A Phase 1a, Randomized, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of a Prototype Human CMV-based Vaccine for Human Immunodeficiency Virus (HIV) in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Number of participants with any treatment-emergent adverse events (AEs)
研究概览
简要总结
This is a Phase 1a, first in human study in which healthy adult participants who are considered to be at low-risk for HIV infection and are seropositive for cytomegalovirus (CMV) will receive two doses of VIR-1111 or placebo. These participants will be assessed for safety, reactogenicity, tolerability and immunogenicity. There is an optional long-term follow-up study that would lengthen study participation for up to 3 years post-first dose.
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 males or healthy females of non-child-bearing potential between the ages of 18 to 50 at the time of screening
- •Positive CMV serostatus
- •Assessed by clinic staff as being low risk for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last protocol visit
- •Willing to use condoms during intercourse through Week 36 or the end of the study
- •Willing to undergo HIV testing, risk reduction counseling, and receive HIV test results
- •Willing to comply with the protocol requirements regarding donation of blood, sperm or other tissues
- •In the opinion of the Investigator, generally in good health as determined from medical history and no clinically significant findings from physical examinations, vital signs, and laboratory values
排除标准
- •Live in a home with children under the age of 6
- •Routine provision of child care to children under the age of 6
- •Have close contact with immunocompromised individuals
- •Have close contact with pregnant women or a partner planning to become pregnant during the course of the study
- •Health care provider who routinely comes into contact with immunosuppressed patients or pregnant women
- •Participant is immunocompromised
- •Participant has an autoimmune disorder
- •Positive HIV test at the time of study screening
- •Receipt of another investigational HIV or CMV vaccine candidate
研究组 & 干预措施
VIR-1111
干预措施: VIR-1111 (Biological)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with any treatment-emergent adverse events (AEs)
时间窗: Day 1 through 36 weeks
A treatment-emergent AE is any AE with an onset date on or after the investigational product start date and no later than 36 weeks after permanent discontinuation of the investigational product.
Number of participants with any serious AEs (SAEs)
时间窗: Day 1 through 36 weeks
An SAE is any life-threatening event or one that results in hospitalization, significant disability/incapacity, death or congenital anomaly/birth defect.
Number of participants with any local site reactogenicity event after first dose
时间窗: Day 1 through 14 days after first dose
Signs and symptoms will be captured at the injection site (e.g., pain/tenderness, swelling, redness and induration) through self-assessment via participant diaries and in-person clinical assessments.
Number of participants with any local site reactogenicity event after second dose
时间窗: Day 1 through 14 days after second dose
Signs and symptoms will be captured at the injection site (e.g., pain/tenderness, swelling, redness and induration) through self-assessment via participant diaries and in-person clinical assessments.
Number of participants with any systemic reactogenicity event after first dose
时间窗: Day 1 through 14 days after first dose
Systemic signs and symptoms (fever, headache, fatigue, arthralgia, myalgia, malaise, nausea, vomiting or chills) through self-assessment via participant diaries and in-person clinical assessments.
Number of participants with any systemic reactogenicity event after second dose
时间窗: Day 1 through 14 days after second dose
Systemic signs and symptoms (fever, headache, fatigue, arthralgia, myalgia, malaise, nausea, vomiting or chills) through self-assessment via participant diaries and in-person clinical assessments.
Number of participants with any treatment-emergent clinical laboratory abnormalities (chemistry, hematology and liver function tests)
时间窗: Day 1 through 36 weeks
A treatment-emergent clinical laboratory abnormality is a clinical laboratory value that increases at least 1 toxicity grade from baseline at any postbaseline timepoint up to 30 days after permanent discontinuation of study drug. Clinical laboratory abnormalities are graded using DAIDS Table for Grading and Severity of Adult and Pediatric Events, Corrected Version 2.1, July 2017.
Number of participants with CMV vector viremia (blood)
时间窗: Day 1 through 36 weeks
Quantitative polymerase chain reaction (qPCR) for CMV will be performed on participant blood samples collected throughout the study. Positive samples will undergo follow-up confirmatory PCR testing to differentiate wild-type CMV from CMV vaccine vector sequences.
Number of participants with CMV vector shedding (urine and saliva)
时间窗: Day 1 through 36 weeks
Quantitative polymerase chain reaction (qPCR) for CMV will be performed on both saliva and urine samples collected from participants throughout the study to monitor for viral shedding. Positive samples will undergo follow-up confirmatory PCR testing to differentiate wild-type CMV from CMV vaccine vector sequences.
次要结局
- Memory phenotype of CMV-specific CD8 T cells via flow cytometry analysis of CD45RA, CCR7, CD27, CD28 AND/OR CD95(0-36 weeks)
- Frequency of CMV-specific CD8 T cells via peptide stimulation, intracellular cytokine staining and flow cytometry to detect IL-2 AND/OR IFNg AND/OR TNFa(0-36 weeks)
- Frequency of CMV-specific CD4 T cells via peptide stimulation, intracellular cytokine staining and flow cytometry to detect IL-2 AND/OR IFNg AND/OR CD154(0-36 weeks)
- Frequency of HIV-1 Clade A Gag-specific CD4 T cells via peptide stimulation, intracellular cytokine staining and flow cytometry to detect IL-2 AND/OR IFNg AND/OR TNFa AND/OR CD154(0-36 weeks)
- Frequency of HIV-1 Clade A Gag-specific CD8 T cells T cells via peptide stimulation, intracellular cytokine staining and flow cytometry to detect IL-2 AND/OR IFNg AND/OR TNFa(0-36 weeks)
- Memory phenotype of CMV-specific CD4 T cells via flow cytometry analysis of CD45RA, CCR7, CD27, CD28 AND/OR CD95.(0-36 weeks)
- Memory phenotype of HIV-1 Clade A Gag-specific CD4 T cells via flow cytometry analysis of CD45RA, CCR7, CD27, CD28 AND/OR CD95(0-36 weeks)
- Memory phenotype of HIV-1 Clade A Gag-specific CD8 T cells via flow cytometry analysis of CD45RA, CCR7, CD27, CD28 AND/OR CD95(0-36 weeks)
- Binding titers of CMV-specific IgG antibodies(0-36 weeks)
- Binding titers of HIV Clade A Gag-specific IgG antibodies(0-36 weeks)