RSV
Conditions
Brief summary
This is a human challenge sequential cohort study involving healthy, non-smoking older adults aged 65-75 years. We aim to enrol 20 participants. There will be a sentinel cohort of 6 participants at the beginning of the study (Group 1). If no pausing rules are met, the remaining 14 participants will be enrolled for a total of 20 enrolled participants (Group 2). The study will consist of three main phases: (1) screening and baseline, (2) inoculation and quarantine, and (3) follow up. All participants will attend a screening visit for a comprehensive health assessment to confirm eligibility. If eligible, participants will take part in an inpatient stay in a quarantine unit, where they will be inoculated with 105 plaque-forming units of RSV B-I54 by intranasal drops. The inoculation dose has been determined in the earlier mentioned outpatient study of the same virus strain, in healthy young adults. Due to the older age range and potentially increased risk of more severe disease, participants will remain within the quarantine unit for 10-days post inoculation and will be closely monitored by clinical review and self-completed symptom diaries. Participants will undergo daily sample collection and will remain in quarantine until the discharge criteria are met at Day 10. After discharge, participants will attend follow-up visits at Day 14, Day 28, and Day 90. Participants in Group 2 will have an additional baseline visit at Day -14 where blood, respiratory (nose and throat) and lower airway (bronchoscopy) samples will be collected. Group 2 participants will also undergo a second bronchoscopy during the inpatient period and the third and final bronchoscopy at Day 28. Clinical outcomes will be determined by symptomatology and viral detection in nasal lavage using quantitative PCR. Based on the first-in-human RSV B characterisation study and recent elderly RSV A challenge data, we anticipate approximately 74% attack rate, with a range of mild-moderate symptoms in the infected individuals. Symptoms typically commence 3 days post-inoculation and worsen to peak around days 5-9 before rapidly resolving without treatment. Timing of viral shedding is expected to correlate closely with symptoms.
Interventions
BIOLOGICALRSV B
RSV B challenge virus
Sponsors
Imperial College London
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Group 1 (Sentinel) Group 2 (Bronchoscopy)
Eligibility
Sex/Gender
ALL
Age
65 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Aged between 65 to 75years (inclusive) at Day 0. 2. Willing and able to commit to participation in the study. 3. Adequate understanding of the study, the procedures involved, and able to provide written informed consent prior to any study procedures. 4. In good health with no history of clinically significant medical conditions (as described in
Exclusion criteria
) that would interfere with participant safety. A forced expiratory volume in 1 second (FEV1) and a forced vital capacity (FVC) \<80% of predicted value calculated using ATS/ERS guidance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number, frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) Adverse Events (AEs) from the viral challenge (Day 0) up to Day 28. | 28 Days | AEs may pertain to: * Solicited symptoms when they are reported as 'severe' or when they last longer than 14 days. * Unsolicited symptoms. |
| Number, frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) Adverse Events (AEs) relating to the bronchoscopy sampling in those undergoing bronchoscopy procedures (Group 2) | 28 Days | * Solicited symptoms when they are reported as 'severe' or when they last longer than 14 days. * Unsolicited symptoms. |
| Occurrence of clinically significant abnormalities and changes from baseline in clinical laboratory tests up to and including Day | 7 days | Occurrence of clinically significant abnormalities and changes from baseline in clinical laboratory tests up to and including Day 7: * Haematology. * Biochemistry. |
| Occurrence of clinically significant abnormalities and changes from baseline in clinical measurements and assessments (physical examination, vital signs, ECG or Spirometry) from viral challenge (Day 0) up to Day 28. | 28 Days | Occurrence of clinically significant abnormalities and changes from baseline in clinical measurements and assessments (physical examination, vital signs, ECG or Spirometry) from viral challenge (Day 0) up to Day 28. |
| Infection rate in older adult participants after inoculation with a GMP wild-type RSV B | 8 Days | Infection defined by: * RSV RNA detectable by qPCR in nasal swab on 2 or more consecutive measurements, the first occurring between 2-8 days (inclusive) post-inoculation. * Infection rate equalling the number of infected participants divided by the sum of all participants inoculated with the virus, expressed as a percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RSV B viral dynamics in upper respiratory samples | 8 Days | Viral load over time, determined by virus-specific qPCR: • Onset of viral shedding (tlag) |
| RSV disease after inoculation with a GMP wild-type RSV B strain | 14 Days | Self-reported solicited symptom scores as recorded by the Modified Jackson score and WURSS-24 questionnaire to establish: o Total symptom score. |
| Systemic antibody response to challenge RSV B infection | 28 Days | Serum neutralizing antibody titre at baseline (day -1) and 28 post-inoculation. |
Contacts
CONTACTPolly Fox-Sheehan, BSc, MSc
PRINCIPAL_INVESTIGATORChristopher Chiu, BMBCh FRCP FRCPath PhD
Imperial College London
Outcome results
None listed