Field Trial of PfSPZ-LARC2 Vaccine in Burkinabe Adults

Summary

This is a phase 2 clinical trial of a Plasmodium falciparum (Pf) late liver stage-arresting replication-competent (LARC) sporozoite (SPZ) vaccine (Sanaria® PfSPZ-LARC2 Vaccine) that will assess field efficacy in Africa.

The PfSPZ comprising PfSPZ-LARC2 Vaccine contain a double deletion of the genes encoding the Mei2 and LINUP proteins, both of which are required for transition from liver to blood stage malaria. As a result, mei2-/linup- parasites undergo developmental arrest in the late liver stages without releasing merozoites into the blood stream. No blood stage parasites are produced, either asexual or sexual, and the parasite life cycle does not progress. Because Pf parasites with the LARC phenotype replicate in the liver before disintegrating, they amplify and diversify parasite protein expression and are expected to be a potent immunogen to induce anti-malarial immunity, equaling or exceeding the potency and efficacy of the replication-competent chemo-attenuated Sanaria® PfSPZ-CVac (chloroquine) vaccine approach. Because the parasites are intrinsically attenuated, they are expected to be safe and well tolerated, similar to radiation-attenuated Sanaria® PfSPZ Vaccine, to the replication deficient, early arresting PfSPZ-GA1 Vaccine, and to the single-gene(mei2)-deleted GA2 (LARC1) parasites tested at the Leiden University Medical Center that provided 90% protection against CHMI after a single dose.

The active treatments to be assessed for efficacy are one immunization of 6.0x10\^5 PfSPZ or two immunizations with 4.0x10\^5 PfSPZ of PfSPZ-LARC2 Vaccine four weeks apart, timed so that the immunization of the one dose regimen coincides with the second immunization of the two dose regimen.

The alternative treatment is immunization with normal saline (placebo group), which is indistinguishable from the test article.

The primary variable of interest is whether and when trial participants develop Pf malaria parasitemia during surveillance. Malaria parasitemia will be detected by thick blood smear (TBS), which will be performed every two weeks starting two weeks after the second vaccination (to allow time for the vaccine to work) and extending to week 26 after the second vaccination (24-week surveillance period). Surveillance will continue for 40 weeks but the primary outcome will be determined at 24 weeks of surveillance so the data are comparable to other studies of PfSPZ vaccines.

Conditions

• Malaria (Plasmodium Falciparum)

Interventions

BIOLOGICAL

Genetically attenuated PfSPZ Vaccine

PfSPZ-LARC2 Vaccine is composed of aseptic, purified, vialed, cryopreserved, genetically altered PfNF54 sporozoites (SPZ).

OTHER

Normal Saline (0.9% Sodium Chloride)

The placebo control is normal saline solution (0.9% sodium chloride) and is also administered by DVI.

Sponsors & Collaborators

• University of Maryland, Baltimore

  collaborator OTHER

• Seattle Children's Hospital

  collaborator OTHER

• University of California, Los Angeles

  collaborator OTHER

• Fred Hutchinson Cancer Center

  collaborator OTHER

• Sanaria Inc.

  lead INDUSTRY

Principal Investigators

• Sodiomon B Sirima, MD PhD · Groupe de Recherche Action en Sante

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-04-04

Primary Completion

2026-12-31

Completion

2027-02-28

FDA Drug

Yes