Seasonal R21 Mass Vaccination for Malaria Elimination

NCT06578572 | Recruiting Phase 3 DMC

• 1 other identifier: LEO29834
• Study Type: interventional
• Target: 16,200
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a cluster randomized trial to determine the impact of seasonal R21/MM mass vaccination (all ages) on malaria transmission and morbidity. Fifty-four villages (30 in The Gambia and 24 in Burkina Faso) will be randomized to either mass vaccination with R21 or no mass vaccination. 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. 1.To assess the safety and tolerability of R21 through spontaneously reported adverse events.
2. 2.To compare in intervention and control clusters the incidence of malaria infection (all age groups) during the malaria transmission season following seasonal mass vaccination with R21 (3 monthly doses).
3. 3.To compare in intervention and control clusters the incidence of clinical malaria (all age groups) after seasonal mass vaccination with R21 (3 monthly doses).
4. 4.To compare in intervention and control clusters the prevalence of malaria (all age groups) at peak transmission after one booster dose of R21.
5. 5.To compare in intervention and control clusters the incidence of malaria infection (all age groups) during the malaria transmission season following one booster dose of R21.
6. 6.To compare in intervention and control clusters the incidence of clinical malaria (all age groups), after one booster dose of R21.
7. 7.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
8. 8.To estimate the cost of seasonal mass vaccination with R21 administration.
9. 9.To estimate the cost-effectiveness of seasonal mass vaccination with R21 compared to standard malaria control measures.

Conditions

Malaria

Keywords

Malaria; Malaria vaccine R21/Matrix M; Mass vaccination; The Gambia; Burkina Faso

Outcome Measures

Primary Outcomes (1)

• Prevalence of malaria infection by PCR in all age groups at peak transmission season (October-November) following the first vaccination with 3 doses.

  A cross-sectional survey will be conducted at peak transmission in October -November 2024 to determine prevalence of malaria infection.

  At 6 months ( October - November 2024) post first round of vaccination

Secondary Outcomes (10)

• Occurrence of Adverse Events (AEs) during follow up.

  Up to 28 days post vaccination

• Incidence of malaria infection in all age groups during the transmission season following mass vaccination with R21

  Up to 6 months post the third vaccination round

• Incidence of clinical malaria in all age groups following mass vaccination with R21.

  Up to 6 months post the third vaccination round

• Prevalence of malaria infection by PCR in all age groups at peak transmission following the booster dose.

  At 6 months ( October - November 2025) post booster dose

• Incidence of malaria infection in all age groups during the transmission season following the booster dose.

  Up to 6 months post booster dose

Study Arms (2)

Experimental Group

EXPERIMENTAL

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 May 2024, with the aim of having completed the vaccination schedule by end of July 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, the first 100 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.

Biological: R21Matrix M

Control Group

NO INTERVENTION

Only standard malaria control measures ( Malaria Chemoprevention (SMC), Intermittent Preventive Treatment during pregnancy (IPTp), Insecticide-Treated bed Nets (ITN), prompt diagnosis and treatment of patients with uncomplicated malaria and Indoor Residual Spraying (IRS)) will be implemented in control villages.

Interventions

R21Matrix M BIOLOGICAL

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 (May, June, and July 2024) plus a booster dose in June 2025.

Experimental Group

Eligibility Criteria

• Age: 5 Months - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age≥ 5 months.
• Willingness to comply with trial procedures.
• Individual written informed consent obtained at the beginning of the study.

You may not qualify if:

• Pregnancy
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g., Kathon, neomycin, betapropiolactone.
• Any history of anaphylaxis in relation to vaccination.
• Known chronic illness.
• 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.

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• National Malaria Control Programme, The Gambia: collaborator

Study Sites (2)

Clinical Research Unit of Nanoro, Burkina Faso

Nanoro, Burkina Faso

RECRUITING

MRC Unit The Gambia at LSHTM

Fajara, 273, The Gambia

RECRUITING

Related Publications (1)

• Dabira ED, Natama HM, Jaiteh F, Grietens KP, Bocoum FY, Ndiath MO, Mohammed N, Gibba B, Hill AVS, Ghani A, Erhart A, Tinto H, D'Alessandro U. Seasonal mass vaccination with R21/Matrix-M for malaria elimination (SERVAL): protocol of the cluster randomised trial. Trials. 2025 Sep 29;26(1):382. doi: 10.1186/s13063-025-09048-6.

  PMID: 41024138 DERIVED

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Umberto D'Alessandro, MD, MSc, PhD

  MRCG at LSHTM

  PRINCIPAL INVESTIGATOR

• Halidou Tinto, PhD

  Clinical Research Unit of Nanoro (CRUN)

  PRINCIPAL INVESTIGATOR

• Edgard Dabira, MD, MSc, PhD

  MRCG at LSHTM

  STUDY DIRECTOR

• Magloire Natama, PhD

  Clinical Research Unit of Nanoro, Burkina Faso

  STUDY DIRECTOR

Central Study Contacts

Umberto D'Alessandro, MD, DHTM, MSc, PhD

CONTACT

+220449544; Umberto.Dalessandro@lshtm.ac.uk

Anette Erhart, MD, MSs, PhD

CONTACT

Annette.Erhart@lshtm.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2024
• First Posted: August 29, 2024
• Study Start: May 30, 2024
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: August 29, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 1 month after the publication date and for a further 24 months
• Access Criteria: Application to the principal investigator with a justification of the request

Locations

TH (1); BU (1)