A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study of LMN-201 for Treatment and Prevention of C. difficile Infection
Abstract
Objectives and Rationale: C. difficile infection (CDI) causes inflammatory colitis that can lead to diarrhea, abdominal pain, fever, malaise, and death. Severe C. difficile colitis is associated with significant morbidity and mortality worldwide. Nearly half a million CDI cases occur annually in the United States. Treatment costs are estimated to exceed $5 billion annually in the U.S. alone. Still, the actual economic burden of the disease is far higher when quality-adjusted life years (QALYs) are measured. Standard of care (SOC) therapy with antibiotics against C. difficile is typically successful in treating initial cases of CDI. However, a challenging clinical problem in treating patients with CDI is the high incidence of recurrence. Approximately 25% of patients successfully treated with vancomycin or metronidazole suffer a recurrence after completing their initial antibiotic therapy. Subsequent recurrence rates are higher (35%-40%) in those treated for a first recurrence and may exceed 50% in those treated for a second or subsequent recurrence. LMN-201 consists of orally delivered whole, dried, non-viable biomass of spirulina (Arthrospira platensis) grown from separate strains that have been engineered to express four therapeutic proteins: *Three toxin-binding proteins that bind and inhibit C. difficile toxin B (TcdB), an essential virulence factor for CDI *One lysozyme-like enzyme that selectively degrades the cell wall of C. difficile and causes rapid destruction of the C. difficile organism Topic Area and Strategic Goal: This proposal addresses the FY22 PRMRP Topic Area of Plant-Based Vaccines and associated FY22 PRMRP Strategic Goal of Treatment by (1) utilizing a plant-based vaccine product comprised of four therapeutic proteins that work synergistically to neutralize both the Clostridioides difficile bacterium and the exotoxin that causes its virulence; (2) using Lumen s spirulina-based, ultra-low-cost drug development and cGMP manufacturing system, (3) with an oral formulation for simple and safe delivery; and (4) testing the biologic s ability to prevent and treat disease in patients recently diagnosed with CDI in a Phase 2/3 clinical trial. Impact: SOC antibiotics alone are ineffective at preventing recurrent disease. Repeated antibiotic exposure increases the risk of recurrence. LMN-201, once demonstrated in this study to be effective in CDI treatment and prevention, could help break this cycle of CDI recurrence. CDI s increasing toll on the U.S. health care system is mirrored in the U.S. military. Military patients hospitalized with CDI had significantly higher hospitalization costs, prolonged hospital stays, and in-hospital mortality. Among U.S. Veterans, postoperative CDI was associated with excessive postoperative morbidity, 30-day mortality, and longer postoperative stays. These findings highlight the urgent need for new approaches for treating and preventing CDI. This study of LMN-201 will accelerate development of this effective therapy available for military Service Members, Beneficiaries, and Civilians with CDI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310959
Entities
People
- Carl Mason
Organizations
- United States Army