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.: PACTR202403820001276 Date of Registration: 28/03/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title MV130 and Pneumococcal Colonisation in Malawi
Official scientific title The Influence of MV130 immunotherapy on Nasal Colonisation in a Controlled Human Infection Model of Pneumococcal Carriage in Malawi
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 (CAP), bacterial meningitis and bacteremia worldwide. Pneumococcal infections cause over one million pneumonia deaths per year in children in the developing world and are also a major burden of otitis media globally. Pneumococcal conjugate vaccines (PCV) represent a great achievement in providing protection from invasive pneumococcal disease, but they are expensive to manufacture, limited in serotype coverage, associated with serotype replacement and are less effective against mucosal infection (13-20%) than against invasive disease. Despite introduction of the PCV 13 vaccine to Malawi in 2011, pneumococcal disease remains the single most important bacterial infection of adults and children. There is persistent nasal carriage of both vaccine type and non-vaccine type Streptococcus pneumoniae in both children and HIV-infected adults. Implications of this is 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 the persistent pneumococcal carriage may indicate sub-optimal or short duration of PCV13 vaccine-induced immunity. Cost-effectiveness estimates for PCV13vaccination are based strongly on improved herd immunity through reduced carriage (reservoir for infection transmission) in vaccinated children. This study will determine potential immunological mechanisms for the differential effects of MV130 on nasal carriage in healthy Malawian populations. The burden of both nasal carriage rates and invasive infection is still high in Malawi. Increased background exposure to pneumococcus is a potential mechanism for reduced vaccine efficacy. Based on our experience in Malawi, and the need to have approximately half of the volunteers experiencing carriage, we will test MV130 effectiveness against a 6B pneumococcal inoculum dose of 160,000 CFU/naris
Type of trial RCT
Acronym (If the trial has an acronym then please provide) MV130
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 02/04/2024
Actual trial start date
Anticipated date of last follow up 30/09/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 106
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
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
Experimental Group MV130 2 sprays (0.2ml) daily 42 days MV130 formulation contains as active ingredient/s different species of whole inactivated bacteria at 300 FTU/mL (equivalent to 109 bacteria/mL) which are frequently present in the respiratory tract: V102 Staphylococcus aureus (15%), V101 Staphylococcus epidermidis (15%), V104 Streptococcus pneumoniae (60%), V113 Klebsiella pneumoniae (4%), V105 Moraxella catarrhalis (3%) and V103 Haemophilus influenzae (3%). Excipients include glycerol, pineapple artificial flavoring, sodium chloride and water for injection. Dose administered sublingual (under the tongue) 53
Control Group Placebo 2 sprays (0.2ml) daily 42 days Placebo contains only excipients. Excipients include glycerol, pineapple artificial flavoring, sodium chloride and water for injection. 53 Placebo
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 • Access to refrigerator or able to come to clinic daily to take dose of drug at study site • Previous pneumococcal vaccination/Immunotherapy or involvement in pneumococcal controlled human infection studies (inoculation with bacteria may confer immunity) • HIV-infection seropositive. HIV self-test kits will be used by participants to confirm infection status in the presence of the research team. • 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. Adult: 18 Year(s)-44 Year(s) 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 18/07/2023 National Health Sciences Research Committee
Ethics Committee Address
Street address City Postal code Country
Ministry of Health and Population, Area 2 Close to Lilongwe 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
No 06/04/2023 Liverpool School of Tropical Medicine Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Pembroke Place, Liverpool, L3 5QA, UK Liverpool L3 5QA United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Neutrophil count and T cell lymphocytes measurement in the nasal mucosa after 14 days of MV130 treatment. 14 days of MV130 treatment
Secondary Outcome Pneumococcal carriage density and duration will also be measured. Innate, humoral, and cellular responses to pneumococcal colonisation will be assessed by immunological assays on collected samples. These data will allow us to define the host variables that predict colonisation and protection due to MV130 administration. Days 2 and 7 following initial pneumococcal challenge
Secondary Outcome Perceptions of and concerns about controlled human infection; experience of engagement activities and consent processes; and participant recommendations for future research. At exit on day 7 assessed through exit interview
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
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 WC1E 6BP, United Kingdom London NW1 2BE 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 L3 5QA United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Prof Daniela Ferreira Pembroke Place, Liverpool, L3 5QA, UK Liverpool L3 5QA United Kingdom
Ashleigh Howard LLSA 01st Daulby Street, L7 8XZ Liverpool L7 8XZ United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Stephen Gordon sgordon@mlw.mw +2651812423 Malawi Liverpool Wellcome Programme, Queen Elizabeth Central Hospital, Chipatala Avenue, Blantyre, Malawi
City Postal code Country Position/Affiliation
Blantyre 00265 Malawi Chief Investigator
Role Name Email Phone Street address
Principal Investigator John Ndaferankhande jndaferankhande@mlw.mw +2651812423 Malawi Liverpool Wellcome Programme, Queen Elizabeth Central Hospital, Chipatala Avenue, Blantyre, Malawi
City Postal code Country Position/Affiliation
Blantyre 00265 Malawi Pharmacist
Role Name Email Phone Street address
Public Enquiries Neema Toto ntoto@mlw.mw +2651812423 Malawi Liverpool Wellcome Programme, Queen Elizabeth Central Hospital, Chipatala Avenue, Blantyre, Malawi
City Postal code Country Position/Affiliation
Blantyre 00265 Malawi Project 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 1 year post trial 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