Pfizer-BioNTech vs Novavax Vaccines for COVID-19

(CIRV2 Trial)

Overseen By Marianne Spevak, BSHS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

Must not be taking: Immune modulators

Disqualifiers: Severe allergy, Recent COVID-19, 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

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares the effectiveness and side effects of two COVID-19 vaccines: the Pfizer-BioNTech mRNA vaccine and the Novavax recombinant protein vaccine. Researchers aim to assess how well these vaccines work and how participants' bodies respond over time. Suitable candidates may have conditions like asthma, heart disease, or diabetes, or possess other risk factors for severe COVID-19, such as low physical activity or a history of smoking. Participants should visit the clinic once and complete online follow-ups for nine months. As a Phase 4 trial, this study involves FDA-approved vaccines and seeks to understand their benefits for a broader patient population.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are actively using immune modulating medications like high-dose steroids or chemotherapy.

What is the safety track record for these treatments?

Research shows that both the Novavax and Pfizer-BioNTech COVID-19 vaccines are safe.

For the Novavax vaccine, safety checks revealed that out of 230 reports, only 19 were serious, with no deaths. Common side effects included pain and redness at the injection site, tiredness, and mild muscle pain. In a larger study, only four to six serious cases occurred among over 40,000 recipients.

For the Pfizer-BioNTech vaccine, studies found that side effects like tiredness and irritability were common, but serious reactions were rare. About 60% of participants reported some kind of systemic reaction, such as fatigue. However, the vaccine is generally well-tolerated.

Both vaccines have FDA approval, underscoring their safety for public use. Participants can expect mild to moderate side effects, but serious issues are uncommon. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they bring different approaches to COVID-19 vaccination. The Pfizer-BioNTech vaccine uses mRNA technology, which instructs cells to produce a protein that triggers an immune response. On the other hand, the Novavax vaccine is a recombinant protein vaccine, which means it contains harmless spike proteins that prompt the body to build immunity against the virus. This diversity in vaccine types could provide broader protection and options for people with varying medical needs or preferences.

What evidence suggests that this trial's treatments could be effective for COVID-19?

This trial will compare the Pfizer-BioNTech COVID-19 vaccine with the Novavax COVID-19 vaccine. Research has shown that the Pfizer-BioNTech vaccine provides strong protection against illness from COVID-19 and serious health issues, helping prevent infection, hospital visits, and death. Meanwhile, earlier studies showed that the Novavax vaccine is about 90% effective in preventing COVID-19, triggering a strong immune response and proving safe for different groups. Both vaccines lower the risk of COVID-19, making them reliable choices for protection. ^{2 6 7 8 9}

Who Is on the Research Team?

Edward Mitre, MD

Principal Investigator

Uniformed Services University of the Health Sciences

Are You a Good Fit for This Trial?

This trial is for healthy volunteers interested in helping compare the immune responses to two FDA-approved COVID-19 vaccines: Novavax's recombinant protein vaccine and Pfizer-BioNTech's mRNA vaccine. Specific eligibility criteria are not provided, but typically participants should meet certain health standards.

Inclusion Criteria

I am between 18 and 79 years old.

I have risk factors for severe COVID and can follow the study requirements.

Exclusion Criteria

History of severe allergy or severe adverse reaction to any component of the mRNA COVID-19 vaccines or the Novavax recombinant COVID-19 vaccine, received a COVID-19 vaccine in the last 3 months, tested positive for COVID-19 in the past 3 months with presence of specific symptoms, active use of immune modulating medications, diagnosed with immunocompromised state, diabetes with the most recent HgbA1C ≥ 7.5, stage III or greater chronic kidney disease, obesity with a BMI ≥ 40, HIV with a CD4 cell count < 500 cells/ul, history of solid organ or bone marrow transplant, active malignancy, chronic liver disease with compensated or decompensated cirrhosis, or liver enzyme levels (AST or ALT) greater than three times the upper limit of normal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive either the Pfizer-BioNTech mRNA COVID-19 vaccine or the Novavax recombinant protein vaccine

1 day

1 visit (in-person)

Follow-up

Participants are monitored for immune response and reactogenicity, with assessments at 30 days and up to 9 months post-vaccination

9 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Novavax COVID-19 Vaccine
• Pfizer-BioNTech COVID-19 Vaccine

Trial Overview

The CIRV2 study is testing how well people's bodies respond to either the Novavax or Pfizer-BioNTech COVID-19 vaccines over time. It's a Phase IV trial where participants will be randomly assigned to receive one of these approved vaccines.

