Synthetic MVA-based Vaccine for COVID-19

Recruiting at 3 trial locations

Overseen By Director Clinical Operations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: GeoVax, Inc.

Must not be taking: Investigational agents, Steroids

Disqualifiers: Diabetes, Obesity, Heart disease, others

Compensation: Varies

Number of Visits: 16

119 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants stop taking daily medications for chronic or ongoing illnesses, except for certain medications like thyroid or estrogen replacement, vitamins, mild antidepressants, and non-immunosuppressive drugs. If you're on other medications, you may need to stop them to participate.

What data supports the effectiveness of the treatment COH04S1 for COVID-19?

Research shows that the COH04S1 vaccine, which uses a modified virus to deliver COVID-19 proteins, helps the body create strong immune responses. It has been effective in animals and humans, providing protection against different COVID-19 variants by stimulating both antibody and T-cell responses, which are important for fighting infections. ^{1 2 3 4 5}

Is the synthetic MVA-based COVID-19 vaccine (COH04S1) safe for humans?

The COH04S1 vaccine, tested in healthy adults, showed safety in early trials. It is based on a modified virus platform that has been used safely in other vaccines for infectious diseases and cancer. ^{5 6 7 8 9}

How is the treatment COH04S1 different from other COVID-19 vaccines?

COH04S1 is unique because it is a synthetic vaccine based on a modified vaccinia Ankara (MVA) vector that targets both the spike and nucleocapsid proteins of the virus, potentially offering broader protection. It can be administered intramuscularly or intranasally, and it induces strong T-cell responses, which are important for long-term immunity. ^{2 3 7 10 11}

What is the purpose of this trial?

This phase I trial evaluates the side effects and best dose of GEO-CM04S1 (previously designated as COH04S1), a synthetic modified vaccinia Ankara (MVA)-based SARS-CoV-2 vaccine, for the prevention of COVID-19 infection. COVID-19 infection is caused by the SARS-CoV-2 virus. SARS-CoV-2 has demonstrated the capability to spread rapidly, leading to significant impacts on healthcare systems and causing societal disruption. GEO-CM04S1 was created by placing small pieces of SARS-CoV-2 DNA (the chemical form of genes) into synthetic MVA, which may be able to induce immunity (the ability to recognize and fight against an infection) to SARS-CoV-2. The purpose of the Phase 1 study is to determine the safety and the optimal dose of the GEO-CM04S1 vaccine. The Phase 2 study is designed as a multi-center, double-blind, randomized, parallel, study to evaluate the safety profile of 2 dose levels of GEO-CM04S1 as a single booster shot to assess the immune response measured by the fold-increase in antibody against SARS-CoV-2 Spike protein at day 28 post-injection among healthy adult volunteers.

Research Team

Chief Medical Officer

Principal Investigator

GeoVax, Inc.

Eligibility Criteria

This trial is for individuals who have received at least two COVID-19 vaccines, haven't had any vaccines in the last month, and are not currently on medications that affect the immune system. They should not have COVID-19 or a history of severe allergic reactions to vaccines. People with certain medical conditions or those taking corticosteroids recently are excluded.

Inclusion Criteria

Answer YES if you do not currently have COVID-19

I have not taken any corticosteroid medication in the last 14 days.

Have you received at least 2 COVID vaccines?

Exclusion Criteria

I have severe migraines but am on effective medication reducing them to less than one per month.

I haven't had strong cancer treatments or immune therapies in the last 30 days.

I do not have conditions like severe diabetes, obesity, heart failure, or lung disease that increase my risk for severe COVID-19.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive GEO-CM04S1 or placebo intramuscularly on day 0 and day 28, with follow-up visits to assess safety and immune response

4 weeks

11 visits (in-person) over 365 days

Phase II Treatment

Participants receive a single booster dose of GEO-CM04S1 at either low or high dose, with follow-up visits to assess safety and immune response

1 week

5 visits (in-person) over 365 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of immune response durability and incidence of COVID-19

12 months

Treatment Details

Interventions

• COH04S1

Trial Overview The trial is testing COH04S1, a synthetic MVA-based SARS-CoV-2 vaccine designed to prevent COVID-19 infection. It involves determining the safest and most effective dose by comparing it with a placebo (a substance with no therapeutic effect).

