Regimen optimization study of PfSPZ Vaccine in Equatoguinean Adults

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 9×10^5 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 9.0×10^5 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 9.0×10^5 PfPSZ and 5 subjects will receive a normal saline (NS) placebo on Days 1, 3, 5, 7, and 113.
Group 2: 21 subjects will receive 9.0×10^5 PfPSZ and 5 subjects will receive NS on Days 1, 3, 5, and 7.
Group 3: 21 subjects will receive 9.0×10^5 PfPSZ and 5 subjects will receive NS on Days 1, 3, 5, 7, and 29.
Group 4: 21 subjects will receive 9.0×10^5 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.

Study type: Interventional
Enrollment: 104 participant
Primary purpose: Prevention
Allocation: Randomized
Interventional Model: Parallel assignment
Masking:Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
NCT number: NCT03590340
Phase: Phase I

Clinical trial registration

Vaccines

Jul 2018 — Mar 2019

Equatorial Guinea

Genome-wide sieve analysis and immunological validation to identify targets of protective efficacy in field trials of a whole-organism malaria vaccine