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

• ClinicalTrials.gov Identifier: NCT04627675
• Recruitment Status: Active, not recruiting
• First Posted: November 13, 2020
• Last Update Posted: June 3, 2021
• Sponsor: Providence Health & Services
• Collaborator: OncoSec Medical Incorporated
• Information provided by (Responsible Party): Providence Health & Services

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
SARS-CoV-2	Drug: CORVax; Drug: IL-12 plasmid; Device: Cliniporator	Phase 1

Detailed Description:

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.

1. B. Age 18-50; CORVax + pIL-12.
2. 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: December 30, 2020
• Estimated Primary Completion Date: July 2021
• Estimated Study Completion Date: May 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Toxicity [ Time Frame: Day 1 ]
   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.)
2. Toxicity [ Time Frame: Day 2 ]
   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.)
3. Toxicity [ Time Frame: Days 3 ]
   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.)
4. Toxicity [ Time Frame: Day 15 ]
   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.)
5. Toxicity [ Time Frame: Day 30 ]
   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.)
6. Toxicity [ Time Frame: Day 31 ]
   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.)
7. Toxicity [ Time Frame: Day 32 ]
   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.)
8. Toxicity [ Time Frame: Day 45 ]
   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.)
9. Toxicity [ Time Frame: Day 60 ]
   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.)
10. Toxicity [ Time Frame: Day 90 ]
    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.)
11. Medically Attended Adverse Events (MAAEs) [ Time Frame: Day 30 ]
    Extended monitoring of Medically Attended Adverse Events (MAAEs) for potentially immune-mediated conditions (pIMMCs).
12. Medically Attended Adverse Events (MAAEs) [ Time Frame: Day 60 ]
    Extended monitoring of Medically Attended Adverse Events (MAAEs) for potentially immune-mediated conditions (pIMMCs)
13. Medically Attended Adverse Events (MAAEs) [ Time Frame: Day 90 ]
    Extended monitoring of Medically Attended Adverse Events (MAAEs) for potentially immune-mediated conditions (pIMMCs)
14. Medically Attended Adverse Events (MAAEs) [ Time Frame: Month 6 ]
    Extended monitoring of Medically Attended Adverse Events (MAAEs) for potentially immune-mediated conditions (pIMMCs)
15. Medically Attended Adverse Events (MAAEs) [ Time Frame: Month 12 ]
    Extended monitoring of Medically Attended Adverse Events (MAAEs) for potentially immune-mediated conditions (pIMMCs)
16. Medically Attended Adverse Events (MAAEs) [ Time Frame: Month 18 ]
    Extended monitoring of Medically Attended Adverse Events (MAAEs) for potentially immune-mediated conditions (pIMMCs)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Oregon

Providence Portland Medical Center

Portland, Oregon, United States, 97213

Sponsors and Collaborators

Providence Health & Services

OncoSec Medical Incorporated

More Information

• Responsible Party: Providence Health & Services
• ClinicalTrials.gov Identifier: NCT04627675
• Other Study ID Numbers: 2020000320 CORVax12
• First Posted: November 13, 2020
• Last Update Posted: June 3, 2021
• Last Verified: June 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: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes