Infant Malaria Vaccine Schedule Optimization
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
1 other identifier
interventional
964
1 country
2
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2025
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 11, 2025
CompletedFirst Posted
Study publicly available on registry
March 17, 2025
CompletedStudy Start
First participant enrolled
May 30, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 27, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 27, 2027
May 15, 2026
May 1, 2026
2.3 years
March 11, 2025
May 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
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.
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.
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).
7 days after each study vaccination
Number of Participants with Unsolicited Adverse Events
28 days after each study vaccination
Number of Participants with Serious Adverse Events
Up to 28 days post 4th vaccine dose.
Number of Participants with Adverse Events of Special Interest
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
Month 15 predose and 28 days after vaccination
GMFR in Anti-CS IgG Titer Post 4th Dose Compared to Pre-4th Dose
Month 15 predose and 28 days after 4th dose
Study Arms (4)
Compressed 6-10-14 Week Schedule: R21/MM Malaria Vaccine
EXPERIMENTALParticipants 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
OTHERParticipants 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
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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.
Interventions
Administered by intramuscular injection. Each 0.5 mL dose contains R21 Malaria Antigen (5 mcg) and Matrix-M1 (Adjuvant) (50 mcg).
Administered by intramuscular injection. Each dose (0.5 mL) contains Normal saline (0.9%).
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\]
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.
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.
Yellow fever vaccine will be locally sourced by each trial site in accordance with the countries' EPI program.
Typhoid conjugate vaccine will be locally sourced by each trial site in accordance with the countries' EPI program.
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- PATHlead
- Agiliscollaborator
- Pharmassist Ltdcollaborator
- MCT-CROcollaborator
- Cytespacecollaborator
- Serum Institute of India Pvt. Ltd.collaborator
Study Sites (2)
Institut de Recherche en Sciences de la Santé (IRSS)
Bobo-Dioulasso, Burkina Faso
Groupe de Recherche Action en Santé (GRAS)
Ouagadougou, Burkina Faso
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- 964 participants will be randomized to an immunization schedule cohort if eligibility is confirmed by the investigator(s) at 42 to 49 days of age. Both the investigators and parent/legal guardian will know which cohort their infant has been assigned to. In Part A of the study, infants were randomized within each immunization schedule category to receive R21/MM or placebo; neither the blinded study staff nor the parent/legal guardian knew whether the infant would receive R21/MM or placebo. After the broad introduction of R21/MM for infants from 5 months of age, participants randomized to receive placebo were withdrawn from the study and referred to start R21/MM vaccinations as part of the routine EPI schedule. In Part B, only infants randomized to the 6-10-14 week immunization schedule will be further randomized to receive R21/MM or placebo for the primary 3 doses; neither the blinded study staff nor the parent/legal guardian will know whether the infant will receive R21/MM or placebo.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 11, 2025
First Posted
March 17, 2025
Study Start
May 30, 2025
Primary Completion (Estimated)
September 27, 2027
Study Completion (Estimated)
September 27, 2027
Last Updated
May 15, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
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.