NCT05913973

Study of the Plasmodium Vivax Transmission-blocking Vaccine Pvs230D1-EPA/Matrix-M to Assess Safety, Immunogenicity, and Transmission-blocking Activity in Healthy Malaria-naive Adults

Phase 1 Dose Escalation Study of The Plasmodium Vivax Transmission-Blocking Vaccine Pvs230D1-EPA/Matrix-M to Assess Safety, Immunogenicity, and Transmission-Blocking Activity in Healthy Malaria-Naive Adults

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 105 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Not accepted

Summary

Background: Malaria is a disease carried by mosquitoes in tropical countries around the world. It can cause symptoms like fever, body aches, and weakness. More than half a million people worldwide died of malaria in 2021, mostly children. Researchers want to find ways to prevent the spread of this disease. Objective: To test the effects of a new malaria vaccine. (Volunteers will not be exposed to malaria.) Eligibility: Healthy adults aged 18 to 50 years. Design: Volunteers will be screened. They will have a physical exam with blood and urine tests. They will take a short quiz to make sure they understand the study. Volunteers will have 3 visits to receive the vaccine. These visits will be about 1 month apart. The vaccine will be injected into the muscle of the upper arm. Volunteers will have 12 additional clinic visits. These will start after the first vaccine visit and continue for 8 months. The visits may include a physical exam and blood tests. There will also be 7 follow-up phone calls. These will occur the day after each vaccine visit and then continue for another 12 months. Participants will be asked how they are doing and whether they have had any changes in their health. ...

Detailed description

Study Description: Single-center, open-label, first-in-human, dose-escalating phase 1 study to characterize the safety, immunogenicity, and transmission-blocking activity in healthy malaria-naive adults of the Plasmodium vivax (P. vivax) transmission-blocking vaccine (TBV), Pvs230D1-EPA combined with adjuvant Matrix-M (MM). Three doses of vaccine will be administered at 1-month intervals (study days 0, 28, and 56). Subjects will be divided into low, intermediate, and high dose groups based on the amount of the antigen component in each vaccine dose: * Group 1 (n = 10): 5 (micro)g Pvs230D1-EPA/50 (micro)g MM * Group 2 (n = 10): 25 (micro)g Pvs230D1-EPA/50 (micro)g MM * Group 3 (n = 10): 50 (micro)g Pvs230D1-EPA/50 (micro)g MM Objectives: Primary Objective -To assess the safety and reactogenicity of Pvs230D1-EPA/MM in healthy malaria-naive adults Exploratory Objectives * To determine the antibody response to Pvs230D1-EPA/MM * To determine the functional response to Pvs230D1-EPA/MM by mosquito feeding assays * To assess cellular and transcriptomic responses to Pvs230D1-EPA/MM * To identify and characterize human monoclonal antibodies (mAbs) with activity against Pvs230D1M Endpoints: Primary Endpoint -Incidence and severity of local and systemic adverse events (AEs) or serious adverse events (SAEs) Exploratory Endpoints * Anti-Pvs230D1M antibody levels as measured by enzyme-linked immunosorbent assay (ELISA) * Transmission-reducing activity (TRA) and/or transmission-blocking activity (TBA) of Pvs230D1-EPA/MM using direct membrane feeding assays (DMFA) * Cellular immune responses and whole genome transcriptional profiles * Isolation of reactive antibodies from sorted B cells

Conditions

• Malaria

Interventions

Type	Name	Description
DRUG	Pvs230D1-EPA/Matrix-M	Pvs230 domain 1 (Pvs230D1) is a recombinant protein consisting of subdomain 1 of native Pvs230 (Val-226 to Gly-427, Figure 2) produced in Pichia pastoris. The synthetic gene sequence was optimized for P. pastoris expression and cloned into the expression vector pPICZ(alpha)A, which also encodes a pre-prosecretory alpha-factor sequence.

Timeline

• Start date: 2023-08-04
• Primary completion: 2025-11-12
• Completion: 2025-11-12
• First posted: 2023-06-22
• Last updated: 2025-12-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study