Sequential Optimization of Dose and Schedule of PfSPZ Vaccine
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      MAVACHE is a sequential dose and schedule optimization trial of intravenous immunization with
      PfSPZ Vaccine in 18 to 54 malaria-naïve, healthy adult volunteers receiving 9x10^5,
      1.35x10^6, or 2.7x10^6 PfSPZ per dose and a total dose between 2.7x10^6 and 8.1x10^6 PfSPZ
      followed by CHMI with 3,200 fully infectious PfSPZ (PfSPZ Challenge).

      PfSPZ Challenge (7G8) to assess vaccine efficacy, safety, tolerability and infectivity of
      ascending PfSPZ doses will be assessed in healthy, malaria-naïve volunteers.
    

Detailed description: 
      The study is to take place at Institut für Tropenmedizin, Eberhard Karls Universität
      Tübingen, Tübingen Germany.

      The study has two phases: 1) dose optimization, and 2) regimen verification. In the first
      phase groups A, B1, B2, C1, C2 and C3 will be vaccinated sequentially in a pre-specified
      order, followed by homologous CHMI with 3,200 PfSPZ Challenge (NF54) three weeks after last
      vaccine injection.

      Dose optimization phase A: 9x10^5 PfSPZ on Days 0, 7 and 28 (n = 6) B1: 1.35x10^6 PfSPZ on
      Days 0 and 7 (n = 6) B2: 1.35x10^6 PfSPZ on Days 0, 7, and 28 (n = 6) C1: 2.7x10^6 PfSPZ on
      Day 0 (n = 6) C2: 2.7x10^6 PfSPZ on Day 0 and 7 (n = 6) C3: 2.7x10^6 PfSPZ on Days 0, 7 and
      28 (n = 6)

      In parallel to CHMI with PfSPZ Challenge (NF54) during the optimization phase, a total of
      nine volunteers will receive either 800, 1,600 or 3,200 PfSPZ Challenge (7G8) (PfSPZ
      Challenge (7G8) dose finding) to assess safety, tolerability and infectivity of PfSPZ
      Challenge (7G8) in malaria-naïve healthy adult volunteers.

      PfSPZ Challenge (7G8) dose finding/infection D1: 800 PfSPZ (n = 3) D2: 1,600 PfSPZ (n = 3)
      D3: 3,200 PfSPZ (n = 3)

      Subsequently, the shortest efficacious regimen (V1) and a three-dose regimen (Day 0, 7 and
      28) of the highest safe dose (V2) will be selected and verified against placebo (normal
      saline (NS)). Groups V1 and V2 will be vaccinated at approximately the same time and undergo
      repeat CHMI three and eight weeks after the last immunization. Volunteers will either receive
      PfSPZ Vaccine or NS as placebo. Allocation will be random and double blind. Repeat CHMI will
      be done with PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8), given in a randomized
      sequence. All immunizations are given by direct venous inoculation (DVI).

      Regimen verification phase V1: Shortest efficacious regimen (n = 12) against placebo (n = 6)
      V2: Maximum regimen (n = 12) against placebo (n = 6) P1: Placebo for V1 group (n=6) P2
      Placebo for V2 group (n=6)
    

Intervention name(s): PfSPZ Vaccine; PfSPZ Challenge (NF54); PfSPZ Challenge (7G8); Normal saline
Intervention type(s): Biological; Biological; Biological; Other
Intervention description(s): Aseptic, purified, vialed, cryopreserved, radiation-attenuated, Plasmodium falciparum sporozoites, strain NF54; Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain NF54; Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain 7G8; 0.9% sodium chloride
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); PfSPZ Challenge (7G8); CHMI