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COVID-19: Phase 2/3 Heterologous Boosting Study With Different Dose Levels of Monovalent SARS-CoV-2 rS Vaccines

Sponsor
Novavax (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05925127
Collaborator
(none)
1,980
Enrollment
48
Locations
7
Arms
7.6
Anticipated Duration (Months)
41.3
Patients Per Site
5.5
Patients Per Site Per Month

Study Details

Study Description

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]).

Condition or Disease Intervention/Treatment Phase
  • Biological: NVX-CoV2373 (5μg)
  • Biological: NVX-CoV2601 (5μg)
  • Biological: NVX-CoV2601(5μg)
  • Biological: NVX-CoV2601 (35μg)
  • Biological: NVX-CoV2601(35μg)
  • Biological: NVX-CoV2601(50μg)
  • Biological: Bivalent BA.4/5
 Phase 2/Phase 3

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 Gto receive a bivalent licensed mRNA vaccine in an open-label fashion.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
1980 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
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
Anticipated Study Start Date :
Aug 30, 2023
Anticipated Primary Completion Date :
Apr 2, 2024
Anticipated Study Completion Date :
Apr 16, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group-A Monovalent NVX-CoV2373 (5 μg)

The Monovalent NVX-CoV2601 of 5 μg of antigen with 50 μg of Matrix-M adjuvant

Biological: NVX-CoV2373 (5μg)
Coformulated prototype SARS-CoV-2 rS vaccine with Matrix-M adjuvant: supplied as a solution for preparation for injection, at a concentration of 10 μg/mL and 100 μg adjuvant per mL, respectively
Experimental: Group-B Monovalent NVX-CoV2601 (5 μg)

Monovalent NVX-CoV2601 (5 μg of antigen with 50 μg of Matrix-M adjuvant)

Biological: NVX-CoV2601 (5μg)
The vaccination regimen will comprise one IM injection on Day 0 at a dose of 5 µg of antigen with 50 µg Matrix-M adjuvant.
Other Names:
  • Omicron XBB.1.5

    		•
    Experimental: Group-C Monovalent NVX-CoV2601 (5 μg)

    Monovalent NVX-CoV2601 (5 μg of antigen with 75 μg of Matrix-M adjuvant)

    Biological: NVX-CoV2601(5μg)
    The vaccination regimen will comprise one IM injection on Day 0 at a dose of 5 µg of antigen with 75 µg Matrix-M adjuvant.
    Other Names:
  • Omicron XBB.1.5

    		•
    Experimental: Group-D Monovalent NVX-CoV2601 (35 μg)

    Monovalent NVX-CoV2373 (35 μg of antigen with 50 μg of Matrix-M adjuvant)

    Biological: NVX-CoV2601 (35μg)
    The vaccination regimen will comprise one IM injection on Day 0 at a dose of 35 µg of antigen with 50 µg Matrix-M adjuvant.
    Other Names:
  • Omicron XBB.1.5

    		•
    Experimental: Group-E Monovalent NVX-CoV2601(35)

    Monovalent NVX-CoV2601 (35 μg of each antigen with a 75 μg of Matrix-M adjuvant)

    Biological: NVX-CoV2601(35μg)
    The vaccination regimen will comprise one IM injection on Day 0 at a dose of 35 µg of antigen with 75 µg Matrix-M adjuvant.
    Other Names:
  • Omicron XBB.1.5

    		•
    Experimental: Group-F Monovalent NVX-CoV2601 (50 μg)

    Monovalent NVX-CoV2601 (50 μg of each antigen with a 100 μg of Matrix-M adjuvant)

    Biological: NVX-CoV2601(50μg)
    The vaccination regimen will comprise one IM injection on Day 0 at a dose of 50 µg of antigen with 100 µg Matrix-M adjuvant
    Other Names:
  • Omicron XBB.1.5

    		•
    Experimental: Group-G Bivalent XBB.1.5

    Bivalent XBB.1.5 Omicron subvariant/prototype COVID-19 licensed mRNA vaccine

    Biological: Bivalent BA.4/5
    The bivalent BA.4/5 (or recommended mRNA vaccine at the time of the conduct of this study) Omicron subvariant/prototype licensed mRNA vaccine will be procured and stored per the manufacturer's instructions. For this vaccine group, treatment will be administered open label as a single IM injection
    Other Names:
  • Omicron Subvariant/Prototype Licensed mRNA Vaccine

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Immunogenicity index-Neutralizing antibody expressed as geometric mean titer ratio[GMTR ]against the Omicron subvariant XBB.1.5 [Day 28]

      Neutralizing antibody To determine if the combination of antigen and adjuvant levels of NVX-CoV2601 GMTR against the Omicron subvariant XBB.1.5 superior(LB of the 95% CI for GMTR > 1.0) to that elicited by NVX-CoV2373

    2. Immunogenicity index-Neutralizing antibody expressed as seroresponse rates (SRRs)against the Omicron subvariant XBB.1.5 [Day 28]

      Neutralizing antibody SRR against the Omicron XBB.1.5 subvariant elicited by NVXCoV2601 is non-inferior (NI)to the SRR elicited by NVX-CoV2373in participants ≥ 50 years of age previously vaccinated with ≥ 3 doses of a COVID-19 prototype or bivalent licensed mRNA vaccine.

    Secondary Outcome Measures

    1. Neutralizing antibody expressed as geometric mean titer ratio[GMTR ]against the Omicron subvariant XBB.1.5 [Day 28]

      Neutralizing antibody (GMTR) at relevant time points Days 28 to 180 from baseline (Day 0) and analyzed by dose (5, 10, and 25 µg)

    2. Immunogenicity index- IgG antibody Anti-S expressed as geometric mean Elisa units GMEUs (EU/mL) [Day 0 to 180]

      Immunoglobulin G (IgG) antibody Anti-S expressed as geometric mean Elisa units GMEUs (EU/mL) at relevant time points (Days 0 to 180) and analyzed by dose (5, 10, and 25 µg)

    3. Immunogenicity index- Neutralizing antibody titers of post-booster by baseline anti-SARS-CoV-2 NP [Day-28]

      Neutralizing antibody titers of post-booster by baseline anti-SARS-CoV-2 NP status day-28

    4. Immunogenicity index- Serum IgG levels to SARS-CoV-2 S protein at Day 28 of post-booster [Day-28]

      Serum IgG levels to SARS-CoV-2 S protein at Day 28 post-booster by baseline anti-SARS-CoV-2 NP status.

    5. Safety Index-Incidence, duration, and severity of solicited local and systemic AEs expressed as GMT [7 days]

      Incidence, duration, and severity of solicited local and systemic AEs for 7 days following vaccination.

    6. 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) [Day 0 to 180]

      Incidence and relationship of Medically Attended Adverse Event(s) (MAAEs), Adverse event(s) of Special Interest (AESIs), and Serious Adverse Event(s) (SAEs) [ Time Frame: Day 0 to Day 180 ] Incidence and relationship of MAAEs, AESIs (predefined list), and SAEs throughout the study

    7. 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). [Day 0 to 180]

      Incidence, Severity, and relationship of unsolicitated Adverse Event(s) Through 28 days after vaccination by vaccine group p(vaccine groups A to G).s the overall safety of single-dose regimens containing NVX-CoV2601, NVX-CoV2373, or mRNA vaccine by vaccine group in participants ≥ 50 years of age previously vaccinated with ≥ 3 doses of a COVID-19 prototype or bivalentlicensed mRNA vaccine.

    8. 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 [Day 0 to 180]

      hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses at relevant time points (Days 0, 28, and 180) and analyzed by dose (5, 10, and 25 µg)

    9. hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMFR [Day 0 to 180]

      : hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses at relevant time points (Days 0, 28, and 180) and analyzed by dose (5, 10, and 25 µg).

    10. hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as SRR [Day 0 to 180]

      hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins at relevant time points (Days 0, 28, and 180)and analyzed by previous vaccine combination received. Derived/calculated endpoints based on these data will include SRRs.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 50 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.

    5. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.

    6. 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.

    7. 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.

    8. 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).

    9. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study.

    10. 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.

    11. 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).

    12. 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).

    13. Participants with a history of myocarditis or pericarditis.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 ARS-Birmingham CRU Birmingham Alabama United States 35216
    2 Tucson Neuroscience Research Tucson Arizona United States 85710
    3 Velocity Clinical Research, Banning Banning California United States 99202
    4 Velocity Clinical Research, Chula Vista Chula Vista California United States 91911
    5 Velocity Clinical Research, San Diego La Mesa California United States 91942
    6 Artemis Institute for Clinical Research Riverside California United States 92503
    7 Artemis - San Diego San Diego California United States 92103
    8 Deland CRU DeLand Florida United States 32720
    9 Wr-Msra, Llc Lake City Florida United States 32055
    10 Professional Urgent Care Services Largo Florida United States 33777
    11 Research Institute of South Florida Miami Florida United States 33173
    12 Suncoast Research Associates, LLC Miami Florida United States 33173
    13 Health Awareness Miami Florida United States 33458
    14 Headlands Research Orlando LLC Orlando Florida United States 32819
    15 Precision Clinical Research, LLC Sunrise Florida United States 33351
    16 TrueBlue Clinical Research Tampa Florida United States 33609
    17 Neurostudies CRU Decatur Georgia United States 30030
    18 Velocity Clinical Research Savannah Georgia United States 31406
    19 CRA Headlands LLC Stockbridge Georgia United States 30281
    20 Velocity Clinical Research Sioux City Iowa United States 51106
    21 Velocity Clinical Research Baton Rouge Louisiana United States 70809
    22 Velocity Clinical Research - Covington Covington Louisiana United States 70433
    23 Velocity Clinical Research, Metairie Metairie Louisiana United States 70006
    24 Activmed Practices and Research, LLC Methuen Massachusetts United States 01844
    25 Velocity Clinical Research, Gulfport Gulfport Mississippi United States 39503
    26 Velocity Clinical Research Grand Island Nebraska United States 68803
    27 Velocity Clinical Research Norfolk Nebraska United States 68701
    28 Velocity Clinical Research Omaha Nebraska United States 68134
    29 Activmed Practices and Research, LLC Portsmouth New Hampshire United States 03801
    30 Velocity Clinical Research Binghamton New York United States 13905
    31 Hypercore (Lucas Research) New Bern North Carolina United States 28562
    32 M3 Wake Research Inc Raleigh North Carolina United States 27612
    33 Trial Management Associates, LLC Wilmington North Carolina United States 28403
    34 Javara Inc./Wake Forest Health Network, LLC Winston-Salem North Carolina United States 27157
    35 Velocity Clinical Research Cincinnati Ohio United States 45219
    36 Velocity Clinical Research Cincinnati Ohio United States 45246
    37 Tekton Research Edmond Oklahoma United States 73013
    38 Lynn Health Science Institute Oklahoma City Oklahoma United States 73112
    39 Velocity Clinical Research, Grants Pass Grants Pass Oregon United States 97527
    40 Velocity Clinical Research, Providence East Greenwich Rhode Island United States 02818
    41 Velocity Clinical Research, Gaffney Gaffney South Carolina United States 29340
    42 Coastal Carolina Research Center an ALCANZA Clinical Research company North Charleston South Carolina United States 29405
    43 Central Texas Clinical Research, LLC Austin Texas United States 78705
    44 Research Your Health Plano Texas United States 75093
    45 Benchmark Research San Angelo Texas United States 76904
    46 Velocity Clinical Research, Salt Lake City West Jordan Utah United States 84088
    47 Health Research of Hampton Roads, Inc Newport News Virginia United States 23606
    48 Clinical Research Partners Richmond Virginia United States 23226

    Sponsors and Collaborators

    • Novavax

    Investigators

    • Study Director: Clinical Development, Novavax

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novavax
    ClinicalTrials.gov Identifier:
    NCT05925127
    Other Study ID Numbers:
    • 2019nCoV-205
    First Posted:
    Jun 29, 2023
    Last Update Posted:
    Jul 6, 2023
    Last Verified:
    Jul 1, 2023
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Additional relevant MeSH terms:
    COVID-19
    Vaccines

    Study Results

    No Results Posted as of Jul 6, 2023