COVID-19 Vaccination Using a 2nd Generation (E1/E2B/E3-Deleted) Adenoviral-COVID-19 in Normal Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT04591717
• Recruitment Status: Completed
• First Posted: October 19, 2020
• Last Update Posted: February 28, 2023
• Sponsor: ImmunityBio, Inc.
• Information provided by (Responsible Party): ImmunityBio, Inc.

Study Description

Brief Summary:

This is a phase 1b, open-label study in adult healthy subjects. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of the hAd5-S-Fusion+N-ETSD vaccine and select a dose for future studies.

Condition or disease	Intervention/treatment	Phase
COVID-19	Biological: hAd5-S-Fusion+N-ETSD vaccine	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1b Open-Label Study of the Safety, Reactogenicity, and Immunogenicity of Prophylactic Vaccination With 2nd Generation (E1/E2B/E3-Deleted) Adenoviral-COVID-19 in Normal Healthy Volunteers
• Actual Study Start Date: October 19, 2020
• Actual Primary Completion Date: April 20, 2022
• Actual Study Completion Date: January 18, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1: 0.5 mL of hAd5-S-Fusion+N-ETSD SC; 0.5 mL of hAd5-S-Fusion+N-ETSD SC (5 × 10e10 VP/dose) on days 1 and 22	Biological: hAd5-S-Fusion+N-ETSD vaccine; The hAd5-S-Fusion+N-ETSD Vaccine is a human adenovirus serotype 5 (hAd5) vector with E1/E2b/E3 deletions expressing SARS-CoV-2 viral antigen spike fusion protein and nucleocapsid with an enhanced T-cell stimulation domain.
Experimental: Cohort 2: 1.0 mL of hAd5-S-Fusion+N-ETSD SC; Cohort 2: 1.0 mL of hAd5-S-Fusion+N-ETSD SC (1 × 10e11 VP/dose) on days 1 and 22	Biological: hAd5-S-Fusion+N-ETSD vaccine; The hAd5-S-Fusion+N-ETSD Vaccine is a human adenovirus serotype 5 (hAd5) vector with E1/E2b/E3 deletions expressing SARS-CoV-2 viral antigen spike fusion protein and nucleocapsid with an enhanced T-cell stimulation domain.
Experimental: Cohort 3a: 1.0 mL of hAd5-S-Fusion+N-ETSD SC and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually; Cohort 3a: 1.0 mL of hAd5-S-Fusion+N-ETSD SC (1 × 10e11 VP/dose) and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on day 1; 1.0 mL of hAd5-S-Fusion+N-ETSD SC (1 × 10e11 VP/dose) and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on day 22	Biological: hAd5-S-Fusion+N-ETSD vaccine; The hAd5-S-Fusion+N-ETSD Vaccine is a human adenovirus serotype 5 (hAd5) vector with E1/E2b/E3 deletions expressing SARS-CoV-2 viral antigen spike fusion protein and nucleocapsid with an enhanced T-cell stimulation domain.
Experimental: Cohort 3b: 1.0 mL of hAd5-S-Fusion+N-ETSD SC and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually; Cohort 3b: 1.0 mL of hAd5-S-Fusion+N-ETSD SC (1 × 10e11 VP/dose) and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on day 1; no vaccine on day 22	Biological: hAd5-S-Fusion+N-ETSD vaccine; The hAd5-S-Fusion+N-ETSD Vaccine is a human adenovirus serotype 5 (hAd5) vector with E1/E2b/E3 deletions expressing SARS-CoV-2 viral antigen spike fusion protein and nucleocapsid with an enhanced T-cell stimulation domain.
Experimental: Cohort 3c: 1.0 mL of hAd5-S-Fusion+N-ETSD SC and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually; Cohort 3c: 1.0 mL of hAd5-S-Fusion+N-ETSD SC (1 × 10e11 VP/dose) and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on day 1; 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on day 22	Biological: hAd5-S-Fusion+N-ETSD vaccine; The hAd5-S-Fusion+N-ETSD Vaccine is a human adenovirus serotype 5 (hAd5) vector with E1/E2b/E3 deletions expressing SARS-CoV-2 viral antigen spike fusion protein and nucleocapsid with an enhanced T-cell stimulation domain.
Experimental: Cohort 3d: 1.0 mL of hAd5-S-Fusion+N-ETSD SC and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually; Cohort 3d: 1.0 mL of hAd5-S-Fusion+N-ETSD SC (1 × 10e11 VP/dose) and 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on day 1; 0.5 mL of hAd5-S-Fusion+N-ETSD sublingually (5 × 10e10 VP/dose) on days 15 and 29	Biological: hAd5-S-Fusion+N-ETSD vaccine; The hAd5-S-Fusion+N-ETSD Vaccine is a human adenovirus serotype 5 (hAd5) vector with E1/E2b/E3 deletions expressing SARS-CoV-2 viral antigen spike fusion protein and nucleocapsid with an enhanced T-cell stimulation domain.

