PfSPZ Vaccine: Dose Optimization With Heterologous Challenge in Healthy Malaria-Naïve Adults
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 2

Summary: 
      This is an open-label evaluation of the safety, tolerability, immunogenicity and efficacy of
      PfSPZ Vaccine administered by direct venous inoculation (DVI) in healthy, malaria-naïve adult
      subjects.
    

Detailed description: 
      The study will be conducted as a collaborative effort between the NMRC, UMB CVD, WRAIR and
      Sanaria, Inc. The study screening, immunizations, and follow-ups for Groups 1 & 2 will take
      place at the UMB CVD. The study screening, immunizations, and follow-ups for Groups 3 & 4
      will take place at the NMRC CTC in Bethesda, MD. The controlled human malaria infections
      (CHMI) will be conducted at WRAIR Entomology, Silver Spring, MD for NMRC subjects, and at UMB
      CVD for UMB CVD subjects.

      There will be 4 groups and a total of 92 subjects (60 immunized subjects and 32 infectivity
      controls). Group 1 (n = 15) subjects will receive PfSPZ Vaccine administered by direct venous
      inoculation (DVI), with 4 doses of 4.5 x 10^5 PfSPZ given every two days, followed by a
      single, boosting dose of 4.5 x 10^5 PfSPZ given 16 weeks later. For participants who were not
      protected after the first CHMI, an additional boosting dose of 4.5x10^5 PfSPZ will be given
      21 weeks later.

      Group 2 (n = 15) subjects will receive PfSPZ Vaccine administered by DVI, with 3 doses of 9.0
      x 10^5 PfSPZ administered every 8 weeks. For participants who were not protected after the
      first CHMI, a boosting dose of 9.0 x 10^5 PfSPZ will be given 21 weeks later.

      Group 3 (n = 15) subjects will receive PfSPZ Vaccine administered by DVI, with 3 doses of 18
      x 10^5 PfSPZ administered every 8 weeks. Following CHMI at 40 weeks, protected subjects and
      one-half of unprotected subjects will receive a final, boosting dose of 18 x 10^5 PfSPZ. The
      remaining half of unprotected subjects will receive a final, boosting dose of 4.5 x 10^5
      PfSPZ.

      Group 4 (n = 15) subjects will receive PfSPZ Vaccine administered by DVI, with 27 x 10^5
      PfSPZ administered once as a priming dose, followed by 2 doses of 9.0 x 10^5 PfSPZ
      administered every 8 weeks. Following CHMI at 40 weeks, protected subjects and one-half of
      unprotected subjects will receive a final, boosting dose of 9 x 10^5 PfSPZ. The remaining
      half of unprotected subjects will receive a final, boosting dose of 2.25 x 10^5 PfSPZ.

      Protective efficacy will be assessed by CHMI, conducted by exposure to the bites of three to
      five mosquitoes infected with heterologous (7G8 or NF135.C10) Pf parasites, with the number
      of mosquitoes depending on the infection intensity in the mosquitoes). At UMB CVD, protective
      efficacy will be assessed at both 28 and 40 weeks after the first immunization, in Groups 1
      and 2, along with 8 infectivity controls for each CHMI. At NMRC, protective efficacy will be
      assessed at 40 weeks (7G8 infected mosquitoes), and 66 weeks (NF135.C10 infected mosquitoes)
      after the first immunization, in Groups 3 and 4. Unprotected subjects in Groups 1 and 2, and
      all subjects in Groups 3 and 4, will be invited to receive a booster vaccination 21 days
      prior to the second CHMI at the respective sites, in order to assess the efficacy of a
      booster dose in previously vaccinated persons. These vaccine subjects may participate in the
      second CHMI whether or not they were protected in the first CHMI, and independent of their
      decision to receive the booster immunization, to serve as controls for the effect of the
      first CHMI on immunity. Subjects may proceed to CHMI provided they have received at least two
      of the three immunizations scheduled for Groups 2-4, or at least two of the four priming
      immunizations as well as the boost scheduled for Group 1. 7G8-infected mosquitoes may be
      substituted for NF135.C10 mosquitoes in case of difficulties with mosquito production.

      Two subjects in each group will serve as "pilot subjects" in the event of first in human
      dosing, and will be immunized approximately 24 hours prior to the rest of the subjects in the
      respective group. If there are no safety concerns identified in the pilot subjects that
      trigger the stopping rules, then the remainder of subjects will be immunized the day after
      the pilot subjects are immunized. Subjects will be followed for 56 days beyond both the week
      40 and week 66 CHMIs.
    

Intervention name(s): PfSPZ Vaccine; CHMI (7G8); CHMI (NF135.C10)
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Aseptic, purified, cryopreserved, radiation-attenuated, Plasmodium falciparum (Pf) sporozoites; CHMI is conducted by exposure to the bites of five mosquitoes infected with heterologous (7G8) Pf parasites.; CHMI is conducted by exposure to the bites of three to five mosquitoes infected with heterologous (NF135.C10) Pf parasites.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Plasmodium falciparum; PfSPZ Vaccine; Sporozoites; Controlled Human Malaria Infection