Safety and Immunogenicity of the Malaria Vaccine, R21/MatrixM, in Healthy Thai Adults
Status:
Not yet recruiting
Trial end date:
2023-04-01
Target enrollment:
Participant gender:
Summary
Malaria remains one of the leading causes of morbidity and mortality worldwide. Plasmodium
falciparum is a complex pathogen with numerous immune evasion mechanisms which has added
layers of complexity to the development of safe and protective vaccines. There remains an
urgent need to identify and develop more protective and more affordable vaccine candidates
that could achieve the World Health Organization (WHO) goal of 75% efficacy against clinical
malaria.
R21 is a novel pre-erythrocytic candidate malaria vaccine. R21 includes Hepatitis B surface
antigen (HBsAg) fused to the C-terminus and central repeats of the circumsporozoite protein
of P. falciparum (CSP), which self-assemble into virus-like particles in yeast. R21 lacks the
excess HBsAg found and comprises only fusion protein moieties.
R21/MatrixM (MM) had a favourable safety profile and was well tolerated. The majority of
adverse events were mild, with the most common event being fever. None of the serious adverse
events were attributed to the vaccine. At one year, vaccine efficacy remained high, at 77%.
Participants vaccinated with R21/MM showed high titres of malaria-specific anti-
Asn-Ala-Asn-Pro (NANP) antibodies 28 days after the third vaccination, which were almost
doubled with the higher adjuvant dose. Titres waned but were boosted to levels similar to
peak titres after the primary series of vaccinations after a fourth dose administered one
year later.
Currently, there are no safety and immunogenicity data for the use of R21/MatrixM in Asian
populations. This trial will generate the required data for the use of this vaccine in Asia.
For integration with the current targeted malaria elimination (TME) activities, which provide
mass drug administrations at months M0, M1, and M2, it would be most efficient and practical
to provide the vaccine at the same intervals.
In summary: The investigators propose to conduct a safety and immunogenicity trial of
R21/MatrixM in Thai adults. The major aims of this study are to 1) assess the safety and
immunogenicity of R21/MatrixM in Thai adults 2) confirm that the co-administration of
antimalarial drugs with the malaria vaccine R21/MatrixM does not reduce the immunogenicity of
the vaccine and 3) assess the absorption and pharmacokinetics of antimalarial drugs
piperaquine, and a single low dose of primaquine (SLDPQ) when co-administered with
R21/MatrixM.
This is a randomized, open label, single centre, Phase 2 study. 120 healthy non-pregnant Thai
adults, aged 18-55 years, inclusive, will be recruited.
Each participant will be randomized into one of the following study arms in a ratio of 5:5:2,
as follows:
1. R21/MatrixM + Dihydroartimisinin (DHA)-Piperaquine (PIP)+ primaquine (PQ) (Group 1,
n=50) will receive R21/MatrixM + 3 doses DHA-PIP+PQ at Month 0, Month 1 and Month 2
2. R21/MatrixM only (Group 2, n=50) will receive R21/MatrixM standard dose at Month 0,
Month 1 and Month 2
3. DHA-PIP+PQ only (Group 3, n=20) will receive 3 doses DHA-PIP+PQ at Month 0, Month 1 and
Month 2