Safety and Immunogenicity of COVID-eVax, a Candidate Plasmid DNA Vaccine for COVID-19, in Healthy Adult Volunteers

Study Overview
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Brief Summary
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This is a multicentre, open-label Phase 1/2 study, with a first-in-human (FIH) dose escalation part (Phase 1 study) followed by an open-label single arm (or two-arms, randomized) dose expansion part (Phase 2 study). The vaccine will be administered by intramuscular (IM) injection followed by electroporation (EP) applied to the injection site. The study is aimed at assessing the safety and immunogenicity of COVID-eVax, a DNA plasmid-based vaccine whose target antigen is a portion of the S protein of SARS-CoV-2 virus (the Receptor Binding Domain located in the CTD1 of the S1 region of the S protein). In animal models COVID-eVax was safe and induced high immunological humoral and cellular response.

Official Title
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A Phase I/II Study to Assess the Safety and Immunogenicity of COVID-eVax, a Candidate Plasmid DNA Vaccine for COVID-19, in Healthy Adult Volunteers

Conditions
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COVID-19, Protection Against COVID-19 and Infections With SARS-CoV- 2, COVID-19 Immunisation

Intervention / Treatment
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* Biological: COVID-eVax
* Device: Cliniporator® and EPSGun


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent obtained before undergoing any study-specific procedure Healthy male or female aged ≥18 and ≤ 65 years Body Mass Index >18.5 and ≤30 kg/m2 Vital signs within the following values or ranges: Body temperature ≤ 37,5 °C Pulse frequency ≥51 and ≤100 beats per minute Diastolic BP ≥60 mmHg, ≤ 90 mmHg Systolic BP ≥ 90 mmHg, ≤ 140 mmHg Respiratory rate ≥ 12 breaths per minute, ≤ 16 breaths per minute ECG at screening normal or with no clinically significant findings (pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome are absolute exclusion criteria) Laboratory examinations within normal reference range or with no clinically significant abnormalities Absence of any respiratory and flu-like symptoms Non-pregnant women of childbearing potential, willing to practice a highly effective method of contraception from enrolment up to study completion or at least 90 days after the last vaccination in case of withdrawal For sexually active men with a female partner of childbearing potential, willingness to use a condom and to refrain from donating sperm from enrolment up to study completion or at least 90 days after the last vaccination in case of withdrawal Agreement to refrain from blood donation during the course of the study Able and willing to comply with all study procedures. Exclusion Criteria: History of confirmed infection with SARS-CoV-2, by positive nasopharyngeal swab or by positive serological test for SARS-CoV-2 antibodies Positive serological test for SARS-CoV-2 antibodies at screening Subjects at high risk of SARS-CoV-2 infection prior or during the trial, including: subjects with any known exposure in the 4 weeks before enrolment close contacts of suspected or confirmed COVID-19 or SARS-CoV-2 infection cases subjects quarantined for any reason frontline healthcare professionals working in Emergency departments, ICU and other higher risk healthcare areas Positive serological tests for: Hepatitis B surface antigen (HBsAg) Hepatitis C antibodies Human Immunodeficiency Virus (HIV) antibodies Subjects with any of the following specific contraindications, even in medical history: Type 2 diabetes or glucose intolerance, even if controlled Hypertension, even if controlled chronic obstructive pulmonary disease (COPD) Any cardiac disease, even if not evident at ECG Pacemaker Use of any investigational drugs/treatments, or enrolment in a clinical trial during the 6 months preceding screening Prior administration of any vaccine in the 2 weeks preceding screening Administration of any monoclonal or polyclonal antibody product within 4 weeks preceding screening Administration of any blood product within 3 months of screening Current or prior administration, within the 6 months preceding screening, of immunosuppressants (inhaled, topical skin and/or eye drop-containing corticosteroids; a short course of corticosteroids, defined as ≤20 mg/day prednisone or equivalent for 10 days, and low-dose methotrexate are allowed until 4 weeks prior to screening) Any prior major surgery or any chemo- or radiation therapy within 5 years of screening Current or suspected immunosuppressive or immunodeficient state, including HIV infection, asplenia, recurrent severe infections Active, known, or suspected autoimmune disease (except mild psoriasis, well-controlled autoimmune thyroid disease, vitiligo or stable coeliac disease not requiring immunosuppressive or immunomodulatory therapy) Bleeding disorders (e.g. coagulopathy or platelet disorder or coagulation factor deficiency) or prior history of significant bleeding or bruising following IM injections or venipuncture History of seizures or mental illness History of allergy to vaccines or of severe allergic reaction of any kind Metal implants within 20 cm of the planned site(s) of injection Presence of keloid scar formation or hypertrophic scar, or other clinically significant medical condition at the planned site(s) of injection Any abnormality or permanent body art (e.g. tattoos) that would interfere with the ability to observe local reactions at the injection site in the deltoid area History of alcohol or drug abuse during the 12 months preceding the screening Pregnancy (i.e. positive pregnancy test) or willingness/intention to become pregnant during the study Breastfeeding Any other clinically relevant disease and condition that, in the opinion of the Investigator, may jeopardize efficacy or safety assessments or may compromise the subject's safety during trial participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5 mg PB<br>0.5 mg PB (Prime-Boost, 4 weeks apart) - Total dose: 1 mg IM injection + electroporation by IGEA Cliniporator® and EPSGun, on Day 1 and Day 29 | Biological: COVID-eVax<br>* Plasmid DNA Vaccine for COVID-19<br>Device: Cliniporator® and EPSGun<br>* IGEA Electroporation Device<br>|
| Experimental: 1 mg PB<br>1 mg PB (Prime-Boost, 4 weeks apart) - Total dose: 2 mg IM injection + electroporation by IGEA Cliniporator® and EPSGun, on Day 1 and Day 29 | Biological: COVID-eVax<br>* Plasmid DNA Vaccine for COVID-19<br>Device: Cliniporator® and EPSGun<br>* IGEA Electroporation Device<br>|
| Experimental: 2 mg PB<br>2 mg PB (Prime-Boost, 4 weeks apart) - Total dose: 4 mg IM injection + electroporation by IGEA Cliniporator® and EPSGun, on Day 1 and Day 29 | Biological: COVID-eVax<br>* Plasmid DNA Vaccine for COVID-19<br>Device: Cliniporator® and EPSGun<br>* IGEA Electroporation Device<br>|
| Experimental: 2 mg P<br>2 mg P (Prime) - Total dose: 2 mg IM injection + electroporation by IGEA Cliniporator® and EPSGun, on Day 1 | Biological: COVID-eVax<br>* Plasmid DNA Vaccine for COVID-19<br>Device: Cliniporator® and EPSGun<br>* IGEA Electroporation Device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of solicited local Adverse events (AEs) at the injection site (for Phase 1) |  | Through 7 days post-each vaccination | 
| Incidence of solicited systemic AEs (for Phase 1) |  | Through 7 days post-each vaccination | 
| Incidence of unsolicited AEs (for Phase 1) |  | through 4 weeks post-each vaccination | 
| White Blood Cell (WBC) levels (for Phase 1) | Change from baseline at specific timepoints | through 4 weeks post-each vaccination | 
| Red Blood Cell (RBC) levels (for Phase 1) | Change from baseline at specific timepoints | through 4 weeks post-each vaccination | 
| Platelets levels (for Phase 1) | Change from baseline at specific timepoints | through 4 weeks post-each vaccination | 
| Alanine Transaminase (ALT) levels (for Phase 1) | Change from baseline at specific timepoints | through 4 weeks post-each vaccination | 
| Aspartate Transaminase (AST) levels (for Phase 1) | Change from baseline at specific timepoints | through 4 weeks post-each vaccination | 
| Creatine Phosphokinase (CPK) levels (for Phase 1) | Change from baseline at specific timepoints | through 4 weeks post-each vaccination | 
| Quantitative antibody titers, binding to the specific SARS-CoV-2 antigen (for Phase 2) | Geometric Mean Titer (GMT) and Geometric Mean Fold Rise (GMFR) from baseline | through 4 weeks post-last vaccination | 
| SARS-CoV-2 neutralizing antibody titer (for Phase 2) | GMT and GMFR from baseline | through 4 weeks post-last vaccination | 
| Change from baseline in antigen-specific cellular immune responses to SARS-CoV-2 (for Phase 2) | Interferon-gamma (IFN-γ) ELISpot | through 4 weeks post-last vaccination | 
| Percentage of subjects who seroconverted (for Phase 2) |  | through 4 weeks post-last vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative antibody titers, binding to the specific SARS-CoV-2 antigen (for Phase 1) | GMT and GMFR from baseline | through 4 weeks post-last vaccination | 
| SARS-CoV-2 neutralizing antibody titer (for Phase 1) | GMT and GMFR from baseline | through 4 weeks post-last vaccination | 
| Change from baseline in antigen-specific cellular immune responses to SARS-CoV-2 (for Phase 1) | Interferon-gamma (IFN-γ) ELISpot | through 4 weeks post-last vaccination | 
| Percentage of subjects who seroconverted (for Phase 1) |  | through 4 weeks post-last vaccination | 
| Incidence of unsolicited AEs (for Phase 1) |  | through study completion (6 months) | 
| Incidence of solicited local AEs at the injection site (for Phase 2) |  | Through 7 days post-each vaccination | 
| Incidence of solicited systemic AEs (for Phase 2) |  | Through 7 days post-each vaccination | 
| Incidence of unsolicited AEs (for Phase 2) |  | through 4 weeks post-each vaccination | 
| White Blood Cell (WBC) levels (for Phase 2) | Change from baseline at specific timepoints | through 4 weeks post-each vaccination | 
| Red Blood Cell (RBC) levels (for Phase 2) | Change from baseline at specific timepoints | through 4 weeks post-each vaccination | 
| Platelets levels (for Phase 2) | Change from baseline at specific timepoints | through 4 weeks post-each vaccination | 
| Alanine Transaminase (ALT) levels (for Phase 2) | Change from baseline at specific timepoints | through 4 weeks post-each vaccination | 
| Aspartate Transaminase (AST) levels (for Phase 2) | Change from baseline at specific timepoints | through 4 weeks post-each vaccination | 
| Creatine Phosphokinase (CPK) levels (for Phase 2) | Change from baseline at specific timepoints | through 4 weeks post-each vaccination | 
| Incidence of unsolicited AEs (for Phase 2) |  | through study completion (6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infections Viral, Coronavirus Disease 2019, Respiratory Tract Infections, Vaccine, SARS-COV-2