NCT04704830

R21/Matrix-M in African Children Against Clinical Malaria

A Phase III Randomized Controlled Multi-centre Trial to Evaluate the Efficacy of the R21/Matrix-M Vaccine in African Children Against Clinical Malaria

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 4,800 (estimated)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 5 Months – 36 Months
• Healthy volunteers: Accepted

Summary

A Phase III randomized controlled multi-centre trial to evaluate the efficacy of the R21/Matrix-M vaccine in African children against clinical malaria

Detailed description

This will be a double-blind, individually randomised trial. In the first phase of the trial, participants were randomised 2:1 to receive R21/Matrix-M malaria vaccine or a control rabies vaccine (Abhayrab). The study groups are as follows: Standard vaccination regime, 5-36 months olds R21/Matrix-M x 3, n = 1600 Control (rabies) vaccine x 3, n = 800 Seasonal vaccination regime, 5-36 month olds R21/Matrix-M x 3, n = 1600 Control (rabies) vaccine x 3, n = 800 In each group, a booster (4th) dose of the same vaccine will be administered 12 months after the third dose. At certain trial sites, participants in the malaria vaccine group may be further randomised 1:1 to receive a single-vial: two-vial formulation of R21/Matrix-M. The trial has been extended for two further years to assess safety and efficacy over a longer period of time. During this time, it will also assess the safety, immunogenicity and efficacy of second and third booster doses. One year after the first booster (fourth dose), participants in the R21/Matrix-M arm will be further randomised 1:1:1:1 to four groups to receive: 1. No booster doses (total of 4 doses of R21/Matrix-M). 2. One booster dose, one year after the first booster dose (total of 5 doses of R21/Matrix-M) 3. One booster dose, two years after the first booster dose (total of 5 doses of R21/Matrix-M) 4. Two booster doses, one year apart (total of 6 doses of R21/Matrix-M) Participants who are not receiving R21/Matrix-M, will receive a control vaccine at the relevant time point of vaccine administration The control vaccine for the second and the third booster will be a licensed Hepatitis A vaccine. Participants will be followed up for 12 months after their third booster. 2400 participants will be enrolled for the standard vaccination regime in: Dande, Burkina Faso; Kilifi, Kenya; and Bagamoyo, Tanzania. In addition, a further 2400 participants will be enrolled for the seasonal vaccination regime in Nanoro, Burkina Faso and Bougouni, Mali. Study population Standard vaccination regime: 5-36 month old children living permanently in the study area who are eligible. Seasonal vaccination regime: 5-36 month old children living permanently in the study area who are eligible. Primary study objectives Efficacy: * To assess the protective efficacy of R21/Matrix-M against clinical malaria caused by Plasmodium falciparum, in 5-36 month old children living in a malaria endemic area, 12 months after completion of the primary course (standard vaccination regime). * To assess the protective efficacy of R21/Matrix-M against clinical malaria caused by Plasmodium falciparum, in 5-36 month old children living in a malaria endemic area, 12 months after completion of the primary course (seasonal vaccination regime). Safety: • To assess the safety and reactogenicity of R21/Matrix-M, in both vaccination regimes, of children living in a malaria endemic area, in the month following each vaccination, and 12 months after completion of the primary course. Secondary objectives * Efficacy against clinical malaria after each booster vaccination * Efficacy against clinical malaria after the primary series and booster vaccination, regardless of vaccination regime * Efficacy against asymptomatic P. falciparum infection. * Efficacy against severe malaria disease. * Efficacy according to different transmission settings. * Efficacy against incident severe anaemia, blood transfusion requirement and malaria hospitalisation. * Safety and reactogenicity (including Serious adverse events (SAEs) and any deaths) following each booster vaccination and for the duration of the study. * Assessment of humoral immunogenicity by anti-CSP antibody concentrations measured 12 months after completion of the primary series of 3 vaccinations and 12 months after booster vaccinations. * Safety, immunogenicity and efficacy of a single- vial formulation of R21/Matrix-M This trial is funded by the Serum Institute of India. The trial has been extended in 2025 for a further two years in both seasonal sites (Nanoro, Burkina Faso and Bougouni, Mali) and one standard site (Dande, Burkina Faso) when children will be of school age. In this extension, participants who received 4 doses of R21/Matrix-M in the previous part of the trial will be randomised to receive a 5th dose of R21/Matrix-M or a control vaccine and will be followed up for 2 years. Participants in the control group from the previous part of the trial will receive one dose of a control vaccine and will be followed up for 2 years. Participants who have received 5 or 6 doses of R21/Matrix-M will not receive further vaccinations but will be followed up for two more years, (a total of 3 years since the last vaccination (R21/Matrix-M or control vaccine)).

Conditions

• Malaria

Interventions

Type	Name	Description
BIOLOGICAL	R21/Matrix-M	Adjuvanted malaria vaccine
BIOLOGICAL	Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine	Placebo Comparator

Timeline

• Start date: 2021-04-29
• Primary completion: 2023-03-21
• Completion: 2028-04-01
• First posted: 2021-01-12
• Last updated: 2026-02-23

Locations

1 site across 1 country: United Kingdom