A Phase I/II Clinical Trial to Evaluate the Safety and Immunogenicity of a Multiclade HIV-1 DNA Plasmid Vaccine, VRC-HIVDNA016-00-VP, Boosted by a Multiclade HIV-1 Recombinant Adenovirus-5 Vector Vaccine, VRC-HIVADV014-00-VP, in HIV Uninfected Adult Volunteers in East Africa
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 326
- 试验地点
- 5
- 主要终点
- Laboratory measures of safety
研究概览
简要总结
The purpose of the study is to determine the safety of and immune response to an investigational HIV vaccine, VRC-HIVDNA016-00-VP, and a vaccine booster, VRC-HIVADV014-00-VP, in HIV uninfected adults from Kenya, Tanzania, and Uganda.
详细描述
The worldwide HIV/AIDS epidemic may only be controlled through development of a safe and effective vaccine that will prevent HIV infection. This study will evaluate the safety and immunogenicity of an experimental adenovirus-vectored multiclade HIV vaccine, VRC-HIVADV014-00-VP, followed with or without a similarly structured DNA plasmid HIV vaccine, VRC-HIVDNA016-00-VP. The DNA in both vaccines codes for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections in the world. HIV uninfected volunteers will be recruited in the East African nations of Kenya, Tanzania, and Uganda.
This study will comprise two parts, 1 and 2. Part 1 will enroll 144 participants who will be randomly assigned to one of four different groups:
- Group 1A participants will receive a low dose of the adenovirus-vectored HIV vaccine or placebo at study entry.
- Group 1B participants will receive a higher dose of the adenovirus-vectored HIV vaccine or placebo at study entry.
- Group 1C will receive the DNA plasmid vaccine or placebo at study entry and Days 28 and 56. They will also receive either a low dose of the adenovirus-vectored HIV vaccine or placebo at Day 168.
- Group 1D will receive the DNA plasmid vaccine or placebo at study entry and Days 28 and 56. They will also receive either a higher dose of the adenovirus-vectored HIV vaccine or placebo at Day 168.
Enrollment into Part 2 (Groups 2A and 2B) will begin after the completion of the safety data evaluation of Groups 3 and 4 and after Part A has been fully enrolled. Group 2A participants will receive the DNA plasmid vaccine or placebo at study entry and Days 28 and 56. They will also receive either a low dose of the adenovirus-vectored HIV vaccine or placebo at Day 168.
There will be 11 study visits over 14 to 16 months for Parts 1 and 2. All study visits will include a physical exam, medical and medication history, vital signs measurement, lymph node assessment, HIV and pregnancy counseling, and blood and urine collection. A home visit will also occur at study entry. A 3-day diary card to report side effects will be completed by participants at study entry and on Days 28, 56, 168, and 210.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Good general health
- •Willing to follow all the requirements of the study and available for follow-up for the duration of the study (14 to 16 months)
- •Able and willing to provide informed consent
- •Willing to undergo HIV testing and counseling and willing to receive HIV test results
- •Willing to not engage in high-risk behavior for HIV infection during the study
- •Willing to provide location and be visited at home
- •Willing to be identified with picture identification for study purposes
- •Willing to use acceptable forms of contraception
- •Pregnant women and those with conditions which render phlebotomy volumes hazardous will be allowed to participate using a minimized phlebotomy schedule
排除标准
- •HIV or HBV infection
- •HIV vaccines in prior HIV vaccine trial
- •Immunosuppressive or cytotoxic medications within the 6 months prior to study entry. Participants who have used corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for acute uncomplicated dermatitis are not excluded.
- •Blood products within 120 days prior to study entry
- •Immunoglobulin within 60 days prior to study entry
- •Live attenuated vaccines within 30 days prior to first study vaccine administration
- •Medically indicated subunit or killed vaccines or allergy treatment with antigen injections within 14 days prior to first study vaccine administration
- •Investigational research agents within 30 days prior to first study vaccine administration
- •Current tuberculosis prophylaxis or therapy
- •Participated in high-risk behavior for HIV infection within 6 months prior to study entry. More information on this criterion can be found in the protocol.
- •Serious adverse reactions to vaccines, such as anaphylaxis, hives, respiratory difficulty, angioedema, or abdominal pain
- •Autoimmune disease or immunodeficiency
- •Unstable asthma or asthma requiring emergent or urgent care, hospitalization, intubation, or oral or intravenous corticosteroids during the 2 years prior to study entry
- •Diabetes mellitus type 1 or
- •Patients with gestational diabetes are not excluded.
- •Thyroid disease, including removal of thyroid or disease requiring medication within 3 years prior to study entry
- •Serious angioedema within 3 years prior to study entry or disease requiring medication within 2 years prior to study entry
- •Uncontrolled hypertension
- •Bleeding disorder
- •Active syphilis
- •Active cancer OR treated cancer that may recur during the duration of the study
- •Seizure disorder. Participants who have had fever-related seizures prior to age 2 are not excluded.
- •Absence of spleen OR partial or complete lack of splenic function
- •Psychiatric condition that may interfere with the study, including past or present psychoses, bipolar disorder, or suicidal attempts
- •Any medical, psychiatric, or social condition that, in the opinion of the investigator, may interfere with the study
- •Any occupational or other responsibility that, in the opinion of the investigator, may interfere with the study
- •Pregnancy, breastfeeding, or plan to become pregnant
- •Any occupational or other responsibility that, in the opinion of the investigator, may interfere with the study
- •Incapacitating illness precluding clinic visits
- •Unable to provide informed consent
- •Prisoners will not be enrolled while incarcerated and if enrolled prior to incarceration, will not be followed while in confinement. Re-consent will not be required upon release from prison.
结局指标
主要结局
Laboratory measures of safety
时间窗: Throughout study
CD4+ and CD8+ T cell responses to HIV-1, as measured by flow cytometry-based intracellular cytokine staining (ICS) assay
时间窗: At Day 196
Local reactogenicity signs and symptoms
时间窗: Throughout study
Systemic reactogenicity signs and symptoms
时间窗: Throughout study
Adverse and serious adverse experiences
时间窗: Throughout study
Unfractionated IFN-gamma ELISPOT responses to HIV-1
时间窗: At Day 196
次要结局
未报告次要终点