Courtney Jones BS, Ken Blount PhD, Tonya Ward PhD, Elena Deych MS, Bill Shannon PhD, MBA
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ASM Microbe 2019
June 20-24, 2019, San Francisco, CA
Background
- RBX2660, a standardized, stabilized microbiota restoration drug has been shown to prevent recurrent Clostridiodies difficile infections (rCDI).
- A preliminary analysis demonstrated decolonization of multidrug-resistant organisms (MDRO) in association with clinical response.
- In parallel, we are developing a MICROBIOME HEALTH INDEX™ (MHI™) to monitor dysbiosis and microbiome restoration.
- Given the public health challenges related with MDROs, we evaluated MHI as a potential sentinel of MDRO colonization among rCDI patients who responded to RBX2660 in a Phase 2 clinical trial.
Methods
- The PUNCH CD2 Phase 2 trial (NCT02299570) compared RBX2660, a microbiota-based investigational drug for treatment of rCDI, to placebo.
- 127 participants were enrolled, randomized, and treated in three cohorts: Group A: two doses of RBX2660; Group B, two placebo doses; Group C, one dose of RBX2660 and one dose of placebo.
- Samples were collected prior to treatment (BL) and 7, 30 & 60 days after treatment.
- This analysis is based on samples from 55 patients who responded to RBX2660 treatment in Groups A and B (pooled) and dosed RBX2660 product samples.
- Stool samples were sequenced using BoosterShot (CoreBiome, Minneapolis, MN), an ultra-shallow shotgun sequencing method.
- MICROBIOME HEALTH INDEX™ (MHI™) values were calculated based on relative abundances at the class level for selected classes.
- Prior receiver operator characteristic analyses defined an MHI cut-point of 8.2 for distinguishing rCDI subjects prior to treatment from the representative microbiome composition of RBX2660.
- Relative abundance of antimicrobial resistance (AMR) genes and enzymes were determined for all samples based on a threshold of ≥ 90% coverage when compared to the MEGARes database .
RBX2660 Efficacy in a Phase 2 Controlled Trial
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Microbiome Composition Shifts Post-RBX2660
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MICROBIOME HEALTH INDEX™ (MHI™) Analysis
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Relationship Between MHI and Antimicrobial Resistance Genes
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Conclusions
- MHI can effectively distinguish patients with dysbiosis from healthier patients, as defined by the RBX2660 product profile and the Human Microbiome Project.
- MHI inversely correlates with AMR gene abundance in a cohort of rCDI patients who had successful response to RBX2660.
- These results suggest MHI as a potential sentinel of MDRO colonization, and this role will be evaluated in future cohorts outside of the rCDI patient population.