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.
Overview
- Phase
- Phase 1
- Intervention
- Rabies vaccine
- Conditions
- Malaria,Falciparum
- Sponsor
- University of Oxford
- Enrollment
- 480
- Locations
- 1
- Primary Endpoint
- 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.
- Status
- Recruiting
- Last Updated
- last year
Overview
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)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy infant aged 5-17 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 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.
Arms & Interventions
Group 1 (Control group)
n= 60. Age= 5-17 months Rabies Vaccine administered on Days 0, 28 and 152.
Intervention: Rabies vaccine
Group 2
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.
Intervention: RH5.1 10μg adjuvated with 50μg Matrix-M
Group 3 (Control Group)
n= 60. Age= 5-17 months Rabies Vaccine administered on Days 0, 28 and 56.
Intervention: Rabies vaccine
Group 4
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.
Intervention: RH5.1 10μg adjuvated with 50μg Matrix-M
Group 5
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.
Intervention: RH5.2 5μg adjuvated with 50μg Matrix-M
Outcomes
Primary Outcomes
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.
Time Frame: The month following each vaccination and at 6 and 12 months after administration of the final dose of vaccine.
Occurrence of solicited systemic reactogenicity signs and symptoms via clinic and home visits
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.
Time Frame: From 14 days after the third study vaccination until 6 months after the third study 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)
Secondary Outcomes
- 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.(At 6 and 12 months after administration of the final dose of vaccine.)
- 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.(From 14 days after the third study vaccination until 12 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(For 12 months after the last vaccination)
- 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.(At 6 and 12 months post third study vaccination.)
- 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.(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.(From 14 days after the third study vaccination until 3 months after the third study vaccination)
- Efficacy against incident severe anaemia and blood transfusion requirement(From 14 days after the third study vaccination until 6 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(At 2 and 6 months post third study vaccination.)