A Phase 1 Open-Label, Dose-Ranging Trial to Determine the Safety and Immunogenicity of an Adenoviral-Vector Based Vaccine (VXA-CoV2-1) Expressing a SARS-CoV-2 Antigen and dsRNA Adjuvant Administered Orally to Healthy Adult Volunteers VXA-CoV2-1.1-S Boost Substudy: Boost at 1 Year Post Initial Vaccination With an Adenoviral-Vector Based Vaccine VXA-CoV2-1.1-S Expressing a SARS-CoV-2 S Protein in a Subset of Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Vaxart
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Frequency of solicited symptoms of reactogenicity
研究概览
简要总结
VXA-CoV2-1 is a non-replicating Ad5 vector adjuvanted oral tableted vaccine being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to evaluate the safety and immunogenicity of VXA-CoV2-1 vaccine with repeat dosing at multiple dose levels. Safety and immunogenicity will be evaluated for up to 12 months after the second dose of VXA-CoV2-1.
详细描述
This is an open-label, dose-ranging trial to determine the safety and immunogenicity of an orally administered adenoviral-vector based vaccine (VXA-COV2-1) expressing a SARS-CoV-2 antigen and dsRNA adjuvant. Post screening activities, healthy adult volunteers aged 18 - 54 yrs old, inclusive, will be enrolled into the study. Participants will receive an oral dose of vaccine at Days 1 and a subject will also receive a second dose at Day 29; total study period will last ~ 2 months during the active phase, with a total 12 month safety follow-up period post last vaccination. Safety, reactogenicity and immunogenicity assessments will be performed at set times during the study active and follow-up periods. Subjects will be monitored for symptoms of COVID-19 throughout the duration of the study follow-up period.
Approximately 10 healthy male and female adult volunteers 18 to 54 years old who were enrolled in the main study will be included in a boost extension substudy for an additional 12 months from dosing for a total participation period of 24-25 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 54 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female between the ages of 18 to 54 years, inclusive.
- •Negative for SARS-CoV-2 infection at the time of screening
- •In generally good health, without significant medical illness
- •Demonstrates comprehension of the protocol procedures and is able to provide written informed consent.
- •Available for all planned visits and willing to complete all protocol defined procedures and assessments
- •Body mass index between 17 and 30 kg/m2 at screening.
- •Female subjects must have a negative pregnancy test at screening and before each vaccination and fulfill an acceptable method of birth control (per protocol)
排除标准
- •Known previous exposure to SARS-CoV-2 or receipt of an investigational product for the prevention or treatment of COVID-19, middle east respiratory syndrome (MERS), or severe acute respiratory syndrome (SARS).
- •Is in a current occupation with high risk of exposure to SARS-CoV-2
- •Individuals with the following underlying medical conditions who are at higher risk (or might be at higher risk) of severe illness from COVID-19 per the CDC's guidance
- •Donation or use of blood or blood products within 4 weeks prior to vaccination or planned donation during the study period.
- •Diagnosed bleeding disorder or significant bruising or bleeding difficulties that could make blood draws problematic.
- •Any condition that resulted in the absence or removal of the spleen.
- •Positive HIV, HBsAg or HCV tests at the screening visit.
- •Stool sample with occult blood at screening.
- •Use of antiviral medications, including anti-retrovirals, or any prescriptive medications for the prevention of COVID-19 within 7 days before vaccination
- •Use of antibiotics, proton pump inhibitors, H2 blockers or antacids or medications known to affect the immune function within 7 to 14 days before vaccination
- •Regular use of nonsteroidal anti-inflammatory drugs, sulfonylureas, and angiotensin II blockers within 7 days before vaccination
- •Acute disease within 72 hours prior to vaccination defined as the presence of a moderate or severe illness
- •History of drug, alcohol or chemical abuse within 1 year of screening or positive urine drug screen for drugs of abuse at screening
- •History of hypersensitivity or allergic reaction to any component of the investigational vaccine
- •Administration of any investigational vaccine, drug or device within 8 weeks preceding vaccination
- •Any other condition that in the clinical judgment of the investigator would jeopardize the safety or rights of a subject participating in the trial, would render the subject unable to comply with the protocol or would interfere with the evaluation of the study endpoints.
- •For subjects being re-evaluated for participation in the VXA-CoV2-1.1-S boost substudy the following will also be exclusionary:
- •Laboratory values outside the range of normal for platelet counts and the following coagulation tests: PT/INR, aPTT, fibrinogen, and D-dimer.
- •Any of the following history or conditions that may lead to higher risk of clotting events and/or thrombocytopenia:
- •e. Family or personal history of bleeding or thrombosis f. History of heparin-related thrombotic events, and/or receiving heparin treatments g. History of autoimmune or inflammatory disease h. Presence of any of the following conditions known to increase risk of thrombosis within 6 months prior to screening:
- •Recent surgery other than removal/biopsy of cutaneous lesions
- •Immobility (confined to bed or wheelchair for 3 or more successive days)
- •Head trauma with loss of consciousness or documented brain injury
- •Receipt of anticoagulants for prophylaxis of thrombosis
- •Recent clinically significant infection
研究组 & 干预措施
High Dose
High Dose (1E11 I.U.) of VXA-CoV2-1 oral tableted vaccine dispensed at Day 1
干预措施: VXA-CoV2-1 (Biological)
Low Dose VXA-CoV2-1
Low dose (1E10 I.U.) of VXA-CoV2-1 oral tableted vaccine dispensed at Day 1. A subset will also receive a second dose at Day 29
干预措施: VXA-CoV2-1 (Biological)
结局指标
主要结局
Frequency of solicited symptoms of reactogenicity
时间窗: Day 1 through Day 8 post each immunization
Subject reported symptoms of local and systemic reactogenicity
Frequency of serious adverse events (SAEs)
时间窗: Day 1 through Day 390
Any adverse events reported following vaccination meeting definition of serious
Grade of solicited symptoms of reactogenicity
时间窗: Day 1 through Day 8 post each immunization
Subject reported symptoms of local and systemic reactogenicity
Frequency of unsolicited adverse events
时间窗: Day 1 through Day 29 post each immunization
Any adverse events observed or reported following vaccination
Grade of unsolicited adverse events
时间窗: Day 1 through Day 29 post each immunization
Any adverse events observed or reported following vaccination
Frequency of medically-attended adverse events (MAAEs)
时间窗: Day 1 through Day 390
Any adverse events reported following vaccination meeting definition of serious
次要结局
- Th1/Th2 polarization(Day 1 through Day 44)
- SARS-CoV-2 specific IgG/IgA(Day 1 through Day 390)
- Neutralizing antibody titers to SARS-CoV-2(Day 1 through Day 390)
- Antigen-specific IgG/IgA antibody secreting (ASCs)(Day 1 through Day 44)