A randomized, double-blind, placebo-controlled, single- and multiple-dose phase 1 study of VE202, a defined bacterial consortium for treatment of inflammatory bowel disease: safety and colonization dynamics of a novel live biotherapeutic product in healthy adults

OBJECTIVES: VE202 is an oral, defined 16-strain bacterial consortium with properties that may diminish dysbiosis and alleviate symptoms of inflammatory bowel disease. This phase 1 study evaluated VE202 safety and tolerability and assessed strain colonization. METHODS: Thirty-one healthy adults received oral vancomycin 125 mg four times daily for 5 days to decrease gut microbial burden, followed by a single dose of VE202 at 1 × 109 or 1 × 1010 colony-forming units (CFUs), or 14-days of the lower dose (1.4 × 1010 total CFU). Adverse events were monitored through week 12, with follow-up at week 24. Stool was collected for VE202 strain detection and abundance during screening and pretreatment, day 2, day 4, day 7, day 14, week 4, week 8, week 12, and optionally at week 24. RESULTS: VE202 and vancomycin pretreatment were well tolerated. Among VE202 recipients, the most frequent adverse events (>20% of subjects) were abdominal discomfort, diarrhea, headache, and fatigue. Most treatment-related adverse events were gastrointestinal. Two serious adverse events were reported; these were not treatment-related and occurred weeks after dosing completion. VE202 strain detection and relative abundance in the vancomycin-perturbed gut occurred as soon as day 2, sustained through 2 weeks postdosing, then declined slowly but remained substantially above baseline through week 24. Colonization was dose- and duration-dependent, with 14-day dosing providing more durable VE202 colonization. CONCLUSION: VE202 was well tolerated. Following antibiotic pretreatment, rapid and durable gut colonization of VE202 strains was observed, most significantly in participants administered multiple doses (NCT03931447).