Combination Vaccine for COVID-19 and Flu

Recruiting at11 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Sanofi

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: Immunodeficiency, Bleeding disorder, Stroke, others

Stay on Your Current Meds

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Study VBT00001 is planned to be a Phase 1/2, randomized, modified double-blind, active-controlled, multi-center study to be conducted in approximately 980 adults aged 50 years and older in the United States. The purpose of the study is to assess the safety and immunogenicity of IIV-HD (high-dose inactivated influenza vaccine) + rC19 (adjuvanted recombinant COVID-19 vaccine) vaccine comprised of IIV-HD combined with different recombinant Spike (rS) antigen levels of rC19 compared to IIV-HD alone, rC19 (dose 1) alone, and IIV-HD and rC19 (dose 1) (coadministered in opposite arms). Placebo will be coadministered in the IIV-HD alone, rC19 (dose 1) alone, and IIV-HD + rC19 study groups to control for the number of injections and to maintain observer-blinding. Thus, each participant will receive two injections at enrollment, one in each deltoid muscle. Study details include: * The study duration will be approximately 12 months * Study intervention will be administered via a single intramuscular (IM) injection into the right and left deltoid muscles on D01 * Dose escalation with sequential enrollment (sentinel cohort followed by main cohort for a given dose) * The visit frequency will be D01, D09 (telephone call), D30, D182 (telephone call), and D366 (telephone call) Number of Participants: Approximately 980 participants are expected to be randomized.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or long-term systemic corticosteroids, you may not be eligible to participate.

What data supports the effectiveness of the treatment IIV-HD + rC19, Spikevax, COVID-19 Vaccine, mRNA, IIV-HD + rC19 (for the combination)?

The research on various COVID-19 vaccines, including mRNA vaccines like Spikevax, shows they can induce strong immune responses and provide protection against different variants of the virus. This suggests that combining these vaccines with flu vaccines could potentially enhance protection against both COVID-19 and flu. ^{1 2 3 4 5}

Is the combination vaccine for COVID-19 and flu generally safe for humans?

The safety data for various COVID-19 vaccines, including those using mRNA technology like Spikevax, show that most adverse events are mild or moderate. Some vaccines have been associated with rare thrombotic events, but ongoing studies and monitoring are needed to fully understand all potential side effects. ^{5 6 7 8 9}

How is the combination vaccine IIV-HD + rC19 different from other COVID-19 and flu vaccines?

The combination vaccine IIV-HD + rC19 is unique because it combines a high-dose influenza vaccine with the Spikevax COVID-19 mRNA vaccine, potentially offering protection against both flu and COVID-19 in a single shot, which is not a standard approach with existing vaccines. ^{4 5 10 11 12}

Research Team

Eligibility Criteria

Adults aged 50 and older who have completed their primary COVID-19 vaccination series plus a booster can join this trial. They must be healthy or have stable pre-existing conditions, able to get shots in both arms, attend all visits, and follow study procedures. Women must not be able to bear children or agree to use contraception.

Inclusion Criteria

I can attend all required visits and follow the study rules.

My eligibility for the trial will be confirmed at my screening visit.

I am 50 years old or older.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two intramuscular injections, one in each deltoid muscle, on Day 01

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and immunogenicity, with follow-up calls and visits at D09, D30, D182, and D366

12 months

1 visit (in-person), 3 visits (telephone calls)

Treatment Details

Interventions

• IIV-HD + rC19 (Cancer Vaccine)

Trial Overview The trial is testing the safety and immune response of a high-dose flu shot combined with different levels of a new COVID-19 vaccine compared to each vaccine alone or with placebo. Participants will receive two injections at the start and will be monitored for about one year.

Participant Groups

Group I: Group 7: IIV-HD + rC19 (dose 4) (in right or left deltoid) and placebo (in opposite deltoid) Experimental Treatment 2 Interventions

two IM injections on D01

Group II: Group 6: IIV-HD + rC19 (dose 3) (in right or left deltoid) and placebo (in opposite deltoid) Experimental Treatment 2 Interventions

two IM injections on D01

Group III: Group 5: IIV-HD + rC19 (dose 2) (in right or left deltoid) and placebo (in opposite deltoid) Experimental Treatment 2 Interventions

two IM injections on D01

Group IV: Group 4: IIV-HD + rC19 (dose 1) (in right or left deltoid) and placebo (in opposite deltoid) Experimental Treatment 2 Interventions

two IM injections on D01

Group V: Group 3: IIV-HD (in right or left deltoid) and rC19 (dose1) (in opposite deltoid) Experimental Treatment 2 Interventions

two IM injections on D01

Group VI: Group 2: rC19 (dose 1) (in right or left deltoid) and placebo (in opposite deltoid) Experimental Treatment 2 Interventions

two IM injections on D01

Group VII: Group 1: IIV-HD (in right or left deltoid) and placebo (in opposite deltoid) Experimental Treatment 2 Interventions

two IM injections on D01

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

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 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]

The Abdala vaccine, a novel SARS-CoV-2 receptor-binding domain vaccine, was found to be safe and well tolerated in a phase 1-2 trial with 792 participants, showing minimal adverse reactions mostly limited to mild injection site discomfort.

The vaccine induced strong immune responses, with seroconversion rates of 95.2% in the 50 µg group and 81% in the 25 µg group after the short immunization schedule, significantly outperforming the placebo group, which had a 0% seroconversion rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and immunogenicity of a SARS-CoV-2 recombinant spike RBD protein vaccine: A randomised, double-blind, placebo-controlled, phase 1-2 clinical trial (ABDALA Study). Hernández-Bernal, F., Ricardo-Cobas, MC., Martín-Bauta, Y., et al.[2022]

The heterologous COVID-19 vaccine using rAd26 and rAd5 vectors was found to be safe and well tolerated among 76 healthy adult participants, with mild adverse events like injection site pain and headache being the most common, and no serious adverse events reported.

Both frozen and lyophilised formulations of the vaccine induced strong immune responses, with 100% of participants producing antibodies against SARS-CoV-2 and significant T-cell responses detected, indicating promising immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Logunov, DY., Dolzhikova, IV., Zubkova, OV., et al.[2022]

References

1. United States 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. [2023]

2. United States 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. [2023]

3. Singapore pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of heterologous booster with protein-based COVID-19 vaccine (NVX-CoV2373) in healthy adults: A comparative analysis with mRNA vaccines. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A Single Dose of a Hybrid hAdV5-Based Anti-COVID-19 Vaccine Induces a Long-Lasting Immune Response and Broad Coverage against VOC. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Immunisation of ferrets and mice with recombinant SARS-CoV-2 spike protein formulated with Advax-SM adjuvant protects against COVID-19 infection. [2022]

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

Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial. [2023]

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

Safety and immunogenicity of a recombinant interferon-armed RBD dimer vaccine (V-01) for COVID-19 in healthy adults: a randomized, double-blind, placebo-controlled, Phase I trial. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and immunogenicity of a SARS-CoV-2 recombinant spike RBD protein vaccine: A randomised, double-blind, placebo-controlled, phase 1-2 clinical trial (ABDALA Study). [2022]

9. Peru pubmed.ncbi.nlm.nih.gov

[COVID-19 vaccine safety]. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. [2022]

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

Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice. [2023]

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

Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2. [2023]