Safety of and Immune Response to a Bird Flu Virus Vaccine (H5N1) in Healthy Adults
Phase 1 Inpatient Study of the Safety and Immunogenicity of Live Influenza A Vaccine H5N1 (6-2) AA ca Recombinant (A/VietNam/1203/2004 x A/AnnArbor/6/60/ca), a Live Attenuated Virus Vaccine Candidate for the Prevention of Avian Influenza H5N1 Infection in the Event of a Pandemic
研究概览
详细说明
AI viruses in their natural reservoir in waterfowl are the source from which novel HA and NA subtypes are introduced into the human population, and have the potential to initiate an influenza pandemic. This study will evaluate the safety and immunogenicity of a live, attenuated recombinant AI virus vaccine, H5N1 (6-2) AA Ca Recombinant (A/VietNam/1203/2004 x A/AnnArbor/6/60/Ca).
Participants in this study will receive one or two doses of the vaccine. There are 3 groups in this study:
- Group 1 will receive two vaccinations at the highest dose.
- Group 2 will receive one vaccination at a dose in-between the lowest and highest doses.
- Group 3 will receive one vaccination at the lowest dose.
Group 1 will enroll first, probably in 2006. Groups 2 and 3 will not enroll until it is determined by safety review that the vaccine is well-tolerated and greater than 80% of Group 1 participants shed vaccine virus or develop a specific immune response to the vaccine.
Participation in this study includes a hospital stay in an isolation unit of the Bayview Medical Center of Johns Hopkins University. All participants will receive the vaccine at study entry and will remain in the isolation unit for a minimum of 14 days after vaccination. A physical exam and a nasal wash will occur daily in the isolation unit until a participant is discharged from the hospital. Participants will be allowed to leave the unit once viral cultures for influenza from nasal washes are negative for at least 3 consecutive days beginning on Day 10. Blood collection will occur at study entry, Day 7, sometime between Days 28 and 35, and sometime between Days 56 and 63.
There will be two separate hospitalizations for Group 1 participants. Group 1 participants will receive their doses of vaccine at study entry and sometime between Days 28 and 35. A physical exam and a nasal wash will occur daily in the isolation unit until a participant is discharged from the hospital. Participants will be allowed to leave the unit once viral cultures for influenza from nasal washes are negative for at least 3 consecutive days beginning on Day 10. Blood collection will occur at 4 or 5 selected timepoints, depending on the timing of the second vaccination.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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Maryland
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Baltimore、Maryland、美国、21205
- Center of Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Good general health
- Available for the duration of the trial
- Willing to use acceptable forms of contraception
Exclusion Criteria:
- Clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease
- Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the ability of the volunteer to understand and cooperate with the study
- Medical, work-related, or family problems as a result of alcohol or illicit drug use in the 12 months prior to study entry
- History of severe allergic reaction or anaphylaxis
- Current asthma or reactive airway disease
- History of Guillain-Barre syndrome
- HIV-1 infected
- Hepatitis C virus infected
- Positive for hepatitis B surface antigen (HBsAg)
- Known immunodeficiency syndrome
- Use of corticosteroids or immunosuppressive drugs within 30 days of study entry. Participants who have used topical corticosteroids are not excluded.
- Live vaccine within 4 weeks of study entry
- Killed vaccine within 2 weeks of study entry
- Absence of spleen
- Blood products within 6 months of study entry
- Current smoker
- Have traveled to the Southern Hemisphere or Asia within 14 days prior to study entry
- Have traveled on a cruise ship within 14 days prior to study entry
- Work in the poultry industry
- Investigational agents within 60 days prior to study entry, or currently participating in another investigational vaccine or drug trial
- Allergy to eggs or egg products
- Purified protein derivative (PPD) positive (positive tuberculosis [TB] test)
- Family member with immunodeficiency
- Other condition that, in the opinion of the investigator, would affect the participant's participation in the study
- Pregnant or breastfeeding
学习计划
研究是如何设计的？
设计细节
- 主要用途：预防
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：1
Two vaccinations of H5N1 VN 2004/AA vaccine at the highest dose
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Live, attenuated recombinant H5N1 (6-2) AA ca Recombinant (A/VietNam/1203/2004 x A/AnnArbor/6/60/ca) vaccine (one of three doses)
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实验性的：2
One vaccination of H5N1 VN 2004/AA vaccine at a dose in-between the lowest and highest doses
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Live, attenuated recombinant H5N1 (6-2) AA ca Recombinant (A/VietNam/1203/2004 x A/AnnArbor/6/60/ca) vaccine (one of three doses)
|
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实验性的：3
One vaccination of H5N1 VN 2004/AA vaccine at the lowest dose
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Live, attenuated recombinant H5N1 (6-2) AA ca Recombinant (A/VietNam/1203/2004 x A/AnnArbor/6/60/ca) vaccine (one of three doses)
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研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
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Frequency of vaccine-related reactogenicity events
大体时间：During the acute monitoring phase of the study
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During the acute monitoring phase of the study
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Anti-H5N1 antibody levels and seroconversion, defined as a greater than fourfold rise in serum hemagglutination inhibiting (HI) and/or neutralizing antibody titer compared to Day 0
大体时间：Throughout study
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Throughout study
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次要结果测量
结果测量 |
大体时间 |
|---|---|
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确定疫苗病毒脱落的表型稳定性
大体时间：在整个学习过程中
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在整个学习过程中
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To determine the number of vaccinees infected with the H5N1 VN 2004/AA ca recombinant vaccine candidate
大体时间：Throughout study
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Throughout study
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If 10^7, 10^5, and 10^3 TCID50 doses of vaccine are administered, to compare the infectivity rates, safety, and immunogenicity between dose groups, and to estimate the HID50 for this vaccine
大体时间：At study completion
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At study completion
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To determine whether immunogenicity is enhanced by a second dose of vaccine, and whether the first dose of vaccine restricts replication of the second dose
大体时间：Throughout study
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Throughout study
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To evaluate T-cell mediated and innate immune responses against the H5N1 VN 2004/AA ca recombinant vaccine candidate
大体时间：Throughout study
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Throughout study
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To develop a serum bank so that the capacity of the H5N1 VN 2004/AA ca recombinant vaccine candidate to elicit HI and neutralizing antibodies to future H5N1 influenza viruses can be tested
大体时间：Throughout study
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Throughout study
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合作者和调查者
调查人员
- 首席研究员：Ruth A. Karron, MD、Center of Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health
出版物和有用的链接
一般刊物
- Stephenson I, Nicholson KG, Wood JM, Zambon MC, Katz JM. Confronting the avian influenza threat: vaccine development for a potential pandemic. Lancet Infect Dis. 2004 Aug;4(8):499-509. doi: 10.1016/S1473-3099(04)01105-3.
- Ferguson NM, Cummings DA, Cauchemez S, Fraser C, Riley S, Meeyai A, Iamsirithaworn S, Burke DS. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature. 2005 Sep 8;437(7056):209-14. doi: 10.1038/nature04017. Epub 2005 Aug 3.
- Karron RA, Talaat K, Luke C, Callahan K, Thumar B, Dilorenzo S, McAuliffe J, Schappell E, Suguitan A, Mills K, Chen G, Lamirande E, Coelingh K, Jin H, Murphy BR, Kemble G, Subbarao K. Evaluation of two live attenuated cold-adapted H5N1 influenza virus vaccines in healthy adults. Vaccine. 2009 Aug 6;27(36):4953-60. doi: 10.1016/j.vaccine.2009.05.099. Epub 2009 Jun 21.
- Joseph T, Subbarao K. Human infections with avian influenza viruses. Md Med. 2005 Winter;6(1):30-2.
- Sims LD, Domenech J, Benigno C, Kahn S, Kamata A, Lubroth J, Martin V, Roeder P. Origin and evolution of highly pathogenic H5N1 avian influenza in Asia. Vet Rec. 2005 Aug 6;157(6):159-64. doi: 10.1136/vr.157.6.159.
- Webby RJ, Perez DR, Coleman JS, Guan Y, Knight JH, Govorkova EA, McClain-Moss LR, Peiris JS, Rehg JE, Tuomanen EI, Webster RG. Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines. Lancet. 2004 Apr 3;363(9415):1099-103. doi: 10.1016/S0140-6736(04)15892-3.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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H5N1 (6-2) AA ca Recombinant (A/VietNam/1203/2004 x A/AnnArbor/6/60/ca)的临床试验
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National Institute of Allergy and Infectious Diseases...Johns Hopkins Bloomberg School of Public Health完全的
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National Institute of Allergy and Infectious Diseases...完全的
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National Institute of Allergy and Infectious Diseases...Johns Hopkins Bloomberg School of Public Health完全的
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National Institute of Allergy and Infectious Diseases...完全的
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Biomedical Advanced Research and Development Authority完全的