A Clinical Trial of the PfSPZ Vaccine Administered by Direct Venous Inoculation in Healthy Malaria-Naïve Adults: Heterologous vs. Homologous Controlled Human Malaria Infection and Reduction in Number of Doses
Condition: Malaria
MeSH terms: Infections; Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This is an open-label evaluation of the safety, tolerability immunogenicity and efficacy of
      the PfSPZ Vaccine administered by Direct Venous Inoculation (DVI) in healthy, malaria-naïve
      subjects. There will be 3 groups and a total of 69 subjects (45 immunized subjects and 24
      infectivity controls).
    

Detailed description: 
      Group 1 (n=15) and Group 2 (n = 15) subjects will receive five doses by DVI of 2.7 x 10^5
      PfSPZ per dose (4 doses at 4 week intervals and the 5th dose 8 weeks after the fourth dose).
      Group 3 (n = 15) will receive 3 doses by DVI of 4. 5 x 10^5 PfSPZ/dose at 8 week intervals.
      Subjects who complete all immunizations will receive a total 13.5 x 10^5 PfSPZ. Protective
      efficacy will be assessed by Controlled Human Malaria Infection (CHMI) by exposure to the
      bites of five Pf-infected mosquitoes. Groups 1 and 3 (n = 30) will undergo each of two CHMIs
      at the same time with mosquitoes infected with PfSPZ (3D7) (homologous) along with 6
      Infectivity Controls. Group 2 will undergo each of two CHMIs separately with mosquitoes
      infected with PfSPZ (7G8) (heterologous) along with 6 Infectivity Controls. CHMI will occur
      at approximately 2 to 3 weeks and 24 weeks after the final immunization. Subjects may proceed
      to CHMI provided they have received no fewer than three scheduled immunizations. Immunized
      subjects may participate in the second CHMI whether or not they were protected in the first
      CHMI; boosting of immune responses in CHMI #1 may lead to protection in CHMI #2.

      One subject in each of Groups 1 and 2 and 3 subjects in Group 3 will be immunized
      approximately 24 hours prior to the rest of the group (referred to as "pilot subjects"). For
      the Group1/Group 2 pilot subjects: the first subject will be immunized and observed on site
      for a minimum of one hour; at this point, the second subject may be immunized and he/she will
      also be observed for a minimum of one hour. For Group 3: the three subjects will be immunized
      sequentially with a minimum 2 hour observation period between subjects (and a two hour
      observation of the third subject as well). If there are no safety concerns identified in the
      pilot subjects after 24 hours that trigger the stopping rules, then the rest of subjects in
      Groups 1, 2 and 3 will be immunized as scheduled. Subjects in Group 3 will receive their
      first immunization approximately 4 weeks after subjects in Groups 1 and 2 receive their first
      immunizations. Subjects will be followed for 8 weeks after the last CHMI for safety purposes.
    

Intervention name(s): PfSPZ Vaccine
Intervention type(s): Biological
Intervention description(s): Suspension of metabolically active, non-replicating (live), radiation-attenuated, purified, cryopreserved, aseptic Plasmodium falciparum (Pf) sporozoites (SPZ)
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: PfSPZ Vaccine; Plasmodium falciparum; Malaria; Controlled Human Malaria Infection (CHMI)