Sahil Khanna MBBS, Dale Gerding MD, Ken Blount PhD, Courtney Jones BS, Bill Shannon PhD MBA, Sharina Carter PhD
- Recurrent Clostridium difficile infections (rCDI) are strongly associated with intestinal dysbiosis.
- RBX2660 is a standardized microbiota-based drug designed to prevent rCDI by potentially restoring a healthier intestinal microbiome.
- The effect of RBX2660 on rCDI patient microbiomes was evaluated by comparing pre- and post-treatment samples collected from a Phase 2 controlled open-label study of RBX2660 to a healthy intestinal microbiome, as defined by the Human Microbiome Project (HMP).
- Prospective, multicenter, controlled open-label Phase 2 study (NCT02589847) consisting of an RBX2660 treatment arm and a historical control group.
- Antibiotics were discontinued 24-48 hours prior to administration of the first enema.
- Participants received up to 2 doses of RBX2660 delivered via enema with doses 7 + 2 days apart.
- Success was defined as the absence of CDI at 8 weeks following completion of the last treatment.
- Patients were classified as a treatment failure if all four (4) of the following criteria were met: recurrence of diarrhea less than 8 weeks after administration of the last assigned study enema, a positive laboratory diagnosis of C. diff icile as conducted and reported by the study investigator, a need for retreatment for CDI, and no other cause for diarrhea.
- Clinical efficcy results have been previously presented (Figure 1).
- Patients in the RBX2660 treatment arm were asked to voluntarily submit stool samples at baseline (pre-treatment) and at multiple time points up to 12 months after treatment.
- Longitudinal sample sets (baseline, 7, and 30 days after treatment) were collected from 17 successful patients (n=45 samples) and 17 failed patients (n=34 samples).
- Stool samples were sequenced using BoosterShot (CoreBiome, Minneapolis, MN), an ultra-shallow shotgun sequencing that generates taxonomic profiles with species-level resolution.
- Relative abundance data from successful patient samples were grouped longitudinally and compared using a Bray-Curtis dissimilarity calculation with non-metric multi-dimensional scaling. Additional analyses were performed based on the Dirichlet-Multinomial distribution to compare group mean relative taxonomic abundances(pi) and within group over dispersion (theta).
- Differentiation between sample communities was visualized using a Kullback-Leibler(KL) divergence analysis model (BioRankings, St. Louis, MO), a measure of the difference between microbial diversity at different time points or between different samples.
- See poster (PDF 426 KB)
- RBX2660 restores a healthier microbiome profile among patients who responded to open-label RBX2660 treatment.
- Patient microbiota trended toward increased diversity relative to baseline following RBX2660 treatment.