An Exploratory Study to Establish the Dose, Safety and Pathogenicity of a SARS-CoV-2 Omicron Challenge Strain (BA.5) in Healthy Participants 18 to 40 Years of Age
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- Hvivo
- 入组人数
- 36
- 试验地点
- 1
- 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 SARS-CoV-2 Omicron Challenge Strain (BA.5) in Healthy Participants 18 to 40 Years of Age
详细描述
This is an exploratory study of an SARS-CoV-2 Omicron (BA.5) challenge strain to determine the optimum safe infectious titer of challenge agent in healthy participants 18 to 40 years of age.
Up to 90 participants who meet all study inclusion and no exclusion criteria will be allocated to one of the three dose escalating cohorts (Dose 1, Dose 2 or Dose 3), with up to 30 participants in each dose group, to receive one dose of SARS-CoV-2 omicron. Based on the outcome of each cohort the next cohort may receive a high or lower dose than the previous cohort.
Each participant will remain in the study for approximately 9 months from screening to the last clinic visit.
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 17 days (from Day -2/-1 to Day 14).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 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 40 years
- •A total body weight ≥50 kg and body mass index (BMI) ≥18 kg/m2 and ≤28kg/m
- •The upper limit of BMI may be increased to ≤30kg/m2 at the PI's discretion, in the case of physically fit muscular individuals.
- •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
- •Participants must have been previously vaccinated with a COVID-19 vaccine licensed for use in the UK and completed the course
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 ≥5 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.
- •History of severe COVID-19 or severe complication of any other viral disease.
- •Participants with no knowledge of their family history, as deemed appropriate by the PI
- •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 COVID-19 vaccine in the last 3 months prior to inoculation and/or a diagnosis of COVID 19 confirmed by a physician within the last 6 months prior to screening or at any time between screening and quarantine admission.
- •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 or recent history or presence of alcohol addiction
- •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
- •Sensitivity to any of the study interventions, challenge agent or components thereof (including lactose), or drug or other allergy that, in the opinion of the PI/investigator, contraindicates participation in the study.
研究组 & 干预措施
Dose 1
Low dose, expected to be approximately 10^4 tissue culture infective dose 50% (TCID50)/mL (titer may be adjusted based on stock titer)
干预措施: SARS-CoV-2 omicron virus dose arm 1 (Biological)
Dose 2
Medium dose, expected to be approximately 10^5 tissue culture infective dose 50% (TCID50)/mL (titer may be adjusted based on stock titer)
干预措施: SARS-CoV-2 omicron virus dose arm 2 (Biological)
Dose 3
High dose, expected to be approximately 10^6 tissue culture infective dose 50% (TCID50)/mL (titer may be adjusted based on stock titer)
干预措施: SARS-CoV-2 omicron virus dose arm 3 (Biological)
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
Number of participants with challenge Agent-emergent adverse events (AEs) at least possibly related to the viral challenge from viral challenge (Day 0) up to the Day 28 follow-up
Occurrence of Serious Adverse Events and Medically Attended Adverse Events, related to the viral challenge
时间窗: Day 0 to Day 180
Occurrence of serious AEs (SAEs) and Medically Attended Adverse Events (MAAEs) related to the viral challenge from viral challenge (Day 0) up to the Day 180 follow-up
Induces laboratory-confirmed infection in ≥40% of inoculated participants
时间窗: Day 1 to Day 14
Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR)-confirmed SARS-CoV-2 omicron 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 14 am).
次要结局
未报告次要终点