Clinical trial NCT04845191: COVID-19 Subcutaneously and Orally Administered Supplemental Vaccine Boost to Enhance T Cell Protection in Those Who Have Already Received EUA S-Based Vaccines
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Covid19
Lead sponsor: ImmunityBio, Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Open label 2 Cohort Phase 1 Study leading to Randomized Phase 2 Study
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1 Safety: Incidence of MAAEs and SAEs
timeFrame: through 1 week post final vaccine administration
measure: Phase 1 Safety: Incidence and severity of solicited local reactogenicity AEs
timeFrame: through 1 week post final vaccine administration
measure: Phase 1 Safety: Incidence and severity of solicited systemic reactogenicity AEs
timeFrame: through 1 week post final vaccine administration
measure: Phase 1 Safety: Incidence and severity of unsolicited AEs
timeFrame: through 1 week post final vaccine administration
measure: Phase 1 Safety: Incidence of MAAEs and SAEs
timeFrame: through 30 days
measure: Phase 1 Safety: Incidence of MAAEs and SAEs
timeFrame: 6 months post final vaccine administration
measure: Phase 1 Safety: Incidence and severity of unsolicited AEs
timeFrame: through 30 days post final vaccine administration
measure: Phase 1 Safety: Incidence of changes of laboratory safety examinations
timeFrame: Day 365
measure: Phase 1 Safety: Vital Sign - Temperature
timeFrame: Day 365
measure: Phase 1 Safety: Vital Sign - Heart Rate
timeFrame: Day 365
measure: Phase 1 Safety: Vital Sign - Blood Pressure
timeFrame: Day 365
measure: Phase 1 Safety: Vital Sign - Respiratory Rate
timeFrame: Day 365
measure: Phase 2 Efficacy: Percent of subjects that show an increase in N-reactive T cells
timeFrame: from baseline to Day 365
Secondary outcomes:
measure: Phase 1 Humoral Immunogenicity: GMT of S-specific and N-specific antibodies
timeFrame: Day 365
measure: Phase 1 Humoral Immunogenicity: GMT of neutralizing antibody
timeFrame: Day 365
measure: Phase 1 Mucosal Immunogenicity: GMT of IgA antibody levels
timeFrame: Day 365
measure: Phase 1 Cellular Immunogenicity: T cell activity
timeFrame: Day 365
measure: Phase 2 Efficacy: Incidence and severity of COVID-19 ≥14 days after vaccination
timeFrame: ≥14 days after vaccination
measure: Phase 2 Efficacy: Mean SARS-CoV-2 viral load
timeFrame: Day 365
measure: Phase 2 Efficacy: Humoral Immunogenicity - GMT of S-specific and N-specific antibodies
timeFrame: Day 365
measure: Phase 2 Efficacy: Humoral Immunogenicity - GMT of neutralizing antibody
timeFrame: Day 365
measure: Phase 2 Efficacy: Mucosal Immunogenicity - GMT of IgA antibody levels
timeFrame: Day 365
measure: Phase 2 Efficacy: Cellular Immunogenicity - T cell activity
timeFrame: Day 365
measure: Phase 2 Safety: Incidence of MAAEs and SAEs
timeFrame: through 1 week post final vaccine administration
measure: Phase 2 Safety: Incidence and severity of solicited local reactogenicity AEs
timeFrame: through 1 week post final vaccine administration
measure: Phase 2 Safety: Incidence and severity of solicited systemic reactogenicity AEs
timeFrame: through 1 week post final vaccine administration
measure: Phase 2 Safety: Incidence and severity of unsolicited AEs
timeFrame: through 1 week post final vaccine administration
measure: Phase 2 Safety: Incidence of MAAEs and SAEs
timeFrame: through 30 days and 6 months post final vaccine administration
measure: Phase 2 Safety: Incidence and severity of unsolicited AEs
timeFrame: through 30 days post final vaccine administration
measure: Phase 2 Safety: Incidence of changes of laboratory safety examinations
timeFrame: Day 365
measure: Phase 2 Safety: Vital Sign - Temperature
timeFrame: Day 365
measure: Phase 2 Safety: Vital Sign - Heart rate
timeFrame: Day 365
measure: Phase 2 Safety: Vital Sign - Blood Pressure
timeFrame: Day 365
measure: Phase 2 Safety: Vital Sign - Respiratory rate
timeFrame: Day 365
Other outcomes:
Locations:
Study officials:
References: