This will be a double-blind, individually randomised trial, to assess the safety, tolerability, immunogenicity, and protective efficacy of two and three doses of the R21/Matrix-M1 malaria vaccine or placebo given at 4 week intervals in healthy women of childbearing potential (WOCBP), who are on pregnancy prevention during vaccination, but report plans to become pregnant in the near future. Participants will be randomised in Year 1 into three groups in a 1:1:1 ratio: * Arm 1 (n=110): will receive three doses of R21/Matrix-M1 malaria vaccine at months 0, 1 and 2. * Arm 2 (n=110): will receive normal saline (placebo) at month 0 and two doses of R21/Matrix-M1 malaria vaccine at months 1 and 2. * Arm 3 (n=110): will receive three of doses normal saline (placebo) at months 0, 1 and 2. In Year 2: Non-pregnant participants in arms 1 and 2 will be randomised in a 1:1 ratio to receive a booster dose of R21/Matrix-M1 malaria vaccine or placebo at the beginning of the malaria transmission season. Participants in the control group (arm 3) will receive normal saline (placebo). Initial follow-up will be for two years after dose three, with an efficacy analysis at 6, 12, 18 and 24 months after dose 3. Participants will be monitored for safety, tolerability, immunogenicity, and malaria infection during the follow-up period. Participants will also be monitored for pregnancy over 12 months post primary and booster vaccination and those who become pregnant will be followed during their pregnancy and for 1 year post-delivery (as well as their offspring) for safety and malaria infection
The design will be a double blind, placebo-controlled study. Malian adult WOCBP between 18 and 35 years of age who consent to participate will be randomised to receive R21/Matrix-M1vaccine or normal saline to assess the safety, immunogenicity and protective efficacy of R21/Matrix-M1 Vaccine. Randomisation and Study Arms Consenting participants who have satisfied all the eligibility criteria and completed the baseline assessment will be individually randomised within the study groups using an electronic randomisation system into three arms in a 1:1:1 ratio. * Arm 1: Participants will receive three doses of R21/Matrix-M1 malaria vaccine at months 0, 1 and 2. * Arm 2: will receive normal saline (placebo) at month 0 and two doses of R21/Matrix-M1 malaria vaccine at month 1 and 2. * Arm 3: will receive three doses of normal saline (placebo) at months 0, 1 and 2. Participants will be assessed for safety, immunogenicity and efficacy for 12 months. After 12 months non-pregnant participants in arms 1 and 2, will be randomised in a 1:1 ratio; half in each of these two arms will receive a booster dose of R21/Matrix-M1 vaccine and half will receive a placebo injection (normal saline) and be followed up for an additional 12 months. All injections will be administered intramuscularly in the deltoid region, preferably of the non-dominant arm. Post third injection, participants will be followed through the malaria transmission (rainy) season, approximately 6 months, and then the ensuing dry season for an additional 6 months. Participants will be monitored for safety, immunogenicity, and protective efficacy (malaria infection) during the follow-up period. For any women who become pregnant during the two-year period (first year and second year) of the trial, follow up will continue through the end of pregnancy, and any viable newborns/infants and their mothers will be followed through the first year of life.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
330
10 µg of R21 and 50 µg of Matrix-M1
Saline and 10 µg of R21 and 50 µg of Matrix-M1
Saline
Koumantou Study Clinic
Bougouni, Sikasso, Mali
RECRUITINGIncidence of local and systemic solicited adverse events (AEs)
\- Incidence of local and systemic solicited adverse events (AEs) graded by severity.
Time frame: Within 7 days after each vaccine administration and over 6 months post third vaccination
Number of participants with P falciparum infection
P. falciparum blood stage infection defined as time to first positive blood smear
Time frame: Over 6 months post third vaccination
Assessment of safety and tolerabilty
* Occurrence of unsolicited adverse events 28 days follow-up following the vaccination. * Occurrence of serious adverse events for the whole study duration including in women who become pregnant.
Time frame: Through study completion, an average of 26 months
Anti-CSP antibody concentrations
Immunological assessment measuring the anti-CSP antibody concentrations in healthy Malian women of child bearing potential
Time frame: Through study completion. Timepoints: baseline, days 70, 84, 140, 196, 434, 448, 504 and 560
Rate of P.falciparum infection during pregnancy
P. falciparum blood stage infection defined as time to first positive blood smear during pregnancy
Time frame: Over 9-months pregnancy
Rate of P.falciparum infection
P. falciparum blood stage infection defined as time to first positive blood smear.
Time frame: Over 12-, 18- and 24-months post third vaccination
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