Outcome Measures

Primary Outcome Measures :

1. Incidence of MAAEs and SAEs [ Time Frame: 1 week ]
   Incidence of MAAEs and SAEs through 1 week post final vaccine administration
2. Incidence and severity of solicited local reactogenicity AEs [ Time Frame: 1 week ]
   Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration
3. Incidence and severity of solicited systemic reactogenicity AEs [ Time Frame: 1 week ]
   Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration
4. Incidence and severity of unsolicited AEs [ Time Frame: 1 week ]
   Incidence and severity of unsolicited AEs through 1 week post final vaccine administration
5. Incidence of MAAEs and SAEs [ Time Frame: 30 days to 6 months ]
   Incidence of MAAEs and SAEs through 30 days and 6 months post final vaccine administration
6. Incidence and severity of unsolicited AEs [ Time Frame: 30 days ]
   Incidence and severity of unsolicited AEs through 30 days post final vaccine administration
7. Incidence of abnormal changes of laboratory safety examinations [ Time Frame: 30 days ]
   Incidence of abnormal changes of laboratory safety examinations
8. Vital Signs - Fever [ Time Frame: 30 days ]

   Changes in vital signs from Grades 1-4:

   - Fever - measured in (°C) or (°F)

9. Vital Signs - Tachycardia [ Time Frame: 30 Days ]

   Changes in vital signs from Grades 1-4:

   - Tachycardia - measured in beats per minute

10. Vital Signs - Bradycardia [ Time Frame: 30 Days ]

    Changes in vital signs from Grades 1-4:

    - Bradycardia - measured in how many beats per minute

11. Vital Signs - Hypertension [ Time Frame: 30 Days ]

    Changes in vital signs from Grades 1-4:

    - Hypertension (systolic/diastolic) - measured in mm Hg

12. Vital Signs - Hypotension [ Time Frame: 30 Days ]

    Changes in vital signs from Grades 1-4:

    - Hypotension (systolic) - measured in mm Hg

13. Vital Signs - Respiratory Rate [ Time Frame: 30 Days ]

    Changes in vital signs from Grades 1-4:

    - Respiratory Rate - measured in how many breaths per minute

14. GMFR in IgG titer [ Time Frame: Day 387 ]
    GMFR in IgG titer
15. GMT of S-specific, RBD-specific, and N-specific antibodies against 2019 novel coronavirus [ Time Frame: Day 387 ]
    GMT of S-specific, RBD-specific, and N-specific antibodies against 2019 novel coronavirus tested by ELISA in serum
16. Percentage of subjects who seroconverted [ Time Frame: Day 387 ]
    Percentage of subjects who seroconverted (as defined as 4-fold change in antibody titer relative to baseline)
17. GMFR in neutralizing antibody [ Time Frame: Day 387 ]
    GMFR in neutralizing antibody
18. GMT [ Time Frame: Day 387 ]
    GMT of neutralizing antibody
19. Seroconversion rate of neutralizing antibody [ Time Frame: Day 387 ]
    Seroconversion rate of neutralizing antibody (as defined as 4-fold change in antibody titer relative to baseline)
20. CD8+ T-Cell activity against SARS-CoV-2 S protein, RBD, and N protein [ Time Frame: Day 387 ]
    CD8+ T-Cell activity against SARS-CoV-2 S protein, RBD, and N protein measured by ELISPOT assay
21. CD4+ T-Cell activity against SARS-CoV-2 S protein, RBD, and N protein [ Time Frame: Day 387 ]
    CD4+ T-Cell activity against SARS-CoV-2 S protein, RBD, and N protein measured by standard immune assay

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Healthy adults, age 18 - 55 years, inclusive, at time of 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, nasopharyngeal [NP] swabs) and venous blood per protocol.
4. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
5. Temperature < 38°C.
6. Negative for SARS-CoV-2 (qPCR or LAMP test) and no known previous COVID-19 exposure or disease.
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, intrauterine devices (IUDs), oral contraceptives, and abstinence.

Exclusion Criteria:

1. Allergy to any component of the investigational vaccine, or a more severe allergic reaction and history of allergies in the past.
2. 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.
3. Live in a nursing home or long-term care facility.
4. Chronic lung disease including chronic obstructive pulmonary disease (COPD) or moderate to severe asthma.
5. Pulmonary fibrosis.
6. Active smoker.
7. Bone marrow or organ transplantation.
8. Obesity (defined as body mass index [BMI] of 30 kg/m2 or higher).
9. Diabetes.
10. Chronic kidney disease.
11. Liver disease.
12. Sickle cell disease.
13. Thalassemia.
14. Doctors, nurses, first responders, and other healthcare workers working in direct contact with COVID-19 patients.
15. Any disease associated with acute fever, or any infection.
16. Self-reported history of severe acute respiratory syndrome (SARS).
17. History of hepatitis B or hepatitis C.
18. HIV or other acquired or hereditary immunodeficiency.
19. Serious cardiovascular diseases, such as heart failure, coronary artery disease, cardiomyopathies, arrhythmia, conduction block, myocardial infarction, pulmonary hypertension, severe hypertension without controllable drugs, etc.
20. Cerebrovascular disease.
21. Cystic fibrosis.
22. Neurologic conditions, such as dementia.
23. Hereditary or acquired angioneurotic edema.
24. Urticaria in the last 12 months.
25. No spleen or functional asplenia.
26. Platelet disorder or other bleeding disorder that may cause injection contraindication.
27. 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.)
28. Prior administration of blood products in last 4 months.
29. Prior administration of other research medicines in last 1 month.
30. Received or plans to receive an attenuated vaccine within 1 month before or after each study vaccination.
31. Received or plans to receive an inactivated vaccine within 14 days before or after each study vaccination.
32. Current treatment with investigational agents for prophylaxis of COVID-19.
33. Have a household contact that has been diagnosed with COVID-19.
34. Current anti-tuberculosis prophylaxis or therapy.
35. 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).
36. According to the judgement of investigator, various medical, psychological, social or other conditions that could affect the subjects ability to sign informed consent.
37. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.

Contacts and Locations

Locations

United States, California

Chan Soon - Shiong Institute for Medicine

El Segundo, California, United States, 90245

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States, 92663

Sponsors and Collaborators

ImmunityBio, Inc.

More Information

• Responsible Party: ImmunityBio, Inc.
• ClinicalTrials.gov Identifier: NCT04591717
• Other Study ID Numbers: QUILT-COVID-19-hAd5-Vaccine
• First Posted: October 19, 2020
• Last Update Posted: February 28, 2023
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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