Development of a Controlled Human Infection Model for Assessment of SARS-CoV-2 Omicron Subvariants
概览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 38
- 主要终点
- To assess the safety of a GMP SARS-CoV-2 EG.5.1 variant challenge virus in vaccinated healthy adult volunteers with or without previous infection and establish the attack rate (target 50-70%) with optimised dose and screening criteria.
概览
简要总结
COVHIC003 is a human infection challenge study in which healthy adults aged 18-50 previously vaccinated with an approved COVID-19 vaccine will be administered a SARS-CoV-2 Omicron EG.5.1 variant given by drops in the nose. The aim is to achieve breakthrough upper-respiratory infection in a proportion of volunteers with mild or no illness, providing information on the course of Omicron infection and the immune response in vaccinated people. This study will establish an optimised challenge dose and model that can then be used to evaluate new vaccines and treatments in follow-on trials. Participants will stay in a quarantine unit for approximately 10-12 days, depending on infection status, and will be closely monitored with regular swabs, blood tests and symptom assessments throughout their stay. They will be followed up by the study team for 6 months after being discharged. This study is sponsored by Imperial College London and forms part of the MUSICC project which is led by Imperial College London and co-funded by the European Union's Horizon Europe Programme and the Coalition for Epidemic Preparedness Innovations (CEPI). Quarantine will take place at specialist facilities in Oxford or at the Royal Free Hospital in London.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •The study informed consent form has been signed and dated by the participant and the Investigator
- •Adults age between 18 and 50 years inclusive (at the time of enrolment)
- •Evidence of having had at least one COVID-19 vaccine, with the last vaccination at least 3 months before enrolment
- •Positive serology for SARS-CoV-2 at (pre)screening
- •Sero-suitable as defined by having serum and/or nasal antibody titres less than a pre-defined cut-off of a defined assay(s) which will be specified in a separate SOP and based on accumulating antibody data
- •People of child-bearing potential (POCBP) must be willing and able to use contraception as described in the study protocol from 2 weeks before the scheduled date of viral challenge until the end discharge from quarantine.
- •Negative urine pregnancy tests will be required at screening and on day 0 prior to inoculation. On admission to the quarantine unit a negative serum beta human chorionic gonadotropin (β-hCG) is required
- •Male participants who are willing to use one of the contraception methods described in the study protocol, from the time of the date of viral challenge until the end of quarantine
- •Agree to abstain from sexual activity or use effective contraception from the start of treatment with Paxlovid until 7 days after completing treatment with Paxlovid should they receive it
- •In good health with no history of clinically significant medical conditions (as described in
排除标准
- •) that would interfere with participant safety, as defined by medical history, physical examination and routine laboratory tests, ECG, and Chest X-Ray and determined by the Investigator at an admission evaluation
- •Participants will have a documented medical history either prior to entering the study and/or following medical history review with the study physician at screening
- •Willing to be registered with The Over-Volunteering Protection Service (TOPS)
- •Willing and able to commit to participation in the study.
- •Exclusion Criteria:
- •History or evidence of any clinically significant or currently active cardiovascular, (including thromboembolic events), respiratory, dermatological, gastrointestinal, endocrine, haematological, hepatic, immunological, rheumatological, metabolic, urological, renal, neurological, psychiatric illness
- •Any significant abnormality altering the anatomy or function of the nose or nasopharynx in a substantial way (including loss of or alterations in smell or taste), a clinically significant history of epistaxis (large nosebleeds) within the last 3 months, nasal or sinus surgery within 6 months of inoculation
- •Clinically-active, symptomatic rhinitis (including hay fever) or history of severe rhinitis, or 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 admission to quarantine
- •History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the Investigator
- •Significant history or presence of drug or alcohol misuse (exceeding \>28 units a week)
研究组 & 干预措施
Group 1a: SARS-CoV-2 Omicron EG.5.1
Starting dose 10^5 TCID50, vaccinated, pre-selection for low serum antibodies, n = up to 12
干预措施: SARS-CoV-2 Omicron EG.5.1 challenge agent 10^5 TCID50 (Biological)
Group 1b: SARS-CoV-2 Omicron EG.5.1
Dose escalate: 10^6 TCID50, vaccinated, pre-selection for low serum antibodies, n = up to 12
干预措施: SARS-CoV-2 Omicron EG.5.1 challenge agent 10^6 TCID50 (Biological)
Group 1c: SARS-CoV-2 Omicron EG.5.1
Dose de-escalate: 10^4 TCID50, vaccinated, pre-selection for low serum antibodies, n = up to 12
干预措施: SARS-CoV-2 Omicron EG.5.1 challenge agent 10^4 TCID50 (Biological)
Group 2: SARS-CoV-2 Omicron EG.5.1
10^6 TCID50 with multiple doses and/or lower sero-screening threshold
干预措施: SARS-CoV-2 Omicron EG.5.1 challenge agent 10^6 TCID50 (Biological)
结局指标
主要结局
To assess the safety of a GMP SARS-CoV-2 EG.5.1 variant challenge virus in vaccinated healthy adult volunteers with or without previous infection and establish the attack rate (target 50-70%) with optimised dose and screening criteria.
时间窗: 28 Days
To assess the safety of a GMP SARS-CoV-2 EG.5.1 variant challenge virus in vaccinated healthy adult volunteers with or without previous infection and establish the attack rate (target 50-70%) with optimised dose and screening criteria. To assess safety and human clinical response to SARS-CoV-2 Omicron EG.5.1 intranasal challenge in both previously infected (unvaccinated or vaccinated) and uninfected vaccinated volunteers. To evaluate the safety of Omicron variant SARS-CoV-2 challenge in healthy participants, by assessing: • Occurrence of AEs within 28 days post-viral challenge (Day 0 to Day 28)
To assess the safety of a GMP SARS-CoV-2 EG.5.1 variant challenge virus in vaccinated healthy adult volunteers with or without previous infection and establish the attack rate (target 50-70%) with optimised dose and screening criteria.
时间窗: 180 Days
To assess the safety of a GMP SARS-CoV-2 EG.5.1 variant challenge virus in vaccinated healthy adult volunteers with or without previous infection and establish the attack rate (target 50-70%) with optimised dose and screening criteria. To assess safety and human clinical response to SARS-CoV-2 Omicron EG.5.1 intranasal challenge in both previously infected (unvaccinated or vaccinated) and uninfected vaccinated volunteers To evaluate the safety of Omicron variant SARS-CoV-2 challenge in healthy participants, by assessing: • • Occurrence of SAEs related to the viral challenge (Day 0 to Day 180)
Selection of the SARS-CoV-2 Omicron EG.5.1 dose(s) required to induce upper respiratory tract infection in 50-75% of previously SARS-CoV-2 infected and uninfected vaccinated volunteers (vaccinated or unvaccinated) healthy volunteers following intranasal
时间窗: 10 Days
Selection of the SARS-CoV-2 Omicron EG.5.1 dose(s) required to induce upper respiratory tract infection in 50-75% of previously SARS-CoV-2 infected and uninfected vaccinated volunteers (vaccinated or unvaccinated) healthy volunteers following intranasal challenge. Laboratory confirmed infection is defined as: two quantifiable (≥LLOQ) RT-PCR measurements from mid turbinate or throat samples, reported on 2 or more consecutive timepoints, starting from Day 2 (inclusive) post-inoculation and up to discharge from quarantine (Day 8 for uninfected participants or Day 10 for infected participants)
次要结局
未报告次要终点