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A phase 1b randomized double-blind placebo-controlled trial was conducted in ulcerative colitis patients to evaluate the safety and efficacy of an oral microbiome drug SER-287, and the effects of vancomycin preconditioning on expansion/engraftment of SER-287 species in the colon.
A phase 1b trial demonstrated that in patients with active mild-to-moderate ulcerative colitis, SER-287 (an oral formulation of Firmicutes spores) following vancomycin preconditioning induced clinical remission in a significantly higher proportion of patients in comparison to the placebo group.
Furthermore, the safety and tolerability of SER-287 were similar to placebo. Vancomycin preconditioning of the gastrointestinal microbiome and daily dosing of SER-287 facilitated the engraftment of SER-287 bacteria.
A
phase 1b randomized double-blind placebo-controlled trial was conducted
in ulcerative colitis patients to evaluate the safety and efficacy of an oral
microbiome drug SER-287, and the effects of vancomycin preconditioning on
expansion/engraftment of SER-287 species in the colon.
The study enrolled 58 adults with active mild-to-moderate ulcerative colitis (modified Mayo scores 4–10, endoscopic subscores ≥1). Participants were given six days of preconditioning with oral vancomycin (125 mg, 4 times daily) or placebo followed by eight weeks of oral SER-287 or placebo.
Ulcerative colitis patients were randomly allocated (2:3:3:3) to groups that received placebo followed by either placebo or SER-287 once weekly, or vancomycin followed by SER-287 once weekly or SER-287 once daily. Safety and changes in microbiome composition were the primary outcome parameters. Clinical remission, clinical response, and endoscopic improvement were the secondary outcome parameters.
The safety and clinical remission (modified Mayo score ≤ 2; endoscopic subscores 0 or 1) were included in the clinical endpoints. The SER-287 engraftment (dose species detected in stool after, but not before, SER-287 administration) was incorporated in the microbiome endpoints.
Engraftment of SER-287 and alterations in microbiome composition and associated metabolites were estimated by analyses of stool specimens collected at baseline, after preconditioning, and during and four weeks after administration of SER-287 or placebo.
A greater proportion of patients in the vancomycin/SER-287 daily group attained clinical remission at week eight in comparison with patients in the placebo/placebo group, placebo/SER-287 weekly group, and vancomycin/SER-287 weekly group, as depicted in the following table and figure:
PBO/PBO: Placebo/placebo group; PBO/SER Wkly:
Placebo/SER-287 weekly group; Vanco/SER Wkly: Vancomycin/SER-287 weekly
group; Vanco/SER Daily: Vancomycin/SER-287 daily group
Compared with the placebo group, elevated numbers of dose species were observed in stool samples from all SER-287 groups by day seven. However, in the placebo/SER-287 weekly group, this difference was not maintained beyond day 7. Compared with the placebo group, an elevated number of dose species were witnessed in the stool collected on day 10 and all subsequent time points, through four weeks post-dosing in the vancomycin groups.
A greater number of SER-287 dose species were witnessed in the stool samples on days 7 and 10 from subjects who received daily vs weekly SER-287 doses. Alterations in the fecal microbiome composition and metabolites were linked with both vancomycin/SER-287 groups. Among groups, the proportions of patients with adverse events did not considerably differ.
The data supports the beneficial impact of SER-287 on the gut microbiota and their associated metabolites through multiple physiological pathways, with pivotal implications for the management of ulcerative colitis.
For
the management of patients with ulcerative colitis, SER-287 depicts a novel
therapeutic paradigm with promising benefits with respect to the safety and
convenience of oral-dosing.
Gastroenterology
A Phase 1b safety study of SER-287, a spore-based microbiome therapeutic, for active mild to moderate ulcerative colitis
Matthew R. Henn et al.
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