Clinical trial NCT06291857: A Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine and Influenza Combination Vaccine
Official title: 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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: COVID-19
Keywords: CIC (Coronavirus Disease 2019 Influenza Combination)
Influenza
Fluzone High-Dose
Lead sponsor: Novavax
Sponsor class: INDUSTRY
First posted: 2024-03-04
Enrollment: 9320
Sex: ALL
Minimum age (years): 65
Maximum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: The study will enroll up to approximately 7,022,000 medically stable (based on history and physical examination) adult male and female participants ≥ 65 65 years of age in Part 1 and up to approximately 2,300 medically stable (based on history and physical examination) adult male and female participants ≥ 65 years of age in Part 2. In Part 1, pParticipants will be randomly assigned to receive either CIC, Novavax COVID-19 Vaccine, tNIV, or Fluzone High-Dose in a 3:2:1:3 ratio, respectively. All participants will receive a single intramuscular (IM) injection on Day 0, will remain on study for immunogenicity data collection through Day 182 and safety data collection through Day 364 (End of Study \[EoS\]).

Eligibility criteria: 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.

Primary outcomes:
measure: Numbers of participants with solicited local and systemic adverse events (AEs)
timeFrame: 7 days post-vaccination
measure: Numbers of participants reporting unsolicited AEs and medically attended adverse events (MAAEs).
timeFrame: 28 days post-vaccination
measure: 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)
timeFrame: Day 0 to Day 364
measure: Hemagglutination Inhibition (HAI) antibody responses of the CIC vaccine compared to Fluzone High-Dose of homologous A and B strains Expressed as GMT
timeFrame: Days 0 and 28
measure: Hemagglutination Inhibition (HAI) antibody responses of the CIC vaccine compared to Fluzone High-Dose of homologous A and B strains Expressed as GMTR
timeFrame: Days 28
measure: Percentage of Participants With a (HAI) antibody responses of the CIC vaccine compared to Fluzone High-Dose for 3 vaccine-homologous influenza strains Expressed as SCR
timeFrame: Days 28
measure: Neutralizing Antibody (NAb) Responses of the CIC vaccine compared to Fluzone High-Dose of homologous A and B strains Expressed as GMT
timeFrame: Days 28
measure: Neutralizing Antibody (NAb) Responses of the CIC vaccine compared to Fluzone High-Dose of homologous A and B strains Expressed as GMTR
timeFrame: Days 28
measure: Percentage of Participants With a (NAb) Responses of the CIC vaccine compared to Fluzone High-Dose of homologous A and B strains Expressed as SCR
timeFrame: Days 28
measure: Hemagglutination Inhibition (HAI) antibody titers specific to HA receptor-binding domains of (tNIV) comparable to Fluzone High-Dose of homologous influenza A and B strains expressed as GMT
timeFrame: Day 28
measure: Hemagglutination Inhibition (HAI) antibody titers specific to HA receptor-binding domains of (tNIV) comparable to Fluzone High-Dose of homologous influenza A and B strains expressed as GMTR
timeFrame: Day 28
measure: Percentage of Participants with (HAI) antibody titers specific to HA receptor-binding domains of (tNIV) comparable to Fluzone High-Dose of homologous influenza A and B strains expressed as SCR
timeFrame: Day 28
Secondary outcomes:
measure: Immunogenicity- HAI antibody titers specific for the HA receptor binding domains of vaccine homologous A and B influenza strains Expressed as Geometric Mean Titers (GMT)
timeFrame: Days 28
measure: Immunogenicity- HAI antibody titers specific for the HA receptor binding domains of vaccine homologous A and B influenza strains Expressed as GMFR
timeFrame: Days 28
measure: Percentage of Participants with HAI antibody titers specific for the HA receptor binding domains of vaccine homologous A and B influenza strains Expressed as SCR
timeFrame: Days 28
measure: HAI antibody titers specific for the HA receptor binding domains of vaccine homologous A and B influenza strains Expressed as GMTR
timeFrame: Days 28
measure: Influenza NAb responses: neutralizing antibody titers specific to vaccine homologous wild-type A and B influenza strains, is expressed as GMT
timeFrame: Days 28
measure: Influenza NAb responses: neutralizing antibody titers specific to vaccine homologous wild-type A and B influenza strains, is expressed as GMFR
timeFrame: Days 28
measure: Percentage of Participants with a NAb responses: neutralizing antibody titers specific to vaccine homologous wild-type A and B influenza strains, is expressed as SCR
timeFrame: Days 28
measure: Influenza NAb responses: neutralizing antibody titers specific to vaccine homologous wild-type A and B influenza strains, is expressed as GMTR
timeFrame: Days 28
measure: Hemagglutination Inhibition (HAI) antibody titers to tNIV and Fluzone High-Dose Expressed as GMT
timeFrame: Day 28
measure: Hemagglutination Inhibition (HAI) antibody titers to tNIV and Fluzone High-Dose Expressed as GMFR
timeFrame: Day 28
measure: Percentage of Participants with (HAI) antibody titers to tNIV and Fluzone High-Dose Expressed as SCR
timeFrame: Day 28
measure: Influenza neutralizing antibody (NAb) responses of trivalent nanoparticle influenza vaccine (tNIV) comparable to Fluzone High-Dose Expressed as GMT
timeFrame: Day 28
measure: Influenza neutralizing antibody (NAb) responses of trivalent nanoparticle influenza vaccine (tNIV) comparable to Fluzone High-Dose Expressed as GMFR
timeFrame: Day 28
measure: Influenza neutralizing antibody (NAb) responses of trivalent nanoparticle influenza vaccine (tNIV) comparable to Fluzone High-Dose Expressed as GMTR
timeFrame: Day 28
measure: Percentage of Participants with (NAb) responses of trivalent nanoparticle influenza vaccine (tNIV) comparable to Fluzone High-Dose Expressed as SCR
timeFrame: Day 28
Other outcomes:
Locations:
city: Bruce
country: Australia
facility: Paratus Clinical Research - Canberra - PPDS
state: Australian Capital Territory
city: Wellers Hill
country: Australia
facility: Momentum Wellers
state: Brisbane
city: Blacktown
country: Australia
facility: Paratus Clinical Research - Western Sydney - PPDS
state: New South Wales
city: Bondi Junction
country: Australia
facility: Key Health- Bondi Junction
state: New South Wales
city: Botany
country: Australia
facility: Emeritus Research - Sydney - PPDS
state: New South Wales
city: Broadmeadow
country: Australia
facility: Genesis Research Services
state: New South Wales
city: Brookvale
country: Australia
facility: Northern Beaches Clinical Research - PPDS
state: New South Wales
city: Coffs Harbour
country: Australia
facility: Northside Health
state: New South Wales
city: Darlinghurst
country: Australia
facility: East Sydney Doctors
state: New South Wales
city: Darlinghurst
country: Australia
facility: Momentum Darlinghurst
state: New South Wales
city: Drummoyne
country: Australia
facility: Oztrials Clinical Research
state: New South Wales
city: Kanwal
country: Australia
facility: Paratus Clinical Research - Central Coast - PPDS
state: New South Wales
city: Kotara
country: Australia
facility: Novatrials
state: New South Wales
city: Maroubra
country: Australia
facility: Australian Clinical Research Network
state: New South Wales
city: Merewether
country: Australia
facility: Hunter Diabetes Centre
state: New South Wales
city: Miranda
country: Australia
facility: Sutherland Shire Clinical Research - PPDS
state: New South Wales
city: North Sydney
country: Australia
facility: Pioneer Clinical Research - North Sydney
state: New South Wales
city: Surry Hills
country: Australia
facility: Taylor Square Private Clinic
state: New South Wales
city: Sydney
country: Australia
facility: Momentum St Leonards
state: New South Wales
city: Sydney
country: Australia
facility: Innovate Clinical Research Pty Ltd
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Clinical Research - PPDS
state: New South Wales
city: Casuarina
country: Australia
facility: Menzies School of Health Research
state: Northern Territory
city: Birtinya
country: Australia
facility: University of the Sunshine Coast, Vitality Village - UniSC Clinical Trials - PPDS
state: Queensland
city: Brisbane
country: Australia
facility: Momentum Taringa
state: Queensland
city: Griffith
country: Australia
facility: Griffith University Clinical Trials Unit
state: Queensland
city: Herston
country: Australia
facility: Nucleus Network Pty Ltd
state: Queensland
city: Herston
country: Australia
facility: Paratus Clinical Research - Brisbane Clinic - PPDS
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane
state: Queensland
city: Adelaide
country: Australia
facility: Cmax - Ppds
state: South Australia
city: Bayswater
country: Australia
facility: Veritus Research - Emeritus - PPDS
state: Victoria
city: Camberwell
country: Australia
facility: Emeritus Research -PPDS
state: Victoria
city: Geelong
country: Australia
facility: Ryrie St, Geelong, VIC 3220, Australia
state: Victoria
city: Melbourne N.
country: Australia
facility: University of Melbourne - Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Doherty Clinical Trials Limited
state: Victoria
city: Melbourne
country: Australia
facility: Nucleus Network Limited
state: Victoria
city: Melbourne
country: Australia
facility: Momentum Sunshine
state: Victoria
city: Midland
country: Australia
facility: Institute for Respiratory Health - Midland
state: Western Australia
city: Nedlands
country: Australia
facility: Telethon Kids Institute
state: Western Australia
city: Perth
country: Australia
facility: CliniTrials
state: Western Australia
city: Tauranga
country: New Zealand
facility: Momentum Tauranga - PPDS
state: Bay Of Plenty
city: Hastings
country: New Zealand
facility: Momentum Hawke's Bay - PPDS
state: Hawke's Bay
city: Dunedin
country: New Zealand
facility: Momentum Dunedin - PPDS
state: Otago
city: Auckland
country: New Zealand
facility: Southern Clinical Trials - Totara - PCRN - PPDS
city: Auckland
country: New Zealand
facility: Pacific Clinical Research Network - Auckland - PCRN - PPDS
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials Ltd - North Shore - PPDS
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials Ltd - PPDS
city: Auckland
country: New Zealand
facility: Momentum Pukekohe - PPDS
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research - Christchurch - PPDS
city: Christchurch
country: New Zealand
facility: Pacific Clinical Research Network - Christchurch - PCRN - PPDS
city: Hamilton
country: New Zealand
facility: Lakeland Clinical Trials - Waikato - PCRN-PPDS
city: Lower Hutt
country: New Zealand
facility: Momentum Lower Hutt - PPDS
city: Nelson
country: New Zealand
facility: Southern Clinical Trials - Tasman - PCRN - PPDS
city: Palmerston North
country: New Zealand
facility: Momentum Palmerston North - PPDS
city: Rotorua
country: New Zealand
facility: Pacific Clinic Research Network - Rotorua - PCRN - PPDS
city: Waikanae
country: New Zealand
facility: Momentum Kapiti - PPDS
city: Wellington
country: New Zealand
facility: Lakeland Clinical Trials - Wellington - PCRN - PPDS
city: Wellington
country: New Zealand
facility: Momentum Wellington - PPDS
city: Wellington
country: New Zealand
facility: Aotearoa Clinical Trials Trust
Study officials:
affiliation: Novavax, Inc.
name: Clinical Development
role: STUDY_DIRECTOR
References: