Reactogenicity, Safety and Immunogenicity of a Live Monovalent А/17/Hong Kong/2017/75108 (H7N9) Influenza Vaccine
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 40
- 主要终点
- Number of Participants with Immediate reactions
研究概览
简要总结
This is a single center phase I, double-blind placebo-controlled study to assess reactogenicity, safety and immunogenicity of a live monovalent A/17/Hong Kong/2017/75108 (H7N9) influenza vaccine in healthy male and female adults, 18 through 49 years of age.
详细描述
This is a phase I, double-blind, individually-randomized (3:1, vaccine:placebo), controlled trial with two groups, LAIV H7N9 and matched placebo. Healthy male and female adults 18 through 49 years of age will be invited to participate. For feasibility reasons and in order for an independent Safety Monitoring Committee (SMC) to review safety data in a portion of subjects initially, the total cohort of 40 subjects will be enrolled in two cohorts: one cohort of 20 subjects, randomized at 3:1 (15 vaccine and 5 placebo), followed two weeks later by a second identically composed cohort of 20 subjects randomized at 3:1 (15 vaccine and 5 placebo). After all volunteers of the first cohort have been observed for the first isolation period (Day 0 to Day 6) after receipt of dose one, an interim safety review will be performed by a SMC. The SMC will review all AEs and shedding data, for all subjects and will advise if the volunteers of the first cohort may receive dose two of study vaccine or placebo and if the additional 20 volunteers of the second cohort may be enrolled into the study. For each cohort, the procedures and timelines are here summarized.
On the day of first screening (S1), about 7 days (between 4 and 14 days) prior to administration of dose one of study vaccine or placebo, subjects will be screened for eligibility through medical history review, physical examination, testing for serologic evidence of chronic viral infection [human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)], routine biochemical and hematological blood tests and routine urinalysis.
For screening for serologic evidence of chronic viral infections, appropriate pre- and post-test counseling must be provided.
Subject screening for eligibility will continue and be completed on the second screening day (S2). This second screening day will occur the same day as scheduled admission to the isolation unit and administration of study vaccine or placebo (Day 0). Women will undergo pregnancy tests using urine samples. All subjects will undergo an ear, nose and throat (ENT) examination and examination by neurologist. Fully eligible subjects will be admitted to the isolation unit. At that time, nasal swabs, nasal wick, saliva and blood specimens will be collected for virologic and immunological testing prior to administration of study vaccine or placebo. Blood and urine specimens will be again collected for routine biochemical and hematological blood tests and urinanalysis; these results will serve to define baseline status for subject prior to receipt of study vaccine or placebo but will not be used for screening purposes. Subjects and investigators conducting assessments of safety will be unaware of which allocation, LAIV H7N9 or matched placebo, is received; study vaccine and placebo will be masked. Subjects will be carefully monitored for adverse reactions while in the isolation unit.
All subjects will remain in the isolation unit for at least 6 days after receipt of study vaccine or placebo. Nasal swabs will be collected daily while subjects are in isolation to test for presence of influenza virus shed in the nasal passage. Any subject exhibiting conjunctivitis will also have a conjunctival swab collected on the day of appearance of the sign. Any subject exhibiting influenza A virus shedding, as determined by real-time RT-PCR positivity on a nasal swabs specimen, in the 2 days prior to each planned discharge day after each dose (Days 5 or 6 or Days 33 or 34) will be kept in the isolation until PCR-diagnosis results confirm that no influenza virus is present in a tested clinical specimens for at least two consecutive days.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Legal male or female adult 18 through 49 years of age at the enrollment visit.
- •Literate and willing to provide written informed consent.
- •A signed informed consent.
- •Free of obvious health problems, as established by the medical history and screening evaluations, including physical examination.
- •Capable and willing to complete diary cards and willing to return for all follow-up visits
- •Willing to comply with the rules of the isolation unit (including willing and able to take oseltamivir influenza antiviral medication, should that be recommended by a study physician).
- •For females, willing to take reliable birth control measures through day 56.
排除标准
- •Participation in another clinical trial involving any therapy within the previous three months or planned enrollment in such a trial during the period of this study.
- •Receipt of any non-study vaccine within four weeks prior to enrollment or refusal to postpone receipt of such vaccines until four weeks after study completion.
- •Practice of nasal irrigation on a regular basis within the past six months or has engaged in nasal irrigation within two weeks prior to enrollment.
- •Recent history of frequent nose bleeds (more than 5 within the past year).
- •Clinically relevant abnormal paranasal anatomy.
- •Recent history (within the past month) of rhino or sinus surgery, or surgery for any traumatic injury of the nose.
- •Current or recent (within two weeks of enrollment) acute respiratory illness with or without fever.
- •Other acute illness at the time of study enrollment.
- •Receipt of immune globulin or other blood products within three months prior to study enrollment or planned receipt of such products during the period of subject participation in the study.
- •Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within six months prior to study enrollment. (For corticosteroids, this means prednisone or equivalent, 0.5 mg per kg per day; topical steroids are allowed, exclusive of nasal.)
