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 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202008503507113 Date of Approval: 03/08/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title PCV13 and Pneumococcal Colonisation in Malawi
Official scientific title The Influence of Pneumococcal Conjugate Vaccine-13 on Nasal Colonisation in a Controlled Human Infection Model of Pneumococcal Carriage in Malawi v1.3 05 Jan 2022
Brief summary describing the background and objectives of the trial Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide.Despite the introduction of the PCV-13 vaccine to Malawi in 2011, pneumococcal disease remains the single most important bacterial infection of adults and children. Data demonstrate that despite an impressive reduction in invasive pneumococcal disease for vaccinated children, there is persistent nasal carriage of both vaccine type and non-vaccine type Streptococcus pneumoniae in both children and HIV-infected adults. The implications of this important finding are that (A) herd effects with PCV13 are not as strong as in Malawi compared to US data, with vaccine type pneumococcus a continued threat to vulnerable adults and children and (B) the persistent pneumococcal carriage may indicate sub-optimal or short duration of PCV13 vaccine-induced immunity. We established a safe and reproducible Controlled Human Infection Model (CHIM) at the Liverpool School of Tropical Medicine (LSTM), U.K. Most recently, we have successfully transferred operating procedures from the LSTM model and safely adapted these for the Malawian context. This study will determine potential immunological mechanisms for the differential effects of PCV-13 on nasal carriage between healthy Malawian and UK populations. The burden of both nasal carriage rates and invasive infection is much higher in Malawian compared to UK populations. Increased background exposure to pneumococcus is a potential mechanism for reduced vaccine efficacy. Therefore, we will test vaccine effectiveness against a sequentially increased pneumococcal exposure dose of 20,000, 80,000 and 160,000 colony forming units per nostril.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PCV13
Disease(s) or condition(s) being studied Respiratory
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 21/03/2021
Actual trial start date 27/04/2021
Anticipated date of last follow up 25/05/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 200
Actual target sample size (number of participants)
Recruitment status 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
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Sterile normal saline 0.5ml intramuscular injection Single dose Sterile 0.9% saline has been chosen as a suitable control due to its long established safety profile in vaccine trials and lack of effect on nasal colonisation/immunity. Saline vaccination is commonly used as a control for vaccine trials including in sub-Saharan Africa and in recently published COVID vaccine studies. Adverse reactions which may occur becasue of this solution, added drugs or the technique of reconstitution or administration include, but are not limited to, air embolization, febrile response, local tendersness, abscess, tissue necrosis or infection at the site of injectin, venous thrombosis or phlebitis extending from the site of injection. 100 Placebo
Experimental Group Prevnar 13 suspension for injection pneumococcal polysaccharide conjugate vaccine 0.5ml intramuscular injection Single dose Prevenar-13 is a safe vaccine with a very low risk of adverse events. It is currently licensed for use in children and in Malawi as part of the Childhood Immunisation programme (effective from 2011). In adults over 50 years of age vaccinated in US clinical trials the most commonly reported side effects to Prevenar-13 vaccination included: injection site pain/swelling/tenderness, fatigue, headache, muscle pain, limitation of arms movement, decreased appetite, chills and rash. 100
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Adults aged 18-40 years - ages chosen to minimise the risk of pneumococcal infection Fluent spoken and written Chichewa or English - to ensure a comprehensive understanding of the research project, their proposed involvement and communication with all members of the research team Previous pneumococcal vaccination. COVID-19 positive at time of screening tests HIV-infection sero positive. HIV self-test kits will be used by participants to confirm infection status in the presence of the research team. Any seropositive participant will be referred to trained personnel certified in HIV Testing Services (HTS) for confirmatory “Determine” and “Unigold” tests. Any participants confirmed as HIV-infection positive will be referred to the governmental system for infection confirmation, treatment and follow up. Close physical contact (e.g. sleeping in the same room or nursing) with at-risk individuals (children under 5 years age, immunosuppressed adults, elderly, chronic ill health). Allergy to penicillin/amoxicillin. Acute illness (current illness, Acute illness within 3 days prior to inoculation, Antibiotic treatment within 2 weeks of inoculation). Chronic illness that may impair immune response or impair ability to comply with study procedures and safety monitoring (e.g. HIV, diabetes). Taking immunosuppressive medication that may include but is not limited to steroids and steroid nasal spray. Pregnancy - minimise risk of pneumococcal disease. Involved in another clinical trial unless observational or in follow-up (non-interventional) phase. History of drug or alcohol abuse. This is very difficult to ascertain in a history therefore we will exclude people reporting drinking alcohol more than twice per week. History of Smoking (Current regular smoker (smokes daily/ smokes > 5 cigarettes per week) - minimise risk of pneumococcal disease. Recent smoker i.e. within the last 6 months - minimise risk of pneumococcal disease. Ex-smoker with a significant smoking history (>10 pack years) – minimise risk of pneumococcal disease) Unable to give informed consent. In case of any uncertainty or concern, the PI will take clinical responsibility for the decision. Participant is positive for Streptococcus pneumoniae serotype 6B on nasal wash sample at visit C. Cur Adult: 19 Year-44 Year 18 Year(s) 40 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 01/05/2020 National Health Sciences Research Committee
Ethics Committee Address
Street address City Postal code Country
National Health Sciences Research Committee, Ministry of Health and Population, Area 2. Close to Lilongwe Private School. Lilongwe 0265 Malawi
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 02/06/2020 Liverpool School of Tropical Medicine Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Pembroke Place, Liverpool, L3 5QA, UK Liverpool 0044 United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Detection of Spn6B in nasal wash by classical microbiology Day 2, 7 or 14 post inoculation
Secondary Outcome Spn6B detected in nasal wash at day 2, 7 or 14 post inoculation. Carriage density by classic microbiology and PCR. Serum and nasal fluid evaluation by ELISA/multiplex and Ig functional assays. Antigen specific and non-specific cellular responses in blood and nasal cells. Participant exit interviews Day 2, 7 or 14 post inoculation
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Malawi Liverpool Wellcome Trust Programme at Queen Elizabeth Central Hospital Queen Elizabeth Central Hospital, Chipatala Avenue. Blantyre. Malawi Blantyre 0265 Malawi
FUNDING SOURCES
Name of source Street address City Postal code Country
The Wellcome Trust 215 Euston Road, London NW1 2BE, UK 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 UK Liverpool 0044 United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Prof Daniela Ferreira 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 Stephen Gordon sgordon@mlw.mw 002651811918 Malawi Liverpool Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Chipatala Avenue, Ginnery Corner, Blantyre. Malawi
City Postal code Country Position/Affiliation
Blantyre 00265 Malawi The Director. Malawi Liverpool Wellcome Trust Clinical Research Programme
Role Name Email Phone Street address
Scientific Enquiries Ben Morton bmorton@mlw.mw 002651811918 Malawi Liverpool Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Chipatala Avenue, Ginnery Corner, Blantyre. Malawi
City Postal code Country Position/Affiliation
Blantyre 00265 Malawi Principal Investigator
Role Name Email Phone Street address
Public Enquiries Markus Gmeiner mgmeiner@mlw.mw 002651811918 Malawi Liverpool Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Chipatala Avenue, Ginnery Corner, Blantyre. Malawi
City Postal code Country Position/Affiliation
Blantyre 00265 Malawi Clinical Research Support Unit Lead
Role Name Email Phone Street address
Public Enquiries Neema Toto ntoto@mlw.mw 002651811918 Malawi Liverpool Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Chipatala Avenue, Ginnery Corner, Blantyre. Malawi
City Postal code Country Position/Affiliation
Blantyre 00265 Malawi Social Scientist and Study Coordinator
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 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