Clinical trial NCT05468736: Study to Evaluate Safety and Immunogenicity of COVID-19 Vaccine in Children 6 Months to < 12 Years
Official title: A Phase 2/3 Age De-escalating Study to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 Recombinant Spike Protein Vaccine (SARS-CoV-2 rS) With Matrix-M™ Adjuvant in Children 6 Months to < 12 Years of Age
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: COVID-19
Lead sponsor: Novavax
Sponsor class: INDUSTRY
First posted: 2022-07-21
Enrollment: 3600
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: This is a Phase 2/3 randomized, observer-blinded, placebo-controlled, age de-escalation trial to evaluate the safety and immunogenicity of 2 primary doses of SARS-CoV-2 rS with Matrix-M™ adjuvant (NVX-CoV2373) given 21 days apart and NVX CoV2373 or a variant-based vaccine given as a booster dose or at crossover in pediatric participants (3 age cohorts; 6 to \< 12 years, 2 to \< 6 years, and 6 to \< 24 months of age). Each age cohort will be conducted in 2 parts starting with the oldest age cohort (6 to \< 12 years of age).

Detailed description: This is a Phase 2/3 randomized, observer-blinded, placebo-controlled, age de-escalation trial to evaluate the safety and immunogenicity of 2 primary doses of SARS-CoV-2 rS with Matrix-M™ adjuvant (NVX-CoV2373) given 21 days apart and NVX CoV2373 or a variant-based vaccine given as a booster dose or at crossover in pediatric participants (3 age cohorts; 6 to \< 12 years, 2 to \< 6 years, and 6 to \< 24 months of age).

Each age cohort will be conducted in 2 parts starting with the oldest age cohort (6 to \< 12 years of age).

Part 1 will enroll approximately 120 healthy or medically stable sentinel participants per age cohort (10% of the intended enrollment population per age cohort, for a total of 360 sentinel participants overall) who will be randomized in a 1:1 ratio to receive 2 doses of NVX-CoV2373 or placebo with doses given 21 days apart.

Part 2 will enroll a larger number of healthy or medically stable participants (N= approximately 1,080 per age cohort), for a total of approximately 3,240 pediatric participants enrolled in Part 2, and a total of approximately 3,600 participants enrolled in the entire trial). Initial randomization in Part 2 will be in a 2:1 ratio, and the safety and effectiveness of 2 doses of NVX-CoV2373 given 21 days apart will be assessed.

Eligibility criteria: Inclusion Criteria:

To be included in this study, each individual must satisfy all of the following criteria:

1. Pediatric participants 6 months to \< 12 years of age at randomization, determined to be healthy or medically stable 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 the normal range prior to the first vaccination, according to the child's age, sex, weight, and height/length.
2. For children from 6 months to \< 12 months of age: born at full-term (≥ 37 weeks gestation) with a minimum birth weight of 2.5 kilograms (kg).
3. Participant and parent(s)/caregiver(s) or legally acceptable representative willing and able to give informed consent and assent, as required, prior to study enrollment and to comply with study procedures.
4. Participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile \[ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy\]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through 3 months after the last vaccination OR agree to consistently use a highly effective contraception method from at least 28 days prior to enrollment and through 3 months after the last vaccination.
5. Agree not to participate in another SARS-CoV-2 prevention trial for the duration of the study.

Exclusion Criteria:

If an individual meets any of the following criteria, he or she is ineligible for this study:

1. Any acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 100.4°F \[≥ 38.0°C\]). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided.
2. Unstable acute or chronic illness. Criteria for unstable medical conditions include:

   1. Substantive changes in chronic prescribed medication (change in class or significant change in dose) in the past 2 months.
   2. Currently undergoing workup of undiagnosed illness that could lead to a diagnosis of a new condition.

   NOTE: Well-controlled human immunodeficiency virus \[HIV\] infection with undetectable HIV ribonucleic acid \[RNA \< 50 copies/mL\] and CD4 count \> 200 cells/µL for at least 1 year, documented within the last 6 months, is NOT considered an unstable chronic illness. Participant's or parent's/caregiver's verbal report will suffice as documentation.
3. Participation in research involving an investigational product (drug/biologic/device) administered within 45 days prior to the first study vaccination.
4. History of a previous laboratory-confirmed diagnosis of SARS-CoV-2 infection or COVID-19.
5. Prior administration of an investigational, authorized, or approved Coronavirus vaccine (ie, against either SARS-CoV, SARS-CoV-2, or MERS CoV) or expected receipt during the period of study follow-up.
6. Previous or current diagnosis of MIS-C.
7. Receipt of medications intended to prevent or treat COVID-19.
8. Received any vaccine within 14 days prior to first study vaccination or planned receipt of any vaccine before Day 49 (ie, 28 days after the second vaccination), except for influenza vaccination, which may be received \> 14 days prior to or \> 14 days after any study vaccination.
9. Known or suspected congenital or acquired immunodeficiency or autoimmune disease/condition; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for \> 14 continuous days) within 90 days prior to first study vaccination. NOTE: An immunosuppressant dose of glucocorticoid is defined as a systemic dose ≥ 20 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids is permitted. Topical tacrolimus and ocular cyclosporin are permitted. Stable autoimmune endocrine disorders (eg, thyroiditis, pancreatitis), including stable diabetes mellitus type 1, or participants with a history of Kawasaki disease are NOT excluded.
10. Received immunoglobulin or blood-derived products within 90 days prior to first study vaccination.
11. Active cancer (malignancy) on chemotherapy within 1 year prior to first study vaccination (with the exception of malignancy cured via excision, at the discretion of the investigator).
12. Any known allergies to products contained in the investigational product.
13. Participants who are breastfeeding a child, pregnant or who plan to become pregnant within 3 months following the last study vaccination.
14. Any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled or could interfere with the evaluation of the trial vaccine or interpretation of study results.
15. Study team member or first-degree relative of any study team member (inclusive of Sponsor, and study site personnel involved in the study).
16. Current participation in any other COVID-19 prevention clinical trial.
17. Participants with a history of myocarditis or pericarditis.

Primary outcomes:
measure: Reactogenicity Incidence and Severity
timeFrame: Day 0 to Day 7
measure: Incidence and Severity of Medically Attended Adverse Events (MAAEs)
timeFrame: Day 0 to Day 28
measure: Incidence and Severity of Unsolicited Adverse Events (AEs)
timeFrame: Day 0 to Day 28
measure: Incidence and Severity of MAAEs Attributed to Study Vaccine
timeFrame: Day 0 to Day 730
measure: Incidence and Severity of Serious Adverse Events (SAEs)
timeFrame: Day 0 to Day 730
measure: Incidence and Severity of Adverse Events of Special Interest (AESIs)
timeFrame: Day 0 to Day 730
measure: Death due to any cause
timeFrame: Day 0 to Day 730
Secondary outcomes:
measure: Participants with PCR positive mild, moderate or severe COVID-19 after the primary series of 2 doses
timeFrame: Day 0 to Day 730
measure: Participants with PCR positive moderate or severe COVID-19 after the primary series of 2 doses
timeFrame: Day 0 to Day 730
measure: Participants with diagnostic test - positive asymptomatic, mild, moderate or severe COVID-19 after the primary series of 2 doses
timeFrame: Day 0 to Day 730
measure: Participants with diagnostic test - positive moderate or severe COVID-19 after the primary series of 2 doses
timeFrame: Day 0 to Day 730
measure: Participants with PCR positive mild, moderate or severe COVID-19 after the booster dose
timeFrame: Day 0 to Day 730
measure: Participants with PCR positive moderate or severe COVID-19 after the booster dose
timeFrame: Day 0 to Day 730
measure: Participants with diagnostic test - positive asymptomatic, mild, moderate or severe COVID-19 after the booster dose
timeFrame: Day 0 to Day 730
measure: Participants with diagnostic test moderate or severe COVID-19 after the booster dose
timeFrame: Day 0 to Day 730
measure: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Specified Time Points
timeFrame: Day 0 to Day 730
measure: Neutralizing antibody response, post-booster, by age cohort,seronegative to anti-SARS-CoV-2 NP antibodies at baseline and pre-booster
timeFrame: Day 0 to Day 28
measure: Neutralizing antibody response, by age cohort, regardless of serostatus at baseline and pre-booster
timeFrame: Day 0 to Day 28
measure: Serum IgG levels to SARS-CoV-2 S protein, post-booster, by age cohort, regardless of serostatus at baseline and pre-booster vaccination
timeFrame: Day 0 to Day 28
measure: Serum IgG levels to SARS-CoV-2 S protein, post booster, by age cohort, regardless of serostatus at baseline and pre-booster
timeFrame: Day 0 to Day 28
measure: Serum IgG levels to SARS-CoV-2 S protein , post booster, by age cohort, regardless of serostatus at baseline and pre-booster
timeFrame: Day 0 to Day 35
measure: Neutralizing antibody response for pediatric participants and adult participants expressed as Geometric Mean Titers (GMT)
timeFrame: Day 35
measure: Neutralizing antibody response for pediatric participants and adult participants expressed as Sero response (SRR)
timeFrame: Day 35
measure: Serum IgG levels to SARS-CoV-2 S protein after second injection of the initial vaccination series
timeFrame: Day 35
measure: Treatment and severity of COVID 19 after a PCR-confirmed case
timeFrame: Day 0 to Day 730
measure: Antibodies to SARS-CoV-2 NP, regardless of whether the infection was symptomatic.
timeFrame: Day 0 to Day 730
measure: Serum IgG levels to SARS-CoV-2 S protein expressed as GMT
timeFrame: Day 180 to Day 730
measure: MN titers to SARS-CoV-2 S protein expressed as GMT
timeFrame: Day 180 to Day 730
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Preferred Research Partners, Inc.
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Research Center
state: California
city: Bellflower
country: United States
facility: Coast Clinical Research, LLC
state: California
city: Fair Oaks
country: United States
facility: Apex Research Group
state: California
city: Long Beach
country: United States
facility: Ark Clinical Research
state: California
city: Ontario
country: United States
facility: Orange County Research Institute
state: California
city: San Diego
country: United States
facility: California Research Foundation
state: California
city: Walnut Creek
country: United States
facility: Clinical Research of California
state: California
city: Boynton Beach
country: United States
facility: Imagine Research of Palm Beach County
state: Florida
city: Brandon
country: United States
facility: Palm Harbor Dermatology PA
state: Florida
city: Jacksonville
country: United States
facility: Westside Center for Clinical Research
state: Florida
city: Miami
country: United States
facility: Cordova Research Institute, LLC
state: Florida
city: Orlando
country: United States
facility: ARS-Nona Pediatric Center
state: Florida
city: Atlanta
country: United States
facility: Morehouse School of Medicine
state: Georgia
city: Chamblee
country: United States
facility: Tekton Research - Atlanta
state: Georgia
city: Idaho Falls
country: United States
facility: Leavitt Clinical Research
state: Idaho
city: Lexington
country: United States
facility: Michael W. Simon, M.D., PSC
state: Kentucky
city: Louisville
country: United States
facility: Bluegrass Clinical Research, Inc./All Children Pediatrics
state: Kentucky
city: Covington
country: United States
facility: Velocity Clinical Research - Covington, LA
state: Louisiana
city: Covington
country: United States
facility: Velocity Clinical Research - Covington
state: Louisiana
city: Lafayette
country: United States
facility: Velocity Clinical Research - Lafayette LA
state: Louisiana
city: Bridgeton
country: United States
facility: Craig A. Spiegel, M.D.
state: Missouri
city: Missoula
country: United States
facility: Boeson Research
state: Montana
city: Lincoln
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Lincoln
country: United States
facility: Be Well Clinical Studies, LLC
state: Nebraska
city: Horseheads
country: United States
facility: Corning Center for Clinical Research
state: New York
city: Beachwood
country: United States
facility: Velocity Clinical Research
state: Ohio
city: Dayton
country: United States
facility: Dayton Clinical Research
state: Ohio
city: South Euclid
country: United States
facility: Senders Pediatrics
state: Ohio
city: Tulsa
country: United States
facility: Lynn Institute of Tulsa
state: Oklahoma
city: Grants Pass
country: United States
facility: Velocity Clinical Research Grants Pass
