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 SARS CoV 2 rS Nanoparticle and Trivalent Hemagglutinin Nanoparticle Influenza Combination Vaccine With Matrix-M™ Adjuvant in Participants ≥ 50 Years of Age

The goal of this Phase 3 study is to compare the effectiveness, safety, and side effects of the CIC vaccine with approved flu vaccines and the Novavax COVID-19 Vaccine with adjuvant.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19
• Intervention / Treatment: Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Biological: Placebo 0.9% sodium chloride for injection; Biological: Novavax COVID-19 Vaccine; Biological: Comparator Influenza Vaccine - Fluarix; Biological: Comparator Influenza Vaccine -Fluarix High Dose

Detailed Description

This is a randomized, observer-blinded, active-controlled Phase 3 study to demonstrate the noninferior immunogenicity of a coronavirus disease 2019 (COVID-19) and influenza combination (CIC) vaccine relative to age-appropriate licensed influenza vaccine comparators in terms of hemagglutinin inhibition (HAI) response and Novavax COVID-19 Vaccine in terms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) response and to further evaluate the safety and immunogenicity of a CIC vaccine.

• Study Type: Interventional
• Enrollment (Estimated): 4000
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 ≥ 50 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 both arms.
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. Women of childbearing potential (defined as any female participant who is NOT surgically sterile [ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through the end of the study OR agree to consistently use a medically acceptable method of contraception from at least 28 days prior to enrollment and through the end of the study.
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] or rapid antigen test) COVID-19 or asymptomatic SARS-CoV-2 infection; either occurring ≤ 8 weeks prior to Screening. (NOTE: Symptomatic COVID-19 or asymptomatic SARS-CoV-2 infection > 8 weeks prior to Screening is NOT exclusionary).
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 (NOTE: stable congestive heart failure is NOT exclusionary);
   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. (f or 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 within 6 weeks 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group-1A CIC; 1M injection of SARs-CoV-2 antigen (35 μg), tNIV antigens, 60 μg/strain and Matrix-M adjuvant (75 μg)	Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Groups 1a and 2a the CIC vaccine regimen will comprise 1 IM injection administered in Arm A (Day 0). CIC vaccine will contain SARs-CoV-2 antigen (35 μg), tNIV antigens (2 influenza A [H1N1 and H3N2] and influenza B-Victoria lineage strains; 60 μg/strain and Matrix-M adjuvant (75 μg); Other Names: COVID-19 and influenza combination
Experimental: Group-1A placebo; IM injection of 0.5 mL	Biological: Placebo 0.9% sodium chloride for injection; In Group 1a, placebo will be administered as a single IM injection of 0.5 mL Arm B on Day 0 as directed by the pharmacy manual. In Group 2a, placebo will be administered as a single IM injection of 0.7 mL Arm B on Day 0.; Other Names: Placebo (0.9% sodium chloride for injection)
Experimental: Group-1B Novavax; IM injection, Each 0.5 mL	Biological: Novavax COVID-19 Vaccine; Novavax COVID-19 Vaccine will be supplied as a suspension in prefilled syringe for IM injection . Each 0.5 mL dose comprises 5 µg SARS-CoV2 S protein and 50 µg Matrix-M adjuvant.; Other Names: Novavax SARS-CoV-2 rS vaccine
Experimental: Group-1B Fluarix; IM injection syringe, at 0.5 mL with 15 µg per strain.	Biological: Comparator Influenza Vaccine - Fluarix; Fluarix is supplied as an injectable suspension for IM injection supplied in a prefilled syringe, at 0.5 mL with 15 µg per strain. In Group 1b, Fluarix will be administered as a single 0.5 mL IM injection in Arm B on Day 0.; Other Names: Fluarix
Active Comparator: Group-2A CIC; 1M injection of SARs-CoV-2 antigen (35 μg), tNIV antigens, 60 μg/strain and Matrix-M adjuvant (75 μg)	Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Groups 1a and 2a the CIC vaccine regimen will comprise 1 IM injection administered in Arm A (Day 0). CIC vaccine will contain SARs-CoV-2 antigen (35 μg), tNIV antigens (2 influenza A [H1N1 and H3N2] and influenza B-Victoria lineage strains; 60 μg/strain and Matrix-M adjuvant (75 μg); Other Names: COVID-19 and influenza combination
Active Comparator: Group-2A Placebo; IM injection of 0.5 mL of placebo	Biological: Placebo 0.9% sodium chloride for injection; In Group 1a, placebo will be administered as a single IM injection of 0.5 mL Arm B on Day 0 as directed by the pharmacy manual. In Group 2a, placebo will be administered as a single IM injection of 0.7 mL Arm B on Day 0.; Other Names: Placebo (0.9% sodium chloride for injection)
Active Comparator: 2B Novavax; IM injection, Each 0.5 mL dose	Biological: Novavax COVID-19 Vaccine; Novavax COVID-19 Vaccine will be supplied as a suspension in prefilled syringe for IM injection . Each 0.5 mL dose comprises 5 µg SARS-CoV2 S protein and 50 µg Matrix-M adjuvant.; Other Names: Novavax SARS-CoV-2 rS vaccine
Active Comparator: Group-2B Fluarix; IM injection in prefilled syringes, at 0.7 mL with 60 µg per strain. of Fluarix	Biological: Comparator Influenza Vaccine -Fluarix High Dose; Fluzone HD is supplied as a suspension for IM injection in prefilled syringes , at 0.7 mL with 60 µg per strain. In Group 2b, Fluzone HD will be administered as a single 0.7 mL IM injection in Arm B on Day 0.; Other Names: Fluzone HD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety- Solicited AEs over 7 days post-vaccination, For both local injection site symptoms/signs and systemic symptoms/signs	Numbers of participants with solicited local and systemic AEs over the 7 days post-vaccination.	7 days post-vaccination
Safety-Unsolicited AEs over 21 days post-vaccination and medically attended adverse events (MAAEs).	Numbers of participants reporting unsolicited AEs and MAAEs over 21 days post-vaccination.	21 days post-vaccination
Safety-Treatment-related MAAEs, serious adverse events (SAEs), and adverse events of special interest (AESIs) (including potential immune-mediated medical conditions [PIMMCs] and myocarditis and/or pericarditis) over 6 months	Numbers of participants with treatment related MAAEs, AESIs (including PIMMC and myocarditis and/or pericarditis), and SAEs will be collected for 6 months (approximately 182 days) post-vaccination.	6 months (approximately 182 days) post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity- HAI antibody titers specific for the HA receptor binding domains of vaccine homologous A and B influenza strains Expressed as GMT	HAI antibody titers specific for the HA receptor binding domains of vaccine response to immunization with CIC, Fluarix or Fluzone HD, and Novavax COVID-19 Vaccine Expressed as Geometric Mean Titers (GMT)	Day-0, 21-, 84-, and 184-days
Immunogenicity- HAI antibody titers specific for the HA receptor binding domains of vaccine homologous A and B influenza strains Expressed as GMFR	HAI antibody titers specific for the HA receptor binding domains of vaccine response to immunization with CIC, Fluarix or Fluzone HD, and Novavax COVID-19 Vaccine Expressed as Geometric mean fold rise (GMFR)	Day- 21-, 84-, and 184-days
Immunogenicity- HAI antibody titers specific for the HA receptor binding domains of vaccine homologous A and B influenza strains Expressed as SCR	HAI antibody titers specific for the HA receptor binding domains of vaccine response to immunization with CIC, Fluarix or Fluzone HD, and Novavax COVID-19 Vaccine Expressed as SCR	Days 21, 84, and 184
Immunogenicity- HAI antibody titers specific for the HA receptor binding domains of vaccine homologous A and B influenza strains Expressed as GMTR	HAI antibody titers specific for the HA receptor binding domains of vaccine response to immunization with CIC, Fluarix or Fluzone HD, and Novavax COVID-19 Vaccine Expressed as GMTR	Days 21, 84, and 184
Influenza NAb responses: neutralizing antibody titers specific to vaccine homologous wild-type A and B influenza strains, is expressed as GMT	Neutralizing antibody titers specific to vaccine homologous wild-type A and B influenza strains, as measured by a neutralization assay CIC, Fluarix or Fluzone HD, and Novavax COVID-19 Vaccine expressed as GMT	Day-0, 21-, 84-, and 184-days
Influenza NAb responses: neutralizing antibody titers specific to vaccine homologous wild-type A and B influenza strains, is expressed as GMFR	Neutralizing antibody titers specific to vaccine homologous wild-type A and B influenza strains, as measured by a neutralization assay CIC, Fluarix or Fluzone HD, and Novavax COVID-19 Vaccine expressed as GMFR	Days 21, 84, and 184
Influenza NAb responses: neutralizing antibody titers specific to vaccine homologous wild-type A and B influenza strains, is expressed as SCR	Neutralizing antibody titers specific to vaccine homologous wild-type A and B influenza strains, as measured by a neutralization assay CIC, Fluarix or Fluzone HD, and Novavax COVID-19 Vaccine expressed as SCR	Days 21, 84, and 184
Influenza NAb responses: neutralizing antibody titers specific to vaccine homologous wild-type A and B influenza strains, is expressed as GMTR	Neutralizing antibody titers specific to vaccine homologous wild-type A and B influenza strains, as measured by a neutralization assay CIC, Fluarix or Fluzone HD, and Novavax COVID-19 Vaccine expressed as GMTR	Days 21, 84, and 184
SARS-CoV-2 NAb responses: neutralizing antibody titers specific to the homologous SARS-CoV-2 strain Expressed as GMT	SARS-CoV-2 NAb responses: neutralizing antibody titers specific to the homologous SARS-CoV-2 strain CIC, Fluarix or Fluzone HD, and Novavax COVID-19 Vaccine expressed as GMT	Days 21, 84, and 184
SARS-CoV-2 NAb responses: neutralizing antibody titers specific to the homologous SARS-CoV-2 strain Expressed as GMFR	SARS-CoV-2 NAb responses: neutralizing antibody titers specific to the homologous SARS-CoV-2 strain CIC, Fluarix or Fluzone HD, and Novavax COVID-19 Vaccine expressed as GMFR	Days 21, 84, and 184
SARS-CoV-2 NAb responses: neutralizing antibody titers specific to the homologous SARS-CoV-2 strain Expressed as SCR	SARS-CoV-2 NAb responses: neutralizing antibody titers specific to the homologous SARS-CoV-2 strain CIC, Fluarix or Fluzone HD, and Novavax COVID-19 Vaccine expressed as SCR	Days 21, 84, and 184
SARS-CoV-2 NAb responses: neutralizing antibody titers specific to the homologous SARS-CoV-2 strain Expressed as GMTR	SARS-CoV-2 NAb responses: neutralizing antibody titers specific to the homologous SARS-CoV-2 strain CIC, Fluarix or Fluzone HD, and Novavax COVID-19 Vaccine expressed as GMTR	Days 21, 84, and 184

Collaborators and Investigators

• Sponsor: Novavax

Study record dates

Study Major Dates

• Study Start (Estimated): August 30, 2024
• Primary Completion (Estimated): March 15, 2025
• Study Completion (Estimated): April 9, 2025

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: March 1, 2024
• First Posted (Actual): March 4, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Influenza; COVID-19
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Orthomyxoviridae Infections; COVID-19; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: CIC-E-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No