COVID-19: Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 3 |
Detailed 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:
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Group A: 1 dose of NVX-CoV2601 (1 on Day 0)
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group-A NVX-CoV2601 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
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.
Other Names:
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| Active Comparator: Group-B Bivalent NVX CoV2373 + NVX CoV2601 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)
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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Safety: Incidence, duration, and severity of solicited local and systemic AEs for 7 days following vaccination [Day 7[ following 1st 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
- Safety: Incidence, severity, and relationship of unsolicited AEs through 28 days after vaccination [Day 28[ following 1st 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.
- 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) [Day 180]
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).
- Immunogenicity index- Neutralizing antibody (NAb) expressed as geometric mean titers (GMTs) to the Omicron XBB.1.5 strain. [Day 28]
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.
- Immunogenicity index- The Neutralizing antibody (NAb) expressed as geometric mean fold rise (GMFR) to the Omicron XBB.1.5 strain. [Day-28]
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).
Secondary Outcome Measures
- Neutralizing antibody (NAb) expressed as geometric mean titers (GMTs) to the Omicron XBB.1.5 strain. [Day- 0,90, and 180]
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).
- Neutralizing antibody (NAb) expressed as geometric mean fold rise (GMFR) to the Omicron XBB.1.5 strain. [0,90, and 180]
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).
- IgG geometric mean ELISA (enzyme-linked immunosorbent assay) units (GMEUs) to the Omicron XBB.1.5 S protein. [Day 0, 28, 90, and 180]
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).
- NAb(neutralizing antibody titers) and IgG GMEUs levels are measured to the ancestral (Wuhan) strain . [Day 0 to 180]
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).
- human angiotensin-converting enzyme-2 (hACE2) receptor binding assay of Omicron XBB.1.5 and ancestral (Wuhan) strains expressed as GMT. [Day 0 to 180]
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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adolescents ≥ 12 to < 18 years of age at screening
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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.
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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.
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Condoms (male or female) with spermicide (if acceptable in country)
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Diaphragm with spermicide
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Cervical cap with spermicide
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Intrauterine device
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Oral or patch contraceptives
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Norplant®, Depo-Provera®, or other in country regulatory approved contraceptive method that is de-signed to protect against pregnancy
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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.
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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.
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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:
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Received COVID-19 vaccines other than Moderna and/or Pfizer-BioNTech in the past, inclusive of clini-cal trial COVID-19 vaccines.
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Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to study vaccination.
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Received influenza vaccination within 14 days prior to study vaccination.
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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.
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Any known allergies to products contained in the investigational product.
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Any history of anaphylaxis to any prior vaccine.
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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.
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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.
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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).
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Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study.
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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.
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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).
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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).
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Participants with a history of myocarditis or pericarditis.
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Respiratory symptoms in the past 3 days (ie, cough, sore throat, difficulty breathing).
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Temperature of > 38°C within 24 hours of planned study vaccination (site measured or participant meas-ured).
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Blood pressure of ≥ 160/100 mmHg.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Novavax
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2019nCoV-314