Herein, we assessed the total AMR gene profile before and after treatment in fecal samples from RBX2660 treatment responders in a Phase 2 rCDI trial.
PUNCH Open Label™ (NCT02589847) – prospective, multicenter, open-label Phase 2 study assessing the efficacy and safety of RBX2660 treatment of recurrent CDI.
PATIENT POPULATION: multi-recurrent CDI (≥ 2 recurrent episodes at enrollment)
TREATMENT: two doses of RBX2660 administered 7 ± 2 days apart
EFFICACY: absence of CDI recurrence at 8 weeks after last study treatment
FAILURE: documented recurrence, including positive laboratory diagnosis for C. difficile
CONTROL GROUP: historical chart review of patients who only received antibiotic therapy for rCDI
Analysis included 66 longitudinally matched samples from 22 treatment responsive participants, including before treatment (BL) and 7 ± 3 and 30 ± 10 days after treatment. Sample set represents 17 trial sites from US and Canada.
All samples were frozen without stabilizers after collection, extracted, and sequenced using a shallow shotgun method.
Sequencing reads were compared to a proprietary database of gene sequences annotated as related to antimicrobial resistance (CosmosID)
≥ 40% sequencing coverage of an AMR gene was considered positive identification in each sample.
AMR gene coverage for participant samples were compared to Human Microbiome Project (HMP) data for which comparable sequencing depth was simulated.
RBX2660 is Efficacious & Durable
119 of 149 RBX2660-treated participants (80%) were responders at 8 weeks after treatment
57 of 110 patients (52%) in the historical control group were recurrence free 8 weeks after antibiotic treatment
Only 3 of 109 evaluable primary RBX2660 responders reported reinfection at 6 months
97% of RBX2660-treated 8-week responders who were evaluable at 6 months remained recurrence free
Follow up ongoing to 24 months
RBX2660 Shifts Microbiome Composition
Participants were dysbiotic at study entry, with decreased Bacteroidia and Clostridia and overabundance of Gammaproteobacteria and Bacilli
Bacteroidia, Clostridia increased and Gammaproteobacteria, Bacilli decreased after treatment; durable to 6 months after treatment
Based on shallow-shotgun sequencing data
Antimicrobial Resistance Genes (AMR) Analysis
Prior to treatment (BL) rCDI participants had significantly higher abundance of antimicrobial resistance (AMR) genes than the HMP healthy population
After treatment (7 and 30 days), participants’ had decreased AMR gene abundance, not significantly different from HMP
In a Phase 2 open label trial, RBX2660 was 80% effective for preventing rCDI, with durable response to at least 6 months.
Responding participants’ microbiomes resolved toward a healthier composition after treatment.
In a 22-participant subgroup analysis, there was a significant decrease in antimicrobial resistance genes from before to after successful response to RBX2660.