Comparative Immunogenicity of Respiratory Virus Vaccines (CIRV2) Study

Henry M. Jackson Foundation for the Advancement of Military Medicine

Status and phase: Enrolling; Phase 4

Conditions: Respiratory Virus Infection; Respiratory Virus; Influenza; Respiratory Viruses; Respiratory Virus Infections; COVID -19; COVID 19; COVID - 19

Treatments: Drug: Pfizer-BioNTech mRNA COVID-19 vaccine; Drug: Novavax recombinant protein vaccine

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT07287137

IDCRP-154

Details and patient eligibility

About

CIRV2 is a Phase IV randomized, open-label, trial of FDA-approved COVID-19 and/or influenza vaccines (no more than minimal risk) with longitudinal follow-up. In 2025 CIRV2 will compare immunogenicity and reactogenicity of the recombinant Novavax COVID-19 vaccine and the mRNA Pfizer-BioNTech COVID-19 vaccine.

Full description

The goal of the Comparative Immunogenicity of Respiratory Virus Vaccines (CIRV2) study is to conduct, on a yearly basis, direct comparisons of immunogenicity and reactogenicity of the most recent versions of FDA-approved vaccines for COVID-19 and/or influenza. Studies will be conducted on individuals that are FDA eligible to receive these vaccines and do not have a medical condition that severely impairs their immune system. For 2025, the study will directly compare the immunogenicity and reactogenicity of the 2025 Novavax recombinant COVID-19 vaccine with the 2025 Pfizer/BioNTech mRNA COVID-19 vaccine.

Enrollment: 54 estimated patients

Sex: All

Ages: 18 to 79 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. 18-79 years old

2. Have a history of any of the following risk factors for severe COVID:

   • Asthma
   • Physical inactivity (defined as <150 mins of moderate activity per week or <75 mins of vigorous activity per week)
   • HIV with CD4 count ≥ 500 cells/ul
   • Current or prior smoker
   • Depression or other mood disorder
   • Schizophrenia spectrum disorder
   • Cerebrovascular disease
   • Heart failure
   • Coronary artery disease
   • Cardiomyopathy
   • Pulmonary embolism
   • Pulmonary hypertension
   • Cystic fibrosis
   • Bronchiectasis
   • Chronic obstructive pulmonary disease
   • Interstitial Lung Disease
   • Stage I or II chronic kidney disease
   • Stage 1 defined as normal GFR (> 90) but with other signs of kidney damage such as proteinuria or hematuria
   • Stage 2 defined as having a glomerular filtration rate (GFR) of 60 - 89 ml/min/1.73m2
   • Gestational diabetes
   • Type 1 diabetes with most recent HgbA1C < 7.5%
   • Type 2 diabetes with most recent HgbA1C < 7.5%
   • Obesity with BMI ≥ 30 and < 40
   • Liver disease without cirrhosis and with liver enzyme levels
   • (AST and ALT) no greater than three times the upper limit of normal

3. Military Health System beneficiary and DEERS eligible

4. Willing to be randomized to receive either the Novavax COVID-19 vaccine or the mRNA Pfizer-BioNTech COVID-19 vaccine

5. Will be able to return for a clinic visit in approximately 30 days and be able to follow-up online for the next 9 months.

Exclusion Criteria

1. History of severe allergy or severe adverse reaction such as myocardial inflammation to any component of the mRNA COVID-19 vaccines or the Novavax recombinant COVID-19 vaccine

2. Received a COVID-19 vaccine in the last 3 months.

3. Tested positive for COVID-19 in the past 3 months.

   - Presence of fever, cough, chills, shortness of breath, runny nose, or sore throat today on day of screening/enrollment visit.

4. Active use of immune modulating medications.

   - Defined as active use of chronic immune modulating medications such as systemic corticosteroids at a dose equivalence of 20 mg prednisone or greater daily for over one month, chemotherapy, cytokine inhibitors, or agents that reduce T cell or B cell numbers or function.

5. Diagnosed with immunocompromised stated.

   - Defined as: presence of a disease that is actively causing severe immune suppression or history of prior splenectomy (removal of spleen).

6. Diabetes with the most recent HgbA1C ≥ 7.5.

7. Stage III or greater chronic kidney disease

   - Defined as estimated glomerular filtration rate < 60 ml/min/1.73m2)

8. Obesity with a BMI ≥ 40

9. HIV with a CD4 cell count < 500 cells/ul

10. History of solid organ or bone marrow transplant.

11. Active malignancy

    - Defined as any cancer that is currently being treated or has shown evidence of progression within the past year.

12. Chronic liver disease with compensated or decompensated cirrhosis, or liver enzyme levels (AST or ALT) greater than three times the upper limit of normal.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 2 patient groups

For fall of 2025, Arm 1 of the study will be the Pfizer-BioNTech mRNA COVID-19 vac

Active Comparator group

Description:

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

Treatment:

Drug: Pfizer-BioNTech mRNA COVID-19 vaccine

For fall of 2025, Arm 2 of the study will be the Novavax recombinant protein vaccine

Active Comparator group

Description:

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

Treatment:

Drug: Novavax recombinant protein vaccine