Immunotherapy of HIV-infected Patients An Open, Dose-escalating Assessment of Vacc-C5 With Either GM-CSF or Alhydrogel as Adjuvant in HIV-1-infected Subjects on Antiretroviral Therapy (ART)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Safety measured as change of AE records, clinical chemistry (incl. CD4, CD8, HIV-1 RNA)and hematology laboratory elevations
研究概览
简要总结
Background:
Despite the introduction of highly effective antiretroviral therapy (ART) regimes, which control the HIV infection and results in increases in CD4 cell counts and an undetectable viral load, many patients suffer from increased morbidity. There is evidence that presence of antibodies against the C5 region of gp120 strongly correlates with slower disease progression, and that loss of antibody responses to this region are associated with progression.
Investigational product:
Vacc-C5 is a single heterodimeric peptide-based HIV therapeutic vaccine corresponding to the C5 region on gp120 and the external domain of gp41. The vaccine is intended to create a non-neutralizing antibody against C5 region.
Study objectives:
- To evaluate safety of the vaccination regimens
- To evaluate C5-specific humoral immune responses (antibodies), T cell responses, T cell activation markers and other immune markers.
详细描述
Background:
Despite the introduction of highly effective antiretroviral therapy (ART) regimes, which control the HIV infection and results in increases in CD4 cell counts and an undetectable viral load, many patients suffer from increased morbidity. There is evidence that presence of antibodies against the C5 region of gp120 strongly correlates with slower disease progression, and that loss of antibody responses to this region are associated with progression.
Investigational product:
Vacc-C5 is a single heterodimeric peptide-based HIV therapeutic vaccine corresponding to the C5 region on gp120 and the external domain of gp41. The rationale behind the Vacc-C5 is the finding that long-term non-progressors (LTNP) subjects have more antibodies towards the C5 part of gp120 than HIV infected subjects with a more rapid disease progression.
The primary objective of Vacc-C5 immunotherapy is to induce a humoral immune response. The vaccine is intended to create a non-neutralizing antibody against the C5 region and to thereby mimic a natural process in HIV-infected long-term non-progressors (LTNP) subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between18 years and 55 years, both genders.
- •HIV positive at least one year.
- •Clinically stable on ART for the last 6 months (changes in therapy is allowed as long as the viral load is stable).
- •Documented viral load (HIV-1 RNA) less than 50 copies/mL for the last six months. Single blips (up to 500 copies/mL) are allowed.
- •Documented pre-study CD4 cell count ≥ 400x106/L for at least six months (if below at screening, a re-analysis is allowed).
- •Nadir (lowest ever) CD4 cell count ≥ 200x106/L (nadir below 200x106/L requires two consecutive analyses).
- •Signed informed consent.
排除标准
- •Reported pre-study AIDS-defining illness within the previous year
- •Malignant disease.
- •On chronic treatment with immunosuppressive therapy.
- •Unacceptable values of the hematologic and clinical chemistry parameters, as judged by the Principle Investigator (or designee), including creatinine values >1.5x upper limit of normal (ULN), and AST (SGOT), ALT (SGPT) and alkaline phosphatase values >2.5x ULN.
- •Concurrent chronic active infection such as viral hepatitis B or C or tuberculosis.
- •Pregnant or breastfeeding women.
- •Women of childbearing potential not using reliable and adequate contraceptive methods (defined as: use of oral, implanted, injectable, mechanical or barrier products for the prevention of pregnancy; practicing abstinence; sterile) during the study, or sexually active male subjects with partners of childbearing potential unwilling to practice effective contraception during the study.
- •Current participation in other clinical therapeutic studies.
- •Incapability of compliance to the treatment protocol, in the opinion of the Investigator.
研究组 & 干预措施
Arm 2=Arm B: Vacc-C5/Alhydrogel
Arm 2=Arm B: Vacc-C5 with Alhydrogel as adjuvant administered intramuscularly.
干预措施: Vacc-C5/Alhydrogel (Drug)
Arm 1= Arm A: Vacc-C5 /GM-CSF.
Arm 1=Arm A: Vacc-C5 with GM-CSF as adjuvant administered intradermally.
干预措施: Vacc-C5/GM-CSF (Drug)
结局指标
主要结局
Safety measured as change of AE records, clinical chemistry (incl. CD4, CD8, HIV-1 RNA)and hematology laboratory elevations
时间窗: From screening and week 1 to weeks 2, 4, 6, 12, 13, 15, 21, 22 and 26
* AEs recorded at each scheduled and unscheduled visit. * Concomitant medications recorded at each scheduled visit. * Vital signs (heart rate, blood pressure) at screening, weeks 1, 4, 6, 12, 13, 15, 21, 22 and 26 (End of study). * Weight at screening and weight at weeks 1, 12 and 26 (End of study). * Clinical laboratory evaluations (clinical chemistry, hematology) at screening, weeks 1, 4, 6, 12, 15, 21 and 26 (End of study). * Viral load (HIV-1 RNA) at screening, weeks 1, 6, 15 and 26 (End of study). * Urine stix at weeks 1, 4, 6, 12, 15, 21 and 26 (End of study).
次要结局
- Change in Humoral and T cell responses(From screening and week 1 to weeks 4, 6, 12, 13, 15, 21, 22 and 26)