week post final vaccine administration | 
| Phase 2 Safety: Incidence and severity of unsolicited AEs | Incidence and severity of unsolicited AEs through 1 week post final vaccine administration | through 1 week post final vaccine administration | 
| Phase 2 Safety: Incidence of MAAEs and SAEs | Incidence of MAAEs and SAEs through 30 days and 6 months post final vaccine administration | through 30 days and 6 months post final vaccine administration | 
| Phase 2 Safety: Incidence and severity of unsolicited AEs | Incidence and severity of unsolicited AEs through 30 days post final vaccine administration | through 30 days post final vaccine administration | 
| Phase 2 Safety: Incidence of changes of laboratory safety examinations | Incidence of abnormal changes of laboratory safety examinations | Day 365 | 
| Phase 2 Safety: Vital Sign - Temperature | Changes in vital signs from Grades 1-4: measured in (°C) or (°F) | Day 365 | 
| Phase 2 Safety: Vital Sign - Heart rate | Changes in vital signs from Grades 1-4: measured by how many heart beats per minute | Day 365 | 
| Phase 2 Safety: Vital Sign - Blood Pressure | Changes in vital signs from Grades 1-4: systolic/diastolic - measured in mm Hg | Day 365 | 
| Phase 2 Safety: Vital Sign - Respiratory rate | Changes in vital signs from Grades 1-4: measured in how many breaths per minute | Day 365 |