Patients Achieve Sustained Clinical Response to C. diff Treatment in Phase 2 Study
In a Phase 2 controlled clinical study, patients with Clostridium difficile infection receiving ridinilazole were found to have achieved better treatment outcomes than those receiving vancomycin.
In the United States alone, Clostridium difficile infection causes more than 400,000 illnesses and 20,000 deaths annually in hospitalized patients—and, with no known cure, the disease poses a significant clinical challenge.
Now, a promising new therapy may be on the way, if the results of a recently published Phase II trial are any indication. According to the findings, which were posted online on April 28th by the journal Lancet Infectious Diseases, ridinilazole (SMT-19969, Summit Therapeutics), a nonabsorbable, small-molecule antimicrobial restricted to the gastrointestinal tract, outperformed vancomycin, the current standard of care in C. diff infection, with a similar safety profile.
“Recurrent infection is a key unmet medical challenge in C. diff infection management,” study co-author Bruce Yacyshyn, MD, Professor of Clinical Medicine and Molecular and Cellular Physiology, University of Cincinnati School of Medicine, told Contagion®. “Being able to maintain a healthy gut microbiome is important in protecting against C. diff infection, [and] an agent, such as ridinilazole, that is highly targeted towards C. diff infection but has minimal impact on the microbiome, is desirable. [Our] Phase 2 data suggest [the drug] is likely to be effective in treating the infection, and minimizing recurrence.”
Dr. Yacyshyn and his colleagues recruited 100 patients who were diagnosed with C. diff infection between June 2014 and August 2015, and randomized 50 to receive vancomycin (125 mg QID for 10 days) and 50 to receive the study drug (200 mg BID for 10 days). In the end, 16 patients did not complete the study, and 11 discontinued treatment prior to the final follow-up; a total of 69 participants (36 in the ridinilazole group and 33 in the vancomycin group) were included in the final analysis. Participants were followed for 30 days.
The authors reported that 24 of the 36 patients in the group recieving ridinilazole achieved sustained clinical response, which was defined as “clinical cure (≤3unformed bowel movements in a 24-hour period or <200 mL unformed stool in rectal collection devices) at test of cure and no recurrence of [C. diff infection] within 30 days” of the final treatment administration, compared to 14 of 33 in the group receiving vancomycin. They noted that the treatment difference of 21.1% (P=0·0004) established the noninferiority of the study drug, which also demonstrated “statistical superiority” at the 10% level.
In all, 82% (41 of 50) of participants in the group receiving ridinilazole reported adverse events, compared to 80% (40 of 50) in the group receiving vancomycin. The adverse events (AE) profile was also similar between the 2 drugs, with instances of nausea, abdominal pain, abdominal distension, vomiting, flatulence, asthenia, edema, urinary tract infections, decreased appetite, dehydration, headache, dizziness, dyspnea, and rash, among others, reported with the study drug. None of these AEs led to treatment discontinuation.
The authors would like to see subsequent “larger registration… Phase 3 studies… further the understanding of the impact, beyond the data already published, of ridinilazole on the microbiome,” Dr. Yacyshyn said. “The key [to successful [C. diff infection] treatment] is to minimize upfront the chance of recurrence, rather than wait to treat recurrences, because each successive recurrence is associated with higher recurrence rates. Thus, optimal treatment upfront with initial infections is critical. Ridinilazole could be used in patients with an initial episode to reduce the impact of recurrent [C. diff infection],” the authors concluded.
Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.