Trial to Evaluate the Safety, Immunogenicity, and Efficacy of Malaria Infection in Malaria Naïve Adults
Condition: Malaria
MeSH terms: Infections; Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a study designed to assess the safety, tolerability, immunogenicity, and protective
      efficacy of 2 heterologous prime-boost vaccine regimens in healthy, malaria naïve adults. The
      study will include 2 vaccine groups and an infectivity control (IC) group consisting of
      non-immunized subjects. Subjects to be immunized will be randomly assigned to one of two
      vaccine groups.
    

Detailed description: 
      This is a study designed to assess the safety, tolerability, immunogenicity, and protective
      efficacy of 2 heterologous prime-boost vaccine regimens in healthy, malaria naïve adults. The
      study will include 2 vaccine groups and an infectivity control (IC) group consisting of
      non-immunized subjects. Subjects to be immunized will be randomly assigned to one of two
      vaccine groups. Approximately 4 weeks after administration of the boosting immunization the
      vaccinated groups and the IC group will participate in CHMI wherein subjects will be exposed
      to the bites of 5 Anopheles stephensi mosquitoes carrying infectious Pf sporozoites within a
      controlled clinical environment. Protection will be determined by the examination of thick
      blood smears through 28 days post-CHMI and by retrospective PCR analysis for the presence of
      blood stage parasites. All groups will be enrolled and evaluated in one cohort. Due to a
      limit in the number of subjects who can undergo malaria challenge at the facility in one day,
      CHMI will be conducted over two days.

      Group 1 (2-antigen): 3 doses at 4 week intervals (Week 0, 4, and 8) of DNA prime with D-C +
      D-A at 2 mg total (1 mg per construct) per dose as two 1 mL IM injections of the blended
      D-CA, one in each arm, via Biojector 2000 needle-free injection device or an equivalent
      disposable syringe needle-free injection device. This will be followed after 16 weeks (Week
      24) by 1 dose of ChAd63-C + ChAd63-A boost, at a total dose of 1 x 1011 virus particles (vp)
      (5 x 1010 vp/construct) as a single IM injection of 0.65mL, using a needle and syringe.

      Group 2 (3-antigen): 3 doses at 4 week intervals (Week 0, 4, and 8) of DNA prime with D-C +
      D-A + D-T at 3 mg total (1 mg per construct) per dose as two 1 mL intramuscular (IM)
      injections of the blended D-CAT, one in each arm, via Biojector 2000 needle-free injection
      device or an equivalent disposable syringe needle-freeinjection device. This will be followed
      after 16 weeks (Week 24) by 1 dose of ChAd63-C + ChAd63-A + ChAd63-T boost, at a total dose
      of 1.5 x 1011 vp (5 x 1010 vp/construct) as a single IM injection of 1.0mL, using a needle
      and syringe.
    

Intervention name(s): D/ChAd63-CA; D/ChAd63-CAT; Infectivity Control (IC) Group
Intervention type(s): Biological; Biological; Other
Intervention description(s): Priming Component (DNA) = NMRC-M3V-D-PfCA (D-CA) Vaccine Boosting Component = ChAd63-PfCA; Priming Component (DNA) = NMRC-M3V-D-PfCAT (D-CAT) Boosting Component = ChAd63-PfCAT; Subjects will be exposed to bites of 5 Anopheles stephensi mosquitoes carrying infectious Pf sporozoites within a controlled clinical environment.
Other intervention name(s): Controlled Human Malaria Infection (CHMI)
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study will include 2 vaccine groups and an infectivity control (IC) group consisting of non-immunized subjects.
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: Malaria Infection