A live biotherapeutic product for adult allogeneic hematopoietic cell transplantation recipients: a partially randomized, placebo-controlled phase 1b trial.

November 3, 2026| Source: Nature medicine

Gastrointestinal (GI) microbiome disruption and impaired GI barrier integrity increase the risk of bloodstream infection (BSI) following allogeneic hematopoietic cell transplant. Here we report results from a two-cohort (open-label, n = 15; randomized, placebo-controlled, n = 45) phase 1b study of SER-155, an investigational, cultivated, multi-strain, oral live biotherapeutic designed to address GI microbiome disruption GI epithelial barrier integrity in allogeneic hematopoietic cell transplant recipients. In cohort 2, 34 of 45 participants received either SER-155 treatment (n = 20, SER-155 following microbiome conditioning with oral vancomycin), or placebo (n = 14), and subsequently received transplant. For the primary safety endpoint, SER-155 was well tolerated, with a safety profile comparable to placebo, no treatment-related serious adverse events and no infections with SER-155 species; the most common adverse events were diarrhea and nausea. Four participants in cohort 1 and four participants in cohort 2 (two participants in the SER-155 arm and two in the placebo arm) died during the study; none was attributable to SER-155. For the primary pharmacokinetic endpoint, engraftment was detected for 16 of 16 SER-155 strains, with a median of 11.5 strains detected after the first treatment course. The key secondary efficacy endpoint revealed a significantly lower incidence of BSI with SER-155 versus placebo (10.0% versus 43%; OR 0.15; 95% CI 0.01-1.13; P = 0.0423; 77% relative risk reduction). Other secondary efficacy endpoints (GI infection, acute graft-versus-host disease ≥grade 2, febrile neutropenia and a composite endpoint of BSI, GI infection or acute graft-versus-host disease) were not statistically significant. The secondary pharmacodynamic endpoint of GI domination by Enterococcus and Enterobacteriaceae spp. was not achieved. ClinicalTrials.gov identifier: NCT04995653 .

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