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

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.

Study Overview

• Status: Recruiting
• Conditions: Clostridioides Difficile Infection
• Intervention / Treatment: Drug: AZD5148; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Camperdown, Australia, 2050
    • Recruiting
    • Research Site
  • Clayton, Australia, 3168
    • Recruiting
    • Research Site
  • Herston, Australia, 4029
    • Recruiting
    • Research Site
  • Melbourne, Australia, 3000
    • Recruiting
    • Research Site
  • South Brisbane, Australia, 4101
    • Recruiting
    • Research Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2X8
      • Withdrawn
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Not yet recruiting
      • Research Site
    • Victoria, British Columbia, Canada, V8T 5G4
      • Withdrawn
      • Research Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • Not yet recruiting
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Not yet recruiting
      • Research Site
    • London, Ontario, Canada, N6A 5A5
      • Not yet recruiting
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3S5
      • Recruiting
      • Research Site
    • Québec, Quebec, Canada, G1V 4T3
      • Recruiting
      • Research Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Not yet recruiting
      • Research Site
• Denmark
  • Aalborg, Denmark, DK9000
    • Not yet recruiting
    • Research Site
  • Aarhus N, Denmark, 8200
    • Recruiting
    • Research Site
  • Hvidovre, Denmark, 2650
    • Recruiting
    • Research Site
  • København Ø, Denmark, 2100
    • Recruiting
    • Research Site
  • Odense C, Denmark, 5000
    • Recruiting
    • Research Site
• France
  • Lyon, France, 69317
    • Recruiting
    • Research Site
  • Montpellier, France, 34295
    • Not yet recruiting
    • Research Site
  • Nantes, France, 44093
    • Recruiting
    • Research Site
  • Nîmes, France, 30029
    • Recruiting
    • Research Site
  • Paris, France, 75014
    • Recruiting
    • Research Site
  • Paris, France, 75475
    • Recruiting
    • Research Site
  • Tours, France, 37044
    • Recruiting
    • Research Site
• Germany
  • Augsburg, Germany, 86156
    • Not yet recruiting
    • Research Site
  • Berlin, Germany, 13353
    • Recruiting
    • Research Site
  • Cologne, Germany, 50937
    • Recruiting
    • Research Site
  • Frankfurt, Germany, 60590
    • Recruiting
    • Research Site
  • Hamburg, Germany, 20246
    • Recruiting
    • Research Site
  • Jena, Germany, 07747
    • Not yet recruiting
    • Research Site
  • Leipzig, Germany, 04103
    • Recruiting
    • Research Site
  • München, Germany, 81675
    • Recruiting
    • Research Site
• Greece
  • Athens, Greece, 11527
    • Not yet recruiting
    • Research Site
  • Athens, Greece, 12462
    • Not yet recruiting
    • Research Site
  • Heraklion, Greece, 71500
    • Not yet recruiting
    • Research Site
  • Ioannina, Greece, 45500
    • Not yet recruiting
    • Research Site
  • Thessaloniki, Greece, 57010
    • Recruiting
    • Research Site
• Hungary
  • Budapest, Hungary, 1082
    • Recruiting
    • Research Site
  • Debrecen, Hungary, 4031
    • Recruiting
    • Research Site
  • Eger, Hungary, 3300
    • Recruiting
    • Research Site
  • Kistarcsa, Hungary, 2143
    • Recruiting
    • Research Site
  • Pécs, Hungary, 7624
    • Recruiting
    • Research Site
• Italy
  • Modena, Italy, 41124
    • Not yet recruiting
    • Research Site
  • Naples, Italy, 80131
    • Not yet recruiting
    • Research Site
  • Palermo, Italy, 90127
    • Recruiting
    • Research Site
  • Pisa, Italy, 56124
    • Recruiting
    • Research Site
  • Roma, Italy, 00161
    • Withdrawn
    • Research Site
  • Varese, Italy, 21100
    • Not yet recruiting
    • Research Site
• Japan
  • Kochi, Japan, 780-8522
    • Recruiting
    • Research Site
  • Kumamoto, Japan, 861-8520
    • Recruiting
    • Research Site
  • Meguro-ku, Japan, 153-0051
    • Recruiting
    • Research Site
  • Nagasaki, Japan, 852-8501
    • Recruiting
    • Research Site
  • Shimonoseki-shi, Japan, 750-8520
    • Recruiting
    • Research Site
  • Yaizu-shi, Japan, 425-8505
    • Recruiting
    • Research Site
• Poland
  • Lublin, Poland, 20-081
    • Withdrawn
    • Research Site
  • Warsaw, Poland, 04-141
    • Withdrawn
    • Research Site
• Spain
  • Alicante, Spain, 03010
    • Recruiting
    • Research Site
  • Badalona, Spain, 08916
    • Recruiting
    • Research Site
  • Madrid, Spain, 28007
    • Recruiting
    • Research Site
  • Madrid, Spain, 28040
    • Recruiting
    • Research Site
  • Madrid, Spain, 28034
    • Not yet recruiting
    • Research Site
  • Madrid, Spain, 28046
    • Recruiting
    • Research Site
  • Majadahonda, Spain, 28220
    • Recruiting
    • Research Site
  • Seville, Spain, 41009
    • Recruiting
    • Research Site
• Sweden
  • Helsingborg, Sweden, 25187
    • Withdrawn
    • Research Site
  • Lund, Sweden, 22185
    • Not yet recruiting
    • Research Site
  • Malmö, Sweden, 20502
    • Not yet recruiting
    • Research Site
  • Västerås, Sweden, 72189
    • Recruiting
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Recruiting
    • Research Site
  • Cambridge, United Kingdom, CB2 0QQ
    • Recruiting
    • Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Withdrawn
      • Research Site
  • California
    • Chula Vista, California, United States, 91911
      • Withdrawn
      • Research Site
    • Sacramento, California, United States, 95817
      • Not yet recruiting
      • Research Site
    • Torrance, California, United States, 90502
      • Recruiting
      • Research Site
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Recruiting
      • Research Site
  • Florida
    • Gainesville, Florida, United States, 32605
      • Recruiting
      • Research Site
    • Hialeah, Florida, United States, 33016
      • Not yet recruiting
      • Research Site
    • Homestead, Florida, United States, 33033
      • Recruiting
      • Research Site
    • Jacksonville, Florida, United States, 32256
      • Recruiting
      • Research Site
    • Miami Lakes, Florida, United States, 33014
      • Withdrawn
      • Research Site
    • Miramar, Florida, United States, 33027
      • Recruiting
      • Research Site
    • Port Orange, Florida, United States, 32127
      • Withdrawn
      • Research Site
    • Tamarac, Florida, United States, 33321
      • Recruiting
      • Research Site
    • Tampa, Florida, United States, 33607
      • Withdrawn
      • Research Site
  • Georgia
    • Athens, Georgia, United States, 30606
      • Recruiting
      • Research Site
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Research Site
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Recruiting
      • Research Site
  • Illinois
    • Burr Ridge, Illinois, United States, 60527
      • Recruiting
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Recruiting
      • Research Site
    • Louisville, Kentucky, United States, 40202
      • Not yet recruiting
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Not yet recruiting
      • Research Site
  • Maryland
    • Glen Burnie, Maryland, United States, 21061
      • Recruiting
      • Research Site
    • Potomac, Maryland, United States, 20854
      • Recruiting
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Research Site
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Research Site
    • Royal Oak, Michigan, United States, 48073
      • Not yet recruiting
      • Research Site
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Not yet recruiting
      • Research Site
    • St Louis, Missouri, United States, 63130
      • Not yet recruiting
      • Research Site
  • New Jersey
    • Union City, New Jersey, United States, 07087
      • Not yet recruiting
      • Research Site
  • New York
    • Hartsdale, New York, United States, 10530
      • Withdrawn
      • Research Site
    • Inwood, New York, United States, 11096
      • Withdrawn
      • Research Site
    • The Bronx, New York, United States, 10451
      • Recruiting
      • Research Site
  • North Carolina
    • Salisbury, North Carolina, United States, 28144
      • Recruiting
      • Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15237
      • Withdrawn
      • Research Site
  • Tennessee
    • Johnson City, Tennessee, United States, 37614
      • Not yet recruiting
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Not yet recruiting
      • Research Site
    • Lynchburg, Virginia, United States, 24501
      • Recruiting
      • Research Site
    • Roanoke, Virginia, United States, 24014
      • Recruiting
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98109
      • Not yet recruiting
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Not yet recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

• Positive local C. difficile toxin test (eg, immune assay or CCNA) on an unformed stool sample collected during this episode, and
• Receipt of standard of care antibacterial drug therapy for C. difficile infection (fidaxomicin, vancomycin or metronidazole) for this episode, with planned duration of at least 10 and at most 25 days at time of IMP administration.

Note: Diarrhea is not required to be present on the day of investigational medicinal product (IMP) administration.

Body weight ≥ 40 kg

Exclusion Criteria:

History of inflammatory bowel disease (eg, ulcerative colitis, Crohn's disease, microscopic colitis).

Participant 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 or bariatric surgery (bariatric surgery which does not disrupt the gastrointestinal lumen, ie, restrictive procedures such as banding, are permitted).

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 25 days of antibacterial drug therapy for C. difficile infection for the qualifying C. difficile infection episode

Treatment with a fecal donor transplant or fecal microbiota product in the 180 days before IMP administration, are receiving or planned administration for the qualifying episode of C. difficile infection, 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD5148: dose A; Participants will receive a single dose A of AZD5148 administered via either intramuscular injection or intravenous push.	Drug: AZD5148; Participants will receive a single dose A of AZD5148 administered via either intramuscular injection or intravenous push.
Placebo Comparator: Placebo; Participants will receive a single dose of placebo via intramuscular or intravenous push.	Other: Placebo; Participants will receive a single dose of placebo (0.9% (w/v) sodium chloride for injection) administered via either intramuscular injection or intravenous push.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First occurrence of recurrence of C difficile infection	rCDI is a recurrence of C difficile infection (CDI) occurring after initial clinical cure of the qualifying CDI. CDI is defined as a history of diarrhea (>=3 unformed stools, ie, type 6 or 7 stool on Bristol Stool Scale in <=24 hours for 2 consecutive calendar days) accompanied by a positive stool test for C difficile toxin.	Day 1 through day 91

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained clinical cure	Sustained clinical cure is defined as achieving initial clinical cure (ICC) of the qualifying CDI and not having an rCDI event through Day 91. ICC is defined as clinical cure for the qualifying CDI episode with a duration of a minimum of 10 days and a maximum of 25 days of standard of care antibacterial drug therapy for CDI.	Day 91
Duration of recurrent C difficile infection	Duration of the first occurrence of confirmed rCDI is calculated from the first day of diarrhea meeting the clinical symptom criteria until the date of clinical cure. Clinical cure is defined as <=2 unformed stools (ie, type 6 or 7 stool on Bristol Stool Scale) in 24 hours for 2 consecutive calendar days after the end of antibacterial drug treatment for the CDI episode.	Day 1 through Day 91
First occurrence of severe recurrent C difficile infection	Severe rCDI is defined as an rCDI event characterized by either: peripheral blood leukocytosis with leukocyte count >15,000 cells/uL or serum creatinine level >1.5 mg/dL.	Day 1 through Day 91
First occurrence of fulminant recurrent C difficile infection	Fulminant rCDI is defined as a severe rCDI event with hypotension or shock, toxic megacolon, or ileus.	Day 1 through Day 91
Severity of participant reported diarrhea symptoms	As reported by patient reported outcome (PRO) instrument for first occurrence of rCDI.	Day 1 through Day 91
Duration of participant reported diarrhea symptoms	As reported by patient reported outcome (PRO) instrument for first occurrence of rCDI.	Day 1 through Day 91
Occurrence of recurrent C difficile related mortality	rCDI related mortality is defined as a death related to rCDI as assessed by the Investigator.	Day 1 through Day 91
Immediate adverse events	Adverse events with a start time within 1 hour post-IMP administration	1 hour post-IMP administration
Injection/Infusion-related reactions	Injection or infusion-related reactions with a start date and time within 24 hours of IMP administration.	24 hours post-IMP administration
Local reactions at the injection/infusion site	Local reactions at the injection or infusion site with a start date through Day 8 post-IMP administration.	Day 1 through Day 8
Serious adverse events	SAEs are adverse events that fulfill any of the SAE criteria and are recorded with a start date from the date of informed consent form signature until the end of the study follow-up (Day 361)	ICF date through Day 361
Medically attended adverse events (MAAEs)	MAAEs are adverse events leading to medically attended visits that were not routine visits, such as ER visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason.	Day 1 through Day 361
Adverse events of special interest (AESIs)	AESIs as defined by Clinical Study Protocol.	Day 1 through Day 361
Related adverse events	Related AEs are adverse events assessed as related to IMP by the Investigator.	Day 1 through Day 361
Adverse events	AEs are defined as any unfavourable medical occurrence in a participant administered the IMP, regardless of the causal relationship to IMP.	Day 1 through Day 91
Pharmacokinetics of AZD5148	PK will be characterized through AZD5148 serum concentrations over time in participants who receive AZD5148.	Day 1 through Day 361
Anti-drug antibodies to AZD5148	Immunogenicity is evaluated through AZD5148 anti-drug antibody responses over time in serum from participants who receive AZD5148.	Day 1 through Day 361

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2025
• Primary Completion (Estimated): April 20, 2027
• Study Completion (Estimated): January 18, 2028

Study Registration Dates

• First Submitted: November 20, 2025
• First Submitted That Met QC Criteria: December 11, 2025
• First Posted (Actual): December 16, 2025

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: C. Diff; CDiff; Clostridioides Difficile infection; Clostridiodes Difficile Infection prevention of recurrence
• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Clostridium Infections
• Other Study ID Numbers: D8820C00003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No