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

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04788459
• Other study ID #: COV-1/2-01
• Secondary ID: 2020-003734-20
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 25, 2021
• Est. completion date: December 7, 2021

Study information

• Verified date: December 2021
• Source: Takis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 68
• Est. completion date: December 7, 2021
• Est. primary completion date: December 7, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Signed and dated informed consent obtained before undergoing any study-specific procedure

2. Healthy male or female aged =18 and = 65 years

3. Body Mass Index >18.5 and =30 kg/m2

4. Vital signs within the following values or ranges:

1. Body temperature = 37,5 °C

2. Pulse frequency =51 and =100 beats per minute

3. Diastolic BP =60 mmHg, = 90 mmHg

4. Systolic BP = 90 mmHg, = 140 mmHg

5. Respiratory rate = 12 breaths per minute, = 16 breaths per minute

5. ECG at screening normal or with no clinically significant findings (pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome are absolute exclusion criteria)

6. Laboratory examinations within normal reference range or with no clinically significant abnormalities

7. Absence of any respiratory and flu-like symptoms

8. 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

9. 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

10. Agreement to refrain from blood donation during the course of the study

11. Able and willing to comply with all study procedures.

Exclusion Criteria:

1. History of confirmed infection with SARS-CoV-2, by positive nasopharyngeal swab or by positive serological test for SARS-CoV-2 antibodies

2. Positive serological test for SARS-CoV-2 antibodies at screening

3. Subjects at high risk of SARS-CoV-2 infection prior or during the trial, including:

1. subjects with any known exposure in the 4 weeks before enrolment

2. close contacts of suspected or confirmed COVID-19 or SARS-CoV-2 infection cases

3. subjects quarantined for any reason

4. frontline healthcare professionals working in Emergency departments, ICU and other higher risk healthcare areas

4. Positive serological tests for:

1. Hepatitis B surface antigen (HBsAg)

2. Hepatitis C antibodies

3. Human Immunodeficiency Virus (HIV) antibodies

5. Subjects with any of the following specific contraindications, even in medical history:

1. Type 2 diabetes or glucose intolerance, even if controlled

2. Hypertension, even if controlled

3. chronic obstructive pulmonary disease (COPD)

4. Any cardiac disease, even if not evident at ECG

5. Pacemaker

6. Use of any investigational drugs/treatments, or enrolment in a clinical trial during the 6 months preceding screening

7. Prior administration of any vaccine in the 2 weeks preceding screening

8. Administration of any monoclonal or polyclonal antibody product within 4 weeks preceding screening

9. Administration of any blood product within 3 months of screening

10. 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)

11. Any prior major surgery or any chemo- or radiation therapy within 5 years of screening

12. Current or suspected immunosuppressive or immunodeficient state, including HIV infection, asplenia, recurrent severe infections

13. 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)

14. 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

15. History of seizures or mental illness

16. History of allergy to vaccines or of severe allergic reaction of any kind

17. Metal implants within 20 cm of the planned site(s) of injection

18. Presence of keloid scar formation or hypertrophic scar, or other clinically significant medical condition at the planned site(s) of injection

19. 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

20. History of alcohol or drug abuse during the 12 months preceding the screening

21. Pregnancy (i.e. positive pregnancy test) or willingness/intention to become pregnant during the study

22. Breastfeeding

23. 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.

Related Conditions & MeSH terms

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

Intervention

Biological:
• COVID-eVax
Plasmid DNA Vaccine for COVID-19

Device:
• Cliniporator® and EPSGun
IGEA Electroporation Device

Locations

Country	Name	City	State
Italy	San Gerardo Hospital	Monza
Italy	Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale	Naples
Italy	INMI Lazzaro Spallanzani	Rome
Italy	- CRC Centro Ricerche Cliniche di Verona	Verona

Sponsors (2)

Lead Sponsor	Collaborator
Takis	Rottapharm Biotech

Country where clinical trial is conducted

Italy, 

Outcome

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