A Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial to Evaluate the Safety and Immunogenicity of the Therion Recombinant Vaccinia-HIV-1 IIIB ENV/GAG/POL Vaccine (TCB-3B) and MN RGP 120/HIV-1 In Alum.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 4
研究概览
简要总结
To evaluate the safety of administering Therion Recombinant Vaccinia-HIV-1 IIIB env/gag/pol Vaccine (TBC-3B) vaccinations to vaccinia-naive individuals. To evaluate the immunogenicity of priming with TBC-3B by the scarification, intradermal, and subcutaneous routes, followed by booster immunization of MN rgp120 HIV-1. To compare the immunogenicity of priming with TBC-3B in vaccinia-naive individuals to vaccinia-immune individuals.
In prior trials evaluating alternative methods of vaccine administration, scarification has been found to be an imprecise method of administration and allows only 1.0 - 2.5 microliters of immunogen to be given. Since it is not feasible to produce vaccine at concentrations higher than 10 to the 10th pfu/ml, this method limits the maximum deliverable dose. Intradermal and subcutaneous injection routes allow larger volumes of vaccinia to be given, i.e.: up to 200 microliters intradermally and up to 100 ml subcutaneously. In the present study, the initial priming dose will be the same administered by all 3 methods; however, the second priming dose administered at 2 months intradermally and subcutaneously will be 2 logs higher in order to achieve boosting of immune responses, particularly to gag and pol components of TBC-3B.
详细描述
In prior trials evaluating alternative methods of vaccine administration, scarification has been found to be an imprecise method of administration and allows only 1.0 - 2.5 microliters of immunogen to be given. Since it is not feasible to produce vaccine at concentrations higher than 10 to the 10th pfu/ml, this method limits the maximum deliverable dose. Intradermal and subcutaneous injection routes allow larger volumes of vaccinia to be given, i.e.: up to 200 microliters intradermally and up to 100 ml subcutaneously. In the present study, the initial priming dose will be the same administered by all 3 methods; however, the second priming dose administered at 2 months intradermally and subcutaneously will be 2 logs higher in order to achieve boosting of immune responses, particularly to gag and pol components of TBC-3B.
After volunteers are recruited, screened and enrolled in the study, they will be randomized to group C, D, or E. Each group will enroll 10 patients and 2 controls. The placebo control for TBC-3B will be standard vaccinia vaccination administered at doses no higher than that administered by scarification; the placebo control for MN rgp120 will be alum. Group C will receive undiluted TBC-3B by scarification, at months 0 and 2. Group D will receive diluted TBC-3B intradermally at month 0 and undiluted TBC-3B at month 2. Group E will receive diluted TBC-3B subcutaneously at month 0 and undiluted TBC-3B at month 2. At months 8 and 12 all groups will receive MN rgp 120/HIV-1 in alum intramuscularly.
研究设计
- 研究类型
- Interventional
- 主要目的
- Prevention
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients must have:
- •Negative FDA-approved ELISA for HIV within 8 weeks of immunization.
- •Normal history and physical examination.
- •Negativity for Hepatitis B surface antigen.
- •Availability for follow-up for planned duration of the study (18 months).
排除标准
- •Co-existing Condition:
- •Patients with the following symptoms or conditions are excluded:
- •Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol. Specifically excluded are people with a history of suicide attempts, recent suicidal ideation or who have past or present psychosis.
- •Active syphilis. NOTE: If the serology is documented to be a false positive or due to a remote (> 6 months) treated infection, the volunteer is eligible.
- •Active tuberculosis. NOTE: Patients with a positive PPD and a normal chest X-ray showing no evidence of TB and not requiring INH therapy are eligible.
- •Household contacts with, or occupational exposure to, people with any of the following:
- •Pregnancy. <12 months of age. Eczema or Immunodeficiency disease. Use of immunosuppressive medications.
- •Patients with the following prior conditions are excluded:
- •History of immunodeficiency, chronic illness, malignancy or autoimmune disease.
- •History of cancer, unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure.
- •Any history of anaphylaxis or history of other serious adverse reactions to vaccines.
- •History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., Stevens-Johnson syndrome, bronchospasm, or hypotension).
- •Eczema within the past year.
- •History of smallpox vaccination.
- •Envelope bands on HIV-1 Western blot within 8 weeks of immunization.
- •Prior Medication: Excluded:
- •Use of immunosuppressive.
- •Live attenuated vaccines within 60 days of study.
- •NOTE: Medically indicated subunit or killed vaccines (e.g. influenza, pneumococcal) do not exclude, but should be given at least 2 weeks prior to HIV immunizations.
- •Experimental agents within 30 days prior to study.
- •Prior receipt of HIV-1 vaccines or placebo recipient in a previous HIV vaccine trial.
- •Receipt of blood products or immunoglobulin within past 6 months.
- •Risk Behavior: Excluded:
- •History of injection drug use within the last 12 months prior to enrollment.
- •Higher or intermediate risk sexual behavior as defined by the AVEG.
- •Lower risk sexual behavior as defined by AIDS Vaccine Evaluation Group (AVEG) procedures.