Controlled Human Malaria Infection (CHMI) After Immunization With Cryopreserved Plasmodium Falciparum Sporozoites Under Chloroquine Prophylaxis
Condition: Malaria; Plasmodium Falciparum
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to determine the safety and tolerability of ID administration of
      PfSPZ Challenge to volunteers taking chloroquine chemoprophylaxis (an approach called
      PfSPZ-CVac).
    

Detailed description: 
      The study is a single centre, double blind, randomized controlled clinical trial. Volunteers,
      investigators and laboratory personnel will be blinded.

      A maximum of 30 volunteers will be randomly divided into four groups. All volunteers will
      receive standard weekly chloroquine chemoprophylaxis for a period of 14 weeks (98 days).
      During this period, groups 1 and 3 will receive six ID injections of PfSPZ Challenge,
      containing a total of 75,000 PfSPZ of the Pf NF54 strain, on days 8, 36 and 64 (immunizations
      1, 2 and 3). The control groups 2 and 4 will receive ID injections with normal saline (NS) on
      the same days.

      Thirty-three days after the last dose of chloroquine, volunteers in groups 1 and 2 will have
      controlled human malaria infection (CHMI) by the bites of five mosquitoes infected with PfSPZ
      of the Pf NF54 strain. If ≥75% of volunteers in group 1 are protected against this homologous
      Pf CHMI, volunteers in groups 3 and 4 will have CHMI by the bites of five mosquitoes infected
      with the heterologous Pf NF135.C10 strain 75 days after the last dose of chloroquine.

      If <75% of volunteers in group 1 are protected against the homologous Pf CHMI, volunteers in
      groups 3 and 4 will receive an additional immunization (immunization 4), which will consist
      of six ID injections on the same day of 75,000 PfSPZ Challenge and NS respectively, at day
      162. In this fourth immunization period chloroquine will be administered for another 6 weeks
      starting at day 154. Finally, 33 days after the last dose of chloroquine, volunteers in
      groups 3 and 4 will have homologous Pf CHMI by the bites of five PfSPZ-infected mosquitoes.

      After CHMI all volunteers will be treated with a curative regimen of Malarone® (each tablet
      containing 250 mg atovaquone and 100 mg proguanil), either at the time of detection of blood
      stage parasitemia or 21 days after exposure to PfSPZ-infected mosquitoes. Volunteers will be
      checked for parasites by thick smear at least twice after treatment.

      If one of the volunteers is not fit to participate in the study on day -1, an alternate
      volunteer who passed screening will replace him or her. For this purpose 3 additional
      volunteers will be screened for possible back up.
    

Intervention name(s): PfSPZ Challenge; Normal Saline (NS)
Intervention type(s): Biological; Biological
Intervention description(s): PfSPZ Challenge is a suspension of aseptic, purified, cryopreserved PfSPZ that are thawed and formulated in diluent on the day of administration.; Normal saline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Malaria; Plasmodium falciparum; PfSPZ Challenge; Chemoprophylaxis; PfSPZ-CVac