Safety and Efficacy Results from a Randomized, Double-Blind, Placebo-Controlled Cohort 2 of a Phase 1b Study of an Investigational Live Biotherapeutic, SER-155, in Adults Undergoing Allo-HCT
Rattachement africain : us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Background Bloodstream infections (BSI) are common in patients undergoing allo-HCT and often arise following pathogen domination of the intestinal microbiome in the setting of GI-barrier dysfunction. SER-155 is an investigational, oral live biotherapeutic comprised of 16 bacterial strains, designed to prevent BSI and infection-associated events. SER-155-001 (NCT04995653) was a 2-cohort Phase 1b study evaluating the safety, PK, and efficacy of SER-155 in adults undergoing allo-HCT. We present data from the randomized, double-blind, placebo-controlled Cohort 2 through day 100 post-HCT. Study Design and Methods Patients were randomized 1:1 to receive oral vancomycin/SER-155 or placebo/placebo, administered in 2 courses pre-HCT and post-neutrophil engraftment ( Fig. 1 ). The primary endpoints were safety and SER-155 strain engraftment (PK). Secondary efficacy endpoints included incidence of BSI, febrile neutropenia (FN), and aGvHD (MAGIC criteria). Exploratory endpoints included antibiotic and hospital utilization. Results Thirty-four patients (SER-155 = 20; placebo = 14) were treated and received allo-HCT (modified intention to treat [mITT-1] population) (Fig. 2 ). Demographics and transplant characteristics were mostly balanced between arms. The majority of SER-155 strains engrafted after each course. As expected for the HCT population, 98% of patients had at least 1 treatment-emergent adverse event (TEAE). Serious TEAEs were reported in 52% of patients in the SER-155 arm and 42% in the placebo arm; the most common system organ class was infections and infestations (SER-155 = 24%; placebo = 37%). No drug-related serious TEAEs were observed and no SER-155 species were identified in any clinical culture specimens. Three patients (SER-155 = 1; placebo = 2) died prior to Day 100; 1 patient (SER-155 arm) died after Day 100; none were deemed drug-related. Incidence of BSI was lower in SER-155 vs placebo-treated patients (10% vs 42.9%, respectively; [OR: 0.15; 95% CI: 0.01, 1.13, p=0.04); all occurred after HCT and pre-neutrophil engraftment. There was a significant difference between arms for Kaplan-Meier estimates of time to BSI ( Fig. 3 ). Systemic treatment antibiotic utilization was lower in SER-155 vs placebo (9.2 vs 21.1 days, respectively; mean difference -11.9 days [95% CI: -23.85, -0.04; p=0.05]). Mean days in hospital were lower in SER-155 vs placebo (19.7 vs 28.7 days; p=0.05 [ post hoc test]). Incidence of FN was numerically lower in SER-155 vs placebo (65% vs 78.6%, respectively; [OR: 0.51; 95% CI: 0.07, 2.99; p=0.47). There were 2 events of aGvHD Grade 2 observed in each arm and no aGvHD ≥ Grade 3 events. Conclusions SER-155 was generally well-tolerated, and most SER-155 strains engrafted in the GI tract. The lower incidence of BSI, fewer days in hospital, and less antibiotic utilization in SER-155 treated patients are encouraging and support further development in allo-HCT.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Safety and Efficacy Results from a Randomized, Double-Blind, Placebo-Controlled Cohort 2 of a Phase 1b Study of an Investigational 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
-
Memorial Sloan Kettering Cancer Center pays non établi dans la noticeÉtablissement de santé
-
University of Chicago Hematology/Oncology pays non établi dans la noticeUniversité ou école supérieure
-
WinnMed pays non établi dans la noticeOrganisation à but non lucratif
-
Mayo Clinic in Florida Department of Hematology/Oncology pays non établi dans la noticeÉtablissement de santé
-
Jacksonville College pays non établi dans la noticeUniversité ou école supérieure
-
Infectious Disease Research Institute pays non établi dans la noticeOrganisation à but non lucratif
-
Fred Hutch Cancer Center pays non établi dans la noticeOrganisation à but non lucratif
-
Cancer Research Center Vaccine and Infectious Disease Division pays non établi dans la noticeOrganisation à but non lucratif
-
City Of Hope National Medical Center pays non établi dans la noticeÉtablissement de santé
-
The University of Texas MD Anderson Cancer Center pays non établi dans la noticeÉtablissement de santé
-
Banner MD Anderson Cancer Center pays non établi dans la noticeÉtablissement de santé
-
University of Florida 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.