Safety and Immunogenicity of a Vaccine Dendritic Cell-based Pulsed With Autologous Heat-inactivated HIV in HIV-1 Infected Patients. Prospective, Randomized, Partially Blinded Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Virological
研究概览
简要总结
single-center, national clinical trial, phase I, randomized (1: 1: 1: 1), prospective, placebo-controlled, partially masked, parallel group. Patients will be assigned to one of the following four arms: 3 immunizations of dendritic cells / 3 immunizations of dendritic cells with pegylated interferon + / 3 immunizations of placebo / 3 immunizations of placebo with pegylated interferon.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- 否
入选标准
- •Patient > 18 years of age;
- •Voluntarily sign informed consent;
- •Men or women with a negative pregnancy test before inclusion in the study;
- •HIV infection tested (with positive antibodies to HIV-1 and a detectable viral load);
- •Patient must be on stable treatment with cART at least 1 year
- •The average of all measurements of CD4 during the year before starting cART should be equal or greater than 350 cells / mm3
- •The number of CD4 + at enrollment must be equal or greater than 450 cells / mm3;
- •Plasma HIV viral load undetectable at least 6 months before the inclusion in the study, at least two determinations (occasional blips above the undetectable level are allowed).
排除标准
- •Treatment with suboptimal regimen (less than 3 antiretroviral drugs) before starting cART;
- •History of C CDC events;
- •Interruption of cART during the inclusion in the study;
- •Pregnancy woman or becoming pregnant in the next months;
- •Active opportunistic infections, or any active infection or cancer within 30 days prior to the screening visit;
- •Therapy with immunomodulatory agents, including cytokines (eg IL-2) and gamma globulins or chemotherapy within 90 days prior to the screening visit;
- •Use of anticoagulant medication;
- •Use of any investigational drug within 90 days prior to study entry;
- •Virological failure prior to antiretroviral treatment and / or mutations that confer resistance to antiretroviral drugs;
- •Uncontrolled psychiatric disorder;
- •Platelet count <80,000 / mm3;
- •Values ??of hemoglobin <12g / dL;
- •Patients with active uncontrolled autoimmune diseases;
- •Using contraindicated drugs in accordance with the Summary of Product Specifications of pegylated interferon;
- •Childbearing, or potential childbearing not using highly effective contraception;
- •Any other problem that according to the investigator could interfere with the evaluation of the objectives.
- •Any contraindication for the use of interferon peg in accordance with the Summary of Product Characteristics.
研究组 & 干预措施
DCV3
Autologus differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus
干预措施: DCV3 (Biological)
DCV3 with PEG-INF
Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus with PEG-INF
干预措施: DCV3 with PEG-INF (Biological)
CD placebo
Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded
干预措施: Placebo (Biological)
CD placebo + PEG-INF
Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded with PEG-INF
干预措施: Placebo with PEG-INF (Biological)
结局指标
主要结局
Virological
时间窗: 12 weeks
Proportion of patients with undetectable viral load (\<37 copies / mL) at 12 weeks
Number of Participants with adverse events of grade 3 or higher
时间窗: 28 weeks
* Local adverse events of grade 3 or higher (pain and skin reactions including induration) * Systemic adverse events of grade 3 or higher (fever, chills, headache, nausea, vomiting, malaise and myalgia) * Clinical or laboratory confirmed grade 3 or higher on physical examination or retests adverse events Any event attributable to the vaccine involving a discontinuation of vaccination regime.
次要结局
- Number of adverse events grade 1 and 2 within 14 days after each immunization (weeks 2, 4 and 6)(6 weeks)
- Changes in the specific immune response(28 weeks)
- Changes in levels of viral reservoir.(28 weeks)
- Evaluation of the specific immune response trought IFN-gamma production in vitro at screening and baseline(week 0)
- Proportion of patients with changes in any value of the levels of inflammatory markers, microbial translocation and immune activation(28 weeks)
- Proportion of patients with viral rebound(15 days)
- Proportion of patients with autoimmunity markers induced by the vaccine as measured by: antithyroid antibodies (antithyroglobulin, antithyroid peroxidase), antinuclear antibodies, antiphospholipid antibodies and rheumatoid factors.(16 weeks)
- Evaluation of the specific immune response thought T-cell proliferation in vitro at screening and baseline(week 0)
- Changes in the transcriptome of patients visits weeks 4, 16 and 28 compared to baseline (week -12)(28 weeks)
- Evaluation of the specific immune response thought dendritic cell maturation markers in vitro at screening and baseline(week 0)
研究者
Judit Pich Martínez
Clinical Research Manager
Fundacion Clinic per a la Recerca Biomédica