A Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine and Influenza Combination Vaccine

A Randomized, Observer-Blinded, Active-Controlled Study to Evaluate the Safety and Immunogenicity of a COVID-19 Influenza Combination Nanoparticle Vaccine and a Standalone Trivalent Nanoparticle Influenza Hemagglutinin Vaccine in Participants ≥ 65 Years of Age.

This is a medical study where participants will be randomly assigned to receive either a new combination vaccine that protects against both COVID-19 and the flu, or a standard flu vaccine. The researchers conducting the study won't know which vaccine each participant receives, ensuring their observations are unbiased. This study compares the new combination vaccine to an already available flu vaccine to see how well it works. It's a large-scale, final-stage study designed to thoroughly check how well the vaccines trigger an immune response (immunogenicity) and how safe they are.

The study enrolled a total of 9,320 medically stable (based on history and physical examination) adult male and female participants ≥ 65 years of age across Part 1 and Part 2.

In Part 1, participants were randomly assigned to receive either CIC, Novavax COVID-19 Vaccine, tNIV, or Fluzone High-Dose in a 3:2:1:3 ratio, respectively. Following the completion of enrollment in Part 1, the remaining participants were enrolled into Part 2 and were randomly assigned to receive either CIC, tNIV, or Fluzone High-Dose in a 5:4:1 ratio, respectively.

All participants received a single intramuscular (IM) injection on Day 0.

Part 1: All participants remained on study for immunogenicity data collection through Day 182 and safety data collection through Day 364 (End of Study [EoS]).

Part 2: Only safety was assessed, and all participants remained on study for safety data collection through Day 364 (EoS).

Inclusion Criteria

To be included in this study, each individual must satisfy all the following criteria:

1. Willing and able to give informed consent prior to study enrollment.

2. Medically stable adult male or female ≥ 65 years of age at Screening.

3. Participants may have 1 or more chronic medical diagnoses, but should be clinically stable as assessed by:

   1. Absence of changes in medical therapy in the past 2 months due to treatment failure or toxicity;
   2. Absence of medical events qualifying as SAEs within 3 months; and
   3. Absence of known, current, and life-limiting diagnoses which render survival to completion of the protocol unlikely in the opinion of the Investigator.

4. The participant has a body mass index (BMI) of 17 to 40 kg/m2, inclusive, at Screening.

5. Participant must be able to receive an injection in the deltoid of at least 1 arm.

6. Able to attend study visits, comply with study requirements, and provide reliable and complete reports of AEs.

7. Participants must have completed a primary vaccination series/booster against SARS CoV-2 with an authorized/approved COVID-19 vaccine, with receipt of last dose of authorized/approved vaccine (with or without boosters[s]) ≥ 8 weeks prior to vaccination.

8. Female participants must be surgically sterile (ie, have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or postmenopausal (defined as amenorrhea at least 12 consecutive months)

9. Participants must agree to not participate in any other SARS-CoV-2 or influenza prevention or treatment studies for the duration of the study. Note: For participants who become hospitalized with COVID-19 or influenza, participation in investigational treatment studies is permitted.

Exclusion Criteria

If an individual meets any of the following criteria, he or she is ineligible for this study:

1. History of laboratory-confirmed (by polymerase chain reaction [PCR], rapid antigen test, or rapid molecular assay) COVID-19, asymptomatic SARS-CoV-2 infection, or influenza within ≤ 8 weeks prior to Screening.

2. Any ongoing, symptomatic acute illness requiring medical or surgical care or chronic illness that required substantive changes in medication in the past 2 months prior to Screening indicating that chronic illness/disease is not stable (at the discretion of the investigator). This includes any current workup of undiagnosed illness that could lead to a new condition.

3. Serious chronic diseases inclusive of:

   1. Uncontrolled hypertension (NOTE: hypertension ≤ 170/100 is NOT exclusionary);
   2. Congestive heart failure requiring hospitalization within 3 months prior to Screening
   3. Chronic obstructive pulmonary disease (COPD) requiring hospitalization within 3 months prior to Screening (NOTE: stable COPD is NOT exclusionary);
   4. Within 3 months prior to Screening, evidence of unstable coronary artery disease as manifested by cardiac interventions (eg, cardiac stent placement, coronary artery bypass graft surgery), new cardiac medications for control of symptoms, or unstable angina (NOTE: stable coronary heart disease is NOT exclusionary);
   5. Hospitalization for diabetic ketoacidosis within 6 months prior to Screening
   6. Chronic kidney disease/renal requiring institution of substantive new therapy within 3 months prior to Screening
   7. Chronic clinically significant gastrointestinal and hepatic diseases requiring hospitalization or institution of substantive new therapy within 3 months prior to Screening. (for example, gastroesophageal reflux disease is NOT exclusionary)
   8. Chronic neurological diseases or neurological compromise preventing access to the study clinic, compliance with protocol, or accurate reporting of safety.

4. Participation in research involving an investigational product (drug/biologic/device) within 90 days before planned date of vaccination.

5. Use of COVID-19 prophylactic or treatment monoclonal antibodies or antibody cocktails within 90 days prior to planned date of vaccination.

6. History of a serious reaction to a prior influenza vaccination or known allergy to constituents of influenza vaccines - including egg proteins - or polysorbate 80; or any known allergies to products contained in the investigational product.

7. Any history of anaphylaxis to any prior vaccine.

8. History of Guillain-Barré Syndrome following a previous influenza vaccine.

9. Receipt of any vaccine in the 4 weeks preceding the study vaccination and any influenza vaccine within 2 months preceding the study vaccination. Note: Routine vaccinations will not be allowed until after study Day 21 and COVID-19 and influenza vaccination will not be allowed until after Day 84.

10. Any known or suspected autoimmune or immunosuppressive illness, congenital or acquired, based on medical history and/or physical examination (NOTE: well-controlled hypothyroidism and mild psoriasis are not exclusionary).

11. Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccines. An immunosuppressant dose of glucocorticoid is defined as a systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids is permitted.

12. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the study vaccine or during the study.

13. Active cancer (malignancy) therapy within 1 year prior to study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma or lentigo maligna and uterine cervical carcinoma in situ without evidence of disease, at the discretion of the investigator).

14. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the EoS.

15. Suspected or known history of alcohol abuse or drug addiction within 2 years prior to study vaccination, which in the opinion of the investigator, might interfere with protocol compliance.

16. Acute disease at the time of enrollment (defined as the presence of a moderate or severe illness with or without fever, or an oral temperature ≥ 38.0°C, on the planned day of vaccine administration).

17. History of myocarditis or pericarditis.

18. Any condition that in the opinion of the investigator would pose a health risk to the participant if enrolled or could interfere with evaluation of the vaccine or interpretation of study results (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting).

19. Study team member or immediate family member of any study team member (inclusive of Sponsor, Contract Research Organization, and study site personnel involved in the conduct or planning of the study).

20. Known history of any prior motor neuropathy.