An Efficacy Study of IV Boosting With ChAd63/MVA ME-TRAP
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Plasmodium falciparum Malaria remains a major global health problem with approximately 200
      million cases and 500,000 deaths worldwide annually, mostly in African infants. Current
      malarial control strategies are threatened by emergence of parasite resistance to drug
      treatment and resistance of the mosquito vector to certain insecticides. A deployable malaria
      vaccine is therefore a key strategy for reducing malaria mortality and progressing towards
      global eradication, but those in clinical trials are currently someway short of WHO targets.

      ChAd63 ME-TRAP and MVA ME-TRAP are leading candidate vaccines being developed by Adrian
      Hill's group at the University of Oxford, and collaborators. Since 2007, testing of these
      vaccines intramuscularly in over 900 volunteers has shown them to be safe, well tolerated and
      capable of delivering partial efficacy against malaria infection. This study will be the
      first time studying the efficacy of giving a boosting dose of the vaccines intravenously in
      what the investigators call a "prime-target" strategy. It follows very encouraging
      pre-clinical work showing this route can target desirable immune responses to the liver to
      fight a crucial stage of malaria infection. An ongoing recent phase I study is dose
      escalating both these vaccines intravenously as a single dose prior to commencing this trial
      where intramuscular and intravenous doses will be combined for the first time. The
      investigators will initially recruit 46 healthy UK adult volunteers who will be enrolled into
      4 vaccination arms (10 volunteers each) and an unvaccinated control group (6 volunteers) who
      will undergo a controlled human malaria infection (CHMI). These are standardised, carefully
      supervised infection experiments used internationally to assess vaccine efficacy. As this is
      the first time giving intramuscular and intravenous doses of these vaccines in a combined
      schedule, the investigators will closely profile the safety and immune response during the
      vaccination follow-up. All trial activity will take place in Oxford.
    

Detailed description: 
      The study is considered of low risk to the health of participants. Volunteers will receive
      investigational vaccines, be infected with malaria by mosquito bite, may develop clinical
      malaria disease, will be treated with antimalarial drugs, and will have blood taken
      regularly. They will also be given the option to undergo a minimally invasive procedure -
      Fine Needle Aspiration of the liver - to examine the immune response in this target organ
      which is also considered to be low risk.

      As this is the first time intravenous dose of the vaccines following intramuscular
      prime/boost doses will be administered, once volunteers have received their intramuscular
      doses the investigators will stagger the intravenous vaccinations to allow for interim safety
      reviews. The first volunteer in groups 1&2, once they have received their two intramuscular
      doses, will receive their intravenous vaccine dose alone and observed for a minimum 8 hours.
      If there have been no concerns identified at the 8 hour and 24 hour reviews identified by the
      CI and Local Safety Committee (LSC) chair, the next two volunteers in these groups will
      receive their intravenous vaccine dose. There will be a further safety 24 hours after these
      volunteers have been vaccinated before the remaining volunteers are vaccinated.

      Volunteers are expected to have both vaccine site reactions (eg, pain, swelling, warmth in
      the arm where the vaccine is given) and systemic reactions to vaccination (eg, fever,
      headache, tiredness, sore muscles and joints). These are expected to resolve completely
      within several days, and symptoms strong enough to prevent usual activities over this time
      are expected to be uncommon.
    

Intervention name(s): ChAd63 ME-TRAP and MVA ME-TRAP vaccination
Intervention type(s): Biological
Intervention description(s): vaccination with ChAd63 ME-TRAP 5x10^10 vp (intramuscularly and intravenously) vaccination with MVA METRAP 2x10^8 pfu (intramuscularly) and MVA METRAP 2x10^7 pfu (intravenously) Group 5 will be challenged with malaria by mosquito bite.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention