Clinical trial NCT05372588: Phase 3 Boosting Study for the SARS-CoV-2 rS Variant Vaccines
Official title: A Multi-Part, Phase 3, Randomized, Observer Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adults Previously Vaccinated With Other COVID-19 Vaccines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
SARS CoV 2 Infection
Keywords: Coronavirus
Lead sponsor: Novavax
Sponsor class: INDUSTRY
First posted: 2022-05-12
Enrollment: 1340
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a Multi-Part, Phase 3, randomized, observer-blinded study to evaluate the safety and immunogenicity of booster doses of Omicron subvariant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant (r) spike (S) protein nanoparticle vaccines (SARS-CoV-2 rS) adjuvanted with Matrix-M™ adjuvant (NVX-CoV2515 \[BA.1\] and NVX-CoV2540 \[BA.5\]) and bivalent (NVX-CoV2373 \[prototype\] + Omicron subvariant) SARS-CoV-2 rS vaccines (NVX-CoV2373 + NVX CoV2515 and NVX CoV2373 + NVX CoV2540) in previously vaccinated adults 18 years of age and older.


Eligibility criteria: Part 1

Inclusion Criteria:

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

1. Adults ≥ 18 and ≤ 64 years of age at screening.
2. Willing and able to give informed consent prior to study enrollment and to comply with study procedures.
3. Female participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile \[ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy\] or postmenopausal \[defined as amenorrhea ≥ 12 consecutive months\]) 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 ≥ 28 days prior to and through the end of the study.
4. Is medically stable, as determined by the investigator (based on a 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 the vaccination.
5. Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study.
6. Have previously received 2 doses of the Moderna and/or Pfizer-BioNTech COVID-19 prototype vaccines with the last dose having been given ≥ 180 days prior to study vaccination or 3 doses of the Moderna and/or Pfizer-BioNTech COVID-19 prototype vaccines with the last dose having been given ≥ 90 days previously prior to the study vaccination.

Exclusion Criteria:

If an individual meets any of the following criteria, he or she is ineligible for this study:

1. Received COVID-19 vaccines other than Moderna and/or Pfizer-BioNTech in the past, inclusive of clinical trial COVID- 19 vaccines.
2. Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to study vaccination.
3. Received any vaccine ≤ 90 days prior to study vaccination, except for influenza vaccination which may be received \> 14 days prior to study vaccination, or rabies vaccine which may be given if medically indicated.
4. Any known allergies to products contained in the investigational product.
5. Any history of anaphylaxis to any prior vaccine.
6. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.
7. Chronic administration (defined as \> 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to study vaccination.
8. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to the first study vaccination, except for rabies immunoglobulin which may be given if medically indicated.
9. Active cancer (malignancy) on 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).
10. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of the study.
11. Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance.
12. Any other 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 study vaccine or interpretation of study results (including neurologic or psychiatric conditions likely to impair the quality of safety reporting).
13. Study team member or immediate family member of any study team member (inclusive of Sponsor, clinical research organization (CRO), and study site personnel involved in the conduct or planning of the study).

Part 2

Inclusion Criteria:

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

1. Adults and adolescents ≥ 18 years of age at screening.
2. Willing and able to give informed consent prior to study enrollment and to comply with study procedures.
3. Female participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile \[ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy\] or postmenopausal \[defined as amenorrhea ≥ 12 consecutive months\]) 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 ≥ 28 days prior to enrollment and through the end of the study.
4. Is 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 the first vaccination.
5. Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study.
6. Have previously received ≥ 3 doses of the Moderna and/or Pfizer-BioNTech monovalent and/or bivalent COVID-19 vaccines with the last dose having been given ≥ 90 days previously prior to first study booster.

Exclusion Criteria:

If an individual meets any of the following criteria, he or she is ineligible for this study:

1. Received COVID-19 vaccines other than Moderna and/or Pfizer-BioNTech in the past, inclusive of clinical trial COVID-19 vaccines.
2. Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to first study vaccination.
3. Received any vaccine ≤ 90 days prior to study vaccination, except for influenza vaccination which may be received \> 14 days prior to first study vaccination, or rabies vaccine which may be given if medically indicated.
4. Any known allergies to products contained in the investigational product.
5. Any history of anaphylaxis to any prior vaccine.
6. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.
7. Chronic administration (defined as \> 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to first study vaccination.
8. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to first study vaccination, except for rabies immunoglobulin which may be given if medically indicated.
9. Active cancer (malignancy) on therapy within 3 years prior to first 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).
10. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study.
11. Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the first study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance.
12. Any other 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 study vaccine or interpretation of study results (including neurologic or psychiatric conditions likely to impair the quality of safety reporting).
13. Study team member or immediate family member of any study team member (inclusive of Sponsor, clinical research organization \[CRO\], and study site personnel involved in the conduct or planning of the study).
14. Participants with a history of myocarditis or pericarditis

Primary outcomes:
measure: Part 1: MN50 geometric mean titers (GMTs) to the Omicron BA.1 subvariant expressed as GMTs
timeFrame: Day 14
measure: Part 1: MN50 titer concentrations to the Omicron BA.1 subvariant vaccine expressed as seroresponse rates (SRRs)
timeFrame: Day 14
measure: Part 2: Neutralizing Antibody (NAb) GMTs to the Omicron BA.5 subvariant expressed as GMTs
timeFrame: Day 28
measure: Part 2: Neutralizing Antibody (NAb) titers to the Omicron BA.5 subvariant expressed as SRRs
timeFrame: Day 28
measure: Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) strain expressed as GMTs
timeFrame: Day 28
Secondary outcomes:
measure: Part 1: MN50 geometric mean titers (GMTs) to the ancestral (Wuhan),and Omicron BA.1 viruses expressed as GMT
timeFrame: Day 0 to Day 240
measure: Part 1: MN50 titer concentrations to the ancestral (Wuhan), and Omicron BA.1 viruses expressed as GMFR
timeFrame: Day 7 to Day 240
measure: Part 1: MN50 titer concentrations to the ancestral (Wuhan), and Omicron BA.1 viruses expressed as SRRs
timeFrame: Day 7 to Day 240
measure: Part 1: Immunoglobulin G (IgG) antibody levels to the ancestral (Wuhan), Omicron BA.1 and Omicron BA.5 viruses expressed as GMT
timeFrame: Day 0 to Day 240
measure: Part 1:IgG antibody levels to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMFR
timeFrame: Day 0 to Day 240
measure: Part 1: IgG antibody levels to the ancestral (Wuhan), Omicron BA.1 and Omicron BA.5 viruses expressed as SRRs
timeFrame: Day 0 to Day 240
measure: Part 1: Human angiotensin-converting enzyme 2 (hACE2) receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMTs
timeFrame: Day 0 to Day 240
measure: Part 1: hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMFR
timeFrame: Day 0 to Day 240
measure: Part 1: hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as SRR
timeFrame: Day 0 to Day 240
measure: Part 1: MN50 GMTs to the to the ancestral (Wuhan) virus expressed as GMT
timeFrame: Day 14
measure: Part 1: MN50 GMTs to the to the ancestral (Wuhan) virus expressed as GMFR
timeFrame: Day 14
measure: Part 1: SRRs in MN50 titer concentrations to the ancestral (Wuhan) virus expressed as SRRs
timeFrame: Day 14
measure: Part 1: MN50 GMTs to the Omicron BA.1 subvariant virus expressed as GMT
timeFrame: Day 14
measure: Part 1: MN50 GMTs to the Omicron BA.1 subvariant virus expressed as GMFR
timeFrame: Day 14
measure: Part 1: MN50 GMTs to the Omicron BA.1 subvariant virus expressed as SRR
timeFrame: Day 14
measure: Part 1 and Part 2: Incidence of solicited local and systemic Adverse Events (AEs)
timeFrame: Day 7
measure: Part 1 and Part 2 : Incidence of unsolicited AEs
timeFrame: Day 28
measure: Part 1 and Part 2 :Incidence and relationship of Medically Attended Adverse Event(s) (MAAEs), Adverse event(s) of Special Interest (AESIs), and Serious Adverse Event(s) (SAEs)
timeFrame: Day 0 to Day 270
measure: Part 1: IgG Geometric Mean Concentrations (GMCs) to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as GMFR
timeFrame: Day 0 to Day 240
measure: Part 1: IgG GMCs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as SRR
timeFrame: Day 0 to Day 240
measure: Part 1: GMTs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as SRR
timeFrame: Day 0 to Day 240
measure: Part 1: GMTs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as GMFR
timeFrame: Day 0 to Day 240
measure: Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) and Omicron BA.5 strains expressed as GMTs
timeFrame: Day 0 to Day 270
measure: Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) and Omicron BA.5 strains expressed as GMFRs
timeFrame: Day 0 to Day 270
measure: Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) and Omicron BA.5 strains expressed as SRRs
timeFrame: Day 0 to Day 270
measure: Part 2: IgG GMEUs antibody levels to the ancestral (Wuhan) and Omicron BA.5 S proteins expressed as GMTs
timeFrame: Day 0 to Day 270
measure: Part 2: IgG GMEUs antibody levels to the ancestral (Wuhan) and Omicron BA.5 S proteins expressed as GMFRs
timeFrame: Day 0 to Day 270
measure: Part 2: IgG GMEUs antibody levels to the ancestral (Wuhan) and Omicron BA.5 S proteins expressed as SRRs
timeFrame: Day 0 to Day 270
measure: Part 2:hACE2 receptor binding inhibition assay to the ancestral (Wuhan),and Omicron BA.5 S proteins expressed as GMTs
timeFrame: Day 0 to Day 270
measure: Part 2:hACE2 receptor binding inhibition assay to the ancestral (Wuhan), and Omicron BA.5 S proteins expressed as GMFRs
timeFrame: Day 0 to Day 270
measure: Part 2:hACE2 receptor binding inhibition assay to the ancestral (Wuhan), and Omicron BA.5 S proteins expressed as SRRs
timeFrame: Day 0 to Day 270
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
state: New South Wales
city: Brookvale
country: Australia
facility: Northern Beaches 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 (ACRN)
state: New South Wales
city: Merewether
country: Australia
facility: AIM Centre (Hunter Diabetes Centre)
state: New South Wales
city: Newcastle
country: Australia
facility: Novatrials
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice
state: New South Whales
city: Albion
country: Australia
facility: Paratus Clinical Research Brisbane
state: Queensland
city: Milton
country: Australia
facility: Core Research Group Pty Ltd
state: Queensland
city: Southport
country: Australia
facility: Griffith University Clinical Trial Unit
state: Queensland
city: Taringa
country: Australia
facility: Data Health Australia PTY Ltd t/a Austrials
state: Queensland
city: Wellers Hill
country: Australia
facility: AusTrials Wellers Hill
state: Queensland
city: Adelaide
country: Australia
facility: Clinical Medical and Analytical Excellence (CMAX)
state: South Australia
city: Box Hill
country: Australia
facility: Eastern Health-Box Hill Hospital
state: Victoria
city: Camberwell
country: Australia
facility: Emeritus Research
state: Victoria
city: Geelong
country: Australia
facility: University Hospital Geelong-Barwon Health
state: Victoria
city: Melbourne
country: Australia
facility: Monash Health -Monash Medical Centre
state: Victoria
Study officials:
affiliation: Novavax, Inc.
name: Clinical Development
role: STUDY_DIRECTOR
References: