Assessment of Safety and Immunogenicity of a Single Vial Presentation of R21/Matrix-M and Co-Administration With EPI Vaccines

This trial has six groups. This will be a double-blind, individually randomised trial, with 1:1 randomisation with the single or two vial presentation of R21/Matrix-M malaria vaccine for study groups 1, 2 and 3. Groups 1, 2 and 3 are to assess the safety and immunogenicity of R21/Matrix-M as a single vial formulation compared with a two-vial formulation, in children aged 5- 36 months, in a malaria endemic area. The age range of 5-36 months has been split into three groups to ensure an even age spread across age groups.

For groups 4 and 5, this is a randomised, open-label study to assess the safety and immunogenicity of R21/Matrix-M when co-administrated with various EPI vaccines at the relevant ages, in a malaria endemic area.

Group 6 is a randomised, open-label study to assess safety and immunogenicity of a delayed, third dose of R21/Matrix-M in 5-36 month old children, in a malaria endemic area.

For groups 1, 2, 3, 5 and 6, participants will be randomised 1:1. For group 4, participants will be randomised 3:3:1.

Approximately 590 children will be recruited across these six study groups.

The primary study objectives are:

Safety

• To assess the safety and reactogenicity of R21/Matrix-M, as a single- vial formulation in 5-36-month old African children.
• To assess the safety and reactogenicity of co-administration of R21/Matrix-M with the EPI vaccines given at 9 months, measles-rubella and yellow fever vaccines, in African children.
• To assess the safety and reactogenicity of co-administration of R21/Matrix-M with the EPI vaccines given at 6, 10 and 14 weeks of age, pentavalent and oral polio vaccine (OPV), in African children.

Immunogenicity

• To assess the immunogenicity of R21/Matrix-M, as a single- vial formulation in 5-36-month-old African children, compared with the two-vial formulation.
• To assess the immunogenicity of EPI vaccines given at 9 months, measles-rubella and yellow fever vaccines, when given with and without R21/Matrix-M
• To assess the immunogenicity of EPI vaccines given at 6, 10 and 14 weeks of age, pentavalent and oral polio vaccines, given as part of EPI at 6, 10 and 14 weeks of age, when given with and without R21/Matrix-M.

The secondary study objectives are:

• To assess the safety and reactogenicity of R21/Matrix-M, as a single- vial formulation in African children compared with the two-vial formulation.
• To assess the safety and reactogenicity of a delayed third dose of R21/Matrix-M in 5-36-month-old African children.
• To assess the immunogenicity of a delayed third dose of R21/Matrix-M in 5-36-month-old African children.

This trial is funded by the Serum Institute of India.

Inclusion criteria

at study entry:

• Age:

• Group 1: The child is 5-11 months of age at the time of randomization (i.e. up to the day before of their first birthday).
• Group 2: The child is 12-23 months of age at the time of randomization (i.e. up to the day before of their second birthday).
• Group 3: The child is 24-36 months of age at the time of randomization (i.e. up to the day of their third birthday).
• Group 4: The child is 6-7 months of age at the time of randomization.
• Group 5: The child is 6 weeks of age at the time of randomization and have not received any dose of the pentavalent vaccine, pneumococcal vaccine, rotavirus vaccine, IPV and only the first dose of the OPV.
• Group 6: The child is aged 5-36 months at the time of their 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.

Exclusion criteria

at study entry:

• The child has previously received a malaria vaccine.
• The child is enrolled in another malaria intervention trial that could interfere with the results of this study.
• The child has a history of allergic disease or reactions likely to be exacerbated by any component of the study vaccines.
• The child has a history of allergic reactions, significant IgE-mediated events or anaphylaxis to previous immunisations.
• The child has major congenital defects.
• The child has anaemia associated with clinical signs of symptoms of decompensation, or a haemoglobin of ≤7.4 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.
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV or asplenia.
• 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.
• Clinically significant laboratory abnormality as judged by the study clinician
• For group 5 only: the child has received any dose of the pentavalent vaccine, pneumococcal vaccine, rotavirus vaccine, IPV or has received more than one dose of the OPV.

Exclusion criteria

during the study (to be checked prior to each vaccination):

• 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.