A Study to Assess the Experimental Malaria Vaccines R78C and RH5.1 Combined With R21/Matrix-M (a "Multi-stage" Malaria Vaccine)

NCT ID: NCT06958198

Last Updated: 2025-12-26

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

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-15

Study Completion Date

2026-10-31

Brief Summary

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This is a Phase Ib age de-escalation, dose escalation, open-label study to assess the safety and immunogenicity of the multi-stage malaria vaccine candidate R21 plus RH5.1 and/or R78C in Matrix-M in adults aged 18-35 years and children aged 5-17 months in Burkina Faso.

Detailed Description

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There will be six study groups. Group 1 will consist of 8 adults who will receive three doses of 5 µg R21 + 10 µg RH5.1 + 10 µg R78C. Group 2 will consist of 8 children who will receive three doses of 5 µg R21 + 10 µg RH5.1. Group 3 will consist of 8 children who will receive three doses of 5 µg R21 + 10 µg R78C. Group 4 will consist of 8 children who will receive three doses of 5 µg R21 + 10 µg RH5.1 +10 µg R78C. Group 5 will consist of 8 children who will receive three doses of 5 µg R21. Group 6 will consist of 16 children who will receive three doses of 10 µg RH5.1 +10 µg R78C. All vaccinations will be given in 50 µg Matrix-M. All groups will receive their vaccinations in a 0-1-6 month regimen.

Groups 1 to 4 and 6 will be recruited in a staggered process. There will be a DSMB review prior to age deescalation. There will also be three sentinel participants per group and DSMB reviews prior to each subsequent (second and third) vaccination. Group 5 can be recruited at any time and without need for sentinel participants or DSMB review.

Conditions

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Malaria,Falciparum

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

This is a Phase Ib age de-escalation, dose escalation, open label study to assess the safety and immunogenicity of the multi-stage malaria vaccine candidate R21 plus RH5.1 and/or R78C in Matrix-M in adults aged 18-35 years and children aged 5-17 months in Burkina Faso. 8 healthy adults aged 18-35 years and 48 children aged 5-17 months living in a malaria endemic area will be recruited at one site in Burkina Faso. Adults will be recruited into one group receiving the combination of R21 + RH5.1 + R78C in Matrix-M. Children will be recruited into four groups receiving the combination of the three vaccines, R21 + RH5.1/Matrix-M, R21 + R78C/Matrix-M, R21/Matrix-M only or RH5.1 + R78C/Matrix-M only.

Follow-up will be for 6 months post third vaccination.
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Group 1(n=8) adults (18-35years)

They will receive three doses of 5 µg R21 + 10 µg RH5.1 + 10 µg R78C, administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182), given as an Intramuscular injection to the deltoid region (adults) or anterolateral thigh (children)

Group Type EXPERIMENTAL

R21

Intervention Type BIOLOGICAL

A protein particle comprising recombinant HBsAg fused to the central repeat and the C-terminus of the circumsporozoite protein

RH5.1

Intervention Type BIOLOGICAL

A soluble protein vaccine against the RH5 antigen

R78C

Intervention Type BIOLOGICAL

A soluble RIPR EGF-CyRPA fusion protein vaccine

Matrix-M™

Intervention Type BIOLOGICAL

A saponin-based vaccine adjuvant

Group 2 (n=8) Children aged between 5-17months

They will receive three doses of 5 µg R21 + 10 µg RH5.1, administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182), given as an Intramuscular injection to the deltoid region (adults) or anterolateral thigh (children)

Group Type EXPERIMENTAL

R21

Intervention Type BIOLOGICAL

A protein particle comprising recombinant HBsAg fused to the central repeat and the C-terminus of the circumsporozoite protein

RH5.1

Intervention Type BIOLOGICAL

A soluble protein vaccine against the RH5 antigen

Matrix-M™

Intervention Type BIOLOGICAL

A saponin-based vaccine adjuvant

Group 3 (n=8) children aged between 5-17 months

They will receive three doses of 5 µg R21 + 10 µg R78C, administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182), given as an Intramuscular injection to the deltoid region (adults) or anterolateral thigh (children)

Group Type EXPERIMENTAL

R21

Intervention Type BIOLOGICAL

A protein particle comprising recombinant HBsAg fused to the central repeat and the C-terminus of the circumsporozoite protein

R78C

Intervention Type BIOLOGICAL

A soluble RIPR EGF-CyRPA fusion protein vaccine

Matrix-M™

Intervention Type BIOLOGICAL

A saponin-based vaccine adjuvant

Group 4 (n=8) Children aged between 5-17 months

They will receive three doses of 5 µg R21 + 10 µg RH5.1 +10 µg R78C , administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182), given as an Intramuscular injection to the deltoid region (adults) or anterolateral thigh (children)

Group Type EXPERIMENTAL

R21

Intervention Type BIOLOGICAL

A protein particle comprising recombinant HBsAg fused to the central repeat and the C-terminus of the circumsporozoite protein

RH5.1

Intervention Type BIOLOGICAL

A soluble protein vaccine against the RH5 antigen

R78C

Intervention Type BIOLOGICAL

A soluble RIPR EGF-CyRPA fusion protein vaccine

Matrix-M™

Intervention Type BIOLOGICAL

A saponin-based vaccine adjuvant

Group 5 (n=8) children aged 5-17 months

They will receive three doses of 5 µg R21, administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182), given as an Intramuscular injection to the deltoid region (adults) or anterolateral thigh (children)

Group Type EXPERIMENTAL

R21

Intervention Type BIOLOGICAL

A protein particle comprising recombinant HBsAg fused to the central repeat and the C-terminus of the circumsporozoite protein

Matrix-M™

Intervention Type BIOLOGICAL

A saponin-based vaccine adjuvant

Group 6 ( n=16) Children 5-17 months

They will receive three doses of 10 µg RH5.1 +10 µg R78C, administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182), given as an Intramuscular injection to the deltoid region (adults) or anterolateral thigh (children)

Group Type EXPERIMENTAL

RH5.1

Intervention Type BIOLOGICAL

A soluble protein vaccine against the RH5 antigen

R78C

Intervention Type BIOLOGICAL

A soluble RIPR EGF-CyRPA fusion protein vaccine

Matrix-M™

Intervention Type BIOLOGICAL

A saponin-based vaccine adjuvant

Interventions

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R21

A protein particle comprising recombinant HBsAg fused to the central repeat and the C-terminus of the circumsporozoite protein

Intervention Type BIOLOGICAL

RH5.1

A soluble protein vaccine against the RH5 antigen

Intervention Type BIOLOGICAL

R78C

A soluble RIPR EGF-CyRPA fusion protein vaccine

Intervention Type BIOLOGICAL

Matrix-M™

A saponin-based vaccine adjuvant

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Group 1: Healthy adult aged 18-35 years at the time of first study vaccination
* Group 2-6: Healthy child aged 5-17 months at the time of first study vaccination
* Group 1: Female participants must be non-pregnant (as demonstrated by a negative urine pregnancy .

test), and practice continuous effective contraception until three months after the final study vaccination

* Participant or parent/guardian provides signed/thumb-printed informed consent
* Participant (and parent/guardian for child participants) resident in the study area villages, and anticipated to be available for vaccination and the duration of follow-up -

Exclusion Criteria

* The participant may not enter the trial if ANY of the following apply:

* Clinically significant congenital abnormalities as judged by the PI or other delegated individual.
* Clinically significant skin disorder (psoriasis, contact dermatitis, etc.), cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness as judged by the PI or other delegated individual.
* History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
* Children with weight-for-age Z score of less than -3 or other clinical signs of malnutrition.
* History of allergic reaction, significant IgE-mediated event, or anaphylaxis to immunisation.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
* Sickle cell disease.
* Clinically significant laboratory abnormality at grade 2 or above as judged by the PI or other delegated individual.
* Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
* Receipt of any vaccine in the 14 days preceding enrolment, or planned receipt of any other vaccine within 28 days following each study vaccination.
* History of vaccination with any malaria vaccine.
* Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
* Suspected or known current alcohol misuse.
* Suspected or known injecting drug use in the 5 years preceding enrolment.
* Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
* Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
* Seropositive for hepatitis B surface antigen (HBsAg), hepatitis C (HCV IgG) or HIV. For children, any history of vertical exposure to HIV infection.
* Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (for corticosteroids, this will mean prednisone, or equivalent, ≥ 0.5 mg/kg/day; inhaled and topical steroids are allowed).
* 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.


The following adverse events associated with vaccine immunisation constitute absolute contraindications to further administration of vaccine. If any of these events occur during the study, the participant must be withdrawn and followed until resolution of the event, as with any adverse event:

* Anaphylactic reaction following administration of vaccine.
* Pregnancy.

The following adverse events constitute contraindications to administration of vaccine at that point in time; if any one of these adverse events occurs at the time scheduled for vaccination, the participant may be vaccinated at a later date, or withdrawn at the discretion of the Investigator. The participant must be followed until resolution of the event as with any adverse event:

* Acute disease at the time of vaccination (acute disease is defined as the presence of a moderate or severe illness with or without fever or symptoms suggestive of possible COVID-19 disease). All vaccines can be administered to persons with a minor illness such as diarrhoea or mild upper respiratory infection without fever, i.e. axillary temperature \< 37.5°C.
* Temperature of \>37.5°C (99.5°F) at the time of vaccination.
Minimum Eligible Age

5 Months

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Institut de Recherche en Sciences de la Sante, Burkina Faso

OTHER_GOV

Sponsor Role collaborator

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role collaborator

Wellcome Trust

OTHER

Sponsor Role collaborator

European Vaccine Initiative

OTHER

Sponsor Role collaborator

Bundesministerium für Forschung, Technologie und Raumfahrt (BMFTR)

UNKNOWN

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Institut de Recherche en Sciences de la Santé

Siglé, Boulkiemdé Province, Burkina Faso

Site Status RECRUITING

Countries

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Burkina Faso

Central Contacts

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Naomi N Kamau

Role: CONTACT

Phone: +44 (0)1865611418

Email: [email protected]

Angela Minassian, Honorary Consultant and CI

Role: CONTACT

Facility Contacts

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Dr Athanase M. Somé, Doctorat en médecine

Role: primary

Other Identifiers

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VAC093

Identifier Type: -

Identifier Source: org_study_id