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

NCT ID: NCT05519839

Last Updated: 2024-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 1579 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-30
• Study Completion Date: 2023-12-24

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.

Conditions

COVID-19; Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Group A (Part 1)

CIC Vaccine Formulation1. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group B (Part 1)

CIC Vaccine Formulation 2. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group C (Part 1)

CIC Vaccine Formulation 3. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group D (Part 1)

CIC Vaccine Formulation 3. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group E (Part 1)

CIC Vaccine Formulation 1. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group F (Part 1)

CIC Vaccine Formulation 2. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group G (Part 1)

CIC Vaccine Formulation 3. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group H (Part 1)

CIC Vaccine Formulation 4. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group I (Part 1)

CIC Vaccine Formulation 5. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group J (Part 1)

CIC Vaccine Formulation 6. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group K (Part 1)

CIC Vaccine Formulation 7. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group L (Part 1)

qNIV Vaccine Formulation 1. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

qNIV Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of in-clinic mix of various doses of qNIV vaccine given on Day 0 and Day 70 .

Group M (Part 1)

qNIV Vaccine Formulation 2. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

qNIV Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of in-clinic mix of various doses of qNIV vaccine given on Day 0 and Day 70 .

Group N (Part 1)

qNIV Vaccine Formulation 3 . 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

qNIV Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of in-clinic mix of various doses of qNIV vaccine given on Day 0 and Day 70 .

Group O (Part 1)

SARS-CoV-2 rS Vaccine Formulation 1. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

SARS-CoV-2 rS Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of in-clinic mix of various doses of SARS-CoV-2 rS vaccine given on Day 0 and Day 70 .

Group P (Part 1)

SARS-CoV-2 rS Vaccine Formulation 2. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

SARS-CoV-2 rS Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of in-clinic mix of various doses of SARS-CoV-2 rS vaccine given on Day 0 and Day 70 .

Group Q (Part 1)

SARS-CoV-2 rS Vaccine Formulation 3. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

SARS-CoV-2 rS Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of in-clinic mix of various doses of SARS-CoV-2 rS vaccine given on Day 0 and Day 70 .

Group R (Part 1)

SARS-CoV-2 rS Vaccine Formulation 4. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70

Group Type: EXPERIMENTAL

SARS-CoV-2 rS Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of in-clinic mix of various doses of SARS-CoV-2 rS vaccine given on Day 0 and Day 70 .

Group S (Part 1)

Influenza Vaccine Formulation 1.

1 intramuscular (IM) doses of vaccine, on Day 0.

Group Type: EXPERIMENTAL

Influenza Vaccine

Intervention Type: DRUG

Intramuscular (deltoid) injections of Comparator influenza vaccine given on Day 0 and Day 70 (if applicable).

Group T (Part 2)

CIC Vaccine Formulation 8. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70 (if applicable).

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group U (Part 2)

CIC Vaccine Formulation 9. 2 intramuscular (IM) doses of vaccine, the first on Day 0 and the second on Day 70 (if applicable).

Group Type: EXPERIMENTAL

CIC Vaccine with Matrix-M Adjuvant

Intervention Type: DRUG

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Group S (Part 1)-Placebo

1 intramuscular (IM) doses of placebo, on Day 70.

Group Type: PLACEBO_COMPARATOR

Placebo Comparator

Intervention Type: OTHER

Intramuscular (deltoid) injection of placebo given on Day 70.

Interventions

qNIV Vaccine with Matrix-M Adjuvant

Intramuscular (deltoid) injections of in-clinic mix of various doses of qNIV vaccine given on Day 0 and Day 70 .

Intervention Type: DRUG

Influenza Vaccine

Intramuscular (deltoid) injections of Comparator influenza vaccine given on Day 0 and Day 70 (if applicable).

Intervention Type: DRUG

CIC Vaccine with Matrix-M Adjuvant

Intramuscular (deltoid) injections of co-formulated mix of various doses and formulations of CIC Vaccine given on Day 0 and Day 70

Intervention Type: DRUG

Placebo Comparator

Intramuscular (deltoid) injection of placebo given on Day 70.

Intervention Type: OTHER

SARS-CoV-2 rS Vaccine with Matrix-M Adjuvant

Intramuscular (deltoid) injections of in-clinic mix of various doses of SARS-CoV-2 rS vaccine given on Day 0 and Day 70 .

Intervention Type: DRUG

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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novavax

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Development

Role: STUDY_DIRECTOR

Novavax, Inc.

Locations

Paratus Clinical Research - Canberra

Bruce, Australian Capital Territory, Australia

Paratus Clinical Research - Western Sydney

Blacktown, New South Wales, Australia

Emeritus Research - Sydney

Botany, New South Wales, Australia

Genesis Central Coast

Broadmeadow, New South Wales, Australia

Northern Beaches Clinical Research

Brookvale, New South Wales, 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

Paratus Clinical Research - Central Coast

Kanwal, New South Wales, Australia

Australian Clinical Research Network

Maroubra, New South Wales, Australia

Hunter Diabetes Centre

Merewether, New South Wales, Australia

Sutherland Clinical Trials

Miranda, New South Wales, Australia

Illawarra Health and Medical Research Institute

Wollongong, New South Wales, Australia

Northside Health

Coffs Harbour, New South Whales, Australia

Novatrials

Kotara, New South Whales, Australia

Menzies Darwin

Tiwi, Norther Territory, Australia

Paratus Clinical Research - Brisbane Clinic

Albion, Queensland, Australia

Mater Adult Hospital

Brisbane, Queensland, Australia

Nucleus Network Pty Ltd

Herston, Queensland, Australia

Core Research Group

Milton, Queensland, Australia

Austrials Pty Ltd - Taringa

Taringa, Queensland, Australia

AusTrials (Wellers Hill)

Tarragindi, Queensland, Australia

CMAX

Adelaide, South Australia, Australia

Emeritus Research

Camberwell, Victoria, Australia

Nucleus Network Limited

Melbourne, Victoria, Australia

P3 Reseach - Hawkes Bay

Havelock North, Hawkes Bay, New Zealand

P3 Research - Palmerston North

Palmerston North, Manawatu-Wanganui, New Zealand

P3 Research - Lower Hutt

Palmerston, Wellington Region, New Zealand

P3 Research Kapiti

Paraparaumu, Wellington Region, 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 Research - Tauranga

Tauranga, , New Zealand

P3 Research - Wellington

Wellington, , New Zealand

Countries

Australia; New Zealand

Other Identifiers

2019nCoV-CIC-E-201

Identifier Type: -

Identifier Source: org_study_id