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.: PACTR202404544467702 Date of Approval: 10/04/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title SERVAL
Official scientific title Seasonal R21 mass vaccination for malaria elimination (SERVAL)
Brief summary describing the background and objectives of the trial Background Malaria remains the most important parasitic disease, particularly in sub-Saharan Africa where progress has stalled since 2014. Therefore the drive towards elimination and eventually eradication would require new tools and improved local capacities for the implementation of increasingly complex control strategies. A vaccine against malaria could be one of these new tools. Mathematical models suggest that mass vaccination with a pre-erythrocytic vaccine (PEV) may substantially reduce population-level malaria transmission. Given R21/MM is a PEV, it protects against infection and may have a substantial effect on malaria transmission when administered to the whole population. We propose to carry out a cluster randomized trial to determine the impact of seasonal R21/MM mass vaccination (all ages) on malaria morbidity and transmission Objectives The primary objective is to compare in intervention and control clusters the prevalence of malaria (all age groups) at peak transmission after seasonal mass vaccination with R21 (3 monthly doses). Secondary objectives are 1) to assess the safety and tolerability of R21 through spontaneously reported adverse events; 2) to compare in intervention and control clusters the incidence of malaria infection (all age groups) 3) to compare in intervention and control clusters the incidence of clinical malaria (all age groups); 4) to determine the coverage of seasonal mass vaccination with R21 (primary series of three vaccinations and booster) in intervention clusters and related socio-cultural factors; 5) to estimate the cost of seasonal mass vaccination with R21 administration and 6)to estimate the cost-effectiveness of seasonal mass vaccination. The exploratory objective is to determine whether serological markers can detect changes in malaria transmission
Type of trial RCT
Acronym (If the trial has an acronym then please provide) SERVAL
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 15/04/2024
Actual trial start date
Anticipated date of last follow up 31/12/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 16200
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 Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group R21Matrix M A mixture of R21/Matrix M at a dose of 5 μg (for children up to 14 years of age) or 10 μg ( for individuals ≥ 15 years old) with 50 μg of Matrix-M will be administered monthly over 3 months (one dose per month over 3 months (April, May, and June 2024) plus a booster dose in June 2025. The study intervention will be implemented for 2 years, covering two malaria transmission seasons. Three monthly doses of R21/MM will be administered to all eligible residents in the 27 intervention villages (15 in The Gambia and 12 in Burkina Faso), starting from April 2024, with the aim of having completed the vaccination schedule by June 2024, before the malaria transmission season starts. A booster vaccine dose will be administered in June 2025 to all eligible individuals who received at least one vaccine dose the previous year. Residents who are eligible but not vaccinated in the previous year, will be offered a complete vaccination schedule, i.e. 3 monthly doses, starting from April. After each vaccination, vaccinated individuals will be visited at home daily, for 3 consecutive days, and then at day 7 after the vaccination to collect local and systemic adverse events (AE). Vaccinated individuals (or their parents) will be asked to report to the nurse based in their study village any illness occurring during the 28 days after vaccination. 8100
Control Group No intervention None None In the control villages, only standard control interventions will be conducted. These interventions e.g., seasonal malaria chemoprevention, insecticide-treated bed nets, intermittent preventive treatment during pregnancy, Indoors residual spraying will be implemented by the National Malaria Control Programme. 8100 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Age≥ 5 months. 2. Willingness to comply with trial procedures. 3. Individual written informed consent obtained at the beginning of the study. 1. Pregnancy 2. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g., Kathon, neomycin, betapropiolactone. 3. Any history of anaphylaxis in relation to vaccination. 4. Known chronic illness. 5. Any other significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial. 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Child: 6 Year-12 Year,Infant: 0 Month(s)-12 Month(s),Infant: 13 Month(s)-24 Month(s),Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 5 Month(s) 100 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 20/11/2023 The Gambian Government MRC Joint Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Atlantic Boulevard Fajara Fajara 273 Gambia
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 18/01/2024 LSHTM Ethics
Ethics Committee Address
Street address City Postal code Country
Keppel Street London WC1E 7HT United Kingdom
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 04/10/2023 Comite d Ethique pour la Recherche en Sante
Ethics Committee Address
Street address City Postal code Country
1200 Logements Ouagadougou 03 BP 70 Burkina Faso
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Prevalence of malaria infection by molecular methods in all age groups at peak transmission season (October-November) following the first vaccination with 3 doses. The primary outcome is evaluated in post intervention November 2024
Secondary Outcome 1. Occurrence of Adverse events (AEs) and serious adverse events (SAEs) during follow up. 2. Incidence of malaria infection in all age groups during the transmission season following mass vaccination with R21. 3. Prevalence of malaria infection by molecular methods in all age groups at peak transmission following the booster dose. 4. Incidence of malaria infection in all age groups during the transmission season following the booster dose. 5. Incidence of clinical malaria in all age groups following the booster dose. 6. Coverage of completed vaccination schedule (3 doses) during the mass vaccination with 3 doses. 7. Coverage of the booster dose. 8. Cost of vaccine administration, both for the mass vaccination campaign with 3 doses and the booster dose. 9. Incremental cost-effectiveness. The secondary outcomes are evaluated in post intervention in Nov 2024 and Nov 2025
Secondary Outcome Secondary outcome - Exploratory outcomes Prevalence of serological markers (AMA-1, MSP-1, GLURP, GexP, RH2030 and Etramp5.Ag1) at peak transmission after mass vaccination campaign with 3 doses and the booster dose. The secondary exploratory outcomes are evaluated in post intervention in Nov 2024 and Nov 2025
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
MRC Unit The Gambia at LSHTM Atlantic Boulevard Fajara Banjul The Gambia Fajara Banjul 273 Gambia
Clinical Research Unit of Nanoro 42 Avenue Kumda Yonre Ouagadougou 11 BP 218 Burkina Faso
FUNDING SOURCES
Name of source Street address City Postal code Country
UK Research and Innovation Tothill Street London SW1H 9NA United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor London School of Hygiene and Tropical Medicine Keppel Street London London WC United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Balla Kandeh Plot 17 Kanifing Institutional Lay Out Kanifing Banjul Gambia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Umberto D Alessandro Umberto.Dalessandro@lshtm.ac.uk +2204495443 Atlantic Boulevard Fajara
City Postal code Country Position/Affiliation
Banjul 272 Gambia MRC Unit The Gambia at LSHTM
Role Name Email Phone Street address
Principal Investigator Halidou Tinto halidoutinto@gmail.com +22625409212 42 Avenue Kumda Yonre
City Postal code Country Position/Affiliation
Ouagadougou Burkina Faso Institute of Health Science Research
Role Name Email Phone Street address
Public Enquiries Umberto D Alessandro Umberto.Dalessandro@lshtm.ac.uk +2204495443 Atlantic Boulevard Fajara
City Postal code Country Position/Affiliation
Banjul Gambia MRC Unit The Gambia at LSHTN
Role Name Email Phone Street address
Scientific Enquiries Umberto D Alessandro Umberto.Dalessandro@lshtm.ac.uk +2204495443 Atlantic Boulevard Fajara
City Postal code Country Position/Affiliation
Banjul 272 Gambia MRC Unit The Gambia at LSHTM
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Anonymised IPD data will be made available from one month after trial publication and for a further 24 months Informed Consent Form,Study Protocol 1 month after the publication date and for a further 24 months Application to the principal investigator with a justification of the request
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