Randomised clinical trial: efficacy and safety of the live biotherapeutic product MRx1234 in patients with irritable bowel syndrome

Background: MRx1234 is a live biotherapeutic product that contains a strain of Blautia hydrogenotrophica. It is in development for the treatment of irritable bowel syndrome (IBS). Aims: To assess the efficacy and safety of MRx1234 in patients with IBS with predominant constipation (IBS-C) or diarrhoea (IBS-D). Methods: We conducted a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Patients aged 18–70 years in two parallel cohorts (IBS-C; IBS-D) were randomised (1:1) to MRx1234 or placebo for 8 weeks. The primary efficacy endpoint was overall responder rate—a composite of improved bowel habit (IBS-C: stool frequency; IBS-D: stool consistency) and abdominal pain intensity—for ≥50% of the treatment period in each cohort. Statistical testing was at a one-sided 0.10 significance level. Results: Of 366 randomised patients (164 IBS-C; 202 IBS-D), 365 received any study medication (177 MRx1234, 188 placebo). Numerically, although not statistically significantly different, more patients who received MRx1234 than placebo were overall responders in the IBS-C (25.0% vs. 17.1%) and IBS-D (23.4% vs. 17.8%) cohorts. Similar results were observed in the additional combined cohort analysis (24.1% vs. 17.5%; p = 0.063). For the components of the primary endpoint, significantly more patients on MRx1234 than placebo reported improvement in bowel habit in the IBS-C, IBS-D and combined cohorts, while improvements in abdominal pain were observed in each cohort. The safety profile of MRx1234 was similar to placebo. Conclusions: MRx1234 has the potential to become a novel, safe treatment option for patients with IBS-C or IBS-D, and for those who have mixed symptoms or transition between subtypes. ClinicalTrials.gov #NCT03721107.