Malaria VaccinesPhase 2NCT06879327
Infant Malaria Vaccine Schedule Optimization
A Phase 2 study testing R21 Matrix-M (R21/MM) Malaria Vaccine, Hexavalent Vaccine and Pneumococcal Polysaccharide Conjugate Vaccine in people with Malaria Vaccines and Malaria (Plasmodium Falciparum), run by PATH at 2 sites in Burkina Faso.
Trial summary
The aim of this study is to identify an optimal infant vaccine schedule for a malaria vaccine which is better aligned with the timing of other vaccine interventions. Read more about this study
- Who is it for?
- Ages 42 to 49 daysHealthy volunteers can take part
- Conditions the study is for
- Malaria Vaccines, Malaria (Plasmodium Falciparum)
- What is being tested?
- R21 Matrix-M (R21/MM) Malaria Vaccine, Hexavalent Vaccine and Pneumococcal Polysaccharide Conjugate Vaccine
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 975 participants
- Where
- 2 sitesBurkina Faso
- Study dates
- 30 May 2025to 18 Oct 2027
- Phase
- Phase 2
- 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 42 to 49 days
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Signed informed consent or thumb-printed and witnessed informed consent obtained from the parent/legal guardian of the infant.
- Infants must have been born full-term (at ≥37 weeks of gestation) and > 2500 grams at birth.
- Immunization schedule Cohorts 1, 2, and 3: Male and female infants 42-49 days (inclusive) of age at time of enrollment.
- Prior to group randomization, for infants in Cohort 1 randomization to receive vaccine dose 1 (Groups 1 and 2 of R21/MM or placebo, respectively) will occur at 42-49 days of age. Infants in Cohorts 2 and 3 will not be randomized to R21/MM or placebo; placebo will no longer be given. Rather infants in these cohorts will receive open-label R21/MM according to the immunization schedule category to which they have been randomized. Infants in Cohort 2, will receive their open-label R21/MM vaccine dose 1 (Group 3) at 2 months (56-63 days of age). Infants in Cohort 3, will receive their open-label R21/MM vaccine dose 1 (Group 5) at 3 months (84-91 days of age).
- The participant's parent/guardian must be willing to avoid travel, particularly in the 28 days after each study vaccination, must confirm willingness to contact the study team in the event of unexpected/unavoidable travel and, for the safety cohort, must confirm availability for the home visits to be conducted by a field worker or nurse to collect solicited AEs over the 7 days (day of vaccination and 6 subsequent days) following each study vaccine.
- The participant's parent/guardian must confirm willingness to bring their child to the study clinic / local health care clinic, and capacity to contact the study team in the event the subject has any illnesses or other health concerns during the study.
- Participants who the investigator believes that their parent/guardian can and will comply with the requirements of the protocol (e.g. return for follow-up visits) may be enrolled in the study.
Who cannot join
- Acute disease at the time of enrolment (acute disease is defined as the presence of a moderate or severe illness with or without fever). This does not include minor illnesses such as diarrhea, mild upper respiratory infection, without low-grade febrile illness, i.e. axillary temperature < 37.5°C or tympanic temperature < 38°C.
- (Note: In case of acute disease, participants may be re-assessed by a study physician for resolution of the condition and enrolled if eligible and still within the visit window).
- Clinically significant pulmonary, cardiovascular, gastrointestinal, endocrine, neurological, skin, hepatic or renal functional abnormality, as determined by medical history, physical examination or laboratory tests 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.
- At time of enrollment, any infant who has received any dose of the hexavalent/pentavalent vaccines, pneumococcal vaccine, rotavirus vaccine, IPV or has received more than one dose of oral polio virus or more than one dose of hepatitis B vaccine.
- Weight-for-length/height Z score of less than -3 or other clinical signs of malnutrition.
- Infant with major congenital defects.
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- The infant has anaemia associated with clinical signs of symptoms of decompensation, or a haemoglobin of ≤ 5.0 g/dL.
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
- Any confirmed or suspected immunosuppressive or immunodeficient state (including HIV or asplenia) or known maternal HIV infection (no HIV testing will be routinely done by the study team).
- Administration of immunoglobulins and/or any blood products/blood transfusion from birth to time of planned administration of the vaccine candidate.
- Previous vaccination of participant or biological mother with a malaria vaccine.
- Participation in another research study involving receipt of an investigational product or planned use during the study period.
- Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.
Trial locations and contacts
2 sites in 1 country.
Burkina Faso2 sites
Institut de Recherche en Sciences de la Santé (IRSS)
Bobo-Dioulasso
Groupe de Recherche Action en Santé (GRAS)
Ouagadougou
About this study
Official title: A Phase 2b Multicenter Randomized, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of R21/Matrix-M Malaria Vaccine in African Infants With Different Immunization Schedules
The aim of this study is to identify an optimal infant vaccine schedule for a malaria vaccine which is better aligned with the timing of other vaccine interventions.
Read the detailed description
The R21/Matrix-M (R21/MM) vaccine has been recommended by the World Health Organization (WHO) to prevent clinical malaria in young children living in moderate to high transmission areas of Sub-Saharan Africa. R21/MM is based on the circumsporozoite protein (CSP) targeting the pre-erythrocytic stage of Plasmodium falciparum. R21/MM elicits high levels of antibodies against the central repeat (Asn-Ala-Asn-Pro [NANP]) of the circumsporozoite protein (CSP) which has been shown to correlate with protection. Currently, R21/MM is recommended to be delivered to young children starting at 5-6 months of age with 3 doses given at monthly intervals, however, there are no existing Essential Programme on Immunization (EPI) vaccine visits scheduled at these ages.
We plan to evaluate, using the R21/MM malaria vaccine as a model system, how age at first vaccine dose and time intervals between doses modify the immunogenicity of the vaccine.
Healthy male or female infants 6 to 7 weeks of age will be randomized to one of three different immunization schedule cohorts: a) a "compressed" conventional schedule at 6-10-14 weeks of age; b) a "relaxed" schedule at 2-4-6 months of age; c) a "relaxed" schedule at 3-6-9 months of age.
In the original study design (Part A of the study), participants in each immunization schedule cohort were randomized in a ratio of 3:1 to receive either R21/MM or placebo - up until September 1, 2025, where upon confirmation of R21/MM rollout into the EPI schedule in the study districts, all participants already enrolled in the "relaxed" 2-4-6 month and "relaxed" 3-6-9 month schedules who had not yet received the first study vaccination, were assigned automatically to receive open-label R21/MM. Recruitment into the study was also paused while the protocol amendment with the revised study design was being developed. At the time of the recruitment being paused, the study had enrolled 644 participants.
All study participants enrolled during Part A of the study were unblinded as they approached 5 months of age and those who were randomized to the placebo arms had all study procedures discontinued, and were referred to local EPI clinics to receive R21/MM vaccinations and withdrawn from the study. Participants who had been randomized and who had received R21/MM at their first study vaccination, were kept on study and continued to receive open-label R21/MM, as per the protocol.
In Part B of the study, as per the revised study design, an additional 320 infants will be enrolled and randomized to the "compressed" 6-10-14 weeks (Cohort 1), "relaxed" 2-4-6 month (Cohort 2) and "relaxed" 3-6-9 month (Cohort 3) immunization schedules initially in a 2:1:1 ratio. Participants enrolled into Cohorts 2 and 3 will all be assigned to receive open-label R21/MM, while those enrolled into Cohort 1 will be randomized (blinded) 1:1 to receive 3 doses of either R21/MM or placebo. Once participants in Cohort 1 complete their 28 day post-3rd dose visit, they will be unblinded. Participants randomized to placebo will rollover to a new cohort, Cohort 4, to receive 3 doses of R21/MM on a 5-6-7-month schedule, aligning with WHO guidelines. Participants randomized into the "relaxed" 2-4-6 month schedule (Cohort 2) and "relaxed" 3-6-9 month schedule (Cohort 3) will receive 3 doses of open-label R21/MM; no placebo participants will be enrolled into Cohorts 2 and 3.
Infants randomized to the respective immunization schedule categories will receive co-administered routine EPI vaccines and participants in all cohorts will receive a 4th dose of R21/MM at Month 15.
- Conditions
- Malaria Vaccines, Malaria (Plasmodium Falciparum)
- Being tested
- R21 Matrix-M (R21/MM) Malaria Vaccine, Placebo, Hexavalent Vaccine, Pneumococcal Polysaccharide Conjugate Vaccine, Rotavirus, Live Attenuated (Oral) Vaccine
- Keywords
- Plasmodium falciparum, R21/Matrix-M Malaria Vaccine
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
R21 Matrix-M (R21/MM) Malaria VaccineBiological
Administered by intramuscular injection. Each 0.5 mL dose contains R21 Malaria Antigen (5 mcg) and Matrix-M1 (Adjuvant) (50 mcg).
PlaceboBiological
Administered by intramuscular injection. Each dose (0.5 mL) contains Normal saline (0.9%).
Hexavalent VaccineBiological
Also called HEXASIIL
Administered by intramuscular injection. Each dose of 0.5 mL contains:
- Diphtheria Toxoid > 30 IU
- Tetanus Toxoid > 40 IU
- B. pertussis (whole cell) > 4 IU
- Hepatitis B surface antigen (HBsAg) (recombinant DNA) 15 mcg
- Inactivated polio vaccine (Salk strains grown on vero cells): Type - 1 (Mahoney strain) 40 D antigen units (DU); Type - 2 (MEF-1 strain) 8 DU; Type - 3 (Saukett strain) 32 DU
- Haemophilus influenzae Type b (Hib) Conjugate Vaccine (Adsorbed) polyribosylribitol phosphate (PRP) 10 mcg conjugated to tetanus toxoid (TT) (carrier protein) 19 to 33 mcg]
Pneumococcal Polysaccharide Conjugate VaccineBiological
Also called PNEUMOSIL
Administered by intramuscular injection. Each 0.5 mL dose contains 2 mcg each Saccharide for serotypes 1, 5, 9V, 14, 19A, 19F, 23F, 7F, 6A and 4 mcg Saccharide for serotype 6B.
Rotavirus, Live Attenuated (Oral) VaccineBiological
Also called ROTASIIL
Administered orally. Each 2.0 mL dose contains: Live Attenuated Bovine-Human Rotavirus Reassortant [G1, G2, G3, G4 and G9], 5.6 focus-forming units (FFU) / serotype.
Measles and Rubella VaccineBiological
Administered by subcutaneous injection. Each 0.5 mL dose contains not less than 1000 cell culture infectious dose 50% (CCID50) of Measles virus and 1000 CCID50 of Rubella virus.
Meningococcal (A, C, Y, W, X) polysaccharide conjugate vaccineBiological
Administered by intramuscular injection. Each 0.5 mL dose contains 5 mcg of each Meningococcal A, C, Y, W, and X polysaccharide, 7.8 to 33.4 mcg of TT and 11.7 to 50.1 mcg of recombinant CRM197.
Yellow Fever vaccineBiological
Yellow fever vaccine will be locally sourced by each trial site in accordance with the countries' EPI program.
Typhoid Conjugate vaccineBiological
Typhoid conjugate vaccine will be locally sourced by each trial site in accordance with the countries' EPI program.
| Study group | Role | What they receive |
|---|---|---|
| Compressed 6-10-14 Week Schedule: R21/MM Malaria Vaccine | Experimental | Participants will receive R21/MM malaria vaccination at 6, 10, and 14 weeks of age, co-administered with hexavalent vaccine, pneumococcal conjugate vaccine (PCV), and oral rotavirus vaccine (RV). At 9 months of age participants will receive measles-rubella (MR) vaccine, yellow fever (YF) vaccine, and typhoid conjugate vaccine (TCV).
Participants will receive a booster dose of R21/MM malaria vaccine at 15 months of age co-administered with Meningococcal (A, C, Y, W, X) Polysaccharide Conjugate Vaccine (MenFive) and the 2nd dose of MR vaccine. Receives: Biological: R21 Matrix-M (R21/MM) Malaria Vaccine; Biological: Hexavalent Vaccine; Biological: Pneumococcal Polysaccharide Conjugate Vaccine; Biological: Rotavirus, Live Attenuated (Oral) Vaccine; Biological: Measles and Rubella Vaccine; Biological: Meningococcal (A, C, Y, W, X) polysaccharide conjugate vaccine; Biological: Yellow Fever vaccine; Biological: Typhoid Conjugate vaccine |
| Compressed 6-10-14 Week Schedule: Placebo / Recommended 5-6-7 Month Schedule: R21/MM Malaria Vaccine | Other | Participants will receive placebo at 6, 10, and 14 weeks of age, co-administered with hexavalent vaccine, PCV, and oral RV. After completion of the 28 day post-Dose 3 visit, these participants will rollover to Cohort 4 (Group 7) to then receive open-label R21/MM vaccine as per the "recommended" schedule at 5-6-7 months of age.
At 9 months of age participants will receive MR and YF vaccines and TCV. Participants will receive a booster dose of R21/MM malaria vaccine at 15 months of age co-administered with the MenFive vaccine and the 2nd dose of MR vaccine. Receives: Biological: R21 Matrix-M (R21/MM) Malaria Vaccine; Biological: Placebo; Biological: Hexavalent Vaccine; Biological: Pneumococcal Polysaccharide Conjugate Vaccine; Biological: Rotavirus, Live Attenuated (Oral) Vaccine; Biological: Measles and Rubella Vaccine; Biological: Meningococcal (A, C, Y, W, X) polysaccharide conjugate vaccine; Biological: Yellow Fever vaccine; Biological: Typhoid Conjugate vaccine |
| Relaxed 2-4-6 Month Schedule: R21/MM Malaria Vaccine | Experimental | Participants will receive R21/MM malaria vaccination at 2, 4, and 6 months of age co-administered with hexavalent vaccine, PCV, and oral RV. At 9 months of age participants will receive MR and YF vaccines and TCV.
Participants will receive a booster dose of R21/MM malaria vaccine at 15 months of age co-administered with the MenFive vaccine and the 2nd dose of MR vaccine. Receives: Biological: R21 Matrix-M (R21/MM) Malaria Vaccine; Biological: Hexavalent Vaccine; Biological: Pneumococcal Polysaccharide Conjugate Vaccine; Biological: Rotavirus, Live Attenuated (Oral) Vaccine; Biological: Measles and Rubella Vaccine; Biological: Meningococcal (A, C, Y, W, X) polysaccharide conjugate vaccine; Biological: Yellow Fever vaccine; Biological: Typhoid Conjugate vaccine |
| Relaxed 3-6-9 Month Schedule: R21/MM Malaria Vaccine | Experimental | Participants will receive R21/MM malaria vaccination at 3, 6, and 9 months of age. Participants will receive the hexavalent vaccine, PCV, and oral RV at 6 weeks, 10 weeks, and 14 weeks of age. At 9 months of age participants will receive MR and YF vaccines and TCV.
Participants will receive a booster dose of R21/MM malaria vaccine at 15 months of age co-administered with the MenFive vaccine and the 2nd dose of MR vaccine. Receives: Biological: R21 Matrix-M (R21/MM) Malaria Vaccine; Biological: Hexavalent Vaccine; Biological: Pneumococcal Polysaccharide Conjugate Vaccine; Biological: Rotavirus, Live Attenuated (Oral) Vaccine; Biological: Measles and Rubella Vaccine; Biological: Meningococcal (A, C, Y, W, X) polysaccharide conjugate vaccine; Biological: Yellow Fever vaccine; Biological: Typhoid Conjugate vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric Mean Titers (GMTs) of Anti-circumsporozoite (CS) Immunoglobulin G (IgG) at Baseline and 28 Days after 3rd Vaccine Dose
The anti-CS antibody responses elicited following the primary 3-dose schedule of R21/MM will be assessed in the "compressed" (6-10-14 week) immunization schedule and the two "relaxed" (2-4-6 month and 3-6-9 month) immunization schedule cohorts.
Measured: Baseline and 28 days after 3rd vaccine dose
Geometric Mean Fold Rise (GMFR) in Anti-CS IgG 28 Days after 3rd Vaccine Dose Compared to Baseline
The anti-CS antibody responses elicited following the primary 3-dose schedule of R21/MM will be assessed in the "compressed" (6-10-14 week) immunization schedule and the two "relaxed" (2-4-6 month and 3-6-9 month) immunization schedule cohorts.
Measured: Baseline and 28 days after 3rd vaccine dose
Number of Participants with Solicited Adverse Events
Local (redness, swelling, and pain at the injection site) and systemic (fever, drowsiness, irritability, decreased appetite) reactions will be collected in a subset of participants (the first 40 participants in each immunization schedule category at each site).
Measured: 7 days after each study vaccination
Number of Participants with Unsolicited Adverse Events
Measured: 28 days after each study vaccination
Number of Participants with Serious Adverse Events
Measured: Up to 28 days post 4th vaccine dose.
Number of Participants with Adverse Events of Special Interest
Measured: Up to 28 days post 4th vaccine dose.
Secondary outcomes (2)
Geometric Mean Titers (GMTs) of Anti-CS IgG Before and 28 Days After 4th Vaccine Dose
The anti-CS antibody responses elicited following the 4th dose of R21/MM will be assessed in the "compressed" (6-10-14 week) immunization schedule and the two "relaxed" (2-4-6 month and 3-6-9 month) immunization schedule cohorts.
Measured: Month 15 predose and 28 days after vaccination
GMFR in Anti-CS IgG Titer Post 4th Dose Compared to Pre-4th Dose
The anti-CS antibody responses elicited following the 4th dose of R21/MM will be assessed in the "compressed" (6-10-14 week) immunization schedule and the two "relaxed" (2-4-6 month and 3-6-9 month) immunization schedule cohorts.
Measured: Month 15 predose and 28 days after 4th dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2025
- Study start30 May 2025
- Primary completion18 Oct 2027 (estimated)
- Study completion18 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malaria VaccinesStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 975 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Collaborators
- Pharmassist Ltd, Serum Institute of India Pvt. Ltd., Agilis, MCT-CRO, Cytespace, CERBA, Christian Medical College, Vellore, India, University College London - Institute of Child Health (UCL-ICH), VisMederi srl, Sienna, Italy
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06879327
- Sponsor's protocol ID
- CVIA 108
- Other IDs
- PACTR202411825510335
- Status last verified
- Sep 2026
- First submitted
- 11 Mar 2025
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: PATH as the Sponsor of the Clinical Study will post the Clinical Trial Data in compliance with the Gates Foundation's Open Access policy and the WHO Joint Statement on Clinical Transparency. The Clinical Trial Data will contain no personally identifiable information (PII) and will be fully anonymized and de-identified.
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b Multicenter Randomized, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of R21/Matrix-M Malaria Vaccine in African Infants With Different Immunization Schedules
- ClinicalTrials.gov ID
- NCT06879327
- Acronym / sponsor ID
- CVIA 108
- Conditions
- Malaria Vaccines, Malaria (Plasmodium Falciparum)
- Keywords
- Plasmodium falciparum, R21/Matrix-M Malaria Vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 975 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Collaborators
- Pharmassist Ltd, Serum Institute of India Pvt. Ltd., Agilis, MCT-CRO, Cytespace, CERBA, Christian Medical College, Vellore, India, University College London - Institute of Child Health (UCL-ICH), VisMederi srl, Sienna, Italy
- Study start
- 30 May 2025 (actual)
- Primary completion
- 18 Oct 2027 (estimated)
- Study completion
- 18 Oct 2027 (estimated)
- First posted
- 17 Mar 2025 (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.
The aim of this study is to identify an optimal infant vaccine schedule for a malaria vaccine which is better aligned with the timing of other vaccine interventions.
Detailed description
The R21/Matrix-M (R21/MM) vaccine has been recommended by the World Health Organization (WHO) to prevent clinical malaria in young children living in moderate to high transmission areas of Sub-Saharan Africa. R21/MM is based on the circumsporozoite protein (CSP) targeting the pre-erythrocytic stage of Plasmodium falciparum. R21/MM elicits high levels of antibodies against the central repeat (Asn-Ala-Asn-Pro [NANP]) of the circumsporozoite protein (CSP) which has been shown to correlate with protection. Currently, R21/MM is recommended to be delivered to young children starting at 5-6 months of age with 3 doses given at monthly intervals, however, there are no existing Essential Programme on Immunization (EPI) vaccine visits scheduled at these ages.
We plan to evaluate, using the R21/MM malaria vaccine as a model system, how age at first vaccine dose and time intervals between doses modify the immunogenicity of the vaccine.
Healthy male or female infants 6 to 7 weeks of age will be randomized to one of three different immunization schedule cohorts: a) a "compressed" conventional schedule at 6-10-14 weeks of age; b) a "relaxed" schedule at 2-4-6 months of age; c) a "relaxed" schedule at 3-6-9 months of age.
In the original study design (Part A of the study), participants in each immunization schedule cohort were randomized in a ratio of 3:1 to receive either R21/MM or placebo - up until September 1, 2025, where upon confirmation of R21/MM rollout into the EPI schedule in the study districts, all participants already enrolled in the "relaxed" 2-4-6 month and "relaxed" 3-6-9 month schedules who had not yet received the first study vaccination, were assigned automatically to receive open-label R21/MM. Recruitment into the study was also paused while the protocol amendment with the revised study design was being developed. At the time of the recruitment being paused, the study had enrolled 644 participants.
All study participants enrolled during Part A of the study were unblinded as they approached 5 months of age and those who were randomized to the placebo arms had all study procedures discontinued, and were referred to local EPI clinics to receive R21/MM vaccinations and withdrawn from the study. Participants who had been randomized and who had received R21/MM at their first study vaccination, were kept on study and continued to receive open-label R21/MM, as per the protocol.
In Part B of the study, as per the revised study design, an additional 320 infants will be enrolled and randomized to the "compressed" 6-10-14 weeks (Cohort 1), "relaxed" 2-4-6 month (Cohort 2) and "relaxed" 3-6-9 month (Cohort 3) immunization schedules initially in a 2:1:1 ratio. Participants enrolled into Cohorts 2 and 3 will all be assigned to receive open-label R21/MM, while those enrolled into Cohort 1 will be randomized (blinded) 1:1 to receive 3 doses of either R21/MM or placebo. Once participants in Cohort 1 complete their 28 day post-3rd dose visit, they will be unblinded. Participants randomized to placebo will rollover to a new cohort, Cohort 4, to receive 3 doses of R21/MM on a 5-6-7-month schedule, aligning with WHO guidelines. Participants randomized into the "relaxed" 2-4-6 month schedule (Cohort 2) and "relaxed" 3-6-9 month schedule (Cohort 3) will receive 3 doses of open-label R21/MM; no placebo participants will be enrolled into Cohorts 2 and 3.
Infants randomized to the respective immunization schedule categories will receive co-administered routine EPI vaccines and participants in all cohorts will receive a 4th dose of R21/MM at Month 15.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Compressed 6-10-14 Week Schedule: R21/MM Malaria Vaccine | Experimental | Biological: R21 Matrix-M (R21/MM) Malaria Vaccine, Biological: Hexavalent Vaccine, Biological: Pneumococcal Polysaccharide Conjugate Vaccine, Biological: Rotavirus, Live Attenuated (Oral) Vaccine, Biological: Measles and Rubella Vaccine, Biological: Meningococcal (A, C, Y, W, X) polysaccharide conjugate vaccine, Biological: Yellow Fever vaccine, Biological: Typhoid Conjugate vaccineParticipants will receive R21/MM malaria vaccination at 6, 10, and 14 weeks of age, co-administered with hexavalent vaccine, pneumococcal conjugate vaccine (PCV), and oral rotavirus vaccine (RV). At 9 months of age participants will receive measles-rubella (MR) vaccine, yellow fever (YF) vaccine, and typhoid conjugate vaccine (TCV). Participants will receive a booster dose of R21/MM malaria vaccine at 15 months of age co-administered with Meningococcal (A, C, Y, W, X) Polysaccharide Conjugate Vaccine (MenFive) and the 2nd dose of MR vaccine. |
| Compressed 6-10-14 Week Schedule: Placebo / Recommended 5-6-7 Month Schedule: R21/MM Malaria Vaccine | Other | Biological: R21 Matrix-M (R21/MM) Malaria Vaccine, Biological: Placebo, Biological: Hexavalent Vaccine, Biological: Pneumococcal Polysaccharide Conjugate Vaccine, Biological: Rotavirus, Live Attenuated (Oral) Vaccine, Biological: Measles and Rubella Vaccine, Biological: Meningococcal (A, C, Y, W, X) polysaccharide conjugate vaccine, Biological: Yellow Fever vaccine, Biological: Typhoid Conjugate vaccineParticipants will receive placebo at 6, 10, and 14 weeks of age, co-administered with hexavalent vaccine, PCV, and oral RV. After completion of the 28 day post-Dose 3 visit, these participants will rollover to Cohort 4 (Group 7) to then receive open-label R21/MM vaccine as per the "recommended" schedule at 5-6-7 months of age. At 9 months of age participants will receive MR and YF vaccines and TCV. Participants will receive a booster dose of R21/MM malaria vaccine at 15 months of age co-administered with the MenFive vaccine and the 2nd dose of MR vaccine. |
| Relaxed 2-4-6 Month Schedule: R21/MM Malaria Vaccine | Experimental | Biological: R21 Matrix-M (R21/MM) Malaria Vaccine, Biological: Hexavalent Vaccine, Biological: Pneumococcal Polysaccharide Conjugate Vaccine, Biological: Rotavirus, Live Attenuated (Oral) Vaccine, Biological: Measles and Rubella Vaccine, Biological: Meningococcal (A, C, Y, W, X) polysaccharide conjugate vaccine, Biological: Yellow Fever vaccine, Biological: Typhoid Conjugate vaccineParticipants will receive R21/MM malaria vaccination at 2, 4, and 6 months of age co-administered with hexavalent vaccine, PCV, and oral RV. At 9 months of age participants will receive MR and YF vaccines and TCV. Participants will receive a booster dose of R21/MM malaria vaccine at 15 months of age co-administered with the MenFive vaccine and the 2nd dose of MR vaccine. |
| Relaxed 3-6-9 Month Schedule: R21/MM Malaria Vaccine | Experimental | Biological: R21 Matrix-M (R21/MM) Malaria Vaccine, Biological: Hexavalent Vaccine, Biological: Pneumococcal Polysaccharide Conjugate Vaccine, Biological: Rotavirus, Live Attenuated (Oral) Vaccine, Biological: Measles and Rubella Vaccine, Biological: Meningococcal (A, C, Y, W, X) polysaccharide conjugate vaccine, Biological: Yellow Fever vaccine, Biological: Typhoid Conjugate vaccineParticipants will receive R21/MM malaria vaccination at 3, 6, and 9 months of age. Participants will receive the hexavalent vaccine, PCV, and oral RV at 6 weeks, 10 weeks, and 14 weeks of age. At 9 months of age participants will receive MR and YF vaccines and TCV. Participants will receive a booster dose of R21/MM malaria vaccine at 15 months of age co-administered with the MenFive vaccine and the 2nd dose of MR vaccine. |
Who may qualify
- Ages
- 42 to 49 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Signed informed consent or thumb-printed and witnessed informed consent obtained from the parent/legal guardian of the infant.
- Infants must have been born full-term (at ≥37 weeks of gestation) and > 2500 grams at birth.
- Immunization schedule Cohorts 1, 2, and 3: Male and female infants 42-49 days (inclusive) of age at time of enrollment.
- Prior to group randomization, for infants in Cohort 1 randomization to receive vaccine dose 1 (Groups 1 and 2 of R21/MM or placebo, respectively) will occur at 42-49 days of age. Infants in Cohorts 2 and 3 will not be randomized to R21/MM or placebo; placebo will no longer be given. Rather infants in these cohorts will receive open-label R21/MM according to the immunization schedule category to which they have been randomized. Infants in Cohort 2, will receive their open-label R21/MM vaccine dose 1 (Group 3) at 2 months (56-63 days of age). Infants in Cohort 3, will receive their open-label R21/MM vaccine dose 1 (Group 5) at 3 months (84-91 days of age).
- The participant's parent/guardian must be willing to avoid travel, particularly in the 28 days after each study vaccination, must confirm willingness to contact the study team in the event of unexpected/unavoidable travel and, for the safety cohort, must confirm availability for the home visits to be conducted by a field worker or nurse to collect solicited AEs over the 7 days (day of vaccination and 6 subsequent days) following each study vaccine.
Key exclusion criteria (13 listed)
- Acute disease at the time of enrolment (acute disease is defined as the presence of a moderate or severe illness with or without fever). This does not include minor illnesses such as diarrhea, mild upper respiratory infection, without low-grade febrile illness, i.e. axillary temperature < 37.5°C or tympanic temperature < 38°C.
- (Note: In case of acute disease, participants may be re-assessed by a study physician for resolution of the condition and enrolled if eligible and still within the visit window).
- Clinically significant pulmonary, cardiovascular, gastrointestinal, endocrine, neurological, skin, hepatic or renal functional abnormality, as determined by medical history, physical examination or laboratory tests 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.
- At time of enrollment, any infant who has received any dose of the hexavalent/pentavalent vaccines, pneumococcal vaccine, rotavirus vaccine, IPV or has received more than one dose of oral polio virus or more than one dose of hepatitis B vaccine.
- Weight-for-length/height Z score of less than -3 or other clinical signs of malnutrition.
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-M (R21/MM) Malaria VaccineAdministered by intramuscular injection. Each 0.5 mL dose contains R21 Malaria Antigen (5 mcg) and Matrix-M1 (Adjuvant) (50 mcg). | Biological | Compressed 6-10-14 Week Schedule: Placebo / Recommended 5-6-7 Month Schedule: R21/MM Malaria Vaccine, Compressed 6-10-14 Week Schedule: R21/MM Malaria Vaccine, Relaxed 2-4-6 Month Schedule: R21/MM Malaria Vaccine, Relaxed 3-6-9 Month Schedule: R21/MM Malaria Vaccine |
| PlaceboAdministered by intramuscular injection. Each dose (0.5 mL) contains Normal saline (0.9%). | Biological | Compressed 6-10-14 Week Schedule: Placebo / Recommended 5-6-7 Month Schedule: R21/MM Malaria Vaccine |
| Hexavalent VaccineAlso: HEXASIILAdministered by intramuscular injection. Each dose of 0.5 mL contains: * Diphtheria Toxoid > 30 IU * Tetanus Toxoid > 40 IU * B. pertussis (whole cell) > 4 IU * Hepatitis B surface antigen (HBsAg) (recombinant DNA) 15 mcg * Inactivated polio vaccine (Salk strains grown on vero cells): Type - 1 (Mahoney strain) 40 D antigen units (DU); Type - 2 (MEF-1 strain) 8 DU; Type - 3 (Saukett strain) 32 DU * Haemophilus influenzae Type b (Hib) Conjugate Vaccine (Adsorbed) polyribosylribitol phosphate (PRP) 10 mcg conjugated to tetanus toxoid (TT) (carrier protein) 19 to 33 mcg] | Biological | Compressed 6-10-14 Week Schedule: Placebo / Recommended 5-6-7 Month Schedule: R21/MM Malaria Vaccine, Compressed 6-10-14 Week Schedule: R21/MM Malaria Vaccine, Relaxed 2-4-6 Month Schedule: R21/MM Malaria Vaccine, Relaxed 3-6-9 Month Schedule: R21/MM Malaria Vaccine |
| Pneumococcal Polysaccharide Conjugate VaccineAlso: PNEUMOSILAdministered by intramuscular injection. Each 0.5 mL dose contains 2 mcg each Saccharide for serotypes 1, 5, 9V, 14, 19A, 19F, 23F, 7F, 6A and 4 mcg Saccharide for serotype 6B. | Biological | Compressed 6-10-14 Week Schedule: Placebo / Recommended 5-6-7 Month Schedule: R21/MM Malaria Vaccine, Compressed 6-10-14 Week Schedule: R21/MM Malaria Vaccine, Relaxed 2-4-6 Month Schedule: R21/MM Malaria Vaccine, Relaxed 3-6-9 Month Schedule: R21/MM Malaria Vaccine |
| Rotavirus, Live Attenuated (Oral) VaccineAlso: ROTASIILAdministered orally. Each 2.0 mL dose contains: Live Attenuated Bovine-Human Rotavirus Reassortant [G1, G2, G3, G4 and G9], 5.6 focus-forming units (FFU) / serotype. | Biological | Compressed 6-10-14 Week Schedule: Placebo / Recommended 5-6-7 Month Schedule: R21/MM Malaria Vaccine, Compressed 6-10-14 Week Schedule: R21/MM Malaria Vaccine, Relaxed 2-4-6 Month Schedule: R21/MM Malaria Vaccine, Relaxed 3-6-9 Month Schedule: R21/MM Malaria Vaccine |
| Measles and Rubella VaccineAdministered by subcutaneous injection. Each 0.5 mL dose contains not less than 1000 cell culture infectious dose 50% (CCID50) of Measles virus and 1000 CCID50 of Rubella virus. | Biological | Compressed 6-10-14 Week Schedule: Placebo / Recommended 5-6-7 Month Schedule: R21/MM Malaria Vaccine, Compressed 6-10-14 Week Schedule: R21/MM Malaria Vaccine, Relaxed 2-4-6 Month Schedule: R21/MM Malaria Vaccine, Relaxed 3-6-9 Month Schedule: R21/MM Malaria Vaccine |
| Meningococcal (A, C, Y, W, X) polysaccharide conjugate vaccineAdministered by intramuscular injection. Each 0.5 mL dose contains 5 mcg of each Meningococcal A, C, Y, W, and X polysaccharide, 7.8 to 33.4 mcg of TT and 11.7 to 50.1 mcg of recombinant CRM197. | Biological | Compressed 6-10-14 Week Schedule: Placebo / Recommended 5-6-7 Month Schedule: R21/MM Malaria Vaccine, Compressed 6-10-14 Week Schedule: R21/MM Malaria Vaccine, Relaxed 2-4-6 Month Schedule: R21/MM Malaria Vaccine, Relaxed 3-6-9 Month Schedule: R21/MM Malaria Vaccine |
| Yellow Fever vaccineYellow fever vaccine will be locally sourced by each trial site in accordance with the countries' EPI program. | Biological | Compressed 6-10-14 Week Schedule: Placebo / Recommended 5-6-7 Month Schedule: R21/MM Malaria Vaccine, Compressed 6-10-14 Week Schedule: R21/MM Malaria Vaccine, Relaxed 2-4-6 Month Schedule: R21/MM Malaria Vaccine, Relaxed 3-6-9 Month Schedule: R21/MM Malaria Vaccine |
| Typhoid Conjugate vaccineTyphoid conjugate vaccine will be locally sourced by each trial site in accordance with the countries' EPI program. | Biological | Compressed 6-10-14 Week Schedule: Placebo / Recommended 5-6-7 Month Schedule: R21/MM Malaria Vaccine, Compressed 6-10-14 Week Schedule: R21/MM Malaria Vaccine, Relaxed 2-4-6 Month Schedule: R21/MM Malaria Vaccine, Relaxed 3-6-9 Month Schedule: R21/MM Malaria Vaccine |
Primary outcome
Geometric Mean Titers (GMTs) of Anti-circumsporozoite (CS) Immunoglobulin G (IgG) at Baseline and 28 Days after 3rd Vaccine Dose
Time frame: Baseline and 28 days after 3rd vaccine dose
The anti-CS antibody responses elicited following the primary 3-dose schedule of R21/MM will be assessed in the "compressed" (6-10-14 week) immunization schedule and the two "relaxed" (2-4-6 month and 3-6-9 month) immunization schedule cohorts.
Geometric Mean Fold Rise (GMFR) in Anti-CS IgG 28 Days after 3rd Vaccine Dose Compared to Baseline
Time frame: Baseline and 28 days after 3rd vaccine dose
The anti-CS antibody responses elicited following the primary 3-dose schedule of R21/MM will be assessed in the "compressed" (6-10-14 week) immunization schedule and the two "relaxed" (2-4-6 month and 3-6-9 month) immunization schedule cohorts.
Number of Participants with Solicited Adverse Events
Time frame: 7 days after each study vaccination
Local (redness, swelling, and pain at the injection site) and systemic (fever, drowsiness, irritability, decreased appetite) reactions will be collected in a subset of participants (the first 40 participants in each immunization schedule category at each site).
Number of Participants with Unsolicited Adverse Events
Time frame: 28 days after each study vaccination
Number of Participants with Serious Adverse Events
Time frame: Up to 28 days post 4th vaccine dose.
Number of Participants with Adverse Events of Special Interest
Time frame: Up to 28 days post 4th vaccine dose.
2 secondary outcomes
Geometric Mean Titers (GMTs) of Anti-CS IgG Before and 28 Days After 4th Vaccine Dose
Time frame: Month 15 predose and 28 days after vaccination
GMFR in Anti-CS IgG Titer Post 4th Dose Compared to Pre-4th Dose
Time frame: Month 15 predose and 28 days after 4th dose
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 29 Sep 2026.
- Individual participant dataSharing planned: Yes. PATH as the Sponsor of the Clinical Study will post the Clinical Trial Data in compliance with the Gates Foundation's Open Access policy and the WHO Joint Statement on Clinical Transparency. The Clinical Trial Data will contain no personally identifiable information (PII) and will be fully anonymized and de-identified.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing R21 Matrix-M (R21/MM) Malaria Vaccine, Hexavalent Vaccine and Pneumococcal Polysaccharide Conjugate Vaccine in people with Malaria Vaccines and Malaria (Plasmodium Falciparum), run by PATH at 2 sites in Burkina Faso.
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 7 inclusion and 13 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 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Burkina Faso. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Geometric Mean Titers (GMTs) of Anti-circumsporozoite (CS) Immunoglobulin G (IgG) at Baseline and 28 Days after 3rd Vaccine Dose (time frame: Baseline and 28 days after 3rd vaccine dose). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Sep 2026.