Methods: rCDIsubjects were randomized to receive blinded treatments of 2 doses of RBX2660 (Group A), 2 doses of placebo (Group B), or 1 dose each of RBX2660 & placebo (Group C), by enema 7 days apart. Subjects submitted stool samples at baseline, day 7, 30, & 60 after treatment. Stool samples from responders to RBX2660 treatment per protocol defined as the absence of CDI for 8 weeks after treatment were compared to non-responders.
Relative taxonomic abundances at the class level were determined using 16s rRNA sequencing analysis for 94 stool samples from 45 patients in Groups A & C. Relative abundance data were grouped longitudinally using Bray-Curtis dissimilarity index. Analyses were performed based on the Dirichlet-Multinomial distribution to compare group mean relative taxonomic abundances; Simpson & Shannon diversity indices were compared among groups longitudinally.
Results: Baseline patient microbiomes were similar across response groups. RBX2660 treatment shifted the relative microbiome densities with taxa-specific increase in Bacteroidia, Clostridia, and decrease in Gamma-proteobacteria abundance. A larger shift from baseline microbiome was seen in responders to RBX2600 compared to non-responders (Figure 1). Microbiome changes in responders were durable to 60 days. RBX2660 treatment increased Shannon and Simpson diversity at 7 days post-treatment in responders but not in non-responders (p<0.05).
Conclusion: RBX2660 treatment shifts patient intestinal microbiomes with greater alterations seen in those with a successful clinical outcome.
Funded by Rebiotix Inc., Roseville, MN.
Figure 1. Responders to RBX2660 have a greater change in taxa abundance from baseline relative to non-responders at 30 days. Dirichlet-Multinomial parameter pi presented as mean (95%CI).
C. Jones, Rebiotix, Inc.: Employee , Salary
B. Shannon, Rebiotix, Inc.: Research Contractor , Consulting fee
S. Carter, Rebiotix, Inc.: Research Contractor , Consulting fee