R21/Matrix-M in African Children Against Clinical Malaria

NCT04704830 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: VAC078
• Study Type: interventional
• Target: 4,800
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Malaria

Outcome Measures

Primary Outcomes (4)

• 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.

  The primary efficacy outcome is clinical malaria, according to the primary case definition: the presence of axillary temperature ≥37.5°C and/ or history of fever within the last 24 hours, and P. falciparum asexual parasitaemia \>5000 parasites/μL.This will assessed separately for seasonal and standard vaccination regimes.

  2 years

• 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.

  * Occurrence of solicited local reactogenicity signs and symptoms for 7 days following the vaccination. * Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination. * Occurrence of unsolicited adverse events for 28 days following the vaccination. * Change from baseline for safety laboratory measures thought to be clinically significant. * Occurrence of serious adverse events for the whole study duration.

  2 years

• School age booster extension: To assess the protective efficacy of R21/Matrix-M against clinical malaria caused by Plasmodium falciparum in school- age children in Burkina Faso and Mali

  * To assess the protective efficacy of an additional late booster of R21/Matrix-M at 24 months against clinical malaria, in school-age children who have previously received four doses of R21/Matrix-M. * To assess the protective efficacy of R21/Matrix-M at 24 months against clinical malaria, in school- age children, who have previously received four doses of R21/Matrix-M. * To assess the protective efficacy of R21/Matrix-M at 12 months against clinical malaria, in school- age children, who have previously received a fifth dose one year after the fourth dose, a delayed fifth dose or six doses of R21/Matrix-M. * To assess the protective efficacy of R21/Matrix-M at 12 months against clinical malaria, in school- age children who have previously received a fifth dose one year after the fourth dose, a delayed fifth dose or six doses of R21/Matrix-M compared to those who received 4 doses.

  12 months and 24 months after school age booster

• School age booster extension: to assess the safety and reactogenicity of an additional late booster of R21/Matrix-M, in school age children living in Burkina Faso and Mali, one month after vaccination

  This will be measured through the occurrence of local and systemic reactogenicity signs and symptoms for 7 days following the school age booster, and the occurrence of unsolicited adverse events for 28 days following this booster.

  One month after the school age booster

Secondary Outcomes (13)

• Protective efficacy of R21/Matrix-M against clinical malaria caused by P.falciparum, in 5-36 month old children living in a malaria endemic area, following the primary vaccination series across both vaccination regimes and following booster vaccinations.

  2 years

• Efficacy of R21/Matrix-M against asymptomatic P.falciparum malaria infection in either vaccination regime, following the primary vaccination series and following each booster vaccination.

  2 years

• Efficacy of R21/Matrix-M against severe malaria disease in either vaccination regime, following the primary vaccination series and following each booster vaccination.

  2 years

• Efficacy of R21/Matrix-M against clinical malaria according to different transmission settings (seasonal and standard vaccination regimes).

  2 years

• Efficacy of R21/Matrix-M against incident severe anaemia and the need for blood transfusion in both vaccination regimes following the primary vaccination series and each booster vaccination.

  2 years

Study Arms (11)

Standard Regime - Group 1-1

EXPERIMENTAL

R21/Matrix-M at primary series and first booster, control vaccine at second and third booster, n = 400, 5-36 months olds

Biological: R21/Matrix-M; Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine

Standard Regime - Group 1-2

EXPERIMENTAL

R21/Matrix-M at primary series, first booster and second booster, control vaccine at third booster, n = 400, 5-36 months olds

Biological: R21/Matrix-M; Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine

Standard Regime - Group 1-3

EXPERIMENTAL

R21/Matrix-M at primary series and first booster, control vaccine at second booster and R21/Matrix-M at third booster, n = 400, 5-36 months olds

Biological: R21/Matrix-M; Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine

Standard Regime - Group 1-4

EXPERIMENTAL

R21/Matrix-M at primary series, first booster, second booster and third booster, n = 400, 5-36 months olds

Biological: R21/Matrix-M

Standard Regime - Group 2

PLACEBO COMPARATOR

Control vaccine at primary series, first booster, second booster and third booster, n=800, 5-36 month olds

Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine

Seasonal Regime - Group 5

EXPERIMENTAL

Group 3-1 for the initial part of the trial and first extension - R21/Matrix-M at primary series and first booster, control vaccine at second and third booster, n = 400, 5-36 months olds. For the school age booster extension, group 3-1 has been randomised into two groups: group 5 and 6. Group 5 will receive another dose of R21/Matrix-M.

Biological: R21/Matrix-M; Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine

Seasonal Regime - Group 3-2

EXPERIMENTAL

R21/Matrix-M at primary series, first booster and second booster, control vaccine at third booster, n = 400, 5-36 months olds. For the school age booster extension, this group will receive no further vaccination and will be followed up for a further two years.

Biological: R21/Matrix-M; Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine

Seasonal Regime - Group 3-3

EXPERIMENTAL

R21/Matrix-M at primary series and first booster, control vaccine at second booster and R21/Matrix-M at third booster, n = 400, 5-36 months olds. For the school age booster extension, this group will receive no further vaccination and will be followed up for a further two years.

Biological: R21/Matrix-M; Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine

Seasonal Regime - Group 3-4

EXPERIMENTAL

R21/Matrix-M at primary series, first booster, second booster and third booster, n = 400, 5-36 months olds. For the school age booster extension, this group will receive no further vaccination and will be followed up for a further two years.

Biological: R21/Matrix-M

Seasonal Regime - Group 4

PLACEBO COMPARATOR

Control vaccine at primary series, first booster, second booster and third booster, n=800, 5-36 month olds. For the school age booster extension, this group will receive one further booster of the control vaccine.

Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine

Seasonal Regime - Group 6

EXPERIMENTAL

Group 3-1 for the initial part of the trial and first extension - R21/Matrix-M at primary series and first booster, control vaccine at second and third booster, n = 400, 5-36 months olds. For the school age booster extension, group 3-1 has been randomised into two groups: group 5 and 6. Group 6 will receive a control vaccine.

Biological: R21/Matrix-M; Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine

Interventions

R21/Matrix-M BIOLOGICAL

Adjuvanted malaria vaccine

Seasonal Regime - Group 3-2; Seasonal Regime - Group 3-3; Seasonal Regime - Group 3-4; Seasonal Regime - Group 5; Seasonal Regime - Group 6; Standard Regime - Group 1-1; Standard Regime - Group 1-2; Standard Regime - Group 1-3; Standard Regime - Group 1-4

Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine BIOLOGICAL

Placebo Comparator

Seasonal Regime - Group 3-2; Seasonal Regime - Group 3-3; Seasonal Regime - Group 4; Seasonal Regime - Group 5; Seasonal Regime - Group 6; Standard Regime - Group 1-1; Standard Regime - Group 1-2; Standard Regime - Group 1-3; Standard Regime - Group 2

Eligibility Criteria

• Age: 5 Months - 36 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• All participants must satisfy the following criteria at study entry:
• The child is 5-36 months of age at the time of first vaccination.
• Signed informed consent/thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child to join the trial.
• The investigator believes that the parents/guardians can and will comply with the requirements of the protocol if the child is enrolled in the study.
• The child is a permanent resident of the study area and likely to remain a resident for the duration of the trial.

You may not qualify if:

• The following criteria should be checked at the time of study entry. If any apply, the participant must not be included:
• The child has previously received a malaria vaccine.
• The child is enrolled in another malaria intervention trial.
• The child has a history of allergic disease or reactions likely to be exacerbated by any component of the malaria or control vaccine.
• The child has a history of allergic reactions, significant IgE-mediated events or anaphylaxis to previous immunisations.
• The child has major congenital defects.
• The child has anaemia associated with clinical signs of symptoms of decompensation, or a haemoglobin of ≤ 5.0 g/dL.
• The child has had a blood transfusion within one month of enrolment.
• The child has been administered immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
• The child has malnutrition requiring hospital admission.
• The child has an acute or chronic, clinically significant pulmonary, cardiovascular, gastrointestinal, endocrine, neurological, skin, hepatic or renal functional abnormality, as determined by medical history, physical examination or laboratory tests.
• The child has received an investigational drug or vaccine other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• The child is currently participating in another clinical trial if likely to affect data interpretation of this trial
• The child has any 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.
• \- Hypersensitivity to neomycin (Hepatitis A vaccine may contain traces of this).

Sponsors & Collaborators

• University of Oxford: lead
• Malaria Research and Training Center, Bamako, Mali: collaborator
• KEMRI-Wellcome Trust Collaborative Research Program: collaborator
• Ifakara Health Institute Clinical Trial Facility, Bagamoyo Research and Training Centre, PO Box 74, Bagamoyo, Tanzania: collaborator
• Institut de Recherche en Sciences de la Sante, Burkina Faso: collaborator
• Institut de Recherche en Sciences de la Sante-Direction Regionale de l'Ouest: collaborator
• London School of Hygiene and Tropical Medicine: collaborator

Study Sites (1)

CCVTM, University of Oxford, Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (1)

• Datoo MS, Dicko A, Tinto H, Ouedraogo JB, Hamaluba M, Olotu A, Beaumont E, Ramos Lopez F, Natama HM, Weston S, Chemba M, Compaore YD, Issiaka D, Salou D, Some AM, Omenda S, Lawrie A, Bejon P, Rao H, Chandramohan D, Roberts R, Bharati S, Stockdale L, Gairola S, Greenwood BM, Ewer KJ, Bradley J, Kulkarni PS, Shaligram U, Hill AVS; R21/Matrix-M Phase 3 Trial Group. Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial. Lancet. 2024 Feb 10;403(10426):533-544. doi: 10.1016/S0140-6736(23)02511-4. Epub 2024 Feb 1.

  PMID: 38310910 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Rabies Vaccines; Hepatitis A Vaccines; Meningococcal Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Viral Hepatitis Vaccines; Bacterial Vaccines

Study Officials

• Adrian VS Hill, PhD

  Jenner Institute, University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: RCT

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 12, 2021
• Study Start: April 29, 2021
• Primary Completion: March 21, 2023
• Study Completion (Estimated): April 1, 2028
• Last Updated: February 23, 2026

Record last verified: 2026-02

Locations

GB (1)