Pharmacokinetic (PK) and Pharmacodynamic (PD) Results from a Randomized, Double-Blind, Placebo-Controlled Cohort 2 of a Phase 1b Study of an Investigational, Oral, Live Biotherapeutic, SER-155, in Adults Undergoing Allo-HCT
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Le résumé fourni par la source
SER-155 is an investigational, live oral biotherapeutic comprised of 16 bacterial strains, designed to prevent bloodstream infections and infection-associated events by engrafting in the gastrointestinal (GI) tract, restructuring the microbiome to reduce pathogen abundance, reducing epithelial barrier damage, and modulating inflammatory responses. SER-155-001 (NCT04995653) evaluated safety, PK and efficacy of SER-155 in adults undergoing allo-HCT. We present PK and PD data from the placebo-controlled Cohort 2. Patients were randomized 1:1 to receive vancomycin/SER-155 or placebo/placebo administered pre-HCT and post-neutrophil engraftment ( Fig. 1 ). Primary endpoints were safety and SER-155 strain engraftment (PK, via molecular probes). PD endpoints included prevalence of GI domination by Enterobacteriaceae , Enterococcaceae , Streptococcaceae and Staphylococcaceae (via WMS), and concentrations of plasma biomarkers. Demographics were balanced between treatment arms. Of 45 patients randomized, 34 (SER-155, 20; placebo, 14) were treated and received allo-HCT; 28 received treatment course 2 after neutrophil engraftment (SER-155, 19; placebo, 9). SER-155 was generally well tolerated: serious TEAEs were similar between arms (SER-155, 52%; placebo, 42%) with no drug-related serious TEAEs observed. SER-155 strain engraftment was observed in the peri-transplant period with a median of 11.5, 7, and 4 strains detected after 1st course, at HCT Day 0, and after neutrophil engraftment, respectively ( Fig. 2 ). A median of 11 strains were observed after the 2nd course and at HCT Day 100. The relative abundance of SER-155 species (via WMS) was significantly higher than baseline at those 3 peri-transplant period time points in post hoc analysis (p < 0.012; median 5% vs. 16%, 14%, 11%, respectively). Prevalence of domination by pathogenic families (³ 30% relative abundance) was low and not significantly different between arms, but comparison was constrained by greater placebo arm subject discontinuation and sample missingness. In a post hoc analysis, domination in the SER-155 arm was substantially lower than in a historical comparator cohort from MSKCC ( Fig. 3) . In a combined analysis of Cohort 2 and open-label Cohort 1, significant differences and trends in markers of inflammation and immunotolerance were observed relative to placebo, including that at the post course 1 timepoint IL10, IL17, and TNFα concentrations were lower in SER-155 vs placebo with reductions of 46% (p=0.01), 63% (p=0.02), and 10% (p=0.06), respectively. SER-155 engraftment was robust with a majority of strains detected after the 1st and 2nd courses, and SER-155 species represented >10% of the GI microbiome during the peri-transplant period. These PK and PD data are consistent with the SER-155 design targets and support further development in allo-HCT.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Pharmacokinetic (PK) and Pharmacodynamic (PD) Results from a Randomized, Double-Blind, Placebo-Controlled Cohort 2 of a Phase 1b Study of an Investigational, Oral, Live Biotherapeutic, SER-155, in Adults Undergoing Allo-HCT
- Date Crossref
- 01/02/2025
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Memorial Sloan Kettering Cancer Center pays non établi dans la noticeÉtablissement de santé
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University of Chicago Hematology/Oncology pays non établi dans la noticeUniversité ou école supérieure
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WinnMed pays non établi dans la noticeOrganisation à but non lucratif
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Mayo Clinic in Florida Department of Hematology/Oncology pays non établi dans la noticeÉtablissement de santé
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Jacksonville College pays non établi dans la noticeUniversité ou école supérieure
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Infectious Disease Research Institute pays non établi dans la noticeOrganisation à but non lucratif
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Fred Hutch Cancer Center pays non établi dans la noticeOrganisation à but non lucratif
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Cancer Research Center Vaccine and Infectious Disease Division pays non établi dans la noticeOrganisation à but non lucratif
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City Of Hope National Medical Center pays non établi dans la noticeÉtablissement de santé
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University of Florida pays non établi dans la noticeUniversité ou école supérieure
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Mayo Clinic in Arizona pays non établi dans la noticeÉtablissement de santé
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University of California Division of Hematology-Oncology pays non établi dans la noticeUniversité ou école supérieure
Memorial Sloan Kettering Cancer Center, Hematology/Oncology — University of Chicago et WinnMed, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.