Dose and schedule optimization of PfSPZ Vaccine CHMI in malaria-naïve, healthy adult volunteers in Germany

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 the last vaccine injection. Dose optimization phase A: 9×10^5 PfSPZ on Days 0, 7 and 28 (n = 6) B1: 1.35×10^6 PfSPZ on Days 0 and 7 (n = 6) B2: 1.35×10^6 PfSPZ on Days 0, 7, and 28 (n = 6) C1: 2.7×10^6 PfSPZ on Day 0 (n = 6) C2: 2.7×10^6 PfSPZ on Day 0 and 7 (n = 6) C3: 2.7×10^6 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 findings) 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 the PfSPZ vaccine or NS as a 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)

Study type: Interventional
Enrollment: 45 participant
Primary purpose: Prevention
Allocation: Randomized
Interventional Model: Parallel assignment
Masking: Quadruple (Participant, Investigator, Care provider, Outcome assessor)
NCT number: NCT02704533
Phase: Phase I

Clinical trial registration

Vaccines

Aug 2016 — Dec 2018

Germany