Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines

COVID-19 Clinical Trial

— COVID-19  

Official title:

A Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adolescents Previously Vaccinated With mRNA COVID-19 Vaccines

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05973006
• Other study ID #: 2019nCoV-314
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 16, 2023
• Est. completion date: August 26, 2024

Study information

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

Clinical Trial Summary

This study is a large-scale investigation (Phase 3) into a new booster shot designed specifically for teenagers. The booster targets a particular variant of COVID-19, Omicron XBB.1.5. The main focus is on safety: researchers want to see if this new booster is safe for teenagers who have already received two doses of the Pfizer or Moderna mRNA COVID-19 vaccines. To ensure a fair comparison, the study will use a double-blind approach. This means two groups of teenagers will receive booster shots, but neither the teenagers nor the researchers giving the shots will know beforehand which version of the booster each person gets. The study will also assess how well the body fights the virus after the booster shot.

Description:

This is a Phase 3, randomized, double-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-CoV2601 [Omicron XBB.1.5]) and bivalent (NVX-CoV2373 [prototype] + NVX CoV2601) in previously vaccinated adolescent participants ≥ 12 to < 18 years of age.

Approximately 400 adolescents who have received a regimen of ≥ 2 doses of the Moderna and/or Pfizer-BioNTech monovalent and/or bivalent COVID-19 vaccines ≥ 90 days previously will be randomized 1:1 to Group A or Group B:

• Group A: 1 dose of NVX-CoV2601 (1 on Day 0)

• Group B: 1 dose of bivalent NVX-CoV2373 + NVX-CoV2601 (1 on Day 0) All participants will remain on study for immunogenicity and safety data collection through Day 180.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 400
• Est. completion date: August 26, 2024
• Est. primary completion date: May 17, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 11 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Adolescents = 12 to < 18 years of age at screening

2. Participant and parent(s)/caregiver(s) or legally acceptable representative willing and able to give in-formed consent and assent, as required, prior to study enrollment and to comply with study procedures.

3. 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 post-menopausal [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 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 monovalent and/or bivalent COVID-19 vaccines with the last dose having been given = 90 days previously prior to study vaccination.

Exclusion Criteria:

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 influenza vaccination within 14 days prior to study vaccination.

4. Received any vaccine = 45 days prior to study vaccination, except for rabies, human papilloma virus (HPV), tetanus-diphtheria (Td), tetanus, diphtheria, and pertussis (TDaP/DTap), hepatitis B virus (HBV), and meningococcal vaccines which may be given as medically indicated.

5. Any known allergies to products contained in the investigational product.

6. Any history of anaphylaxis to any prior vaccine.

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

8. Chronic administration (defined as > 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to study vaccination.

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.

9. 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.

10. 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).

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

12. 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.

13. 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).

14. 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).

15. Participants with a history of myocarditis or pericarditis.

16. Respiratory symptoms in the past 3 days (ie, cough, sore throat, difficulty breathing).

17. Temperature of > 38°C within 24 hours of planned study vaccination (site measured or participant measured).

18. Blood pressure of = 160/100 mmHg.

Related Conditions & MeSH terms

• COVID-19

Intervention

Biological:
• NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine
Coformulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine with Matrix-M adjuvant: supplied as a solution for preparation for injection, at a concentration of 10 µg antigen and 100 µg adjuvant per mL. All injections will be administered in a 0.5 mL injection volume at a dose of 5 µg antigen with 50 µg Matrix-M adjuvant.
• Prototype/XBB.1.5 Bivalent Vaccine (5 µg)
A site-mixed bivalent vaccine prepared by combining 0.25 mL of NVX-CoV2373 and 0.25 mL NVX-CoV2601. All injections will be administered in a 0.5 mL injection volume at a dose of 5 µg total antigen (2.5 µg prototype antigen + 2.5 µg Omicron XBB.1.5 antigen) with 50 µg Matrix-M adjuvant.

Locations

Country	Name	City	State
United States	Benchmark Research	Austin	Texas
United States	Velocity Clinical Research	Cincinnati	Ohio
United States	South Texas Clinical Research	Corpus Christi	Texas
United States	Alfa Medical Research	Davie	Florida
United States	DM Clinical Research	Houston	Texas
United States	Westside Center for Clinical Research	Jacksonville	Florida
United States	Medical Colleagues of Texas, LLP	Katy	Texas
United States	Velocity Clinical Research	Lafayette	Louisiana
United States	Johnson County Clinical Trials	Lenexa	Kansas
United States	Velocity Clinical Research	Meridian	Idaho
United States	ITB Research	Miami	Florida
United States	Clinical Research Associates, Inc	Nashville	Tennessee
United States	Alliance for Multispecialty Research, LLC (AMR)	Newton	Kansas
United States	Research Your Health	Plano	Texas
United States	Mountain View CCT Research	Pleasant View	Utah
United States	DM Clinical Research - Chicago	River Forest	Illinois
United States	Tekton Research	San Antonio	Texas
United States	Tekton Research	Tulsa	Oklahoma
United States	Velocity Clinical Research	Vestal	New York
United States	AMR	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Novavax

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Incidence, duration, and severity of solicited local and systemic AEs for 7 days following vaccination	Incidence, duration, and severity of solicited local and systemic adverse events (AEs) To assess the overall safety of 1 heterologous booster dose of NVX CoV2601 and the bivalent vaccine (NVX CoV2373 + NVX-CoV2601) for 7 days following vaccination	Day 7
Primary	Safety: Incidence, severity, and relationship of unsolicited AEs through 28 days after vaccination	Incidence, severity, and relationship of unsolicited AEs to assess the overall safety of 1 heterologous booster dose of NVX CoV2601 and the bivalent vaccine (NVX CoV2373 + NVX-CoV2601) through 28 days after vaccination.	Day 28
Primary	Safety: Incidence and severity of (MAAEs) attributed to study vaccine, (AESIs) (PIMMCs), myocarditis and/or pericarditis, and complications specific to COVID-19), and serious adverse events (SAEs)	Incidence and severity of medically attended adverse events (MAAEs) attributed to study vaccine, adverse events of special interest (AESIs) (predefined list including potential immune-mediated medical conditions (PIMMCs), myocarditis and/or pericarditis, and complications specific to COVID-19), and serious adverse events (SAEs) o assess the overall safety of 1 heterologous booster dose of NVX CoV2601 and the bivalent vaccine (NVX CoV2373 + NVX-CoV2601)through day 180 or end of study (EOS).	Day 180
Primary	Immunogenicity index- Neutralizing antibody (NAb) expressed as geometric mean titers (GMTs) to the Omicron XBB.1.5 strain.	The neutralizing antibody (NAb) response induced by NVX CoV2601 and the bivalent vaccine (NVX CoV2373 + NVX-CoV2601) against the Omicron XBB.1.5 strain assessed at Day 28 following initial study vaccination.	Day 28
Primary	Immunogenicity index- The Neutralizing antibody (NAb) expressed as geometric mean fold rise (GMFR) to the Omicron XBB.1.5 strain.	the neutralizing antibody (NAb) response induced by NVX CoV2601 and the bivalent vaccine (NVX CoV2373 + NVX-CoV2601) against the Omicron XBB.1.5 strain, assessed at Day 28 from baseline (Day 0).	Day 28
Secondary	Neutralizing antibody (NAb) expressed as geometric mean titers (GMTs) to the Omicron XBB.1.5 strain.	the neutralizing antibody NAb response induced by NVX CoV2601 and the bivalent vaccine (NVX CoV2373 + NVX-CoV2601) against the Omicron XBB.1.5 strain over time. at relevant time points (Days 0, 90, and 180).	Day 0 to Day 180
Secondary	Neutralizing antibody (NAb) expressed as geometric mean fold rise (GMFR) to the Omicron XBB.1.5 strain.	The neutralizing antibody NAb response induced by NVX CoV2601 and the bivalent vaccine (NVX CoV2373 + NVX-CoV2601) against the Omicron XBB.1.5 strain over time. at relevant time points (Days 0, 90, and 180).	Day 0 to Day 180
Secondary	IgG geometric mean ELISA (enzyme-linked immunosorbent assay) units (GMEUs) to the Omicron XBB.1.5 S protein.	The immunoglobulin G (IgG) antibody levels induced by NVX CoV2601 and the bivalent vaccine (NVX CoV2373 + NVX-CoV2601) against the Omicron XBB.1.5 strain over time.at relevant time points (Days 0, 28, 90, and 180).	Day 0 to Day 180
Secondary	NAb(neutralizing antibody titers) and IgG GMEUs levels are measured to the ancestral (Wuhan) strain .	The NAb and IgG antibody responses induced by NVX CoV2601 and the bivalent vaccine (NVX CoV2373 + NVX-CoV2601) against the ancestral (Wuhan) strain at relevant time points (Days 0, 28, 90, and 180).	Day 0 to 180
Secondary	human angiotensin-converting enzyme-2 (hACE2) receptor binding assay of Omicron XBB.1.5 and ancestral (Wuhan) strains expressed as GMT.	The antibody responses in a human angiotensin-converting enzyme-2 (hACE2) receptor binding inhibition assay induced by NVX CoV2601 and the bivalent vaccine (NVX CoV2373 + NVX-CoV2601) to the Omicron XBB.1.5 and ancestral (Wuhan) strains to relevant time points (Days 0, 28, 90, and 180). expressed as GMT	Day 0 to 180