A Two-arm, Non-randomised, Open-label Experimental Medicine Study to Compare Immune Responses Between Healthy Volunteers Aged 18-55years Receiving Either an Intranasal Live-attenuated Influenza Vaccine or Viral Challenge With GMP Influenza A/Belgium/4217/2015 (H3N2)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Peak symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-40
研究概览
简要总结
This experimental medicine study aims to compare immune responses in healthy adult volunteers aged 18-55 years against influenza vaccination and infection in the upper and lower respiratory tract, following administration of a live-attenuated influenza vaccine delivered by nasal spray versus influenza A (H3N2) viral challenge.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults aged between 18-55 years inclusive
- •Sero-suitable as defined by a serum micro-neutralisation titre <1:20
- •Female participant who is not of child-bearing potential as assessed by an investigator OR is willing and able to use contraception as described in the protocol
- •Male participants who are willing to use one of the contraception methods described in the protocol
- •In good health with no clinically significant medical conditions
排除标准
- •History of clinically significant/currently active conditions;
- •Cardiovascular, thromboembolic/cerebrovascular disease.
- •Types of chronic respiratory disease in adulthood.
- •Significant wheeze in the past
- •Respiratory symptoms including wheeze, resulting in hospitalisation
- •Known bronchial hyperactivity to viruses
- •Diabetes mellitus
- •Migraine with associated symptoms like hemiplegia/vision loss. Cluster headache/migraine/prophylactic treatment for migraine.
- •History of autoimmune disease/known immunodeficiency of any cause
- •Immunosuppression.
- •Known coagulation disorder/anticoagulant therapy
- •Psychiatric illness including participants with a history of depression and/or anxiety with associated psychiatric comorbidities
- •Other major disease that, under the PI's discretion, could interfere with the participant completing the study.
- •Concurrent serious illness including history of malignancy that could interfere with the study or a participant completing the study.
- •Known IgA deficiency/immotile cilia syndrome/Kartagener's syndrome
- •Significant abnormality altering the anatomy/function of the nose or nasopharynx, a clinically significant history of epistaxis within the last 3 months, nasal/sinus surgery within 6 months of Day 0, including nasopharyngeal malignancy, arterio-venous malformation, or undiagnosed nasopharyngeal mass
- •Inhaled bronchodilator/inhaled steroid use within the last 12 months before Day 0
- •Acute upper respiratory tract infection in the past 6 weeks.
- •Receipt of systemic glucocorticoids (in a dose ≥ 5 mg prednisone daily or equivalent) within one month, or any other cytotoxic or immunosuppressive drug within 6 months before Day 0
- •Receipt of any vaccine within 30 days of Day -14
- •Any significant medical condition/prescribed drug, under the PI's discretion
- •Presence of cold-like symptoms and/or fever on Day -14 or Day
- •Receipt of blood/blood products/loss (including blood donations) of 550 mL or more of blood during the 3 months prior to Day -
- •Significant history/presence of drug/alcohol misuse by self-report.
- •Current use of drugs through nose inhalation or inhaled route including recreational drugs.
- •Regular smoking and/or vaping and/or using nicotine-containing products in the past 3 months OR >5 pack-year lifetime history by self-report (5 pack years is equivalent to one pack of 20 cigarettes per day for 5 years).
- •History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food/drug, as assessed by the PI.
- •Clinically active rhinitis (including hay fever)/history of moderate to severe rhinitis/history of seasonal allergic rhinitis likely to be active at the time of inclusion into the study and/or requiring regular nasal corticosteroids on an at least weekly basis, within 30 days of enrolment.
- •Anyone with any of the following contraindications to receiving the Fluenz Tetra Vaccine:
- •Allergy to gentamicin, gelatin or the other ingredients of the fluenz vaccine.
研究组 & 干预措施
IAV Challenge
干预措施: Influenza challenge virus (Biological)
LAIV
干预措施: FLUENZ (Biological)
结局指标
主要结局
Peak symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-40
时间窗: 14 days
Peak self-reported symptom scores by modified Jackson score from the viral challenge (Day 0) up to Day 14 follow-up
Average duration of symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-40
时间窗: 14 days
Average duration of self-reported symptom scores by modified Jackson score from the viral challenge (Day 0) up to Day 14 follow-up
To confirm symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-40 by Area Under the Curve
时间窗: 14 days
Self-reported symptom scores by modified Jackson score from the viral challenge (Day 0) up to Day 14 follow-up (Area Under the Curve)
Peak symptoms related to inoculation with LAIV in healthy adults aged 18-40
时间窗: 14 days
Peak self-reported symptom scores by modified Jackson score from the vaccination (Day 0) up to Day 14 follow-up
Average duration of symptoms related to inoculation with LAIV in healthy adults aged 18-40
时间窗: 14 days
Average duration of self-reported symptom scores by modified Jackson score from the vaccination (Day 0) up to Day 14 follow-up (Peak, Duration, Area Under the Curve)
To confirm symptoms related to inoculation with LAIV in healthy adults aged 18-40 by Area Under the Curve
时间窗: 14 days
Delf-reported symptom scores by modified Jackson score from the vaccination (Day 0) up to Day 14 follow-up (Area Under the Curve)
Peak symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-55
时间窗: 14 days
Peak self-reported symptom scores by modified Jackson score from the viral challenge (Day 0) up to Day 14 follow-up
Average duration of symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-55
时间窗: 14 days
Average duration of self-reported symptom scores by modified Jackson score from the viral challenge (Day 0) up to Day 14 follow-up
To confirm symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-55 by Area Under the Curve
时间窗: 14 days
Self-reported symptom scores by modified Jackson score from the viral challenge (Day 0) up to Day 14 follow-up (Area Under the Curve)
Peak symptoms related to inoculation with LAIV in healthy adults aged 18-55
时间窗: 14 days
Peak self-reported symptom scores by modified Jackson score from the vaccination (Day 0) up to Day 14 follow-up
Average duration of symptoms related to inoculation with LAIV in healthy adults aged 18-55
时间窗: 14 days
Average duration of self-reported symptom scores by modified Jackson score from the vaccination (Day 0) up to Day 14 follow-up (Peak, Duration, Area Under the Curve)
To confirm symptoms related to inoculation with LAIV in healthy adults aged 18-55 by Area Under the Curve
时间窗: 14 days
Delf-reported symptom scores by modified Jackson score from the vaccination (Day 0) up to Day 14 follow-up (Area Under the Curve)
次要结局
- To assess influenza viral dynamics in upper respiratory samples(28 days)
- To assess antibody levels in blood before and after influenza challenge infection(28 days)
- To assess LAIV viral dynamics by RT-PCR in upper respiratory samples(28 days)
- To assess antibody levels in blood before and after LAIV(28 days)