A Phase 0 Study Exploring the Use of Vaccine and Antigen Challenges for Immune Monitoring in Healthy Volunteers
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Cohort 3 and Cohort 4: Change from Baseline in Activation Status of Inflammatory Mediators (Soluble Cytokines and Chemokines)
研究概览
简要总结
The purpose of this study is to characterize the immune response in vivo using approved vaccines and antigen challenges, as well as a skin wounding challenge to stimulate the immune system.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Have a body mass index (BMI) between 18 and 30 kilogram per square meter (kg/m^2) (BMI = weight/height^2), inclusive, and a body weight of no less than 50 kilogram (kg)
- •Healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) (for Cohort 3) performed at screening. Any abnormalities, must be considered not clinically significant and this determination must be recorded in the participant's source documents and initialed by the investigator
- •Healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, blood coagulation, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
- •Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
- •All women must have a negative highly sensitive serum (Beta-human chorionic gonadotropin [Beta-hCG]) pregnancy test at screening and a negative urine pregnancy test predose on Day 1
排除标准
- •History of any type of immunodeficiency or autoimmune disease or disease treatment associated with immune suppression or lymphopenia. These include but are not limited to bone marrow or organ transplantation, lymphoproliferative disorders, T- or B-cell deficiency syndromes, splenectomy, functional asplenia and chronic granulomatous disease
- •History of liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, bleeding disorders, rheumatologic, psychiatric, or metabolic disturbances, and atopic dermatitis
- •Known allergies, hypersensitivity, or intolerance to any of the interventions in this study or their excipients
- •History of severe allergic reaction, angioedema, or anaphylaxis to drugs or food
- •Contraindications to the use of any of the study interventions per prescribing information
研究组 & 干预措施
Cohort 1: Vaccine Challenge Imvanex
Participants will receive single dose of Imvanex subcutaneously on Day 1. Participants will also be included in the DREEM EEG substudy.
干预措施: Imvanex (Biological)
Cohort 2: Vaccine Challenge Shingrix
Participants will receive single dose of Shingrix intramuscularly on Day 1. Participants will also be included in the DREEM EEG substudy.
干预措施: Shingrix (Biological)
Cohort 3: Antigen Challenge Lipopolysaccharides (LPS)
Participants will receive a single dose of LPS intravenously (IV) on Day 1. Participants will also be included in the DREEM EEG substudy and vital patch physIQ platform substudy.
干预措施: LPS (Biological)
Cohort 4: Antigen Challenge Candin
Participants will receive one single injection of Candin and one single injection of saline control intradermally on Day 1. Participants will also be included in the DREEM EEG substudy.
干预措施: Candin (Biological)
Cohort 4: Antigen Challenge Candin
Participants will receive one single injection of Candin and one single injection of saline control intradermally on Day 1. Participants will also be included in the DREEM EEG substudy.
干预措施: Saline Control (Other)
Cohort 5: Skin Wounding Challenge
3 punch biopsies will be performed per standard dermatologic practice guidelines. Lower abdomen tissue biopsy specimens will be collected on Day 1.
干预措施: Skin Biopsy (Other)
结局指标
主要结局
Cohort 3 and Cohort 4: Change from Baseline in Activation Status of Inflammatory Mediators (Soluble Cytokines and Chemokines)
时间窗: Baseline up to 14 days
Soluble cytokines and chemokines will be measured by immunoassay.
Cohort 3 and Cohort 4: Change from Baseline of Immune Cell Populations
时间窗: Baseline up to 14 days
Change from baseline in immune cell populations will be measured in peripheral blood samples or tissues of healthy volunteers.
Cohort 1 and Cohort 2: Change from Baseline in Cell Surface Antigen Phenotype
时间窗: Baseline up to 90 days
Change from baseline in cell surface antigen phenotype will be measured in peripheral blood samples or tissues of healthy volunteers.
Cohort 3 and Cohort 4: Change from Baseline in Activation Status of Inflammatory Mediators (Cell-bound and Tissue-associated Proteins)
时间窗: Baseline up to 14 days
Cell-bound and tissue-associated proteins will be measured by established methods including flow cytometry and immunohistochemistry.
Cohort 1 and Cohort 2: Change from Baseline in Expression of Inflammatory Mediators
时间窗: Baseline up to 90 days
Transcriptional changes in gene expression will be measured by established methods such as ribonucleic acid (RNA) microarray, RNAseq, and single cell RNA sequencing, and will be reported in number of gene transcripts per sample or per cell.
Cohort 3 and Cohort 4: Change from Baseline in Expression of Inflammatory Mediators
时间窗: Baseline up to 14 days
Transcriptional changes in gene expression will be measured by established methods such as ribonucleic acid (RNA) microarray, RNAseq, and single cell RNA sequencing, and will be reported in number of gene transcripts per sample or per cell.
Cohort 1 and Cohort 2: Change from Baseline of Immune Cell Populations
时间窗: Baseline up to 90 days
Change from baseline in immune cell populations will be measured in peripheral blood samples or tissues of healthy volunteers.
