NCT04368988已完成1 期
A 2-Part, Phase 1/2, Randomized, Observer-Blinded Study To Evaluate The Safety And Immunogenicity Of A SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Or Without MATRIX-M™ Adjuvant In Healthy Subjects
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Novavax
- 入组人数
- 1,419
- 试验地点
- 35
- 主要终点
- Serum IgG Antibody Levels Expressed as GMEUs - Phase 2
研究概览
简要总结
2019nCoV-101 is a 2-part, randomized, observer-blinded, placebo-controlled, Phase 1/2 trial. Part 1 (Phase 1) of the study is designed to evaluate the safety and immunogenicity of SARS-CoV-2 rS nanoparticle vaccine with or without Matrix-M adjuvant in 131 healthy participants ≥ 18 to 59 (inclusive) years of age at 2 sites in Australia. An interim analysis of Part 1 safety and immunogenicity will be performed prior to optional expansion to Part 2. Part 2 (Phase 2) of the study is designed to evaluate the immunogenicity, safety, and preliminary efficacy of a single construct of SARS-CoV-2 rS nanoparticle vaccine with Matrix-M adjuvant in up to 1,500 healthy participants ≥ 18 to 84 (inclusive) years of age at up to 40 sites across Australia and/or the United States.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 84 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult males or females between 18 and 59 years of age, inclusive, at screening. Healthy status will be determined by the investigator based on medical history, clinical laboratory results, vital sign measurements, and physical examination at screening.
- •The participant has a body mass index 17 to 35 kg/m2, inclusive, at screening.
- •Willing and able to give informed consent prior to study enrollment and comply with study procedures.
- •Female participants of childbearing potential (defined as any female who has experienced menarche and who is NOT surgically sterile [ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months or documented plasma follicle-stimulating hormone (FSH) level ≥40 mIU/mL]) must agree to be heterosexually inactive from at least 21 days prior to enrollment and through 6 months after the last vaccination OR agree to consistently use any of the described methods of contraception from at least 21 days prior to enrollment and through 6 months after the last vaccination.
排除标准
- •Any ongoing, symptomatic acute or chronic illness requiring medical or surgical care, inclusive of changes in medication in the past 2 months indicating that chronic illness/disease is not stable (at the discretion of the investigator). This includes any current workup of undiagnosed illness that could lead to a new condition.
- •Chronic disease inclusive of: a) hypertension uncontrolled for age according to the Eighth Joint National Committee (JNC 8) guidelines; b) congestive heart failure by New York Heart Association (NYHA) functional classification of greater or equal to II; c) chronic obstructive pulmonary disease by Global Initiative for Obstructive Lung Disease (GOLD) classification of greater or equal to 2; d) recent (within 6 months prior to first study vaccination) exacerbation of coronary artery disease as manifested by cardiac intervention, addition of new cardiac medications for control of symptoms, or unstable angina; e) asthma (diagnosed by spirometry showing reversibility of disease and must meet at least the Step 1 classification with current prescription/use of medications to control symptoms); f) diabetes requiring use of medicine (insulin or oral) or not controlled with diet.
- •Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination.
- •History of a confirmed diagnosis of SARS or COVID-19 disease (confirmed by a specific test for each disease) or known exposure to a SARS-CoV-2 positive confirmed close contact (eg, family member, housemate, daycare provider, aged parent requiring care), at the discretion of the investigator.
- •Currently working in an occupation with a high risk of exposure to SARS-CoV-2 (eg, healthcare worker, emergency response personnel).
- •Currently taking any product (investigational or off-label) for prevention of COVID-19 disease.
- •Positive rapid test for SARS-CoV-2 (either ELISA IgG or PCR) at screening or prior to first vaccination. Testing may be repeated during the screening period if exposure to SARS-CoV-2 is suspected, at the discretion of the investigator.
- •Received influenza vaccination within 14 days prior to first study vaccination, or any other vaccine within 4 weeks prior to first study vaccination.
- •Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital).
- •Chronic administration (defined as more than 14 continuous days) of immunosuppressant, systemic glucocorticosteroids, or other immune-modifying drugs within 90 days prior to first study vaccination; or anticipation of the need for immunosuppressive treatment within 6 months after last vaccination.
- •Received immunoglobulin, blood-derived products, or other immunosuppressant drugs within 90 days prior to first study vaccination.
- •Any acute illness concurrent or within 14 days prior to first study vaccination (medical history and/or physical examination) or documented temperature of >38°C during this period. This includes respiratory or constitutional symptoms consistent with SARS-CoV-2 (COVID-19) exposure (ie, cough, sore throat, difficulty breathing).
- •Known disturbance of coagulation (iatrogenic or congenital).
- •Evidence of Hepatitis B or C or HIV by laboratory testing.
- •A positive test result for drugs of abuse (except a positive test result associated with prescription medication that has been reviewed and approved by the investigator) or alcohol at screening.
- •Any neurological disease or history of significant neurological disorder (eg, meningitis, seizures, multiple sclerosis, vasculitis, migraines, Guillain-Barré syndrome [genetic/congenital or acquired]).
- •Active cancer (malignancy) within 5 years prior to first study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma, at the discretion of the investigator)
- •Vital sign (blood pressure, pulse, temperature) abnormalities of toxicity grade >
- •Clinical laboratory abnormalities of toxicity grade >1 for selected serum chemistry and hematology parameters
- •Any known allergies to products contained in the investigational product or latex allergy.
- •Women who are pregnant, breastfeeding or who plan to become pregnant during the study.
- •History of alcohol abuse or drug addiction within 1 year prior to the first study vaccination.
- •Any 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 deemed likely to impair the quality of safety reporting).
- •Study team member or first-degree relative of any study team member (inclusive of sponsor, PPD, and site personnel involved in the study).
- •Inclusion Criteria (Part 2):
- •Healthy adult males or females between 18 and 84 years of age, inclusive, at screening who are of legal adult age in their local jurisdiction. Healthy status will be determined by the investigator based on medical history, clinical laboratory results, vital sign measurements, and physical examination at screening.
- •The participant has a body mass index 17 to 35 kg/m2, inclusive, at screening.
- •Willing and able to give informed consent prior to study enrollment and comply with study procedures.
- •Female participants of childbearing potential (defined as any female who has experienced menarche and who is NOT surgically sterile [ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months or documented plasma FSH level ≥40 mIU/mL]) must agree to be heterosexually inactive from at least 21 days prior to enrollment and through 6 months after the last vaccination OR agree to consistently use any of the following methods of contraception from at least 21 days prior to enrollment and through 6 months after the last vaccination.
- •Exclusion Criteria (Part 2):
- •Participants who are having any current workup of undiagnosed illness within the last 8 weeks, which is either participant-reported or has been clinician-assessed, that could lead to a new condition diagnosis.
- •Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination.
- •History of a confirmed diagnosis of SARS or history of a confirmed diagnosis of COVID-19 disease resulting in medical intervention.
- •Received influenza vaccination within 14 days prior to first study vaccination, or any other vaccine within 4 weeks prior to first study vaccination.
- •Have clinically significant chronic cardiovascular, endocrine, gastrointestinal/ hepatic, renal, neurological, respiratory, or other medical disorders not excluded by other exclusion criteria, that are assessed by the Investigator as being clinically unstable within the prior 4 weeks evidenced by: a) hospitalization for the condition, including day surgical interventions, b) new significant organ function deterioration, c) needing addition of new treatments or major dose adjustments of current treatments.
- •Diabetes mellitus requiring insulin therapy (either type 1 or type 2 diabetes mellitus).
- •Chronic obstructive pulmonary disease with a history of an acute exacerbation of any severity in the prior year.
- •Any history of congestive heart failure.
- •Any history of chronic kidney disease (the presence of impaired or reduced kidney function lasting at least 3 months). Clinical validation of potential cases of chronic kidney disease should be conducted.
- •Evidence of unstable coronary artery disease as manifested by cardiac intervention, addition of new cardiac medications for control of symptoms, or unstable angina in the past 3 months.
- •History of chronic neurological disorders that have required prior specialist physician review for diagnosis and management (such as multiple sclerosis, dementia, transient ischemic attacks, Parkinson's disease, degenerative neurological conditions, neuropathy, and epilepsy) or a history of stroke or previous neurological disorder within 12 months with residual symptoms. Participants with a history of migraine or chronic headaches or nerve root compression that have been stable on treatment for the last 4 weeks are not excluded.
- •Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital).
- •Chronic administration (defined as more than 14 continuous days) of immunosuppressants, systemic glucocorticosteroids reaching an immunosuppressive dose, or other immune-modifying drugs within 90 days prior to first study vaccination.
- •Received immunoglobulin, blood-derived products, or other immunosuppressant drugs within 90 days prior to first study vaccination.
- •Known disturbance of coagulation (iatrogenic or congenital).
- •Active cancer (malignancy) within 5 years prior to first study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma, at the discretion of the investigator).
- •Any known allergies to products contained in the investigational product or latex allergy.
- •Women who are breastfeeding or who plan to become pregnant during the study.
- •History of alcohol abuse or drug addiction within one year prior to the first study vaccination.
- •Any condition that, in the opinion of the investigator, would pose a health risk to the subject if enrolled or could interfere with evaluation of the study vaccine or interpretation of study results (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting).
- 另有 1 项未显示
结局指标
主要结局
Serum IgG Antibody Levels Expressed as GMEUs - Phase 2
时间窗: Day 35
Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs for the two-dose regimens by dose at Day 35 regardless of baseline immune status and stratified by baseline immune status.
Serum IgG Antibody Levels Expressed as SCRs - Phase 2
时间窗: Day 35
Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs (≥4-fold rises) for the two-dose regimens by dose at Day 35 regardless of baseline immune status and stratified by baseline immune status.
Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs) - Phase 1
时间窗: 35 days
Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs through Day 35. SCR is the proportion of participants with ≥4-fold rises in ELISA units.
Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs) - Phase 1
时间窗: 35 days
Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs through Day 35.
Participants with Solicited Adverse Events (AEs) - Phase 2
时间窗: 28 days
Percentage of participants with solicited AEs (local, systemic) for 7 days following each primary vaccination (Days 0 and 21) by severity score, duration, and peak intensity.
Participants with Unsolicited AEs - Phase 2
时间窗: 35 days
Percentage of participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, all medically attended adverse events \[MAAEs\]) through the 35 days by Medical Dictionary of Regulatory Activities (MedDRA) classification, severity score, and relatedness.
Participants with Solicited Adverse Events (AEs) - Phase 1
时间窗: 28 days
Percentage of participants with solicited AEs (local, systemic) for 7 days following each primary vaccination (Days 0, 21) by severity score, duration, and peak intensity.
Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs) - Phase 1
时间窗: 35 days
Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by enzyme-linked immunosorbent assay (ELISA) expressed as GMTs through Day 35.
Serum IgG Antibody Levels Expressed as GMFRs - Phase 2
时间窗: Day 35
Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs for the two-dose regimens by dose at Day 35 regardless of baseline immune status and stratified by baseline immune status.
Safety Laboratory Values (Serum Chemistry, Hematology) - Phase 1
时间窗: 28 days
Safety laboratory values (serum chemistry, hematology) by FDA toxicity scoring (absolute and change from baseline where identified) at 7 days after each vaccination.
次要结局
- Neutralizing Antibody Activity Expressed as GMFRs - Phase 2(357 days)
- Participants with MAAEs - Phase 1(105 days)
- Assessment of Serum IgG Antibody Levels Expressed as GMFRs at Multiple Time Points - Phase 1(189 days)
- ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs - Phase 1(189 days)
- Neutralizing Antibody Activity Expressed as GMFRs - Phase 1(49 days)
- Assessment of Serum IgG Antibody Levels Expressed as GMTs - Phase 2(35 days)
- Assessment of Serum IgG Antibody Levels Expressed as SCRs (≥ 4-fold change) - Phase 2(35 days)
- Assessment of Serum IgG Antibody Levels Expressed as GMEUs at Multiple Time Points - Phase 2(357 days)
- Participants with Abnormal Vital Signs - Phase 1(21 days)
- Participants with Related MAAEs; Serious Adverse Events (SAEs); and Adverse Events of Special Interest (AESI) - Phase 1(386 days)
- Angiotensin-Converting Enzyme 2 (ACE2) Receptor Binding Inhibition Assay Expressed as GMTs - Phase 1(189 days)
- Neutralizing Antibody Activity Expressed as SRRs - Phase 1(49 days)
- Neutralizing Antibody Activity Expressed as SCRs (≥ 4-fold change) - Phase 2(357 days)
- Participants with Unsolicited AEs - Phase 1(49 days)
- Changes from Baseline in Body Temperature - Phase 1(189 days)
- Changes from Baseline in Blood Pressure - Phase 1(189 days)
- Changes from Baseline in Pulse Rate - Phase 1(189 days)
- Assessment of Serum IgG Antibody Levels Expressed as GMTs at Multiple Time Points - Phase 1(189 days)
- Neutralizing Antibody Activity Expressed as GMTs - Phase 1(49 days)
- Neutralizing Antibody Activity Expressed as SCRs - Phase 1(49 days)
- Assessment of Serum IgG Antibody Levels Expressed by Seroresponse Rates (SRRs) at Multiple Time Points - Phase 1(189 days)
- Assessment of Cell-Mediated (T helper 1 [Th1]/T helper 2 [Th2]) Pathways - Phase 1(28 days)
- Assessment of Serum IgG Antibody Levels Expressed as SCRs (≥ 4-fold change) at Multiple Time Points - Phase 2(357 days)
- Assessment of Serum IgG Antibody Levels Expressed as SCRs at Multiple Time Points - Phase 1(189 days)
- ACE2 Receptor Binding Inhibition Assay Expressed as SCRs - Phase 1(189 days)
- ACE2 Receptor Binding Inhibition Assay Expressed as SRRs - Phase 1(189 days)
- Assessment of Serum IgG Antibody Levels Expressed as GMFRs - Phase 2(35 days)
- ACE2 Receptor Binding Inhibition Assay Expressed as GMTs - Phase 2(357 days)
- Assessment of Serum IgG Antibody Levels Expressed as GMFRs - Phase 2 Boost(546 days)
- Assessment of Serum IgG Antibody Levels Expressed as GMFRs at Multiple Time Points - Phase 2(357 days)
- ACE2 Receptor Binding Inhibition Assay Expressed as SCRs - Phase 2(357 days)
- ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs - Phase 2(357 days)
- Assessment of Cell-Mediated (Th1/Th2) Pathways - Phase 2(28 days)
- Neutralizing Antibody Activity Expressed as GMTs - Phase 2(357 days)
- Changes from Baseline in Body Temperature - Phase 2(189 days)
- Changes from Baseline in Blood Pressure - Phase 2(189 days)
- Assessment of SARS-CoV-2 by Qualitative PCR - Phase 2(161 days)
- Assessment of Serum IgG Antibody Levels Expressed as GMTs - Phase 2 Boost(546 days)
- Participants with Related MAAEs; SAEs; and AESIs - Phase 2(357 days)
- Participants with SARS-CoV-2 Positivity - Phase 2(161 days)
- Participants with MAAEs - Phase 2(217 days)
- Participants with Abnormal Vital Signs - Phase 2(21 days)
- Changes from Baseline in Pulse Rate - Phase 2(189 days)
研究者
研究点 (35)
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