Safety, immunogenicity and efficacy of PfSPZ vaccine in HIV negative and HIV positive Tanzanian adults

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 4.5×10^5 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 a 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. The 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, the transition to the main HIV positive group (Group 2b) will take into account the SMC recommendation(s).

Study type: Interventional
Enrollment: 21 participants
Primary purpose: Prevention
Allocation:Randomized
Interventional Model: Parallel assignment
Masking : Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
NCT number: NCT03420053
Phase: Phase I

Clinical trial registration

Vaccines (Immune Correlates)

Feb 2018 — Aug 2018

Tanzania

Development of non-human primate models to assess immunological mechanisms and antigenic targets of protective sporozoite (SPZ) vaccines and establish superior efficacy of next generation SPZ vaccines