Cohort 3 and Cohort 4: Change from Baseline in Cell Surface Antigen Phenotype
时间窗: Baseline up to 14 days
Change from baseline in cell surface antigen phenotype will be measured in peripheral blood samples or tissues of healthy volunteers.
Cohort 5: Change from Baseline in Cell Surface Antigen Phenotype
时间窗: Baseline up to 10 days
Change from baseline in cell surface antigen phenotype will be measured in tissues of healthy volunteers.
Cohort 5: Change from Baseline in Activation Status of Inflammatory Mediators (Soluble Cytokines and Chemokines)
时间窗: Baseline up to 10 days
Soluble cytokines and chemokines will be measured by immunoassay.
Cohort 5: Change from Baseline in Expression of Inflammatory Mediators
时间窗: Baseline up to 10 days
Transcriptional changes in gene expression will be measured by established methods such as RNA microarray, RNAseq, and single cell RNA sequencing, and will be reported in number of gene transcripts per sample or per cell.
Cohort 5: Change from Baseline of Immune Cell Populations
时间窗: Baseline up to 10 days
Change from baseline in immune cell populations will be measured in tissues of healthy volunteers.
Cohort 1 and Cohort 2: Change from Baseline in Activation Status of Inflammatory Mediators (Soluble Cytokines and Chemokines)
时间窗: Baseline up to 90 days
Soluble cytokines and chemokines will be measured by immunoassay.
Cohort 1 and Cohort 2: Change from Baseline in Activation Status of Inflammatory Mediators (Cell-bound and Tissue-associated Proteins)
时间窗: Baseline up to 90 days
Cell-bound and tissue-associated proteins will be measured by established methods including flow cytometry and immunohistochemistry.
Cohort 5: Change from Baseline in Activation Status of Inflammatory Mediators (Cell-bound and Tissue-associated Proteins)
时间窗: Baseline up to 10 days
Cell-bound and tissue-associated proteins will be measured by established methods including flow cytometry and immunohistochemistry.
次要结局
- Change in Standard Deviation from Baseline of Immune Cell Populations Within a Participant(Cohort 1 and Cohort 2: Baseline up to 90 days; Cohort 3 and Cohort 4: Baseline up to 14 days; Cohort 5: Baseline up to 10 days)
- Change in Standard Deviation from Baseline of Immune Cell Populations Between Participants(Cohort 1 and Cohort 2: Baseline up to 90 days; Cohort 3 and Cohort 4: Baseline up to 14 days; Cohort 5: Baseline up to 10 days)
- Change in Standard Deviation from Baseline in Cell Surface Antigen Phenotype Within a Participant(Cohort 1 and Cohort 2: Baseline up to 90 days; Cohort 3 and Cohort 4: Baseline up to 14 days; Cohort 5: Baseline up to 10 days)
- Change in Standard Deviation from Baseline in Expression of Inflammatory Mediators Between Participants(Cohort 1 and Cohort 2: Baseline up to 90 days; Cohort 3 and Cohort 4: Baseline up to 14 days; Cohort 5: Baseline up to 10 days)
- Correlation of Genomics with Vaccine/Antigen Immune Response Phenotype(Cohort 1 and Cohort 2: Baseline up to 90 days; Cohort 3 and Cohort 4: Baseline up to 14 days)
- Change in Standard Deviation from Baseline in Activation Status of Inflammatory Mediators Between Participants(Cohort 1 and Cohort 2: Baseline up to 90 days; Cohort 3 and Cohort 4: Baseline up to 14 days; Cohort 5: Baseline up to 10 days)
- Correlation of Baseline Immune Cell Populations with Vaccine/Antigen Immune Response Phenotype(Cohort 1 and Cohort 2: Baseline up to 90 days; Cohort 3 and Cohort 4: Baseline up to 14 days)
- Change in Standard Deviation from Baseline in Cell Surface Antigen Phenotype Between Participants(Cohort 1 and Cohort 2: Baseline up to 90 days; Cohort 3 and Cohort 4: Baseline up to 14 days; Cohort 5: Baseline up to 10 days)
- Correlation of Soluble Proteins with Vaccine/Antigen Immune Response Phenotype(Cohort 1 and Cohort 2: Baseline up to 90 days; Cohort 3 and Cohort 4: Baseline up to 14 days)
- Change in Standard Deviation from Baseline in Activation Status of Inflammatory Mediators Within a Participant(Cohort 1 and Cohort 2: Baseline up to 90 days; Cohort 3 and Cohort 4: Baseline up to 14 days; Cohort 5: Baseline up to 10 days)
- Change in Standard Deviation from Baseline in Expression of Inflammatory Mediators Within a Participant(Cohort 1 and Cohort 2: Baseline up to 90 days; Cohort 3 and Cohort 4: Baseline up to 14 days; Cohort 5: Baseline up to 10 days)
- Correlation of Serology with Vaccine/Antigen Immune Response Phenotype(Cohort 1 and Cohort 2: Baseline up to 90 days; Cohort 3 and Cohort 4: Baseline up to 14 days)