CVXGA Vaccine for Coronavirus

Not currently recruiting at 55 trial locations

Overseen By Shishir K Khetan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CyanVac LLC

Must not be taking: Intranasal medications, Immunosuppressants

Disqualifiers: Acute illness, Positive COVID-19, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new COVID-19 vaccine, CVXGA, against an existing vaccine, COMIRNATY, to determine its safety and effectiveness in preventing COVID-19 symptoms. Participants will receive either the new vaccine or the existing one to compare outcomes. The study seeks healthy adults who have completed their initial COVID-19 vaccine series and have not been vaccinated in the last six months. Participants must also agree to avoid other COVID-19 prevention trials or treatments during this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications, especially those affecting the immune system, may need to be paused or adjusted. It's best to discuss your specific medications with the trial team.

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

Research shows that CVXGA, a nasal spray COVID-19 vaccine, is generally safe. Studies have found that it creates a strong immune response with few side effects, meaning most people don't experience major issues. In earlier research, participants reported only a few minor problems, suggesting the vaccine is quite safe. Additionally, CVXGA appears to protect against different virus variants.

Since the trial is in Phase 2, the researchers are focusing on collecting more information about the vaccine's safety. This phase usually includes more participants than earlier ones to better understand the vaccine's safety profile. While not yet approved for everyone, these trials help confirm that the vaccine could be safe for larger groups. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard COVID-19 vaccines like mRNA-based COMIRNATY®, CVXGA uses a recombinant parainfluenza virus type 5 (PIV5) engineered to express the SARS-CoV-2 spike protein. This unique approach could induce a broader immune response by leveraging the PIV5 vector, which might offer enhanced protection. Researchers are excited about CVXGA because it represents a novel mechanism of action that could potentially improve vaccine efficacy and durability against the virus.

What evidence suggests that the CVXGA vaccine might be an effective treatment for coronavirus?

Research shows that the CVXGA (CVXGA50) vaccine, which participants in this trial may receive, holds promise as a COVID-19 vaccine. Previous studies found that it can trigger an immune response with few side effects. Administered as a nasal spray, the vaccine might offer strong protection against different virus strains. Animal studies indicate that this vaccine can protect well against various COVID-19 variants. These findings suggest CVXGA could be a powerful tool in preventing COVID-19 infections. Meanwhile, another group in this trial will receive COMIRNATY® as the comparator vaccine. ^{1 3 4 6 7}

Who Is on the Research Team?

Hong Jin

Principal Investigator

CyanVac LLC

Are You a Good Fit for This Trial?

This trial is for up to 10,016 healthy adults to test a new intranasal COVID-19 vaccine called CVXGA. Participants should not have received any other COVID-19 vaccines recently and must be at risk of SARS-CoV-2 infection.

Inclusion Criteria

Is medically stable, as determined by the site investigator (based on review of health status, vital signs, medical history, and physical examination)

Agrees to not participate in any other SARS-CoV-2 infection prevention trial (vaccine, drug, biologic, or pre-exposure prophylaxis [PrEP]) during participation in the study

I received my last COVID-19 vaccine over 6 months ago.

Exclusion Criteria

Current or planned participation in any other interventional clinical trial

Has an acute illness, as determined by the site investigator, within 72 hours prior to Screening or study vaccination

Has had a positive COVID-19 test within the 90 days prior to Screening or study vaccination

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of CVXGA (CVXGA50) intranasally or a single dose of IM COMIRNATY, with placebo administration as applicable

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after vaccination, including assessment of symptomatic and asymptomatic COVID-19 cases

12 months

Approximately 6-7 visits (in-person)

Safety Monitoring

Monitoring for solicited and unsolicited adverse events, including local and systemic reactogenicity symptoms

30 days

What Are the Treatments Tested in This Trial?

Interventions

• CVXGA (CVXGA50)

Trial Overview The study compares the safety and effectiveness of a single dose of CVXGA, an experimental nasal spray vaccine, against COMIRNATY®, an approved mRNA COVID-19 vaccine. It's randomized and double-blind, meaning participants are assigned by chance to receive one or the other without knowing which they get.

