Clinical trial NCT06578572: Seasonal R21 Mass Vaccination for Malaria Elimination
Official title: Seasonal R21 Mass Vaccination for Malaria Elimination
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Malaria
Keywords: Malaria
Malaria vaccine R21/Matrix M
Mass vaccination
The Gambia
Burkina Faso
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: National Malaria Control Programme, The Gambia
First posted: 2024-08-29
Enrollment: 16200
Sex: ALL
Minimum age (years): 5
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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. 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) during the malaria transmission season following seasonal mass vaccination with R21 (3 monthly doses).
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. To compare in intervention and control clusters the prevalence of malaria (all age groups) at peak transmission after one booster dose of R21.
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. To compare in intervention and control clusters the incidence of clinical malaria (all age groups), after one booster dose of R21.
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. To estimate the cost of seasonal mass vaccination with R21 administration.
9. To estimate the cost-effectiveness of seasonal mass vaccination with R21 compared to standard malaria control measures.

The exploratory objective is to determine whether serological markers can detect changes in malaria transmission following mass vaccination with R21.

Detailed description: This is a cluster-randomized controlled trial. 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. Therefore,15 medium-sized (200-600 people) villages in The Gambia and 12 medium-sized (200-600 people) villages in Burkina Faso will receive the intervention. All study villages will receive standard control intervention, e.g., seasonal malaria chemoprevention, insecticide-treated bed nets, implemented by the National Malaria Control Program and according the National Strategic Plan for malaria control. Mass vaccination will be completed before the start of the malaria transmission season, i.e. July.

A cross-sectional survey to estimate malaria prevalence will be implemented at peak transmission, both following the mass vaccination with 3 doses (first year) and the booster dose (second year). A blood sample will be collected during the malaria transmission season from a cohort of randomly selected individuals to determine the incidence of malaria infection. A system of passive case detection to determine the incidence of clinical malaria will be set up throughout the study period, with special attention to the malaria transmission season (July-December).

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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.

Primary outcomes:
measure: Prevalence of malaria infection by PCR in all age groups at peak transmission season (October-November) following the first vaccination with 3 doses.
timeFrame: At 6 months ( October - November 2024) post first round of vaccination
Secondary outcomes:
measure: Occurrence of Adverse Events (AEs) during follow up.
timeFrame: Up to 28 days post vaccination
measure: Incidence of malaria infection in all age groups during the transmission season following mass vaccination with R21
timeFrame: Up to 6 months post the third vaccination round
measure: Incidence of clinical malaria in all age groups following mass vaccination with R21.
timeFrame: Up to 6 months post the third vaccination round
measure: Prevalence of malaria infection by PCR in all age groups at peak transmission following the booster dose.
timeFrame: At 6 months ( October - November 2025) post booster dose
measure: Incidence of malaria infection in all age groups during the transmission season following the booster dose.
timeFrame: Up to 6 months post booster dose
measure: Incidence of clinical malaria in all age groups following the booster dose.
timeFrame: Up to 6 months post the third vaccination round
measure: Coverage of completed vaccination schedule (3 doses) during the mass vaccination with 3 doses.
timeFrame: Up to 4 weeks post the third vaccination round
measure: Coverage of at least one vaccine dose administered during the mass vaccination with 3 doses
timeFrame: Up to 4 weeks post the third vaccination round
measure: Coverage of the booster dose
timeFrame: Up to 4 weeks post booster dose
measure: Cost of vaccine administration and cost effectiveness, both for the mass vaccination campaign with 3 doses and the booster dose.
timeFrame: Up to 6 months post booster dose
Other outcomes:
Locations:
city: Nanoro
country: Burkina Faso
facility: Clinical Research Unit of Nanoro, Burkina Faso
city: Fajara
country: Gambia
facility: MRC Unit The Gambia at LSHTM
Study officials:
affiliation: MRCG at LSHTM
name: Umberto D'Alessandro, MD, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Research Unit of Nanoro (CRUN)
name: Halidou Tinto, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: MRCG at LSHTM
name: Edgard Dabira, MD, MSc, PhD
role: STUDY_DIRECTOR
affiliation: Clinical Research Unit of Nanoro, Burkina Faso
name: Magloire Natama, PhD
role: STUDY_DIRECTOR
References: