Integrating Malaria Vaccine With Seasonal Malaria Chemoprevention in West Africa (IMVACS)

This is a multi-site, multi-disciplinary, Phase-4 two-arm cluster-randomised non-inferiority trial in Burkina Faso and Mali to evaluate the effectiveness and real-life impact of a novel integrated delivery strategy of the R21 malaria vaccine alongside SMC among children in areas with highly seasonal malaria transmission. In this study, a cluster is defined as the catchment area of a health centre. Clusters will be randomised to receive either year-round age-based routine EPI vaccination for children aged 5-36 months ("Routine EPI Vaccination") in Burkina Faso or an annual campaign of the 3-dose primary series in children aged 5-36 months prior to the malaria season and SMC delivery (''Routine Pre-SMC vaccination'') in Mali versus an annual campaign of the 3-dose primary series aligned with SMC distribution in children aged 3-59 months ("Integrated SMC Vaccination") in each country. Effectiveness will be assessed in terms of clinical malaria, vaccine coverage, acceptability, feasibility, and cost-effectiveness.

Malaria incidence will be determined using routine surveillance activities for clinical malaria detection and reporting in each country. Cross-sectional surveys will be conducted to determine the prevalence of parasitaemia in the communities. In addition, the acceptability, feasibility, coverage and cost-effectiveness of the different delivery systems of R21/Matrix-M will be assessed.

Study Overview

• Status: Recruiting
• Conditions: Malaria Vaccine
• Intervention / Treatment: Other: Annual campaign of the 3-dose primary series vaccine R21/Matrix-M aligned with SMC distribution in children aged 3-59 months

• Study Type: Interventional
• Enrollment (Estimated): 40000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Valérie Briand; Phone Number: +331 40 21 55 55; Email: valerie.briand@epicentre.msf.org
• Study Contact Backup: Name: Soazic Gardais; Phone Number: +331 40 21 55 55; Email: soazic.gardais@epicentre.msf.org

Study Locations

• Burkina Faso
  • Ouagadougou, Burkina Faso
    • Recruiting
    • Institut de Recherche en Sciences de la Santé, Direction Régionale du Centre-Ouest
    • Contact: Natama Hamtandi Magloire; Phone Number: +226 57471950; Email: natamagloire@gmail.com
    • Principal Investigator: Natama Hamtandi Magloire
• Mali
  • Bamako, Mali
    • Recruiting
    • University of Sciences Techniques and Technologies of Bamako
    • Contact: Kassoum Kayentao; Phone Number: +223 76460173; Email: kayentao@icermali.org
    • Principal Investigator: Kassoum Kayentao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

Control arms :

• Children aged 5-36 months in Burkina Faso and Mali at the time of first study vaccination;
• Resident in the catchment area of a health centre assigned to the control arm;
• Willingness to comply with the study procedures;
• Written informed consent from Parent/Guardian.

Intervention arms :

• Children aged 3-59 months at the time of first study vaccination;
• Resident in the catchment area of a health centre assigned to the intervention arm;
• Willingness to comply with the study procedures;
• Written informed consent from Parent/Guardian.

Exclusion Criteria:

1. History of allergic disease or reactions likely to be exacerbated by any component of the Vaccines;
2. Any history of anaphylaxis in relation to vaccination;
3. Known chronic illness;
4. 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;
5. History of vaccination with another malaria vaccine. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Arm; Children aged 5-36 months will receive R21 via routine EPI vaccination (Year round in Burkina faso, or prior to the malaria season and SMC delivery in Mali)
Other: Integrated SMC Vaccination; Children aged 3-59 months will receive 3-dose primary series aligned with SMC distribution in an annual campaign	Other: Annual campaign of the 3-dose primary series vaccine R21/Matrix-M aligned with SMC distribution in children aged 3-59 months; in the intenvention arm, the children will get the vaccine R21 Matrix M together with the CPS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Malaria Incidence on 5-36 months at 12 months	Malaria incidence among children aged 5-36 months over 12 months post first dose using routine surveillance activities for clinical malaria detection and reporting	from enrollment to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Malaria incidence among children aged 5-36 months over 24 and 36 months	Malaria incidence among children aged 5-36 months over 24 and 36 months post first dose using routine surveillance activities for clinical malaria detection and reporting;	From enrollment to 2 years after booster
Malaria incidence among children aged 3-59 months over 24 and 36 months	Malaria incidence among children aged 3-59 months over 24 and 36 months post first dose using routine surveillance activities for clinical malaria detection and reporting	From enrollment to 2 years after booster
Malaria prevalence at peak transmission	Malaria prevalence at peak transmission in November after SMC campaigns in 2025 and 2026	From enrollment to 2 years after booster dose
Vaccine coverage	Pourcentage of children who has received 3 or 4 doses at 24 months post 1st vaccination	From enrollment to months 24
Occurrence of adverse events (AEs) and serious adverse events (SAEs) following R21/Matrix-M vaccination;	Occurrence of adverse events (AEs) and serious adverse events (SAEs) following R21/Matrix-M vaccination	From enrollment to months 4
Acceptability	Qualitative interviews and FGDs among policy makers, health managers, health providers and caregivers	From 12 months after study start to 36 months
Stakeholder perceptions of the feasibility on the vaccine delivery strategy in each group	Acceptability and feasibility studies will use qualitative longitudinal study (QLS) research methods. We will apply an ecological framework approach with emphasis on the interplay and inter-dependency between individual, interpersonal, organizational, and policy levels. Qualitative data will be collected through ethnographic immersion, in-depth interviews, group interviews and focus group discussions. No quantitative measurements will be made.	From enrollment to months 36
Contextual and behavioural factors impeding or facilitating R21/Matrix-M vaccine uptake	Interviews and FGD - will be explained in a parallel protocol	From enrollment to months 24
Stakeholders and caregivers perceptions of the factors that enhance and/or constrain the succesful co,pletion of four doses of R21 and the key drivers of vaccination coverage	The study will cover a full, two-year R21/Matrix-M delivery cycle with data collection at two time points in each arm: soon after the primary series is delivered, and soon after the booster dose is provided a year later. This longitudinal approach will enable us to explore and chart dynamic processes as they occur, barriers and facilitators, and acceptability over time. It is inherently suitable for studying R21/Matrix-M introduction, requiring prolonged and repeated involvement by patients and providers. This approach is also necessary to explore the drivers of vaccine hesitancy which is not a static state; vaccine decision-making changes over time as caregivers experience different influences and nudges along the way. Qualitative data will be collected through ethnographic immersion, in-depth interviews, group interviews and focus group discussions to explore factors in the service delivery, household, and broader social environments that will lead to R21 adoption and adherence. A	From enrollment to months 24 and 36
Incremental costs (per child vaccinated) and cost-effectiveness (per malaria case and separately, per DALY averted) of each vaccination strategy, calculated from a societal perspective	Costs associated with the different vaccination strategies will be estimated by collecting data on direct and indirect costs to health systems and opportunity costs to vaccinees and their caregivers (beneficiaries). Beneficiary costs will be collected during household surveys, via case report forms developed to collect data on direct costs (transport, food, medication) and indirect costs (time and income loss) incurred by their household related to each intervention arm. Provider costs will be collected using custom built spreadsheets structured to comprehensively capture the resources used for all intervention delivery related activities (excluding research activities) by cost category (person time, equipment, consumables including vaccines, storage, transport, overheads and other costs) by arm. Malaria incidence estimates (primary clinical outcome) will be used to calculate malaria cases and DALYs averted by arm, adjusted for intervention coverage (using the coverage survey data).	From enrollment to months 36

Collaborators and Investigators

• Sponsor: Epicentre
• Collaborators: Liverpool School of Tropical Medicine; R-Evolution Worldwide; CNRST Burkina Faso; USTTB Mali

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 20, 2025
• First Submitted That Met QC Criteria: February 28, 2025
• First Posted (Actual): March 5, 2025

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: pediatric; vaccine; malaria; CPS; R21
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria
• Other Study ID Numbers: IMVACS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No