COVID-19 Infections and Infestations
Conditions
Interventions
This is a dose optimisation study in which increasing titres of Delta variant SARS-CoV-2 (1x101 TCID50, 1x102 TCID50and 1x103 TCID50 or higher, as necessary) will be given via nasal administration to
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. An informed consent form has been signed and dated by the participant and the Investigator. 2. Adults age between 18 and 30 years inclusive (at the time of consent) 3. Evidence of having had a complete COVID-19 vaccination course with the last vaccination at least 14 days before enrolment 4. Sero suitable as defined by: positive anti-S AND negative anti-N antibody detection OR positive anti-S AND positive anti-N antibody. Those with an indeterminate anti-N antibody result and no history of laboratory-confirmed SARS-CoV-2 infection may be included or excluded at the CI/PI’s discretion on a case-by-case basis. detection (at the CI/PI’s discretion). 5. Female participants with a documented menstrual period within 28 days before the inoculation (unless using a contraceptive method that suppressed menstruation as indicated in the study protocol) and willing and able to use contraception as described in the study protocol from 2 weeks before the scheduled date of viral challenge until 6 months after receipt of the final dose of study virus or intervention treatment (whichever occurs last). 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 (ß-hCG) is required. 6. Men 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 6 months after receipt of the final dose of study medication (if applicable). 7. In good health with no history of clinically significant medical conditions (as described in Exclusion criteria) that would interfere with subject 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. 8. Subjects will have a documented medical history either prior to entering the study and/or following medical history review with the study physician at screening. 9. Willing and able to commit to participation in the study.
Exclusion criteria
Exclusion criteria: 1. 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. 2. 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 within the last 3 months, nasal or sinus surgery within 6 months of inoculation. 3. Clinically active rhinitis (including hay fever) or history of moderate to severe rhinitis, or history of seasonal allergic rhinitis likely to be active at the time of inclusion and/or requiring regular nasal corticosteroids on an at least weekly basis, within 30 days of admission to quarantine. 4. History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI. 5. History or presence of alcohol addiction, or excessive use of alcohol or use of drugs of abuse 6. Psychiatric illness including subjects with a history of depression and/or anxiety with associated severe psychiatric comorbidities, for example psychosis. Specifically, (a) Subjects with history of anxiety-related symptoms of any severity within the last 2 years if the Generalized Anxiety Disorder-7 score is > = 4; (b)Subjects with a history of depression of any severity within the last 2 years if the Patient Health Questionnaire-9 score is > = 4 7. Subjects who have smoked > = 5 pack years at any time. 8. Family history of 1st degree relative aged 50 years or less with sudden cardiac or unexplained death 9. Family History of Severe COVID or response to any other viral disease e.g. Guillain–Barré 10. A total body weight of = 28 kg/m2. The upper limit of BMI may be increased to 37.9ºC) on Day -2, Day -1 and/or pre-challenge on Day 0. 17. Evidence of any respiratory viruses (on nasopharyngeal swab analysis) prior to challenge virus inoculation on admission to the quarantine unit. 18. Evidence of a live vaccine within 60 days prior to the planned date of viral challenge, a non-live vaccine within 30 days prior to the planned date of viral challenge or intention to receive any vaccination(s) before the day 28 follow-up visit. 19. Receipt of blood or bloo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety profile as measured by: 1.1. Occurrence of adverse events (AEs) from the viral challenge (Day 0) up to Day 28 follow up. 1.2. Occurrence of serious adverse events (SAEs) from the viral challenge (Day 0) up to Day 28 follow up. 2. Laboratory confirmed infection in =50% of participants (ideally =70%). Laboratory confirmed infection is defined by: two quantifiable greater than lower limit of quantification (viral load =LLOQ) RT-PCR measurements from mid turbinate and/or throat samples, reported on 2 or more consecutive timepoints, starting from Day 2 post-inoculation and up to discharge from quarantine. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.SARS-CoV-2 breakthrough infection rates and viral dynamics (AUC, peak, duration, incubation period) in upper respiratory samples - qRT-PCR (for SARS-CoV-2 RNA) and cell culture (to for live SARS-CoV-2 virus) are performed daily during quarantine 2. Incidence of symptomatic SARS-CoV-2 breakthrough infection in vaccinated participants and to assess the nature and severity of SARS-CoV-2 induced symptoms (sum, AUC, peak, peak daily, frequency) – symptom diaries are completed three times a day, at baseline, daily during quarantine and at all follow up visits. Tertiary/Exploratory 1. Safety of the SARS-CoV-2 Delta variant human challenge model – safety laboratory tests, concomitant medications, spirometry, smell (using the UPSIT test), cognition (using the CogAssess app), are measured at baseline, during quarantine and at follow up visits 2. Infection rate, viral dynamics and symptoms of SARS-CoV-2 Delta virus with SARS-CoV-2 pre-Alpha virus challenge 3. SARS-CoV-2 viral dynamics in saliva (AUC, peak, duration, incubation period) - qRT-PCR (for SARS-CoV-2 RNA) is performed from samples collected daily during quarantine 4. SARS-CoV-2 viral infection rates in stool – stool swabs are collected when bowels are opened during quarantine and tested by qRT-PCR 5. Detection of SARS-CoV-2 breakthrough infection by lateral flow antigen tests, which will be tested daily during quarantine 6. Host-pathogen relationship in the SARS-CoV-2 Delta human challenge model (including humoral and cellular immunity, proteomics, transcriptomics, host and viral genomics, microbiome and systems biology) – blood, nasal, throat and stool samples are collected at baseline, during quarantine and at follow up visits 7. Environmental contamination in SARS-CoV-2 Delta-infected participants including during manoeuvres such as singing and reading aloud – air sampling, exhaled breath, hand and surface swabs are collected daily during quarantine and tested by qRT-PCR and cell culture. 8. Changes in the v | — |
Countries
England, United Kingdom
Contacts
Public ContactPolly Fox
Outcome results
None listed