NMRC-M3V-Ad-PfCA Vaccine - Clinical Trial 1
Condition: Plasmodium Falciparum
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to determine whether a new investigational malaria vaccine is
      safe, well tolerated and effective against experimental exposure to malaria when given to
      healthy people with no previous exposure to malaria. The vaccine consists of a modified form
      of a relatively common virus, adenovirus, that has been rendered incapable of replicating
      itself and modified to deliver the malaria gene of interest to the body's cells allowing the
      cell to manufacture the protein encoded by the gene and present it to the body's immune
      system in a more natural and presumably effective way.
    

Detailed description: 
      The vaccine, called NMRC-M3V-Ad-PfCA (key: NMRC + Multi-antigen Multi-stage, Malaria Vaccine
      + Adenovectored + P. falciparum CSP & AMA1 antigens), is a combination of two recombinant
      adenovirus-derived constructs (adenovectors), one expressing the pre-erythrocytic stage
      antigen circumsporozoite protein (CSP) and the other expressing the erythrocytic stage
      antigen Apical Membrane Antigen 1 (AMA1), both from the 3D7 strain of P. falciparum. The
      vector is an attenuated, replication-deficient adenovirus derived from wildtype serotype 5
      adenovirus through the deletion of several genes. The vaccine is formulated in a buffered
      saline solution (Final Formulation Buffer = FFB).

      This is a Phase 1/2a, randomized, open-label, dose-escalating trial of the NMRC-M3V-Ad-PfCA
      vaccine administered intramuscularly to healthy, malaria-naïve adult volunteers. All
      volunteers will be seronegative (< 1:500, by a luciferase-based neutralizing antibody assay;
      VRC, Bethesda) for adenovirus serotype 5. In the first part of the study (dose-escalation
      phase, Part A), 1 x 10^10 particle units (pu) per construct or 2 x 10^10 pu total will be
      administered to six volunteers as a single dose to assess safety, and 4 weeks later, 5 x
      10^10 pu per construct or 1 x 10^11 pu total dose (five-fold dose escalation) will be
      administered to six additional volunteers. In the second part of the study
      (regimen-comparison phase, Part B), three regimens for administration will be compared: one
      dose, two doses administered ten days apart, and two doses administered 16 weeks apart.
      Separate groups will receive one dose of the individual components of the vaccine
      (NMRC-MV-Ad-PfC and NMRC-MV-Ad-PfA). Following immunization, volunteers participating in the
      regimen-comparison phase as well as several non-immunized control volunteers (serving as
      infectivity controls) will be challenged with P. falciparum sporozoites in order to assess
      vaccine efficacy against non-immunized controls challenged at the same time. The proposed
      design of the regimen-comparison phase will provide information to direct selection of an
      appropriate dosing regimen for subsequent studies, and will also indicate whether the two
      constituent antigens, when co-formulated, act synergistically, independently, or interfere
      with each other in the induction of antigen-specific immune responses and protective
      immunity.
    

Intervention name(s): NMRC-M3V-Ad-PfCA; NMRC-MV-Ad-PfC, NMRC-M3V-Ad-PfCA
Intervention type(s): Biological; Biological
Intervention description(s): Malaria Vaccine; Malaria Vaccines
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Malaria Vaccine; Adenovirus; Plasmodium falciparum