Study to Evaluate Safety, Immunogenicity and Efficacy of PfSPZ Vaccine in HIV Negative and HIV Positive Tanzanian Adults
Condition: Malaria; Malaria,Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a randomized, double-blind, placebo-controlled trial to evaluate safety and
      tolerability of PfSPZ Vaccine administered as five doses of 9.0x10^5 PfSPZ or normal saline
      at 0, +2, +4, +6 and +28 days to healthy HIV negative adult volunteers and healthy HIV
      positive volunteers in Tanzania.
    

Detailed description: 
      This trial is a single center trial designed to assess the safety, tolerability,
      immunogenicity and efficacy of PfSPZ Vaccine (9.0x10^5 PfSPZ given at 0, +2, +4, +6 and +28
      days (Group 1, HIV negative, and Group 2, HIV positive)). Controls will receive parallel
      injections with normal saline (NS). All administrations of PfSPZ or NS will be by direct
      venous inoculation (DVI).

      Twenty-one male and female adult volunteers, aged from 18 to 45 years, who live in and around
      the Bagamoyo township, will be enrolled based on pre-defined inclusion and exclusion
      criteria. 12/21 subjects will be HIV positive volunteers (who clinical stage 1) on stable
      anti-retroviral therapy (ART) for at least 3 months with a CD4+ cell count above 500 cells/μL
      at screening. The rest (9/21) will be healthy HIV negative adults.

      Treatment allocation will be double-blind within Group 1 and 2b but not between the groups or
      subgroups. Immunizations will begin with healthy HIV negative volunteers first (Group 1),
      before inoculation of HIV positive volunteers (Groups 2a and 2b). Transitioning from
      immunization of HIV negative to immunization of HIV positive will begin by immunizing a
      sentinel group of 3 HIV positive individuals with a reduced vaccine dose of 4.5x10^5 PfSPZ
      (Group 2a). This transition will be staggered by at least two (2) weeks, to allow for a
      safety data review. If the safety data do not meet pause criteria, this will signal a "go"
      for transitioning to immunizations of sentinel group of three (3) HIV positive volunteers. If
      pause criteria are met, there will be no immediate transition, and instead an ad-hoc meeting
      of the Safety Monitoring Committee (SMC) will be called for an independent review and
      recommendation. Transition from the unblinded HIV positive sentinel Group 2a to the full
      study cohort of double blinded placebo controlled HIV positive volunteers (Group 2b), will
      also be staggered for at least two (2) weeks. There will be a scheduled review by the SMC of
      safety data collected from the sentinel HIV positive group for up to 7 days after the fourth
      immunization. After the safety review, transition to the main HIV positive group (Group 2b)
      will take into account the SMC recommendation(s).
    

Intervention name(s): PfSPZ Vaccine; Normal Saline Placebo; PfSPZ Challenge
Intervention type(s): Biological; Other; Biological
Intervention description(s): Aseptic, purified, metabolically active, non-replicating, radiation-attenuated, cryopreserved Pf sporozoites.; 0.9% sodium chloride solution; Aseptic, purified, live, infectious, cryopreserved Pf sporozoites.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: PfSPZ Vaccine; HIV+; Plasmodium falciparum; Sporozoites