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

ImmunityBio, Inc.

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Conditions

Covid19

Interventions

hAd5-S-Fusion+N-ETSD vaccineBIOLOGICAL

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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. 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, NP swabs and/or saliva sample) 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. 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: 1. Persistent grade ≥ 2 AEs related to previous COVID-19 vaccination at the time of enrollment. 2. Allergy to any component of the investigational vaccine, or a more severe allergic reaction and history of allergies in the past. 3. 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. 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. Extreme obesity (defined as BMI of 35 kg/m2 or higher). 8. Diabetes. 9. Chronic kidney disease. 10. Liver disease. 11. Sickle cell disease. 12. Thalassemia. 13. Any disease associated with acute fever, or any infection. 14. Self-reported history of SARS. 15. History of hepatitis B or hepatitis C. 16. HIV or other acquired or hereditary immunodeficiency. 17. Serious cardiovascular diseases, such as heart failure, coronary artery disease, cardiomyopathies, arrhythmia, conduction block, myocardial infarction, pulmonary hypertension, severe hypertension without controllable drugs, etc. 18. Cerebrovascular disease. 19. Cystic fibrosis. 20. Neurologic conditions, such as dementia. 21. Hereditary or acquired angioneurotic edema. 22. No spleen or functional asplenia. 23. Platelet disorder or other bleeding disorder that may cause injection contraindication. 24. 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.) 25. Prior administration of blood products in last 4 months. 26. 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). 27. According to the judgement of investigator, various medical, psychological, social or other conditions that could affect the subjects ability to sign informed consent. 28. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.

Outcomes

Primary Outcomes

Phase 1 Safety: Incidence of MAAEs and SAEs

Incidence of MAAEs and SAEs through 1 week post final vaccine administration

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: through 1 week post final vaccine administration

Phase 1 Safety: Incidence of MAAEs and SAEs

Incidence of MAAEs and SAEs through 30 days

Time frame: through 30 days

Phase 1 Safety: Incidence of MAAEs and SAEs

Incidence of MAAEs and SAEs at 6 months post final vaccine administration

Time frame: 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

Time frame: through 30 days post final vaccine administration

Data from ClinicalTrials.gov

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Secondary Outcomes

Phase 1 Humoral Immunogenicity: GMT of S-specific and N-specific antibodies

GMT of S-specific and N-specific antibodies against 2019 novel coronavirus

Time frame: Day 365

Phase 1 Humoral Immunogenicity: GMT of neutralizing antibody

GMT of neutralizing antibody

Time frame: Day 365

Phase 1 Mucosal Immunogenicity: GMT of IgA antibody levels

GMT of IgA antibody levels

Time frame: 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.

Time frame: 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.

Time frame: ≥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

Time frame: 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

Time frame: Day 365

Phase 2 Efficacy: Humoral Immunogenicity - GMT of neutralizing antibody

GMT of neutralizing antibody

Time frame: Day 365

Phase 2 Efficacy: Mucosal Immunogenicity - GMT of IgA antibody levels

GMT of IgA antibody levels

Time frame: Day 365

Phase 2 Efficacy: Cellular Immunogenicity - T cell activity

T cell activity against SARS-CoV-2 S protein and N protein measured

Time frame: Day 365

Phase 2 Safety: Incidence of MAAEs and SAEs

Incidence of MAAEs and SAEs through 1 week post final vaccine administration

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Day 365

Phase 2 Safety: Vital Sign - Temperature

Changes in vital signs from Grades 1-4: measured in (°C) or (°F)

Time frame: 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

Time frame: Day 365

Phase 2 Safety: Vital Sign - Blood Pressure

Changes in vital signs from Grades 1-4: systolic/diastolic - measured in mm Hg

Time frame: Day 365

Phase 2 Safety: Vital Sign - Respiratory rate

Changes in vital signs from Grades 1-4: measured in how many breaths per minute

Time frame: Day 365