Dendritic Cell Vaccine, AV-COVID-19, to Prevent COVID-19 Infection

Study Overview
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Brief Summary
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This is an adaptive Phase I trial of a vaccine consisting of autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein, with or without GM-CSF, to prevent COVID-19 in adults.

Detailed Description
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Subjects eligible for treatment will be those who at baseline, are not actively infected with SARS-CoV-2, have no evidence of prior infection with SARS-CoV- 2 based on serologic testing, and give informed consent for a vaccination with AV-COVID-19. The patient population will include the elderly and others at higher risk for poor outcomes after COVID-19 infection. For this reason, individuals will not be excluded solely on the basis of age, body mass index, history of hypertension, diabetes, cancer, or autoimmune disease. After enrolling for screening, subjects will undergo a nasal swab test to exclude active COVID-19 infection and a rapid test for anti-coronavirus antibodies to exclude pre-existing anti-SARS-CoV-2 antibodies. 50 mL of blood will be collected, from which peripheral blood monocytes will be isolated and differentiated into DC before incubation with SARS-CoV-2 S-protein, during which time the protein is digested into 9 to 25 amino acid peptide sequences presented on the dendrites of DC in conjunction with histocompatibility class I and class II molecules. Safety and quality testing will be performed on a small quantity of the batch, and the remaining AV-COVID-19 will be cryopreserved for shipping to the treatment site. Once the Study Drug is ready, if eligible, the subject will be seen at Study Week-0 for treatment. Prior to injection of the Study Drug, a nasal swab test will be collected to confirm that they are still negative for COVID-19, and blood will be drawn to determine baseline levels of anti-SARS-CoV-2 antibodies. At the treatment site, the product will be thawed and admixed with saline or (saline with GM-CSF), and within 5 hours of thawing, will be injected SC via a 25- gauge needle

Official Title
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Adaptive Phase I Clinical Trial of Preventive Vaccine Consisting of Autologous Dendritic Cells Previously Incubated With S-protein From SARS-CoV-2, in Subjects Negative for COVID-19 Infection and Anti-SARS-CoV-2 Antibodies

Conditions
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COVID-19

Intervention / Treatment
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* Biological: AV-COVID-19
* Other: GM-CSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older, relatively good health, negative for pre-existing SARS-CoV-2 antibodies, negative for SARS-CoV-2 infection Exclusion Criteria: Active COVID-19 infection by PCR testing, pre-existing SARS-CoV-2 antibodies, pregnant, known hypersensitivity to GM-CSF, known immune deficiency disease, on active treatment with immunosuppressive agent or corticosteroid, participated in previous COVID-19 trial

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.1 mg antigen, 0 mcg GM-CSF<br>Dendritic cells previously incubated with 0.1 mcg antigen | Biological: AV-COVID-19<br>* Autologous dendritic cells previously incubated with SARS-CoV-2 spike protein<br>|
| Experimental: 0.33 mg antigen, 0 mcg GM-CSF<br>Dendritic cells previously incubated with 0.33 mcg antigen | Biological: AV-COVID-19<br>* Autologous dendritic cells previously incubated with SARS-CoV-2 spike protein<br>|
| Experimental: 1.0 mg antigen, 0 mcg GM-CSF<br>Dendritic cells previously incubated with 1.0 mcg antigen | Biological: AV-COVID-19<br>* Autologous dendritic cells previously incubated with SARS-CoV-2 spike protein<br>|
| Experimental: 0.1 mg antigen, 250 mcg GM-CSF<br>Dendritic cells previously incubated with 0.1 mcg antigen, admixed with 250 mcg GM-CSF | Biological: AV-COVID-19<br>* Autologous dendritic cells previously incubated with SARS-CoV-2 spike protein<br>Other: GM-CSF<br>* GM-CSF as an adjuvant<br>|
| Experimental: 0.33 mg antigen, 250 mcg GM-CSF<br>Dendritic cells previously incubated with 0.33 mcg antigen, admixed with 250 mcg GM-CSF | Biological: AV-COVID-19<br>* Autologous dendritic cells previously incubated with SARS-CoV-2 spike protein<br>Other: GM-CSF<br>* GM-CSF as an adjuvant<br>|
| Experimental: 1.0 mg antigen, 250 mcg GM-CSF<br>Dendritic cells previously incubated with 1.0 mcg antigen, admixed with 250 mcg GM-CSF | Biological: AV-COVID-19<br>* Autologous dendritic cells previously incubated with SARS-CoV-2 spike protein<br>Other: GM-CSF<br>* GM-CSF as an adjuvant<br>|
| Experimental: 0.1 mg antigen, 500 mcg GM-CSF<br>Dendritic cells previously incubated with 0.1 mcg antigen, admixed with 500 mcg GM-CSF | Biological: AV-COVID-19<br>* Autologous dendritic cells previously incubated with SARS-CoV-2 spike protein<br>Other: GM-CSF<br>* GM-CSF as an adjuvant<br>|
| Experimental: 0.33 mg antigen, 500 mcg GM-CSF<br>Dendritic cells previously incubated with 0.33 mcg antigen, admixed with 500 mcg GM-CSF | Biological: AV-COVID-19<br>* Autologous dendritic cells previously incubated with SARS-CoV-2 spike protein<br>Other: GM-CSF<br>* GM-CSF as an adjuvant<br>|
| Experimental: 1.0 mg antigen, 500 mcg GM-CSF<br>Dendritic cells previously incubated with 1.0 mcg antigen, admixed with 500 mcg GM-CSF | Biological: AV-COVID-19<br>* Autologous dendritic cells previously incubated with SARS-CoV-2 spike protein<br>Other: GM-CSF<br>* GM-CSF as an adjuvant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (safety) | Collection of adverse event incidence and severity in all treatment arms | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish optimal dose formulation | Measurement of antibodies in subject blood | 1 month | 
| Duration of detection of antibodies against SARS-CoV-2 | Measurement of antibodies in subject blood | 1 month |