Respiratory infections, respiratory syncytial virus and pneumococcus Infections and Infestations
Conditions
Interventions
The study has a follow-up duration of 60 days and up to 9 clinical visits during that period.
In Phase A: Up to 10 Healthy volunteers will be challenged with either Spn6B or RSV-A at day 0 followed b
nasal washes (whereby the nose is irrigated with normal saline and the liquid that is prod
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Healthy adults aged 18-55 years (inclusive, at the time of consent) 2. Fluent spoken English – to ensure a comprehensive understanding of the research project 3. Capacity to provide written informed consent in English 4. Females of childbearing potential with a negative urine pregnancy test at screening and willing to practice adequate contraceptive measures as per UK Clinical Trial Facilitation Group during the study. 5. Willing to provide their household contacts with the Close Contact Screening Information Letter 6. For Phase C, RSV neutralising antibody titre in the lowest 10th percentile of screened participants
Exclusion criteria
Exclusion criteria: 1. Research participant: 1.1. Currently involved in another study unless observational or non-interventional. Exceptions may be applied at the discretion of the Chief Investigator to ensure no harm comes to the participants (e.g. excessive blood sampling or nasal sampling) 1.2. Participated in a previous Spn6B EHPC study < = 3 years or an Spn3 EHPC study < = 1 year before screening 2. Unable to travel to outpatient clinic for visits without using public transport 3. Unable to wear an FFP2 mask 4. Nasal carriage: Participants who have natural pneumococcal or RSV-A nasal carriage identified at visit 1 will be excluded before randomisation (see table 2A). 5. Vaccination: 5.1. No live vaccination within four weeks prior to enrolment (defined as time of first inoculation) 5.2. Previous pneumococcal or (investigational) RSV vaccination (including in a research study) 6. Allergy to beta-lactam antibiotics (including penicillin and amoxicillin) 7. Medical history leading to increased risk of severe infection, illness including but not limited to: 7.1. Asplenia or dysfunction of the spleen 7.2. Chronic respiratory disease (e.g. asthma [requiring medication (including salbutamol inhaler) within last 12 months], COPD, bronchiectasis and sleep apnoea) 7.3. Chronic heart disease (e.g. angina, ischaemic heart disease, chronic heart failure) – controlled and stable hypertension may be included 7.4. Chronic kidney disease (e.g. nephrotic syndrome, kidney transplant, requires dialysis) 7.5. Chronic liver disease (e.g. cirrhosis, biliary atresia, hepatitis) 7.6. Chronic neurological disease that limits mobility, bulbar or respiratory function (including stroke, Parkinson’s disease, dementia and multiple sclerosis) 7.7. Diabetes mellitus (including diet controlled) 7.8. Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 12 months or long-term systemic corticosteroid, Roaccutane, or disease modifying anti-rheumatoid drugs therapy (for more than 7 consecutive days within the 3 months prior to enrolment). 7.9. Individuals with cochlear ear implants 7.10. Individuals with major cerebrospinal fluid leaks (e.g. following traumatic, major skull surgery, or requiring CSF shunts) 7.11. Subjects with known or suspected immune deficiency (e.g. known IgA deficiency, immotile cilia syndrome, or Kartagener’s syndrome) 7.12. History of frequent nose bleeds 7.13. Bleeding disorders 8. Current medical issues 8.1. Acute upper respiratory tract infection in the four weeks preceding recruitment (as per definition in Annex 1) 8.2. Any uncontrolled medical or surgical condition (e.g. mental health conditions, epilepsy, narcolepsy or chronic pain) at the discretion of the study doctor 9. Any major pneumococcal illness or pneumonia requiring hospitalisation in the last 10 years 10. Medication 10.1 Any medication that may affect the immune system in the last 3 months (e.g. systemic steroids [IM/IV], Roaccutane, disease modifying anti-rheumatoid drugs) 10.2 Long-term antibiotic use 10.3 Recipient of monoclonal antibodies for any indication 10.4 Recipient of blood transfusion products within the last year 10.5 Any medication that may affect the coagulation system in the last 3 months (excluding aspirin) 10.6 Use of any medication or other product (prescription or over-the-counter) for symptoms of rhinitis or nasal congestion within the last 1 month 11. Maternal 11.1. Female participants who are pregnant 11.2. Female
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Presence of Spn6B detected by classical microbiology in at least one nasal wash sample at any timepoint following Spn6B challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Absence of SAEs measured in Phase A before progression to Phase B: Timepoints: Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60 2. Presence of Spn6B detected by RT-qPCR in at least one nasal wash sample at any timepoint following Spn6B challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60 3. Presence of Spn6B detected by combined RT-qPCR and classical microbiology in at least one nasal wash sample at any timepoint following Spn6B challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60 4. Spn6B density detected by combined RT-qPCR and classical microbiology in nasal wash sample at any timepoint following Spn6B challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60 5. Spn6B presence and density detected by combined RT-qPCR and classical microbiology in nasal wash sample at any timepoint following Spn6B challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60 6. Presence of RSV-A detected by RT-qPCR in at least one nasal wash sample at any timepoint following RSV-A challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60 7. RSV-A presence and viral load detected by RT-qPCR in nasal wash sample at any timepoint following RSV-A challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60 8. Number of URTI and LRTI symptoms per participant after secondary challenge. Timepoints: Day 9, Day 14, day 21 and Day 60 9. Shedding of pathogens from the nose and throat will be assessed by: 9.1.Coughing plate (Spn6B colonies detected by classical microbiology after Spn6B challenge: timepoints D2, D6, D9 and D14). 9.2. Hand swab after nose touching (Spn6B colonies/DNA copies detected by classical microbiology and RT-qPCR after Spn6B challenge: timepoints D2, D6, D9 and D14). 9.3. Facemasks assessments (RSV viral load quantification by RT-qPCR Spn6B colonies/DNA copies quantification by classical microbiology and RT-qPCR; timepoints: D6 and D14) 10. Self-collected home samples (nasopharyngeal swabs) collected once per week for 2 weeks from househol | — |
Countries
United Kingdom
Contacts
Public ContactCarla Solórzano Gonzalez
Outcome results
None listed