ANZCTR - Registration

Registration number

NCT05519839

Ethics application status

Date submitted

26/08/2022

Date registered

29/08/2022

Date last updated

13/05/2024

Titles & IDs

Public title

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

Scientific 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

Secondary ID [1]

2019nCoV-CIC-E-201

Universal Trial Number (UTN)

Trial acronym

COVID-19

Linked study record

Health condition

Health condition(s) or problem(s) studied:

COVID-19

Influenza

Condition category

Condition code

Infection

Other infectious diseases

Respiratory

Other respiratory disorders / diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - CIC Vaccine
Treatment: Drugs - CIC Vaccine
Treatment: Drugs - qNIV Vaccine
Treatment: Drugs - SARS-CoV-2 rS Vaccine
Treatment: Drugs - Influenza Vaccine
Treatment: Drugs - CIC Vaccine

Experimental: Group A (Part 1) - CIC Vaccine Formulation 1 doses of Formulation 1. 1 dose on Days 0.

Experimental: Group B (Part 1) - CIC Vaccine Formulation 1 doses of Formulation 2. 1 dose on Days 0.

Experimental: Group C (Part 1) - CIC Vaccine Formulation 1 doses of Formulation 3. 1 dose on Days 0.

Experimental: Group D (Part 1) - CIC Vaccine Formulation1 doses of Formulation 4. 1 dose on Days 0.

Experimental: Group E (Part 1) - CIC Vaccine Formulation 1 doses of Formulation 5. 1 dose on Days 0.

Experimental: Group F (Part 1) - CIC Vaccine Formulation 1 doses of Formulation 6. 1 dose on Days 0.

Experimental: Group G (Part 1) - CIC Vaccine Formulation 1 doses of Formulation 7. 1 dose on Days 0.

Experimental: Group H (Part 1) - CIC Vaccine Formulation 1 doses of Formulation 8. 1 dose on Days 0.

Experimental: Group I (Part 1) - CIC Vaccine Formulation 1 doses of Formulation 9. 1 dose on Days 0.

Experimental: Group J (Part 1) - CIC Vaccine Formulation 1 doses of Formulation 10. 1 dose on Days 0.

Experimental: Group K (Part 1) - CIC Vaccine Formulation 1 doses of Formulation 11. 1 dose on Days 0.

Experimental: Group L (Part 1) - qNIV Vaccine Formulation 1 doses of Formulation 12. 1 dose on Days 0.

Experimental: Group M (Part 1) - qNIV Vaccine Formulation 1 doses of Formulation 13. 1 dose on Days 0.

Experimental: Group N (Part 1) - CIC Vaccine Formulation 1 doses of Formulation 14. 1 dose on Days 0.

Experimental: Group O (Part 1) - SARS-CoV-2 rS Vaccine Formulation 1 doses of Formulation 15. 1 dose on Days 0.

Experimental: Group P (Part 1) - Reference Vaccine Formulation 1 doses of Formulation 16. 1 dose on Days 0.

Experimental: Group Q (Part 1) - Reference Vaccine Formulation 1 doses of Formulation 17. 1 dose on Days 0.

Experimental: Group R (Part 1) - Reference Vaccine Formulation 1 doses of Formulation 18. 1 dose on Days 0.

Experimental: Group S (Part 1) - Comparator Influenza Vaccine Formulation 1 doses of Formulation 19. 1 dose on Days 0.

Experimental: Group T (Part 1) - Comparator Influenza Vaccine Formulation 1 doses of Formulation 20. 1 dose on Days 0.

Experimental: Group U (Part 2) - CIC Vaccine Formulation 1 doses of Formulation 1. 1 dose on Days 0.

Experimental: Group V (Part 2) - CIC Vaccine Formulation 1 doses of Formulation 2. 1 dose on Days 0.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: Influenza Vaccine
Intramuscular (deltoid) injections of Comparator influenza on Day 0.

Treatment: Drugs: 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.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Part 1 and Part 2 : Number of participants with solicited local and systemic Adverse Events (AEs)

Timepoint [1]

Day 0 to Day 7

Primary outcome [2]

Part 1 and Part 2 : Percentage of participants with all AEs

Timepoint [2]

Day 0 to Day 21

Primary outcome [3]

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)

Timepoint [3]

Day 0 to Day 182

Secondary outcome [1]

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)

Timepoint [1]

Day 0 to Day 84

Secondary outcome [2]

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)

Timepoint [2]

Day 0 to Day 84

Secondary outcome [3]

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)

Timepoint [3]

Day 0 to Day 84

Secondary outcome [4]

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)

Timepoint [4]

Day 0 to Day 84

Secondary outcome [5]

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)

Timepoint [5]

Day 0 to Day 84

Secondary outcome [6]

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

Timepoint [6]

Day 0 to Day 84

Secondary outcome [7]

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

Timepoint [7]

Day 0 to Day 84

Secondary outcome [8]

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

Timepoint [8]

Day 0 to Day 84

Secondary outcome [9]

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

Timepoint [9]

Day 0 to Day 84

Secondary outcome [10]

Part 1 and Part 2: Serum Immunoglobulin G (IgG) to the SARS-CoV-2 spike protein expressed as GMEU

Timepoint [10]

Day 0 to Day 84

Secondary outcome [11]

Part 1 and Part 2: Serum IgG to the SARS-CoV-2 spike protein expressed as GMFR

Timepoint [11]

Day 0 to Day 84

Secondary outcome [12]

Part 1 and Part 2: Serum IgG to the SARS-CoV-2 spike protein expressed as SCR

Timepoint [12]

Day 0 to Day 84

Secondary outcome [13]

Part 1 and Part 2: Serum IgG to the SARS-CoV-2 spike protein expressed as Geometric Mean ELISA Unit Ratio (GMEUR)

Timepoint [13]

Day 0 to Day 84

Secondary outcome [14]

Part 1 and Part 2: Microneutralization assay (MN) 50 GMTs to the SARS-CoV-2 expressed as GMTs

Timepoint [14]

Day 0 to Day 84

Secondary outcome [15]

Part 1 and Part 2: MN50 GMTs to the SARS-CoV-2 expressed as GMFR

Timepoint [15]

Day 0 to Day 84

Secondary outcome [16]

Part 1 and Part 2: MN50 GMTs to the SARS-CoV-2 expressed as SCR

Timepoint [16]

Day 0 to Day 84

Secondary outcome [17]

Part 1 and Part 2: MN50 GMTs to the SARS-CoV-2 expressed as GMTR

Timepoint [17]

Day 0 to Day 84

Eligibility

Key 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.

Minimum age

50 Years

Maximum age

80 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key 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.

Study design

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

Actual

30/12/2022

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

24/12/2023

Sample size

Target

Accrual to date

Final

1579

Recruitment in Australia

Recruitment state(s)

ACT,NSW,New South WhalesNorther TerritoryQLD,SA,VIC

Recruitment hospital [1]

Paratus Clinical Research - Canberra - Bruce

Recruitment hospital [2]

Paratus Clinical Research - Western Sydney - Blacktown

Recruitment hospital [3]

Emeritus Research - Sydney - Botany

Recruitment hospital [4]

Genesis Central Coast - Broadmeadow

Recruitment hospital [5]

Northern Beaches Clinical Research - Brookvale

Recruitment hospital [6]

East Sydney Doctors - Darlinghurst

Recruitment hospital [7]

Holdsworth House Medical Brisbane - Darlinghurst

Recruitment hospital [8]

Oztrials Clinical Research - Drummoyne

Recruitment hospital [9]

Paratus Clinical Research - Central Coast - Kanwal

Recruitment hospital [10]

Australian Clinical Research Network - Maroubra

Recruitment hospital [11]

Hunter Diabetes Centre - Merewether

Recruitment hospital [12]

Sutherland Clinical Trials - Miranda

Recruitment hospital [13]

Illawarra Health and Medical Research Institute - Wollongong

Recruitment hospital [14]

Northside Health - Coffs Harbour

Recruitment hospital [15]

Novatrials - Kotara

Recruitment hospital [16]

Menzies Darwin - Tiwi

Recruitment hospital [17]

Paratus Clinical Research - Brisbane Clinic - Albion

Recruitment hospital [18]

Mater Adult Hospital - Brisbane

Recruitment hospital [19]

Nucleus Network Pty Ltd - Herston

Recruitment hospital [20]

Core Research Group - Milton

Recruitment hospital [21]

Austrials Pty Ltd - Taringa - Taringa

Recruitment hospital [22]

AusTrials (Wellers Hill) - Tarragindi

Recruitment hospital [23]

CMAX - Adelaide

Recruitment hospital [24]

Emeritus Research - Camberwell

Recruitment hospital [25]

Nucleus Network Limited - Melbourne

Recruitment postcode(s) [1]

- Bruce

Recruitment postcode(s) [2]

2148 - Blacktown

Recruitment postcode(s) [3]

- Botany

Recruitment postcode(s) [4]

- Broadmeadow

Recruitment postcode(s) [5]

- Brookvale

Recruitment postcode(s) [6]

- Darlinghurst

Recruitment postcode(s) [7]

- Drummoyne

Recruitment postcode(s) [8]

- Kanwal

Recruitment postcode(s) [9]

- Maroubra

Recruitment postcode(s) [10]

- Merewether

Recruitment postcode(s) [11]

- Miranda

Recruitment postcode(s) [12]

- Wollongong

Recruitment postcode(s) [13]

2450 - Coffs Harbour

Recruitment postcode(s) [14]

2289 - Kotara

Recruitment postcode(s) [15]

- Tiwi

Recruitment postcode(s) [16]

- Albion

Recruitment postcode(s) [17]

- Brisbane

Recruitment postcode(s) [18]

- Herston

Recruitment postcode(s) [19]

- Milton

Recruitment postcode(s) [20]

- Taringa

Recruitment postcode(s) [21]

- Tarragindi

Recruitment postcode(s) [22]

- Adelaide

Recruitment postcode(s) [23]

- Camberwell

Recruitment postcode(s) [24]

- Melbourne

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Hawkes Bay

Country [2]

New Zealand

State/province [2]

Manawatu-Wanganui

Country [3]

New Zealand

State/province [3]

Wellington

Country [4]

New Zealand

State/province [4]

Auckland

Country [5]

New Zealand

State/province [5]

Christchurch

Country [6]

New Zealand

State/province [6]

Dunedin

Country [7]

New Zealand

State/province [7]

Tauranga

Funding & Sponsors

Primary sponsor type

Commercial sector/Industry

Name

Novavax

Country

Ethics approval

Ethics application status

Summary

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.

Trial website

https://clinicaltrials.gov/ct2/show/NCT05519839

Public notes

Contacts

Principal investigator

Name

Clinical Development

Address

Novavax, Inc.

Country

Phone

Email

Contact person for public queries

Name

Address

Country

Phone

Email

Contact person for scientific queries

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05519839