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

Study Overview
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Brief Summary
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This is 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.

Detailed Description
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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.

Official Title
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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

Conditions
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COVID-19

Intervention / Treatment
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* Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine
* Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adolescents ≥ 12 to < 18 years of age at screening 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. 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. Condoms (male or female) with spermicide (if acceptable in country) Diaphragm with spermicide Cervical cap with spermicide Intrauterine device Oral or patch contraceptives Norplant®, Depo-Provera®, or other in country regulatory approved contraceptive method that is de-signed to protect against pregnancy Abstinence, as a form of contraception, is acceptable if in line with the participant's lifestyle NOTE: Periodic abstinence (eg, calendar, ovulation, sympto-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Is medically stable, as determined by the investigator (based on review of health status, vital signs [to in-clude body temperature], medical history, and targeted physical examination [to include body weight]). Vital signs must be within medically acceptable ranges prior to the vaccination. Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study. NOTE: For participants who become hospitalized with COVID-19, participation in investigational treatment studies is permitted. 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: Received COVID-19 vaccines other than Moderna and/or Pfizer-BioNTech in the past, inclusive of clini-cal trial COVID-19 vaccines. Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to study vaccination. Received influenza vaccination within 14 days prior to study vaccination. 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. Any known allergies to products contained in the investigational product. Any history of anaphylaxis to any prior vaccine. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing im-munomodulatory therapy. NOTE: Stable endocrine disorders (eg, thyroiditis, pancreatitis), including stable diabetes mellitus with no history of diabetic ketoacidosis) are NOT excluded. Chronic administration (defined as > 14 continuous days) of immunosuppressant, systemic glucocorti-coids, 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. 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. 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). Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study. 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. 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 (includ-ing neurologic or psychiatric conditions likely to impair the quality of safety reporting). 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). Participants with a history of myocarditis or pericarditis. Respiratory symptoms in the past 3 days (ie, cough, sore throat, difficulty breathing). Temperature of > 38°C within 24 hours of planned study vaccination (site measured or participant meas-ured). Blood pressure of ≥ 160/100 mmHg.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group-A NVX-CoV2601<br>The Monovalent NVX-CoV2601 of 5 μg of antigen with 50 μg of Matrix-M adjuvant | Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine<br>* 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.<br>* Other names: NVX-CoV2601;|
| Active Comparator: Group-B Bivalent NVX CoV2373 + NVX CoV2601<br>The Bivalent NVX CoV2373 + NVX CoV2601 of 5 μg of each antigen with a total of 50 μg of Matrix-M adjuvant | Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)<br>* 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.<br>* Other names: Omicron XBB.1.5 (sub-variant)SARS-CoV-2 rS /Matrix-M Adjuvant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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[ following 1st vaccination] | 
| 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[ following 1st vaccination] | 
| 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 | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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- 0,90, and 180 | 
| 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). | 0,90, and 180 | 
| 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, 28, 90, and 180 | 
| 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 | 
| 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 |