A Randomised, Open Labelled, Phase I, Safety, Toxicity, and Exploratory Immunogenicity Evaluation of Therapeutic Immunisation +/- IL-2, GM-CSF and Growth Hormone in HIV-1 Infected Subjects Receiving Highly Active Anti-retroviral Therapy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- The primary outcome will be analysis of safety and toxicity data in relation to grade 3 or above laboratory or clinical serious adverse event (SAE) which can be attributed to the treatments given
研究概览
简要总结
For several years there has been interest in why some people with HIV-1 progress more slowly to disease and have longer survival without Highly Active Antiretroviral Therapy (HAART) than others. The investigators and others have identified a few HIV positive individuals who can control their viral load for many years without HAART, these rare individuals do not lose their HIV-1-specific cellular immune responses, which are very important for controlling viral load. This group is referred to as long-term non-progressors (LTNP). Unlike LTNP the majority of HIV-1 infected individuals are chronic progressors (CP) who do not make effective HIV-1-specific cellular immune responses, even when on HAART. We propose to use a novel DNA vaccine boosted with immune based therapy (cytokines and hormones) to try to regenerate the missing HIV-1-specific cellular immune responses to make chronically infected HIV-1+ persons more like LTNP.
By injecting this novel DNA vaccine and immune based therapy into the people who are already infected with HIV-1, the immune system may be stimulated to mount a greater immune response not only to the vaccines but also to real HIV-1 particles and HIV-1-infected cells.
详细描述
This will be a randomised, Phase I, open label comparative study running for 52 weeks (2 screen visits 2 weeks apart followed by 48 weeks of study). 50 patients will be screened in the initial phase of which 30 clade B infected individuals will be randomised into the study, which will consist of 3 arms:
Arm 1 will ascertain vaccine safety and toxicity in the presence of cytokine/hormone therapy.
Arm 2 will identify vaccine safety and toxicity.
Arm 3 will indicate safety and toxicity of cytokine/hormone therapy.
The target patients are chronically HIV-1 clade B infected persons who will have had a nadir CD4 T-cell count of >200 cells/ul blood before they started ART. The current CD4 T-cell count should be >400 cells/ul blood. Patients may have received ART for any length of time, but currently should be receiving NNRTI or boosted-PI based HAART, and have a viral load below the level of detection (50 copies/ml plasma). Patients will be bled on two occasions before commencing IBT regimens, in order to establish baselines, and then at regular intervals thereafter (weeks 0,1,2,4,6,8,12,16,24 and 48).
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
- None
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
- •Documented HIV-1 positive result.
- •Stable on HAART.
- •Two screening viral loads of <50 cps/ml on 2 consecutive occasions at least one month apart.
- •CD4 T cell count of >400 cells/ul.
- •Nadir CD4 T cell count of >200 cells/ul.
- •Over 18 years of age.
- •Willing and able to provide informed consent.
- •Female subjects must not be pregnant or lactating.
- •Subjects must be using adequate double barrier method of contraception as appropriate.
排除标准
- •Prior therapeutic vaccination.
- •Acute illness within 2 weeks of the start of the study.
- •Prior immunomodulatory therapy (e.g. IL-2, rhGH, GCSF, GM-CSF, HU)
- •Receiving immunosuppressive medication (e.g. Steroids)
- •Participation in other vaccine trials currently
- •Patients with diabetes mellitus type 2
- •Patients with cardiac abnormalities
- •Patients with pre-existing autoimmune disease
- •Patients with active neoplasia
- •Patients with evidence of any progression or recurrence of an underlying intra-cranial lesion
研究组 & 干预措施
Vaccine and cytokines
Day 0: Patients receive GTU-MultiHIV B clade vaccine 1mg/ml administered as 10 intradermal injections of 100 µl/injection.
Day 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections.
Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC.
Further vaccine boosters are given on day 42 and day 84. GTU-MultiHIV B clade vaccine 1mg/ml being administered as 10 intradermal injections of 100 µl/injection.
干预措施: GTU-MultiHIV B clade vaccine1mg (Biological)
Vaccine and cytokines
Day 0: Patients receive GTU-MultiHIV B clade vaccine 1mg/ml administered as 10 intradermal injections of 100 µl/injection.
Day 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections.
Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC.
Further vaccine boosters are given on day 42 and day 84. GTU-MultiHIV B clade vaccine 1mg/ml being administered as 10 intradermal injections of 100 µl/injection.
干预措施: Interleukin-2 (Drug)
Vaccine and cytokines
Day 0: Patients receive GTU-MultiHIV B clade vaccine 1mg/ml administered as 10 intradermal injections of 100 µl/injection.
Day 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections.
Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC.
Further vaccine boosters are given on day 42 and day 84. GTU-MultiHIV B clade vaccine 1mg/ml being administered as 10 intradermal injections of 100 µl/injection.
干预措施: GM-CSF (Drug)
Vaccine and cytokines
Day 0: Patients receive GTU-MultiHIV B clade vaccine 1mg/ml administered as 10 intradermal injections of 100 µl/injection.
Day 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections.
Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC.
Further vaccine boosters are given on day 42 and day 84. GTU-MultiHIV B clade vaccine 1mg/ml being administered as 10 intradermal injections of 100 µl/injection.
干预措施: Growth Hormone (Drug)
Vaccine alone
Day 0: Patients are given GTU-MultiHIV B clade vaccine 1mg/ml administered as 10 intradermal injections of 100 µl/injections.
Day 42: GTU-MultiHIV B clade vaccine as day 0.
Day 84: GTU-MultiHIV B clade vaccine as day 0.
干预措施: GTU-MultiHIV B clade vaccine1mg (Biological)
Cytokines alone
Day 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections.
Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC.
干预措施: Interleukin-2 (Drug)
Cytokines alone
Day 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections.
Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC.
干预措施: GM-CSF (Drug)
Cytokines alone
Day 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections.
Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC.
干预措施: Growth Hormone (Drug)
结局指标
主要结局
The primary outcome will be analysis of safety and toxicity data in relation to grade 3 or above laboratory or clinical serious adverse event (SAE) which can be attributed to the treatments given
时间窗: Weekly
次要结局
- The secondary immunological outcomes will be percentage change from baseline to study time point in defined cellular immune responses.(weekly)