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

Phase 1/2 Study of the Safety, Reactogenicity, and Immunogenicity of a 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

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, sublingual, and oral (capsule) administration.

Study Overview

• Status: Withdrawn
• Conditions: Covid19
• Intervention / Treatment: Biological: hAd5-S-Fusion+N-ETSD vaccine

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1: hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous; 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; Vaccine containing both full length wild type SARS-CoV-2 spike gene optimized for better spike protein expression, and full length wild type SARS-CoV-2 nucleocapsid gene modified to also contain an enhanced T cell stimulation domain (ETSD) to enhance cell-mediated immunity.
EXPERIMENTAL: Cohort 2: hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous and 1 × 10e10 IU/dose Sublingual; Cohort 2 (n=20): hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous and 1 × 10e10 IU/dose Sublingual on Day 1	Biological: hAd5-S-Fusion+N-ETSD vaccine; Vaccine containing both full length wild type SARS-CoV-2 spike gene optimized for better spike protein expression, and full length wild type SARS-CoV-2 nucleocapsid gene modified to also contain an enhanced T cell stimulation domain (ETSD) to enhance cell-mediated immunity.

What is the study measuring?

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 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
Phase 1 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

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 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
Phase 1 Cellular Immunogenicity: T cell activity	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

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2021
• Primary Completion (ANTICIPATED): March 1, 2022
• Study Completion (ANTICIPATED): August 1, 2022

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 9, 2021
• First Posted (ACTUAL): April 13, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 4, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: COVID-4.006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No