COVID-19 and Flu Vaccines for Pregnant Women

Recruiting at 5 trial locations

Overseen By Grace Davis, MS

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Duke University

Must not be taking: Immunosuppressants, Anticancer chemotherapy

Disqualifiers: Immunosuppression, Hepatitis B, Hepatitis C, 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: 1

350 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a prospective, randomized clinical trial. During this study,pregnant participants will be randomly assigned to receive IIV and mRNA COVID-19 vaccine either simultaneously or sequentially (7-14 days apart). All participants will receive an mRNA COVID-19 vaccine at Visit 1 (Day 1). Solicited local and systemic symptoms of reactogenicity will be assessed on day of visit for Visits 1 and 2 and daily during the 6 days following each visit using either electronic or paper symptoms diaries, depending on study participant preference. Serious adverse events (SAE) and adverse events of special interest (AESI) will be collected throughout the duration of the study. Pregnant people will be followed through delivery with comprehensive obstetric and infant outcomes obtained from medical record review for 90 days post-delivery. Maternal serum samples will be collected for antibody titers relevant to Influenza and COVID-19 prior to vaccination, at Day 29 (both groups), as well as Days 36-43 if in sequential group. When feasible, maternal blood at delivery and cord blood serum will be analyzed for serological analyses of placental influenza and COVID-19 antibody transfer (cord blood: maternal antibody ratio) will be determined.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medications or have certain health conditions, you may not be eligible to participate. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment involving COVID-19 and flu vaccines for pregnant women?

Research shows that the quadrivalent inactivated influenza vaccine (IIV4) is safe for pregnant women and can protect against seasonal flu. Additionally, studies suggest that cell-based versions of this vaccine may offer better protection in certain flu seasons compared to egg-derived versions. ^{1 2 3 4 5}

Is the quadrivalent inactivated influenza vaccine safe for pregnant women?

Studies have shown that the quadrivalent inactivated influenza vaccine (IIV4) is generally safe for pregnant women, with no significant increase in adverse events reported during pregnancy or for infants. ^{1 2 3 6 7}

How is the treatment with IIV4 and mRNA COVID-19 vaccine unique for pregnant women?

This treatment is unique because it combines a quadrivalent inactivated influenza vaccine (IIV4), which protects against four strains of the flu, with an mRNA COVID-19 vaccine, offering dual protection against both influenza and COVID-19 for pregnant women and their infants. The combination aims to provide comprehensive protection during pregnancy, a time when women are at higher risk for severe illness from these infections. ^{1 2 8 9 10}

Research Team

Elizabeth Barnett, MD

Principal Investigator

Boston Medical Center

Geeta Swamy, MD

Principal Investigator

Duke University

Tarayn Fairlie, MD

Principal Investigator

Centers for Disease Control and Prevention

Matthew Zuber, MD

Principal Investigator

Wake Forest University

Elizabeth Schlaudecker, MD

Principal Investigator

Cincinnati Children's Hospital Medical Center

Satoshi Kamidani, MD, PhD

Principal Investigator

Emory University

Eligibility Criteria

This clinical trial is for pregnant individuals who are willing to receive both the mRNA COVID-19 vaccine and the IIV4 influenza vaccine. Participants will be monitored through delivery and up to 90 days post-delivery, with eligibility criteria not fully disclosed in the provided information.

Inclusion Criteria

I can speak English, Spanish, or Haitian/Creole.

I plan to participate in the entire study and follow all procedures.

I plan to get the mRNA COVID-19 vaccine.

Exclusion Criteria

Severe allergic reaction to any component of the vaccine, including egg protein, or after previous dose of any influenza vaccine

I have had MIS-C (if a child) or MIS-A (if an adult).

Intending to deliver at a site un-affiliated with the study team

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive mRNA COVID-19 vaccine and IIV either simultaneously or sequentially

1 day

Visit 1 (in-person), Visit 2 (in-person for sequential group)

Reactogenicity Monitoring

Participants are monitored for local and systemic symptoms of reactogenicity for 6 days following each vaccination visit

6 days post each vaccination visit

Follow-up

Participants are monitored through delivery with comprehensive obstetric and infant outcomes obtained from medical record review for 90 days post-delivery

90 days post-delivery

Treatment Details

Interventions

• IIV4 (quadrivalent inactivated influenza vaccine)
• mRNA COVID-19 vaccine

Trial Overview The study tests whether getting an mRNA COVID-19 vaccine at the same time as an IIV4 flu shot affects safety or birth outcomes differently than getting them separately (7-14 days apart). It's a randomized trial where participants' symptoms are tracked closely after vaccination.

Participant Groups

Group I: Simultaneous Vaccination Group Experimental Treatment 2 Interventions

Subjects will receive a dose of mRNA COVID-19 vaccine and IIV at Visit 1.

Group II: Sequential Vaccination Group Experimental Treatment 2 Interventions

Subjects will receive a dose of mRNA COVID-19 vaccine at Visit 2 and a dose of IIV at Visit 2.

IIV4 (quadrivalent inactivated influenza vaccine) is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Fluzone Quadrivalent for:

• Prevention of influenza A and B virus infection in individuals 6 months of age and older

Approved in European Union as Fluarix Quadrivalent for:

• Prevention of influenza A and B virus infection in individuals 6 months of age and older

Approved in Canada as Flulaval Quadrivalent for:

• Prevention of influenza A and B virus infection in individuals 6 months of age and older

Approved in Japan as Agriflu Quadrivalent for:

• Prevention of influenza A and B virus infection in individuals 6 months of age and older

Approved in Switzerland as Flucelvax Quadrivalent for:

• Prevention of influenza A and B virus infection in individuals 6 months of age and older

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Findings from Research

In a study of 665 pregnant individuals who received the quadrivalent inactivated influenza vaccine (IIV4c) over three influenza seasons, 99.1% had live births, indicating a high safety profile for the vaccine during pregnancy.

The rates of adverse outcomes such as preterm birth (9.2%), low birth weight (5.8%), and major congenital malformations (1.9%) were comparable to those reported in US surveillance systems, suggesting that IIV4c does not increase risks compared to the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in Pregnant Persons Immunized with a Cell-Based Quadrivalent Inactivated Influenza Vaccine: A Prospective Observational Cohort Study. Robinson, C., Van Boxmeer, J., Tilson, H., et al.[2023]

In a study of 483 pregnant individuals vaccinated with the quadrivalent inactivated influenza vaccine (IIV4) over four flu seasons, 98.8% reported live births, indicating a high safety profile for the vaccine during pregnancy.

The rates of adverse infant outcomes, such as preterm birth (7.2%), low birth weight (5.4%), and major congenital malformations (0.8%), were found to be lower than or similar to the general population, suggesting that IIV4 does not pose significant safety concerns for pregnant individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Cohort Study on Pregnancy Outcomes of Persons Immunized with a Seasonal Quadrivalent Inactivated Influenza Vaccine during Pregnancy. Robinson, C., Oberye, J., van Boxmeer, J., et al.[2023]

The Fluzone® Quadrivalent (IIV4) vaccine was monitored for safety in pregnant women, with 239 exposure reports collected from August 2013 to September 2019, showing no new safety concerns related to maternal or neonatal outcomes.

Among the reported outcomes, over 85% of neonates were full-term births, and all infants with available information had normal APGAR scores, indicating that the vaccine is safe for use during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to quadrivalent influenza vaccine during pregnancy: Results from a global pregnancy registry. Ledlie, S., Gandhi-Banga, S., Shrestha, A., et al.[2022]

In a study involving over 10 million individuals vaccinated during the 2018-2019 flu season, the cell-propagated inactivated quadrivalent influenza vaccine (ccIIV4) showed a 7.6% greater effectiveness in reducing influenza-related medical encounters compared to the egg-derived vaccine (eIIV4).

The effectiveness of ccIIV4 varied by age group, with the highest relative vaccine effectiveness observed in younger adults (ages 18-49) at 7.5%, suggesting that ccIIV4 may provide better protection, especially in populations where egg-derived vaccines may be less effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative Effectiveness of the Cell-derived Inactivated Quadrivalent Influenza Vaccine Versus Egg-derived Inactivated Quadrivalent Influenza Vaccines in Preventing Influenza-related Medical Encounters During the 2018-2019 Influenza Season in the United States. Boikos, C., Fischer, L., O'Brien, D., et al.[2021]

The inactivated quadrivalent influenza vaccine (IIV4) was found to be safe and well-tolerated in a phase III trial involving 1,648 adults and 329 children/adolescents, with no serious adverse events reported.

