Regimen Optimization Trial of PfSPZ Vaccine in Equatorial Guinea
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase 1, randomized regimen optimization study of PfSPZ Vaccine in healthy
      Equatoguinean volunteers to determine if a condensed, rapid immunization regimen is safe and
      efficacious. Four different regimens 4 weeks or less in duration will be evaluated for
      safety, tolerability, immunogenicity, and protective efficacy in comparison to a gold
      standard 16-week regimen.
    

Detailed description: 
      This double-blind, placebo-controlled clinical trial will be conducted in 104 Equatoguinean
      healthy men and women 18-45 years of age divided into four groups of 26 subjects receiving
      one of four dosing regimens. The study is designed to test the hypothesis that 2 or 4 doses
      of 9x10^5 PfSPZ of PfSPZ Vaccine administered by direct venous inoculation (DVI) over 6-7
      days as the priming immunization, with or without a boosting immunization at 4 or 16 weeks
      after the last priming dose, will (1) be safe and well tolerated; and (2) induce immunity
      leading to protection against homologous controlled human malaria infection (CHMI) performed
      at 8 weeks after the final immunization by DVI injection of PfSPZ Challenge. The first
      regimen will test the radiation-attenuated whole sporozoite PfSPZ Vaccine in a dose of
      9.0x10^5 administered by DVI with four priming immunizations followed by a boost after 16
      weeks. The second regimen will follow the same dosing and administering schedule, but without
      the boost after 16 weeks to study if a boost may be necessary. The third regimen will follow
      the first regimen with the interval duration to the boost shortened to only 4 weeks. In the
      fourth and final regimen, the vaccine will be administered two times instead of four followed
      by a boost in 4 weeks to evaluate if two priming immunizations will be sufficient to confer
      protection. In summary:

        -  Group 1: 21 subjects will receive 9.0x10^5 PfPSZ and 5 subjects will receive normal
           saline (NS) placebo on Days 1, 3, 5, 7, and 113.

        -  Group 2: 21 subjects will receive 9.0x10^5 PfPSZ and 5 subjects will receive NS on Days
           1, 3, 5, and 7.

        -  Group 3: 21 subjects will receive 9.0x10^5 PfPSZ and 5 subjects will receive NS on Days
           1, 3, 5, 7, and 29.

        -  Group 4: 21 subjects will receive 9.0x10^5 PfPSZ and 5 subjects will receive NS on Days
           1 and 8.

      The safety and tolerability of each regimen will be measured by recording (1) solicited and
      unsolicited adverse events, (2) immunogenicity by assessing humoral and cellular immune
      responses pre- and post-vaccination, and (3) vaccine efficacy (VE) by measuring protection
      against homologous CHMI administered by DVI of PfSPZ Challenge (NF54) at 8 weeks post-final
      vaccination.
    

Intervention name(s): PfSPZ Vaccine; Normal saline; PfSPZ Challenge (for CHMI)
Intervention type(s): Biological; Other; Biological
Intervention description(s): Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine); Normal saline is 0.9% sodium chloride; Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain NF54
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Plasmodium falciparum; PfSPZ Vaccine; PfSPZ Challenge (NF54); CHMI