- •Participation in any previous trial of any H7 or H5 containing influenza vaccine.
- •History of bronchial asthma.
- •Hypersensitivity and allergy reactions after previous administration of any vaccine.
- •History of wheezing after past receipt of any live influenza vaccine.
- •Other AE following immunization (body temperature more than 40°C, collapse, non-febrile seizures, anaphylaxis), at least possibly related to previous receipt of any vaccine (not only influenza).
- •Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein.
- •Seasonal (autumnal) hypersensitivity to the natural environment.
- •Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, metabolic, neurologic, psychiatric or renal functional abnormality, as determined by medical history, physical examination or clinical laboratory screening tests, which in the opinion of the investigator, might interfere with the study objectives. Subjects with physical examination findings or clinical laboratory screening results which would be graded 2 or higher on the AE severity grading scale (see Attachments) will be excluded from entry into the study and will be excluded from receipt of dose two of study vaccine or placebo.
- •History of leukemia or any other blood or solid organ cancer.
- •History of thrombocytopenic purpura or known bleeding disorder.
- •History of seizures.
- •Known or suspected immunosuppressive or immunodeficient condition of any kind, including HIV infection.
- •Known chronic HBV or HCV infection.
- •Known tuberculosis infection or evidence of previous tuberculosis exposure according to anamnesis and/or available medical records.
- •History of chronic alcohol abuse and/or illegal drug use.
- •Claustrophobia or sociophobia according to anamnesis and/or available medical records.
- •Pregnancy or lactation. (A negative pregnancy test will be required before administration of study vaccine or placebo for all women of childbearing potential.)
- •Any condition that, in the opinion of the investigator, would increase the health risk to the subject if he/she participates in the study or would interfere with the evaluation of the study objectives.
- •Allergic, including anaphylactic, reactions to the introduction of any vaccines in the subject's medical history (not only flu vaccine).
研究组 & 干预措施
H7N9 LAIV
H7N9 live influenza vaccine at study entry (dose 1) and four weeks post-dose one (dose 2), subjects will receive two, 0.25 ml intranasal doses of study vaccine (total dose 0.50 ml at each study vaccine administration).
干预措施: H7N9 LAIV (Biological)
Placebo
Lyophilized purified allantoic fluid of chicken embryos with stabilizers at study entry (dose 1) and four weeks post-dose one (dose 2), subjects will receive two, 0.25 ml intranasal doses of placebo (total dose 0.50 ml at each placebo administration).
干预措施: Placebo (Biological)
Placebo
Lyophilized purified allantoic fluid of chicken embryos with stabilizers at study entry (dose 1) and four weeks post-dose one (dose 2), subjects will receive two, 0.25 ml intranasal doses of placebo (total dose 0.50 ml at each placebo administration).
干预措施: H7N9 LAIV (Biological)
H7N9 LAIV
H7N9 live influenza vaccine at study entry (dose 1) and four weeks post-dose one (dose 2), subjects will receive two, 0.25 ml intranasal doses of study vaccine (total dose 0.50 ml at each study vaccine administration).
干预措施: Placebo (Biological)
结局指标
主要结局
Number of Participants with Immediate reactions
时间窗: 2 hours
Proportion of subjects experiencing immediate reactions (related or not related to the study) occuring within two hours of administration of any dose, measured as observed by study staff or reported by the subject to study staff
Number of Participants with Solicited adverse events
时间窗: greater than two hours after administration of any dose of study vaccine or placebo through 6 days following any dose
Proportion of subjects experiencing adverse events (related or not related to the study) commonly associated with intranasal vaccination (solicited local and systemic reactions) occurring greater than two hours after administration of any dose of study vaccine or placebo through 6 days following any dose, measured as observed by study staff or reported by the subject to study staff.
Number of Participants with Changes from baseline in laboratory findings and instrumental tests (ECG, echocardiogram, and spirometry)
时间窗: Days 3, 6, 31 and 34
Proportion of subjects experiencing all other adverse events (including unsolicited events) occurring during the 6 days following any dose, measured as observed by study staff or reported by the subject to study staff. This includes abnormal laboratory findings from blood specimens and urinalysis collected on Days 3, 6, 31 and 34; IgE level data for Days 0, 3, 28, and 56, as well as instrumental test data (ECG, echocardiogram, and spirometry) on the third day after each vaccination.
Number of Participants with Serious adverse events (SAEs)
时间窗: 4 weeks of receipt of any dose
Proportion of subjects experiencing all serious adverse events (SAEs) occurring within 4 weeks of receipt of any dose, as observed by study staff, reported by the subject to study staff, or noted by the subject on a diary card. This includes abnormal laboratory findings from blood specimens collected on Days 28 (pre-vaccination) and 56.
次要结局
- Number of Participants with Virus shedding at Days 0-6 after each dose(Days 0-6 after each dose)
- Number and name of mutations leading to any loss of attenuation phenotype of the vaccine virus (genetic stability)(Days 0-6 after each dose)
- Number of Participants with Immune responses(Days 0, 3, 28, and 56)