How Is the Trial Designed?

Group I: CVXGA (CVXGA50) Experimental Treatment 1 Intervention

CVXGA is a recombinant parainfluenza virus type 5 (PIV5) engineered to express SARS-CoV-2 S gene from the KP.2 strain.

Group II: COMIRNATY® Active Control 1 Intervention

COMIRNATY® (COVID-19 vaccine, mRNA) suspension for injection, for intramuscular use, 2024-2025 Formula (BioNTech Manufacturing GmbH \[Mainz, Germany\] and Pfizer Inc. \[New York, NY\]) will be used as the comparator vaccine for this study.

Who Is Running the Clinical Trial?

CyanVac LLC

Lead Sponsor

Trials

3

Recruited

10,300+

Biomedical Advanced Research and Development Authority

Collaborator

Trials

108

Recruited

574,000+

Published Research Related to This Trial

The intranasal CVXGA1 vaccine, which uses a parainfluenza virus vector, has shown strong efficacy in animal models by inducing neutralizing antibodies against multiple SARS-CoV-2 variants and protecting against both homologous and heterologous virus challenges.

When used as a booster after mRNA vaccines, CVXGA1 and other PIV5-vectored vaccines produced higher levels of cross-reactive neutralizing antibodies compared to three doses of mRNA vaccines, suggesting they could enhance protection against emerging variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Parainfluenza Virus 5 (PIV5)-vectored Intranasal COVID-19 Vaccine as a Single Dose Vaccine and as a Booster against SARS-CoV-2 Variants. Beavis, AC., Li, Z., Briggs, K., et al.[2023]

In a large study involving nearly 885,000 vaccinated individuals, the BNT162b2 mRNA vaccine was found to have a low risk of serious adverse events, with a notable but rare increase in myocarditis risk (2.7 events per 100,000 persons).

Compared to the risks associated with SARS-CoV-2 infection, which showed a significantly higher risk of myocarditis (11 events per 100,000 persons) and other serious conditions, the vaccine's safety profile is favorable, indicating that vaccination is safer than infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. Barda, N., Dagan, N., Ben-Shlomo, Y., et al.[2023]

The dNS1-RBD intranasal vaccine demonstrated a favorable safety profile in a large phase 3 trial with 31,038 participants, showing no serious adverse events or deaths, and common side effects were similar to those of the placebo group.

The vaccine provided a protective efficacy of 28.2% against symptomatic SARS-CoV-2 infections caused by omicron variants, although it did not meet the predefined success criterion of over 30% efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the intranasal spray SARS-CoV-2 vaccine dNS1-RBD: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Zhu, F., Huang, S., Liu, X., et al.[2023]

The intranasally delivered Gam-COVID-Vac (Sputnik V) vaccine demonstrated a strong immune response lasting at least 180 days in mice, indicating its potential effectiveness in providing long-term protection against COVID-19.

In non-human primates, the vaccine showed significant production of neutralizing antibodies and T-cell responses, and it provided sterilizing immunity in mice, preventing severe disease and death from SARS-CoV-2, suggesting it could be a valuable option for both initial vaccination and booster doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and protectivity of intranasally delivered vector-based heterologous prime-boost COVID-19 vaccine Sputnik V in mice and non-human primates. Tukhvatulin, AI., Gordeychuk, IV., Dolzhikova, IV., et al.[2022]

The intranasal vaccine developed using a modified human parainfluenza virus (BC-PIV) effectively induced strong immune responses in mice and hamsters, producing high levels of neutralizing antibodies against the SARS-CoV-2 spike protein.

Single-dose vaccination in hamsters provided complete protection against SARS-CoV-2 in the lungs for up to 11 weeks, demonstrating the vaccine's potential to prevent virus transmission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-propagative human parainfluenza virus type 2 nasal vaccine robustly protects the upper and lower airways against SARS-CoV-2. Ohtsuka, J., Imai, M., Fukumura, M., et al.[2021]

The optimized vaccine candidate, CVXGA1, which uses parainfluenza virus 5 to express the SARS-CoV-2 spike protein, effectively protects against severe COVID-19 in a mouse model and prevents virus transmission in ferrets.

This intranasal vaccine strategy significantly reduces SARS-CoV-2 replication in the upper respiratory tract, which is crucial for blocking transmission and preventing disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protection of K18-hACE2 mice and ferrets against SARS-CoV-2 challenge by a single-dose mucosal immunization with a parainfluenza virus 5-based COVID-19 vaccine. An, D., Li, K., Rowe, DK., et al.[2022]

A study involving 451 adults showed that inhaled adenovirus-vectored COVID-19 vaccines, including a bivalent and a variant-specific option, were safe and well tolerated, with mostly mild to moderate side effects and no serious adverse events reported.

The bivalent vaccine induced a significantly higher level of neutralizing antibodies against the Omicron variant compared to the standard vaccine, suggesting it may provide enhanced protection against SARS-CoV-2 variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of heterologous boosting with orally administered aerosolized bivalent adenovirus type-5 vectored COVID-19 vaccine and B.1.1.529 variant adenovirus type-5 vectored COVID-19 vaccine in adults 18 years and older: a randomized, double blinded, parallel controlled trial. Xu, JW., Wang, BS., Gao, P., et al.[2023]

The experimental intranasal vaccine AVX/COVID-12-HEXAPRO demonstrated strong safety and immunogenicity in a pig model, showing no adverse reactions and eliciting robust neutralizing antibody responses against SARS-CoV-2 variants.

This vaccine could potentially address global demand for COVID-19 vaccines, as it can be produced locally and at a lower cost, making it a promising candidate for future vaccination strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate, AVX/COVID-12-HEXAPRO (Patria), in Pigs. Lara-Puente, JH., Carreño, JM., Sun, W., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05736835?term=intranasal%20vaccine&cond=COVID-19&viewType=Table&rank=6

A Phase 2 Trial of the Immunogenicity and Safety ... This is a randomized, placebo controlled, blinded study to evaluate the immunogenicity and safety of CVXGA. Trial Population: Up to 400 healthy adults ...

2. science.org science.org/doi/10.1126/sciadv.adw0896

vectored COVID-19 vaccine in adults and teens in an open ... The data indicate that CVXGA1 is a potentially effective intranasal COVID-19 vaccine that is immunogenic with minimal reactogenicity.

3. bluelakebiotechnology.com bluelakebiotechnology.com/news/preclinical-intranasal-covid-19-vaccine-candidate-data-demonstrate-durable-immune-response-and-broad-protection

Preclinical Intranasal COVID-19 Vaccine Candidate Data ... CVXGA1 provided strong protection against infection by the WA1 strain and multiple SARS-CoV-2 variants. Notably, the data suggest that CVXGA1 ...

4. journals.asm.org journals.asm.org/doi/10.1128/jvi.01989-24

Efficacy of parainfluenza virus 5 (PIV5)-vectored intranasal ... This work demonstrates the protective efficacy and strong boosting effect of an intranasal viral-vectored vaccine against SARS-CoV-2 variants in hamsters.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40614182/

vectored COVID-19 vaccine in adults and teens in an open ... The data indicate that CVXGA1 is a potentially effective intranasal COVID-19 vaccine that is immunogenic with minimal reactogenicity.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11998504/

Efficacy of parainfluenza virus 5 (PIV5)-vectored intranasal ... In this work, we examined the efficacy of CVXGA1 and other recombinant PIV5 vaccines expressing S from SARS-CoV-2 beta, gamma, delta, or omicron ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04954287

Phase 1 Study of Intranasal PIV5 COVID-19 Vaccine ... This Phase 1 trial is an open-label trial to evaluate the safety, reactogenicity and immunogenicity of two dosages (10^6 PFU and 10^7 PFU) of intranasal CVXGA1 ...