A Study of AdCh63 ME-TRAP Alone and With MVA ME-TRAP
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
      ME-TRAP, simian adenovirus encoding Plasmodium falciparum antigens. This follows promising
      phase I clinical studies of MVA ME-TRAP and preclinical studies of AdCh63 and MVA ME-TRAP
      used together in prime-boost regimes. All volunteers recruited will be healthy adults. They
      will be primed with various doses of AdCh63 ME-TRAP administered intradermally or
      intramuscularly. Some of the volunteers will receive a booster vaccination with MVA ME-TRAP
      at various doses administered via the intradermal or 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: 
      ME-TRAP insert contains a fusion protein of multiple epitopes (ME) and the Plasmodium
      falciparum pre-erythrocytic thrombospondin-related adhesion protein (TRAP). The 'ME' is a
      string of 20 epitopes fused to the thrombospondin-related adhesion protein. TRAP was selected
      as it is well characterized and has a protective homologue in rodents. We have safely
      administered ME-TRAP to over 700 volunteers in the UK and Africa.

      MVA vector proved to be non-contagious and avirulent. Viral replication is blocked late
      during infection of cells but importantly viral and recombinant protein synthesis is
      unimpaired even during this abortive infection. Replication-deficient recombinant MVA has
      been viewed as an exceptionally safe viral vector. When tested in animal model studies
      recombinant MVAs have been shown to be avirulent, yet protectively immunogenic as vaccines
      against viral diseases and cancer. Recent studies in macaques severely immuno-suppressed by
      SIV infection have further supported the view that MVA should be safe in immuno-compromised
      humans.

      Simian adenoviruses have not been used previously in a clinical trial in humans. However,
      they are under active development as vaccines for HIV, (by GSK), and for HCV, (Merck).
    

Intervention name(s): AdCh63 ME-TRAP; AdCh63 ME-TRAP; MVA ME-TRAP
Intervention type(s): Biological; Biological
Intervention description(s): A:Intradermal injection 1x10^8 vp at day 0
A:Intradermal injection 1x10^9 vp at day 0
A:Intradermal injection 1x10^10 vp at day 0
A:Intradermal injection 5x10^10 vp at day 0
5:Intramuscular injection 1x10^10 vp at day 0
6A:Intramuscular injection 5x10^10 vp at day 0
7A: Intramuscular injection 2x10^11 vp at day 0; B: AdCh63 ME-TRAP intradermally at dose of 1x10^8 vp at day 0; MVA ME-TRAP intradermally at dose of 2x10^8 pfu at day 56 (+/- 7 days)
B: AdCh63 ME-TRAP intradermally at dose of 1x10^9 vp at day 0; MVA ME-TRAP intradermally at dose of 2x10^8 pfu at day 56 (+/- 7 days)
B: AdCh63 ME-TRAP intradermally at dose of 1x10^10 vp at day 0; MVA ME-TRAP intradermally at dose of 2x10^8 pfu at day 56 (+/- 7 days)
B: AdCh63 ME-TRAP intradermally at dose of 5x10^10 vp at day 0; MVA ME-TRAP intradermally at dose of 2x10^8 pfu at day 56 (+/- 7 days)
6B: AdCh63 ME-TRAP intramuscularly at dose of 5x10^10 vp at day 0; MVA ME-TRAP intradermally at dose of 2x10^8 pfu at day 56 (+/- 7 days)
7B and 7C: AdCh63 ME-TRAP intramuscularly at dose of 2x10^11 vp at day 0; MVA ME-TRAP intradermally at dose of 2x10^8 pfu at day 56 (+/- 7 days)
Other intervention name(s): Simian adenovirus expressing P. falciparum antigens ME-TRAP; Simian adenovirus, modified vaccinia Ankara virus
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention