Valneva SE and LimmaTech Biologics AG announced the first vaccination in a Phase 2b controlled human infection model (CHIM) study of Shigella4V2 (S4V2), a tetravalent bioconjugate shigellosis vaccine candidate. Valneva holds an exclusive worldwide license for S4V2 from LimmaTech. The study aims to assess the safety and preliminary efficacy of S4V2 against Shigella infection.
Study Design and Objectives
The Phase 2b CHIM study (NCT06615375) will enroll approximately 120 healthy, Shigella-naïve participants aged 18 to 50 years across three sites in the United States. The study employs a parallel-group, randomized, double-blind, multicenter, placebo-controlled design. It involves two stages: dose confirmation and challenge with the Shigella sonnei strain 53G one month post-vaccination. The primary objective is to compare the infection rate of shigellosis in the S4V2-vaccinated group versus the placebo group, thus evaluating S4V2's protective capability.
Management Perspectives
Thomas Lingelbach, CEO of Valneva, emphasized the value of human challenge studies in understanding disease onset and development within a controlled setting. He stated that this CHIM study is a part of their risk-mitigating development strategy for S4V2, aiming to provide initial efficacy results before advancing to further CHIM and Phase 3 studies.
Dr. Patricia Martin, COO of LimmaTech, highlighted the trial's significance for the S4V2 program and their collaboration with Valneva to deliver an effective shigellosis vaccine. She noted that this marks a crucial step toward LimmaTech's goal of developing vaccines against serious diseases and antimicrobial-resistant pathogens.
Additional Clinical Development
In addition to the CHIM study, LimmaTech plans to initiate a Phase 2 pediatric study in Low- and Middle-Income Countries before the end of 2024. Valneva will then take over further development, including CMC (chemistry, manufacturing and controls) and regulatory activities, and will manage worldwide commercialization upon approval.
Regulatory Status and Disease Burden
S4V2 was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) last month, acknowledging its potential to address a serious condition and an unmet medical need. Shigellosis is a major global health concern, ranking as the second leading cause of fatal diarrheal disease worldwide. There is currently no approved Shigella vaccine available, and the WHO has identified Shigella vaccine development as a priority.
Shigellosis, caused by Shigella bacteria, results in an estimated 165 million infections annually, with 62.3 million cases occurring in children under five years. The disease contributes to approximately 600,000 deaths each year. While treatment involves oral rehydration and antibiotics, increasing antibiotic resistance poses a significant challenge. The absence of a licensed Shigella vaccine underscores the urgency for new preventive measures.
