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

Phase 1

Withdrawn

• Conditions: Covid19
• Interventions: Biological: hAd5-S-Fusion+N-ETSD vaccine

• Registration Number: NCT04845191
• Lead Sponsor: ImmunityBio, Inc.

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2021-04
• Study First Submitted: 2021-04-09
• Study First Submitted QC: 2021-04-12
• Study First Posted: 2021-04-14
• Study Start: 2021-12
• Primary Completion: 2021-12
• Study Completion: 2021-12-14
• Last Update Submitted: 2025-02-20
• Last Update Posted: 2025-02-21

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Experimental: Cohort 2: hAd5-S-Fusion+N-ETSD Subcutaneous and Oral	hAd5-S-Fusion+N-ETSD vaccine	Cohort 2 (n=20): hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous and 1 × 10e10 IU/dose Oral on Day 1
Experimental: Cohort 1: hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous	hAd5-S-Fusion+N-ETSD vaccine	Cohort 1 (n=20): hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous on Day 1

Primary Outcome Measures

Name	Time	Method
Phase 1 Safety: Incidence and severity of solicited local reactogenicity AEs	through 1 week post final vaccine administration	Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration
Phase 1 Safety: Incidence and severity of solicited systemic reactogenicity AEs	through 1 week post final vaccine administration	Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration
Phase 1 Safety: Vital Sign - Blood Pressure	Day 365	Changes in vital signs from Grades 1-4: systolic/diastolic - measured in mm Hg
Phase 1 Safety: Vital Sign - Respiratory Rate	Day 365	Changes in vital signs from Grades 1-4: measured in how many breaths per minute
Phase 1 Safety: Incidence of MAAEs and SAEs	6 months post final vaccine administration	Incidence of MAAEs and SAEs at 6 months post final vaccine administration
Phase 1 Safety: Incidence of changes of laboratory safety examinations	Day 365	Incidence of abnormal changes of laboratory safety examinations
Phase 1 Safety: Vital Sign - Temperature	Day 365	Changes in vital signs from Grades 1-4: measured in (°C) or (°F)
Phase 1 Safety: Vital Sign - Heart Rate	Day 365	Changes in vital signs from Grades 1-4: measured by how many heart beats per minute
Phase 1 Safety: Incidence and severity of unsolicited AEs	through 30 days post final vaccine administration	Incidence and severity of unsolicited AEs through 30 days post final vaccine administration
Phase 2 Efficacy: Percent of subjects that show an increase in N-reactive T cells	from baseline to Day 365	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)

Secondary Outcome Measures

Name	Time	Method
Phase 1 Humoral Immunogenicity: GMT of S-specific and N-specific antibodies	Day 365	GMT of S-specific and N-specific antibodies against 2019 novel coronavirus
Phase 2 Efficacy: Humoral Immunogenicity - GMT of S-specific and N-specific antibodies	Day 365	GMT of S-specific and N-specific antibodies against 2019 novel coronavirus
Phase 2 Efficacy: Mucosal Immunogenicity - GMT of IgA antibody levels	Day 365	GMT of IgA antibody levels
Phase 2 Safety: Incidence and severity of solicited systemic reactogenicity AEs	through 1 week post final vaccine administration	Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration
Phase 2 Safety: Incidence of changes of laboratory safety examinations	Day 365	Incidence of abnormal changes of laboratory safety examinations
Phase 2 Safety: Vital Sign - Heart rate	Day 365	Changes in vital signs from Grades 1-4: measured by how many heart beats per minute
Phase 2 Safety: Vital Sign - Blood Pressure	Day 365	Changes in vital signs from Grades 1-4: systolic/diastolic - measured in mm Hg
Phase 1 Humoral Immunogenicity: GMT of neutralizing antibody	Day 365	GMT of neutralizing antibody
Phase 2 Efficacy: Humoral Immunogenicity - GMT of neutralizing antibody	Day 365	GMT of neutralizing antibody
Phase 2 Efficacy: Cellular Immunogenicity - T cell activity	Day 365	T cell activity against SARS-CoV-2 S protein and N protein measured
Phase 2 Safety: Incidence and severity of solicited local reactogenicity AEs	through 1 week post final vaccine administration	Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration
Phase 2 Safety: Incidence and severity of unsolicited AEs	through 30 days post final vaccine administration	Incidence and severity of unsolicited AEs through 30 days post final vaccine administration
Phase 2 Safety: Vital Sign - Respiratory rate	Day 365	Changes in vital signs from Grades 1-4: measured in how many breaths per minute
Phase 2 Efficacy: Mean SARS-CoV-2 viral load	Day 365	Mean SARS-CoV-2 viral load for subjects with confirmed COVID-19 ≥14 days after vaccination
Phase 2 Efficacy: Incidence and severity of COVID-19 ≥14 days after vaccination	≥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.
Phase 2 Safety: Incidence of MAAEs and SAEs	through 30 days and 6 months post final vaccine administration	Incidence of MAAEs and SAEs through 30 days and 6 months post final vaccine administration
Phase 2 Safety: Vital Sign - Temperature	Day 365	Changes in vital signs from Grades 1-4: measured in (°C) or (°F)
Phase 1 Cellular Immunogenicity: T cell activity	Day 365	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.
Phase 1 Mucosal Immunogenicity: GMT of IgA antibody levels	Day 365	GMT of IgA antibody levels