An Exploratory Study to Establish the Dose, Safety and Pathogenicity of a New Influenza A H3N2 Challenge Strain in Healthy Participants 18 to 55 Years of Age
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Hvivo
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- Occurrence of adverse events related to the viral challenge
研究概览
简要总结
An Exploratory Study to Establish the Dose, Safety and Pathogenicity of a New Influenza A H3N2 Challenge Strain in Healthy Participants 18 to 55 Years of Age
In Part A, up to 40 participants will be randomly allocated to one of two groups to be given one of two virus doses (Virus Dose 1 or Virus Dose 2).
Based on the outcome of Part A, participants in Part B, may be given Virus Dose 1, Virus Dose 2, or another virus dose (e.g., Virus Dose 3)
详细描述
This is an exploratory study of an influenza A/England/7763/2022 H3N2 challenge strain, to determine the optimum safe infectious titer of challenge agent, in healthy participants 18 to 55 years of age.
A total of up to 80 participants may be given the influenza A/England/7763/2022 H3N2 challenge agent. Each participant will remain in the study for approximately 4 months from screening to the last clinic visit.
The study will consist of 2 parts, in Part A of the study, up to 40 participants will be randomly allocated to one of two groups to be given one of two virus doses (Virus Dose 1 or Virus Dose 2). Based on the outcome of Part A, additional participants may be enrolled into the optional Part B of the study and may be given Virus Dose 1, Virus Dose 2, and/or another virus dose (e.g., Virus Dose 3)
The study is divided into three phases:
- Screening phase: Screening will occur between Day -90 to Day -2/-1.
- Quarantine phase: Participants will stay in the quarantine unit for approximately 8 days (from Day -2/-1 to Day 8).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Single (Participant)
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
- •Written informed consent
- •Adult male or female aged between 18 and 55 years
- •A total body weight ≥50 kg and body mass index (BMI) ≥18 kg/m2 and ≤35kg/m
- •In good health with no history, or current evidence, of clinically significant medical conditions, and no clinically significant test abnormalities that will interfere with participant safety.
- •Documented medical history
- •Adherence to contraception requirements
- •Serosuitable for the challenge virus
排除标准
- •History of, or currently active, symptoms or signs suggestive of upper or lower respiratory tract (LRT) infection within 4 weeks prior to the first study visit.
- •Any history or evidence of any clinically significant or currently active disease.
- •Any participants who have smoked ≥10 pack years at any time.
- •Female participants who are breastfeeding, or have been pregnant within 6 months prior to the study, or have a positive pregnancy test at any point during screening or prior to inoculation.
- •Any history of anaphylaxis and/or a any history of severe allergic reaction.
- •Venous access deemed inadequate for the phlebotomy and cannulation demands of the study.
- •Lifetime history of anaphylaxis and/or a lifetime history of severe allergic reaction.
- •Significant abnormality of the nose, includes loss of or alterations in smell or taste, nasal polyps, epistaxis, nasal or sinus surgery.
- •Recent vaccinations or intention to receive vaccination before the Day 28 follow up visit.
- •Receipt of blood or blood products, or loss (including blood donations) of 550 mL or more of blood during the 3 months prior to the planned inoculation or planned during the 3 months after the final visit.
- •Recent receipt of investigational drugs or challenge viruses.
- •Use or anticipated use during the conduct of the study of concomitant medications (prescription and/or non-prescription), including vitamins or herbal and dietary supplements within the specified windows.
- •Positive drugs of abuse test, recent history or presence of alcohol addiction, excessive consumption of xanthine containing substances or a presence of significant signs and symptoms of nicotine withdrawal on first study visit.
- •A forced expiratory volume in 1 second (FEV1) <80%.
- •Positive HIV, hepatitis B virus, or hepatitis C virus test.
- •Presence of fever, defined as participant presenting with a temperature reading of ≥37.9°C on Day -2/-1 and/or pre-inoculation on Day
- •Those employed or immediate relatives of those employed at hVIVO or the sponsor.
- •Any other reason, in the opinion of the investigator deems the participant unsuitable for the study
研究组 & 干预措施
Dose 3
Optional: TBD, depending on outcome of Part A
干预措施: Influenza A H3N2 virus dose arm 3 (Other)
Dose 1
Medium dose, expected to be approximately 10^4.5 tissue culture infective dose 50% (TCID50)/mL (titer may be adjusted based on stock titer)
干预措施: Influenza A H3N2 virus dose arm 1 (Other)
Dose 2
High dose, expected to be approximately 10^5.5 tissue culture infective dose 50% (TCID50)/mL (titer may be adjusted based on stock titer)
干预措施: Influenza A H3N2 virus dose arm 2 (Other)
结局指标
主要结局
Occurrence of adverse events related to the viral challenge
时间窗: Day 0 to Day 28
Occurrence of adverse events (AEs) related to the viral challenge from viral challenge (Day 0) to the Day 28 follow-up visit.
Occurrence of serious adverse events related to the viral challenge
时间窗: Day 0 to Day 28
Occurrence of serious adverse events (SAEs) related to the viral challenge from viral challenge (Day 0) to the Day 28 follow-up visit.
Induces laboratory-confirmed infection in ≥40% of inoculated participants
时间窗: Day 1 to Day 8
Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR)-confirmed influenza infection, defined as 2 quantifiable (≥ lower limit of quantification \[LLOQ\]) qRT-PCR measurements (reported over 4 planned consecutive assessments within 48 hours), from Day 1 pm to planned discharge from quarantine (Day 8 am).
Occurrence of Adverse Events Related to the Viral Challenge
时间窗: Day 0 to Day 28
Occurrence of adverse events (AEs) related to the viral challenge from viral challenge (Day 0) to the Day 28 follow-up visit.
Occurrence of Serious Adverse Events Related to the Viral Challenge
时间窗: Day 0 to Day 28
Occurrence of serious adverse events (SAEs) related to the viral challenge from viral challenge (Day 0) to the Day 28 follow-up visit.
Induces Laboratory-confirmed Infection in ≥40% of Inoculated Participants
时间窗: Day 1 to Day 8
Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR)-confirmed influenza infection, defined as 2 quantifiable (≥ lower limit of quantification \[LLOQ\]) qRT-PCR measurements (reported over 4 planned consecutive assessments within 48 hours), from Day 1 pm to planned discharge from quarantine (Day 8 am).
次要结局
- Incidence of Viral Culture-confirmed Influenza Infection.(Day 1 to Day 8)
- VL-AUC of Influenza Challenge Virus as Determined by qRT-PCR(Day 1 to Day 8)
- Peak Viral Load of Influenza Challenge Virus as Determined by qRT-PCR(Day 1 to Day 8)
- VL-AUC of Influenza Challenge Virus as Determined by Viral Culture(Day 1 to Day 8)
- Peak Viral Load of Influenza Challenge Virus as Determined by Viral Culture(Day 1 to Day 8)
- Area Under the Total Clinical Symptoms Score-time Curve (TSS-AUC)(Day 1 to Day 8)
- Peak Total Symptoms Diary Card Score(Day 1 to Day 8)
- Peak Daily Symptoms Diary Card Score(Day 1 to Day 8)
- Laboratory-confirmed Febrile Influenza Infection(Day 1 to Day 8)
- qRT-PCR-confirmed Influenza-like Illness (Centers for Disease and Control [CDC])(Day 1 to Day 8)
- qRT-PCR-confirmed Influenza-like Illness (World Health Organization [WHO])(Day 1 to Day 8)
- Laboratory-confirmed Moderately Severe Symptomatic Influenza Infection(Day 1 to Day 8)
- Laboratory-confirmed Symptomatic Influenza Infection(Day 1 to Day 8)
- Viral Culture Laboratory-confirmed Moderately Severe Symptomatic Influenza Infection(Day 1 to Day 8)