Ridinilazole Beats Standard of Care in Phase 2 C difficile Study
Favorable sustained clinical response seen with novel antimicrobial ridinilazole compared with conventional therapy. Photo Credit: CDC/James Archer.
According to results of a phase 2 study published in Lancet Infectious Diseases, ridinilazole demonstrated statistical superiority over standard-of-care vancomycin in producing sustained clinical response in patients with Clostridium difficile infection (CDI).1 Ridinilazole, currently being developed by Summit Therapeutics, is a novel, orally administered small molecule antimicrobial that specifically targets C difficile isolates while sparing normal gut microbiota.
In an email interview with Infectious Disease Advisor, Richard Vickers, PhD, chief scientific officer at Summit Therapeutics and lead investigator of the CoDIFy Study Group, reported that prevention of recurrent infections is one of the central unmet medical needs in CDI. “Current mainstay agents, such as metronidazole and vancomycin, are fairly effective at treating the initial infection, but due to their broad spectrum of activity they cause collateral damage to the gut microbiome during therapy. This can precipitate recurrent infection, which impacts patient welfare and is both challenging for physicians to manage and a major burden on healthcare resources.”
The investigators randomly assigned patients with CDI to receive ridinilazole 200 mg orally twice daily for 10 days (n=50) or vancomycin 125 mg 4 times daily (n=50) for 10 days. Patients in the ridinilazole group also received 2 doses of placebo daily in order to maintain the same dosing schedule as the vancomycin group.
The primary end point of sustained clinical response was achieved by 66.7% (24/36) patients in the modified intent-to-treat (ITT) population who received ridinilazole vs 42.4% (14/33) of patients in the modified ITT population who received vancomycin (treatment difference 21.1%, 90% CI: 3.1-39.1; P=.0004). Sustained clinical response, a well-established measure of CDI antibiotic efficacy, is defined as cure at the end of therapy (less than or equal to 3 unformed bowel movements in a 24-hour period or <200 mL unformed stool in rectal collection devices) and no recurrence of CDI in the following 30 days. “The superiority in [sustained clinical response] was driven by a reduction in rates of recurrent CDI with ridinilazole compared with vancomycin, which is due to the highly targeted spectrum of activity of ridinilazole that prevents collateral damage to the gut microbiome during therapy,” noted Dr Vickers. Recurrence, analyzed only in patients who achieved clinical cure, occurred in 14.3% (4/28) of ridinilazole recipients and 34.8% (8/23) of vancomycin recipients. Adverse event rates were similar among both treatment groups.
In an accompanying editorial, Simon Goldenberg, MD, of King's College, London and Guy's and St. Thomas' NHS Foundation Trust, London, noted several factors that “somewhat limited” the study, including an over-representation of younger patients, an unusually low percentage of patients with severe disease, and a lack of clarity as to why only 64% (21/33) of the sites in this multicenter trial recruited patients to the study. “Discounting these shortcomings,” he wrote, “it is rare for a study of an antimicrobial to show statistical superiority over the standard of care.”2
Quotes were lightly edited for clarity.
- Vickers RJ, Tillotson GS, Nathan R, et al. Efficacy and safety of ridinilazole compared with vancomycin for the treatment of Clostridium difficile infection: a phase 2, randomised, double-blind, active-controlled, non-inferiority study [published online April 28, 20170. Lancet Infect Dis. doi:10.1016/S1473-3099(17)30235-9
- Goldenberg SD. Expanding the armamentarium for the treatment of Clostridium difficile infection [published online April 28, 2017]. Lancet Infect Dis. doi:10.1016/S1473-3099(17)30237-2