A Phase I, Dose Escalation, Safety, and Immunogenicity Trial of an Alphavirus Replicon HIV-1 Subtype C Gag Vaccine (AVX101) in Healthy HIV-1 Uninfected Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 13
- 主要终点
- Grade IV adverse events
研究概览
简要总结
The purpose of this study is to evaluate the safety of and immune response to an alphavirus replicon, HIV-1 subtype C gag vaccine, AVX101, in HIV uninfected adults in the United States, South Africa, and Botswana.
详细描述
HIV-1 subtype C is the prevailing subtype of HIV found in sub-Saharan Africa and is primarily responsible for the HIV/AIDS epidemic in southern Africa. Thus, development of a preventive subtype C vaccine is critically important in controlling the spread of HIV in this part of the world. This study will determine the safety and immunogenicity of an alphavirus replicon HIV-1 subtype C gag vaccine, AVX101, in HIV uninfected adults. This vaccine utilizes a propagation-defective replicon vector system derived from an attenuated strain of Venezuelan Equine Encephalitis (VEE) virus. The vaccine replicon expresses the gag gene from a South African subtype C isolate of HIV-1. Participants will be recruited in the United States, South Africa, and Botswana.
The study will last for 1 year. Participants will be enrolled sequentially, from lowest to highest dose of vaccine, into one of four groups. Groups will begin enrollment only following safety review of the previous group. Participants will be randomly assigned to receive active vaccine or placebo. During the study, participants will receive either 3 injections of one of four possible doses of the vaccine or 3 injections of placebo. Injections will be given at study entry and at Days 28 and 84. At screening, participants will undergo medical history assessment, a complete physical, HIV testing and counseling, and blood and urine collection; they will also be interviewed and asked to complete a questionnaire. After screening, there will be 8 study visits; the visits will occur at Days 14, 28, 42, 84, 98, 168, 273, and 364. Participants will be interviewed and asked to fill out a questionnaire at each study visit; participants will undergo a physical, additional HIV testing and counseling, and blood and urine collection at selected visits.
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
- •HIV uninfected
- •At low risk for HIV infection
- •Willing to receive HIV test results
- •Good general health
- •Acceptable methods of contraception for females of reproductive potential
- •Hepatitis B surface antigen negative
- •Anti-hepatitis C virus antibody (anti-HCV) negative or negative HCV PCR if anti-HCV is positive
- •Meets educational requirements of the study
排除标准
- •HIV vaccines or placebos in prior HIV vaccine trial
- •Immunosuppressive medications within 168 days prior to first study vaccine administration
- •Blood products within 120 days prior to first study vaccine administration
- •Immunoglobulin within 60 days prior to first study vaccine administration
- •Live attenuated vaccines within 30 days prior to first study vaccine administration
- •Investigational research agents within 30 days prior to first study vaccine administration
- •Subunit or killed vaccines within 14 days prior to first study vaccine administration
- •Allergy treatment with antigen injections within 30 days prior to first vaccine administration
- •Current tuberculosis prophylaxis or therapy
- •Serious adverse reaction to a vaccine. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
- •Autoimmune disease or immunodeficiency
- •Active syphilis
- •Unstable asthma
- •Type 1 or type 2 diabetes mellitus
- •Thyroid disease requiring treatment in the past 12 months
- •Serious angioedema within the past 3 years
- •Uncontrolled hypertension
- •Bleeding disorder
- •Malignancy unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period
- •Seizure disorder requiring medication within the past 3 years
- •Mental illness that would interfere with compliance with the protocol
- •Other conditions that, in the judgment of the investigator, would interfere with the study
- •Pregnant or breastfeeding
研究组 & 干预措施
Placebo
phosphate buffered saline, pH 7.2, HSA, sodium gluconate, and sucrose
干预措施: placebo (Other)
结局指标
主要结局
Grade IV adverse events
时间窗: 1 year
The sample size at each vaccine dose level was selected such that the stopping rule for not escalating the dose (2 or more vaccine-related Grade IV adverse experiences) would be met with high probability if the true toxicity rate was above 15-20%, and such that dose escalation would occur with high probability if the true toxicity rate was less than 5%.
次要结局
- Replication-competent viral vector viremia(2 weeks after each vaccine dose)
- Intracellular cytokine staining (ICS) assay(3 months)
- IFN-gamma ELISpot assay(3 months)
- Antibodies to VEE virus(1 year)
- Local and systemic adverse events(7 days after each dose)
- Binding antibodies by ELISA(1 year)
- Chromium release CTL assay(3 months)