Phase I/II Study of COVID-19 DNA Vaccine (AG0302-COVID19 High-dose)

Study Overview
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Brief Summary
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This study will assess the safety and immunogenicity of AG0302-COVID19 in healthy volunteers.

Detailed Description
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This is a Phase I/II, multi-center, randomized, open-label, uncontrolled trial. Approximately 400 healthy volunteers, male or female, aged 18 years or older, will be randomized to one of the following five groups: [IM Groups] Group A: Vaccination 2 mg, three times at 2-week intervals (n = 80) Group B: Vaccination 4 mg, twice at 4-week intervals (n = 80) Group C: Vaccination 8 mg, twice at 4-week intervals(n = 80) [ID Groups] Group D: Vaccination 1 mg, three times at 2-week intervals (n = 80) Group E: Vaccination 1 mg, twice at 4-week intervals (n = 80)

Official Title
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A Randomized, Open-label, Uncontrolled, Phase I/II Study to Assess Safety and Immunogenicity of Two or Three Dosing of Intramuscular/Intradermal AG0302-COVID19

Conditions
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COVID-19 Lower Respiratory Infection

Intervention / Treatment
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* Biological: AG0302-COVID19 for Intramuscular Injection
* Biological: AG0302-COVID19 for Intramuscular Injection
* Biological: AG0302-COVID19 for Intramuscular Injection
* Biological: AG0302-COVID19 for Intradermal Injection
* Biological: AG0302-COVID19 for Intradermal Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have obtained written consent voluntarily to participate in this clinical trial Subjects whose age at the time of obtaining consent is 18 years or older Subjects who are negative for SARS-CoV-2 by PCR test Subjects who are negative for both SARS-CoV-2 IgM antibody and SARS-CoV-2 IgG antibody by antibody test Exclusion Criteria: Subjects with symptoms of suspected COVID-19 infection (respiratory symptoms, headache, malaise, olfactory disorders, taste disorders, etc.) Subjects with a history of COVID-19 (hearing from subjects) Subjects with a history of vaccination for the prevention of COVID-19 Subjects who have participated in unapproved vaccine clinical trials within 1 year before the start of this study Subjects with an axillary temperature of 37.5 degrees or higher at the time of screening Subjects with an axillary temperature of 37.5 degrees or higher before the first vaccination Subjects who have a history of anaphylaxis Subjects who have a history of hypersensitivity to the ingredients of the investigational drug Subjects who have a current or history of serious renal, cardiovascular, respiratory, liver, kidney, gastrointestinal, and neuropsychiatric diseases Subjects with a history of convulsion or epilepsy Subjects with a history of diagnosis of immunodeficiency Subjects who have a close relative (within 3rd degree) of congenital immunodeficiency Subjects who have current bronchial asthma Subjects who have had a fever of 39.0 degrees or higher within 2 days after vaccination, or who have been suspected of having an allergy such as a systemic rash. Females who wish to become pregnant from the time of obtaining consent to 12 weeks after the first vaccination, and pregnant females who are breast-feeding. In addition, females who may become pregnant and their male sexual partners should use appropriate contraceptives (pill), condoms, vasectomy, tubal ligation, diaphragm, intrauterine devices, spermicides, intrauterine hormone-releasing system, etc. from the study entry date until 12 weeks after the first vaccination Subjects who have participated in clinical trials of other unapproved drugs and received the investigational drug within 4 weeks before the start of this clinical trial (starting from vaccination day) Subjects who have been received a live vaccine, inactivated vaccine, or toxoid within 4 weeks before the start of this clinical trial (starting from vaccination day) Subjects who have been administered with drugs that affect the immune system (excluding external preparations) such as immunomodulators (DMARDs, etc.), immunosuppressants, biologics, etc. within 4 weeks before vaccination Subjects who received blood transfusion or gamma globulin therapy within 12 weeks before vaccination, or high-dose gamma globulin therapy (200 mg/kg or more) within 24 weeks before vaccination Subjects who have a history of overseas travel within 4 weeks before the start of the clinical trial (starting from vaccination day) Subjects who are unable to comply with the clinical trial protocol and follow up (for mental, family, social or geographical reasons) Subjects who are judged to be ineligible for this clinical trial by the investigator

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: Group A<br> | Biological: AG0302-COVID19 for Intramuscular Injection<br>* Vaccination 2 mg of AG0302-COVID19 three times at 2-week intervals<br>|
| Experimental: Group B<br> | Biological: AG0302-COVID19 for Intramuscular Injection<br>* Vaccination 4 mg of AG0302-COVID19 twice at 4-week intervals<br>|
| Experimental: Group C<br> | Biological: AG0302-COVID19 for Intramuscular Injection<br>* Vaccination 8 mg of AG0302-COVID19 twice at 4-week intervals<br>|
| Experimental: Group D<br> | Biological: AG0302-COVID19 for Intradermal Injection<br>* Vaccination 1 mg of AG0302-COVID19 three times at 2-week intervals<br>|
| Experimental: Group E<br> | Biological: AG0302-COVID19 for Intradermal Injection<br>* Vaccination 1 mg of AG0302-COVID19 twice at 4-week intervals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Frequency and severity of each adverse event, solicited local and systemic AEs from the first vaccination to 12 weeks after first vaccination | Week 1 through Week 13 | 
| Immunogenicity | Change in the neutralizing activity against pseudovirus of SARS-CoV-2 [ID50] | Week 13 | 
| Immunogenicity | Change in Geometric mean titer (GMT) of serum anti-SARS-CoV-2 Spike (S) glycoprotein-specific antibody | Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in GMT of anti-SARS-CoV-2 Spike (S) glycoprotein-specific antibody |  | Weeks 5, 7, 9, 13, 17, 21, 25, 37, 53 | 
| Change in the neutralizing activity against pseudovirus of SARS-CoV-2 |  | Weeks 5, 7, 9, 13, 17, 21, 25, 37, 53 | 
| Seroconversion rate from baseline (defined as a 4-fold or greater increase) in the neutralizing activity against pseudovirus of SARS-CoV-2 [ID50] |  | Weeks 5, 7, 9, 13, 17, 21, 25, 37, 53 | 
| Change in IFN-gamma production against SARS-CoV-2 spike (S) glycoprotein by T cells in peripheral blood mononuclear cells |  | Weeks 5, 7, 9, 13 | 
| IgG subclasses (IgG1 and IgG2) of anti-SARS-CoV-2 spike (S) glycoprotein-specific antibody |  | Weeks 1, 9, 13 | 
| Adverse events |  | Week 13 through Week 53 | 
| Rate of SARS-CoV-2 positive and incidence rate of COVID-19 after the first vaccination |  | Week 1 through Week 53 | 
| Rate of swelling and leakage of the drug to the vaccination site during intradermal vaccination |  | Weeks 1, 3, 5 | 
| Number of defects in preparation and vaccination during intradermal vaccination |  | Week 1 through Week 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, COVID-19, SARS-CoV-2