CORVax12: SARS-CoV-2 Spike (S) Protein Plasmid DNA Vaccine Trial for COVID-19 (SARS-CoV-2)

Study Overview
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Brief Summary
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This is a Phase 1, open-label study to evaluate the safety profile of CORVax +/- pIL-12, (electroporated SARS-CoV-2 spike (S) protein plasmid DNA vaccine with or without the combination of electroporated IL-12p70 plasmid.

Detailed Description
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This is a Phase 1, open-label study to evaluate the safety profile of CORVax +/- pIL-12, (electroporated SARS-CoV-2 spike (S) protein plasmid DNA vaccine with or without the combination of electroporated IL-12p70 plasmid), given as prime & boost doses, four weeks apart, in healthy volunteers, divided into age groups of 18-50 versus > 50 years old. IL-12p70 plasmid DNA electroporation (tavokinogene telseplasmid) has been extensively studied in over 209 subjects across 11 trials including later stage human cancer trials with more than 1000 administrations. The IGEA CLINIPORATOR® system is approved for clinical use in Europe, but remains investigational in this study. One participant will initially be enrolled to each of four cohorts and monitored over a 7-day DLT window: 1A. Age 18-50; CORVax. B. Age 18-50; CORVax + pIL-12. A. Age > 50; CORVax. 2B. Age > 50; CORVax + pIL-12. If after 7 days, no DLT are observed, the cohort may proceed to enroll a second participant. If after monitoring the second participant for 7 days, no DLT are observed, the cohort may proceed to enroll a third participant. If after monitoring the third participant for 7 days, no DLT are observed, the cohort may proceed to enroll six additional participants, for a total of nine participants per cohort using a (1+1+1, +6) design.

Official Title
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CORVax12 - a Phase I Trial of SARS-CoV-2 Spike (S) Protein Plasmid DNA Vaccine (CORVax) +/- pIL-12 (Tavokinogene Telseplasmid) in Healthy Volunteers, With Immunodynamic Biomarker Monitoring of Coordinated Cellular/Humoral Response

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Drug: CORVax
* Drug: IL-12 plasmid
* Device: Cliniporator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult volunteers ages 18 years and above, who are able to provide written informed consent and willing to allow storage and future use of samples for SARS-CoV-2 related research. Women of childbearing potential (WOCBP) must have negative serum or urine pregnancy on each day of vaccine administration. Males and women of childbearing potential must agree to take appropriate precautions to avoid pregnancy during treatment and through 180 days after last dose of IP. Exclusion Criteria: Current or previous SARS-CoV-2 infection or receipt of an experimental treatment for prevention of SARS-CoV-2. Administration of any vaccine within 4 weeks of first dose. Any laboratory abnormalities at baseline greater than Grade 1 per the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/toxicity-grading-scale-healthy-adult-and-adolescent-volunteers-enrolled-preventive-vaccine-clinical Any history of cardiac arrhythmia. Any history of epilepsy or seizure within the last five years. Use of immunosuppressive medication within 14 days before the first dose of study drug. Anticipated treatment with TNF-α inhibitors (e.g., infliximab, adalimumab, or etanercept). Pregnancy or breastfeeding. Body mass index of 35 kg/m2 or more. Administration of any monoclonal or polyclonal antibody product within 4 weeks of the first dose. Chronic liver disease or cirrhosis. Previous major surgery or any radiation therapy within 4 weeks of group assignment. Any pre-excitation syndromes (e.g., Wolff- Parkinson-White syndrome). Metal implants within 20cm of the planned site(s) of injection; presence of keloid scar formation or hypertrophic scar as a clinically significant medical condition at the planned site(s) of injection; tattoos covering the injection site area. Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator. History of allogeneic organ transplantation. History of primary immunodeficiency. Known HIV, hepatitis B virus, or hepatitis C virus infection. Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Uncontrolled intercurrent illness, including but not limited to symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, unstable cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent. Comorbidities, controlled or otherwise, associated with higher risk for severe COVID-19 illness - because our understanding of the pathogenesis of SARS-CoV-2 continues to evolve, this will be based on most current information available at time of screening regarding risk factors for severe disease, using resources such as those described on the Centers for Disease Control website: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-at-higher-risk.html Subjects at high-risk for SARS-CoV-2 exposure per investigator, including healthcare workers, first responders, and individuals with known exposure to individuals infected with SARS-CoV-2. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice). History of autoimmune or inflammatory disorders including but not limited to inflammatory bowel disease (e.g., colitis or Crohn's disease), diverticulitis (with the exception of diverticulosis), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, (see Appendix 2). Known allergy or hypersensitivity to study drug(s) or compounds of similar biologic composition to the study drug(s), or any of the study drug excipients. Investigator discretion relating to any condition which might interfere with study requirements.

