A Study of AdCh63 AMA1 Alone and With MVA AMA1
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This is an open label phase I study, to assess the safety of a novel malaria vaccine, AdCh63
      AMA1, simian adenovirus encoding Plasmodium falciparum blood stage antigen, Apical Membrane
      Antigen -1. All volunteers recruited will be healthy adults. They will be primed with various
      doses of AdCh63 AMA1 administered intramuscularly. Some of the volunteers will receive a
      booster vaccination with MVA AMA1 administered via intramuscular route. Safety data will be
      collected for each of the eight regimens. Secondary aims of this study will be to assess the
      immune responses generated by each of these regimes.
    

Detailed description: 
      AMA1 is a type I integral membrane protein. It is produced by mature P. falciparum schizonts
      in infected erythrocytes AMA1 has become a leading candidate vaccine antigen. This is based
      on several facts, most notably that in several field studies an association was found between
      antibodies to the ectodomain of AMA1 and protection against clinical malaria. Also, in the
      Gambia, presence of antibodies to AMA1 and MSP-1 has been shown to enhance clearance of
      chloroquine resistant parasites in vivo.

      There are a number of trials currently ongoing in Oxford which are aimed at examining a
      simian adenovirus as a delivery vehicle and liver and blood stage malaria antigens as
      inserts. AdCh63 is currently in use with the MSP-1 insert, a blood stage antigen, in a phase
      I dose escalation clinical trial in Oxford (VAC037 / GTAC 166). The trial design includes
      AdCh63 MSP-1 administered alone and with MVA MSP-1 as part of a heterologous prime boost
      schedule, with sporozoite challenge of 3 volunteers in the higher dose group. At the most
      recent interim analysis, AdCh63 MSP-1 demonstrates an excellent safety profile.

      Also, AdCh63 is currently in use with the ME-TRAP insert, a liver stage antigen in a phase I
      dose escalation clinical trial in Oxford, (VAC033 / GTAC133) and a phase I/IIa trial with
      sporozoite challenge (MAL034 / OXREC: 09/H064/9). AdCh63 ME-TRAP has been administered alone
      and with MVA ME-TRAP as part of a heterologous prime boost schedule at various doses with
      excellent safety and immunogenicity to 87 volunteers at time of interim analysis.
    

Intervention name(s): AdCh63 AMA1; AdCh63 AMa1 and MVA AMA1
Intervention type(s): Biological; Biological
Intervention description(s): Group 1A - single dose of AdCH63 AMA1 5x10^9 vp intramuscularly Group 2A - single dose of AdCH63 AMA1 5x10^10 vp intramuscularly; Group 1B - single dose of AdCH63 AMA1 5x10^9 vp intramuscularly and single dose of MVA AMA1 5x10^8 pfu 8 weeks later intramuscularly Group 2B - single dose of AdCH63 AMA1 5x10^10 vp intramuscularly and single dose of MVA AMA1 5x10^8 pfu 8 weeks later intramuscularly
Other intervention name(s): Simian adenovirus expressing malaria antigen AMA1; Simian adenovirus, modified vaccinia Ankara virus expressing malaria antigen AMA1
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention