Evaluation of a Therapeutic Immunization Strategy Associating a DNA Vaccine (GTU-MultiHIV B) Followed by a Lipopeptide Vaccine (LIPO-5) in the Control of Viral Replication Following Antiretroviral Treatment Interruption in HIV-1 Infected Patients With a CD4 Cell Count ≥ 600/mm3
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 103
- 试验地点
- 2
- 主要终点
- Plasma HIV-1 RNA level
研究概览
简要总结
The combination of GTU-MultiHIV B DNA and LIPO-5 vaccines in a prime-boost strategy is expected to induce strong and diverse HIV-specific immune responses in HIV-infected patients. The investigators will carry out the clinical therapeutic immunization "proof of concept" trial in HIV infected patients. The investigators propose a multi-center double blind randomized versus placebo phase II clinical trial in patients who are chronic asymptomatic HIV-infected patients, with undetectable viral load while treated with a potent combination of antiviral drugs. Patients will continue antiviral therapy combined with either therapeutic vaccination or placebo vaccination. Patients will undergo the procedure which includes a prime with the GTU-MultiHIV B DNA vaccine or placebo administered by IM injections via Biojector (a needle-free injection system) followed by a boost of LIPO-5 vaccine or placebo also given IM.
In total, 105 HIV-1 patients will be enrolled: 35 in the placebo arm and 70 in the vaccine arm. Patients will receive antiretroviral treatments and 3 administrations of DNA vaccine or its placebo at weeks 0, 4 and 12 (corresponding to prime vaccinations). They also receive 2 doses of LIPO-5 vaccines or its placebo at week 20 and 24 (corresponding to boost vaccinations). At week 36 antiretroviral treatments will be interrupted until week 48. Patients will be intensely monitored during the treatment interruption period. After start of cART treatment (at the latest in W48), a data collection from clinical car will be carried out. A blood sample with W74 will allow to study the persistence ot the immunizing responses, 1 year after the injection of the last vaccine/placebo.
The primary efficacy endpoint is a plasma HIV-1 RNA level at week 48 (e.g. 12 weeks after stopping all antiviral treatment).
The main hypothesis for conducting a phase II randomized trial is that immune responses in vaccinated patients may be associated with a better control of viral replication following c-ART interruption as compared to placebo-vaccinated patients.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Vaccine placebos
Vaccine placebos corresponding to the dilutant of these vaccines
干预措施: Placebos of GTU-multiHIV B and LIPO-5 vaccines (Biological)
Vaccine arm
干预措施: GTU-multHIV B vaccine and LIPO-5 vaccine (Biological)
结局指标
主要结局
Plasma HIV-1 RNA level
时间窗: week 48 (W48)
次要结局
- Plasma HIV-RNA after stopping antiviral treatment(W40, W44, W48 and W74)
- Percentage of patients with plasma HIV-RNA below 10 000 copies/mL(W48)
- Ultrasensitive proviral DNA(W-3, W20, W32 and W44)
- CD4 T cell counts(W40, W44 and W48 or prior HAART resumption and W74)
- Percentages of patients who resumed HAART(between W36 and W48)
- Percentages of patients who reached CD4 cell counts < 350/mm3 confirmed two weeks apart(between W36 and W48)
- Strength of HIV-specific CD4/CD8 responses(W0, W16, W28, W48 or at the time of failure anw W74)
- Proportion of responders to at least one HIV peptide pool(W0, W16, W28, W48 or at the time of failure and W74)
- Breadth of CD4/CD8+ HIV-specific responses defined as the number of HIV pools recognized among the 18 pools(W0, W16, W28, W48 or at the time of failure and W74)
- Polyfunctionality of HIV specific T cell responses evaluated by the mean proportion of CD4/CD8+ T cells producing IL-2 and/or IFN-g following ex-vivo stimulation with HIV-1 peptide pools(W0, W16, W28, W48 and W74)
- Adverse Events > grade 2(W0, W4, W12, W16, W20, W24, W28, W32, W36, W38, W40, W42, W44, W48 and W74)
- AIDS-defining events and serious non-AIDS events defined as cardiovascular diseases, kidney diseases, end stage liver diseases, non-AIDS defining malignancies except basal cellular skin cancer, and bacterial infections(W0, W4, W12, W16, W20, W24, W28, W32, W36, W38, W40, W42, W44, W48 and W74)
- Analysis of predictive factors for plasma HIV-RNA(W48)