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

COVID-19 Clinical Trial

— COVID-19  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05519839
• Other study ID #: 2019nCoV-CIC-E-201
• Status: Completed
• Phase: Phase 2
• Start date: December 30, 2022
• Est. completion date: December 24, 2023

Study information

• Verified date: May 2024
• Source: Novavax
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1579
• Est. completion date: December 24, 2023
• Est. primary completion date: July 25, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Influenza
• Influenza, Human

Intervention

Drug:
• CIC Vaccine
Intramuscular (deltoid) injections of in-clinic mix of various doses of qNIV, SARS-CoV-2 rS, and 50 µg Matrix-M1 Adjuvant (CIC Vaccine) on Day 0.
• CIC Vaccine
Intramuscular (deltoid) injections of in-clinic mix of various doses of qNIV, SARS-CoV-2 rS, and 75 µg Matrix-M1 Adjuvant (CIC Vaccine) on Day 0.
• qNIV Vaccine
Intramuscular (deltoid) injections of in-clinic mix of various doses of qNIV and 75 µg Matrix-M1 Adjuvant (Influenza Vaccine) on Day 0.
• SARS-CoV-2 rS Vaccine
Intramuscular (deltoid) injections of in-clinic mix of various doses of SARS-CoV-2 rS, Diluent, and 50 µg Matrix-M1 Adjuvant (SARS-CoV-2 rS Vaccine) on Day 0.
• Influenza Vaccine
Intramuscular (deltoid) injections of Comparator influenza on Day 0.
• CIC Vaccine
Intramuscular (deltoid) injections of co-formulated mix of various doses of qNIV2, SARS-CoV-2 rS, and 50 µg Matrix-M1 Adjuvant (CIC Vaccine) on Day 0.

Locations

Country	Name	City	State
Australia	CMAX	Adelaide	South Australia
Australia	Paratus Clinical Research - Brisbane Clinic	Albion	Queensland
Australia	Paratus Clinical Research - Western Sydney	Blacktown	New South Wales
Australia	Emeritus Research - Sydney	Botany	New South Wales
Australia	Mater Adult Hospital	Brisbane	Queensland
Australia	Genesis Central Coast	Broadmeadow	New South Wales
Australia	Northern Beaches Clinical Research	Brookvale	New South Wales
Australia	Paratus Clinical Research - Canberra	Bruce	Australian Capital Territory
Australia	Emeritus Research	Camberwell	Victoria
Australia	Northside Health	Coffs Harbour	New South Whales
Australia	East Sydney Doctors	Darlinghurst	New South Wales
Australia	Holdsworth House Medical Brisbane	Darlinghurst	New South Wales
Australia	Oztrials Clinical Research	Drummoyne	New South Wales
Australia	Nucleus Network Pty Ltd	Herston	Queensland
Australia	Paratus Clinical Research - Central Coast	Kanwal	New South Wales
Australia	Novatrials	Kotara	New South Whales
Australia	Australian Clinical Research Network	Maroubra	New South Wales
Australia	Nucleus Network Limited	Melbourne	Victoria
Australia	Hunter Diabetes Centre	Merewether	New South Wales
Australia	Core Research Group	Milton	Queensland
Australia	Sutherland Clinical Trials	Miranda	New South Wales
Australia	Austrials Pty Ltd - Taringa	Taringa	Queensland
Australia	AusTrials (Wellers Hill)	Tarragindi	Queensland
Australia	Menzies Darwin	Tiwi	Norther Territory
Australia	Illawarra Health and Medical Research Institute	Wollongong	New South Wales
New Zealand	Middlemore Clinical Trials	Auckland
New Zealand	Optimal Clinical Trials Ltd	Auckland
New Zealand	New Zealand Clinical Research - Christchurch	Christchurch
New Zealand	P3 Research - Dunedin	Dunedin
New Zealand	P3 Reseach - Hawkes Bay	Havelock North	Hawkes Bay
New Zealand	P3 Research - Lower Hutt	Palmerston	Wellington
New Zealand	P3 Research - Palmerston North	Palmerston North	Manawatu-Wanganui
New Zealand	P3 Research Kapiti	Paraparaumu	Wellington
New Zealand	P3 Research - Tauranga	Tauranga
New Zealand	P3 Research - Wellington	Wellington

Sponsors (1)

Lead Sponsor	Collaborator
Novavax

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 and Part 2 : Number of participants with solicited local and systemic Adverse Events (AEs)	Numbers of participants with solicited local and systemic AEs over the 7 days post-vaccination.	Day 0 to Day 7
Primary	Part 1 and Part 2 : Percentage of participants with all AEs	Proportions of participants reporting all AEs, solicited and unsolicited, over 21 days post-vaccination.	Day 0 to Day 21
Primary	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)	Proportions of participants with MAAEs, AESIs (including PIMMCs and myocarditis and/or pericarditis), SAEs, will be collected for 6 months (approximately 182 days) post-vaccination	Day 0 to Day 182
Secondary	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)	HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s), and antigenically drifted influenza strains. Derived/calculated endpoints based on GMT, defined as the antilog of the mean of the log-transformed HAI titers on Days 0, 7, 21, 84, and other follow-up time points	Day 0 to Day 84
Secondary	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)	HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s), and antigenically drifted influenza strains. Derived/calculated endpoints based on Geometric mean fold rise (GMFRPost/Pre) - defined as the within group ratio of post-vaccination to pre-vaccination (Day 0) HAI GMTs within the same vaccine group on Days 7, 21, 84, and other follow-up time points.	Day 0 to Day 84
Secondary	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)	HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s), and antigenically drifted influenza strains. Derived/calculated endpoints based on Seroconversion rate (SCR) - defined as proportion of participants in a given Vaccine Group with either a baseline reciprocal (Day 0) titer of < 10 and a post-vaccination reciprocal titer = 40, or a baseline reciprocal (Day 0) titer of = 10 and a post-vaccination titer = 4-fold higher than the baseline titer as measured on Days 7, 21, 84, and other follow-up time points	Day 0 to Day 84
Secondary	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)	HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s), and antigenically drifted influenza strains. Derived/calculated endpoints based on Seroprotection rate (SPR) - defined as the proportion of participants with a reciprocal HAI titer = 40 on Days 7, 21, 84, and other follow-up time points.	Day 0 to Day 84
Secondary	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)	HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s), and antigenically drifted influenza strains. Derived/calculated endpoints based on GMTR between select treatment arms at Days 7, 21, 84, and other follow-up time points post-vaccination (adjusted for intergroup variation in baseline [pre-vaccination] titers).	Day 0 to Day 84
Secondary	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	Microneutralization (MN50) antibody responses: neutralizing antibody titers specific to vaccine homologous wild-type A and B strain(s) and/or antigenically drifted influenza strains, as measured by a MN assay expressed as GMTs.	Day 0 to Day 84
Secondary	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	Microneutralization (MN50) antibody responses: neutralizing antibody titers specific to vaccine homologous wild-type A and B strain(s) and/or antigenically drifted influenza strains, as measured by a MN assay expressed as GMFR	Day 0 to Day 84
Secondary	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	Microneutralization (MN50) antibody responses: neutralizing antibody titers specific to vaccine homologous wild-type A and B strain(s) and/or antigenically drifted influenza strains, as measured by a MN assay expressed as SCR.	Day 0 to Day 84
Secondary	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	Microneutralization (MN50) antibody responses: neutralizing antibody titers specific to vaccine homologous wild-type A and B strain(s) and/or antigenically drifted influenza strains, as measured by a MN assay expressed as GMTR.	Day 0 to Day 84
Secondary	Part 1 and Part 2: Serum Immunoglobulin G (IgG) to the SARS-CoV-2 spike protein expressed as GMEU	IgG geometric mean enzyme-linked immunosorbent assay (ELISA) unit (GMEU) concentrations (EU/mL) to the SARS-CoV-2 S protein from the matched vaccine construct (and mismatched variant if available), at Days 0, 7, 21, 84, and other follow-up time points, expressed as GMEU.	Day 0 to Day 84
Secondary	Part 1 and Part 2: Serum IgG to the SARS-CoV-2 spike protein expressed as GMFR	IgG geometric mean enzyme-linked immunosorbent assay (ELISA) unit (GMEU) concentrations (EU/mL) to the SARS-CoV-2 S protein from the matched vaccine construct (and mismatched variant if available), at Days 0, 7, 21, 84, and other follow-up time points, expressed as GMFR.	Day 0 to Day 84
Secondary	Part 1 and Part 2: Serum IgG to the SARS-CoV-2 spike protein expressed as SCR	IgG geometric mean enzyme-linked immunosorbent assay (ELISA) unit (GMEU) concentrations (EU/mL) to the SARS-CoV-2 S protein from the matched vaccine construct (and mismatched variant if available), at Days 0, 7, 21, 84, and other follow-up time points expressed as SCR.	Day 0 to Day 84
Secondary	Part 1 and Part 2: Serum IgG to the SARS-CoV-2 spike protein expressed as Geometric Mean ELISA Unit Ratio (GMEUR)	IgG geometric mean enzyme-linked immunosorbent assay (ELISA) unit (GMEU) concentrations (EU/mL) to the SARS-CoV-2 S protein from the matched vaccine construct (and mismatched variant if available), at Days 0, 7, 21, 84, and other follow-up time points, expressed as GMEUR.	Day 0 to Day 84
Secondary	Part 1 and Part 2: Microneutralization assay (MN) 50 GMTs to the SARS-CoV-2 expressed as GMTs	MN50 GMTs to the SARS-CoV-2 from the matched vaccine construct (and mismatched variant if available), at Days 0, 7, 21, 84, and other follow-up time points, expressed as GMTs.	Day 0 to Day 84
Secondary	Part 1 and Part 2: MN50 GMTs to the SARS-CoV-2 expressed as GMFR	MN50 GMTs to the SARS-CoV-2 from the matched vaccine construct (and mismatched variant if available), at Days 0, 7, 21, 84, and other follow-up time points expressed as GMFR.	Day 0 to Day 84
Secondary	Part 1 and Part 2: MN50 GMTs to the SARS-CoV-2 expressed as SCR	MN50 GMTs to the SARS-CoV-2 from the matched vaccine construct (and mismatched variant if available), at Days 0, 7, 21, 84, and other follow-up time points expressed as SCR.	Day 0 to Day 84
Secondary	Part 1 and Part 2: MN50 GMTs to the SARS-CoV-2 expressed as GMTR	MN50 GMTs to the SARS-CoV-2 from the matched vaccine construct (and mismatched variant if available), at Days 0, 7, 21, 84, and other follow-up time points expressed as GMTR	Day 0 to Day 84