A Phase 3, Randomized, Observer-Blinded, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in Adult Participants ≥ 18 Years With a Pediatric Expansion in Adolescents (12 to < 18 Years)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Novavax
- 入组人数
- 33,000
- 试验地点
- 290
- 主要终点
- Pediatric Expansion: Reactogenicity Incidence and Severity
研究概览
简要总结
This is a phase 3, randomized, observer-blinded, placebo-controlled study to evaluate the efficacy, safety, and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant in adult participants and adolescent participants. Additionally providing a Booster Dose to fully vaccinated participants. A substudy is to be conducted at selected sites to evaluate the safety and immunogenicity of a fourth dose (second booster) of NVX-CoV2373 in adults and adolescents, previously fully vaccinated and subsequently boosted with a third dose (first booster)
详细描述
This is a Phase 3, randomized, observer-blinded, placebo-controlled study to evaluate the efficacy, safety, and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant in adult participants ≥ 18 years of age (Adult Main Study) and adolescent participants 12 to <18 years (Pediatric Expansion). Additionally, a Booster Amendment will allow for the evaluation of a booster dose of SARS-CoV-2 rS with Matrix-M1 adjuvant in participants who completed the primary series of active vaccine in the Adult Main Study or Pediatric Expansion, as well as in participants who previously completed the primary series of an authorized/approved COVID-19 vaccine. Additionally, a sub-study conducted at specific sites will allow for the evaluation of a second booster dose of SARS-CoV-2 rS with Matrix-M1 adjuvant in participants who completed the primary series of active vaccine in the Adult Main Study and Pediatric Expansion as well as a booster dose in the Booster Amendment of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult Participants :
- •Each participant in the Adult Main Study and/or the Booster Amendment must meet all of the following criteria to be enrolled in this study:
- •Adults ≥ 18 years of age at screening who, by virtue of age, race, ethnicity or life circumstances, are considered at substantial risk of exposure to and infection with SARS CoV-
- •Willing and able to give informed consent 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 [i.e., hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months]) 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 medically acceptable method of contraception from at least 28 days prior to enrollment and through 3 months after the last vaccination.
- •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 first vaccination.
- •Agree to not participate in any other SARS-CoV-2 prevention trial during the study follow-up.
- •For the Booster Amendment only, active participants who received a full dose regimen of active vaccine (SARS-CoV-2 rS with Matrix-M1 adjuvant) or any authorized/approved COVID-19 vaccine are eligible for participation. Such participants must demonstrate receipt by producing valid documentation of vaccination at the booster visit.
- •Pediatric Participants :
- •Each participant in the Pediatric Expansion and/or the Booster Amendment must meet all of the following criteria to be enrolled in this study:
- •Pediatric participants 12 to < 18 years of age at screening, 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 medically acceptable ranges prior to the first vaccination.
- •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.
- •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 medically acceptable method of contraception from at least 28 days prior to enrollment and through 3 months after the last vaccination.
- •Agree to not participate in another SARS-CoV-2 prevention trial during the study follow-up.
- •For the Booster Amendment only, active participants who received a full dose regimen of active vaccine (SARS-CoV-2 rS with Matrix-M1 adjuvant) or any authorized/approved COVID-19 vaccine are eligible for participation. Such participants must demonstrate receipt by producing valid documentation of vaccination.
- •Site-Specific Sub Study:
- •Each participant in the Substudy must meet all of the following criteria to be enrolled in this study:
- •Be an active, enrolled participant in the 2019nCoV-301 study.
- •Adults 18 years of age or older or adolescents 12 to < 18 years of age at initial screening for the parent study.
- •Willing and able to give informed consent prior to substudy enrollment and to comply with extra study procedures.
- •Documented receipt of the 2 doses of the primary series of NVX-CoV2373 and the booster (third dose) of NVX-CoV2373 in the parent protocol. The booster dose must have been administered at least 6 months prior to entering the substudy.
- •Participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile or postmenopausal) must agree to be heterosexually inactive from at least 28 days prior to entering and through the end of the substudy OR agree to consistently use a medically acceptable method of contraception for the 28 days of follow-up for the substudy.
- •Is medically stable, as determined by the investigator (based on review of health status, vital signs (to include body temperature) and targeted physical examination (if medically indicated by reported symptoms). Vital signs must be within medically acceptable ranges prior to administration of study vaccination.
- •Agree to not participate in any other non-NVX-CoV2373 study during the substudy.
- •Note: For participants who develop COVID-19, anti-SARS-CoV-2 therapy (approved, authorized or investigational) is permitted.
排除标准
- •Adult and adolescent participants meeting any of the following criteria will be excluded from the study:
- •Unstable acute or chronic illness. Criteria for unstable medical conditions include:
- •Substantive changes in chronic prescribed medication (change in class or significant change in dose) in the past 2 months.
- •Currently undergoing workup of undiagnosed illness that could lead to diagnosis of a new condition.
- •Note: Well-controlled human immunodeficiency virus [HIV] with undetectable HIV 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.
- •Participation in research involving an investigational product (drug/biologic/device) administered within 45 days prior to first study vaccination.
- •History of a previous laboratory-confirmed diagnosis of SARS-CoV-2 infection or COVID-
- •A previous diagnosis of COVID-19 during participation in this trial is not exclusionary for the Booster Amendment.
- •Received any vaccine within 4 days prior to first study vaccination or planned receipt of any vaccine before Day 49 (i.e., 28 days after second vaccination), except for influenza vaccination, which may be received ≥ 4 days prior to or ≥ 7 days after either study vaccination. Rabies vaccine, at any time it is medically indicated, is not exclusionary. Prior receipt of another approved or authorized COVID-19 vaccine prior to booster injection is not exclusionary in the Booster Amendment. Such participants must provide documentation of vaccine and date(s) of administration.
- •Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) or therapy that causes clinically significant immunosuppression. NOTE: Stable endocrine disorders (eg, thyroiditis, pancreatitis, including stable diabetes mellitus) are NOT excluded.
- •Chronic administration (defined as > 14 continuous days) of immunosuppressant or systemic glucocorticoids causing clinically significant immunocompromise, within 90 days prior to first study vaccination and/or third (booster) 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.
- •Received immunoglobulin or blood-derived products, within 90 days prior to first study vaccination and/or third (booster) vaccination.
- •Active cancer (malignancy) on chemotherapy that is judged to cause clinically significant immunocompromise within 1 year prior to first study vaccination (with the exception of malignancy cured via excision, at the discretion of the investigator). This criterion is not applicable to participants diagnosed during participation in this trial who accept participation in the Booster Amendment.
- •Any known allergies to products contained in the investigational product.
- •Participants who are breastfeeding, pregnant, or who plan to become pregnant within 3 months following last study vaccination.
- •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 trial vaccine or interpretation of study results.
- •Study team member or first-degree relative of any study team member (inclusive of Sponsor, and study site personnel involved in the study).
- •Current participation in any other COVID-19 prevention clinical trial.
- •Adult participants who have not received a full dose of any authorized/approved COVID-19 vaccine and are unable to provide valid documentation of vaccination will be excluded from the Booster Amendment.
- •Adult and adolescent participants meeting any of the following criteria will be excluded from the substudy:
- •History of laboratory-confirmed (by PCR or other antigen testing) COVID-19 infection ≤ 4 months prior to entering the substudy.
- •Known to be clinically significantly immunocompromised.
- •Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to entering substudy.
- •Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of substudy.
- •History of confirmed myocarditis and/or pericarditis since enrollment to the parent study.
- •Any condition that, in the opinion of the investigator, might pose a health risk to the participant, interfere with protocol compliance or interfere with evaluation of the trial vaccine.
- •Study team member or immediate family member of any study team member (inclusive of Sponsor, CRO, and study site personnel involved in the conduct or planning of the substudy).
结局指标
主要结局
Pediatric Expansion: Reactogenicity Incidence and Severity
时间窗: Day 0 to Day 27
Reactogenicity incidence and severity (mild, moderate or severe) recorded by all participants on their electronic patient-reported outcome diary application (eDiary) on days of vaccination and subsequent 6 days (total 7 days after each vaccine injection).
Pediatric Expansion: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Specified Time Points until Month 24
时间窗: Day 90 to Day 750
Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine and AESIs through specified time points until Month 24 or the EoS.
Adult Main Study and Pediatric Expansion: Participants with Symptomatic Mild, Moderate, or Severe Coronavirus Disease 2019 (COVID-19)
时间窗: Day 28 to Day 750
Number of participants with first occurrence of positive (+) polymerase chain reaction (PCR)-confirmed SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19, with each symptom lasting for at least 2 consecutive days, with onset from Day 28 (7 days after second vaccination dose) through the length of the study.
Pediatric Expansion: Incidence and Severity of Unsolicited Adverse Events (AEs) Through Day 49
时间窗: Day 0 to Day 49
Number of participants with mild, moderate, or severe AEs through Day 49 i.e. 28 days after second injection of each set of vaccinations (initial and crossover).
Pediatric Expansion: Incidence and Severity of Serious Adverse Events (SAEs) Through Specified Time Points
时间窗: Day 90 to Day 750
Number of participants with mild, moderate, or severe SAEs attributed to study vaccine through specified time points approximately every 3 and 6 months.
Pediatric Expansion: Incidence and Severity of Adverse Events of Special Interest (AESIs) Through Specified Time Points
时间窗: Day 90 to Day 750
Number of participants with mild, moderate, or severe AESIs attributed to study vaccine through specified time points approximately every 3 and 6 months.
Pediatric Expansion: Incidence and Severity of Medically Attended Adverse Events (MAAEs) Through Day 49
时间窗: Day 0 to Day 49
Number of participants with mild, moderate, or severe MAAEs through Day 49 i.e. 28 days after second injection of each set of vaccinations (initial and crossover).
Pediatric Expansion: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Specified Time Points
时间窗: Day 90 to Day 750
Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine through specified time points approximately every 3 and 6 months.
Pediatric Expansion: Incidence and Severity of SAEs Attributed to Study Vaccine Through Specified Time Points until Month 24
时间窗: Day 90 to Day 750
Number of participants with mild, moderate, or severe SAEs attributed to study vaccine and AESIs through specified time points until Month 24 or the EoS.
Pediatric Expansion: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Specified Time Points
时间窗: Day 35
Number of participants with antibodies to SARS-CoV-2 NP at Day 35 to determine natural infection and to determine the incidence of asymptomatic infection acquired during study follow-up.
Pediatric Expansion: Incidence and Severity of AESIs Attributed to Study Vaccine Through Specified Time Points until Month 24
时间窗: Day 90 to Day 750
Number of participants with mild, moderate, or severe AESIs attributed to study vaccine and AESIs through specified time points until Month 24 or the EoS.
Pediatric Expansion: Deaths Due to Any Cause
时间窗: Day 0 to Day 750
Number of participants who died during the study due to any cause.
次要结局
- Adult Main Study and Pediatric Expansion: Description of Course, Treatment and Severity of COVID-19(Day 28 to Day 750)
- Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as Geometric Mean Titers (GMTs)(Day 0 to Day 750)
- Adult Main Study and Pediatric Expansion: hACE2 Receptor Binding Inhibition Assay Expressed as GMFRs(Day 0 to Day 750)
- Adult Main Study and Pediatric Expansion: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMTs at Later Time Points(Day 165 to Day 750)
- Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as GMTs at Later Time Points(Day 165 to Day 750)
- Adult Main Study : Deaths Due to Any Cause(Day 0 to Day 750)
- Adult Main Study and Pediatric Expansion: Participants with Symptomatic Moderate or Severe COVID-19(Day 28 to Day 750)
- Adult Main Study and Pediatric Expansion: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMTs(Day 0 to Day 750)
- Adult Main Study and Pediatric Expansion: Participants with Any Symptomatic COVID-19(Day 28 to Day 750)
- Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as Geometric Mean Fold Rises (GMFRs)(Day 0 to Day 750)
- Adult Main Study and Pediatric Expansion: Serum IgG Antibody Levels Expressed as GMFRs(Day 0 to Day 750)
- Adult Main Study and Pediatric Expansion: Human Angiotensin-Converting Enzyme 2 (hACE2) Receptor Binding Inhibition Assay Expressed as GMTs(Day 0 to Day 750)
- Adult Main Study and Pediatric Expansion: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMFRs at Later Time Points(Day 165 to Day 750)
- Adult Main Study and Pediatric Expansion: hACE2 Receptor Binding Inhibition Assay Expressed as GMTs at Later Time Points(Day 165 to Day 750)
- Adult Main Study and Pediatric Expansion: hACE2 Receptor Binding Inhibition Assay Expressed as GMFRs at Later Time Points(Day 165 to Day 750)
- Adult Main Study: Incidence and Severity of Adverse Events of Special Interest (AESIs) Attributed to Study Vaccine Through Specified Time Points(Day 90 to Day 750)
- Adult Main Study and Pediatric Expansion: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Any Time Point(Day 0 to Day 750)
- Adult Main Study: IgG antibodies to SARS-CoV-2 rS at Day 35 After First Crossover Vaccination(Day 35 after the first crossover vaccination)
- Adult Main Study and Pediatric Expansion: Participants with 1st episode of positive Polymerase Chain Reaction (PCR) for Coronavirus Disease 2019 (COVID-19) due to a variant not considered as a "variant of concern/interest"(Day 28 to Day 750)
- Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as GMFRs at Later Time Points(Day 165 to Day 750)
- Adult Main Study: Reactogenicity Incidence and Severity(Day 0 to Day 27)
- Adult Main Study: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Specified Time Points(Day 90 to Day 750)
- Adult Main Study: Incidence and Severity of Serious Adverse Events (SAEs) Attributed to Study Vaccine Through Specified Time Points(Day 90 to Day 750)
- Adult Main Study: Incidence and Severity of SAEs Attributed to Study Vaccine Through Specified Time Points until Month 24(Day 90 to Day 750)
- Adult Main Study and Pediatric Expansion: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Specified Time Points(Day 0 to Day 750)
- Adult Main Study: Incidence and Severity of Medically Attended Adverse Events (MAAEs) Through Day 49(Day 0 to Day 49)
- Adult Main Study: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Specified Time Points until Month 24(Day 360 to Day 750)
- Adult Main Study: Incidence and Severity of Unsolicited Adverse Events (AEs) Through Day 49(Day 0 to Day 49)
- Adult Main Study: Incidence and Severity of AESIs Attributed to Study Vaccine Through Specified Time Points until Month 24(Day 360 to Day 750)