Summary
A small phase 1b trial reported fewer bloodstream infections among donor stem-cell transplant recipients given SER-155 with vancomycin conditioning than among placebo recipients. The result is an early clinical signal from a small group, and the tested regimen combined both treatments.
A phase 1b trial in adults receiving donor stem-cell transplants reported fewer bloodstream infections in participants given SER-155 with vancomycin conditioning than in those given placebo. In the trial’s efficacy group, infections occurred in 2 of 20 participants in the SER-155 group and 6 of 14 in the placebo group between transplant day 0 and day 100. The report gives a P value of 0.0423, while its odds-ratio estimate was imprecise: 0.15, with a 95% confidence interval of 0.01–1.13, which includes no difference.
SER-155 is an investigational oral product containing 16 cultivated human-commensal bacterial strains. The study tested it as part of a regimen that included oral vancomycin before each treatment course, so the results apply to the combined regimen rather than isolating the effect of SER-155 alone.
What the trial tested
The study had an initial open-label cohort and a second, randomized, placebo-controlled cohort. In the latter, 45 participants were randomized; 34 received study treatment and proceeded to transplant, forming the efficacy group. Participants in the SER-155 group received four days of oral vancomycin, followed by ten days of daily oral SER-155. A second course was given after neutrophil engraftment. The placebo group received placebos in place of both vancomycin and SER-155. Participants also received antibacterial prophylaxis as part of transplant care.
The treatment is designed to alter the gut microbiome. Transplant conditioning and antibiotics can disrupt gut bacteria and damage the intestinal barrier. Researchers reasoned that restoring some microbial functions could help limit harmful bacteria and reduce the chance of microbes reaching the bloodstream.
The trial’s primary clinical focus was safety; bloodstream infection was a key secondary efficacy outcome. In addition to the difference in infection rates, the study detected all 16 SER-155 strains in at least one treated participant. After the first course, a median of 11.5 strains were detected per participant. Exploratory analyses found changes in microbiome composition and lower stool albumin after the first course; stool albumin was used as a marker of intestinal barrier damage.
Safety and how to read the result
The researchers reported that SER-155 was generally well tolerated, with a safety profile comparable to placebo. There were no treatment-related serious adverse events and no infections with SER-155 bacterial species identified in clinical samples. Diarrhea and nausea were among the more common adverse events in the SER-155 group. Across both cohorts, investigators did not attribute any of the eight deaths during the study to SER-155.
The infection finding is promising but preliminary: it rests on eight events in a small efficacy group, and the reported odds-ratio confidence interval is wide. Use of post-transplant cyclophosphamide, a regimen for preventing graft-versus-host disease, was also more common in the placebo group than in the SER-155 group. A post hoc analysis adjusted for this difference and still found an association between SER-155 treatment and lower infection incidence, but a larger randomized trial is needed to assess the result more securely.
Other secondary outcomes—including gastrointestinal infections, acute graft-versus-host disease of grade 2 or higher, febrile neutropenia and a composite of these outcomes—did not differ significantly between groups. The study also did not meet its secondary endpoint for reducing gut domination by certain bacterial families. Further trials will need to establish whether the lower bloodstream-infection rate is reproducible and how much of any effect comes from the bacterial product versus the vancomycin conditioning regimen.