Pan African Clinical Trials Registry

South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202309751708712 Date of Registration: 13/09/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Experimental Human Pneumococcal Challenge with Streptococcus pneumoniae serotype 3
Official scientific title Serotype 3 Dose ranging and reproducibility Experimental Human Pneumococcal Challenge in healthy volunteers
Brief summary describing the background and objectives of the trial Streptococcus pneumoniae (SPN) is a major cause of morbidity and mortality from a lower respiratory tract infection globally, as well as causing pneumonia, meningitis, and sepsis. Nasopharyngeal carriage of pneumococcus is a prerequisite for pneumococcal disease and transmission of the bacterium and thus represents a risk to carriers themselves and to the wider community. Since the global introduction of pneumococcal conjugated vaccines (PCVs), the rates of pneumococcal disease have declined for many of the vaccine type (VT) serotypes but serotype 3 (SPN3) continues to cause significant disease. This may be due to the higher ‘force of infection’ where intense transmission overcomes vaccine-induced immunity or it may be a unique property of the type 3 capsule which is abundant and shed in large quantities by the bacteria. The Experimental Human Pneumococcal Challenge (EHPC) model, developed by our team, is a unique method of determining pneumococcal colonisation rates, understanding the impact of colonisation on acquired immunity and for testing pneumococcal vaccines. This safe and reproducible EHPC model has been established in Liverpool and transferred to Malawi using SPN6B and has demonstrated acceptability to local stakeholders and feasibility in healthy adults. To increase the relevance of the EHPC model and its use for vaccine development, we will develop a serotype 3 EHPC model to address some pertinent questions on the burden of pneumococcal disease in Malawi and similar sub-Saharan African settings. The study will consist of a dose ranging and safety study and a reproducibility study. Sequential cohorts of 10 healthy participants will be challenged with escalating doses of SPN3 in the dose ranging study, aiming to reach 60% carriage. Nasal wash samples will be collected for determination of carriage. The reproducibility part of the study will ideally use a dose that results in ≥60% of carriage, and with a high safety profile. A total of 33 participants will be enrolled in this cohort to check for reproducibility of the carriage rate. Various samples will be collected for determination of both local and systemic immunological responses to pneumococcal challenge.
Type of trial Observational
Acronym (If the trial has an acronym then please provide) SPN3
Disease(s) or condition(s) being studied Ear, Nose and Throat,Respiratory
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Controlled human infection model or human infection study
Anticipated trial start date 18/09/2023
Actual trial start date
Anticipated date of last follow up 31/05/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 83
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Single Group Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Streptococcus pneumoniae serotype 3 10,000, 20,000, 80,000, 160,000 or 320,000 cfu/naris 28 days per cohort/dose Type 3 Streptococcus pneumoniae typed, sequenced and penicillin sensitive 10
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Healthy adults aged 18-50 years. • Fluent spoken English and/or Chichewa. • Capacity to give informed consent • HIV negative • Access to their own mobile telephone • Currently involved in another study unless observational or non-interventional. • Participant in any previous EHPC trial in past year • Previous pneumococcal vaccination. This can be self-reported or confirmed from the health passport if deemed necessary at clinician discretion. • HIV positive • Allergy to penicillin/amoxicillin • Chronic ill health including immunosuppressive history, diabetes, asthma (on regular medication), recurrent otitis media or other respiratory disease. • Medication that may affect the immune system e.g., steroids, inflammation altering or disease-modifying anti-rheumatoid drugs. • Long term use of antibiotics for chronic infection. • Major pneumococcal illness requiring hospitalisation in the last 10 years. • Other conditions considered by the clinical team as a concern for participant safety or integrity of the study • Significant mental health problems (uncontrolled condition or requiring previous admission to a psychiatric unit) that would impair ability to participate • Direct caring role or close contact with individuals at higher risk of infection; Children under 5 years age, adults with chronic ill health or immunosuppression, hospital patients • Current or ex-smoker (daily cigarettes, daily e-cigarettes/vaping and daily smoking of recreational drugs) in the last 6 months. Participants who smoke <5 cigarettes per week may be included. Previous significant smoking history (>20 cigarettes per day for 20 years or equivalent [>20 pack years]. • Currently pregnant/lactating/ Intending on becoming pregnant during the study • History of or current drug or alcohol abuse; Men should not drink >3 units/day regularly. Women should not drink >2 units/day regularly. • Overseas travel planned in follow up period of study visits • Natural SPN3 colonisation in baseline nasal wash Adult: 18 Year(s)-44 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 50 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 05/05/2023 National Health Sciences Research Committee
Ethics Committee Address
Street address City Postal code Country
Ministry of Health and Population, Area 2, Close to Lilongwe Primary School Lilongwe 0265 Malawi
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Detection of SPN3 in nasal wash by classical microbiology at any time point Days 2, 7, 13, 16, 21, 28
Secondary Outcome Carriage duration and density by classical microbiology and PCR. Pneumococcal carriage rate following experimental pneumococcal inoculation with different doses. Musocal immune cell populations and dynamics in nasal cells. Mucosal and systemic SPN3 polysaccharide-specific antibodies at baseline and after SPN3 experimental inoculation. Participant exit interviews Days 2, 7, 13, 16, 21, 28 in the reproducibility study arm
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Malawi Liverpool Wellcome Programme at Queen Elizabeth Central Hospital Queen Elizabeth Central Hospital, Chipatala Avenue Blantyre 0265 Malawi
FUNDING SOURCES
Name of source Street address City Postal code Country
The Wellcome Trust 215 Euston Road, London NW1 2BE London 0044 United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Liverpool School of Tropical Medicine Pembroke Place, Liverpool L3 5QA Liverpool 0044 United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Prof Daniela Ferriera Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA Liverpool 0044 United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Tarsizio Chikaonda tchikaonda@mlw.mw 002651811918 Malawi-Liverpool Wellcome Programme, Queen Elizabethe Central Hospital, Chipatala Avenue, Ginnery Corner
City Postal code Country Position/Affiliation
Blantyre 00265 Malawi Laboratory Lead Scientist. Malawi Liverpool Wellcome Programme
Role Name Email Phone Street address
Scientific Enquiries Stephen Gordon sgordon@mlw.mw 002651811918 Malawi-Liverpool Wellcome Programme, Queen Elizabethe Central Hospital, Chipatala Avenue, Ginnery Corner
City Postal code Country Position/Affiliation
Blantyre 00265 Malawi Chief Investigator. Malawi Accelerated Research in Vaccines by Experimental Laboratory Systems. Malawi Liverpool Wellcome Programme
Role Name Email Phone Street address
Public Enquiries Neema Toto ntoto@mlw.mw 002651811918 Malawi-Liverpool Wellcome Programme, Queen Elizabeth Central Hospital, Chipatala Avenue, Ginnery Corner
City Postal code Country Position/Affiliation
Blantyre 00265 Malawi Senior Study coordinator. Malawi Liverpool Wellcome Programme.
Role Name Email Phone Street address
Public Enquiries Anthony Emeritus Chirwa achirwa@mlw.mw 002651811918 Malawi-Liverpool Wellcome Programme, Queen Elizabeth Central Hospital, Chipatala Avenue, Ginnery Corner
City Postal code Country Position/Affiliation
Blabtyre 00265 Malawi Study Physician. MARVELS. Malawi Liverpool Wellcome Programme
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data will be available upon specific request to the chief investigator with the decision to share made using prospective, transparent and objective criteria and contingent on signed data sharing agreements. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol Within 12 months of study completion Controlled according to a prospective data sharing and access policy developed by the MARVELS team. Criteria for release will be transparent and objective according to pre-defined rules in the policy.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information