Comparison of Two Strategies for Administering the R21-Matrix M Vaccine in a Context of Seasonal Malaria Transmission in Chad (COSAV-R21)

Epicentre

Status and phase: Enrolling; Phase 4

Conditions: Malaria Infection; Malaria Vaccines

Treatments: Other: "Synchronised" arm (intervention)

Study type: Interventional

Funder types: Other

Identifiers

NCT07038837

COSAV-R21

Details and patient eligibility

About

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.

Enrollment: 70,000 estimated patients

Sex: All

Ages: 6 to 59 months old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• • Routine arm

  1. Aged 6 to 11 months at the time of the first R21/MM vaccination (dose 1).

  2. Residing in a village participating in the study and randomized to the routine arm.

  3. Oral consent provided by the child's parent/guardian.

     • Synchronised arm
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  1. Aged 6 to 59 months at the time of the first R21/MM vaccination (dose 1) during the first 3 rounds of SMC (2025).
  2. Residing in a village participating in the study and randomized to the synchronized arm.
  3. Oral consent provided by the child's parent/guardian.

Exclusion criteria

• Exclusion criteria for both arms according to Chad national EPI guidelines

Malaria vaccine is not recommended for children with known severe hypersensitivity:

• To a previous dose of a malaria vaccine
• To a previous dose of hepatitis B vaccine
• One of the components of the R21/MM vaccine

Mild illness - including respiratory tract infections, mild diarrhoea and fever below 38.5° C - is not a contraindication to R21/MM vaccination. Malnutrition and being HIV-seropositive are also not contraindications to R21/MM vaccination.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70,000 participants in 2 patient groups

"Routine" arm (control)

No Intervention group

Description:

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.

"Synchronised" arm (intervention)

Experimental group

Description:

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.

Treatment:

Other: "Synchronised" arm (intervention)