3 Key Takeaways
Plain English Summary- 01Core Finding
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.
- 02Study Evidence
Tested in a randomized controlled trial (n = 15) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
What This Means for You
The key secondary efficacy (real-world effectiveness in the trial) endpoint revealed a significantly lower incidence of BSI with SER-155 versus placebo (a clinically meaningful level 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..
The Discovery
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 (inactive comparison treatment), 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.
How It Works, Simply
This infectious disease research focuses on gut bacteria. Researchers evaluated it using a randomized controlled trial (n = 15) at the randomized clinical trial stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
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.
- 02Study Evidence
Tested in a randomized controlled trial (n = 15) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (n = 15) · Randomized Clinical Trial
Biological Pathway & Modality
Gut bacteria
Intervention: A live biotherapeutic product for adult allogeneic hematopoietic cell
Experimental Findings & Endpoints
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.
Clinical Translation & Practice Context
The key secondary efficacy endpoint revealed a significantly lower incidence of BSI with SER-155 versus placebo (a clinically meaningful level 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..
The Bottom Line · Clinical Pearl
“The secondary pharmacodynamic endpoint of GI domination by Enterococcus and Enterobacteriaceae spp. was not achieved. .”
Published in Nature Medicine · Current Stage: Randomized Clinical Trial