Clinical trial NCT06879327: Infant Malaria Vaccine Schedule Optimization
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Malaria Vaccines
Keywords: Plasmodium falciparum
R21/Matrix-M Malaria Vaccine
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Serum Institute of India PVT LTD (SII)
name: Agilis
name: Pharmassist Ltd
name: MCT-CRO
name: Cytespace
First posted: 2025-03-17
Enrollment: 1200
Sex: ALL
Minimum age (years): 42
Maximum age (years): 49
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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 and the ensuant efficacy in protecting infants against clinical Plasmodium falciparum malaria.

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. Participants in each immunization schedule cohort will be randomized in a ratio of 3:1 to receive 4 doses of either R21/MM or placebo with a 4th dose to be administered at 15 months of age.

Infants randomized to the respective immunization schedule categories will receive co-administered routine EPI vaccines. The study will include the provision of a three dose R21/MM compressed schedule to all participants randomized to the placebo arms upon completion of the study at Month 27 of life.

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.

Primary outcomes:
measure: Geometric Mean Titers (GMTs) of Anti-circumsporozoite (CS) Immunoglobulin G (IgG) at Baseline and 28 Days after 3rd Vaccine Dose
timeFrame: Baseline and 28 days after 3rd vaccine dose
measure: Geometric Mean Fold Rise (GMFR) in Anti-CS IgG 28 Days after 3rd Vaccine Dose Compared to Baseline
timeFrame: Baseline and 28 days after 3rd vaccine dose
measure: Number of Participants with Solicited Adverse Events
timeFrame: 7 days after each study vaccination
measure: Number of Participants with Unsolicited Adverse Events
timeFrame: 28 days after each study vaccination
measure: Number of Participants with Serious Adverse Events
timeFrame: Up to 27 months of age
measure: Number of Participants with Adverse Events of Special Interest
timeFrame: Up to 27 months of age
Secondary outcomes:
measure: Geometric Mean Titers (GMTs) of Anti-CS IgG Before and 28 Days After 4th Vaccine Dose
timeFrame: Month 15 predose and 28 days after vaccination
measure: Fold Increase in Anti-CS IgG Titer Post 4th Dose Compared to Pre-4th Dose
timeFrame: Month 15 predose and 28 days after 4th dose
measure: Number of Clinical Malaria Episodes per Person-year Meeting the Primary Case Definition up to 27 Months
timeFrame: From 6 weeks of age to 27 months of age
measure: Number of Clinical Malaria Episodes per Person-year Meeting the Primary Case Definition up to 15 Months
timeFrame: From 6 weeks of age to 15 months of age
measure: Number of Clinical Malaria Episodes per Person-year Meeting the Primary Case Definition from 15.5 to 27 Months
timeFrame: From 15.5 months (2 weeks after the 4th vaccination) to 27 months of age
measure: Number of Clinical Malaria Episodes per Person-year Meeting the Secondary Case Definition up to 27 Months
timeFrame: From 6 weeks of age to 27 months of age
measure: Number of Clinical Malaria Episodes per Person-year Meeting the Secondary Case Definition up to 15 Months
timeFrame: From 6 weeks of age to 15 months of age
measure: Number of Clinical Malaria Episodes per Person-year Meeting the Secondary Case Definition from 15.5 to 27 Months
timeFrame: From 15.5 months (2 weeks after the 4th vaccination) to 27 months of age
Other outcomes:
Locations:
city: Bobo-Dioulasso
country: Burkina Faso
facility: Institut de Recherche en Science de la Santé (IRSS)
city: Ouagadougou
country: Burkina Faso
facility: Groupe de Recherche Action en Santé (GRAS)
Study officials:
References: