A Study to Assess the Experimental Malaria Vaccines R78C and RH5.1 With Matrix-M in Combination With R21/Matrix-M (VAC087)

University of Oxford

Status and phase: Not yet enrolling; Phase 2

Conditions: Malaria,Falciparum

Treatments: Biological: Rabivax-S; Biological: Avaxim 80; Biological: RH5.1; Biological: R78C; Biological: R21; Biological: Matrix-M™; Biological: Menveo

Study type: Interventional

Funder types: Other

Identifiers

NCT07183371

VAC087

Details and patient eligibility

About

This is a Phase IIb randomised controlled trial of the safety, immunogenicity and efficacy of the malaria vaccine candidates R78C with Matrix-M™, and the combination of RH5.1 and R21 with Matrix-M™, in children aged 5-36 months in Burkina Faso.

Full description

There will be three study groups, each comprising of 120 children aged between 5 and 36 months at the time of first vaccination living in a malaria endemic area and will be recruited at one site in Burkina Faso. Participants will be randomised to receive either three doses of the malaria candidate vaccines R78C/Matrix-M and three doses of a commercially available rabies vaccine, three doses of RH5.1+R78C/Matrix-M and three doses of R21/Matrix-M or six doses of commercially available control vaccines.

Follow up will be for six months following the last vaccination.

Enrollment: 360 estimated patients

Sex: All

Ages: 5 to 36 months old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: Only participants who meet all the inclusion criteria will be enrolled into the trial:

• Healthy infant aged 5-36 months at the time of first study vaccination
• Parent/guardian provides signed/thumb-printed informed consent
• Infant and parent/guardian 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.
• 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 another 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.
• Known maternal HIV infection (no testing will be done by the study team).
• 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.

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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360 participants in 3 patient groups, including a placebo group

Group 1 (n=120) children 5-36 months

Experimental group

Description:

They will receive three doses of 10 µg R78C + 50 µg Matrix-M, administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182). A commercially available rabies vaccine, Rabivax-S, will be administered at Month 3 (Day 98), Month 4 (Day 126) and Month 5 (Day 154). All will be given as a intramuscular injections.

Treatment:

Biological: Matrix-M™

Biological: R78C

Biological: Rabivax-S

Group 2 (n=120) children 5-36 months

Experimental group

Description:

They will receive three doses of 10 µg RH5.1 + 10 µg R78C + 50 µg Matrix-M, administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182). 5 µg R21 + 50 µg Matrix-M will be administered at Month 3 (Day 98), Month 4 (Day 126) and Month 5 (Day 154), also given as Intramuscular injections. All will be given as intramuscular injections.

Treatment:

Biological: Matrix-M™

Biological: R21

Biological: R78C

Biological: RH5.1

Group 3 (n=120) children 5-36 months

Placebo Comparator group

Description:

Participants will receive six doses of commercially available control vaccines. This consists of the Hepatitis A vaccine, Avaxim 80, which will be given at Month 0 (Day 0) and Month 6 (Day 182), the meningitis vaccine, Menveo, given at Month 1 (Day 28), and a rabies vaccine, Rabivax-S, given at Month 3 (Day 98), Month 4 (Day 126) and Month 5 (Day 154). All will be given as a intramuscular injections.

Treatment:

Biological: Menveo

Biological: Avaxim 80

Biological: Rabivax-S