Optimization of Controlled Human Malarial Infection by Injection of P. Falciparum Sporozoites in Non-Immune Adults
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      The study is designed to establish the best dose to safely infect healthy individuals with
      Plasmodium falciparum sporozoites (PfSPZ) by injection.

      The goal of this study is to achieve infections in human volunteers with infection rates of
      100% and pre-patent periods of less than 12 days.
    

Detailed description: 
      This is an single center,open label, escalated and controlled human pilot study to optimize
      CHMI (controlled human malaria infection) administered by PfSPZ Challenge. The study was
      designed with an escalated dosing design in order to answer two questions:

        1. Does altering the volume of administration, alter infectivity of PfSPZ Challenge
           administered IM (intramuscular)? By varying the volume of inoculation of the 2,500 dose
           of PfSPZ administered IM we try to increase infection rates and decrease pre-patent
           period (Part A).

        2. When administered in the optimum volume determined in Part A, does increasing the dose
           increase the infectivity and decrease the pre-patent period of PfSPZ Challenge? By
           increasing the dose of PfSPZ we try to decrease the pre-patent period at the higher dose
           (Part B).

      Besides increasing the infectivity rate, we aim to reduce the pre-patent period to ~11 days.

      In Part A of the trial, the volume of inoculation will vary in order to identify the optimal
      volume needed for a dose of 2,500 PfSPZ to induce the greatest infection rate (defined as
      highest percentage of infected volunteers and shortest pre-patent period.)

      The outcome variables of part A are:

        1. Number of volunteers infected per group.

        2. Pre-patent period by thick blood smear in individuals in each group.

        3. Pre-patent period by quantitative PCR (qPCR) in individuals in each group.

        4. Parasite density when parasites first detected by thick blood smear and qPCR.

        5. Peak parasite density during the first 48 hours after first detection by qPCR.

      During Part A, an interim analysis will be performed in order to determine the optimal volume
      of inoculation that will be used during Part B. The variables that will be taken into account
      for this interim analysis will be: 1) number of volunteers infected per group and 2)
      pre-patent period by thick blood smear in individuals in each group.

      Part B will assess the effect of the optimal volume of inoculation determined in part A when
      administered with different PfSPZ doses, compared to the dose of 25,000 PfSPZ in 50 µL

      However, i) If the optimal volume in Part A is 10 µL, then Group 6 will receive 100,000 PfSPZ
      (2 inoculations of 50,000 PfSPZ) instead of 125,000 PfSPZ, as the PfSPZs are vialed at
      100,000 PfSPZ in 20 µL.

      ii) If the optimal volume in Part A is 50µL, then Group 5 will be modified to avoid
      duplication of regimens between groups 4 and 5. In this case, volunteers in group 5 will be
      administered a dose of 25,000 PfSPZ administered ID (intradermal) in four 10 µL injections.
      (Every volunteer will receive 4 ID injections of 6,250 PfSPZ in a volume of 10 µL each, with
      2 injections in each arm respectively).

      The outcome variables in this part of the study are:

        1. Number of volunteers infected per group.

        2. Pre-patent period by thick blood smear in individuals in each group.

        3. Pre-patent period by qPCR in individuals in each group.

        4. Parasite density when parasites first detected by qPCR.

        5. Peak parasite density during the first 48 hours after first detection by qPCR.

        6. Estimated number (±95% confidence interval) of liver stage schizonts per volunteer and
           mean (±95% confidence interval) for each group.

      All volunteers recruited will be healthy adults aged between 18 and 45 years. Safety and
      infectivity data will be collected for each of the regimens and dose-levels. Volunteers and
      clinical investigators will not be blinded to group allocation, however laboratory
      investigators processing blood films and samples for qPCR analysis will be blinded to group
      allocation.
    

Intervention name(s): PfSPZ Challenge
Intervention type(s): Biological
Intervention description(s): Aseptic, purified, vialed, cryopreserved fully infectious NF54 P. falciparum sporozoites
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: Malaria; Plasmodium falciparum