Combination Vaccine for COVID-19 and Flu
Recruiting in Palo Alto (17 mi)
+11 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Sanofi
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.
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.
124510Do 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.
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.
34678What 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.
4591112Eligibility 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 am 50 years old or older.
I can receive injections in both of my shoulders.
I am a woman able to have children and have a negative pregnancy test.
I am fully vaccinated and boosted against COVID-19.
Participant Groups
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.
7Treatment groups
Experimental Treatment
Group I: Group 7: IIV-HD + rC19 (dose 4) (in right or left deltoid) and placebo (in opposite deltoid)Experimental Treatment2 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 Treatment2 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 Treatment2 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 Treatment2 Interventions
two IM injections on D01
Group V: Group 3: IIV-HD (in right or left deltoid) and rC19 (dose1) (in opposite deltoid)Experimental Treatment2 Interventions
two IM injections on D01
Group VI: Group 2: rC19 (dose 1) (in right or left deltoid) and placebo (in opposite deltoid)Experimental Treatment2 Interventions
two IM injections on D01
Group VII: Group 1: IIV-HD (in right or left deltoid) and placebo (in opposite deltoid)Experimental Treatment2 Interventions
two IM injections on D01
IIV-HD + rC19 is already approved in United States, European Union for the following indications:
๐บ๐ธ Approved in United States as Spikevax for:
- Active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older.
๐ช๐บ Approved in European Union as Spikevax for:
- Active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Simon Williamson Clinic - Birmingham- Site Number : 8400003Birmingham, AL
AES - DRS - Optimal Research Alabama - Huntsville Site Number : 8400006Huntsville, AL
Orange Grove Family Practice- Site Number : 8400012Tucson, AZ
Synexus Clinical Research US, Inc. - The Villages Site Number : 8400011The Villages, FL
More Trial Locations
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Who is running the clinical trial?
SanofiLead Sponsor
References
Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice. [2023]An effective vaccine is essential to controlling the spread of SARS-CoV-2 virus. Here, we describe an influenza-virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 Spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ฮNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ฮNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ฮNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ฮNA(RBD)-Flu at scale by leveraging existing platforms for production of influenza vaccines.
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]We developed a heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-S and rAd5-S). We aimed to assess the safety and immunogenicity of two formulations (frozen and lyophilised) of this vaccine.
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]Safe and effective vaccines are still urgently needed to cope with the ongoing COVID-19 pandemic. Recently, we developed a recombinant COVID-19 vaccine (V-01) containing fusion protein (IFN-PADRE-RBD-Fc dimer) as antigen verified to induce protective immunity against SARS-CoV-2 challenge in pre-clinical study, which supported progression to Phase I clinical trials in humans. A Randomized, double-blind, placebo-controlled Phase I clinical trial was initiated at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China) in February 2021. Healthy adults aged between 18 and 59 years and over 60 years were sequentially enrolled and randomly allocated into three subgroups (1:1:1) either to receive the vaccine (10, 25, and 50 ฮผg) or placebo (V-01: Placebo = 4:1) intramuscularly with a 21-day interval by a sentinel and dose escalation design. The data showed a promising safety profile with approximately 25% vaccine-related overall adverse events (AEs) within 30 days and no grade 3 or worse AEs. Besides, V-01 provoked rapid and strong immune responses, elicited substantially high-titre neutralizing antibodies and anti-RBD IgG peaked at day 35 or 49 after first dose, presented with encouraging immunogenicity at low dose (10 ฮผg) subgroup and elderly participants, which showed great promise to be used as all-aged (18 and above) vaccine against COVID-19. Taken together, our preliminary findings indicate that V-01 is safe and well tolerated, capable of inducing rapid and strong immune responses, and warrants further testing in Phase II/III clinical trials.
