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

COVID-19 Clinical Trial

— COVID-19  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05925127
• Other study ID #: 2019nCoV-205
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: October 16, 2023
• Est. completion date: November 14, 2024

Study information

• Verified date: May 2024
• Source: Novavax
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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]).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 994
• Est. completion date: November 14, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

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
• 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.
• 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.
• 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.
• 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.
• 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
• 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

Locations

Country	Name	City	State
United States	Central Texas Clinical Research, LLC	Austin	Texas
United States	Velocity Clinical Research, Banning	Banning	California
United States	Velocity Clinical Research	Baton Rouge	Louisiana
United States	Velocity Clinical Research	Binghamton	New York
United States	ARS-Birmingham CRU	Birmingham	Alabama
United States	Velocity Clinical Research, Chula Vista	Chula Vista	California
United States	Velocity Clinical Research	Cincinnati	Ohio
United States	Velocity Clinical Research	Cincinnati	Ohio
United States	Velocity Clinical Research - Covington	Covington	Louisiana
United States	Neurostudies CRU	Decatur	Georgia
United States	Deland CRU	DeLand	Florida
United States	Velocity Clinical Research, Providence	East Greenwich	Rhode Island
United States	Tekton Research	Edmond	Oklahoma
United States	Velocity Clinical Research, Gaffney	Gaffney	South Carolina
United States	Velocity Clinical Research	Grand Island	Nebraska
United States	Velocity Clinical Research, Grants Pass	Grants Pass	Oregon
United States	Velocity Clinical Research, Gulfport	Gulfport	Mississippi
United States	Health Awareness	Jupiter	Florida
United States	Velocity Clinical Research, San Diego	La Mesa	California
United States	Wr-Msra, Llc	Lake City	Florida
United States	Professional Urgent Care Services	Largo	Florida
United States	Velocity Clinical Research	Meridian	Idaho
United States	Velocity Clinical Research, Metairie	Metairie	Louisiana
United States	Activmed Practices and Research, LLC	Methuen	Massachusetts
United States	Research Institute of South Florida	Miami	Florida
United States	Suncoast Research Associates, LLC	Miami	Florida
United States	Hypercore (Lucas Research)	New Bern	North Carolina
United States	Health Research of Hampton Roads, Inc	Newport News	Virginia
United States	Velocity Clinical Research	Norfolk	Nebraska
United States	Coastal Carolina Research Center an ALCANZA Clinical Research company	North Charleston	South Carolina
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Velocity Clinical Research	Omaha	Nebraska
United States	Headlands Research Orlando LLC	Orlando	Florida
United States	Research Your Health	Plano	Texas
United States	Activmed Practices and Research, LLC	Portsmouth	New Hampshire
United States	M3 Wake Research Inc	Raleigh	North Carolina
United States	Clinical Research Partners	Richmond	Virginia
United States	Artemis Institute for Clinical Research	Riverside	California
United States	Benchmark Research	San Angelo	Texas
United States	Artemis - San Diego	San Diego	California
United States	WR-MCCR	San Diego	California
United States	Velocity Clinical Research	Savannah	Georgia
United States	Velocity Clinical Research	Sioux City	Iowa
United States	CRA Headlands LLC	Stockbridge	Georgia
United States	Precision Clinical Research, LLC	Sunrise	Florida
United States	TrueBlue Clinical Research	Tampa	Florida
United States	Tucson Neuroscience Research	Tucson	Arizona
United States	Velocity Clinical Research, Salt Lake City	West Jordan	Utah
United States	Trial Management Associates, LLC	Wilmington	North Carolina
United States	Javara Inc./Wake Forest Health Network, LLC	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novavax

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunogenicity index-Neutralizing antibody expressed as geometric mean titer ratio[GMTR ]against the Omicron subvariant XBB.1.5	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	Day 28
Primary	Immunogenicity index-Neutralizing antibody expressed as seroresponse rates (SRRs)against the Omicron subvariant XBB.1.5	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.	Day 28
Secondary	Neutralizing antibody expressed as geometric mean titer ratio[GMTR ]against the Omicron subvariant XBB.1.5	Neutralizing antibody (GMTR) at relevant time points Days 28 to 180 from baseline (Day 0) and analyzed by dose (5, 10, and 25 µg)	Day 28
Secondary	Immunogenicity index- IgG antibody Anti-S expressed as geometric mean Elisa units GMEUs (EU/mL)	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)	Day 0 to 180
Secondary	Immunogenicity index- Neutralizing antibody titers of post-booster by baseline anti-SARS-CoV-2 NP	Neutralizing antibody titers of post-booster by baseline anti-SARS-CoV-2 NP status day-28	Day-28
Secondary	Immunogenicity index- Serum IgG levels to SARS-CoV-2 S protein at Day 28 of post-booster	Serum IgG levels to SARS-CoV-2 S protein at Day 28 post-booster by baseline anti-SARS-CoV-2 NP status.	Day-28
Secondary	Safety Index-Incidence, duration, and severity of solicited local and systemic AEs expressed as GMT	Incidence, duration, and severity of solicited local and systemic AEs for 7 days following vaccination.	7 days
Secondary	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)	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	Day 0 to 180
Secondary	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).	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.	Day 0 to 180
Secondary	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	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)	Day 0 to 180
Secondary	hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMFR	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).	Day 0 to 180
Secondary	hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as SRR	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.	Day 0 to 180

External Links

•   Novavax's COVID Vaccine: Explained