Participant Groups

Group I: Phase II Arm II (high dose COH04S1 booster) Experimental Treatment 1 Intervention

Participants receive high dose COH04S1 booster IM in non-dominant upper arm on day 1 in the absence of unacceptable toxicity.

Group II: Phase II Arm I (low dose COH04S1 booster) Experimental Treatment 1 Intervention

Participants receive low dose COH04S1 booster IM in non-dominant upper arm on day 1 in the absence of unacceptable toxicity.

Group III: Phase I Arm I (COH04S1) Experimental Treatment 1 Intervention

Participants receive COH04S1 IM in the non-dominant upper arm on day 0 and day 28 in the absence of unacceptable toxicity.

Group IV: Phase I Arm II (COH04S1, placebo) Active Control 2 Interventions

Participants receive COH04S1 IM in the non-dominant upper arm on day 0 and placebo IM in the non-dominant upper arm on day 28 in the absence of unacceptable toxicity.

Group V: Phase I Arm III (placebo) Placebo Group 1 Intervention

Participants receive placebo IM in the non-dominant upper arm on day 0 and day 28 in the absence of unacceptable toxicity.

Who Is Running the Clinical Trial?

GeoVax, Inc.

Lead Sponsor

Trials

6

Recruited

440+

City of Hope Medical Center

Collaborator

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The MVA-CoV2-S vaccine candidate effectively protected K18-hACE2 transgenic mice from lethal SARS-CoV-2 infection, preventing virus replication in the lungs and reducing lung damage, indicating strong efficacy.

Two doses of the vaccine induced high levels of IgG and neutralizing antibodies against the virus and its variants, and also established long-term immune memory, suggesting potential for effective human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice. Lázaro-Frías, A., Pérez, P., Zamora, C., et al.[2022]

The COH04S1 vaccine, a synthetic multiantigen MVA-based COVID-19 vaccine, successfully stimulated strong immune responses, including both humoral and cellular immunity, in a phase 1 trial with healthy adults.

Both COH04S1 and the mRNA vaccine BNT162b2 maintained robust T cell immunity for at least six months, providing a critical second line of defense against SARS-CoV-2 variants, despite reduced neutralizing antibody activity against variants like Delta and Omicron.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine-induced spike- and nucleocapsid-specific cellular responses maintain potent cross-reactivity to SARS-CoV-2 Delta and Omicron variants. Chiuppesi, F., Zaia, JA., Faircloth, K., et al.[2022]

The synthetic SARS-CoV-2 spike glycoprotein-coated lipid vesicles (S-LVs) induced high levels of neutralizing antibodies and T helper cell responses in cynomolgus macaques, demonstrating strong immunogenicity against multiple variants of the virus.

Vaccinated macaques achieved complete protection from SARS-CoV-2 infection, indicating that the S-LV vaccine candidate not only elicits a robust immune response but also provides sterilizing immunity, making it a promising candidate for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection. Sulbaran, G., Maisonnasse, P., Amen, A., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Mucosal vaccination induces protection against SARS-CoV-2 in the absence of detectable neutralizing antibodies. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Vaccine-induced spike- and nucleocapsid-specific cellular responses maintain potent cross-reactivity to SARS-CoV-2 Delta and Omicron variants. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

COH04S1 and beta sequence-modified vaccine protect hamsters from SARS-CoV-2 variants. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a synthetic multiantigen modified vaccinia virus Ankara-based COVID-19 vaccine (COH04S1): an open-label and randomised, phase 1 trial. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Vaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

COVID-19 Infection Detection and Prevention by SARS-CoV-2 Active Antigens: A Synthetic Vaccine Approach. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Synthetic multiantigen MVA vaccine COH04S1 protects against SARS-CoV-2 in Syrian hamsters and non-human primates. [2022]