IIV4 induced strong antibody responses to all four influenza strains it targets, meeting all immunogenicity criteria set by the European Medicines Agency, and showed comparable efficacy to the trivalent vaccine (IIV3) in both age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial. Cadorna-Carlos, JB., Nolan, T., Borja-Tabora, CF., et al.[2015]

The study involving 661 children aged 6 months to under 18 years demonstrated that the high-dose quadrivalent influenza vaccine (IIV4-HD) is safe, with no serious adverse events reported and similar rates of mild reactions compared to the standard-dose vaccine.

IIV4-HD at a dose of 60 µg significantly improved immune responses, particularly in younger children (6 months to <3 years), showing higher antibody titers against various influenza strains compared to the standard-dose vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through Chang, LJ., Anderson, EJ., Jeanfreau, R., et al.[2021]

The inactivated quadrivalent influenza vaccine (IIV4) demonstrated good immunogenicity, with seroconversion rates of over 60% for all four influenza strains tested, indicating it effectively stimulates the immune response in healthy individuals aged 3 years and older.

IIV4 was found to be non-inferior to the trivalent vaccine (IIV3) for the A strains and superior for the additional B strains, while showing no significant safety concerns, as no serious adverse events were reported and adverse reactions were similar across all groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: A randomized, double-blind, controlled phase III study in healthy population aged ≥3 years. Chu, K., Xu, K., Tang, R., et al.[2022]

The quadrivalent inactivated influenza vaccine (QIV) was found to be effective in reducing the risk of laboratory-confirmed influenza by 43.5% in pregnant women and 31.4% in their infants during the 2019-2020 influenza season, based on a study of 636 pregnant women and 474 infants.

The study utilized a Bayesian beta-binomial model to analyze the data, demonstrating that maternal vaccination significantly lowers the likelihood of both mothers and their infants contracting influenza.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of maternal vaccination with quadrivalent inactivated influenza vaccine in pregnant women and their infants in 2019-2020. Maltezou, HC., Stavros, S., Asimakopoulos, G., et al.[2022]

A randomized phase IV study involving 346 pregnant women showed that the quadrivalent inactivated influenza vaccine (IIV4) is as safe and immunogenic as the trivalent inactivated influenza vaccine (IIV3), with both vaccines effectively increasing antibody levels against influenza strains.

IIV4 provided higher antibody responses for an additional B strain compared to IIV3, and both vaccines successfully transferred protective antibodies to newborns, ensuring indirect protection against influenza for infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in pregnant women: a randomized, observer-blind trial. Vesikari, T., Virta, M., Heinonen, S., et al.[2021]

The inactivated quadrivalent influenza vaccine is safe and effective for preventing influenza in pregnant women and their children, and it can be administered during any trimester of pregnancy.

Despite the safety and effectiveness of the vaccine, vaccination coverage among pregnant women remains low, highlighting the need for increased awareness and recommendations for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccination in pregnancy - current data on safety and effectiveness. Nitsch-Osuch, AS., Bomba-Opon, D., Jasik, M.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Outcomes in Pregnant Persons Immunized with a Cell-Based Quadrivalent Inactivated Influenza Vaccine: A Prospective Observational Cohort Study. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A Prospective Cohort Study on Pregnancy Outcomes of Persons Immunized with a Seasonal Quadrivalent Inactivated Influenza Vaccine during Pregnancy. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Exposure to quadrivalent influenza vaccine during pregnancy: Results from a global pregnancy registry. [2022]

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

Relative Effectiveness of the Cell-derived Inactivated Quadrivalent Influenza Vaccine Versus Egg-derived Inactivated Quadrivalent Influenza Vaccines in Preventing Influenza-related Medical Encounters During the 2018-2019 Influenza Season in the United States. [2021]

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

Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: A randomized, double-blind, controlled phase III study in healthy population aged ≥3 years. [2022]

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

Effectiveness of maternal vaccination with quadrivalent inactivated influenza vaccine in pregnant women and their infants in 2019-2020. [2022]

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

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in pregnant women: a randomized, observer-blind trial. [2021]

10. Poland pubmed.ncbi.nlm.nih.gov

Influenza vaccination in pregnancy - current data on safety and effectiveness. [2021]