FMT capsules (MBK-01) compared to fidaxomicin for the treatment of primary and recurrent Clostridioides difficile infection

Objectives: Clostridioides difficile infection (ICD) is a major cause of nosocomial diarrhea, with high recurrence rates following standard antibiotic treatments. Fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI (rCDI), though its efficacy in primary CDI remains under investigation. This study evaluates the safety and efficacy of MBK-01, a novel oral FMT capsule, compared to fidaxomicin, the current standard of care, in both primary and rCDI. Methods : In this randomized, open-label, multicenter phase III trial, patients with primary or rCDI were randomized to receive MBK01 (with or without a short period of prior antibiotic treatment) or fidaxomicin (200 mg/12h for 10 days). The primary endpoint was absence of recurrence at 8 weeks post-treatment. Secondary endpoints included time to recurrence and adverse events at 6 months. The study is registered with ClinicalTrials.gov (NCT05201079). Results : 92 patients with CDI (45 in the MBK-01 group and 47 in the fidaxomicin group) were enrolled across 21 centers in Spain. MBK-01 demonstrated non-inferiority to fidaxomicin, with recurrence rate differences of 11.69% in the overall population (p=0.013), -1.06% in primary CDI cases (p=0.013), 42.79% in recurrent episodes (p=0.003), and 20% in participants without prior antibiotic treatment (p=0.008). Additionally, in rCDI, MBK-01 showed superiority compared to fidaxomicin (p=0.014). Notably, MBK-01 achieved 100% effectiveness in participants without antibiotic pre-treatment, versus 80% for fidaxomicin. The median time to recurrence in the overall population was similar. MBK-01 was associated with fewer treatment-related adverse events. Conclusions : MBK-01 represents a safe, effective, and less antibiotic-dependent option for CDI, particularly in recurrent cases. Its efficacy in primary CDI and favorable safety profile suggests that MBK-01 could serve as first-line therapy, potentially reducing antibiotic reliance and improving outcomes. These findings support broader use of microbiota-based therapies in the management of CDI. Clinical trial number: NCT05201079