Clinical trial NCT05790889: A Study to Test Experimental Blood Stage Malaria Vaccine in Burkina Faso.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Malaria,Falciparum
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Institut de Recherche en Sciences de la Sante, Burkina Faso
name: European and Developing Countries Clinical Trials Partnership (EDCTP)
name: Wellcome Trust
First posted: 2023-03-30
Enrollment: 480
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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

Detailed 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)

Eligibility criteria: 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.

Primary outcomes:
measure: To assess the protective efficacy against clinical malaria of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area for 6 months after the last vaccination.
timeFrame: From 14 days after the third study vaccination until 6 months after the third study vaccination.
measure: To assess the safety and reactogenicity of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area.
timeFrame: The month following each vaccination and at 6 and 12 months after administration of the final dose of vaccine.
Secondary outcomes:
measure: To assess the humoral immunogenicity of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area.
timeFrame: Immunology blood samples will be collected at screening, day of vaccination (V) 1, 14 & 28 days post V2, day of V3, 14 days post V3, 2, 6 and 12 months post V3.
measure: To assess the protective efficacy against clinical malaria of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area for 3 months after the last vaccination.
timeFrame: From 14 days after the third study vaccination until 3 months after the third study vaccination
measure: To assess the protective efficacy against clinical malaria of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area
timeFrame: For 12 months after the last vaccination
measure: To assess the protective efficacy against asymptomatic P. falciparum infection of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area, by qPCR.
timeFrame: At 6 and 12 months after administration of the final dose of vaccine.
measure: To assess the protective efficacy against asymptomatic P. falciparum infection against gametocytaemia of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area, by qPCR.
timeFrame: At 6 and 12 months post third study vaccination.
measure: To assess the protective efficacy against clinical malaria of RH5.1 in Matrix-M and RH5.2-VLP in Matrix-M in 5-17 months old children living in a malaria-endemic area for 12 months after the last vaccination.
timeFrame: From 14 days after the third study vaccination until 12 months after the third study vaccination
measure: To assess the protective efficacy against gametocytaemia of RH5.1 in Matrix-M and RH5.2-VLP in Matrix-M in 5-17 months old children living in a malaria-endemic area, by qPCR at 2 and 6 months after administration of the final dose of vaccine
timeFrame: At 2 and 6 months post third study vaccination.
measure: Efficacy against incident severe anaemia and blood transfusion requirement
timeFrame: From 14 days after the third study vaccination until 6 months after the third study vaccination.
Other outcomes:
Locations:
city: Sigle
country: Burkina Faso
facility: Institut de Recherche en Sciences de la Santé
state: Boulkiemdé Province
Study officials:
affiliation: Honorary Consultant and Chief Investigator - Project clinical trials
name: Angela Minassian
role: PRINCIPAL_INVESTIGATOR
References: