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
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)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
480
Vaccine
Vaccine
Vaccine
Institut de Recherche en Sciences de la Santé
Siglé, Boulkiemdé Province, Burkina Faso
RECRUITINGTo 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.
Time to first episode of clinical malaria (defined as the presence of axillary temperature higher than 37.5 degree celsius and P. Falciparum parasite density \>5000 asexual forms/µL)
Time frame: From 14 days after the third study vaccination until 6 months after the third study vaccination.
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.
Occurrence of solicited systemic reactogenicity signs and symptoms via clinic and home visits
Time frame: The month following each vaccination and at 6 and 12 months after administration of the final dose of vaccine.
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.
The following measures will be assessed * Serum ELISA response: 1\. Quantitative antigen-specific IgG antibody levels (µg/mL readout) over time - analysis of peak responses and longevity; 2. Antigen-specific antibody subclass/isotype measurement; 3. Antigen-specific antibody avidity measurement; In vitro GIA against 3D7 clone P. falciparum parasites using purified total IgG and a single-cycle pLDH readout assay * Purified IgG ELISA versus GIA titration "Quality Analysis"
Time frame: 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.
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.
Time to first episode of clinical malaria (defined as the presence of axillary temperature ≥37.5°C and P. falciparum parasite density \>5000 asexual forms/µL).
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Time frame: From 14 days after the third study vaccination until 3 months after the third study vaccination
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
Occurrence of solicited local reactogenicity signs and symptoms via clinic and home visits
Time frame: For 12 months after the last vaccination
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.
Efficacy tested by conducting qPCR analysis
Time frame: At 6 and 12 months after administration of the final dose of vaccine.
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.
The proportion of participants in each study arm that show presence of parasite density \>5000 asexual forms/µL as measured by quantitative reverse-transcriptase PCR PLUS presence of axillary temperature \<37.5°C and absence of history of fever within the last 24 hours. The proportion of participants in each study arm that show presence of parasite density \>0 asexual forms/µL as measured by quantitative reverse-transcriptase PCR PLUS presence of axillary temperature \<37.5°C and absence of history of fever within the last 24 hours.
Time frame: At 6 and 12 months post third study vaccination.
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.
Time to first episode of clinical malaria (defined as the presence of axillary temperature ≥37.5°C and P. falciparum parasite density \>5000 asexual forms/µL).
Time frame: From 14 days after the third study vaccination until 12 months after the third study vaccination
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
The proportion of participants in each study arm that show presence of gametocytes \>0 gametocytes/μL as measured by quantitative reverse-transcriptase PCR.
Time frame: At 2 and 6 months post third study vaccination.
Efficacy against incident severe anaemia and blood transfusion requirement
The proportion of participants in each study arm with documented Hb \<5.0 g/dL identified at clinical presentation in association with P. falciparum asexual parasitaemia \> 5000 parasites/µL. The proportion of participants in each study arm with documented Hb \<5.0 g/dL identified at clinical presentation and requirement for a blood transfusion.
Time frame: From 14 days after the third study vaccination until 6 months after the third study vaccination.