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

NCT ID: NCT05155579

Last Updated: 2025-09-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

593 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-14

Study Completion Date

2025-05-27

Brief Summary

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This is a Phase Ib trial conducted in Bougouni, Mali to evaluate the safety and immunogenicity of R21/Matrix-M in a single and two vial presentation, with different immunisation schedules, and when co-administered with EPI vaccines in African children.

Detailed Description

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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.

Conditions

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Malaria

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

RCT
Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators
For groups 1, 2 and 3, participants and investigators will be blinded to group allocation. Study staff involved in storage and preparation of the vaccine will be aware of vaccine assignment but these staff will play no other role in the study. The Sponsor team will remain blinded with the exception of designated members of the laboratory team that will perform the final evaluation of the data. For groups 4 and 5, no study staff or participants will be blinded as the number of vaccinations in each group is different. For group 6, no study staff or participants will be blinded as the schedule of vaccinations in each group is different.

Study Groups

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Groups 1a, 2a and 3a

60 children, aged 5-36 months, who will receive 4 doses of 5µg R21/50µg Matrix-M as a two vial formulation. The first three doses will be given one month apart, followed by a booster vaccination 12 months after the third dose. The age range of 5-36 months has been split into three groups to ensure an even age spread across age groups. Group 1a is 20 children aged 5-11 months, group 2a is 20 children aged 12-23 months, and group 3a is 20 children aged 24-36 months.

Group Type EXPERIMENTAL

R21/Matrix-M - two vial formulation

Intervention Type BIOLOGICAL

Adjuvanted malaria vaccine in a double vial formulation

Group 1b, 2b and 3b

60 children, aged 5-36 months, who will receive 4 doses of 5µg R21/50µg Matrix-M as a single vial formulation. The first three doses will be given one month apart, followed by a booster vaccination 12 months after the third dose. The age range of 5-36 months has been split into three groups to ensure an even age spread across age groups. Group 1b is 20 children aged 5-11 months, group 2b is 20 children aged 12-23 months, and group 3b is 20 children aged 24-36 months.

Group Type EXPERIMENTAL

R21/Matrix-M - single vial formulation

Intervention Type BIOLOGICAL

Adjuvanted malaria vaccine in a single vial formulation

Group 4a

150 participants, aged 6-7 months at the time of randomisation (to ensure third vaccination is given at approximately 9 months), who will receive 3 doses of 5µg R21/50µg Matrix-M one month apart. At the time of the third dose they will receive their measles-rubella and yellow fever vaccinations at the same time as R21/Matrix-M.

Group Type EXPERIMENTAL

R21/Matrix-M - single vial formulation

Intervention Type BIOLOGICAL

Adjuvanted malaria vaccine in a single vial formulation

Licensed vaccine - Measles-rubella

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Licensed vaccine - Yellow fever

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Group 4b

150 participants, aged 6-7 months at the time of randomisation, who will receive a measles-rubella and yellow fever vaccination 2 months after randomisation.

Group Type ACTIVE_COMPARATOR

Licensed vaccine - Measles-rubella

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Licensed vaccine - Yellow fever

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Group 4c

Group 4c is 50 participants, aged 6-7 months at the time of randomisation, who will receive 3 doses of 5µg R21/50µg Matrix-M one month apart.

Group Type EXPERIMENTAL

R21/Matrix-M - single vial formulation

Intervention Type BIOLOGICAL

Adjuvanted malaria vaccine in a single vial formulation

Group 5a

30 children who will receive 3 doses of 5µg R21/50µg Matrix-M, pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.

Group Type EXPERIMENTAL

R21/Matrix-M - single vial formulation

Intervention Type BIOLOGICAL

Adjuvanted malaria vaccine in a single vial formulation

Licensed vaccine - Pentavalent (diphtheria, tetanus, pertussis, hepatitis B and Hib)

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Licensed vaccine - Oral Polio Vaccine (OPV)

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Licensed vaccine - Rotavirus

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Licensed vaccine - Pneumococcal vaccine

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Licensed vaccine - Inactivated Polio Vaccine (IPV)

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Group 5b

30 children who will receive 3 doses of pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.

Group Type ACTIVE_COMPARATOR

Licensed vaccine - Pentavalent (diphtheria, tetanus, pertussis, hepatitis B and Hib)

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Licensed vaccine - Oral Polio Vaccine (OPV)

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Licensed vaccine - Rotavirus

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Licensed vaccine - Pneumococcal vaccine

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Licensed vaccine - Inactivated Polio Vaccine (IPV)

Intervention Type BIOLOGICAL

Licensed vaccine part of the EPI vaccination schedule

Group 6a

30 children, aged 5-36 months, who will receive 3 doses of 5µg R21/50µg Matrix-M. The first two doses one month apart and the third dose 6 months after the first dose.

Group Type EXPERIMENTAL

R21/Matrix-M - single vial formulation

Intervention Type BIOLOGICAL

Adjuvanted malaria vaccine in a single vial formulation

Group 6b

30 children, aged 5-36 months, who will receive 3 doses of 5µg R21/50µg Matrix-M. The first two doses one month apart and the third dose 12 months after the first dose.

Group Type EXPERIMENTAL

R21/Matrix-M - single vial formulation

Intervention Type BIOLOGICAL

Adjuvanted malaria vaccine in a single vial formulation

Interventions

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R21/Matrix-M - single vial formulation

Adjuvanted malaria vaccine in a single vial formulation

Intervention Type BIOLOGICAL

R21/Matrix-M - two vial formulation

Adjuvanted malaria vaccine in a double vial formulation

Intervention Type BIOLOGICAL

Licensed vaccine - Measles-rubella

Licensed vaccine part of the EPI vaccination schedule

Intervention Type BIOLOGICAL

Licensed vaccine - Yellow fever

Licensed vaccine part of the EPI vaccination schedule

Intervention Type BIOLOGICAL

Licensed vaccine - Pentavalent (diphtheria, tetanus, pertussis, hepatitis B and Hib)

Licensed vaccine part of the EPI vaccination schedule

Intervention Type BIOLOGICAL

Licensed vaccine - Oral Polio Vaccine (OPV)

Licensed vaccine part of the EPI vaccination schedule

Intervention Type BIOLOGICAL

Licensed vaccine - Rotavirus

Licensed vaccine part of the EPI vaccination schedule

Intervention Type BIOLOGICAL

Licensed vaccine - Pneumococcal vaccine

Licensed vaccine part of the EPI vaccination schedule

Intervention Type BIOLOGICAL

Licensed vaccine - Inactivated Polio Vaccine (IPV)

Licensed vaccine part of the EPI vaccination schedule

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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

* 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.


• 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.
Minimum Eligible Age

6 Weeks

Maximum Eligible Age

36 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Malaria Research and Training Center, Bamako, Mali

OTHER

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adrian Hill

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Locations

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Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, University of Sciences Techniques and Technologies of Bamako

Bamako, , Mali

Site Status

CCVTM, University of Oxford

Oxford, , United Kingdom

Site Status

Countries

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Mali United Kingdom

Other Identifiers

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VAC088

Identifier Type: -

Identifier Source: org_study_id

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