Immunisation of ferrets and mice with recombinant SARS-CoV-2 spike protein formulated with Advax-SM adjuvant protects against COVID-19 infection. [2022]The development of a safe and effective vaccine is a key requirement to overcoming the COVID-19 pandemic. Recombinant proteins represent the most reliable and safe vaccine approach but generally require a suitable adjuvant for robust and durable immunity. We used the SARS-CoV-2 genomic sequence and in silico structural modelling to design a recombinant spike protein vaccine (Covax-19โข). A synthetic gene encoding the spike extracellular domain (ECD) was inserted into a baculovirus backbone to express the protein in insect cell cultures. The spike ECD was formulated with Advax-SM adjuvant and first tested for immunogenicity in C57BL/6 and BALB/c mice. Covax-19 vaccine induced high spike protein binding antibody levels that neutralised the original lineage B.1.319 virus from which the vaccine spike protein was derived, as well as the variant B.1.1.7 lineage virus. Covax-19 vaccine also induced a high frequency of spike-specific CD4 + and CD8 + memory T-cells with a dominant Th1 phenotype associated with the ability to kill spike-labelled target cells in vivo. Ferrets immunised with Covax-19 vaccine intramuscularly twice 2 weeks apart made spike receptor binding domain (RBD) IgG and were protected against an intranasal challenge with SARS-CoV-2 virus given two weeks after the last immunisation. Notably, ferrets that received the two higher doses of Covax-19 vaccine had no detectable virus in their lungs or in nasal washes at day 3 post-challenge, suggesting that in addition to lung protection, Covax-19 vaccine may have the potential to reduce virus transmission. This data supports advancement of Covax-19 vaccine into human clinical trials.
A Single Dose of a Hybrid hAdV5-Based Anti-COVID-19 Vaccine Induces a Long-Lasting Immune Response and Broad Coverage against VOC. [2022]Most approved vaccines against COVID-19 have to be administered in a prime/boost regimen. We engineered a novel vaccine based on a chimeric human adenovirus 5 (hAdV5) vector. The vaccine (named CoroVaxG.3) is based on three pillars: (i) high expression of Spike to enhance its immunodominance by using a potent promoter and an mRNA stabilizer; (ii) enhanced infection of muscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; (iii) use of Spike stabilized in a prefusion conformation. The transduction with CoroVaxG.3-expressing Spike (D614G) dramatically enhanced the Spike expression in human muscle cells, monocytes and dendritic cells compared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3 induced a potent humoral immunity with a balanced Th1/Th2 ratio and potent T-cell immunity, both lasting for at least 5 months. Sera from CoroVaxG.3-vaccinated mice was able to neutralize pseudoviruses expressing B.1 (wild type D614G), B.1.117 (alpha), P.1 (gamma) and B.1.617.2 (delta) Spikes, as well as an authentic P.1 SARS-CoV-2 isolate. Neutralizing antibodies did not wane even after 5 months, making this kind of vaccine a likely candidate to enter clinical trials.
Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial. [2023]Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD).
[COVID-19 vaccine safety]. [2022]The development and production of safe and effective vaccines against coronavirus disease 2019 (COVID-19) provides hope for controlling the current pandemic. Adverse events following immunization are unwanted responses or unintended events that must be carefully monitored, as all vaccines, including those developed against SARS-CoV-2, are required to meet safety criteria for administration in humans. Information was collected from the PubMed/Medline database during the months of August 2020 to November 2021. Most adverse events reported in clinical trials were mild or moderate; however, thrombotic events associated with some viral vector-based vaccines against COVID-19 were identified in follow-up studies, although completion of the various ongoing studies and post-marketing surveillance is required to determine all potential adverse events, as well as those of special interest.
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]Multiple vaccine candidates against COVID-19 are currently being evaluated. We evaluate the safety and immunogenicity protein of a novel SARS-CoV-2 virus receptor-binding domain (RBD) vaccine.
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]Immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has greatly reduced coronavirus disease 2019 (COVID-19)-related deaths and hospitalizations, but waning immunity and the emergence of variants capable of immune escape indicate the need for novel SARS-CoV-2 vaccines. An intranasal parainfluenza virus 5 (PIV5)-vectored COVID-19 vaccine CVXGA1 has been proven efficacious in animal models and blocks contact transmission of SARS-CoV-2 in ferrets. CVXGA1 vaccine is currently in human clinical trials in the United States. This work investigates the immunogenicity and efficacy of CVXGA1 and other PIV5-vectored vaccines expressing additional antigen SARS-CoV-2 nucleoprotein (N) or SARS-CoV-2 variant spike (S) proteins of beta, delta, gamma, and omicron variants against homologous and heterologous challenges in hamsters. A single intranasal dose of CVXGA1 induces neutralizing antibodies against SARS-CoV-2 WA1 (ancestral), delta variant, and omicron variant and protects against both homologous and heterologous virus challenges. Compared to mRNA COVID-19 vaccine, neutralizing antibody titers induced by CVXGA1 were well-maintained over time. When administered as a boost following two doses of a mRNA COVID-19 vaccine, PIV5-vectored vaccines expressing the S protein from WA1 (CVXGA1), delta, or omicron variants generate higher levels of cross-reactive neutralizing antibodies compared to three doses of a mRNA vaccine. In addition to the S protein, the N protein provides added protection as assessed by the highest body weight gain post-challenge infection. Our data indicates that PIV5-vectored COVID-19 vaccines, such as CVXGA1, can serve as booster vaccines against emerging variants.
Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2. [2023]Current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease, and a decrease in mortality rates. However, SARS-CoV-2 variants are continuously evolving, and development of new accessible COVID-19 vaccines is essential to mitigate the pandemic. Here, we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine (PHH-1V) consisting of an RBD fusion heterodimer comprising the B.1.351 and B.1.1.7 SARS-CoV-2 variants formulated in SQBA adjuvant, an oil-in-water emulsion. A prime-boost immunisation with PHH-1V in BALB/c and K18-hACE2 mice induced a CD4+ and CD8+ T cell response and RBD-binding antibodies with neutralizing activity against several variants, and also showed a good tolerability profile. Significantly, RBD fusion heterodimer vaccination conferred 100% efficacy, preventing mortality in SARS-CoV-2 infected K18-hACE2 mice, but also reducing Beta, Delta and Omicron infection in lower respiratory airways. These findings demonstrate the feasibility of this recombinant vaccine strategy.
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]Vaccination strategies that can induce a broad spectrum immune response are important to enhance protection against SARS-CoV-2 variants. We conducted a randomized, double-blind and parallel controlled trial to evaluate the safety and immunogenicity of the bivalent (5×1010viral particles) and B.1.1.529 variant (5×1010viral particles) adenovirus type-5 (Ad5) vectored COVID-19 vaccines administrated via inhalation. A total of 451 eligible subjects aged 18 years and older who had been vaccinated with three doses of inactivated COVID-19 vaccines were randomly assigned to inhale one dose of either the B.1.1.529 variant Ad5 vectored COVID-19 vaccine (Ad5-nCoVO-IH group, N=150), bivalent Ad5 vectored COVID-19 vaccine (Ad5-nCoV/O-IH group, N=151), or Ad5 vectored COVID-19 vaccine (5×1010viral particles; Ad5-nCoV-IH group, N=150). Primary safety outcomes including adverse reactions reported by 37 (24.67%) participants in the Ad5-nCoVO-IH group, 28 (18.54%) in the Ad5-nCoV/O-IH group, and 26 (17.33%) in the Ad5-nCoV-IH group with mainly mild to moderate dry mouth, oropharyngeal pain, headache, myalgia, cough, fever and fatigue. No serious adverse events related to the vaccine were reported. All investigational vaccines were immunogenic, with the difference in the GMTs of neutralizing antibodies against Omicron BA.1 was statistically significant between Ad5-nCoV/O-IH (43.70) and Ad5-nCoV-IH (29.25) at 28 days after vaccination (P=0.0238). The seroconversion rates of neutralizing antibodies against BA.1 in Ad5-nCoVO-IH, Ad5-nCoV/O-IH, and Ad5-nCoV-IH groups were 56.00%, 59.60% and 48.67% with no significant difference among the groups. Overall, the investigational vaccines were demonstrated to be safe and well tolerated in adults, and was highly effective in inducing mucosal immunities in addition to humoral and cellular immune responses defending against SARS-CoV-2 variants.Trial registration: Chictr.org identifier: ChiCTR2200063996.
Immunogenicity and safety of heterologous booster with protein-based COVID-19 vaccine (NVX-CoV2373) in healthy adults: A comparative analysis with mRNA vaccines. [2023]Information on the protein-based severe acute respiratory syndrome (SARS-CoV-2) vaccine-NVX-CoV2373 (Novavax), as a heterologous booster remains limited. We investigated the immunogenicity and adverse events of NVX-CoV2373 as a second booster and compared them with those of mRNA vaccines in healthy adults.