Clostridioides Difficile Infection
Conditions
Keywords
Clostridioides Difficile infection, C. Diff, CDiff, Clostridiodes Difficile Infection prevention of recurrence
Brief summary
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.
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.
Interventions
DRUGAZD5148
Participants will receive a single dose A of AZD5148 administered via either intramuscular injection or intravenous push.
OTHERPlacebo
Participants will receive a single dose of placebo (0.9% (w/v) sodium chloride for injection) administered via either intramuscular injection or intravenous push.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind: Participant, Care Provider, Investigator, Outcomes Assessor
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| First occurrence of recurrence of C difficile infection | Day 1 through day 91 | Recurrence of C difficile infection (rCDI) occurring after initial clinical cure (ICC) of the qualifying C difficile infection (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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained clinical cure | Day 91 | Sustained clinical cure is defined as achieving 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 28 days of antibacterial drug therapy for CDI. |
| Duration of recurrent C difficile infection | Day 1 through Day 91 | 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. |
| First occurrence of severe recurrent C difficile infection | Day 1 through Day 91 | 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. |
| First occurrence of fulminant recurrent C difficile infection | Day 1 through Day 91 | Fulminant rCDI is defined as a severe rCDI event with hypotension or shock, toxic megacolon, or ileus. |
| Severity of participant reported diarrhea symptoms | Day 1 through Day 91 | As reported by patient reported outcome (PRO) instrument for first occurrence of rCDI. |
| Duration of participant reported diarrhea symptoms | Day 1 through Day 91 | As reported by patient reported outcome (PRO) instrument for first occurrence of rCDI. |
| First occurrence of hospitalization due to recurrent C difficile infection | Day 1 through Day 91 | Hospitalization due to rCDI is defined as a confirmed rCDI event and a hospitalization related to the rCDI event. |
| Duration of hospitalizations due to recurrent C difficile infection | Day 1 though Day 91 | The sum of all hospitalization durations related to the first recurrent CDI that leads to hospitalization. |
| Occurrence of recurrent C difficile related mortality | Day 1 through Day 91 | rCDI related mortality is defined as a death related to rCDI as assessed by the Investigator. |
| Immediate adverse events | 1 hour post-IMP administration | Adverse events with a start time within 1 hour post-IMP administration |
| Injection/Infusion-related reactions | 24 hours post-IMP administration | Injection or infusion-related reactions with a start date and time within 24 hours of IMP administration. |
| Local reactions at the injection/infusion site | Day 1 through Day 8 | Local reactions at the injection or infusion site with a start date through Day 8 post-IMP administration. |
| Serious adverse events | ICF date through Day 361 | 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) |
| Medically attended adverse events (MAAEs) | Day 1 through Day 361 | 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. |
| Adverse events of special interest (AESIs) | Day 1 through Day 361 | AESIs as defined by Clinical Study Protocol. |
| Related adverse events | Day 1 through Day 361 | Related AEs are adverse events assessed as related to IMP by the Investigator. |
| Adverse events | Day 1 through Day 91 | AEs are defined as any unfavourable medical occurrence in a participant administered the IMP, regardless of the causal relationship to IMP. |
| Pharmacokinetics of AZD5148 | Day 1 through Day 361 | PK will be characterized through AZD5148 serum concentrations over time in participants who receive AZD5148. |
| Anti-drug antibodies to AZD5148 | Day 1 through Day 361 | Immunogenicity is evaluated through AZD5148 anti-drug antibody responses over time in serum from participants who receive AZD5148. |
Countries
Australia, Canada, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Poland, Spain, Sweden, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed