Effect of Plasmodium Falciparum Exposure and Sickle Cell Trait on Infection Rates and Kinetics After IV Administration of PfSPZ Challenge
Condition: Plasmodium Falciparum Malaria; Malaria
MeSH terms: Infections; Malaria; Malaria, Falciparum; Sickle Cell Trait
Study type: Interventional
Phase: Phase 1

Summary: 
      The study is designed to establish infectivity of Plasmodium falciparum sporozoites (PfSPZ)
      via intravenous (IV) administration in three groups with different malaria immunity-status:

        1. Adults with a history of lifelong malaria exposure without sickle cell trait (HbAA)

        2. Adults with a history of lifelong malaria exposure with sickle cell trait (HbAS)

        3. Adults without previous malaria episodes without sickle cell trait (HbAA)

      Initially a dose of 3,200 PfSPZ will be given and the time until thick blood smear positivity
      after challenge will be assessed. If in any of the groups with a history of lifelong malaria
      exposure, 50% or less of individuals become thick blood smear positive during the 28 days
      post injection of PfSPZ Challenge, the dose will be increased 4-fold to 12,800 PfSPZ in this
      group.
    

Detailed description: 
      LACHMI-001 is a partially-blinded, human pilot trial to study immunity against P. falciparum
      malaria in a controlled infection setting. The main objective is to characterise the role of
      sickle cell trait and naturally acquired immunity in development of malaria, defined by
      positive smear for P. falciparum and signs or symptoms associated with malaria. Three groups
      of volunteers will receive radical cure treatment and subsequently PfSPZ Challenge by IV
      administration. The groups are:

        1. Adults with naturally acquired immunity and HbAA (Group IA, n=10-20)

        2. Adults with naturally acquired immunity and HbAS (Group IS, n=10-20)

        3. Adults without previous exposure to malaria and HbAA (Group NI, n=5)

      The initial challenge dose of 3,200 PfSPZ administered once intravenously leads to consistent
      infection in naïve adults (15/15 in prior studies) and thus should infect all volunteers in
      Group 3. However, volunteers with naturally acquired immunity or sickle cell trait might
      require a higher dose. Thus if 50% or less of volunteers become parasitemic in Groups IA or
      IS, 10 additional volunteers will be enrolled and challenged with 12,800 PfSPZ. All
      volunteers will be healthy adults aged 18 to 30 years. Safety and infectivity data will be
      collected for each of the regimens and dose-levels. Effective treatment is initiated
      immediately upon development of parasitemia together with the presence of symptoms associated
      with malaria.

      Laboratory staff reading blood films and processing samples will be blinded to group
      allocation. Volunteers and clinical investigators will be blinded to group allocation among
      the IA and IS groups.
    

Intervention name(s): PfSPZ Challenge
Intervention type(s): Biological
Intervention description(s): live, aseptic, cryopreserved P. falciparum sporozoites
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Plasmodium falciparum malaria; Malaria; PfSPZ Challenge; Controlled Human Malaria Infection (CHMI); Sickle Cell Trait; Sporozoites