A Phase 4 interventional study of "Synchronised" arm (intervention) in Malaria Infection and Malaria Vaccines, sponsored by Epicentre. Recruiting at 1 site in Chad. Open to participants aged 6 Months to 59 Months, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-04-15.
Sponsored by Epicentre · Phase 4, Interventional, and Prevention
This is a two-arm, cluster-randomised, phase IV trial conducted in Chad to assess the protective efficacy and impact in real-life conditions of a new strategy for administering the R21/MM malaria vaccine, synchronized within a seasonal malaria chemoprevention (SMC) campaign, among children living in areas of high seasonal malaria transmission.
In this study, a cluster is defined as the catchment area of a primary care health centre. In Chad, each catchment area is known as a 'zone of responsibility' (French: Zone de Responsibilité' [ZR]).
Twenty-six (26) of the total 27 ZRs in the districts of Moïssala and Dembo will be randomized in a 1:1 ratio to receive a 4-dose (3 primary doses + 1 booster) R21/MM schedule either (1) integrated into the routine EPI vaccination program (the "Routine" control arm), or (2) synchronized with an annual seasonal malaria chemoprevention (SMC) campaign (the "Synchronized" intervention arm).
Malaria incidence: R21/MM effectiveness will be assessed using the incidence of biologically confirmed clinical malaria (trial primary endpoint). The incidence of clinical malaria will be determined through enhanced surveillance of malaria cases in health centres and hospitals over a 17-month period (August 2025 - December 2026).
Coverage surveys: Cross-sectional surveys (cluster sampling) will be carried out to measure R21/MM vaccine coverage, SMC coverage, coverage of other malaria prevention measures, and coverage of other EPI vaccines.
Nested case-control study: A sub-sample of children admitted to Moïssala District Hospital with severe clinical malaria will be offered the opportunity to participate in a nested case-control study designed to estimate the individual protective efficacy of R21/MM against severe malaria.
Aditionnaly, the INTEGREVAC ancillary study's objective is to evaluate the cost-effectiveness, acceptability and feasibility of the synchronised vaccination strategy in the context of the ongoing COSAV-R21 trial, to inform policy decisions for the effective deployment of malaria vaccines in SMC implementation areas.
Methodology and planned work:
(i) A qualitative study using in-depth interviews (IDIs) and group discussions with key stakeholders at the national, health facility, and community levels, including caregivers of children eligible for vaccination, in Chad, at several points during the trial. We will explore stakeholders' and beneficiaries' perceptions and experiences of the synchronised SMC vaccination strategy (trial intervention arm) compared to age-based vaccine administration under the routine immunisation programme (trial control arm), as well as considerations for implementing these strategies. Interviews with healthcare providers, including those administering R21 and SMC, and community members will assess the feasibility of implementing the integrated vaccination strategy via SMC.
(ii) An economic evaluation including a cost-effectiveness analysis and a nested equity analysis will be conducted. The economic evaluation will include a cost analysis to carefully identify and measure the additional costs associated with adding malaria vaccination to the EPI delivery platform and, separately, to the SMC delivery channel. Analysis of key cost drivers will enable us to identify potential efficiency savings, provide evidence for country funding requests (e.g., to GAVI and the Global Fund) and for the malaria vaccine strategy budgeting/planning process. Cost-effectiveness and equity analyses of each vaccine delivery strategy will provide evidence to help national programmes plan future malaria vaccine delivery and inform global guidance and on methods of delivering these vaccines, while providing valuable evidence on the real-world cost-effectiveness of malaria vaccination.
(iii) Impact modelling will estimate the costs, impact, and cost-effectiveness of scaling up the intervention approach to the whole of Chad, under different temporal and spatial scenarios.
1,184 studies on the registry are indexed under Malaria; 79 are open to participants now.
This study's planned enrollment of 70,000 is above the median of 252 across 937 interventional studies indexed under Malaria.
Browse Malaria studies →Epicentre is the lead sponsor of 49 studies on the registry; 6 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Routine arm
Oral consent provided by the child's parent/guardian.
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Exclusion Criteria:
Malaria vaccine is not recommended for children with known severe :
Mild illness - including respiratory tract infections, mild diarrhoea and fever below 38.5° C - is not a to R21/MM vaccination. Malnutrition and being -seropositive are also not contraindications to R21/MM vaccination.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
primary series (3 doses) of R21/Matrix M administered throughout the year as part of the routine Expanded Programme on Immunisation (EPI), followed by a single booster six months after the 3rd dose.
primary series (3 doses) of R21/MatrixM synchronized with a seasonal malaria chemoprevention (SMC) campaign, followed by a single booster 12 months after 1st dose was introduced.
Other: "Synchronised" arm (intervention)
Vaccines received together with CPS
Malaria incidence in children who were aged 6-11 months when receiving their first dose R21/MM
To assess whether the R21/MM vaccine synchronized with SMC is non-inferior in preventing malaria (based on malaria incidence) compared to R21/MM administered as part of routine EPI in children who were aged 6-11 months when receiving their first dose R21
Time frame: From enrollment to Month 17 (Aug 2025- december 2026)
Malaria incidence
Incidence of clinical malaria (biologically confirmed by RDT) in each study arm among children aged 6-59 months, irrespective of R21/MM vaccination status
Time frame: from enrolment to Month 17 (Aug 2025- Dec 2026)
R21/MM vaccination coverage
Proportion of children having received the appropriate number of doses for their age
Time frame: from enrolment to Month 17 (Aug 2025- Dec 2026)
Coverage of other malaria prevention measures
SMC coverage: average number of doses received per child and proportion of children receiving 0 and 5 doses
Time frame: From enrolment to month 17 (Aug 2025- Dec 2026)
Coverage of other malaria prevention measures
Proportion of children possessing, and proportion of children using, a long-lasting insecticidal net (LLIN) on the day before completing the coverage survey questionnaire
Time frame: from enrolment to Month 17 (Aug 2025- Dec 2026)
Coverage of other EPI antigens
o Proportion of age-eligible children vaccinated against measles-1 and measles-2.
Time frame: from enrolment to Month 17 (Aug 2025- Dec 2026)
Protective efficacy against severe malaria
Protective efficacy of vaccination with R21/MM will be measured at the individual level against severe malaria confirmed by RDT and microscopy. The protective efficacy will be calculated from the relative risk (RR) of developing severe malaria in vaccinated and unvaccinated children.
Time frame: From enrollment to Month 17 (Aug 2025- december 2026)
Proportional morbidity
o Proportion of all-cause morbidity registered at health centres attributed to uncomplicated malaria
Time frame: From enrollment to Month 17 (Aug 2025- december 2026)
R21/MM safety
Frequency of reported serious adverse events (SAEs), adverse events following immunization (AEFI), Serious AEFIs and reported adverse events of special interest (AESIs) following R21/MM vaccination
Time frame: From enrollment to Month 17 (Aug 2025- december 2026)
Acceptability of the synchronized strategy
Acceptability of R21 vaccination synchronized with SMC together with factors that promote or hinder the completeness of the R21 schedule. Views of policy makers, healthcare providers and caregivers collected through in-depth interviews and focus group discussions.
Time frame: from month 6 to month 24
Feasibility of the synchronized strategy
Feasibility of administering 4 doses of R21 via SMC vs. the EPI platform assessed through qualitative interviews and focus group discussions
Time frame: from Month 6 to Month 24
Cost-effectiveness
Costs to beneficiaries : Unit costs borne by beneficiaries (children and their guardians/parents) for R21 vacicnation, SMC, treatment of malaria episodes if the child has suffered one, per study arm (total cost of malaria prevention and treatment). Provider-related costs (including the health system, the research project and implementation partners) incurred in R21 vaccination by study arm. Differential cost-effectiveness ratio (ICER) per malaria case prevented by the intervention (malaria vaccination via SMC) compared to the control (R21 vaccination via EPI. The ratio of these total costs per unit of effectiveness (malaria case averted, Disavility-adjusted life year) defines cost-effectiveness.
Time frame: From first enrolment to 24 months
Fidelity of implementation of R21 vaccine delivery
We will document how the R21 vaccine administration was implemented in practice. Factors considered will include vaccine availability, accessibility of vaccination sites, staff training, community engagement efforts, adherence to vaccination schedules, quality and satisfaction with services, and any adaptations made. Data will be collected through desk review of programmatic documents, quantitative questionnaires and qualitative interviews.
Time frame: From 6 months to 24 months
Equity
Explore the equity of each strategy from the perspective of wealth/poverty status and gender/sex- of vaccinated (or unvaccinated) children in Dembo and Moïssala R21 vaccination coverage (including children who have not received any doses and children who are fully vaccinated) will be presented by wealth quintile and separately by sex/gender between study arms Questions on assets and household composition will be asked during the cross-sectional household coverage surveys
Time frame: from enrolment to Month 17 (Aug 2025- Dec 2026)
Impact modelling
Assess, over time and based on historical data, the impact of malaria vaccination and SMC on the malaria burdeb at the district level in Moïssala and at the subnational level, using mathematical models parameterised with data obtained during the CoSAV-R21 trial.
Time frame: From Month 18 to Month 36
Plan to share: Undecided
No publications or documents are linked to this record.
Started Jun 2025 (actual). Primary completion is estimated for Dec 2026, 18 months after the start.
Of 48 non-industry phase 4 interventional studies under Malaria, half reached primary completion within 18 months of starting (the median), counting those still running; a quarter within 7 and three quarters within 29. This study's planned 18 months is close to that.
Counting every sponsor, half of 49 studies reached it within 19 months; a quarter within 7 and three quarters within 32.
How these figures are worked out, and which studies are left out of them.
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