Synthetic MVA-based Vaccine for COVID-19

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new synthetic vaccine designed to protect against COVID-19. The research aims to find the safest dose and assess how well it boosts immunity, the body's defense against infection. In Phase 1, participants receive either the vaccine or a placebo to evaluate safety. Phase 2 focuses on the immune response to different booster doses. Healthy adults with no history of COVID-19 who have received a prior COVID-19 mRNA vaccine might be a good fit for this trial. As a Phase 1 and Phase 2 trial, participants will be among the first to receive this new vaccine and help determine its effectiveness in boosting immunity.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the COH04S1 vaccine, a type of COVID-19 vaccine, has been tested in earlier studies to assess its safety. In one study, most participants tolerated the vaccine well, experiencing no serious side effects.

Common side effects were mild, such as pain at the injection site, fatigue, and headaches, similar to those of other vaccines. No severe side effects directly linked to the vaccine were reported, suggesting it is relatively safe. However, more studies are ongoing to confirm this.

The vaccine uses a method called MVA (modified vaccinia Ankara), which has been safely used in other vaccines, indicating its potential safety as a COVID-19 vaccine. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about COH04S1 because it uses a synthetic Modified Vaccinia Ankara (MVA) vector, which is different from the mRNA technology used in most current COVID-19 vaccines like Pfizer-BioNTech and Moderna. This unique approach could potentially offer a broader immune response by presenting multiple antigens to the immune system. Additionally, COH04S1 is administered via an intramuscular injection in the non-dominant arm, making it straightforward and familiar for healthcare professionals to deliver. The vaccine's potential to be used as both a primary series and a booster—at varying doses—offers flexibility in enhancing and prolonging immune protection against COVID-19.

What evidence suggests that this vaccine might be an effective treatment for COVID-19?

Research has shown that the COH04S1 vaccine looks promising in early studies. It was safe and successfully triggered a strong immune response in initial tests. Participants in this trial may receive COH04S1 in different dosages or as a booster. Studies have demonstrated that COH04S1 can protect against the original COVID-19 virus and some variants, like Beta and Delta, in animal tests. These results suggest that the vaccine may help the body recognize and fight off COVID-19. This vaccine uses a man-made virus to train the immune system, a method that has worked well in similar vaccines. ^{2 3 4 6 7}

Who Is on the Research Team?

Chief Medical Officer

Principal Investigator

GeoVax, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8782996/

Synthetic multiantigen MVA vaccine COH04S1 protects ... Several SARS-CoV-2 vaccines were developed in response to the COVID-19 pandemic with unprecedented pace and showed 62–95% efficacy in Phase 3 clinical trials, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04639466

NCT04639466 | A Synthetic MVA-based SARS-CoV-2 ... This phase I trial evaluates the side effects and best dose of GEO-CM04S1 (previously designated as COH04S1), a synthetic modified vaccinia Ankara ...

3. nature.com nature.com/articles/s41541-023-00640-y

Synthetic multiantigen MVA vaccine COH04S1 and variant- ... Several studies report reduced clinical effectiveness against Omicron variants by approved COVID-19 vaccines, which were designed to elicit ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666524722000271

Safety and immunogenicity of a synthetic multiantigen ... Importantly, since MVA-attenuated poxviral vectors have been shown to be highly tolerable and immunogenic even in immunosuppressed patients, COH04S1 could find ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36928589/

Synthetic multiantigen MVA vaccine COH04S1 and ... - PubMed COH04S1 demonstrated efficacy against ancestral virus and Beta and Delta variants in animal models and was safe and immunogenic in a Phase 1 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8906816/

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

7. geovax.com geovax.com/investors/press-releases/geovax-next-generation-covid-19-vaccine-demonstrates-potent-antibody-and-cellular-immunity-in-immunocompromised-patients

GeoVax Next-Generation COVID-19 Vaccine ... GEO-CM04S1 is based on GeoVax's MVA viral vector platform, which supports the presentation of multiple vaccine antigens to the immune system in ...