Vedanta Biosciences initiates the Phase 3 RESTORATiVE303 clinical trial, marking a pivotal moment in the battle against this recurrent infection.
Vedanta Biosciences has initiated dosing for the Phase 3 RESTORATiVE303 clinical trial of VE303, a live biotherapeutic product aimed at preventing recurrent Clostridioides difficile infection (rCDI).
The primary objective of the RESTORATiVE303 study is to evaluate the safety and recurrence rate of CDI at Week 8 among participants who undergo a 14-day treatment with either VE303 or a matching placebo. This assessment remains consistent for both Stage 1 (rCDI) and Stage 2 (high-risk primary CDI).1
In the trial, participants assigned to the VE303 group will consume 3 capsules of VE303 daily for 14 days following the completion of standard antibiotic treatment lasting between 10 to 21 days for the qualifying CDI episode. Conversely, those in the placebo group will take 3 placebo capsules daily for the same duration after completing antibiotic treatment.
This international trial spans approximately 200 sites across 22 countries on 4 continents and employs a double-blind, randomised, placebo-controlled design.
Vedanta Biosciences Chief Medical Officer, Jeffrey Silber, highlighted the significance of the trial, stating, “Building on the successes of earlier VE303 clinical studies, RESTORATiVE303 is the first pivotal Phase 3 study of a live biotherapeutic product for prevention of recurrent CDI, a potentially serious infection affecting up to 175,000 patients and resulting in approximately 20,000 deaths annually in the US.”2
The dosing regimen and trial design are informed by insights from a preceding Phase 2 study, where VE303 demonstrated promise by meeting its primary endpoint of reducing CDI recurrence at 8 weeks. Furthermore, it exhibited a well-tolerated profile.
The phase 2 study was designed to determine dosing for Phase 3 trials, participants were divided into 3 groups, with 30 participants receiving a high dose of VE303 (8.0 × 109 colony-forming units [CFUs]), 27 receiving a low dose (1.6 × 109 CFUs) (n = 27), and 22 receiving a placebo once daily for 14 days. Investigators looked at CDI recurrence at 8 weeks based on combined clinical and laboratory assessment.3
CDI recurrence was reported among 13.8% of participants in the high-dose group, 37% in the low-dose group, and 45.5% in the placebo group. In the high-dose group, all recurrences occurred by Day 11.3
The Phase 3 RESTORATiVE303 clinical trial marks a major advancement in tackling rCDI. Vedanta Biosciences is leading a worldwide endeavor to assess VE303's effectiveness and safety. With backing from the Phase 2 trial, VE303 is positioned to mitigate rCDI's impact and improve patient outcomes globally. As the trial continues, the joint efforts of researchers and participants aim to enhance our grasp of this challenging infection, fostering hope for better patient care ahead.