How Is the Trial Designed?

Group I: For fall of 2025, Arm 1 of the study will be the Pfizer-BioNTech mRNA COVID-19 vac Active Control 1 Intervention

Arm 1 of the study will be Pfizer-BioNTech mRNA COVID-19 vaccine

Group II: For fall of 2025, Arm 2 of the study will be the Novavax recombinant protein vaccine Active Control 1 Intervention

Arm 2 of the study will be the Novavax recombinant protein vaccine

Who Is Running the Clinical Trial?

Henry M. Jackson Foundation for the Advancement of Military Medicine

Lead Sponsor

Trials

103

Recruited

94,300+

U.S. Food and Drug Administration (FDA)

Collaborator

Trials

2

Recruited

470+

Centers for Disease Control and Prevention

Collaborator

Trials

902

Recruited

25,020,000+

Citations

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ir.novavax.com/press-releases/2025-08-27-Novavaxs-Nuvaxovid-TM-2025-2026-Formula-COVID-19-Vaccine-Approved-in-the-U-S

Novavax's Nuvaxovid™ 2025-2026 Formula COVID-19 ...

Both clinical and preclinical data from Nuvaxovid confirm that the JN. 1 strain vaccination induces immunity across currently circulating JN.

2.

cdc.gov

cdc.gov/acip/grade/covid-19-novavax.html

Novavax COVID-19 Vaccine | ACIP

The initial GRADE evidence level was type 1 (high) for each outcome because the body of evidence was from a randomized controlled trial (Table 4) ...

3.

ama-assn.org

ama-assn.org/public-health/infectious-diseases/what-doctors-wish-patients-knew-about-novavax-covid-19-vaccine

What doctors wish patients knew about the Novavax ...

Effectiveness of Novavax is tricky​​ “The study data submitted to FDA says, overall, it was about 90% effective at preventing COVID,” said Dr. Fryhofer. “However ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0264410X2500074X

Efficacy, immunogenicity, and safety of the Novavax COVID ...

Overall, the Novavax COVID-19 vaccine was immunogenic and had a tolerable safety profile across diverse populations of IIC; some outcomes varied ...

5.

yalemedicine.org

yalemedicine.org/news/covid-19-vaccine-comparison

Comparing the COVID-19 Vaccines: How Are They Different?

Earlier studies of its original vaccine showed it to be 90% effective overall against lab-confirmed, symptomatic infection and 100% effective ...

6.

cdc.gov

cdc.gov/mmwr/volumes/72/wr/mm7231a4.htm

Safety Monitoring of Novavax COVID-19 Vaccine ... - CDC

Among the 230 reports received, 19 (8.3%) were classified as serious; no deaths were reported after vaccination. Serious reports included one ...

7.

fda.gov

fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert-and-Patient-Package-Insert-NUVAXOVID.pdf

Package Insert and Patient Package Insert - NUVAXOVID

COVID-19 Vaccine, Adjuvanted (2023-2024 Formula). 76. Safety data accrued in Studies 1, 5, 6, and 7 are relevant to NUVAXOVID because the vaccines. 77.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9397598/

Safety and Adverse Events Related to Inactivated COVID-19 ...

The most common local side effects are pain, redness, and swelling at the injection site; while fatigue, body pain, headache, muscle pain, fever, and malaise ...

9.

yalemedicine.org

yalemedicine.org/news/novavax-covid-vaccine

Novavax's COVID-19 Vaccine: Your Questions Answered

You should not get the Novavax vaccine if you've had a severe allergic reaction to a previous dose of it, or a severe reaction to any of the ...