A Pilot Study to Test Activity of Antimalarial Drugs Against an Induced Malaria Infection in Healthy Volunteers
Condition: Healthy; Non-smokers
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a pilot study of a protocol for inducing a falciparum malaria infection in healthy
      volunteers in order to test the activity of novel agents being developed as drugs for the
      treatment of uncomplicated malaria. In this pilot study, 16 healthy male volunteers will be
      administered a low level malaria infection via infected human red blood cells. After 6 days
      they will be administered one of two registered antimalarial treatments (8 volunteers for
      each treatment) in order to define the rate of clearance of the infection. This information
      will be used to design similar future studies for the initial assessment of the efficacy of
      novel antimalarial drugs in development.
    

Detailed description: 
      This is a single-center, controlled, randomized, study using a BSP inoculum challenge as a
      model to assess the activity of antimalarial agents. The study will be conducted in 2 cohorts
      (n = 6 and n = 10). Cohort 2 will not commence until at least after day 12 of cohort 1 and
      review by Safety Review Team following day 9 exit of cohort 1. The participants will be
      randomized 1:1 to the two registered antimalarials. This is an enabling study using
      registered antimalarial drugs as reference treatments (one slow acting and one fast acting),
      aimed to inform trial design, endpoints and testing regimens for assessing new candidate
      antimalarial drugs in development. The study will follow the sequence of the challenge
      inoculation, reference treatment and follow-up.

      Healthy male participants will be inoculated on Day 1 with ~1,800 Plasmodium
      falciparum-infected human erythrocytes administered intravenously. On an outpatient basis,
      participants will be monitored morning (AM) and night (PM) from day 3 to day 5 for adverse
      events and the unexpected early onset of symptoms, signs or parasitological evidence of
      malaria. On day 5 evening, participants will be admitted to the study unit and confined for
      safety monitoring and antimalarial treatment. Reference treatment administration will begin
      on the evening of Day 6 and continued on Day 7 and 8 (3 days of treatment).

      If clinical or parasitologic evidence of malaria (either the identification of two or more
      malaria parasites on a malaria thick film, platelet count less than 100 x109/L, or the onset
      of clinical features of malaria) occurs before day 6 evening, allocated treatment will begin
      at this time.

      Following treatment, participants will be followed up as inpatients for at least 86 hours, (4
      evenings) to ensure tolerance of the therapy and clinical response, then if clinically well
      on an outpatient basis for safety and continued presence of malaria parasites via PCR and
      thick blood film review.

      Adverse events will be monitored via telephone monitoring, within the clinical research unit
      and on outpatient review after malaria challenge inoculation and antimalarial study drug
      administration. Blood samples for safety evaluation, malaria monitoring, and red blood cell
      antibodies will be drawn at baseline and at nominated times after malaria challenge.
    

Intervention name(s): Blood stage parasite (BSP) inoculum
Intervention type(s): Biological
Intervention description(s): Inoculum of human red blood cells infected with falciparum malaria administered intravenously on Day 1
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Keywords: Health male volunteers; Male volunteers aged 18-45 years; Non-smokers and in good health