Clinical trial NCT05973006: Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: Novavax
Sponsor class: INDUSTRY
First posted: 2023-08-02
Enrollment: 400
Sex: ALL
Minimum age (years): 11
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief 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.

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:

* 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety: Incidence, duration, and severity of solicited local and systemic AEs for 7 days following vaccination
timeFrame: Day 7
measure: Safety: Incidence, severity, and relationship of unsolicited AEs through 28 days after vaccination
timeFrame: Day 28
measure: 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)
timeFrame: Day 180
measure: Immunogenicity index- Neutralizing antibody (NAb) expressed as geometric mean titers (GMTs) to the Omicron XBB.1.5 strain.
timeFrame: Day 28
measure: Immunogenicity index- The Neutralizing antibody (NAb) expressed as geometric mean fold rise (GMFR) to the Omicron XBB.1.5 strain.
timeFrame: Day 28
Secondary outcomes:
measure: Neutralizing antibody (NAb) expressed as geometric mean titers (GMTs) to the Omicron XBB.1.5 strain.
timeFrame: Day 0 to Day 180
measure: Neutralizing antibody (NAb) expressed as geometric mean fold rise (GMFR) to the Omicron XBB.1.5 strain.
timeFrame: Day 0 to Day 180
measure: IgG geometric mean ELISA (enzyme-linked immunosorbent assay) units (GMEUs) to the Omicron XBB.1.5 S protein.
timeFrame: Day 0 to Day 180
measure: NAb(neutralizing antibody titers) and IgG GMEUs levels are measured to the ancestral (Wuhan) strain .
timeFrame: Day 0 to 180
measure: human angiotensin-converting enzyme-2 (hACE2) receptor binding assay of Omicron XBB.1.5 and ancestral (Wuhan) strains expressed as GMT.
timeFrame: Day 0 to 180
Other outcomes:
Locations:
city: Davie
country: United States
facility: Alfa Medical Research
state: Florida
city: Jacksonville
country: United States
facility: Westside Center for Clinical Research
state: Florida
city: Miami
country: United States
facility: ITB Research
state: Florida
city: Meridian
country: United States
facility: Velocity Clinical Research
state: Idaho
city: River Forest
country: United States
facility: DM Clinical Research - Chicago
state: Illinois
city: Lenexa
country: United States
facility: Johnson County Clinical Trials
state: Kansas
city: Newton
country: United States
facility: Alliance for Multispecialty Research, LLC (AMR)
state: Kansas
city: Wichita
country: United States
facility: AMR
state: Kansas
city: Lafayette
country: United States
facility: Velocity Clinical Research
state: Louisiana
city: Vestal
country: United States
facility: Velocity Clinical Research
state: New York
city: Cincinnati
country: United States
facility: Velocity Clinical Research
state: Ohio
city: Tulsa
country: United States
facility: Tekton Research
state: Oklahoma
city: Nashville
country: United States
facility: Clinical Research Associates, Inc
state: Tennessee
city: Austin
country: United States
facility: Benchmark Research
state: Texas
city: Corpus Christi
country: United States
facility: South Texas Clinical Research
state: Texas
city: Houston
country: United States
facility: DM Clinical Research
state: Texas
city: Katy
country: United States
facility: Medical Colleagues of Texas, LLP
state: Texas
city: Plano
country: United States
facility: Research Your Health
state: Texas
city: San Antonio
country: United States
facility: Tekton Research
state: Texas
city: Pleasant View
country: United States
facility: Mountain View CCT Research
state: Utah
Study officials:
affiliation: Novavax
name: Clinical Development
role: STUDY_DIRECTOR
References: