A Randomized, Observer-Blinded, Phase 1/2 Study With an Open-Label Group to Evaluate the Safety and Immunogenicity of SII Vaccine Constructs Based on SARS-CoV-2 Variants in Adults
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Novavax
- 试验地点
- 8
- 主要终点
- MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as GMT
研究概览
简要总结
This is a randomized, observer-blinded, Phase 1/2 study with an open-label group to evaluate the safety and immunogenicity of 3 novel SARS-CoV-2 variant vaccine constructs adjuvanted with Matrix-M1 adjuvant. Investigational products will include a monovalent SII SARS-CoV-2 B.1.351 (Beta) variant vaccine (SII B.1.351), a bivalent SII vaccine containing antigen for both the ancestral strain and B.1.351 (Beta) variant of SARS-CoV-2 (SII Bivalent), and a monovalent SII SARS-CoV-2 B.1.617.2 (Delta) variant vaccine (SII B.1.617.2).
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 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults 18 to 64 years of age, inclusive, at screening.
- •Willing and able to give informed consent prior to study enrollment and to comply with study procedures.
- •Female 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 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 the end of the study OR agree to consistently use a medically acceptable method of contraception listed below from at least 28 days prior to enrollment and through the end of the study.
- •Condoms (male or female) with spermicide (if acceptable in country)
- •Diaphragm with spermicide
- •Cervical cap with spermicide
- •Intrauterine device
- •Oral or patch contraceptives
- •Norplant®, Depo-Provera®, or other in-country regulatory approved contraceptive method that is designed to protect against pregnancy
- •Abstinence, as a form of contraception, is acceptable if in line with the participant's lifestyle
- •Is medically stable, as determined by the investigator (based on a 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.
- •Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study.
- •For previously vaccinated Participants (Groups C, D and H):
- •Documented receipt of 2 doses of the investigational Novavax vaccine with Matrix-M1 adjuvant (NVX-CoV2373) administered approximately 21 days apart or 2 doses of a TGA-authorized/approved COVID-19 vaccine administered at least 60 days prior to first study vaccination.
排除标准
- •If an individual meets any of the following criteria, he or she is ineligible for this study:
- •History of laboratory-confirmed (by PCR or serology to SARS-CoV-2) COVID-19 infection at any time prior to randomization/enrollment.
- •Previous receipt of any investigational or authorized/approved vaccine, prophylactic or therapeutic agent for the prevention or treatment of SARS-CoV-2 infection, except for previously vaccinated participants.
- •Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to first study vaccination.
- •Received influenza vaccination within 14 days prior to first study vaccination, or any other vaccine within 30 days prior to the first study vaccination.
- •Any known allergies to products contained in the investigational product.
- •Any history of anaphylaxis to any prior vaccine.
- •Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.
- •Chronic administration (defined as > 14 continuous days) of immunosuppressants, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to first study vaccination.
- •Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to first study vaccination.
- •Active cancer (malignancy) on therapy within 3 years prior to first 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).
- •Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study.
- •Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the first study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance.
- •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).
- •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 study).
结局指标
主要结局
MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as GMT
时间窗: Day 14 and Day 35
(MN50) geometric mean titers (GMTs) to the SARS-CoV-2 B.1.351 (Beta) variant at Day 14 (one-dose regimen; Groups C and D) and Day 35 (two-dose regimen; Groups A and B);
MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta)expressed as SCRs/SRRs
时间窗: Day 14 and Day 35
SCRs/SRRs (proportion of participants who achieve ≥ 4-fold increase from baseline) in MN50 titer concentrations to the SARS-CoV-2 Delta variant following their last vaccination.
MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs
时间窗: Day 14 and Day 35
Seroconversion rates (SCRs) or seroresponse rates (SRRs) (proportion of participants who achieve ≥ 4-fold increase from baseline) in MN50 titer concentrations to the SARS-CoV-2 B.1.351 (Beta) variant following their last vaccination.
Incidence, duration, and severity of solicited local and systemic adverse events (AEs)
时间窗: Day 0 to Day 7
Incidence, duration, and severity of solicited local and systemic adverse events (AEs) for 7 days following each vaccination
Incidence and relationship of medically attended adverse events (MAAEs), adverse events of special interest (AESIs) (predefined list), and serious adverse events (SAEs)
时间窗: Day 0 to Day 217
Incidence and relationship of medically attended adverse events (MAAEs), adverse events of special interest (AESIs) (predefined list), and serious adverse events (SAEs) throughout the study.
MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta)expressed as GMT
时间窗: Day 14 and Day 35
Neutralizing antibody MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta) variant at Day 14 (one-dose regimen; Group H) and Day 35 (two-dose regimen; Group G);
Incidence, duration, severity, and relationship of unsolicited AEs through 28 days
时间窗: Day 0 to Day 28
Incidence, duration, severity, and relationship of unsolicited AEs through 28 days after the last vaccination
次要结局
- MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in previously vaccinated patients(Day 0 to Day 189)
- MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in participants seronegative at baseline(Day 0 to Day 217)
- MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta)expressed as SCRs/ SRRs in previously vaccinated participants(Day 0 to Day 189)
- IgG geometric mean concentrations (GMCs) to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in participants seronegative at baseline(Day 0 to Day 217)
- IgG geometric mean concentrations (GMCs) to the B.1.617.2 (Delta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein in previously vaccinated participants(Day 0 to Day 189)
- MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs in participants seronegative at baseline.(Day 0 to Day 217)
- MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta) expressed as GMFR in participants seronegative at baseline(Day 0 to Day 217)
- MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta) expressed as GMFR in previously vaccinated participants(Day 0 to Day 189)
- IgG geometric mean concentrations (GMCs) to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in previously vaccinated participants(Day 0 to Day 189)
- Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in previously vaccinated participants(Day 0 to Day 189)
- Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs in previously vaccinated participants(Day 0 to Day 189)
- MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs in previously vaccinated patients(Day 0 to Day 189)
- MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta)expressed as SCRs/ SRRs in participants seronegative at baseline(Day 0 to Day 217)
- Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in participants seronegative at baseline(Day 0 to Day 217)
- Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs in participants seronegative at baseline(Day 0 to Day 217)
- IgG geometric mean concentrations (GMCs) to the B.1.617.2 (Delta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein in participants seronegative at baseline(Day 0 to Day 217)
- Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.617.2 (Delta) expressed as GMFR in participants seronegative at baseline(Day 0 to Day 217)
- Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.617.2 (Delta) expressed as GMFR in previously vaccinated participants(Day 0 to Day 189)
- Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.617.2 (Delta) expressed as SCRs/SRRs in participants seronegative at baseline(Day 0 to Day 217)
- Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.617.2 (Delta) expressed as SCRs/SRRs in previously vaccinated participants(Day 0 to Day 189)