A 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL

Study Overview
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Brief Summary
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This is a phase 2/3, multicenter, randomized, placebo-controlled, observer-blind study assessing the safety, tolerability, immunogenicity, and efficacy of prophylactic hAd5-S-Fusion+N-ETSD against COVID-19. It is intended that a minimum of 25% of subjects will be in the >55-year stratum. Safety, immunogenicity, and efficacy assessments will be conducted per the Schedule of Events (SoE) and subjects are expected to participate for up to a maximum of approximately 2 years.

Official Title
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A Phase 2/3, Placebo-Controlled, Randomized, Observer-Blind Study To Evaluate the Safety, Tolerability, Immunogenicity, and Efficacy of a 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL

Conditions
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COVID-19

Intervention / Treatment
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* Biological: hAd5-S-Fusion+N-ETSD
* Biological: Placebo (0.9% (w/v) saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects are eligible to be included in the study only if all of the following criteria apply: Age and Sex: Male or female participants ≥16 years of age, at randomization. • Refer to Appendix 2 for reproductive criteria for male and female participants. Type of Participant and Disease Characteristics: Participants who are willing and able to comply with all scheduled assessments, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures. Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study. Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included. Specific criteria for Phase 3 participants with known stable infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) can be found in Appendix 3. Participants who, in the judgment of the investigator, are at higher risk for SARS-CoV-2 infection and subsequent development of COVID-19 (including, but not limited to, use of mass transportation, relevant demographics, and frontline essential workers). Informed Consent: Capable of giving personal signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions: Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Phase 2 only: Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s). Receipt of medications intended to prevent COVID-19. Previous clinical or microbiological diagnosis of COVID-19. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate subcutaneous injection. Women who are pregnant or breastfeeding. Prior/Concomitant Therapy: Previous vaccination with any coronavirus vaccine. Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study. Prior/Concurrent Clinical Study Experience: Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation. Other Exclusions Investigator site staff or Sponsor employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The first 200 subjects randomized will comprise the phase 2 portion of the study. Enrollment may continue during this period and these subjects would be included in the phase 3 portion of the study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hAd5-S-Fusion+N-ETSD<br>Prime (SC, Day 1) + Boost (SC, Day 22) @ 1x10^11 VP/dose | Biological: hAd5-S-Fusion+N-ETSD<br>* Clear and colorless liquid. Each vaccine is supplied in a 2-mL vial containing 1.0 mL of extractable vaccine at a concentration of 1 × 10^11 viral particles/mL.<br>|
| Placebo Comparator: Placebo<br>Prime (SC, Day 1) + Boost (SC, Day 22) | Biological: Placebo (0.9% (w/v) saline)<br>* Clear and colorless liquid.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COVID-19 incidence based on central laboratory or locally confirmed nucleic acid amplification test (NAAT) in subjects with no serological or virological evidence (up to 14 days after receipt of the last dose) of past SARS-CoV-2 infection | To evaluate the efficacy of prophylactic hAd5-SFusion+ N-ETSD against confirmed COVID-19 in subjects without serological or virological evidence of infection before vaccination | 14 days after receipt of the last dose | 
| COVID-19 incidence based on central laboratory or locally confirmed NAAT in subjects with and without serological or virological evidence of infection before vaccination | To evaluate the efficacy of prophylactic hAd5-SFusion+ N-ETSD against confirmed COVID-19 in subjects with and without serological or virological evidence of infection before vaccination | Before vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed NAAT severe COVID-19 incidence in subjects with no serological or virological evidence of past SARS-CoV-2 infection | To evaluate the efficacy of prophylactic hAd5-SFusion+ N-ETSD against confirmed severe COVID-19 in subjects without serological or virological evidence of infection before vaccination | Before vaccination | 
| Confirmed NAAT severe COVID-19 incidence in subjects with and without serological or virological evidence of infection before vaccination | To evaluate the efficacy of prophylactic hAd5-SFusion+N-ETSD against confirmed severe COVID-19 in subjects with and without serological or virological evidence of infection before vaccination | Before vaccination | 
| COVID-19 incidence based on central laboratory or locally confirmed (according to the CDC-defined symptoms) in subjects with no serological or virological evidence (up to 14 days after receipt of the last dose) of past SARS-CoV-2 infection | To describe the efficacy of prophylactic hAd5-SFusion+N-ETSD against confirmed COVID-19 (according to the CDC defined symptoms) in subjects without serological or virological evidence of infection before vaccination | 14 days after receipt of the last dose | 
| COVID-19 incidence based on central laboratory or locally confirmed (according to the CDC-defined symptoms) in subjects with and without serological or virological evidence of infection before vaccination | To describe the efficacy of prophylactic hAd5-SFusion+N-ETSD against confirmed COVID-19 (according to the CDCdefined symptoms) in subjects with and without serological or virological evidence of infection before vaccination | Before vaccination |