state: Oregon
city: Greenville
country: United States
facility: Tribe Clinical Research
state: South Carolina
city: Chattanooga
country: United States
facility: WR - ClinSearch, LLC
state: Tennessee
city: Nashville
country: United States
facility: Clinical Research Associates, Inc.
state: Tennessee
city: Beaumont
country: United States
facility: Tekton Research Beaumont
state: Texas
city: Brownsville
country: United States
facility: PanAmerican Clinical Research
state: Texas
city: Corpus Christi
country: United States
facility: South Texas Clinical Research
state: Texas
city: Dickinson
country: United States
facility: Bay Colony Pediatrics
state: Texas
city: Houston
country: United States
facility: Trio Clinical Trials
state: Texas
city: Houston
country: United States
facility: Mercury Clinical Research
state: Texas
city: Plano
country: United States
facility: Research Your Health
state: Texas
city: Richmond
country: United States
facility: Mercury Clinical Research - Pediatric Center
state: Texas
city: San Antonio
country: United States
facility: Tekton Research
state: Texas
city: Layton
country: United States
facility: Alliance for Multispecialty Research
state: Utah
city: Roy
country: United States
facility: Alliance for Multispecialty Research c/o Wee Care Pediatrics - Roy
state: Utah
city: West Jordan
country: United States
facility: Velocity Clinical Research - West Jordan
state: Utah
city: Richmond
country: United States
facility: Clinical Research Partners, LLC
state: Virginia
city: Medellin
country: Colombia
facility: Fundacion Centro de Investigacion Clinica - CIC
state: Antioquia
city: Barranquilla
country: Colombia
facility: Clinica de la costa
state: Atlantico
city: Puente Aranda
country: Colombia
facility: Centro de Atencion e Investigacion Medica S.A.S-CAIMED
state: Bogota
city: Yopal
country: Colombia
facility: Centro de Atencion e Investigacion Medica - CAIMED
state: Casanare
city: Floridablanca
country: Colombia
facility: Fundacion Oftalmologica de Santander - FOSCAL
state: Santander
city: Cali
country: Colombia
facility: Centro de Estudios en Infectologia Pediatrica S.A.S.CEIP
state: Valle Del Cauca
city: Santo Domingo
country: Dominican Republic
facility: PROBEBE en Hospital Universitario Maternidad Nuestra Senora de la Altagracia
state: Distrito Nacional
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dermatologico y Cirugia de Piel Dr. Huberto Bogaert Diaz IDCP
state: Distrito Nacional
city: Santo Domingo
country: Dominican Republic
facility: MEDYVAC INTERNACIONAL SRL en Clinica Cruz Jiminian
state: Distrito Nacional
city: Santo Domingo
country: Dominican Republic
facility: Registrum Group (Hospital Regional Marcelino Velez)
state: Distrito Nacional
city: Santo Domingo
country: Dominican Republic
facility: Registrum Group (Hospital Materno Infantil San Lorenzo de Los Mina)
state: Distrito Nacional
city: Guatemala
country: Guatemala
facility: Centro de Investigaciones Pediátricas (CIP)
city: Guatemala
country: Guatemala
facility: SMI (Servicios Medicos Integrales)
city: Guatemala
country: Guatemala
facility: CECLISA
city: San Pedro Sula
country: Honduras
facility: DEMEDICA
state: Cortés
city: Tegucigalpa
country: Honduras
facility: Inverime S.A.
state: Francisco Morazan
city: Tegucigalpa
country: Honduras
facility: Investigacion Sin Limites
state: Francisco Morazan
city: Tlalpan
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
state: Ciudad De Mexico
city: Guadalajara
country: Mexico
facility: Panamerican Clinical Research S.A de C.V.
state: Jalisco
city: Tlalpan
country: Mexico
facility: Innovacion y Desarrollo en Ciencias de la Salud (IDeCSa)
state: Mexico City
city: Cuernavaca
country: Mexico
facility: Panamerican Clinical Research, Mexico S.A de C.V.
state: Morelos
city: Mérida
country: Mexico
facility: Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion Clinica en Yucatan S.C.P.
state: Yucatan
city: Queretaro
country: Mexico
facility: Panamerican Clinical Research Mexico S.A. de C.V. (Queretaro Site)
city: Tlalnepantla
country: Mexico
facility: Clinical Research Institute S.C.
city: Veracruz
country: Mexico
facility: FAICIC S. de R.L. de C.V.
city: San Juan
country: Philippines
facility: University of the Philippines Manila - National Institutes of Health (NIH) - Institute of
state: Batangas
city: Manila
country: Philippines
facility: Manila Doctors Hospital
state: Metro Manila
city: Manila
country: Philippines
facility: University of the Philippines - Philippine General Hospital
state: Metro Manila
city: Quezon City
country: Philippines
facility: National Children's Hospital
state: Metro Manila
city: Quezon City
country: Philippines
facility: FEU-NRMF
state: Metro Manila
city: Lucena
country: Philippines
facility: Medical Mission Group Hospital-Lucban and Southern Luzon State University
state: Quezon
city: Boksburg
country: South Africa
facility: REIMED Riger Park
state: Gauteng
city: Ga-Tshwene
country: South Africa
facility: Setshaba Research Centre
state: Gauteng
city: Johannesburg
country: South Africa
facility: Soweto Clinical Trials Centre
state: Gauteng
city: Johannesburg
country: South Africa
facility: WiWits RHI - Shandukani Research Centre
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits Vida Nkanyezi Site- Rahima Moosa Mother and Child Hospital
state: Gauteng
city: Soweto
country: South Africa
facility: Wits Vida- Chris Hani Baragwanath Hospital
state: Gauteng
city: Thabazimbi
country: South Africa
facility: Limpopo Clinical Research Initiative
state: Limpopo
city: Bellville
country: South Africa
facility: Tiervlei Trial Centre
state: Western Cape
city: Paarl
country: South Africa
facility: Be Part Yoluntu Centre - Paarl
state: Western Cape
city: Worcester
country: South Africa
facility: Stellenbosch University Worcester
state: Western Cape
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
state: A Coruña
city: Leganés
country: Spain
facility: Hospital Universitario Severo Ochoa
state: Madrid
city: Torrejon de Ardoz
country: Spain
facility: Hospital Universitario de Torrejon
state: Madrid
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Corby
country: United Kingdom
facility: Lakeside Healthcare Research
state: Northamptonshire
city: London
country: United Kingdom
facility: St Georges Hospital
Study officials:
affiliation: Novavax, Inc.
name: Clinical Development
role: STUDY_DIRECTOR
References: