A Phase 2/3, Randomized, Double-Blind Study to Evaluate the Safety and Immunogenicity of Different Booster Dose Levels of Monovalent SARS-CoV-2 rS Vaccines in Adults ≥ 50 Years Previously Vaccinated With COVID-19 mRNA Vaccines
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Novavax
- 入组人数
- 994
- 试验地点
- 40
- 主要终点
- Immunogenicity index-Neutralizing antibody expressed as geometric mean titer ratio[GMTR ]against the Omicron subvariant XBB.1.5
研究概览
简要总结
This is a Phase 2/3, randomized, double-blind study to evaluate the safety and immunogenicity of different booster dose levels of the monovalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant (r) spike (S) protein nanoparticle (SARS-CoV-2 rS) vaccines with Matrix-M™ adjuvant (NVX-CoV2373 [prototype Wuhan vaccine with Matrix-M adjuvant] or NVX-CoV2601 [Omicron XBB.1.5 subvariant vaccine with Matrix-M adjuvant]).
详细描述
The ongoing COVID-19 pandemic has reached a stage where it is necessary to stablish the framework for periodic national vaccination campaigns.The present study aims to investigate the safety and immunogenicity of different booster dose levels of monovalent and bivalent vaccines in adults ≥ 50 years of age who have already been immunized with ≥ 3 doses of a COVID-19 prototype or bivalent licensed mRNA vaccine. The Boosters of investigational products will be administered ≥ 90 days after the participants received their third dose of a COVID-19 prototype or bivalent licensed mRNA vaccine.
Approximately 1,980 participants ≥ 50 years of age who have received a regimen of ≥ 3 doses of a coronavirus disease 2019(COVID-19) vaccine (the last vaccine could have been a bivalent licensed mRNA vaccine) will be included in this study. The last COVID-19 vaccine dose should have been administered ≥ 90 days prior to Day 0.
Approximately 1,800 participants will be randomly assigned in a 1:2:2:2:2:1 ratio to receive NVX-CoV2373 or NVC-CoV2601 in a double-blinded fashion into 1 of 6 monovalent vaccine groups (vaccine groups A to G). Following completion of enrollment into the 6 monovalent vaccine groups, 180 participants will be enrolled in vaccine group G to receive a bivalent licensed mRNA vaccine in an open-label fashion.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults ≥ 50 years of age 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 ≥ 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.
- •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 initial study vaccination.
- •Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study.
- •Have previously received ≥ 3 doses of a COVID-19 prototype or bivalent licensed mRNAvaccine with the last dose having been given ≥ 90 days previously prior to first study booster.
排除标准
- •Received COVID-19 vaccines other than a COVID-19 prototype or bivalent licensed mRNA vaccine in the past, inclusive of clinical trial COVID-19 vaccines.
- •Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to study vaccination.
- •Received influenza vaccination within 14 days prior to first study vaccination, or any other vaccine within 30 days prior to 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 immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to study vaccination. NOTE: 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. Use of inhaled glucocorticoids is prohibited.
- •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.
- •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).
- •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 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, contract research organization (CRO), and study site personnel involved in the conduct or planning of the study).
- •Participants with a history of myocarditis or pericarditis.
研究组 & 干预措施
Group-A Monovalent NVX-CoV2373 (5 μg)
The Monovalent NVX-CoV2601 of 5 μg of antigen with 50 μg of Matrix-M adjuvant
干预措施: NVX-CoV2373 (5μg) (Biological)
Group-B Monovalent NVX-CoV2601 (5 μg)
Monovalent NVX-CoV2601 (5 μg of antigen with 50 μg of Matrix-M adjuvant)
干预措施: NVX-CoV2601 (5μg) (Biological)
Group-C Monovalent NVX-CoV2601 (5 μg)
Monovalent NVX-CoV2601 (5 μg of antigen with 75 μg of Matrix-M adjuvant)
干预措施: NVX-CoV2601(5μg) (Biological)
Group-D Monovalent NVX-CoV2601 (35 μg)
Monovalent NVX-CoV2373 (35 μg of antigen with 50 μg of Matrix-M adjuvant)
干预措施: NVX-CoV2601 (35μg) (Biological)
Group-E Monovalent NVX-CoV2601(35)
Monovalent NVX-CoV2601 (35 μg of each antigen with a 75 μg of Matrix-M adjuvant)
干预措施: NVX-CoV2601(35μg) (Biological)
Group-F Monovalent NVX-CoV2601 (50 μg)
Monovalent NVX-CoV2601 (50 μg of each antigen with a 100 μg of Matrix-M adjuvant)
干预措施: NVX-CoV2601(50μg) (Biological)
Group-G Bivalent XBB.1.5
Bivalent XBB.1.5 Omicron subvariant/prototype COVID-19 licensed mRNA vaccine
干预措施: Bivalent BA.4/5 (Biological)
结局指标
主要结局
Immunogenicity index-Neutralizing antibody expressed as geometric mean titer ratio[GMTR ]against the Omicron subvariant XBB.1.5
时间窗: Day 28
Neutralizing antibody To determine if the combination of antigen and adjuvant levels of NVX-CoV2601 GMTR against the Omicron subvariant XBB.1.5 superior(LB of the 95% CI for GMTR \> 1.0) to that elicited by NVX-CoV2373
Immunogenicity index-Neutralizing antibody expressed as seroresponse rates (SRRs)against the Omicron subvariant XBB.1.5
时间窗: Day 28
Neutralizing antibody SRR against the Omicron XBB.1.5 subvariant elicited by NVXCoV2601 is non-inferior (NI)to the SRR elicited by NVX-CoV2373in participants ≥ 50 years of age previously vaccinated with ≥ 3 doses of a COVID-19 prototype or bivalent licensed mRNA vaccine.
次要结局
- Immunogenicity index- Neutralizing antibody titers of post-booster by baseline anti-SARS-CoV-2 NP(Day-28)
- Safety Index-Incidence, duration, and severity of solicited local and systemic AEs expressed as GMT(7 days)
- Safety Index -Incidence and relationship of Medically Attended Adverse Event(s) (MAAEs), Adverse event(s) of Special Interest (AESIs), and Serious Adverse Event(s) (SAEs)(Day 0 to 180)
- hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMFR(Day 0 to 180)
- hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as SRR(Day 0 to 180)
- Neutralizing antibody expressed as geometric mean titer ratio[GMTR ]against the Omicron subvariant XBB.1.5(Day 28)
- Immunogenicity index- IgG antibody Anti-S expressed as geometric mean Elisa units GMEUs (EU/mL)(Day 0 to 180)
- Safety Index -Incidence, Severity, and relationship of unsolicitated Adverse Event(s) Through 28 days after vaccination by vaccine group p(vaccine groups A to G).(Day 0 to 180)
- Immunogenicity index- Serum IgG levels to SARS-CoV-2 S protein at Day 28 of post-booster(Day-28)
- Human angiotensin-converting enzyme 2 (hACE2) receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMTs(Day 0 to 180)