Safety, Immunogenicity and Efficacy of R21 Matrix-M in 5-17 Month Old Children in Nanoro, Burkina Faso
Condition: Malaria,Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a double blind randomised controlled clinical trial to evaluate the efficacy of R21
      adjuvanted with Matrix-M in healthy 5-17 month old children in a malaria endemic area.
    

Detailed description: 
      In this double-blind, randomised, controlled, phase 2b trial, the low-dose circumsporozoite
      protein-based vaccine R21, with two different doses of adjuvant Matrix-M (MM), was given to
      children aged 5-17 months in Nanoro, Burkina Faso-a highly seasonal malaria transmission
      setting. Three vaccinations were administered at 4-week intervals before the malaria season,
      with a fourth dose 1 year later. All vaccines were administered intramuscularly into the
      thigh. Group 1 received 5 μg R21 plus 25 μg MM, group 2 received 5 μg R21 plus 50 μg MM, and
      group 3, the control group, received rabies vaccinations. Children were randomly assigned
      (1:1:1) to groups 1-3. An independent statistician generated a random allocation list, using
      block randomisation with variable block sizes, which was used to assign participants.
      Participants, their families, and the local study team were all masked to group allocation.
      Only the pharmacists preparing the vaccine were unmasked to group allocation. Vaccine safety,
      immunogenicity, and efficacy were evaluated over 1 year. The primary objective assessed
      protective efficacy of R21 plus MM (R21/MM) from 14 days after the third vaccination to 6
      months.

      From May 7 to June 13, 2019, 498 children aged 5-17 months were screened, and 48 were
      excluded. 450 children were enrolled and received at least one vaccination. 150 children were
      allocated to group 1, 150 children were allocated to group 2, and 150 children were allocated
      to group 3. The final vaccination of the primary series was administered on Aug 7, 2019.
      R21/MM had a favourable safety profile and was well tolerated.

      Please see publication for more details: Lancet. 2021 May 15;397(10287):1809-1818. doi:
      10.1016/S0140-6736(21)00943-0

      After the first booster vaccination, participants in Groups 1 and 2 were further randomised
      2:1 to receive R21 with Matrix-M: control. The trial was extended by a further two years with
      yearly boosters of R21/MM or rabies vaccine. Groups 1 and 2 were subdivided and randomized
      2:1 to receive R21/MM or rabies vaccine as the second booster. Group 3 received control
      rabies vaccine as they had done previously. The second boosting occurred between June and
      July 2021 where 368 participants were boosted. In May 2022 it was decided to amend the
      protocol to allow for groups 1a and 2a (malaria vaccine groups) to be randomised 1:1 to
      receive either the R21/Matrix-M vaccine or a control rabies vaccine a year after the previous
      booster vaccine. The third boosting occurred between June and July 2022 where 357
      participants were boosted.

      Between June 2, and July 2, 2020, 409 children returned to receive a booster vaccine. Each
      child received the same vaccination for the booster as they received in the primary series of
      vaccinations; 132 participants received 5 μg R21 adjuvanted with 25 μg Matrix-M, 137 received
      5 μg R21 adjuvanted with 50 μg Matrix-M, and 140 received the control vaccine.

      A booster dose of R21/Matrix-M at 1 year following the primary three-dose regimen was
      administered. The trial is ongoing to assess long-term follow-up of these participants and
      the value of further booster

      Please see publication for more details of results of two year follow up: Lancet Infect Dis.
      2022 Dec;22(12):1728-1736. doi: 10.1016/S1473-3099(22)00442-X.

      The trial is currently in follow-up and the last volunteer last visit is expected to occur in
      July 2023.
    

Intervention name(s): R21 adjuvanted with 25mcg Matrix-M; Rabies Vaccine; R21 adjuvanted with 50mcg Matrix-M
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Vaccine; Vaccine; vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment