Prevention of Recurrent C. Difficile Infection Study With AZD5148 Monoclonal Antibody

A Phase IIb, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AZD5148 for Prevention of Recurrence of Clostridioides Difficile Infection in Individuals 18 Years of Age and Above

The purpose of this study is to evaluate the efficacy and safety of AZD5148 for prevention of recurrence of Clostridioides difficile infection in Individuals 18 years of age and above.

Approximately 230 participants will be enrolled and randomized 1:1 to receive a single dose of either AZD5148 or placebo (normal saline). Route of administration (intramuscular or intravenous push) will be according to the Investigator's choice. Stratification will be based on geographical region.

Study details include:

• Up to 2 site visits for confirmation of eligibility and dose administration, including stool sample collection;
• Up to 7 planned visits;
• Contacts initiated by site staff -weekly, later monthly follow up;
• Electronic diary completion.

Inclusion Criteria:

Participant must be ≥ 18 years of age at the time of signing the informed consent, capable of giving signed informed consent.

Participants with a qualifying C. difficile infection episode at the time of providing informed consent defined by:

• History of 3 or more unformed stools (Bristol stool scale 6 or 7) in ≤ 24 hours for 2 consecutive calendar days, (Note: Diarrhea is not required to be present on the day of IMP administration) and
• Positive local C. difficile toxin test (eg, immune assay or CCNA) on a stool sample collected during this episode, as part of routine clinical care (Note: Toxin testing, where not part of routine clinical care, may be conducted as a pre- screening activity; if this occurs, participant consent is required), and
• Planned initiation or receipt of antibacterial drug therapy for C. difficile infection (fidaxomicin, vancomycin or metronidazole) for this episode,

Note: At the time of randomization and IMP administration, the participant must have started receiving the antibacterial drug therapy with a planned total treatment duration of at least 10 and at most 28 days at time of IMP administration. IMP can be administered at any point during the antibacterial drug therapy.

Body weight ≥ 35 kg

Exclusion Criteria:

Participants with a history of uncontrolled inflammatory bowel disease. Participants with a history of inflammatory bowel disease may be included if, in the opinion of the Investigator, their disease is clinically controlled and presenting symptoms are more likely attributable to CDI than to a flare of inflammatory bowel disease.

Participants with a non - CDI (C. difficile infection) condition such that the participant routinely passes loose stool (eg, patients with an ostomy)

Planned surgery for C. difficile infection within 24 hours of enrollment

Current toxic megacolon and/or small bowel ileus

Any history of total colectomy

Major gastrointestinal surgery as assessed by the Investigator (eg, significant bowel resection or diversion) within 90 days before enrollment (this does not include appendectomy or cholecystectomy)

Due to receive more than 28 days of antibacterial drug therapy for the qualifying C. difficile infection episode

Participants receiving a fecal microbiota transplant, fecal microbiota product, or live biotherapeutic product for the qualifying CDI episode, or planned administration during the 180 days after IMP administration.

Treatment with bezlotoxumab in the 180 days before IMP administration, are receiving or planned administration for the qualifying episode of CDI, or planned administration during the 180 days after IMP administration.