SAN DIEGO, CA—A single infusion of the human monoclonal antibody bezlotoxumab (BEZ), with or without actoxumab (ACT), improves prevention of recurrent C. difficile infection (rCDI), according to a presentation at IDWeek 2015 of data combined from the double-blind, randomized Phase 3 MODIFY I and MODIFY II studies.
“In patients receiving standard of care therapy for CDI and rCDI, a single infusion of ACT+BEZ or BEZ alone decreased rCDI, both overall and in at-risk subgroups, increased global cure vs. placebo over 12 weeks, and was generally well tolerated with a safety profile similar to placebo,” reported Mark Wilcox, MD, Leeds Teaching Hospital, Leeds, England, and colleagues.
In both studies, patients were administered an oral standard of care that included metronidazole, vancomycin or fidaxomicin. Patients also received either placebo, BEZ alone (10mg/kg), or BEZ+ACT (10mg/kg each).
Data analysis included a total of 2,327 patients enrolled in 30 countries who received a study infusion, Dr. Wilcox said. Data were excluded for a MODIFY I ACT-alone [10mg/kg] study arm because this part of the study was halted for “efficacy and safety reasons” after an interim analysis, Dr. Wilcox and coauthors noted.
Seventeen percent of patients overall had severe CDI and 11% were infected with the 027 ribotype; 27% of patients had a history of prior CDI.
“rCDI rates were significantly lower for ACT+BEZ (15.4%) and for BEZ alone (16.5%) vs. placebo” (26.6%; both P<0.0001), Dr. Wilcox reported. rCDI rates were lower than placebo in subgroups with rCDI risk factors like patient age ≥65 years, prior history of CDI, 027 ribotype infection, or severe CDI.
Moreover, global cure was superior for BEZ alone (63.5%) vs. placebo [53.7%; P=0.0001] and higher for ACT+BEZ (58.1%; P=0.0426) vs. placebo. Safety endpoints were comparable for ACT+BEZ and BEZ alone vs. placebo.
The most frequent adverse events (AE) through Week 4 of therapy included diarrhea (5.9% for patients in the ACT+BEZ study arm; 6.0% for BEZ alone; 5.8% for placebo); nausea (6.0%, 6.6%, 5.8%, respectively); and CDI associated with life-threatening or prolonged hospitalization (3.5%, 2.9%, 6.1%, respectively).
Through Week 12, there were 51 deaths (6.6%) in the ACT+BEZ study group, 56 deaths (7.1%) in the BEZ-alone group, and 59 deaths (7.6%) in the placebo group, the coauthors reported.