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.

Overview

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)

Interventions

• Biological Rabies vaccine
  Vaccine
• Biological RH5.1 10μg adjuvated with 50μg Matrix-M
  Vaccine
• Biological RH5.2 5μg adjuvated with 50μg Matrix-M
  Vaccine

Primary outcome measures

• 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.]
• 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.]

Secondary outcome measures (8)

• 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. [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 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 [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. [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. [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 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 [Time frame: At 2 and 6 months post third study vaccination.]
• Efficacy against incident severe anaemia and blood transfusion requirement [Time frame: From 14 days after the third study vaccination until 6 months after the third study vaccination.]

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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

Burkina Faso · 1 center

• Institut de Recherche en Sciences de la Santé — Siglé

Publications

• Natama HM, Salkeld J, Some A, Soremekun S, Diallo S, Traore O, Rouamba T, Ouedraogo F, Ouedraogo E, Dabone KCS, Kone NA, Compaore ZMJ, Kafando M, Bonko MDA, Konate F, Sorgho H, Nielsen CM, Pipini D, Diouf A, King LDW, Shaligram U, Long CA, Cho JS, Lawrie AM, Skinner K, Roberts R, Miura K, Bradley J, Silk SE, Draper SJ, Tinto H, Minassian AM. Safety and efficacy of the blood-stage malaria vaccine R PMID 39672183

Identifiers

NCT: NCT05790889 · VAC091

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