Clinical trial NCT05519839: A Study to Evaluate the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine
Official title: A Phase 2, Randomized, Observer-Blinded Study to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 rS Nanoparticle and Quadrivalent Hemagglutinin Nanoparticle Influenza Combination Vaccine With Matrix-M™ Adjuvant in Healthy Participants ≥ 50 to ≤ 80 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Influenza
Keywords: Coronavirus
Influenza
Lead sponsor: Novavax
Sponsor class: INDUSTRY
First posted: 2022-08-29
Enrollment: 1579
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a randomized, observer-blinded, Phase 2 study evaluating the safety and immunogenicity of a severe acute respiratory syndrome coronavirus 2 (SARSCoV2) recombinant spike (rS) (SARS-CoV-2 rS) nanoparticle and quadrivalent hemagglutinin (HA) nanoparticle influenza vaccine (qNIV) combination vaccine with Matrix-M™ adjuvant; this combination vaccine.

Detailed description: The study will enroll approximately 2300 (1520 in Part 1 and 800 in Part 2) healthy (based on history and physical examination) adult male and female participants 50 to 80 years of age, inclusive, targeting participants, who must have completed a primary vaccination series against SARS-CoV-2 with an authorized COVID-19 vaccine (and fulfill national recommendations for his/her age and morbidity category) with receipt of second/last dose of authorized vaccine (with or without boosters\[s\]) ≥ 3 months prior to enrollment. Randomization will be stratified by age ≥ 50 to \< 65 or ≥ 65 to ≤ 80 years to distribute the proportions of each age stratum evenly across vaccine groups.

Eligibility criteria: Inclusion Criteria:

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

1. Medically stable adult male or females ≥ 50 to ≤ 80 years of age at screening.
2. 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.
3. The participant has a body mass index (BMI) of 17 to 40 kg/m2, inclusive, at screening.
4. Willing and able to give informed consent prior to study enrollment.
5. Able to attend study visits, comply with study requirements, and provide reliable and complete reports of AEs.
6. Participants must have completed a primary vaccination series against SARS-CoV-2 with an authorized COVID 19 vaccine (and fulfill national recommendations for his/her age and morbidity category) with receipt of second/last dose of authorized vaccine (with or without boosters\[s\]) ≥ 8 weeks prior to enrollment (first study vaccination).
7. 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 listed below from at least 28 days prior to enrollment and through the end of the study

   1. Condoms (male or female) with spermicide (if acceptable in country)
   2. Diaphragm with spermicide
   3. Cervical cap with spermicide
   4. Intrauterine device
   5. Oral or patch contraceptives
   6. Norplant®, Depo-Provera®, or other in-country regulatory approved contraceptive method that is designed to protect against pregnancy
   7. Abstinence, as a form of contraception, is acceptable if in line with the participant's lifestyle
8. Participants must be healthy and medically stable, as determined by the investigator (based on review of health status, vital signs \[to include body temperature\], medical history, and targeted physical examination \[to include body weight\]). Vital signs must be within medically acceptable ranges prior to vaccination.
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, 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 ≤ 8 weeks prior to enrollment.

   (NOTE: Symptomatic COVID-19 or asymptomatic SARS-CoV-2 infection \> 8 weeks prior to enrollment is NOT exclusionary)
2. Any ongoing, symptomatic acute illness requiring medical or surgical care or chronic illness that required changes in medication in the past 2 months 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: well controlled hypertension ≤ grade 2 in NOT exclusionary);
   2. Congestive heart failure with a history of an acute exacerbation of any severity in the prior 2 years (NOTE:

      mild well-controlled congestive heart failure is NOT exclusionary);
   3. Chronic obstructive pulmonary disease (COPD) with a history of an acute exacerbation of any severity in the prior 2 years (NOTE: mild well-controlled COPD is NOT exclusionary);
   4. In the past 3 months, evidence of unstable coronary artery disease as manifested by cardiac interventions (eg, cardiac stent placement, coronary artery bypass grafting \[CABG\]) surgery, new cardiac medications for control of symptoms, or unstable angina (NOTE: stable coronary heart disease is NOT exclusionary);
   5. Asthma with a history of exacerbation in the prior 2 years or worsening of asthma symptoms or requiring changes in asthma control medications in the past 2 months (NOTE: well-controlled asthma is NOT exclusionary).
   6. Type 1 or type 2 diabetes (adult onset) requiring insulin (NOTE: non-insulin dependent type 2 diabetes is NOT exclusionary);
   7. Chronic kidney disease/renal insufficiency;
   8. Chronic gastrointestinal and hepatic diseases; or
   9. Chronic neurological diseases (such as multiple sclerosis, dementia, Parkinson's disease, degenerative neurological conditions, neuropathy, or epilepsy), history of stroke within 12 months with residual symptoms, or previous neurological disorder within 12 months with residual symptoms (NOTE: history of migraine or chronic headaches or nerve root compression that have been stable on treatment for the last 4 weeks are NOT exclusionary).
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 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 8 weeks preceding the study vaccination. Note: Routine vaccinations will not be allowed until after study Day 21 and COVID 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: mild psoriasis is 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 3 years 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 end of study (EoS).
15. Known disturbance of coagulation.
16. 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.
17. 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).
18. History of myocarditis or pericarditis.
19. 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).
20. 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.

Primary outcomes:
measure: Part 1 and Part 2 : Number of participants with solicited local and systemic Adverse Events (AEs)
timeFrame: Day 0 to Day 7
measure: Part 1 and Part 2 : Percentage of participants with all AEs
timeFrame: Day 0 to Day 21
measure: Part 1 and Part 2 : Percentage of participants with Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs) and Serious Adverse Events (SAEs)
timeFrame: Day 0 to Day 182
Secondary outcomes:
measure: Part 1 and Part 2 : Hemagglutination Inhibition (HAI) Titers Specific for Vaccine Homologous A and B Influenza Strain(s) and Antigenically Drifted Influenza Strains Expressed as Geometric Mean Titer (GMT)
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2 : Hemagglutination Inhibition (HAI) Titers Specific for Vaccine Homologous A and B Influenza Strain(s) and Antigenically Drifted Influenza Strains Expressed as Geometric Mean Fold Rise (GMFR)
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2 : Hemagglutination Inhibition (HAI) Titers Specific for Vaccine Homologous A and B Influenza Strain(s) and Antigenically Drifted Influenza Strains Expressed as Seroconversion Rate (SCR)
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2 : Hemagglutination Inhibition (HAI) Titers Specific for Vaccine Homologous A and B Influenza Strain(s) and Antigenically Drifted Influenza Strains Expressed as Seroprotection Rate (SPR)
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2 : Hemagglutination Inhibition (HAI) Titers Specific for Vaccine Homologous A and B Influenza Strain(s) and Antigenically Drifted Influenza Strains Expressed as Geometric Mean Titer Ratio (GMTR)
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2: Neutralizing Antibody Titers Specific for Vaccine Homologous A and B Influenza Strain(s) and/or Antigenically Drifted Influenza Strains Expressed as GMTs
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2 : Neutralizing Antibody Titers Specific for Vaccine Homologous A and B Influenza Strain(s) and/or Antigenically Drifted Influenza Strains Expressed as GMFR
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2: Neutralizing Antibody Titers Specific for Vaccine Homologous A and B Influenza Strain(s) and/or Antigenically Drifted Influenza Strains Expressed as SCR
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2: Neutralizing Antibody Titers Specific for Vaccine Homologous A and B Influenza Strain(s) and/or Antigenically Drifted Influenza Strains Expressed as GMTR
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2: Serum Immunoglobulin G (IgG) to the SARS-CoV-2 spike protein expressed as GMEU
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2: Serum IgG to the SARS-CoV-2 spike protein expressed as GMFR
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2: Serum IgG to the SARS-CoV-2 spike protein expressed as SCR
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2: Serum IgG to the SARS-CoV-2 spike protein expressed as Geometric Mean ELISA Unit Ratio (GMEUR)
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2: Microneutralization assay (MN) 50 GMTs to the SARS-CoV-2 expressed as GMTs
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2: MN50 GMTs to the SARS-CoV-2 expressed as GMFR
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2: MN50 GMTs to the SARS-CoV-2 expressed as SCR
timeFrame: Day 0 to Day 84
measure: Part 1 and Part 2: MN50 GMTs to the SARS-CoV-2 expressed as GMTR
timeFrame: Day 0 to Day 84
Other outcomes:
Locations:
city: Bruce
country: Australia
facility: Paratus Clinical Research - Canberra
state: Australian Capital Territory
city: Blacktown
country: Australia
facility: Paratus Clinical Research - Western Sydney
state: New South Wales
city: Botany
country: Australia
facility: Emeritus Research - Sydney
state: New South Wales
city: Broadmeadow
country: Australia
facility: Genesis Central Coast
state: New South Wales
city: Brookvale
country: Australia
facility: Northern Beaches Clinical Research
state: New South Wales
city: Darlinghurst
country: Australia
facility: East Sydney Doctors
state: New South Wales
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Brisbane
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
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 Clinical Trials
state: New South Wales
city: Wollongong
country: Australia
facility: Illawarra Health and Medical Research Institute
state: New South Wales
city: Coffs Harbour
country: Australia
facility: Northside Health
state: New South Whales
city: Kotara
country: Australia
facility: Novatrials
state: New South Whales
city: Tiwi
country: Australia
facility: Menzies Darwin
state: Norther Territory
city: Albion
country: Australia
facility: Paratus Clinical Research - Brisbane Clinic
state: Queensland
city: Brisbane
country: Australia
facility: Mater Adult Hospital
state: Queensland
city: Herston
country: Australia
facility: Nucleus Network Pty Ltd
state: Queensland
city: Milton
country: Australia
facility: Core Research Group
state: Queensland
city: Taringa
country: Australia
facility: Austrials Pty Ltd - Taringa
state: Queensland
city: Tarragindi
country: Australia
facility: AusTrials (Wellers Hill)
state: Queensland
city: Adelaide
country: Australia
facility: CMAX
state: South Australia
city: Camberwell
country: Australia
facility: Emeritus Research
state: Victoria
city: Melbourne
country: Australia
facility: Nucleus Network Limited
state: Victoria
city: Havelock North
country: New Zealand
facility: P3 Reseach - Hawkes Bay
state: Hawkes Bay
city: Palmerston North
country: New Zealand
facility: P3 Research - Palmerston North
state: Manawatu-Wanganui
city: Palmerston
country: New Zealand
facility: P3 Research - Lower Hutt
state: Wellington
city: Paraparaumu
country: New Zealand
facility: P3 Research Kapiti
state: Wellington
city: Auckland
country: New Zealand
facility: Middlemore Clinical Trials
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials Ltd
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research - Christchurch
city: Dunedin
country: New Zealand
facility: P3 Research - Dunedin
city: Tauranga
country: New Zealand
facility: P3 Research - Tauranga
city: Wellington
country: New Zealand
facility: P3 Research - Wellington
Study officials:
affiliation: Novavax, Inc.
name: Clinical Development
role: STUDY_DIRECTOR
References: