Adaptive Phase I Clinical Trial of Preventive Vaccine Consisting of Autologous Dendritic Cells Previously Incubated With S-protein From SARS-CoV-2, in Subjects Negative for COVID-19 Infection and Anti-SARS-CoV-2 Antibodies
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Safety Laboratory Values (Serum Chemistry)
研究概览
简要总结
This is an adaptive Phase I trial of a vaccine consisting of autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein, with or without GM-CSF, to prevent COVID-19 in adults.
详细描述
Subjects eligible for treatment will be those who at baseline, are not actively infected with SARS-CoV-2, have no evidence of prior infection with SARSCoV- 2 based on serologic testing, and give informed consent for a vaccination with AV-COVID-19. The patient population will include the elderly and others at higher risk for poor outcomes after COVID-19 infection. For this reason, individuals will not be excluded solely on the basis of age, body mass index, history of hypertension, diabetes, cancer, or autoimmune disease.
After enrolling for screening, subjects will undergo a nasal swab test to exclude active COVID-19 infection and a rapid test for anti-coronavirus antibodies to exclude pre-existing anti-SARS-CoV-2 antibodies. 50 mL of blood will be collected, from which peripheral blood monocytes will be isolated and differentiated into DC before incubation with SARS-CoV-2 S-protein, during which time the protein is digested into 9 to 25 amino acid peptide sequences presented on the dendrites of DC in conjunction with histocompatibility class I and class II molecules. Safety and quality testing will be performed on a small quantity of the batch, and the remaining AV-COVID-19 will be cryopreserved for shipping to the treatment site.
Once the Study Drug is ready, if eligible, the subject will be seen at Study Week-0 for treatment. Prior to injection of the Study Drug, a nasal swab test will be collected to confirm that they are still negative for COVID-19, and blood will be drawn to determine baseline levels of anti-SARS-CoV-2 antibodies. At the treatment site, the product will be thawed and admixed with saline or (saline with GM-CSF), and within 5 hours of thawing, will be injected SC via a 25- gauge needle
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18 years or older,
- •in relatively good health with adequate physical and mental function
- •including factors associated with in increased risk for medical complications associated with COVID-19 infection or increased risk for exposure to SARS-CoV-2
排除标准
- •Active COVID-19 infection by PCR testing
- •Pre-existing IgG or IgM SARS-CoV-2 antibodies
- •Pregnant, Known hypersensitivity to GM-CSF
- •Known active immune deficiency disease or active HIV
- •HBV, HCV, On active treatment with corticosteroids or other immunosuppressive agent
- •Participated in previous COVID-19 vaccine study
结局指标
主要结局
Safety Laboratory Values (Serum Chemistry)
时间窗: until follow up day 7
Safety laboratory values (Serum Chemistry) by FDA toxicity scoring (absolute and change from baseline where identified) at 7 days after each vaccination.
Frequency of Unsolicited AE and Adverse Events of Special Interest (AESIs)
时间窗: until follow up day 90
Percentage of participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, all MAAEs) or AESIs (potential immune-mediated medical conditions or AEs relevant to COVID-19) through the first 90 days by MedDRA classification, severity score, and relatedness.
Frequency of any serious adverse events (SAEs)
时间窗: until follow up day 365
Percentage of participants with serious undesirable effect associated with the use of a medical product in a patient, which consist of death, life-threatening, hospitalization, disability or permanent damage, congenital anomaly/birth defect, required intervention to prevent permanent impairment or damage (devices), dan other serious important medical events
Frequency of any new-onset chronic medical conditions (NOCMCs)
时间窗: until follow up day 365
NOCMCs will be documented from the time of study vaccination through approximately 1 year after study vaccination
Frequency of medically attended adverse events (MAAEs)
时间窗: until follow up day 365
Percentage of participants with MAAEs, defined as AEs that lead to an unscheduled visit to a healthcare practitioner, through Day 365 by MedDRA classification, severity score, and relatedness.
Frequency of solicited local and systemic reactogenicity adverse events (AEs)
时间窗: until follow up day 7
Percentage of participants with solicited AEs (local, systemic) for 7 days following vaccination by severity score, duration, and peak intensity.
Safety Laboratory Values (Hematology)
时间窗: until follow up day 7
Safety laboratory values (Hematology) by FDA toxicity scoring (absolute and change from baseline where identified) at 7 days after each vaccination.
次要结局
- Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs)(until follow up day 28)
- Neutralizing Antibody Activity Expressed as SCRs(until follow up day 28)
- Duration of detection IgG and neutralizing antibody againts SARS-CoV-2in blood after vaccination(until follow up month 12)
- Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs)(until follow up day 28)
- Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs)(until follow up day 28)
- Optimal dose of SARS-CoV2 antigen and GM-CSF(until follow up month one)
- Neutralizing Antibody Activity Expressed as GMTs(until follow up day 28)
- Neutralizing Antibody Activity Expressed as GMFRs(until follow up day 28)
- Assessment of Cell-Mediated (T helper 1 [Th1]/T helper 2 [Th2]) Pathways(until follow up day 28)