Clinical trial NCT05925127: Phase 2/3 Heterologous Boosting Study With Different Dose Levels of Monovalent SARS-CoV-2 rS Vaccines
Official title: A Phase 2/3, Randomized, Double-Blind Study to Evaluate the Safety and Immunogenicity of Different Booster Dose Levels of Monovalent SARS-CoV-2 rS Vaccines in Adults ≥ 50 Years Previously Vaccinated With COVID-19 mRNA Vaccines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: COVID-19
Lead sponsor: Novavax
Sponsor class: INDUSTRY
First posted: 2023-06-29
Enrollment: 994
Sex: ALL
Minimum age (years): 50
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: This is a Phase 2/3, randomized, double-blind study to evaluate the safety and immunogenicity of different booster dose levels of the monovalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant (r) spike (S) protein nanoparticle (SARS-CoV-2 rS) vaccines with Matrix-M™ adjuvant (NVX-CoV2373 \[prototype Wuhan vaccine with Matrix-M adjuvant\] or NVX-CoV2601 \[Omicron XBB.1.5 subvariant vaccine with Matrix-M adjuvant\]).

Detailed description: The ongoing COVID-19 pandemic has reached a stage where it is necessary to stablish the framework for periodic national vaccination campaigns.The present study aims to investigate the safety and immunogenicity of different booster dose levels of monovalent and bivalent vaccines in adults ≥ 50 years of age who have already been immunized with ≥ 3 doses of a COVID-19 prototype or bivalent licensed mRNA vaccine. The Boosters of investigational products will be administered ≥ 90 days after the participants received their third dose of a COVID-19 prototype or bivalent licensed mRNA vaccine.

Approximately 1,980 participants ≥ 50 years of age who have received a regimen of ≥ 3 doses of a coronavirus disease 2019(COVID-19) vaccine (the last vaccine could have been a bivalent licensed mRNA vaccine) will be included in this study. The last COVID-19 vaccine dose should have been administered ≥ 90 days prior to Day 0.

Approximately 1,800 participants will be randomly assigned in a 1:2:2:2:2:1 ratio to receive NVX-CoV2373 or NVC-CoV2601 in a double-blinded fashion into 1 of 6 monovalent vaccine groups (vaccine groups A to G). Following completion of enrollment into the 6 monovalent vaccine groups, 180 participants will be enrolled in vaccine group G to receive a bivalent licensed mRNA vaccine in an open-label fashion.

Eligibility criteria: Inclusion Criteria:

1. Adults ≥ 50 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 initial study 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 a COVID-19 prototype or bivalent licensed mRNAvaccine with the last dose having been given ≥ 90 days previously prior to first study booster.

Exclusion Criteria:

1. Received COVID-19 vaccines other than a COVID-19 prototype or bivalent licensed mRNA vaccine 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 influenza vaccination within 14 days prior to first study vaccination, or any other vaccine within 30 days prior to first study vaccination.
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. NOTE: An immunosuppressant dose of glucocorticoid is defined as a systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical or intranasal glucocorticoids is permitted. Topical tacrolimus and ocular cyclosporin are permitted. Use of inhaled glucocorticoids is prohibited.

8. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to 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 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, contract 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: Immunogenicity index-Neutralizing antibody expressed as geometric mean titer ratio[GMTR ]against the Omicron subvariant XBB.1.5
timeFrame: Day 28
measure: Immunogenicity index-Neutralizing antibody expressed as seroresponse rates (SRRs)against the Omicron subvariant XBB.1.5
timeFrame: Day 28
Secondary outcomes:
measure: Neutralizing antibody expressed as geometric mean titer ratio[GMTR ]against the Omicron subvariant XBB.1.5
timeFrame: Day 28
measure: Immunogenicity index- IgG antibody Anti-S expressed as geometric mean Elisa units GMEUs (EU/mL)
timeFrame: Day 0 to 180
measure: Immunogenicity index- Neutralizing antibody titers of post-booster by baseline anti-SARS-CoV-2 NP
timeFrame: Day-28
measure: Immunogenicity index- Serum IgG levels to SARS-CoV-2 S protein at Day 28 of post-booster
timeFrame: Day-28
measure: Safety Index-Incidence, duration, and severity of solicited local and systemic AEs expressed as GMT
timeFrame: 7 days
measure: Safety Index -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 180
measure: Safety Index -Incidence, Severity, and relationship of unsolicitated Adverse Event(s) Through 28 days after vaccination by vaccine group p(vaccine groups A to G).
timeFrame: Day 0 to 180
measure: 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 180
measure: hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMFR
timeFrame: Day 0 to 180
measure: 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 180
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: ARS-Birmingham CRU
state: Alabama
city: Tucson
country: United States
facility: Tucson Neuroscience Research
state: Arizona
city: Banning
country: United States
facility: Velocity Clinical Research, Banning
state: California
city: Chula Vista
country: United States
facility: Velocity Clinical Research, Chula Vista
state: California
city: La Mesa
country: United States
facility: Velocity Clinical Research, San Diego
state: California
city: Riverside
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Diego
country: United States
facility: Artemis - San Diego
state: California
city: San Diego
country: United States
facility: WR-MCCR
state: California
city: DeLand
country: United States
facility: Deland CRU
state: Florida
city: Jupiter
country: United States
facility: Health Awareness
state: Florida
city: Lake City
country: United States
facility: Wr-Msra, Llc
state: Florida
city: Largo
country: United States
facility: Professional Urgent Care Services
state: Florida
city: Miami
country: United States
facility: Research Institute of South Florida
state: Florida
city: Miami
country: United States
facility: Suncoast Research Associates, LLC
state: Florida
city: Orlando
country: United States
facility: Headlands Research Orlando LLC
state: Florida
city: Sunrise
country: United States
facility: Precision Clinical Research, LLC
state: Florida
city: Tampa
country: United States
facility: TrueBlue Clinical Research
state: Florida
city: Decatur
country: United States
facility: Neurostudies CRU
state: Georgia
city: Savannah
country: United States
facility: Velocity Clinical Research
state: Georgia
city: Stockbridge
country: United States
facility: CRA Headlands LLC
state: Georgia
city: Meridian
country: United States
facility: Velocity Clinical Research
state: Idaho
city: Sioux City
country: United States
facility: Velocity Clinical Research
state: Iowa
city: Baton Rouge
country: United States
facility: Velocity Clinical Research
state: Louisiana
city: Covington
country: United States
facility: Velocity Clinical Research - Covington
state: Louisiana
city: Metairie
country: United States
facility: Velocity Clinical Research, Metairie
state: Louisiana
city: Methuen
country: United States
facility: Activmed Practices and Research, LLC
state: Massachusetts
city: Gulfport
country: United States
facility: Velocity Clinical Research, Gulfport
state: Mississippi
city: Grand Island
country: United States
facility: Velocity Clinical Research
state: Nebraska
city: Norfolk
country: United States
facility: Velocity Clinical Research
state: Nebraska
city: Omaha
country: United States
facility: Velocity Clinical Research
state: Nebraska
city: Portsmouth
country: United States
facility: Activmed Practices and Research, LLC
state: New Hampshire
city: Binghamton
country: United States
facility: Velocity Clinical Research
state: New York
city: New Bern
country: United States
facility: Hypercore (Lucas Research)
state: North Carolina
city: Raleigh
country: United States
facility: M3 Wake Research Inc
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Javara Inc./Wake Forest Health Network, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Velocity Clinical Research
state: Ohio
city: Cincinnati
country: United States
facility: Velocity Clinical Research
state: Ohio
city: Edmond
country: United States
facility: Tekton Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Grants Pass
country: United States
facility: Velocity Clinical Research, Grants Pass
state: Oregon
city: East Greenwich
country: United States
facility: Velocity Clinical Research, Providence
state: Rhode Island
city: Gaffney
country: United States
facility: Velocity Clinical Research, Gaffney
state: South Carolina
city: North Charleston
country: United States
facility: Coastal Carolina Research Center an ALCANZA Clinical Research company
state: South Carolina
city: Austin
country: United States
facility: Central Texas Clinical Research, LLC
state: Texas
city: Plano
country: United States
facility: Research Your Health
state: Texas
city: San Angelo
country: United States
facility: Benchmark Research
state: Texas
city: West Jordan
country: United States
facility: Velocity Clinical Research, Salt Lake City
state: Utah
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc
state: Virginia
city: Richmond
country: United States
facility: Clinical Research Partners
state: Virginia
Study officials:
affiliation: Novavax
name: Clinical Development
role: STUDY_DIRECTOR
References: