Optimizing the infant schedule for the R21/Matrix‑M malaria vaccine

A Phase 2b Multicenter Randomized, Placebo-Controlled, Double-Blind, Study to Evaluate the Safety, Immunogenicity and Efficacy of R21/Matrix-M Malaria Vaccine in African Infants With Different Immunization Schedules

This trial will test three different timing schedules of the R21/Matrix‑M malaria vaccine in healthy infants to see which timing gives the best immune response and protection against Plasmodium falciparum.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 1200 (estimated)
• Ages: 42 Days to 49 Days
• Sex: All
• Sponsor: Path (Academic / other)
• Locations: 2 sites (Bobo-Dioulasso and 1 other locations)
• Trial ID: NCT06879327 on ClinicalTrials.gov

What this trial studies

This randomized, placebo-controlled Phase 2 trial enrolls healthy full-term infants and compares three immunization schedules that start at roughly 6 weeks, 2 months, or 3 months of age to determine how age at first dose and spacing between doses affect immunogenicity and protection against clinical P. falciparum malaria. Within each schedule cohort infants are randomized 3:1 to receive four doses of R21/Matrix‑M or placebo, with a fourth booster administered at 15 months, and routine EPI vaccines (hexavalent, pneumococcal conjugate, and rotavirus) can be given per schedule. Primary outcomes include antibody responses to the circumsporozoite protein and incidence of clinical malaria, with safety and reactogenicity monitored closely. The trial is conducted at research centers in Bobo‑Dioulasso and Ouagadougou, Burkina Faso, sponsored by PATH with collaborators including the Serum Institute of India and local partners.

Who should consider this trial

Good fit: Healthy full-term infants (≥37 weeks gestation and >2500 g) who are 42–49 days, 56–63 days, or 84–91 days old at enrollment depending on the cohort, with a parent/guardian able to provide consent and adhere to visit and travel requirements, are eligible candidates.

Not a fit: Preterm or low-birth-weight infants, children outside the enrolled age windows, infants with contraindications to vaccination, or infants living in low-transmission areas may not receive direct benefit from participation.

Why it matters

Potential benefit: If successful, an optimized schedule could align the R21/MM vaccine with routine infant immunizations and improve protection for young children in high-transmission settings.

How similar studies have performed: Earlier trials of R21/Matrix‑M have produced strong antibody responses and shown clinical efficacy that contributed to WHO recommendation, but direct comparisons of different infant timing and spacing schedules are a novel question.

Eligibility criteria

Inclusion Criteria:

* 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. 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. For infants in Cohort 2, randomization to receive vaccine dose 1 (Groups 3 and 4 of R21/MM or placebo, respectively) will occur at 2 months (56-63 days of age). For infants in Cohort 3, randomization to receive vaccine dose 1 (Groups 5 and 6 of R21/MM or placebo, respectively) will occur 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 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.

Exclusion Criteria:

* Acute disease at the time of enrolment (acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to participants with a minor illness such as diarrhea, mild upper respiratory infection, without low-grade febrile illness, i.e. axillary temperature \< 37.5°C).
* 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-height/length Z score of less than -3 or other clinical signs of malnutrition.
* Infant with major congenital defects.
* 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.

Where this trial is running

Bobo-Dioulasso and 1 other locations

• Institut de Recherche en Science de la Santé (IRSS) — Bobo-Dioulasso, Burkina Faso (Recruiting)
• Groupe de Recherche Action en Santé (GRAS) — Ouagadougou, Burkina Faso (Recruiting)

Study contacts

• Study coordinator: Michael Thigpen, MD

Conditions Malaria Vaccines; Plasmodium falciparum; R21/Matrix-M Malaria Vaccine