A Study to Test Experimental Blood Stage Malaria Vaccine in Burkina Faso.

University of Oxford

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Malaria,Falciparum

Treatments: Biological: RH5.2 5μg adjuvated with 50μg Matrix-M; Biological: RH5.1 10μg adjuvated with 50μg Matrix-M; Biological: Rabies vaccine

Study type: Interventional

Funder types: Other

Identifiers

NCT05790889

VAC091

Details and patient eligibility

About

This is a Phase IIb randomised controlled trial of the safety, immunogenicity and efficacy of the blood-stage malaria vaccine candidates RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in infants aged 5-17 months in Burkina Faso

Full description

During the initial recruitment to Groups 1 and 2, participants will be randomised 1:2 to receive vaccination with the rabies control vaccination or RH5.1/Matrix-M.

During recruitment to Groups 3, 4 and 5, participants will be randomised 1:2:2 to receive vaccination with rabies control vaccination, RH5.1/Matrix-M or RH5.2-VLP/Matrix-M Efficacy of vaccination will be assessed by comparing the incidence of malaria cases in the pooled control groups (Groups 1 and 3) to the incidence of malaria in each investigational vaccine group (Groups 2,4 and 5).

There are three study vaccines: the IMP, 10μg RH5.1 adjuvanted with Matrix-M; 5μg RH5.2-VLP and Rabies Vaccine. Participants will receive the first vaccination of RH5.1 10μg with 50μg Matrix-M (Groups 2 and 4) or RH5.2 5μg with 50μg Matrix-M (Group 5). After approximately 4 weeks, a second dose will be administered, followed by a third and final vaccination approximately 4 weeks later (Groups 3-5) or approximately 4 months later (Groups 1-2). Second and third vaccinations will be administered at the same dose of both vaccine and adjuvant as at the initial vaccination and will be given within the window period of 5 months. Volunteers will be followed for 12 months from final vaccination.

The trial is funded by EDCTP grant number RIA2016V-1649-MMVC and by a Wellcome Trust Translational Award (205981/Z/17/Z)

Enrollment: 480 estimated patients

Sex: All

Ages: 5 to 17 months old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy infant aged 5-17 months at the time of first study vaccination
2. Parent/guardian provides signed/thumb-printed informed consent
3. Infant and parent/guardian resident in the study area villages and anticipated to be available for vaccination and follow-up for 12 months following last dose of vaccination.

Exclusion criteria

• 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 immunization.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
• Sickle cell disease.
• Clinically significant laboratory abnormality as judged by the study clinician.
• 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 7 days preceding enrolment, or planned receipt of any other vaccine within 7 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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480 participants in 5 patient groups, including a placebo group

Group 1 (Control group)

Placebo Comparator group

Description:

n= 60. Age= 5-17 months Rabies Vaccine administered on Days 0, 28 and 152.

Treatment:

Biological: Rabies vaccine

Group 2

Experimental group

Description:

n=120 Age= 5-17 months First vaccination of RH5.1 10μg with 50μg Matrix-M will be administered on day 0, followed by a second dose administered on Day 28, followed by a third and final dose at Day 152.

Treatment:

Biological: RH5.1 10μg adjuvated with 50μg Matrix-M

Group 3 (Control Group)

Placebo Comparator group

Description:

n= 60. Age= 5-17 months Rabies Vaccine administered on Days 0, 28 and 56.

Treatment:

Biological: Rabies vaccine

Group 4

Experimental group

Description:

n=120 Age= 5-17 months First vaccination of RH5.1 10μg with 50μg Matrix-M will be administered on day 0, followed by a second dose administered on Day 28, followed by a third and final dose at Day 56.

Treatment:

Biological: RH5.1 10μg adjuvated with 50μg Matrix-M

Group 5

Experimental group

Description:

n=120 Age= 5-17 months First vaccination of RH5.2-VLP 5μg with 50μg Matrix-M will be administered on day 0, followed by a second dose administered on Day 28, followed by a third and final dose at Day 56.

Treatment:

Biological: RH5.2 5μg adjuvated with 50μg Matrix-M