NCT03883113已完成2 期
Efficacy of MVA-NP+M1 in the Influenza H3N2 Human Challenge Model
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 145
- 试验地点
- 2
- 主要终点
- Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR
研究概览
简要总结
A Phase 2, single center, randomized, double blind study evaluating the safety, efficacy, and immunogenicity of MVA NP+M1 in the H3N2 human influenza challenge model; on healthy adult volunteers.
详细描述
The study consists of an outpatient vaccination phase (155 participants), and at least 2 months later an inpatient challenge phase (134 participants). Participants are randomized 93:62 to receive either MVA-NP+M1 or Placebo. Up to 20 participants will be challenged over several 3-week blocks, and the remainder at the final 3-week block for a total of 80 MVA-NP+M1 and 54 Placebo recipients challenged.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males and females aged ≥18 and ≤55 years of age at the point of enrolment.
- •Non-smokers or those who stopped smoking ≥ 3 months prior to screening 1 visit.
- •Willingness to remain in isolation for the duration of the study.
- •A female participant is eligible for this study if she is not pregnant or breast feeding and 1 of the following:
- •Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year).
- •Of childbearing potential but has been and agrees to continue practicing highly effective contraception or abstinence (if this is the preferred and usual lifestyle of the participant) from 6 months prior to vaccination to 6 months after administration of the influenza challenge virus. Highly effective methods of contraception include 1 or more of the following:
- •i. male partner who is sterile (vasectomised) prior to the female participants entry into the study and is the sole sexual partner for the female participant; ii. hormonal (oral, intravaginal, transdermal, implantable or injectable); iii. an intrauterine hormone-releasing system (IUS); iv. an intrauterine device (IUD) with a documented failure rate of < 1%; v. bilateral tubal occlusion.
- •Pre-challenge serum microneutralization test (MNT) against A/Belgium/4217/2015 (H3N2) challenge strain < 20.
排除标准
- •BMI < 19 and >
- •Presence of any significant acute or chronic, uncontrolled medical (or psychiatric) illness including a history of chronic respiratory illness.
- •History of seasonal hay fever or a clinically significant seasonal allergic rhinitis (SAR), including the use of symptomatic prescription only medication and non-prescription medication.
- •History or evidence of autoimmune disease or known immunodeficiency of any cause - with the exception of atopic dermatitis/eczema and atopic rhinitis.
- •Any history of anaphylaxis in reaction to vaccination or history of allergic reactions likely to be exacerbated by any component of the vaccine.
- •History of lung disease (Asthma, COPD).
- •Current smokers or those who stopped smoking < 3months prior to screening 1 visit.
- •Positive diagnostic tests for HIV, Hepatitis B or Hepatitis C indicating active infection.
- •Evidence of drug abuse or a positive urine drug screen or alcohol breath test.
- •Chronic use of any medication or other product (prescription or over-the-counter), for symptoms of rhinitis or nasal congestion or for any chronic nasopharyngeal complaint, or chronic use of any intranasal medication for any indication that has not ceased within 30 days prior to screening
- •Receipt of any investigational drug within 3 months prior to vaccination, or prior participation in a clinical trial of any influenza vaccine, or any investigational vaccine or experimental influenza viral challenge delivered directly to the respiratory tract within 1 year prior to challenge.
- •Receipt of the 2018/2019 seasonal flu vaccine.
- •Receipt of any live vaccines within the 4 weeks prior to vaccination.
- •Any laboratory test which is abnormal and which is deemed by the Investigator(s) to be clinically significant.
- •Receipt of any systemic chemotherapy agent at any time.
- •Physician reported influenza or a syndrome consistent with influenza (as judged by the investigator) in the previous 6 months.
- •Known allergy to treatments for influenza (including but not limited to oseltamivir).
- •History of frequent epistaxis (nose bleeds).
- •Any nasal or sinus surgery within 6 months of Viral Challenge or any significant abnormality, either of which results in alteration of the anatomy of the nose or nasopharynx (including significant nasal polyps).
- •Volunteers with household contacts who are at risk for serious or severe complications of influenza disease including, but not limited to: persons ≥ 65 years; presence of significant chronic cardiopulmonary, metabolic, renal, or neurological conditions; immunosuppression due to any condition or therapies; BMI >
- •Participants that are an employee or family member of the Investigator or study site personnel may not be enrolled.
- •Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study.
- •EXCLUSION (CHALLENGE PERIOD ONLY)
- •Abnormal spirometry assessed to be clinically significant.
- •Known close contact with anyone known to have influenza in the past 7 days at the time of quarantine.
- •Influenza-like illness (ILI) symptoms as assessed at the admission to clinic on Day -2 prior to challenge.
- •Presence of fever, defined as participant presenting with a temperature reading of > 38.0°C on admission to quarantine.
- •Qualitative Polymerase chain reaction (PCR) results positive for viral infection. However, participants may be included into later challenge cohort.
- •Acute use of any medication or other product, prescription or over-the-counter, for symptoms of rhinitis or nasal congestion within 7 days prior to challenge. This includes any oral corticosteroid or beta agonist containing nasal spray.
结局指标
主要结局
Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR
时间窗: Throughout 9 days (Day2, Day3, Day4, Day5, Day6, Day7, Day8, Day9, Day10) after viral Inoculation (Day1) of the challenge phase. Nasal swabs taken twice a day (b.i.d) at least 8 hours apart.
Measure of nasopharyngeal viral shedding during challenge; recorded as viral area under curve (vAUC) as determined by quantitative real time polymerase chain reaction (qRT-PCR). vAUC is calculated by plotting the log viral particles number/ml for each time point against time and is using the trapezoidal rule.
次要结局
- Time to Start of Viral Shedding (qCulture) From Virus Inoculation(9 days from day 2 to day 10)
- Time to Peak of Viral Shedding (qCulture) From the Viral Inoculation(9 days from day 2 to day 10)
- Duration of Viral Shedding (qPCR) After the Virus Inoculation(9 days from day2 to day10)
- Duration of Viral Shedding (qCulture) After the Virus Inoculation(9 days from day 2 to day 10)
- Percentage of Participants With Quantitative Culture Attack Rate of Challenge Agent (qCulture)(9 days from day 2 to day 10)
- Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms(17 days following vaccination)
- Percentage of Participants With Attack Rate of Challenge Agent (qRT-PCR)(9 days from day 2 to day 10)
- Peak Viral Shedding (qPCR) After the Virus Inoculation(9 days from Day 2 to Day 10)
- Peak Viral Shedding (qCulture) After Virus Inoculation(9 days from day 2 to day 10)
- Average Total Mucus Production(11 days from Day 1 to Day 11)
- Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms(7 days following vaccination)
- Time to Peak of Viral Shedding (qPCR) From the Viral Inoculation(9 days from day 2 to day 10)
- Number and Percentage of Virologically Confirmed Influenza-Like Illness(9 days from day 2 to day 10)
- Time to Start of Viral Shedding (qPCR) From Virus Inoculation(9 days from day 2 to day 10)
- Total Area Under the Curve (AUC) of Self-reported Influenza Total Symptom Score (SSC AUC)(11 days from Day 1 to Day 11)
- Total Days of Fever(11 days from Day 1 to Day 11)
- T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence(3 months (day 0, day 8 and day 28 of the vaccination period and day -1 and day 28 of the challenge period))
研究者
研究点 (2)
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