Age De-escalation Safety Trial of PfSPZ-LARC2 Vaccine in Burkina Faso

Summary

This is a first-in-humans randomized, double-blind, placebo-controlled, age de-escalation Phase 1 trial of Plasmodium falciparum (Pf) late liver stage-arresting replication-competent (LARC) sporozoite (SPZ) malaria vaccine (Sanaria® PfSPZ-LARC2 Vaccine) administered to healthy, malaria-exposed adults and children by direct venous inoculation (DVI) to determine safety, tolerability, and immunogenicity. The PfSPZ comprising PfSPZ-LARC2 Vaccine contain a double gene deletion, of the Mei2 and LINUP genes. As a result, they 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). 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). Because the parasites are intrinsically attenuated, they are also expected to be safe and well tolerated, similar to radiation-attenuated Sanaria® PfSPZ Vaccine and to the single-gene(Mei2)-deleted GA2 parasites (also LARC phenotype) tested at the Leiden University Medical Center (LUMC), which, like PfSPZ-LARC2 Vaccine, disintegrate after replicating in the liver. PfSPZ-LARC2 Vaccine thus avoids the safety concerns associated with PfSPZ-CVac, which uses fully infectious, non-attenuated parasites to achieve replication and depends on co-administered chloroquine for attenuation. In summary, the genetically attenuated PfSPZ-LARC2 Vaccine should combine the best-in-class immunogenic potency and protective efficacy of PfSPZ-CVac (chloroquine) with the excellent safety and tolerability of intrinsically attenuated PfSPZ Vaccine and GA2 vaccine.

This trial is designed to test the hypotheses that:

1. The vaccine is safe and well tolerated in each age group.
2. The true rate of breakthrough blood stage infection (or other concerning adverse events) is less than about 5%, with an 95% confidence level (this will be the level of confidence that there are no breakthroughs if no breakthroughs occur in the 50 participants receiving PfSPZ-LARC2 Vaccine).

Conditions

• Malaria Falciparum
• Malaria Infection

Interventions

BIOLOGICAL

PfSPZ-LARC2 Vaccine

The PfSPZ comprising PfSPZ-LARC2 Vaccine contain a double genetic deletion, of the Mei2 and LINUP genes, and undergo developmental arrest in the late liver stages without releasing merozoites into the blood stream (no blood stage parasites are produced)

BIOLOGICAL

Normal Saline (Placebo)

Normal Saline Placebo

Sponsors & Collaborators

• University of Maryland, Baltimore

  collaborator OTHER

• Groupe de Recherche Action en Sante

  collaborator OTHER

• Seattle Children's Hospital

  collaborator OTHER

• Sanaria Inc.

  lead INDUSTRY

Principal Investigators

• Thomas L Dr. Thomas L. Richie, MD PhD · Sanaria Inc.

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

SEQUENTIAL

Eligibility

Min Age

1 Year

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-03-04

Primary Completion

2026-02-18

Completion

2026-02-18

FDA Drug

Yes

Countries

• Burkina Faso

Study Locations