Efficacy and Safety of AZD5148 for the Prevention of Recurrent Clostridioides difficile Infection in Adults: A Phase IIb, Randomized, Placebo-Controlled Study

The primary objective is to evaluate the efficacy of AZD5148, administered as a single intramuscular or intravenous dose during standard of care antibacterial therapy, in reducing the recurrence of Clostridioides difficile infection compared to placebo through Day 91. The secondary objective includes evaluating the efficacy of the single-dose administration in achieving sustained clinical cure through Day 91. Trial scope: 2, 4, 5, 6, 7.

The study involves a total of 137 patients. The population consists of both male and female individuals. Eligible participants must be at least 18 years of age and have a body weight of 40 kg or greater. The study targets individuals experiencing a recurrence of Clostridioides difficile infection. Inclusion requires a history of three or more unformed stools on the Bristol stool scale within 24 hours for two consecutive days, alongside a positive local toxin test. Participants must be receiving standard of care antibacterial drug therapy, such as fidaxomicin, vancomycin, or metronidazole, for a planned duration of 10 to 25 days at the time of investigational medicinal product administration.

This Phase IIb, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of AZD5148, a humanised IgG1 kappa (YTE) monoclonal antibody, for the prevention of recurrence of Clostridioides difficile infection. Participants aged 18 years or older who are receiving standard of care antibacterial drug therapy will undergo a screening process to confirm eligibility based on clinical and laboratory criteria. Following screening, eligible individuals will be randomized to receive either a single dose of AZD5148 via intravenous infusion or a placebo. The primary endpoint is the first occurrence of recurrent infection, while secondary endpoints include sustained clinical cure. The study involves monitoring participants through Day 91 to assess the reduction in infection recurrence. The overall duration of the trial is subject to recruitment and follow-up requirements.

AZD5148 is an experimental humanised IgG1 kappa (YTE) monoclonal antibody directed against Clostridioides difficile toxin B. This investigation utilizes the substance in a solution for injection via intravenous infusion. The medication is administered as a single dose in conjunction with standard of care antibacterial drug therapy for Clostridioides difficile infection.

The placebo group receives a placebo for AZD5148 as a comparator treatment during the study period.

The efficacy of AZD5148 is evaluated through the assessment of the recurrence of Clostridioides difficile infection. The primary endpoint is defined as the first occurrence of recurrent Clostridioides difficile infection through Day 91. Secondary efficacy assessment includes the rate of sustained clinical cure, which is defined as the achievement of initial clinical cure without subsequent recurrence.