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

• ClinicalTrials.gov Identifier: NCT04845191
• Recruitment Status: Withdrawn
• First Posted: April 14, 2021
• Last Update Posted: January 4, 2022
• Sponsor: ImmunityBio, Inc.
• Information provided by (Responsible Party): ImmunityBio, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Covid19	Biological: hAd5-S-Fusion+N-ETSD vaccine	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Open label 2 Cohort Phase 1 Study leading to Randomized Phase 2 Study
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: December 2021
• Estimated Primary Completion Date: March 2022
• Estimated Study Completion Date: August 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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; 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.
Experimental: Experimental: Cohort 2: hAd5-S-Fusion+N-ETSD Subcutaneous and Oral; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. Phase 1 Safety: Incidence of MAAEs and SAEs [ Time Frame: through 1 week post final vaccine administration ]
   Incidence of MAAEs and SAEs through 1 week post final vaccine administration
2. Phase 1 Safety: Incidence and severity of solicited local reactogenicity AEs [ Time Frame: through 1 week post final vaccine administration ]
   Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration
3. Phase 1 Safety: Incidence and severity of solicited systemic reactogenicity AEs [ Time Frame: through 1 week post final vaccine administration ]
   Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration
4. Phase 1 Safety: Incidence and severity of unsolicited AEs [ Time Frame: through 1 week post final vaccine administration ]
   Incidence and severity of unsolicited AEs through 1 week post final vaccine administration
5. Phase 1 Safety: Incidence of MAAEs and SAEs [ Time Frame: through 30 days ]
   Incidence of MAAEs and SAEs through 30 days
6. Phase 1 Safety: Incidence of MAAEs and SAEs [ Time Frame: 6 months post final vaccine administration ]
   Incidence of MAAEs and SAEs at 6 months post final vaccine administration
7. Phase 1 Safety: Incidence and severity of unsolicited AEs [ Time Frame: through 30 days post final vaccine administration ]
   Incidence and severity of unsolicited AEs through 30 days post final vaccine administration
8. Phase 1 Safety: Incidence of changes of laboratory safety examinations [ Time Frame: Day 365 ]
   Incidence of abnormal changes of laboratory safety examinations
9. Phase 1 Safety: Vital Sign - Temperature [ Time Frame: Day 365 ]

   Changes in vital signs from Grades 1-4:

   measured in (°C) or (°F)

10. Phase 1 Safety: Vital Sign - Heart Rate [ Time Frame: Day 365 ]

    Changes in vital signs from Grades 1-4:

    measured by how many heart beats per minute

11. Phase 1 Safety: Vital Sign - Blood Pressure [ Time Frame: Day 365 ]

    Changes in vital signs from Grades 1-4:

    systolic/diastolic - measured in mm Hg

12. Phase 1 Safety: Vital Sign - Respiratory Rate [ Time Frame: Day 365 ]

    Changes in vital signs from Grades 1-4:

    measured in how many breaths per minute

13. Phase 2 Efficacy: Percent of subjects that show an increase in N-reactive T cells [ Time Frame: 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 :

1. Phase 1 Humoral Immunogenicity: GMT of S-specific and N-specific antibodies [ Time Frame: Day 365 ]
   GMT of S-specific and N-specific antibodies against 2019 novel coronavirus
2. Phase 1 Humoral Immunogenicity: GMT of neutralizing antibody [ Time Frame: Day 365 ]
   GMT of neutralizing antibody
3. Phase 1 Mucosal Immunogenicity: GMT of IgA antibody levels [ Time Frame: Day 365 ]
   GMT of IgA antibody levels
4. Phase 1 Cellular Immunogenicity: T cell activity [ Time Frame: 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.
5. Phase 2 Efficacy: Incidence and severity of COVID-19 ≥14 days after vaccination [ Time Frame: ≥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.
6. Phase 2 Efficacy: Mean SARS-CoV-2 viral load [ Time Frame: Day 365 ]
   Mean SARS-CoV-2 viral load for subjects with confirmed COVID-19 ≥14 days after vaccination
7. Phase 2 Efficacy: Humoral Immunogenicity - GMT of S-specific and N-specific antibodies [ Time Frame: Day 365 ]
   GMT of S-specific and N-specific antibodies against 2019 novel coronavirus
8. Phase 2 Efficacy: Humoral Immunogenicity - GMT of neutralizing antibody [ Time Frame: Day 365 ]
   GMT of neutralizing antibody
9. Phase 2 Efficacy: Mucosal Immunogenicity - GMT of IgA antibody levels [ Time Frame: Day 365 ]
   GMT of IgA antibody levels
10. Phase 2 Efficacy: Cellular Immunogenicity - T cell activity [ Time Frame: Day 365 ]
    T cell activity against SARS-CoV-2 S protein and N protein measured
11. Phase 2 Safety: Incidence of MAAEs and SAEs [ Time Frame: through 1 week post final vaccine administration ]
    Incidence of MAAEs and SAEs through 1 week post final vaccine administration
12. Phase 2 Safety: Incidence and severity of solicited local reactogenicity AEs [ Time Frame: through 1 week post final vaccine administration ]
    Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration
13. Phase 2 Safety: Incidence and severity of solicited systemic reactogenicity AEs [ Time Frame: through 1 week post final vaccine administration ]
    Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration
14. Phase 2 Safety: Incidence and severity of unsolicited AEs [ Time Frame: through 1 week post final vaccine administration ]
    Incidence and severity of unsolicited AEs through 1 week post final vaccine administration
15. Phase 2 Safety: Incidence of MAAEs and SAEs [ Time Frame: 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
16. Phase 2 Safety: Incidence and severity of unsolicited AEs [ Time Frame: through 30 days post final vaccine administration ]
    Incidence and severity of unsolicited AEs through 30 days post final vaccine administration
17. Phase 2 Safety: Incidence of changes of laboratory safety examinations [ Time Frame: Day 365 ]
    Incidence of abnormal changes of laboratory safety examinations
18. Phase 2 Safety: Vital Sign - Temperature [ Time Frame: Day 365 ]

    Changes in vital signs from Grades 1-4:

    measured in (°C) or (°F)

19. Phase 2 Safety: Vital Sign - Heart rate [ Time Frame: Day 365 ]

    Changes in vital signs from Grades 1-4:

    measured by how many heart beats per minute

20. Phase 2 Safety: Vital Sign - Blood Pressure [ Time Frame: Day 365 ]

    Changes in vital signs from Grades 1-4:

    systolic/diastolic - measured in mm Hg

21. Phase 2 Safety: Vital Sign - Respiratory rate [ Time Frame: Day 365 ]

    Changes in vital signs from Grades 1-4:

    measured in how many breaths per minute

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: ImmunityBio, Inc.
• ClinicalTrials.gov Identifier: NCT04845191
• Other Study ID Numbers: COVID-4.009
• First Posted: April 14, 2021
• Last Update Posted: January 4, 2022
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases