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

• ClinicalTrials.gov Identifier: NCT04732468
• Recruitment Status: Active, not recruiting
• First Posted: February 1, 2021
• Last Update Posted: July 20, 2021
• 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 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.

Condition or disease	Intervention/treatment	Phase
Covid19	Biological: hAd5-S-Fusion+N-ETSD (Suspension for injection); Drug: hAd5-SFusion+ N-ETSD (Oral capsule)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 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 Subcutaneously and Orally Administered Prophylactic Vaccination With 2nd Generation (E1/E2B/E3-Deleted) Adenoviral COVID-19 in Normal Healthy Volunteers
• Actual Study Start Date: February 24, 2021
• Estimated Primary Completion Date: April 2022
• Estimated Study Completion Date: April 2022

Arms and Interventions

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) will be 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) will be 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) will be 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) will be 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.

Outcome Measures

Primary Outcome Measures :

1. Incidence of MAAEs and SAEs [ Time Frame: 1 week post final vaccine administration ]
   Incidence of medically-attended adverse events (MAAEs) and serious adverse events (SAEs) through 1 week post final vaccine administration
2. Incidence and severity of solicited local reactogenicity AEs [ Time Frame: 1 week post final vaccine administration ]
   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 post final vaccine administration ]
   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 post final vaccine administration ]
   Incidence and severity of unsolicited AEs through 1 week post final vaccine administration
5. Incidence of MAAEs and SAEs [ Time Frame: 30 days post final vaccine ]
   Incidence of MAAEs and SAEs through 30 days post final vaccine administration
6. Incidence of MAAEs and SAEs [ Time Frame: 6 months post final vaccine ]
   Incidence of MAAEs and SAEs through 6 months post final vaccine
7. Incidence and severity of unsolicited AEs [ Time Frame: 30 days post final vaccine administration ]
   Incidence and severity of unsolicited AEs through 30 days post final vaccine administration
8. Incidence of changes of laboratory safety examinations [ Time Frame: Day 387 ]
   Incidence of abnormal changes of laboratory safety examinations
9. Vital Sign - Temperature [ Time Frame: Day 387 ]

   Changes in vital signs from Grades 1-4:

   Temperature - measured in (°C) or (°F)

10. Vital Sign - Heart rate [ Time Frame: Day 387 ]

    Changes in vital signs from Grades 1-4:

    Heart rate - measured by how many heart beats per minute

11. Vital Sign - Blood Pressure [ Time Frame: Day 387 ]

    Changes in vital signs from Grades 1-4:

    Systolic/Diastolic - measured in mm Hg

12. Vital Sign - Respiratory Rate [ Time Frame: Day 387 ]

    Changes in vital signs from Grades 1-4:

    Respiratory Rate - measured in how many breaths per minute

Secondary Outcome Measures :

1. GMFR in IgG titer [ Time Frame: Day 387 ]
   Geometric mean fold rise (GMFR) in IgG titer
2. GMT of S-specific, RBD-specific, and N-specific antibodies [ Time Frame: Day 387 ]
   Geometric mean titer (GMT) of S-specific, RBD-specific, and N-specific antibodies against 2019 novel coronavirus tested by ELISA in serum
3. 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)
4. GMFR in neutralizing antibody [ Time Frame: Day 387 ]
   GMFR in neutralizing antibody, in the absence of evidence of incident natural infection
5. GMT of neutralizing antibody [ Time Frame: Day 387 ]
   GMT in neutralizing antibody, in the absence of evidence of incident natural infection
6. 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)
7. 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
8. 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. 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.

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: NCT04732468
• Other Study ID Numbers: COVID-4.005
• First Posted: February 1, 2021
• Last Update Posted: July 20, 2021
• Last Verified: January 2021

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