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1A: Age 18-50; CORVax<br>Healthy volunteers age 18-50 will receive CORVax | Drug: CORVax<br>* DNA-encodable coronaviral vaccine<br>Device: Cliniporator<br>* electroporation system<br>|
| Experimental: 1B: Age 18-50; CORVax + pIL-12<br>Healthy volunteers age 18-50 will receive CORVax + pIL-12 | Drug: CORVax<br>* DNA-encodable coronaviral vaccine<br>Drug: IL-12 plasmid<br>* cytokine<br>Device: Cliniporator<br>* electroporation system<br>|
| Experimental: 2A: Age > 50; CORVax<br>Healthy volunteers age > 50 will receive CORVax | Drug: CORVax<br>* DNA-encodable coronaviral vaccine<br>Device: Cliniporator<br>* electroporation system<br>|
| Experimental: 2B: Age > 50; CORVax + pIL-12<br>Healthy volunteers age > 50 will receive CORVax + pIL-12 | Drug: CORVax<br>* DNA-encodable coronaviral vaccine<br>Drug: IL-12 plasmid<br>* cytokine<br>Device: Cliniporator<br>* electroporation system<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity | Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Grade 1 mild is the minimum value and Grade 4 life threatening is the maximum value.) | Day 1 | 
| Toxicity | Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Grade 1 mild is the minimum value and Grade 4 life threatening is the maximum value.) | Day 2 | 
| Toxicity | Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Grade 1 mild is the minimum value and Grade 4 life threatening is the maximum value.) | Days 3 | 
| Toxicity | Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Grade 1 mild is the minimum value and Grade 4 life threatening is the maximum value.) | Day 15 | 
| Toxicity | Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Grade 1 mild is the minimum value and Grade 4 life threatening is the maximum value.) | Day 30 | 
| Toxicity | Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Grade 1 mild is the minimum value and Grade 4 life threatening is the maximum value.) | Day 31 | 
| Toxicity | Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Grade 1 mild is the minimum value and Grade 4 life threatening is the maximum value.) | Day 32 | 
| Toxicity | Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Grade 1 mild is the minimum value and Grade 4 life threatening is the maximum value.) | Day 45 | 
| Toxicity | Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Grade 1 mild is the minimum value and Grade 4 life threatening is the maximum value.) | Day 60 | 
| Toxicity | Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Grade 1 mild is the minimum value and Grade 4 life threatening is the maximum value.) | Day 90 | 
| Medically Attended Adverse Events (MAAEs) | Extended monitoring of Medically Attended Adverse Events (MAAEs) for potentially immune-mediated conditions (pIMMCs). | Day 30 | 
| Medically Attended Adverse Events (MAAEs) | Extended monitoring of Medically Attended Adverse Events (MAAEs) for potentially immune-mediated conditions (pIMMCs) | Day 60 | 
| Medically Attended Adverse Events (MAAEs) | Extended monitoring of Medically Attended Adverse Events (MAAEs) for potentially immune-mediated conditions (pIMMCs) | Day 90 | 
| Medically Attended Adverse Events (MAAEs) | Extended monitoring of Medically Attended Adverse Events (MAAEs) for potentially immune-mediated conditions (pIMMCs) | Month 6 | 
| Medically Attended Adverse Events (MAAEs) | Extended monitoring of Medically Attended Adverse Events (MAAEs) for potentially immune-mediated conditions (pIMMCs) | Month 12 | 
| Medically Attended Adverse Events (MAAEs) | Extended monitoring of Medically Attended Adverse Events (MAAEs) for potentially immune-mediated conditions (pIMMCs) | Month 18 |