COVID-19 Oral and Subcutaneous Vaccination Using a 2nd Generation (E1/E2B/E3-Deleted) Adenovirus Platform in Healthy Volunteers in USA

Phase 1b Open-Label Study of the Safety, Reactogenicity, and Immunogenicity of Subcutaneously and Orally Administered Prophylactic Vaccination With 2nd Generation (E1/E2B/E3-Deleted) Adenoviral COVID-19 in Normal Healthy Volunteers

This is a phase 1b, open-label study in adult healthy subjects. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity the combination of hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) and to select an optimal combination dose for future studies.

Study Overview

• Status: Terminated
• Conditions: Covid19
• Intervention / Treatment: Biological: hAd5-S-Fusion+N-ETSD (Suspension for injection); Drug: hAd5-SFusion+ N-ETSD (Oral capsule)

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • El Segundo, California, United States, 90245
      • Chan Soon - Shiong Institute for Medicine
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian

Participation Criteria

Eligibility Criteria

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

Description

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. Ability to swallow a capsule.
6. Temperature < 38°C.
7. Negative for SARS-CoV-2 (qPCR or LAMP test) and no known previous COVID-19 exposure or disease.
8. 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. Current or former 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, authorized, or approved 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1- hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-SFusion+ N-ETSD (Oral capsule); For subjects in cohort 1, hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-SFusion+N-ETSD (Oral capsule) were administered on day 1 (prime) and hAd5-S-Fusion+N-ETSD (Suspension for injection) again on day 22 (boost).	Biological: hAd5-S-Fusion+N-ETSD (Suspension for injection); 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.; Drug: hAd5-SFusion+ N-ETSD (Oral capsule); 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- hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-SFusion+ N-ETSD (Oral capsule); For subjects in cohort 2, hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-SFusion+N-ETSD (Oral capsule) were administered on day 1 (prime) and hAd5-S-Fusion+N-ETSD (Oral capsule) on day 22 (boost).	Biological: hAd5-S-Fusion+N-ETSD (Suspension for injection); 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.; Drug: hAd5-SFusion+ N-ETSD (Oral capsule); 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 3 - hAd5-S-Fusion+N-ETSD (Oral capsule); For subjects in cohort 3, hAd5-S-Fusion+N-ETSD (Oral capsule) were administered on days 1 (prime) and on day 22 (boost).	Drug: hAd5-SFusion+ N-ETSD (Oral capsule); 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 4 - hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule); For subjects in cohort 4, hAd5-S-Fusion+N-ETSD (Suspension for injection) and hAd5-S-Fusion+N-ETSD (Oral capsule) were administered on day 1 (prime) and hAd5-SFusion+N-ETSD (Oral capsule) will be administered on days 15 (boost) and 22 (boost).	Biological: hAd5-S-Fusion+N-ETSD (Suspension for injection); 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.; Drug: hAd5-SFusion+ N-ETSD (Oral capsule); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Solicited Local Reactogenicity AEs	Incidence of Solicited Local Treatment-Related Reactogenicity Adverse Events Through 1 Week Post Final Vaccine	1 week post final vaccine administration
Incidence of Solicited Systemic Treatment-Related Reactogenicity AEs	Incidence of Solicited Systemic Treatment-Related Reactogenicity Adverse Events Through 1 Week Post Final Vaccine Administration	1 week post final vaccine administration
Incidence of Unsolicited AEs	Incidence of Unsolicited AEs Through 1 Week Post Final Vaccine Administration	1 week post final vaccine administration
Incidence of Unsolicited Treatment-Related AEs	Incidence of Unsolicited Treatment-Related Adverse Events Through 1 Week Post Final Vaccine Administration	1 week post final vaccine administration
Incidence of Unsolicited AEs	Incidence of Unsolicited Adverse Events Through 30 Days Post Final Vaccine Administration	30 days post final vaccine
Incidence of Unsolicited Treatment-Related AEs	Incidence of Unsolicited Treatment-Related Adverse Events Through 30 Days Post Final Vaccine Administration	30 Days Post Final
Incidence of MAAEs	Incidence of Medically Attended Adverse Events Through 6 Months Post Final Vaccine Administration	6 Months post final vaccine administration
Incidence of Serious AEs	Incidence of Serious Adverse Events Through 6 Months Post- Final Vaccine Administration	6 Months Post Final Vaccine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects who seroconverted	Percentage of subjects who seroconverted (as defined as 4-fold change in antibody titer relative to baseline)	Day 387
Seroconversion rate of neutralizing antibody	Seroconversion rate of neutralizing antibody (as defined as 4-fold change in antibody titer relative to baseline)	Day 387
CD8+ T-Cell activity against SARS-CoV-2 S protein, RBD, and N protein	CD8+ T-Cell activity against SARS-CoV-2 S protein, RBD, and N protein measured by ELISPOT assay	Day 387
CD4+ T-Cell activity against SARS-CoV-2 S protein, RBD, and N protein	CD4+ T-Cell activity against SARS-CoV-2 S protein, RBD, and N protein measured by standard immune assay	Day 387
GMFR in IgG titer	Geometric mean fold rise (GMFR) in IgG titer	Day 387
GMT of S-specific, RBD-specific, and N-specific antibodies	Geometric mean titer (GMT) of S-specific, RBD-specific, and N-specific antibodies against 2019 novel coronavirus tested by ELISA in serum	Day 387
GMFR in neutralizing antibody	GMFR in neutralizing antibody, in the absence of evidence of incident natural infection	Day 387
GMT of neutralizing antibody	GMT in neutralizing antibody, in the absence of evidence of incident natural infection	Day 387

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Actual): July 11, 2022
• Study Completion (Actual): January 9, 2023

Study Registration Dates

• First Submitted: January 27, 2021
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (Actual): February 1, 2021

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 10, 2024
• Last Verified: September 1, 2024

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-4.005

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