Most adverse events reported were mild or moderate and found in a similar percentage of patients regardless of treatment cohort.
New findings suggest individuals who received RBX2660 for reduction of recurrent clostridioides difficile infection (CDI) had consistent treatment success when compared to placebo, across all CDI subgroups.
The study investigators additionally found most adverse events were mild or moderate and were reported in a similar percentage of patients regardless of treatment or stratification by Charlson Comorbidity Index (CCI) score.
“These data highlight the potential of RBX2660 to consistently and safely reduce CDI recurrence regardless of baseline comorbidities,” wrote study author Paul Feuerstadt, MD, Division of Gastroenterology, Yale University School of Medicine.
The findings were presented at the 2022 Digestive Disease Week Annual Meeting in San Diego, California.
As a standardized, microbiota-based investigational live biotherapeutic product, RBX2660 has recently been investigated as a treatment option for recurrent CDI. The product is administered as a single-dose via rectal administration without needing sedation, colonoscopy, or bowel preparation before administration.
The current study investigated the safety and efficacy of RBX2660 in patients stratified by CCI scores in the phase 3, multicenter, randomized, double-blind, placebo PUNCH CD3. The participants were ≥18 years old with ≥1 recurrence of CDI who completed standard-of-care antibiotic treatment prior to receiving either RBX2660 or placebo with a 2:1 randomization.
Investigators defined treatment success as remaining recurrence-free for 8 weeks after treatment and were monitored for recurrence and adverse events for up to 6 months following intervention. In the analysis, individuals were stratified by underlying comorbidities through baseline CCI scores at screening, considered 0 - 2 (mild), 3 - 4 (moderate), and 5+ (severe). Treatment adverse events were additionally summarized for the double-blind treatment period within 8 weeks.
From 262 individuals in the modified intent-to-treat study population, 107, 71, and 84 individuals were classified at screening as having mild, moderate, and severe CCI, respectively. Study investigators noted the mean participant age increased with increased comorbidities, from 45.8 years in the RBX2660 cohort with mild CCI scores to 76.0 years in the RBX2660 cohort with severe CCI scores.
Further, investigators found individuals with mild CCI scores had fewer prior CDI episodes than those with moderate and severe CCI scores. Data show 47 patients (69.1%) in the RBX2660 cohort with mild CCI scores had ≤3 CDI episodes before treatment, compared to 29 patients (58.0%) with moderate CCI scores and 35 patients (59.3%) with severe CCI scores.
Data across all CCI subgroups show individuals receiving RBX2660 had consistent and greater treatment rates, compared to placebo. It showed the absolute difference in treatment success rates between RBX2660 and placebo increased with increasing comorbidity burden (CCI, 0 - 2, 5%; CCI, 3 - 4, 11%; CCI 5+, 16%).
Regarding safety, most adverse events were mild or moderate regardless of underlying comorbidities, according to investigators. They noted severe adverse events were infrequent and reported in a similar percentage of participants regardless of underlying comorbidities. A single participant with a severe CDI score who received RBX2660 experienced an adverse event leading to death.
However, investigators determined no deaths or potentially life-threatening treatment adverse events were considered related to RBX2660 or its administration.
The study, “Treatment Success of RBX2660 in Reducing Recurrent Clostridioides Difficile Infection in Patients with Underlying Comorbidities,” was presented at DDW 2022.