Randomized, Double-Blind, Placebo-Controlled, Single-Center, Phase 1 Study in Healthy Volunteers to Evaluate the Safety and Immunogenicity of AGS-v PLUS, a Universal Mosquito-Borne Disease and Mosquito Control Vaccine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 2
- 主要终点
- Mean log10 Titer in Serum AGS-v PLUS Specific Immunoglobulin Titers
研究概览
简要总结
The purpose of this study is to evaluate the safety and immunogenicity of AGS-v PLUS, a universal mosquito-borne disease and mosquito control vaccine, in healthy volunteers.
详细描述
This study will evaluate the safety and immunogenicity of AGS-v PLUS, a universal mosquito-borne disease and mosquito control vaccine, in healthy volunteers.
Participants will be randomly assigned to five groups.
Participants in Group 1 will receive placebo on Days 1 and 22.
Participants in Group 2 will receive unadjuvanted AGS-v PLUS vaccine on Days 1 and 22.
Participants in Group 3 will receive Montanide ISA-51 adjuvanted AGS-v PLUS vaccine on Day 1 and placebo on Day 22.
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy women and men who are greater than or equal to 18 and less than or equal to 50 years of age.
- •Willingness to complete all study visits and comply with all study requirements.
- •A male participant is eligible for the study if he agrees to practicing abstinence or using a condom with spermicide plus an acceptable form of contraception (see inclusion criteria below) being used by any female partner from 4 weeks before study start to 12 weeks after the second vaccine administration.
- •A female participant is eligible for this study if she is not pregnant or breast feeding and 1 of the following:
- •Of non-child bearing potential (i.e., women who have had a hysterectomy or tubal ligation, or are postmenopausal, as defined by no menses in greater than or equal to 1 year).
- •Of childbearing potential but agrees to practice effective contraception or abstinence for 4 weeks before study initiation and 12 weeks after the second vaccine administration. Acceptable methods of contraception include a female partner who is the sole sexual partner of the female participant, a male partner who is sterile and is the sole sexual partner of the female participant, or a male partner who uses a condom with spermicide plus 1 or more of the following: 1) implants of levonorgestrel; 2) injectable progestogen; 3) an intrauterine device with a documented failure rate of less than 1%; 4) oral contraceptives; and 5) double barrier method including diaphragm.
- •Willing to have samples stored for future research.
- •Agrees to abstain from alcohol intake for 24 hours before each study visit.
- •Agrees to not donate blood or blood products throughout the study.
- •Score greater than or equal to 70% on comprehension quiz at screening
排除标准
- •Participant has any underlying or current medical condition, which, in the opinion of the Investigator, would interfere with the participation in the study.
- •Individual with body mass index (BMI) less than or equal to 18 and greater than or equal to
- •Participants who have a clinically significant (as determined by the PI or designee) baseline Grade 1 or greater toxicity, or any Grade 2 or greater toxicity (regardless of clinical significance) by the toxicity table.
- •Receipt of blood or blood products including immunoglobulin within 3 months before enrollment.
- •Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is greater) before enrollment.
- •Receipt of any unlicensed vaccine within 6 months before enrollment.
- •Participated in study NCT03055000 testing safety and immunogenicity of AGS-v.
- •Self-reported or known history of alcoholism or drug abuse within 6 months before enrollment.
- •Self-reported or known history of psychiatric or psychological issues that require treatment and are deemed by the PI or designee to be a contraindication to protocol participation.
- •History of a previous severe allergic reaction with generalized urticaria, angioedema, anaphylaxis or anaphylactoid reaction.
- •Any condition or event that, in the judgment of the PI or designee, is a contraindication to protocol participation or impairs the volunteer's ability to give informed consent.
- •Known allergy to any vaccine component, including adjuvants.
- •History of severe immunization reaction.
- •Severe allergic reaction to mosquito bites (anaphylaxis)
- •Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 30 days before study vaccination
- •Have taken high-dose inhaled corticosteroids* within 30 days before each study vaccination (* High-dose defined per age as using inhaled high dose per reference chart: https://www.nhlbi.nih.gov/sites/default/files/media/docs/asthma_qrg_0_0.pdf)
- •Received or plan to receive a licensed, live vaccine within 30 days before or after the study vaccination
- •Received or plan to receive a licensed, inactivated vaccine within 14 days before or after study vaccination
- •Serologic evidence of infection with HIV, hepatitis B virus, or hepatitis C virus
- •Ongoing chronic skin condition, or acute skin condition at the time of vaccination or mosquito feeding, except for mild eczema.
- •History of keloid formation after previous biopsies, lacerations, abrasions, surgeries, or other skin procedures (e.g., cosmetic piercings) that are deemed by the PI or designee to be a contraindication to protocol participation.
- •Pregnancy, breastfeeding, or planning to become pregnant up to one month after mosquito feeding.
结局指标
主要结局
Mean log10 Titer in Serum AGS-v PLUS Specific Immunoglobulin Titers
时间窗: Day 43
Mean log10 titer in serum AGS-v PLUS specific immunoglobulin E (IgE), immunoglobulin G (IgG), and immunoglobulin M (IgM) titers were assessed using enzyme-linked immunosorbent assay (ELISA)
Mean log10 Concentration in Th1 and Th2 Cytokine Responses
时间窗: Day 43
Mean log10 concentration in Th1 (IFN-gamma) and Th2 (IL-4) cytokine responses after in vitro exposure of peripheral blood mononuclear cells (PBMCs) with AGS-v PLUS antigens assessed using enzyme-linked immunosorbent assay (ELISA)
Mean log10 Fold Change in Serum AGS-v PLUS Specific Immunoglobulin Titer
时间窗: Day 1 and Day 43
Mean log10 fold change in serum AGS-v PLUS specific immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin E (IgE) titers from day 1 to day 43 assessed using enzyme-linked immunosorbent assay (ELISA). The fold change from day 1 to day 43 is calculated by dividing the antibody titer for a specific isotype i.e. IgE at day 43 by the titer at day 1. In order to stabilize the variance, the log10 of the fold change was used in the analyses.
Incidence of Severity of Treatment Emergent Adverse Events (AEs) by Grade
时间窗: 1 year
A treatment emergent adverse event is any untoward medical occurrence in a human subject that manifest after administration of the study treatment, whether or not considered related to the treatment. AE severity was graded using FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, September 2007 or the following grading scale: Grade 1 (Mild) Events causing no or minimal interference with daily activity and not requiring medical intervention Grade 2 (Moderate) Events causing greater than minimal interference with daily activity but not requiring medical intervention Grade 3 (Severe) Events causing inability to perform daily activity and/or requiring medical intervention Grade 4 (Potentially Life-Threatening)\* Events causing inability to perform basic self-care functions OR medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death Grade 5 (Death) Events causing death
Mean log10 Fold Change in Th1 and Th2 Cytokine Responses
时间窗: Day 1 and Day 43
Mean log10 fold change in Th1 (IFN-gamma) and Th2 (IL-4) cytokine responses after in vitro exposure of peripheral blood mononuclear cells (PBMCs) with AGS-v PLUS antigens from day 1 to day 43 assessed using enzyme-linked immunosorbent assay (ELISA). The fold change from day 1 to day 43 is calculated by dividing the antigen titer for a specific isotype i.e. IFN-gamma at day 43 by the titer at day 1. In order to stabilize the variance, the log10 of the fold change was used in the analyses.
次要结局
- Mean log10 Concentration in Th1 and Th2 Cytokine Responses(Day 50)
- Mean Number of Eggs Laid Per Mosquito Post Feeding(Day 43)
- Mean log10 Titer in Serum AGS-v PLUS Specific Immunoglobulin Titer(Day 50)
- Mean log10 Fold Change in Th1 and Th2 Cytokine Responses(Day 43 and Day 50)
- Mean log10 Fold Change in Serum AGS-v PLUS Specific Immunoglobulin Titer(Day 43 and Day 50)
- Mean Days of Mosquitoes Survival Post Feeding(Day 43)