MalariaPhase 3NCT04704830
R21/Matrix-M in African Children Against Clinical Malaria
A Phase 3 study testing R21/Matrix-M and Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine in people with Malaria, run by University of Oxford at 1 site in United Kingdom.
Trial 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 Read more about this study
- Who is it for?
- Ages 5 to 36 monthsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- R21/Matrix-M and Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4,800 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 29 Apr 2021to Apr 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 36 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- Children currently meeting the WHO criteria for HIV disease of stage 3 or 4 severity. A previous history of stage 3 or 4 disease is not an exclusion. Note: There will be no routine testing for HIV. Positive diagnoses will be recorded at screening if known.
- 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.
- Additional exclusion criteria for second phase of the trial (addition of second and third booster doses)
- Hypersensitivity to neomycin (Hepatitis A vaccine may contain traces of this).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
CCVTM, University of Oxford, Churchill Hospital
Oxford, OX3 7LE
About this study
Official title: A Phase III Randomized Controlled Multi-centre Trial to Evaluate the Efficacy of the R21/Matrix-M Vaccine 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
Read the 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:
- No booster doses (total of 4 doses of R21/Matrix-M).
- One booster dose, one year after the first booster dose (total of 5 doses of R21/Matrix-M)
- One booster dose, two years after the first booster dose (total of 5 doses of R21/Matrix-M)
- 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
- Being tested
- R21/Matrix-M, Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
R21/Matrix-MBiological
Adjuvanted malaria vaccine
Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccineBiological
Placebo Comparator
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: R21/Matrix-M; Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
- Efficacy against clinical malaria following the primary series, regardless of vaccination regime.
- Efficacy against clinical malaria after each booster vaccination. This will be assessed for the seasonal vaccination regime, standard vaccination regime and across both vaccination regimes together.
Clinical malaria is defined (according to the primary case definition) as 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.
Measured: 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.
Asymptomatic malaria, defined by: Presence of axillary temperature <37.5°C and absence history of fever within the last 24 hours AND P. falciparum asexual parasitaemia > 0 parasites/μL.
Measured: 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.
Severe malaria, defined by the primary case definition:
Presence of P. falciparum asexual parasitaemia > 5000 parasites/μL
AND one of more of the following criteria of disease severity:
- Prostration
- Respiratory distress
- Blantyre coma score ≤ 2
- Seizures: 2 or more
- Hypoglycaemia < 2.2 mmol/L
- Acidosis BE ≤-10.0 mmol/L
- Lactate ≥ 5.0 mmol/L
- Anaemia < 5.0 g/dL AND without any of the following diagnosis of co-morbidity
- Pneumonia (confirmed by X-ray)
- Meningitis (confirmed by Cerebrospinal Fluid examination)
- Sepsis (with Positive blood culture)
- Gastroenteritis with dehydration
Measured: 2 years
Efficacy of R21/Matrix-M against clinical malaria according to different transmission settings (seasonal and standard vaccination regimes).
Clinical malaria is defined (according to the primary case definition) as 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.
Measured: 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.
Incident severe anaemia according to the primary case definition: Documented Hb <5.0 g/dL identified at clinical presentation in association with P. falciparum asexual parasitaemia > 5000 parasites/μL.
Incident severe anaemia according to the secondary case definitions:
- Documented Hb <5.0 g/dL identified at clinical presentation in association with P. falciparum asexual parasitaemia > 0 parasites/μL
- Documented Hb <5.0 g/dL identified at clinical presentation and requirement for a blood transfusion
- Documented Hb <5.0 g/dL identified at clinical presentation
Prevalent severe anaemia defined as: Documented Hb <5.0 g/dL
Prevalent moderate anaemia defined as: Documented Hb <8.0 g/dL
Prevalent mild anaemia defined as: Documented Hb <10.0 g/dl
Measured: 2 years
Efficacy of R21/Matrix-M against malaria hospitalisation following the primary vaccination series and each booster vaccination.
Malaria hospitalisation defined by the primary case definition: Medical hospitalisation with confirmed P. falciparum asexual parasitaemia > 5000 parasites/μL.
Malaria hospitalisation defined by the secondary case definition: Medical hospitalisation which, in the judgement of the principal investigator, P. falciparum was the sole reason or major contributing factor.
Measured: 2 years
Safety, reactogenicity, humoral immunogenicity and efficacy of R21/Matrix-M as a single-vial formulation, compared with the two-vial formulation.
Safety and reactogenicity of the single-vial formulation will be assessed as per the primary safety outcome (#2).
Efficacy of the single-vial formulation will be assessed as per the primary efficacy outcome (#1).
Immunogenicity will be assessed as per the secondary immunogenicity outcome (#11).
Measured: 2 years
Safety and reactogenicity (including Serious adverse events (SAEs) and any deaths) following each booster vaccination and for the duration of the study.
Safety as per the primary outcome measures for safety but to be assessed post boost vaccinations.
Measured: 2 years
Humoral immunogenicity by anti-CSP antibody concentrations measured 12 months after completion of the primary series of 3 vaccinations and 12 months after each booster vaccination.
- Comparison of immunogenicity (antibody responses to CSP) in the R21/Matrix-M vaccination groups with those in the control vaccine groups and the durability of responses
- Serology to quantify antibodies to the vaccine components (regions of the CS antigen including the NANP repeat region and other elements of the protein as well as antibodies to HBsAg).
Measured: 2 years
School age booster extension: Efficacy
- Efficacy against clinical malaria at 6, 12 and 18 months after receiving a school age booster.
- Efficacy against asymptomatic P. falciparum infection at 6, 12, 18 and 24 months after receiving a school age booster.
- Efficacy against severe malaria disease at 12 and 24 months after receiving a school age booster.
- Efficacy against severe anaemia at 12 and 24 months after receiving a school age booster.
Measured: 6, 12, 18 and 24 months after receiving a school age booster
School age booster extension: Safety and reactogenicity
Safety and reactogenicity (including Serious adverse events (SAEs) and any deaths) following the school age booster vaccination and for the duration of the study.
Measured: Two years after school age booster
School age booster: Immunogenicity
- To evaluate immunogenicity, magnitude, quality and functionality of induced antibodies to the circumsporozoite protein, antibodies to HBsAg and other exploratory immunological endpoints in all vaccination groups.
- To assess vaccine-induced potential immune correlates of vaccine efficacy.
Measured: 28 days post school age booster, 1 year post school age booster and 2 years post school age booster
School age booster extension: Impact
- Assessment of impact of a school age booster of R21/Matrix-M on school attendance.
- Assessment of public health impact and cost-effectiveness of a school-age booster through modelling.
Measured: 2 years after school age booster
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2021
- Study start29 Apr 2021
- Primary completion21 Mar 2023
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- RCT
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 4,800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Institut de Recherche en Sciences de la Sante, Burkina Faso, Institut de Recherche en Sciences de la Sante-Direction Regionale de l'Ouest, Malaria Research and Training Center, Bamako, Mali, KEMRI-Wellcome Trust Collaborative Research Program, Ifakara Health Institute Clinical Trial Facility, Bagamoyo Research and Training Centre, PO Box 74, Bagamoyo, Tanzania, London School of Hygiene and Tropical Medicine
- Responsible party
- Sponsor
- Investigators
- Adrian VS Hill, PhD, Principal investigator, Jenner Institute, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04704830
- Sponsor's protocol ID
- VAC078
- Status last verified
- Feb 2026
- First submitted
- 7 Jan 2021
- Last updated
- 23 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 38310910
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized Controlled Multi-centre Trial to Evaluate the Efficacy of the R21/Matrix-M Vaccine in African Children Against Clinical Malaria
- ClinicalTrials.gov ID
- NCT04704830
- Acronym / sponsor ID
- VAC078
- Conditions
- Malaria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 4,800 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Institut de Recherche en Sciences de la Sante, Burkina Faso, Institut de Recherche en Sciences de la Sante-Direction Regionale de l'Ouest, Malaria Research and Training Center, Bamako, Mali, KEMRI-Wellcome Trust Collaborative Research Program, Ifakara Health Institute Clinical Trial Facility, Bagamoyo Research and Training Centre, PO Box 74, Bagamoyo, Tanzania, London School of Hygiene and Tropical Medicine
- Study start
- 29 Apr 2021 (actual)
- Primary completion
- 21 Mar 2023 (actual)
- Study completion
- Apr 2028 (estimated)
- First posted
- 12 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- No booster doses (total of 4 doses of R21/Matrix-M).
- One booster dose, one year after the first booster dose (total of 5 doses of R21/Matrix-M)
- One booster dose, two years after the first booster dose (total of 5 doses of R21/Matrix-M)
- 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)).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 11
- Model description
- RCT
| Arm | Type | Receives |
|---|---|---|
| Standard Regime - Group 1-1 | Experimental | Biological: R21/Matrix-M, Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccineR21/Matrix-M at primary series and first booster, control vaccine at second and third booster, n = 400, 5-36 months olds |
| Standard Regime - Group 1-2 | Experimental | Biological: R21/Matrix-M, Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccineR21/Matrix-M at primary series, first booster and second booster, control vaccine at third booster, n = 400, 5-36 months olds |
| Standard Regime - Group 1-3 | Experimental | Biological: R21/Matrix-M, Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccineR21/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 |
| Standard Regime - Group 1-4 | Experimental | Biological: R21/Matrix-MR21/Matrix-M at primary series, first booster, second booster and third booster, n = 400, 5-36 months olds |
| Standard Regime - Group 2 | Placebo comparator | Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccineControl vaccine at primary series, first booster, second booster and third booster, n=800, 5-36 month olds |
| Seasonal Regime - Group 5 | Experimental | Biological: R21/Matrix-M, Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccineGroup 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. |
| Seasonal Regime - Group 3-2 | Experimental | Biological: R21/Matrix-M, Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccineR21/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. |
| Seasonal Regime - Group 3-3 | Experimental | Biological: R21/Matrix-M, Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccineR21/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. |
| Seasonal Regime - Group 3-4 | Experimental | Biological: R21/Matrix-MR21/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. |
| Seasonal Regime - Group 4 | Placebo comparator | Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccineControl 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. |
| Seasonal Regime - Group 6 | Experimental | Biological: R21/Matrix-M, Biological: Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccineGroup 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. |
Who may qualify
- Ages
- 5 to 36 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| R21/Matrix-MAdjuvanted malaria vaccine | Biological | 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 vaccinePlacebo Comparator | Biological | 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 |
Primary outcome
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.
Time frame: 2 years
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.
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.
Time frame: 2 years
* 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.
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
Time frame: 12 months and 24 months after school age booster
* 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.
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
Time frame: One month after the school age booster
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.
13 secondary outcomes
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.
Time frame: 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.
Time frame: 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.
Time frame: 2 years
Efficacy of R21/Matrix-M against clinical malaria according to different transmission settings (seasonal and standard vaccination regimes).
Time frame: 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.
Time frame: 2 years
Efficacy of R21/Matrix-M against malaria hospitalisation following the primary vaccination series and each booster vaccination.
Time frame: 2 years
Safety, reactogenicity, humoral immunogenicity and efficacy of R21/Matrix-M as a single-vial formulation, compared with the two-vial formulation.
Time frame: 2 years
Safety and reactogenicity (including Serious adverse events (SAEs) and any deaths) following each booster vaccination and for the duration of the study.
Time frame: 2 years
Humoral immunogenicity by anti-CSP antibody concentrations measured 12 months after completion of the primary series of 3 vaccinations and 12 months after each booster vaccination.
Time frame: 2 years
School age booster extension: Efficacy
Time frame: 6, 12, 18 and 24 months after receiving a school age booster
School age booster extension: Safety and reactogenicity
Time frame: Two years after school age booster
School age booster: Immunogenicity
Time frame: 28 days post school age booster, 1 year post school age booster and 2 years post school age booster
School age booster extension: Impact
Time frame: 2 years after school age booster
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2026.
- Derived from this study: PubMed 38310910Datoo 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adrian VS Hill, PhD principal investigator
Jenner Institute, University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing R21/Matrix-M and Rabies vaccine, Hepatitis A vaccine or Meningococcal vaccine in people with Malaria, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04704830, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2026.