A Phase I Double-Blind Study to Evaluate the Safety and Immunogenicity of HIV Prime/Boost Vaccine Using DNA and MVA for HIV-1/AIDS
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Occurrence, intensity and relationship to vaccination of local and systemic adverse events
研究概览
简要总结
This is a randomized, double-blind placebo-controlled dose-escalation clinical trial to evaluate the safety and the immunogenicity of DNA and modified vaccinia virus Ankara (MVA) HIV-1 vaccines in subjects receiving stable highly active antiretroviral therapy (HAART) who have an HIV-1 RNA < 50 copies/mm3 and CD4+ T cells count ≥ 350 cells/mm3.
详细描述
HIV-infected patients treated with antiretroviral therapy for prolonged periods of time may show decreased levels of HIV-specific immune responses. In these patients, a prime-boost vaccine strategy may induce both humoral and cell-mediated immunity. The hypothesis of this study is that the vaccine strategy selected will be both safe and immunogenic in the patient population being tested.
Patients continue antiretroviral medications throughout the course of this study. Three groups of patients receive dose-escalation (0.5mg, 2mg or 4mg) intramuscular injections of DNA vaccine (D-GPEi) respectively, the other three groups of patients receive dose-escalation (3×10^7pfu, 1×10^8pfu or 3×10^8pfu) intradermal injections of MVA vaccine (M-GPE), two weeks post immunization of lower dose, if the vaccine is safe and well tolerant, the next dose of immunization will begin. After the maximum tolerated dose of DNA and MVA is identified, DNA prime/ MVA boosting will be tested in another two groups of patients. Lower or the maximum tolerated dose of D-GPEi was used at week 0 and 1, lower or the maximum tolerated dose of M-GPE was used at week 2 and 3, patients are monitored for safety 72 hours after each immunization. In addition, each patient records adverse events in a diary. Patients have regular physical exams, pregnancy tests, and blood drawn for virologic and immunologic assessments. The induction of HIV-specific responses will be measured.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Are willing to participate this study and available for follow-up for the duration of the study.
- •Men and women aged 18-50 years.
- •Are HIV-positive.
- •Have been taking stable anti-HIV drugs for at least 6 months.
- •CD4 count ≥ 350 cells/mm3
- •Plasma viral load < 50 copies/ml.
- •Willing to use acceptable forms of contraception at least 21 days prior to first vaccination until 56 days after the last vaccination.
排除标准
- •Pregnancy or breast-feeding.
- •History of previous vaccination with an HIV-1 vaccine.
- •Use of immunoinhibitory agents, such as corticosteroids or cytotoxic drugs by oral administration, injection route or inhalation route within 6 months of study entry (But corticosteroids used for allergic rhinitis and skin topical application of corticosteroids were not included); Use of immunomodulatory agents including but not limited to interleukin-2(IL-2） and granulocyte-macrophage colony-stimulating factor (GM-CSF) within 30 days of study entry.
- •Use of blood products within 3 months of study entry.
- •Use of other experimental drugs within 3 months of study entry.
- •Any immunization within 3 months of study entry.
- •Comply with any of the following items： Active pulmonary tuberculosis； History of serious adverse reaction to other vaccines； Serious asthma； Have untreated thyroid disease; Syphilis
- •Laboratory values（Comply with any of the following items）:
- •Hemoglobin < 100 g/L (male subjects)，<90 g/L (female subjects)； Absolute neutrophil count ≤ 1000 cells/mm3； Serum creatinine ≥15 mg/L，endogenous creatinine clearance rate <50 ml/min； alanine aminotransferase（ALT）, aspartate aminotransferase(AST) ≥3× upper limit of normal range； Total bilirubin ≥2× upper limit of normal range
- •Clinically significant electrocardiogram changes.
- •Hypertension ( If it is well controlled by medication and is less than 150/100mmHg , should not be excluded) and other cardiac disease；
- •Any medical, psychiatric, social condition, occupational reason judged by the investigator that would limit the evaluation of a subject.
结局指标
主要结局
Occurrence, intensity and relationship to vaccination of local and systemic adverse events
时间窗: 8 months
To evaluate the safety and tolerance of a DNA and a replication-defective MVA vaccine expressing HIV-1 gag-pol and env in HIV-1 infected subjects on highly active antiretroviral therapy. Frequency and severity of adverse events, laboratory abnormalities, and local and systemic reactogenicity signs and symptoms following vaccinations
次要结局
- Immunogenicity of vaccine(14 months)
研究者
Yi Zeng
Departement Director
Centers for Disease Control and Prevention, China